Jeff Evans

The final dose of the standard four-dose vaccination series with inactivated poliovirus should be administered at 4 years of age or older after a minimum interval of 6 months after the third dose, according to updated recommendations from the Advisory Committee on Immunization Practices.

In addition, the committee advises using the minimum age of 6 weeks for the first dose and the minimum interval of 4 weeks between the following two doses “only if the vaccine recipient is at risk for imminent exposure to circulating poliovirus.”

This condensed vaccination schedule is not advisable in other situations because shorter intervals and an earlier start date lead to lower seroconversion rates. The normal four-dose schedule for inactivated poliovirus vaccine (IPV) sets doses at ages 2 months, 4 months, 6-18 months, and 4-6 years (MMWR 2009;58:829-30).

ACIP also clarified the poliovirus vaccination schedule that should be used with the combination vaccine DTaP-IPV/Hib (Pentacel). When four doses of DTaP-IPV/Hib are administered at ages 2, 4, 6, and 15-18 months, ACIP recommends using an additional fifth booster dose of IPV (Ipol) or DTaP-IPV (Kinrix) at age 4-6 years, with a minimum interval of at least 6 months between the fourth and fifth dose.

The final dose of the standard four-dose vaccination series with inactivated poliovirus should be administered at 4 years of age or older after a minimum interval of 6 months after the third dose, according to updated recommendations from the Advisory Committee on Immunization Practices.

In addition, the committee advises using the minimum age of 6 weeks for the first dose and the minimum interval of 4 weeks between the following two doses “only if the vaccine recipient is at risk for imminent exposure to circulating poliovirus.”

This condensed vaccination schedule is not advisable in other situations because shorter intervals and an earlier start date lead to lower seroconversion rates. The normal four-dose schedule for inactivated poliovirus vaccine (IPV) sets doses at ages 2 months, 4 months, 6-18 months, and 4-6 years (MMWR 2009;58:829-30).

ACIP also clarified the poliovirus vaccination schedule that should be used with the combination vaccine DTaP-IPV/Hib (Pentacel). When four doses of DTaP-IPV/Hib are administered at ages 2, 4, 6, and 15-18 months, ACIP recommends using an additional fifth booster dose of IPV (Ipol) or DTaP-IPV (Kinrix) at age 4-6 years, with a minimum interval of at least 6 months between the fourth and fifth dose.

The final dose of the standard four-dose vaccination series with inactivated poliovirus should be administered at 4 years of age or older after a minimum interval of 6 months after the third dose, according to updated recommendations from the Advisory Committee on Immunization Practices.

In addition, the committee advises using the minimum age of 6 weeks for the first dose and the minimum interval of 4 weeks between the following two doses “only if the vaccine recipient is at risk for imminent exposure to circulating poliovirus.”

This condensed vaccination schedule is not advisable in other situations because shorter intervals and an earlier start date lead to lower seroconversion rates. The normal four-dose schedule for inactivated poliovirus vaccine (IPV) sets doses at ages 2 months, 4 months, 6-18 months, and 4-6 years (MMWR 2009;58:829-30).

ACIP also clarified the poliovirus vaccination schedule that should be used with the combination vaccine DTaP-IPV/Hib (Pentacel). When four doses of DTaP-IPV/Hib are administered at ages 2, 4, 6, and 15-18 months, ACIP recommends using an additional fifth booster dose of IPV (Ipol) or DTaP-IPV (Kinrix) at age 4-6 years, with a minimum interval of at least 6 months between the fourth and fifth dose.

WASHINGTON — A low level of growth hormone in obese adults is independently associated with increased carotid intima media thickness, which may translate into an elevated risk of cardiovascular disease and a severe metabolic phenotype, according to the results of a prospective, observational study.

Building on evidence gathered from previous studies of growth hormone (GH) levels in obese men and women, Dr. Hideo Makimura and his colleagues in the neuroendocrine unit and program in nutritional metabolism at Massachusetts General Hospital, Boston, analyzed stimulated GH secretion levels and other cardiometabolic risk factors in 102 lean and obese individuals.

“Taken together, these data suggest [that] strategies to increase growth hormone secretion may improve cardiovascular risk in obesity,” Dr. Makimura said during the presentation of his study at the annual meeting of the Endocrine Society.

Studies including frequent blood sampling of GH have shown 75% less 24-hour GH secretion in obese men, compared with age-matched lean men. Other studies have found that 64% of obese men have a peak stimulated GH level of less than 9 mcg/L in standardized GH-releasing hormone-arginine testing, whereas less than 1% of lean men have such a level. Reduced GH has been associated with an increase in carotid intima media thickness (cIMT), a measure of atherosclerosis, in overweight and obese women.

Dr. Makimura and his associates followed 33 lean individuals, 55 obese individuals who had sufficient growth hormone, and 14 obese individuals who were deficient in growth hormone (peak stimulation GH level of 4.2 mcg/L or less). The groups had mean ages in the low to mid 40s. The participants were matched for age, sex, race, tobacco use, and blood pressure. The obese groups also were matched for body mass index and visceral adiposity.

Lean individuals had a mean BMI of 22.5 kg/m

In a univariate analysis, peak GH negatively correlated with cIMT. GH-deficient obese participants had a greater mean cIMT than did lean participants, but there was no significant difference in cIMT between the obese groups.

The researchers obtained the same results when they used more liberal cutoffs, defining GH deficiency as peak stimulated GH secretion concentrations of less than 5 mcg/L or less than 9 mcg/L.

Dr. Makimura and his associates found in univariate analyses that peak stimulated GH also was negatively correlated with the amount of visceral adipose tissue, as well as with LDL cholesterol, triglycerides, C-reactive protein, tumor necrosis factor-alpha, and measures of insulin sensitivity.

The association between peak stimulated GH and cIMT remained significant in separate multivariate regression analyses that controlled for demographic factors, traditional cardiovascular disease risk factors (tobacco use, systolic blood pressure, and levels of cholesterol and fasting blood glucose), metabolic variables (visceral adipose tissue, BMI, HDL and LDL cholesterol, triglycerides, fasting glucose, and fasting insulin), or inflammatory markers (C-reactive protein, adiponectin, and tumor necrosis factor-alpha).

Dr. Makimura concluded that these GH-related cardiometabolic risk factors may mediate the association between reduced GH secretion in obesity and increased cIMT.

The study was funded by grants from the National Institutes of Health. Dr. Makimura disclosed no relevant conflicts of interest.

WASHINGTON — A low level of growth hormone in obese adults is independently associated with increased carotid intima media thickness, which may translate into an elevated risk of cardiovascular disease and a severe metabolic phenotype, according to the results of a prospective, observational study.

Building on evidence gathered from previous studies of growth hormone (GH) levels in obese men and women, Dr. Hideo Makimura and his colleagues in the neuroendocrine unit and program in nutritional metabolism at Massachusetts General Hospital, Boston, analyzed stimulated GH secretion levels and other cardiometabolic risk factors in 102 lean and obese individuals.

“Taken together, these data suggest [that] strategies to increase growth hormone secretion may improve cardiovascular risk in obesity,” Dr. Makimura said during the presentation of his study at the annual meeting of the Endocrine Society.

Studies including frequent blood sampling of GH have shown 75% less 24-hour GH secretion in obese men, compared with age-matched lean men. Other studies have found that 64% of obese men have a peak stimulated GH level of less than 9 mcg/L in standardized GH-releasing hormone-arginine testing, whereas less than 1% of lean men have such a level. Reduced GH has been associated with an increase in carotid intima media thickness (cIMT), a measure of atherosclerosis, in overweight and obese women.

Dr. Makimura and his associates followed 33 lean individuals, 55 obese individuals who had sufficient growth hormone, and 14 obese individuals who were deficient in growth hormone (peak stimulation GH level of 4.2 mcg/L or less). The groups had mean ages in the low to mid 40s. The participants were matched for age, sex, race, tobacco use, and blood pressure. The obese groups also were matched for body mass index and visceral adiposity.

Lean individuals had a mean BMI of 22.5 kg/m

In a univariate analysis, peak GH negatively correlated with cIMT. GH-deficient obese participants had a greater mean cIMT than did lean participants, but there was no significant difference in cIMT between the obese groups.

The researchers obtained the same results when they used more liberal cutoffs, defining GH deficiency as peak stimulated GH secretion concentrations of less than 5 mcg/L or less than 9 mcg/L.

Dr. Makimura and his associates found in univariate analyses that peak stimulated GH also was negatively correlated with the amount of visceral adipose tissue, as well as with LDL cholesterol, triglycerides, C-reactive protein, tumor necrosis factor-alpha, and measures of insulin sensitivity.

The association between peak stimulated GH and cIMT remained significant in separate multivariate regression analyses that controlled for demographic factors, traditional cardiovascular disease risk factors (tobacco use, systolic blood pressure, and levels of cholesterol and fasting blood glucose), metabolic variables (visceral adipose tissue, BMI, HDL and LDL cholesterol, triglycerides, fasting glucose, and fasting insulin), or inflammatory markers (C-reactive protein, adiponectin, and tumor necrosis factor-alpha).

Dr. Makimura concluded that these GH-related cardiometabolic risk factors may mediate the association between reduced GH secretion in obesity and increased cIMT.

The study was funded by grants from the National Institutes of Health. Dr. Makimura disclosed no relevant conflicts of interest.

WASHINGTON — A low level of growth hormone in obese adults is independently associated with increased carotid intima media thickness, which may translate into an elevated risk of cardiovascular disease and a severe metabolic phenotype, according to the results of a prospective, observational study.

Building on evidence gathered from previous studies of growth hormone (GH) levels in obese men and women, Dr. Hideo Makimura and his colleagues in the neuroendocrine unit and program in nutritional metabolism at Massachusetts General Hospital, Boston, analyzed stimulated GH secretion levels and other cardiometabolic risk factors in 102 lean and obese individuals.

“Taken together, these data suggest [that] strategies to increase growth hormone secretion may improve cardiovascular risk in obesity,” Dr. Makimura said during the presentation of his study at the annual meeting of the Endocrine Society.

Studies including frequent blood sampling of GH have shown 75% less 24-hour GH secretion in obese men, compared with age-matched lean men. Other studies have found that 64% of obese men have a peak stimulated GH level of less than 9 mcg/L in standardized GH-releasing hormone-arginine testing, whereas less than 1% of lean men have such a level. Reduced GH has been associated with an increase in carotid intima media thickness (cIMT), a measure of atherosclerosis, in overweight and obese women.

Dr. Makimura and his associates followed 33 lean individuals, 55 obese individuals who had sufficient growth hormone, and 14 obese individuals who were deficient in growth hormone (peak stimulation GH level of 4.2 mcg/L or less). The groups had mean ages in the low to mid 40s. The participants were matched for age, sex, race, tobacco use, and blood pressure. The obese groups also were matched for body mass index and visceral adiposity.

Lean individuals had a mean BMI of 22.5 kg/m

In a univariate analysis, peak GH negatively correlated with cIMT. GH-deficient obese participants had a greater mean cIMT than did lean participants, but there was no significant difference in cIMT between the obese groups.

The researchers obtained the same results when they used more liberal cutoffs, defining GH deficiency as peak stimulated GH secretion concentrations of less than 5 mcg/L or less than 9 mcg/L.

Dr. Makimura and his associates found in univariate analyses that peak stimulated GH also was negatively correlated with the amount of visceral adipose tissue, as well as with LDL cholesterol, triglycerides, C-reactive protein, tumor necrosis factor-alpha, and measures of insulin sensitivity.

The association between peak stimulated GH and cIMT remained significant in separate multivariate regression analyses that controlled for demographic factors, traditional cardiovascular disease risk factors (tobacco use, systolic blood pressure, and levels of cholesterol and fasting blood glucose), metabolic variables (visceral adipose tissue, BMI, HDL and LDL cholesterol, triglycerides, fasting glucose, and fasting insulin), or inflammatory markers (C-reactive protein, adiponectin, and tumor necrosis factor-alpha).

Dr. Makimura concluded that these GH-related cardiometabolic risk factors may mediate the association between reduced GH secretion in obesity and increased cIMT.

The study was funded by grants from the National Institutes of Health. Dr. Makimura disclosed no relevant conflicts of interest.

WASHINGTON — Female infants born to women with polycystic ovary syndrome do not appear to have high levels of androgens or to be small for gestational age, according to the results of a prospective, case-control study.

In fact, offspring born to mothers with polycystic ovary syndrome (PCOS) were more likely than were controls to be large for gestational age, according to the study.

Findings from clinical and animal-based studies suggest that PCOS may originate during fetal development. Prenatal exposure to androgens has been shown to induce a PCOS phenotype in sheep, monkeys, and rats. In humans, retrospective studies have shown that girls with PCOS features and premature menarche had been significantly small for their gestational age, according to Helen Anderson of the division of endocrinology, metabolism, and molecular medicine at Northwestern University, Chicago.

To determine if the intrauterine environment of women with PCOS alters fetal growth and androgen levels, Ms. Anderson and her associates compared singleton pregnancies in 39 women with PCOS and 31 healthy controls. The participants were non-Hispanic white women who met National Institute of Child Health and Human Development criteria for PCOS. None of the participants had a history of gestational diabetes, preexisting medical conditions, or complications during pregnancy.

Compared with healthy controls, a larger percentage of women with PCOS were nulliparous (64% vs. 39%) or had undergone ovulation induction or in vitro fertilization (77% vs. 6%). Women with PCOS were slightly, but significantly, younger than were the healthy control women (30 years vs. 32 years). Although PCOS women had a slightly higher mean body mass index than did controls, they had comparable maternal weight gains.

The birth cohort consisted of more females (43) than males (27) because the investigators were primarily interested in female offspring, and they excluded women known to be carrying a male fetus.

Overall, the gestational age and birth weight of infants did not differ between women with and without PCOS. However, when Ms. Anderson and her colleagues stratified the analysis according to size at gestational age, a significantly greater proportion of the infants born to women with PCOS were large for gestational age compared with healthy controls (23% vs. 3%).

“This may be secondary to the increased nutritional flow across the placenta,” as elevated levels of insulin and glucose have been demonstrated in pregnant women with PCOS, Ms. Anderson said at the annual meeting of the Endocrine Society.

Analyses of the steroid hormones in whole (mixed arterial and venous) cord blood showed that the female offspring of PCOS women had significantly lower levels of androstenedione and estradiol.

However, female offspring had no differences in levels of testosterone, dihydrotestosterone, and dehydroepiandrosterone, although Ms. Anderson said that many of the testosterone and dihydrotestosterone values were at the low end of detectability for the assays.

Female offspring from either group of women showed no differences in levels of 17-hydroxy-progesterone or in the ratio of testosterone to estradiol levels.

The National Institutes of Health funded the study. Ms. Anderson reported having no conflicts of interest to disclose.

The female offspring of PCOS women had significantly lower levels of androstenedione and estradiol.

Source MS. ANDERSON

WASHINGTON — Female infants born to women with polycystic ovary syndrome do not appear to have high levels of androgens or to be small for gestational age, according to the results of a prospective, case-control study.

In fact, offspring born to mothers with polycystic ovary syndrome (PCOS) were more likely than were controls to be large for gestational age, according to the study.

Findings from clinical and animal-based studies suggest that PCOS may originate during fetal development. Prenatal exposure to androgens has been shown to induce a PCOS phenotype in sheep, monkeys, and rats. In humans, retrospective studies have shown that girls with PCOS features and premature menarche had been significantly small for their gestational age, according to Helen Anderson of the division of endocrinology, metabolism, and molecular medicine at Northwestern University, Chicago.

To determine if the intrauterine environment of women with PCOS alters fetal growth and androgen levels, Ms. Anderson and her associates compared singleton pregnancies in 39 women with PCOS and 31 healthy controls. The participants were non-Hispanic white women who met National Institute of Child Health and Human Development criteria for PCOS. None of the participants had a history of gestational diabetes, preexisting medical conditions, or complications during pregnancy.

Compared with healthy controls, a larger percentage of women with PCOS were nulliparous (64% vs. 39%) or had undergone ovulation induction or in vitro fertilization (77% vs. 6%). Women with PCOS were slightly, but significantly, younger than were the healthy control women (30 years vs. 32 years). Although PCOS women had a slightly higher mean body mass index than did controls, they had comparable maternal weight gains.

The birth cohort consisted of more females (43) than males (27) because the investigators were primarily interested in female offspring, and they excluded women known to be carrying a male fetus.

Overall, the gestational age and birth weight of infants did not differ between women with and without PCOS. However, when Ms. Anderson and her colleagues stratified the analysis according to size at gestational age, a significantly greater proportion of the infants born to women with PCOS were large for gestational age compared with healthy controls (23% vs. 3%).

“This may be secondary to the increased nutritional flow across the placenta,” as elevated levels of insulin and glucose have been demonstrated in pregnant women with PCOS, Ms. Anderson said at the annual meeting of the Endocrine Society.

Analyses of the steroid hormones in whole (mixed arterial and venous) cord blood showed that the female offspring of PCOS women had significantly lower levels of androstenedione and estradiol.

However, female offspring had no differences in levels of testosterone, dihydrotestosterone, and dehydroepiandrosterone, although Ms. Anderson said that many of the testosterone and dihydrotestosterone values were at the low end of detectability for the assays.

Female offspring from either group of women showed no differences in levels of 17-hydroxy-progesterone or in the ratio of testosterone to estradiol levels.

The National Institutes of Health funded the study. Ms. Anderson reported having no conflicts of interest to disclose.

The female offspring of PCOS women had significantly lower levels of androstenedione and estradiol.

Source MS. ANDERSON

WASHINGTON — Female infants born to women with polycystic ovary syndrome do not appear to have high levels of androgens or to be small for gestational age, according to the results of a prospective, case-control study.

In fact, offspring born to mothers with polycystic ovary syndrome (PCOS) were more likely than were controls to be large for gestational age, according to the study.

Findings from clinical and animal-based studies suggest that PCOS may originate during fetal development. Prenatal exposure to androgens has been shown to induce a PCOS phenotype in sheep, monkeys, and rats. In humans, retrospective studies have shown that girls with PCOS features and premature menarche had been significantly small for their gestational age, according to Helen Anderson of the division of endocrinology, metabolism, and molecular medicine at Northwestern University, Chicago.

To determine if the intrauterine environment of women with PCOS alters fetal growth and androgen levels, Ms. Anderson and her associates compared singleton pregnancies in 39 women with PCOS and 31 healthy controls. The participants were non-Hispanic white women who met National Institute of Child Health and Human Development criteria for PCOS. None of the participants had a history of gestational diabetes, preexisting medical conditions, or complications during pregnancy.

Compared with healthy controls, a larger percentage of women with PCOS were nulliparous (64% vs. 39%) or had undergone ovulation induction or in vitro fertilization (77% vs. 6%). Women with PCOS were slightly, but significantly, younger than were the healthy control women (30 years vs. 32 years). Although PCOS women had a slightly higher mean body mass index than did controls, they had comparable maternal weight gains.

The birth cohort consisted of more females (43) than males (27) because the investigators were primarily interested in female offspring, and they excluded women known to be carrying a male fetus.

Overall, the gestational age and birth weight of infants did not differ between women with and without PCOS. However, when Ms. Anderson and her colleagues stratified the analysis according to size at gestational age, a significantly greater proportion of the infants born to women with PCOS were large for gestational age compared with healthy controls (23% vs. 3%).

“This may be secondary to the increased nutritional flow across the placenta,” as elevated levels of insulin and glucose have been demonstrated in pregnant women with PCOS, Ms. Anderson said at the annual meeting of the Endocrine Society.

Analyses of the steroid hormones in whole (mixed arterial and venous) cord blood showed that the female offspring of PCOS women had significantly lower levels of androstenedione and estradiol.

However, female offspring had no differences in levels of testosterone, dihydrotestosterone, and dehydroepiandrosterone, although Ms. Anderson said that many of the testosterone and dihydrotestosterone values were at the low end of detectability for the assays.

Female offspring from either group of women showed no differences in levels of 17-hydroxy-progesterone or in the ratio of testosterone to estradiol levels.

The National Institutes of Health funded the study. Ms. Anderson reported having no conflicts of interest to disclose.

The female offspring of PCOS women had significantly lower levels of androstenedione and estradiol.

Source MS. ANDERSON

WASHINGTON — A low level of growth hormone in obese adults is independently associated with increased carotid intima media thickness, which may translate into an elevated risk of cardiovascular disease and a severe metabolic phenotype, according to the results of a prospective, observational study.

Building on evidence gathered from previous studies of growth hormone (GH) levels in obese men and women, Dr. Hideo Makimura and his colleagues in the neuroendocrine unit and program in nutritional metabolism at Massachusetts General Hospital, Boston, analyzed stimulated GH secretion levels and other cardiometabolic risk factors in 102 lean and obese individuals.

“Taken together, these data suggest that strategies to increase growth hormone secretion may improve cardiovascular risk in obesity,” Dr. Makimura said during the presentation of his study at the annual meeting of the Endocrine Society.

Studies including frequent blood sampling of GH have shown 75% less 24-hour GH secretion in obese men, compared with age-matched lean men. Other studies have found that 64% of obese men have a peak stimulated GH level of less than 9 mcg/L in standardized GH-releasing hormone-arginine testing, whereas less than 1% of lean men have such a level.

Reduced GH has been associated with an increase in carotid intima media thickness (cIMT), a measure of atherosclerosis, in 45 overweight and obese women.

Dr. Makimura and his associates followed 33 lean individuals, 55 obese individuals who had sufficient growth hormone, and 14 obese individuals who were deficient in growth hormone (peak stimulation GH level of 4.2 mcg/L or less). The groups had mean ages in the low to mid 40s.

The participants were matched for age, sex, race, tobacco use, and blood pressure. The obese groups also were matched for body mass index and visceral adiposity measured by an abdominal CT scan. None of the participants was known to have hypopituitarism.

Lean individuals had a mean BMI of 22.5 kg/m

In a univariate analysis, peak growth hormone correlated negatively with cIMT. GH-deficient obese participants had a greater mean cIMT than did lean participants, but there was no statistically significant difference in cIMT between the obese groups.

The researchers obtained the same results when they used more liberal cutoffs that defined GH deficiency as peak stimulated GH secretion concentrations of less than 5 mcg/L or less than 9 mcg/L.

Dr. Makimura and his associates found in univariate analyses that peak stimulated GH also was negatively correlated with the amount of visceral adipose tissue, as well as with LDL cholesterol, triglycerides, C-reactive protein, tumor necrosis factor-alpha, and measures of insulin sensitivity. Other univariate analyses revealed positive correlations between peak stimulated GH and both HDL cholesterol and adiponectin.

The association between peak stimulated GH and cIMT remained significant in separate multivariate regression analyses that controlled for demographic factors, traditional cardiovascular disease risk factors (tobacco use, systolic blood pressure, and levels of cholesterol and fasting blood glucose), metabolic variables (visceral adipose tissue, BMI, HDL and LDL cholesterol, triglycerides, fasting glucose, and fasting insulin), or inflammatory markers (C-reactive protein, adiponectin, and tumor necrosis factor-alpha).

Dr. Makimura concluded that these GH-related cardiometabolic risk factors may mediate the association between reduced GH secretion in obesity and increased cIMT.

The study was funded by grants from the National Institutes of Health. Dr. Makimura disclosed no relevant conflicts of interest.

WASHINGTON — A low level of growth hormone in obese adults is independently associated with increased carotid intima media thickness, which may translate into an elevated risk of cardiovascular disease and a severe metabolic phenotype, according to the results of a prospective, observational study.

Building on evidence gathered from previous studies of growth hormone (GH) levels in obese men and women, Dr. Hideo Makimura and his colleagues in the neuroendocrine unit and program in nutritional metabolism at Massachusetts General Hospital, Boston, analyzed stimulated GH secretion levels and other cardiometabolic risk factors in 102 lean and obese individuals.

“Taken together, these data suggest that strategies to increase growth hormone secretion may improve cardiovascular risk in obesity,” Dr. Makimura said during the presentation of his study at the annual meeting of the Endocrine Society.

Studies including frequent blood sampling of GH have shown 75% less 24-hour GH secretion in obese men, compared with age-matched lean men. Other studies have found that 64% of obese men have a peak stimulated GH level of less than 9 mcg/L in standardized GH-releasing hormone-arginine testing, whereas less than 1% of lean men have such a level.

Reduced GH has been associated with an increase in carotid intima media thickness (cIMT), a measure of atherosclerosis, in 45 overweight and obese women.

Dr. Makimura and his associates followed 33 lean individuals, 55 obese individuals who had sufficient growth hormone, and 14 obese individuals who were deficient in growth hormone (peak stimulation GH level of 4.2 mcg/L or less). The groups had mean ages in the low to mid 40s.

The participants were matched for age, sex, race, tobacco use, and blood pressure. The obese groups also were matched for body mass index and visceral adiposity measured by an abdominal CT scan. None of the participants was known to have hypopituitarism.

Lean individuals had a mean BMI of 22.5 kg/m

In a univariate analysis, peak growth hormone correlated negatively with cIMT. GH-deficient obese participants had a greater mean cIMT than did lean participants, but there was no statistically significant difference in cIMT between the obese groups.

The researchers obtained the same results when they used more liberal cutoffs that defined GH deficiency as peak stimulated GH secretion concentrations of less than 5 mcg/L or less than 9 mcg/L.

Dr. Makimura and his associates found in univariate analyses that peak stimulated GH also was negatively correlated with the amount of visceral adipose tissue, as well as with LDL cholesterol, triglycerides, C-reactive protein, tumor necrosis factor-alpha, and measures of insulin sensitivity. Other univariate analyses revealed positive correlations between peak stimulated GH and both HDL cholesterol and adiponectin.

The association between peak stimulated GH and cIMT remained significant in separate multivariate regression analyses that controlled for demographic factors, traditional cardiovascular disease risk factors (tobacco use, systolic blood pressure, and levels of cholesterol and fasting blood glucose), metabolic variables (visceral adipose tissue, BMI, HDL and LDL cholesterol, triglycerides, fasting glucose, and fasting insulin), or inflammatory markers (C-reactive protein, adiponectin, and tumor necrosis factor-alpha).

Dr. Makimura concluded that these GH-related cardiometabolic risk factors may mediate the association between reduced GH secretion in obesity and increased cIMT.

The study was funded by grants from the National Institutes of Health. Dr. Makimura disclosed no relevant conflicts of interest.

WASHINGTON — A low level of growth hormone in obese adults is independently associated with increased carotid intima media thickness, which may translate into an elevated risk of cardiovascular disease and a severe metabolic phenotype, according to the results of a prospective, observational study.

Building on evidence gathered from previous studies of growth hormone (GH) levels in obese men and women, Dr. Hideo Makimura and his colleagues in the neuroendocrine unit and program in nutritional metabolism at Massachusetts General Hospital, Boston, analyzed stimulated GH secretion levels and other cardiometabolic risk factors in 102 lean and obese individuals.

“Taken together, these data suggest that strategies to increase growth hormone secretion may improve cardiovascular risk in obesity,” Dr. Makimura said during the presentation of his study at the annual meeting of the Endocrine Society.

Studies including frequent blood sampling of GH have shown 75% less 24-hour GH secretion in obese men, compared with age-matched lean men. Other studies have found that 64% of obese men have a peak stimulated GH level of less than 9 mcg/L in standardized GH-releasing hormone-arginine testing, whereas less than 1% of lean men have such a level.

Reduced GH has been associated with an increase in carotid intima media thickness (cIMT), a measure of atherosclerosis, in 45 overweight and obese women.

Dr. Makimura and his associates followed 33 lean individuals, 55 obese individuals who had sufficient growth hormone, and 14 obese individuals who were deficient in growth hormone (peak stimulation GH level of 4.2 mcg/L or less). The groups had mean ages in the low to mid 40s.

The participants were matched for age, sex, race, tobacco use, and blood pressure. The obese groups also were matched for body mass index and visceral adiposity measured by an abdominal CT scan. None of the participants was known to have hypopituitarism.

Lean individuals had a mean BMI of 22.5 kg/m

In a univariate analysis, peak growth hormone correlated negatively with cIMT. GH-deficient obese participants had a greater mean cIMT than did lean participants, but there was no statistically significant difference in cIMT between the obese groups.

The researchers obtained the same results when they used more liberal cutoffs that defined GH deficiency as peak stimulated GH secretion concentrations of less than 5 mcg/L or less than 9 mcg/L.

Dr. Makimura and his associates found in univariate analyses that peak stimulated GH also was negatively correlated with the amount of visceral adipose tissue, as well as with LDL cholesterol, triglycerides, C-reactive protein, tumor necrosis factor-alpha, and measures of insulin sensitivity. Other univariate analyses revealed positive correlations between peak stimulated GH and both HDL cholesterol and adiponectin.

The association between peak stimulated GH and cIMT remained significant in separate multivariate regression analyses that controlled for demographic factors, traditional cardiovascular disease risk factors (tobacco use, systolic blood pressure, and levels of cholesterol and fasting blood glucose), metabolic variables (visceral adipose tissue, BMI, HDL and LDL cholesterol, triglycerides, fasting glucose, and fasting insulin), or inflammatory markers (C-reactive protein, adiponectin, and tumor necrosis factor-alpha).

Dr. Makimura concluded that these GH-related cardiometabolic risk factors may mediate the association between reduced GH secretion in obesity and increased cIMT.

The study was funded by grants from the National Institutes of Health. Dr. Makimura disclosed no relevant conflicts of interest.

WASHINGTON — Adult bariatric surgery patients need to be monitored in the long-term postoperative period for nutritional deficiencies, risks to bone and joint health, and changes in obesity-related comorbidities, according to a draft of new guidelines from the Endocrine Society.

The guidelines will focus primarily on long-term patient management, because immediate postoperative care is largely the purview of the surgeons who performed the operation, Dr. Lee M. Kaplan, a member of the seven-person task force that is writing the guidelines, said at the society's annual meeting.

Each bariatric procedure is unique in its potential nutritional complications and endocrinologic effects, so it is important to take their differential mechanisms and effects into consideration, said Dr. Kaplan, a gastroenterologist and director of the Massachusetts General Hospital Weight Center, Boston.

The American Society of Nutrition and the European Society for Endocrinology supported the formulation of the guidelines. The American Gastroenterological Association has been invited to participate.

Virtually all of the advice is based on expert opinion because there is little high-level evidence, Dr. Kaplan said.

The guidelines advise clinicians to provide appropriate long-term dietary and behavioral management and to assess whether additional surgeries would provide greater long-term benefits, such as converting a laparoscopic adjustable gastric band to a Roux-en-Y gastric bypass (RYGB), changing the length of an intestinal limb after RYGB, or adding a RYGB onto a sleeve gastrectomy.

The task force did not make specific recommendations for nutritional screening or supplement use, but advised that patients should eat 60-120 grams of protein per day to prevent the loss of lean body mass.

The draft guidelines advise long-term vitamin and mineral supplementation as needed, depending on the procedure, and periodic monitoring for micronutrient deficiencies in the first 2-3 weeks after surgery and for macronutrient deficiencies in the first several months.

Monitoring for signs of macronutrient deficiencies, such as hypoalbuminemia (which is associated with protein malnutrition) and ketosis, is important for patients who have undergone biliopancreatic diversion plus duodenal switch (BPD-DS), according to the guidelines.

But micronutrient deficiencies are far more common than macronutrient deficiencies in bariatric surgery patients, Dr. Kaplan said. Deficiencies in iron, vitamin B₁₂, calcium, and vitamin D occur most often with BPD-DS and RYGB. A deficiency in vitamin B₁ (thiamine) can be induced through excessive vomiting, which occurs most often with overadjusted gastric bands. Fat-soluble vitamin deficiencies develop most often with BPD-DS, but vitamin K deficiency is known to develop in some patients with RYGB. Folic acid deficiencies are not as common as they used to be after bariatric surgery because of wide use of multivitamins with folic acid.

The task force advised that the physician and nurse members of the patient's management team should be familiar with the management of type 1 and 2 diabetes in the postoperative period. They also recommended that lipid abnormalities should be treated according to National Cholesterol Education Program guidelines.

In addition to weight loss, clinicians should shoot for reductions in hemoglobin A_1c to less than 7%, fasting blood glucose to 110 mg/dL or less, and postprandial blood glucose to 180 mg/dL or less.

Patients undergoing bypass operations should have calcium, phosphorus, and alkaline phosphatase levels measured every 6 months and dual-energy x-ray absorptiometry scans annually, as well as routine postoperative calcium and vitamin D supplementation.

For patients with frequent preoperative episodes of gout, the task force recommended prophylactic therapy because of an increased risk for disease flares in the postoperative period.

Postoperative constipation occurs much more often than does diarrhea in bariatric surgery patients, Dr. Kaplan said, so the guidelines recommend a low-quantity fluid diet in the immediate postoperative period with a gradual progression of food consistency over time.

The guidelines also advise periodic monitoring of liver enzymes. Postoperative hypoglycemia, which may occur through stimulation of pancreatic beta-cell function, needs to be carefully monitored as well.

Dr. Kaplan serves as the principal investigator for studies with Merck & Co., Johnson & Johnson, and GI Dynamics; as an advisory group member for Merck & Co., Johnson & Johnson, Stryker Development, and C.R. Bard; and as a scientific board member for Gelesis and GI Dynamics.

WASHINGTON — Adult bariatric surgery patients need to be monitored in the long-term postoperative period for nutritional deficiencies, risks to bone and joint health, and changes in obesity-related comorbidities, according to a draft of new guidelines from the Endocrine Society.

The guidelines will focus primarily on long-term patient management, because immediate postoperative care is largely the purview of the surgeons who performed the operation, Dr. Lee M. Kaplan, a member of the seven-person task force that is writing the guidelines, said at the society's annual meeting.

Each bariatric procedure is unique in its potential nutritional complications and endocrinologic effects, so it is important to take their differential mechanisms and effects into consideration, said Dr. Kaplan, a gastroenterologist and director of the Massachusetts General Hospital Weight Center, Boston.

The American Society of Nutrition and the European Society for Endocrinology supported the formulation of the guidelines. The American Gastroenterological Association has been invited to participate.

Virtually all of the advice is based on expert opinion because there is little high-level evidence, Dr. Kaplan said.

The guidelines advise clinicians to provide appropriate long-term dietary and behavioral management and to assess whether additional surgeries would provide greater long-term benefits, such as converting a laparoscopic adjustable gastric band to a Roux-en-Y gastric bypass (RYGB), changing the length of an intestinal limb after RYGB, or adding a RYGB onto a sleeve gastrectomy.

The task force did not make specific recommendations for nutritional screening or supplement use, but advised that patients should eat 60-120 grams of protein per day to prevent the loss of lean body mass.

The draft guidelines advise long-term vitamin and mineral supplementation as needed, depending on the procedure, and periodic monitoring for micronutrient deficiencies in the first 2-3 weeks after surgery and for macronutrient deficiencies in the first several months.

Monitoring for signs of macronutrient deficiencies, such as hypoalbuminemia (which is associated with protein malnutrition) and ketosis, is important for patients who have undergone biliopancreatic diversion plus duodenal switch (BPD-DS), according to the guidelines.

But micronutrient deficiencies are far more common than macronutrient deficiencies in bariatric surgery patients, Dr. Kaplan said. Deficiencies in iron, vitamin B₁₂, calcium, and vitamin D occur most often with BPD-DS and RYGB. A deficiency in vitamin B₁ (thiamine) can be induced through excessive vomiting, which occurs most often with overadjusted gastric bands. Fat-soluble vitamin deficiencies develop most often with BPD-DS, but vitamin K deficiency is known to develop in some patients with RYGB. Folic acid deficiencies are not as common as they used to be after bariatric surgery because of wide use of multivitamins with folic acid.

The task force advised that the physician and nurse members of the patient's management team should be familiar with the management of type 1 and 2 diabetes in the postoperative period. They also recommended that lipid abnormalities should be treated according to National Cholesterol Education Program guidelines.

In addition to weight loss, clinicians should shoot for reductions in hemoglobin A_1c to less than 7%, fasting blood glucose to 110 mg/dL or less, and postprandial blood glucose to 180 mg/dL or less.

Patients undergoing bypass operations should have calcium, phosphorus, and alkaline phosphatase levels measured every 6 months and dual-energy x-ray absorptiometry scans annually, as well as routine postoperative calcium and vitamin D supplementation.

For patients with frequent preoperative episodes of gout, the task force recommended prophylactic therapy because of an increased risk for disease flares in the postoperative period.

Postoperative constipation occurs much more often than does diarrhea in bariatric surgery patients, Dr. Kaplan said, so the guidelines recommend a low-quantity fluid diet in the immediate postoperative period with a gradual progression of food consistency over time.

The guidelines also advise periodic monitoring of liver enzymes. Postoperative hypoglycemia, which may occur through stimulation of pancreatic beta-cell function, needs to be carefully monitored as well.

Dr. Kaplan serves as the principal investigator for studies with Merck & Co., Johnson & Johnson, and GI Dynamics; as an advisory group member for Merck & Co., Johnson & Johnson, Stryker Development, and C.R. Bard; and as a scientific board member for Gelesis and GI Dynamics.

WASHINGTON — Adult bariatric surgery patients need to be monitored in the long-term postoperative period for nutritional deficiencies, risks to bone and joint health, and changes in obesity-related comorbidities, according to a draft of new guidelines from the Endocrine Society.

The guidelines will focus primarily on long-term patient management, because immediate postoperative care is largely the purview of the surgeons who performed the operation, Dr. Lee M. Kaplan, a member of the seven-person task force that is writing the guidelines, said at the society's annual meeting.

Each bariatric procedure is unique in its potential nutritional complications and endocrinologic effects, so it is important to take their differential mechanisms and effects into consideration, said Dr. Kaplan, a gastroenterologist and director of the Massachusetts General Hospital Weight Center, Boston.

The American Society of Nutrition and the European Society for Endocrinology supported the formulation of the guidelines. The American Gastroenterological Association has been invited to participate.

Virtually all of the advice is based on expert opinion because there is little high-level evidence, Dr. Kaplan said.

The guidelines advise clinicians to provide appropriate long-term dietary and behavioral management and to assess whether additional surgeries would provide greater long-term benefits, such as converting a laparoscopic adjustable gastric band to a Roux-en-Y gastric bypass (RYGB), changing the length of an intestinal limb after RYGB, or adding a RYGB onto a sleeve gastrectomy.

The task force did not make specific recommendations for nutritional screening or supplement use, but advised that patients should eat 60-120 grams of protein per day to prevent the loss of lean body mass.

The draft guidelines advise long-term vitamin and mineral supplementation as needed, depending on the procedure, and periodic monitoring for micronutrient deficiencies in the first 2-3 weeks after surgery and for macronutrient deficiencies in the first several months.

Monitoring for signs of macronutrient deficiencies, such as hypoalbuminemia (which is associated with protein malnutrition) and ketosis, is important for patients who have undergone biliopancreatic diversion plus duodenal switch (BPD-DS), according to the guidelines.

But micronutrient deficiencies are far more common than macronutrient deficiencies in bariatric surgery patients, Dr. Kaplan said. Deficiencies in iron, vitamin B₁₂, calcium, and vitamin D occur most often with BPD-DS and RYGB. A deficiency in vitamin B₁ (thiamine) can be induced through excessive vomiting, which occurs most often with overadjusted gastric bands. Fat-soluble vitamin deficiencies develop most often with BPD-DS, but vitamin K deficiency is known to develop in some patients with RYGB. Folic acid deficiencies are not as common as they used to be after bariatric surgery because of wide use of multivitamins with folic acid.

The task force advised that the physician and nurse members of the patient's management team should be familiar with the management of type 1 and 2 diabetes in the postoperative period. They also recommended that lipid abnormalities should be treated according to National Cholesterol Education Program guidelines.

In addition to weight loss, clinicians should shoot for reductions in hemoglobin A_1c to less than 7%, fasting blood glucose to 110 mg/dL or less, and postprandial blood glucose to 180 mg/dL or less.

Patients undergoing bypass operations should have calcium, phosphorus, and alkaline phosphatase levels measured every 6 months and dual-energy x-ray absorptiometry scans annually, as well as routine postoperative calcium and vitamin D supplementation.

For patients with frequent preoperative episodes of gout, the task force recommended prophylactic therapy because of an increased risk for disease flares in the postoperative period.

Postoperative constipation occurs much more often than does diarrhea in bariatric surgery patients, Dr. Kaplan said, so the guidelines recommend a low-quantity fluid diet in the immediate postoperative period with a gradual progression of food consistency over time.

The guidelines also advise periodic monitoring of liver enzymes. Postoperative hypoglycemia, which may occur through stimulation of pancreatic beta-cell function, needs to be carefully monitored as well.

Dr. Kaplan serves as the principal investigator for studies with Merck & Co., Johnson & Johnson, and GI Dynamics; as an advisory group member for Merck & Co., Johnson & Johnson, Stryker Development, and C.R. Bard; and as a scientific board member for Gelesis and GI Dynamics.

WASHINGTON — Adult bariatric surgery patients need to be monitored in the long-term postoperative period for nutritional deficiencies, risks to bone and joint health, and changes in obesity-related comorbidities, according to a draft of new guidelines from the Endocrine Society.

The guidelines will focus primarily on long-term patient management, because immediate postoperative care is largely the purview of the surgeons who performed the operation, Dr. Lee M. Kaplan, a member of the seven-person task force that is writing the guidelines, said at the society's annual meeting.

Each bariatric procedure is unique in its potential nutritional complications and endocrinologic effects, so it is important to take their differential mechanisms and effects into consideration, said Dr. Kaplan, a gastroenterologist and director of the Massachusetts General Hospital Weight Center, Boston.

The American Society of Nutrition and the European Society for Endocrinology supported the formulation of the guidelines. The American Gastroenterological Association has been invited to participate.

Virtually all of the recommendations are based on expert opinion because of a lack of high-level evidence, Dr. Kaplan said.

The guidelines advise clinicians to provide appropriate long-term dietary and behavioral management and to assess whether additional surgeries would provide greater long-term benefits, such as converting a laparoscopic adjustable gastric band to a Roux-en-Y gastric bypass (RYGB), changing the length of an intestinal limb after RYGB, or adding a RYGB onto a sleeve gastrectomy.

The task force did not make specific recommendations for nutritional screening or supplement use, but advised that patients should eat 60-120 g of protein per day to prevent the loss of lean body mass. “That's particularly important for the nonbypass operations, which work in part by food restriction, and are associated with a greater lean body mass loss than the gastric bypass,” he said.

The draft guidelines recommend long-term vitamin and mineral supplementation as needed, depending on the surgical procedure, and periodic monitoring for micronutrient deficiencies in the first 2-3 weeks after surgery and for macronutrient deficiencies in the first several months.

Monitoring for signs of macronutrient deficiencies, such as hypoalbuminemia (which is associated with protein malnutrition) and ketosis, is especially important for patients who have undergone biliopancreatic diversion plus duodenal switch (BPD-DS), according to the guidelines.

But micronutrient deficiencies are far more common than macronutrient deficiencies in bariatric surgery patients, Dr. Kaplan said. Deficiencies in iron, vitamin B₁₂, calcium, and vitamin D occur most often with BPD-DS and RYGB. A deficiency in vitamin B₁ (thiamine) can be induced through excessive vomiting, which occurs most often with overadjusted gastric bands. Fat-soluble vitamin deficiencies develop most often with BPD-DS, but vitamin K deficiency is known to develop in some patients with RYGB. Folic acid deficiencies are not as common as they used to be after bariatric surgery because of wide use of multivitamins with folic acid. Deficiencies in minerals such as selenium, zinc, and copper are fairly rare, he said.

The task force advised that the physician and nurse members of the patient's management team should be familiar with the management of type 1 and 2 diabetes in the postoperative period. They also recommended that lipid abnormalities should be treated according to National Cholesterol Education Program guidelines.

In addition to weight loss, clinicians should shoot for reductions in hemoglobin A_1c to less than 7%, fasting blood glucose to 110 mg/dL or less, and postprandial blood glucose to 180 mg/dL or less.

Dr. Kaplan noted that a study reported at the meeting found that bariatric surgery increased the risk for fractures, but it is unclear how the risk may differ between the various types of bariatric procedures.

“This is an area where we're going to have substantial additions to the final guidelines,” Dr. Kaplan said.

Patients undergoing bypass operations should have calcium, phosphorus, and alkaline phosphatase levels measured every 6 months and dual energy x-ray absorptiometry scans annually.

The task force also suggested routine postoperative calcium and vitamin D supplementation.

For patients with frequent preoperative episodes of gout, the task force recommended prophylactic therapy because of an increased risk for disease flares in the postoperative period.

Postoperative constipation occurs much more often than does diarrhea in bariatric surgery patients, Dr. Kaplan said, so the guidelines recommend a low-quantity fluid diet in the immediate postoperative period with a gradual progression of food consistency over time.

The guidelines also advise periodic monitoring of liver enzymes because some patients have increases in liver enzyme levels despite the improvement of fatty liver disease in most patients. Postoperative hypoglycemia, which may occur through stimulation of pancreatic beta-cell function, needs to be carefully monitored as well.

The panelists did not reach a consensus on the relative importance of factors that contribute to weight regain, including physiologic factors, surgical failure (breakdown of anastomoses or suture lines or device failure), and noncompliance.

One audience member noted that the draft guidelines lack any mention of kidney stones, which are common in gastric bypass patients, and should be monitored with urine oxalate levels. Other audience members called for sections in the guidelines on dosing medications in bariatric surgery patients, such as GLP-1 medications and thyroxine in patients with hypothyroidism.

Dr. Kaplan serves as the principal investigator for studies with Merck & Co., Johnson & Johnson, and GI Dynamics; as an advisory group member for Merck & Co., Johnson & Johnson, Stryker Development, and C.R. Bard; and as a scientific board member for Gelesis and GI Dynamics.

WASHINGTON — Adult bariatric surgery patients need to be monitored in the long-term postoperative period for nutritional deficiencies, risks to bone and joint health, and changes in obesity-related comorbidities, according to a draft of new guidelines from the Endocrine Society.

The guidelines will focus primarily on long-term patient management, because immediate postoperative care is largely the purview of the surgeons who performed the operation, Dr. Lee M. Kaplan, a member of the seven-person task force that is writing the guidelines, said at the society's annual meeting.

Each bariatric procedure is unique in its potential nutritional complications and endocrinologic effects, so it is important to take their differential mechanisms and effects into consideration, said Dr. Kaplan, a gastroenterologist and director of the Massachusetts General Hospital Weight Center, Boston.

The American Society of Nutrition and the European Society for Endocrinology supported the formulation of the guidelines. The American Gastroenterological Association has been invited to participate.

Virtually all of the recommendations are based on expert opinion because of a lack of high-level evidence, Dr. Kaplan said.

The guidelines advise clinicians to provide appropriate long-term dietary and behavioral management and to assess whether additional surgeries would provide greater long-term benefits, such as converting a laparoscopic adjustable gastric band to a Roux-en-Y gastric bypass (RYGB), changing the length of an intestinal limb after RYGB, or adding a RYGB onto a sleeve gastrectomy.

The task force did not make specific recommendations for nutritional screening or supplement use, but advised that patients should eat 60-120 g of protein per day to prevent the loss of lean body mass. “That's particularly important for the nonbypass operations, which work in part by food restriction, and are associated with a greater lean body mass loss than the gastric bypass,” he said.

The draft guidelines recommend long-term vitamin and mineral supplementation as needed, depending on the surgical procedure, and periodic monitoring for micronutrient deficiencies in the first 2-3 weeks after surgery and for macronutrient deficiencies in the first several months.

Monitoring for signs of macronutrient deficiencies, such as hypoalbuminemia (which is associated with protein malnutrition) and ketosis, is especially important for patients who have undergone biliopancreatic diversion plus duodenal switch (BPD-DS), according to the guidelines.

But micronutrient deficiencies are far more common than macronutrient deficiencies in bariatric surgery patients, Dr. Kaplan said. Deficiencies in iron, vitamin B₁₂, calcium, and vitamin D occur most often with BPD-DS and RYGB. A deficiency in vitamin B₁ (thiamine) can be induced through excessive vomiting, which occurs most often with overadjusted gastric bands. Fat-soluble vitamin deficiencies develop most often with BPD-DS, but vitamin K deficiency is known to develop in some patients with RYGB. Folic acid deficiencies are not as common as they used to be after bariatric surgery because of wide use of multivitamins with folic acid. Deficiencies in minerals such as selenium, zinc, and copper are fairly rare, he said.

The task force advised that the physician and nurse members of the patient's management team should be familiar with the management of type 1 and 2 diabetes in the postoperative period. They also recommended that lipid abnormalities should be treated according to National Cholesterol Education Program guidelines.

In addition to weight loss, clinicians should shoot for reductions in hemoglobin A_1c to less than 7%, fasting blood glucose to 110 mg/dL or less, and postprandial blood glucose to 180 mg/dL or less.

Dr. Kaplan noted that a study reported at the meeting found that bariatric surgery increased the risk for fractures, but it is unclear how the risk may differ between the various types of bariatric procedures.

“This is an area where we're going to have substantial additions to the final guidelines,” Dr. Kaplan said.

Patients undergoing bypass operations should have calcium, phosphorus, and alkaline phosphatase levels measured every 6 months and dual energy x-ray absorptiometry scans annually.

The task force also suggested routine postoperative calcium and vitamin D supplementation.

For patients with frequent preoperative episodes of gout, the task force recommended prophylactic therapy because of an increased risk for disease flares in the postoperative period.

Postoperative constipation occurs much more often than does diarrhea in bariatric surgery patients, Dr. Kaplan said, so the guidelines recommend a low-quantity fluid diet in the immediate postoperative period with a gradual progression of food consistency over time.

The guidelines also advise periodic monitoring of liver enzymes because some patients have increases in liver enzyme levels despite the improvement of fatty liver disease in most patients. Postoperative hypoglycemia, which may occur through stimulation of pancreatic beta-cell function, needs to be carefully monitored as well.

The panelists did not reach a consensus on the relative importance of factors that contribute to weight regain, including physiologic factors, surgical failure (breakdown of anastomoses or suture lines or device failure), and noncompliance.

One audience member noted that the draft guidelines lack any mention of kidney stones, which are common in gastric bypass patients, and should be monitored with urine oxalate levels. Other audience members called for sections in the guidelines on dosing medications in bariatric surgery patients, such as GLP-1 medications and thyroxine in patients with hypothyroidism.

Dr. Kaplan serves as the principal investigator for studies with Merck & Co., Johnson & Johnson, and GI Dynamics; as an advisory group member for Merck & Co., Johnson & Johnson, Stryker Development, and C.R. Bard; and as a scientific board member for Gelesis and GI Dynamics.

WASHINGTON — Adult bariatric surgery patients need to be monitored in the long-term postoperative period for nutritional deficiencies, risks to bone and joint health, and changes in obesity-related comorbidities, according to a draft of new guidelines from the Endocrine Society.

The guidelines will focus primarily on long-term patient management, because immediate postoperative care is largely the purview of the surgeons who performed the operation, Dr. Lee M. Kaplan, a member of the seven-person task force that is writing the guidelines, said at the society's annual meeting.

Each bariatric procedure is unique in its potential nutritional complications and endocrinologic effects, so it is important to take their differential mechanisms and effects into consideration, said Dr. Kaplan, a gastroenterologist and director of the Massachusetts General Hospital Weight Center, Boston.

The American Society of Nutrition and the European Society for Endocrinology supported the formulation of the guidelines. The American Gastroenterological Association has been invited to participate.

Virtually all of the recommendations are based on expert opinion because of a lack of high-level evidence, Dr. Kaplan said.

The guidelines advise clinicians to provide appropriate long-term dietary and behavioral management and to assess whether additional surgeries would provide greater long-term benefits, such as converting a laparoscopic adjustable gastric band to a Roux-en-Y gastric bypass (RYGB), changing the length of an intestinal limb after RYGB, or adding a RYGB onto a sleeve gastrectomy.

The task force did not make specific recommendations for nutritional screening or supplement use, but advised that patients should eat 60-120 g of protein per day to prevent the loss of lean body mass. “That's particularly important for the nonbypass operations, which work in part by food restriction, and are associated with a greater lean body mass loss than the gastric bypass,” he said.

The draft guidelines recommend long-term vitamin and mineral supplementation as needed, depending on the surgical procedure, and periodic monitoring for micronutrient deficiencies in the first 2-3 weeks after surgery and for macronutrient deficiencies in the first several months.

Monitoring for signs of macronutrient deficiencies, such as hypoalbuminemia (which is associated with protein malnutrition) and ketosis, is especially important for patients who have undergone biliopancreatic diversion plus duodenal switch (BPD-DS), according to the guidelines.

But micronutrient deficiencies are far more common than macronutrient deficiencies in bariatric surgery patients, Dr. Kaplan said. Deficiencies in iron, vitamin B₁₂, calcium, and vitamin D occur most often with BPD-DS and RYGB. A deficiency in vitamin B₁ (thiamine) can be induced through excessive vomiting, which occurs most often with overadjusted gastric bands. Fat-soluble vitamin deficiencies develop most often with BPD-DS, but vitamin K deficiency is known to develop in some patients with RYGB. Folic acid deficiencies are not as common as they used to be after bariatric surgery because of wide use of multivitamins with folic acid. Deficiencies in minerals such as selenium, zinc, and copper are fairly rare, he said.

The task force advised that the physician and nurse members of the patient's management team should be familiar with the management of type 1 and 2 diabetes in the postoperative period. They also recommended that lipid abnormalities should be treated according to National Cholesterol Education Program guidelines.

In addition to weight loss, clinicians should shoot for reductions in hemoglobin A_1c to less than 7%, fasting blood glucose to 110 mg/dL or less, and postprandial blood glucose to 180 mg/dL or less.

Dr. Kaplan noted that a study reported at the meeting found that bariatric surgery increased the risk for fractures, but it is unclear how the risk may differ between the various types of bariatric procedures.

“This is an area where we're going to have substantial additions to the final guidelines,” Dr. Kaplan said.

Patients undergoing bypass operations should have calcium, phosphorus, and alkaline phosphatase levels measured every 6 months and dual energy x-ray absorptiometry scans annually.

The task force also suggested routine postoperative calcium and vitamin D supplementation.

For patients with frequent preoperative episodes of gout, the task force recommended prophylactic therapy because of an increased risk for disease flares in the postoperative period.

Postoperative constipation occurs much more often than does diarrhea in bariatric surgery patients, Dr. Kaplan said, so the guidelines recommend a low-quantity fluid diet in the immediate postoperative period with a gradual progression of food consistency over time.

The guidelines also advise periodic monitoring of liver enzymes because some patients have increases in liver enzyme levels despite the improvement of fatty liver disease in most patients. Postoperative hypoglycemia, which may occur through stimulation of pancreatic beta-cell function, needs to be carefully monitored as well.

The panelists did not reach a consensus on the relative importance of factors that contribute to weight regain, including physiologic factors, surgical failure (breakdown of anastomoses or suture lines or device failure), and noncompliance.

One audience member noted that the draft guidelines lack any mention of kidney stones, which are common in gastric bypass patients, and should be monitored with urine oxalate levels. Other audience members called for sections in the guidelines on dosing medications in bariatric surgery patients, such as GLP-1 medications and thyroxine in patients with hypothyroidism.

Dr. Kaplan serves as the principal investigator for studies with Merck & Co., Johnson & Johnson, and GI Dynamics; as an advisory group member for Merck & Co., Johnson & Johnson, Stryker Development, and C.R. Bard; and as a scientific board member for Gelesis and GI Dynamics.

The risk for developing Parkinson's disease that is associated with pesticide exposure appears to be especially high in people who are professionally exposed to the chemicals and those who carry certain polymorphisms for glutathione S-transferase genes, according to findings from two new case-control studies.

The studies strengthen the already well-documented association between pesticide exposure and Parkinson's disease (PD) by including a more detailed assessment of exposure to the chemicals for analyzing dose-effect relationships, especially for different classes of insecticides, fungicides, and herbicides, as well as examining the role of genetic traits in determining individual susceptibility to PD.

Dr. Alexis Elbaz of the Institut National de la Santé et de la Recherche Médicale, Paris, and his colleagues conducted extensive in-person interviews about professional exposure to pesticides with 247 patients with PD and 676 matching control patients. All of the participants came from the same French health insurance organization for workers in agriculture and related occupations. The patients with PD had been diagnosed a median of 1.5 years before the study (Ann. Neurol. 2009 [doi:10.1002/ana.21717

Dr. Elbaz and his associates found that for men, the odds of developing PD increased with the number of years of professional use of pesticides. This relationship was stronger for men with PD onset after age 65 years than it was for men with younger onset. Women with pesticide exposure also were significantly more likely to develop PD than were those without exposure.

Only insecticide exposure in men was associated with a significantly increased odds of developing PD (odds ratio 2.2). This association followed a dose-effect relationship, which was strongest for older-onset PD patients. In women, only fungicide exposure was associated with significantly increased odds of developing PD (odds ratio 3.5).

In multivariate analyses of men overall and of men with older-onset PD, only organochlorine insecticides remained associated with PD after adjusting for other pesticide families that the men had been exposed to.

The finding that the association between PD and professional pesticide use was stronger for older males is “consistent with the view that genetic susceptibility plays a stronger role in younger-onset cases, while environmental factors play a stronger role for older-onset cases,” the investigators wrote.

This was supported in the study by a similar number of years of pesticide exposure between both older-onset cases (13 years) and in younger-onset cases (12 years) and a higher cumulative lifetime hours of exposure for younger-onset cases (88 hours), compared with older-onset cases (52 hours).

In a separate study, Dr. Ruey-Meei Wu of the department of neurology at National Taiwan University Hospital, Taipei, and her coinvestigators genotyped 125 patients (69 women) with sporadic idiopathic PD and 162 age- and gender-matched control patients (90 women) from a rural area of southern Taiwan for four glutathione S-transferase (GST) genes (GSTM1, GSTP1, GSTT1, and GSTZ1).

Overall, 69 PD patients and 70 control patients were exposed to pesticides used in professional farming or gardening. These patients had been exposed to pesticides for a range of 1 to 50 years, Dr. Wu and her colleagues reported at a poster session of the International Congress of Parkinson's Disease and Movement Disorders in Paris.

GST polymorphisms have been reported to reduce the efficiency of the substrate selectivity or stability of the enzymes. In brain tissue, GSTs function as scavengers that eliminate the formation of intracellular free radicals that are generated from metabolic activity. GSTs have the potential to modify a person's susceptibility to developing PD after pesticide exposure by increasing oxidative stress in the brain, leading to the degeneration of dopaminergic neurons, Dr. Wu said in an interview.

Pesticide exposure was an independent risk factor for PD. Only the GSTP1 Val 105 polymorphism, which occurred in about 20% of the patients, significantly increased the risk for the development of PD. This polymorphism raised the odds of developing PD by a factor of 2.2. The risk for PD was greatest among patients who had been exposed to pesticides for more than 35 years.

Those who carried the GSTP1 Val 105 polymorphism and were exposed to pesticides had even higher risk of developing PD. There was a trend for increasing PD risk that became stronger and more significant in pesticide-exposed patients who carried an additional putative high-risk GST genotype.

None of the investigators in either study had any conflicts of interest to declare.

The risk of Parkinson's disease with professional pesticide exposure may increase with genetic susceptibility and older age. ©LOOK PHOTO/

The risk for developing Parkinson's disease that is associated with pesticide exposure appears to be especially high in people who are professionally exposed to the chemicals and those who carry certain polymorphisms for glutathione S-transferase genes, according to findings from two new case-control studies.

The studies strengthen the already well-documented association between pesticide exposure and Parkinson's disease (PD) by including a more detailed assessment of exposure to the chemicals for analyzing dose-effect relationships, especially for different classes of insecticides, fungicides, and herbicides, as well as examining the role of genetic traits in determining individual susceptibility to PD.

Dr. Alexis Elbaz of the Institut National de la Santé et de la Recherche Médicale, Paris, and his colleagues conducted extensive in-person interviews about professional exposure to pesticides with 247 patients with PD and 676 matching control patients. All of the participants came from the same French health insurance organization for workers in agriculture and related occupations. The patients with PD had been diagnosed a median of 1.5 years before the study (Ann. Neurol. 2009 [doi:10.1002/ana.21717

Dr. Elbaz and his associates found that for men, the odds of developing PD increased with the number of years of professional use of pesticides. This relationship was stronger for men with PD onset after age 65 years than it was for men with younger onset. Women with pesticide exposure also were significantly more likely to develop PD than were those without exposure.

Only insecticide exposure in men was associated with a significantly increased odds of developing PD (odds ratio 2.2). This association followed a dose-effect relationship, which was strongest for older-onset PD patients. In women, only fungicide exposure was associated with significantly increased odds of developing PD (odds ratio 3.5).

In multivariate analyses of men overall and of men with older-onset PD, only organochlorine insecticides remained associated with PD after adjusting for other pesticide families that the men had been exposed to.

The finding that the association between PD and professional pesticide use was stronger for older males is “consistent with the view that genetic susceptibility plays a stronger role in younger-onset cases, while environmental factors play a stronger role for older-onset cases,” the investigators wrote.

This was supported in the study by a similar number of years of pesticide exposure between both older-onset cases (13 years) and in younger-onset cases (12 years) and a higher cumulative lifetime hours of exposure for younger-onset cases (88 hours), compared with older-onset cases (52 hours).

In a separate study, Dr. Ruey-Meei Wu of the department of neurology at National Taiwan University Hospital, Taipei, and her coinvestigators genotyped 125 patients (69 women) with sporadic idiopathic PD and 162 age- and gender-matched control patients (90 women) from a rural area of southern Taiwan for four glutathione S-transferase (GST) genes (GSTM1, GSTP1, GSTT1, and GSTZ1).

Overall, 69 PD patients and 70 control patients were exposed to pesticides used in professional farming or gardening. These patients had been exposed to pesticides for a range of 1 to 50 years, Dr. Wu and her colleagues reported at a poster session of the International Congress of Parkinson's Disease and Movement Disorders in Paris.

GST polymorphisms have been reported to reduce the efficiency of the substrate selectivity or stability of the enzymes. In brain tissue, GSTs function as scavengers that eliminate the formation of intracellular free radicals that are generated from metabolic activity. GSTs have the potential to modify a person's susceptibility to developing PD after pesticide exposure by increasing oxidative stress in the brain, leading to the degeneration of dopaminergic neurons, Dr. Wu said in an interview.

Pesticide exposure was an independent risk factor for PD. Only the GSTP1 Val 105 polymorphism, which occurred in about 20% of the patients, significantly increased the risk for the development of PD. This polymorphism raised the odds of developing PD by a factor of 2.2. The risk for PD was greatest among patients who had been exposed to pesticides for more than 35 years.

Those who carried the GSTP1 Val 105 polymorphism and were exposed to pesticides had even higher risk of developing PD. There was a trend for increasing PD risk that became stronger and more significant in pesticide-exposed patients who carried an additional putative high-risk GST genotype.

None of the investigators in either study had any conflicts of interest to declare.

The risk of Parkinson's disease with professional pesticide exposure may increase with genetic susceptibility and older age. ©LOOK PHOTO/

The risk for developing Parkinson's disease that is associated with pesticide exposure appears to be especially high in people who are professionally exposed to the chemicals and those who carry certain polymorphisms for glutathione S-transferase genes, according to findings from two new case-control studies.

The studies strengthen the already well-documented association between pesticide exposure and Parkinson's disease (PD) by including a more detailed assessment of exposure to the chemicals for analyzing dose-effect relationships, especially for different classes of insecticides, fungicides, and herbicides, as well as examining the role of genetic traits in determining individual susceptibility to PD.

Dr. Alexis Elbaz of the Institut National de la Santé et de la Recherche Médicale, Paris, and his colleagues conducted extensive in-person interviews about professional exposure to pesticides with 247 patients with PD and 676 matching control patients. All of the participants came from the same French health insurance organization for workers in agriculture and related occupations. The patients with PD had been diagnosed a median of 1.5 years before the study (Ann. Neurol. 2009 [doi:10.1002/ana.21717

Dr. Elbaz and his associates found that for men, the odds of developing PD increased with the number of years of professional use of pesticides. This relationship was stronger for men with PD onset after age 65 years than it was for men with younger onset. Women with pesticide exposure also were significantly more likely to develop PD than were those without exposure.

Only insecticide exposure in men was associated with a significantly increased odds of developing PD (odds ratio 2.2). This association followed a dose-effect relationship, which was strongest for older-onset PD patients. In women, only fungicide exposure was associated with significantly increased odds of developing PD (odds ratio 3.5).

In multivariate analyses of men overall and of men with older-onset PD, only organochlorine insecticides remained associated with PD after adjusting for other pesticide families that the men had been exposed to.

The finding that the association between PD and professional pesticide use was stronger for older males is “consistent with the view that genetic susceptibility plays a stronger role in younger-onset cases, while environmental factors play a stronger role for older-onset cases,” the investigators wrote.

This was supported in the study by a similar number of years of pesticide exposure between both older-onset cases (13 years) and in younger-onset cases (12 years) and a higher cumulative lifetime hours of exposure for younger-onset cases (88 hours), compared with older-onset cases (52 hours).

In a separate study, Dr. Ruey-Meei Wu of the department of neurology at National Taiwan University Hospital, Taipei, and her coinvestigators genotyped 125 patients (69 women) with sporadic idiopathic PD and 162 age- and gender-matched control patients (90 women) from a rural area of southern Taiwan for four glutathione S-transferase (GST) genes (GSTM1, GSTP1, GSTT1, and GSTZ1).

Overall, 69 PD patients and 70 control patients were exposed to pesticides used in professional farming or gardening. These patients had been exposed to pesticides for a range of 1 to 50 years, Dr. Wu and her colleagues reported at a poster session of the International Congress of Parkinson's Disease and Movement Disorders in Paris.

GST polymorphisms have been reported to reduce the efficiency of the substrate selectivity or stability of the enzymes. In brain tissue, GSTs function as scavengers that eliminate the formation of intracellular free radicals that are generated from metabolic activity. GSTs have the potential to modify a person's susceptibility to developing PD after pesticide exposure by increasing oxidative stress in the brain, leading to the degeneration of dopaminergic neurons, Dr. Wu said in an interview.

Pesticide exposure was an independent risk factor for PD. Only the GSTP1 Val 105 polymorphism, which occurred in about 20% of the patients, significantly increased the risk for the development of PD. This polymorphism raised the odds of developing PD by a factor of 2.2. The risk for PD was greatest among patients who had been exposed to pesticides for more than 35 years.

Those who carried the GSTP1 Val 105 polymorphism and were exposed to pesticides had even higher risk of developing PD. There was a trend for increasing PD risk that became stronger and more significant in pesticide-exposed patients who carried an additional putative high-risk GST genotype.

None of the investigators in either study had any conflicts of interest to declare.

The risk of Parkinson's disease with professional pesticide exposure may increase with genetic susceptibility and older age. ©LOOK PHOTO/

SEATTLE — Children and adolescents who have an acute demyelinating syndrome or multiple sclerosis may experience lasting impairment in brain growth or cognition, according to two prospective studies.

In one study, Dr. Douglas L. Arnold and his fellow researchers found a slower-than-expected rate of brain growth over 1 year in children with a history of one acute demyelinating event.

In a second study of children and adolescents with multiple sclerosis, Christine Till, Ph.D., and her coinvestigators found total brain volume of T2 lesions on MRI was significantly associated with cognitive impairment, which occurred in about one-third of the subjects.

“These findings are important because they indicate an effect of inflammatory activity on cognitive function,” particularly on tests that depend on integrated neural networks or efficient communication across multiple brain regions, she said.

Dr. Arnold of the Montreal Neurological Institute and Hospital at McGill University, Montreal, and his associates compared brain volume changes over 1 year using T1-weighted MRI scans in 31 children with acute demyelinating syndromes (ADS) and in 31 healthy age- and gender-matched control patients from the National Institutes of Health MRI Study of Normal Brain Development (www.brain-child.org

The rate of brain growth decreased in both groups during the year and tended to level off after 10 years of age. Before 10 years of age, ADS patients did not show atrophy, but instead showed a failure of age-anticipated brain growth. The rate of brain growth was significantly lower in 13 ADS patients younger than 10 years than it was in 12 healthy control patients (0.62%/year vs. 2.26%/year), Dr. Arnold reported at the annual meeting of the American Academy of Neurology.

However, no difference was found in the rate of brain growth after 10 years of age in 18 ADS patients (0.18%/year) and 19 healthy control patients (0.06%/year).

There appears to be a “heightened vulnerability of the more immature CNS to inflammatory brain injury, despite the capacity of younger brains to adapt … [or] respond to injury of certain sorts. This inflammation seems to interrupt some critical developmental processes and result in this failure of age-anticipated growth,” he said.

The researchers are acquiring additional data to find any corresponding neuropsychological changes and to determine whether there is any spatial localization of the changes in brain growth.

Dr. Arnold and some of his coinvestigators reported receiving research support and personal compensation from companies that manufacture drugs for MS.

The study was supported by the Multiple Sclerosis Scientific Research Foundation of Canada and the Canadian Institutes of Health Research.

In the second study, Dr. Till and her colleagues looked for signs of cognitive impairment in 32 children who presented to the pediatric MS clinic at the Hospital for Sick Children, Toronto, during 2007-2008.

Prior studies in children have shown reductions in processing speed, memory, attention, and executive function, which generally occur with greater severity at a younger age of onset and with longer disease duration.

But the “association between cognitive impairment and MRI lesion load has not been investigated in children with MS,” said Dr. Till, of the department of psychology at York University, Toronto.

Of the 32 patients, 3 were excluded from the analysis because of excessive head motion during the MRI scans, and 1 patient was excluded because of a change in diagnosis. The remaining 28 patients (22 females) were a mean of 16 years old and had a mean disease duration of 4.5 years with a relapsing-remitting course. Their median Expanded Disability Status Scale Score was 1 and 23 (82%) of them were receiving disease-modifying treatment during the study.

Of the 28 children, 10 (36%) had cognitive impairment, which Dr. Till and her associates defined as scores more than 1.5 standard deviations below the mean for their age on at least 3 of the 17 different tests in the battery. Attention and processing speed were the most commonly impaired measurements. More than 20% of the children had impaired visuomotor integration on a test that required them to copy designs of increasing complexity as well as a test that assessed cognitive flexibility and working memory.

The cognitively impaired children were younger at disease onset than were cognitively normal children (9.7 years vs. 12.5 years). Children who were cognitively impaired also had experienced a longer disease duration than did those who were cognitively normal (6.1 years vs. 3.7 years). However, the differences in both comparisons did not reach statistical significance (P = .07).

Total brain T2 lesion volume was most strongly correlated with attention, processing speed, and a global cognitive composite score. But total brain T1 lesion volume did not correlate with any of the neuropsychological testing outcomes.

In multiple linear regression models, age at disease onset was the main significant predictor of verbal intelligence and processing speed, accounting for 23%-37% of the total variation in the two. The addition of total brain lesion volume to these models accounted for another 4%-11% of the total variation.

The total brain T2 lesion volume was the main significant predictor of the global cognitive composite score as well as scores on the sustained visual attention test, after controlling for covariates.

Dr. Till said she had no conflict of interest to disclose. Two of her research collaborators disclosed receiving compensation for speaking for manufacturers of drugs for MS.

SEATTLE — Children and adolescents who have an acute demyelinating syndrome or multiple sclerosis may experience lasting impairment in brain growth or cognition, according to two prospective studies.

In one study, Dr. Douglas L. Arnold and his fellow researchers found a slower-than-expected rate of brain growth over 1 year in children with a history of one acute demyelinating event.

In a second study of children and adolescents with multiple sclerosis, Christine Till, Ph.D., and her coinvestigators found total brain volume of T2 lesions on MRI was significantly associated with cognitive impairment, which occurred in about one-third of the subjects.

“These findings are important because they indicate an effect of inflammatory activity on cognitive function,” particularly on tests that depend on integrated neural networks or efficient communication across multiple brain regions, she said.

Dr. Arnold of the Montreal Neurological Institute and Hospital at McGill University, Montreal, and his associates compared brain volume changes over 1 year using T1-weighted MRI scans in 31 children with acute demyelinating syndromes (ADS) and in 31 healthy age- and gender-matched control patients from the National Institutes of Health MRI Study of Normal Brain Development (www.brain-child.org

The rate of brain growth decreased in both groups during the year and tended to level off after 10 years of age. Before 10 years of age, ADS patients did not show atrophy, but instead showed a failure of age-anticipated brain growth. The rate of brain growth was significantly lower in 13 ADS patients younger than 10 years than it was in 12 healthy control patients (0.62%/year vs. 2.26%/year), Dr. Arnold reported at the annual meeting of the American Academy of Neurology.

However, no difference was found in the rate of brain growth after 10 years of age in 18 ADS patients (0.18%/year) and 19 healthy control patients (0.06%/year).

There appears to be a “heightened vulnerability of the more immature CNS to inflammatory brain injury, despite the capacity of younger brains to adapt … [or] respond to injury of certain sorts. This inflammation seems to interrupt some critical developmental processes and result in this failure of age-anticipated growth,” he said.

The researchers are acquiring additional data to find any corresponding neuropsychological changes and to determine whether there is any spatial localization of the changes in brain growth.

Dr. Arnold and some of his coinvestigators reported receiving research support and personal compensation from companies that manufacture drugs for MS.

The study was supported by the Multiple Sclerosis Scientific Research Foundation of Canada and the Canadian Institutes of Health Research.

In the second study, Dr. Till and her colleagues looked for signs of cognitive impairment in 32 children who presented to the pediatric MS clinic at the Hospital for Sick Children, Toronto, during 2007-2008.

Prior studies in children have shown reductions in processing speed, memory, attention, and executive function, which generally occur with greater severity at a younger age of onset and with longer disease duration.

But the “association between cognitive impairment and MRI lesion load has not been investigated in children with MS,” said Dr. Till, of the department of psychology at York University, Toronto.

Of the 32 patients, 3 were excluded from the analysis because of excessive head motion during the MRI scans, and 1 patient was excluded because of a change in diagnosis. The remaining 28 patients (22 females) were a mean of 16 years old and had a mean disease duration of 4.5 years with a relapsing-remitting course. Their median Expanded Disability Status Scale Score was 1 and 23 (82%) of them were receiving disease-modifying treatment during the study.

Of the 28 children, 10 (36%) had cognitive impairment, which Dr. Till and her associates defined as scores more than 1.5 standard deviations below the mean for their age on at least 3 of the 17 different tests in the battery. Attention and processing speed were the most commonly impaired measurements. More than 20% of the children had impaired visuomotor integration on a test that required them to copy designs of increasing complexity as well as a test that assessed cognitive flexibility and working memory.

The cognitively impaired children were younger at disease onset than were cognitively normal children (9.7 years vs. 12.5 years). Children who were cognitively impaired also had experienced a longer disease duration than did those who were cognitively normal (6.1 years vs. 3.7 years). However, the differences in both comparisons did not reach statistical significance (P = .07).

Total brain T2 lesion volume was most strongly correlated with attention, processing speed, and a global cognitive composite score. But total brain T1 lesion volume did not correlate with any of the neuropsychological testing outcomes.

In multiple linear regression models, age at disease onset was the main significant predictor of verbal intelligence and processing speed, accounting for 23%-37% of the total variation in the two. The addition of total brain lesion volume to these models accounted for another 4%-11% of the total variation.

The total brain T2 lesion volume was the main significant predictor of the global cognitive composite score as well as scores on the sustained visual attention test, after controlling for covariates.

Dr. Till said she had no conflict of interest to disclose. Two of her research collaborators disclosed receiving compensation for speaking for manufacturers of drugs for MS.

SEATTLE — Children and adolescents who have an acute demyelinating syndrome or multiple sclerosis may experience lasting impairment in brain growth or cognition, according to two prospective studies.

In one study, Dr. Douglas L. Arnold and his fellow researchers found a slower-than-expected rate of brain growth over 1 year in children with a history of one acute demyelinating event.

In a second study of children and adolescents with multiple sclerosis, Christine Till, Ph.D., and her coinvestigators found total brain volume of T2 lesions on MRI was significantly associated with cognitive impairment, which occurred in about one-third of the subjects.

“These findings are important because they indicate an effect of inflammatory activity on cognitive function,” particularly on tests that depend on integrated neural networks or efficient communication across multiple brain regions, she said.

Dr. Arnold of the Montreal Neurological Institute and Hospital at McGill University, Montreal, and his associates compared brain volume changes over 1 year using T1-weighted MRI scans in 31 children with acute demyelinating syndromes (ADS) and in 31 healthy age- and gender-matched control patients from the National Institutes of Health MRI Study of Normal Brain Development (www.brain-child.org

The rate of brain growth decreased in both groups during the year and tended to level off after 10 years of age. Before 10 years of age, ADS patients did not show atrophy, but instead showed a failure of age-anticipated brain growth. The rate of brain growth was significantly lower in 13 ADS patients younger than 10 years than it was in 12 healthy control patients (0.62%/year vs. 2.26%/year), Dr. Arnold reported at the annual meeting of the American Academy of Neurology.

However, no difference was found in the rate of brain growth after 10 years of age in 18 ADS patients (0.18%/year) and 19 healthy control patients (0.06%/year).

There appears to be a “heightened vulnerability of the more immature CNS to inflammatory brain injury, despite the capacity of younger brains to adapt … [or] respond to injury of certain sorts. This inflammation seems to interrupt some critical developmental processes and result in this failure of age-anticipated growth,” he said.

The researchers are acquiring additional data to find any corresponding neuropsychological changes and to determine whether there is any spatial localization of the changes in brain growth.

Dr. Arnold and some of his coinvestigators reported receiving research support and personal compensation from companies that manufacture drugs for MS.

The study was supported by the Multiple Sclerosis Scientific Research Foundation of Canada and the Canadian Institutes of Health Research.

In the second study, Dr. Till and her colleagues looked for signs of cognitive impairment in 32 children who presented to the pediatric MS clinic at the Hospital for Sick Children, Toronto, during 2007-2008.

Prior studies in children have shown reductions in processing speed, memory, attention, and executive function, which generally occur with greater severity at a younger age of onset and with longer disease duration.

But the “association between cognitive impairment and MRI lesion load has not been investigated in children with MS,” said Dr. Till, of the department of psychology at York University, Toronto.

Of the 32 patients, 3 were excluded from the analysis because of excessive head motion during the MRI scans, and 1 patient was excluded because of a change in diagnosis. The remaining 28 patients (22 females) were a mean of 16 years old and had a mean disease duration of 4.5 years with a relapsing-remitting course. Their median Expanded Disability Status Scale Score was 1 and 23 (82%) of them were receiving disease-modifying treatment during the study.

Of the 28 children, 10 (36%) had cognitive impairment, which Dr. Till and her associates defined as scores more than 1.5 standard deviations below the mean for their age on at least 3 of the 17 different tests in the battery. Attention and processing speed were the most commonly impaired measurements. More than 20% of the children had impaired visuomotor integration on a test that required them to copy designs of increasing complexity as well as a test that assessed cognitive flexibility and working memory.

The cognitively impaired children were younger at disease onset than were cognitively normal children (9.7 years vs. 12.5 years). Children who were cognitively impaired also had experienced a longer disease duration than did those who were cognitively normal (6.1 years vs. 3.7 years). However, the differences in both comparisons did not reach statistical significance (P = .07).

Total brain T2 lesion volume was most strongly correlated with attention, processing speed, and a global cognitive composite score. But total brain T1 lesion volume did not correlate with any of the neuropsychological testing outcomes.

In multiple linear regression models, age at disease onset was the main significant predictor of verbal intelligence and processing speed, accounting for 23%-37% of the total variation in the two. The addition of total brain lesion volume to these models accounted for another 4%-11% of the total variation.

The total brain T2 lesion volume was the main significant predictor of the global cognitive composite score as well as scores on the sustained visual attention test, after controlling for covariates.

Dr. Till said she had no conflict of interest to disclose. Two of her research collaborators disclosed receiving compensation for speaking for manufacturers of drugs for MS.

The risk for developing Parkinson's disease that is associated with pesticide exposure appears to be especially high in people who are professionally exposed to the chemicals and those who carry certain polymorphisms for glutathione S-transferase genes, according to data from two new case-control studies.

The studies strengthen the already well-documented association between pesticide exposure and Parkinson's disease (PD) by including a more detailed assessment of exposure to the chemicals for analyzing dose-effect relationships, especially for different classes of insecticides, fungicides, and herbicides, as well as examining the role of genetic traits in determining individual susceptibility to PD.

Dr. Alexis Elbaz of the Institut National de la Santé et de la Recherche Médicale, Paris, and his colleagues conducted extensive in-person interviews about professional exposure to pesticides with 247 patients with PD and 676 matching control patients. All of the participants came from the same French health insurance organization for workers in agriculture and related occupations. The patients with PD had been diagnosed a median of 1.5 years before the study (Ann. Neurol. 2009 [doi:10.1002/ana.21717

Dr. Elbaz and his associates found that for men, the odds of developing PD increased with the number of years of professional use of pesticides. This relationship was stronger for men with PD onset after age 65 years than it was for men with younger onset. Women with pesticide exposure also were significantly more likely to develop PD than were those without exposure.

Of the three broad categories of pesticides that the investigators analyzed–insecticides, fungicides, and herbicides–only insecticide exposure in men was associated with a significantly increased odds of developing PD (odds ratio 2.2). This association followed a dose-effect relationship, which was strongest for older-onset PD patients. In women, only fungicide exposure was associated with significantly increased odds of developing PD (odds ratio 3.5). In multivariate analyses of men overall and of men with older-onset PD, only organochlorine insecticides remained associated with PD after adjusting for other pesticide families that the men had been exposed to.

During 1941-1990, patients with older-onset PD had used organochlorines in each 10-year period more often than their matched controls had, whereas there was no difference in use during the same periods between patients with younger-onset PD and their matched controls. Each control group used organochlorines, as well as insecticides and pesticides, at similar frequencies.

The finding that the association between PD and professional pesticide use was stronger for older males is “consistent with the view that genetic susceptibility plays a stronger role in younger-onset cases, while environmental factors play a stronger role for older-onset cases,” the investigators wrote.

In a separate study, Dr. Ruey-Meei Wu of the department of neurology at National Taiwan University Hospital, Taipei, and her colleagues genotyped 125 patients (69 women) with sporadic idiopathic PD and 162 age- and gender-matched control patients (90 women) from a rural area of southern Taiwan for four glutathione S-transferase (GST) genes (GSTM1, GSTP1, GSTT1, and GSTZ1). Overall, 69 PD patients and 70 control patients were exposed to pesticides (herbicides, insecticides, and fungicides) used in professional farming or gardening. These patients had been exposed to pesticides for a range of 1 to 50 years, Dr. Wu and her colleagues reported at a poster session of the International Congress of Parkinson's Disease and Movement Disorders in Paris.

GST polymorphisms have been reported to reduce the efficiency of the substrate selectivity or stability of the enzymes. In brain tissue, GSTs function as scavengers that eliminate the formation of intracellular free radicals that are generated from the metabolism of drugs, toxins such as pesticides, or xenobiotics. GSTs have the potential to modify a person's susceptibility to developing PD after pesticide exposure by increasing oxidative stress in the brain, leading to the degeneration of dopaminergic neurons, Dr. Wu said in an interview.

Pesticide exposure was an independent risk factor for PD. Only the GSTP1 Val 105 polymorphism, which occurred in about 20% of the patients, significantly increased the risk for the development of PD. This polymorphism raised the odds of developing PD by a factor of 2.2. The risk for PD was greatest among patients who had been exposed to pesticides for more than 35 years.

Those who carried the GSTP1 Val 105 polymorphism and were exposed to pesticides had even higher risk of developing PD. There was a trend for increasing PD risk that became stronger and more significant in pesticide-exposed patients who carried an additional putative high-risk GST genotype.

None of the investigators in either study had any conflicts of interest to declare.

The odds of developing Parkinson's disease rose with the number of years of professional use of pesticides.©LOOK PHOTO/

The risk for developing Parkinson's disease that is associated with pesticide exposure appears to be especially high in people who are professionally exposed to the chemicals and those who carry certain polymorphisms for glutathione S-transferase genes, according to data from two new case-control studies.

The studies strengthen the already well-documented association between pesticide exposure and Parkinson's disease (PD) by including a more detailed assessment of exposure to the chemicals for analyzing dose-effect relationships, especially for different classes of insecticides, fungicides, and herbicides, as well as examining the role of genetic traits in determining individual susceptibility to PD.

Dr. Alexis Elbaz of the Institut National de la Santé et de la Recherche Médicale, Paris, and his colleagues conducted extensive in-person interviews about professional exposure to pesticides with 247 patients with PD and 676 matching control patients. All of the participants came from the same French health insurance organization for workers in agriculture and related occupations. The patients with PD had been diagnosed a median of 1.5 years before the study (Ann. Neurol. 2009 [doi:10.1002/ana.21717

Dr. Elbaz and his associates found that for men, the odds of developing PD increased with the number of years of professional use of pesticides. This relationship was stronger for men with PD onset after age 65 years than it was for men with younger onset. Women with pesticide exposure also were significantly more likely to develop PD than were those without exposure.

Of the three broad categories of pesticides that the investigators analyzed–insecticides, fungicides, and herbicides–only insecticide exposure in men was associated with a significantly increased odds of developing PD (odds ratio 2.2). This association followed a dose-effect relationship, which was strongest for older-onset PD patients. In women, only fungicide exposure was associated with significantly increased odds of developing PD (odds ratio 3.5). In multivariate analyses of men overall and of men with older-onset PD, only organochlorine insecticides remained associated with PD after adjusting for other pesticide families that the men had been exposed to.

During 1941-1990, patients with older-onset PD had used organochlorines in each 10-year period more often than their matched controls had, whereas there was no difference in use during the same periods between patients with younger-onset PD and their matched controls. Each control group used organochlorines, as well as insecticides and pesticides, at similar frequencies.

The finding that the association between PD and professional pesticide use was stronger for older males is “consistent with the view that genetic susceptibility plays a stronger role in younger-onset cases, while environmental factors play a stronger role for older-onset cases,” the investigators wrote.

In a separate study, Dr. Ruey-Meei Wu of the department of neurology at National Taiwan University Hospital, Taipei, and her colleagues genotyped 125 patients (69 women) with sporadic idiopathic PD and 162 age- and gender-matched control patients (90 women) from a rural area of southern Taiwan for four glutathione S-transferase (GST) genes (GSTM1, GSTP1, GSTT1, and GSTZ1). Overall, 69 PD patients and 70 control patients were exposed to pesticides (herbicides, insecticides, and fungicides) used in professional farming or gardening. These patients had been exposed to pesticides for a range of 1 to 50 years, Dr. Wu and her colleagues reported at a poster session of the International Congress of Parkinson's Disease and Movement Disorders in Paris.

GST polymorphisms have been reported to reduce the efficiency of the substrate selectivity or stability of the enzymes. In brain tissue, GSTs function as scavengers that eliminate the formation of intracellular free radicals that are generated from the metabolism of drugs, toxins such as pesticides, or xenobiotics. GSTs have the potential to modify a person's susceptibility to developing PD after pesticide exposure by increasing oxidative stress in the brain, leading to the degeneration of dopaminergic neurons, Dr. Wu said in an interview.

Pesticide exposure was an independent risk factor for PD. Only the GSTP1 Val 105 polymorphism, which occurred in about 20% of the patients, significantly increased the risk for the development of PD. This polymorphism raised the odds of developing PD by a factor of 2.2. The risk for PD was greatest among patients who had been exposed to pesticides for more than 35 years.

Those who carried the GSTP1 Val 105 polymorphism and were exposed to pesticides had even higher risk of developing PD. There was a trend for increasing PD risk that became stronger and more significant in pesticide-exposed patients who carried an additional putative high-risk GST genotype.

None of the investigators in either study had any conflicts of interest to declare.

The odds of developing Parkinson's disease rose with the number of years of professional use of pesticides.©LOOK PHOTO/

The risk for developing Parkinson's disease that is associated with pesticide exposure appears to be especially high in people who are professionally exposed to the chemicals and those who carry certain polymorphisms for glutathione S-transferase genes, according to data from two new case-control studies.

The studies strengthen the already well-documented association between pesticide exposure and Parkinson's disease (PD) by including a more detailed assessment of exposure to the chemicals for analyzing dose-effect relationships, especially for different classes of insecticides, fungicides, and herbicides, as well as examining the role of genetic traits in determining individual susceptibility to PD.

Dr. Alexis Elbaz of the Institut National de la Santé et de la Recherche Médicale, Paris, and his colleagues conducted extensive in-person interviews about professional exposure to pesticides with 247 patients with PD and 676 matching control patients. All of the participants came from the same French health insurance organization for workers in agriculture and related occupations. The patients with PD had been diagnosed a median of 1.5 years before the study (Ann. Neurol. 2009 [doi:10.1002/ana.21717

Dr. Elbaz and his associates found that for men, the odds of developing PD increased with the number of years of professional use of pesticides. This relationship was stronger for men with PD onset after age 65 years than it was for men with younger onset. Women with pesticide exposure also were significantly more likely to develop PD than were those without exposure.

Of the three broad categories of pesticides that the investigators analyzed–insecticides, fungicides, and herbicides–only insecticide exposure in men was associated with a significantly increased odds of developing PD (odds ratio 2.2). This association followed a dose-effect relationship, which was strongest for older-onset PD patients. In women, only fungicide exposure was associated with significantly increased odds of developing PD (odds ratio 3.5). In multivariate analyses of men overall and of men with older-onset PD, only organochlorine insecticides remained associated with PD after adjusting for other pesticide families that the men had been exposed to.

During 1941-1990, patients with older-onset PD had used organochlorines in each 10-year period more often than their matched controls had, whereas there was no difference in use during the same periods between patients with younger-onset PD and their matched controls. Each control group used organochlorines, as well as insecticides and pesticides, at similar frequencies.

The finding that the association between PD and professional pesticide use was stronger for older males is “consistent with the view that genetic susceptibility plays a stronger role in younger-onset cases, while environmental factors play a stronger role for older-onset cases,” the investigators wrote.

In a separate study, Dr. Ruey-Meei Wu of the department of neurology at National Taiwan University Hospital, Taipei, and her colleagues genotyped 125 patients (69 women) with sporadic idiopathic PD and 162 age- and gender-matched control patients (90 women) from a rural area of southern Taiwan for four glutathione S-transferase (GST) genes (GSTM1, GSTP1, GSTT1, and GSTZ1). Overall, 69 PD patients and 70 control patients were exposed to pesticides (herbicides, insecticides, and fungicides) used in professional farming or gardening. These patients had been exposed to pesticides for a range of 1 to 50 years, Dr. Wu and her colleagues reported at a poster session of the International Congress of Parkinson's Disease and Movement Disorders in Paris.

GST polymorphisms have been reported to reduce the efficiency of the substrate selectivity or stability of the enzymes. In brain tissue, GSTs function as scavengers that eliminate the formation of intracellular free radicals that are generated from the metabolism of drugs, toxins such as pesticides, or xenobiotics. GSTs have the potential to modify a person's susceptibility to developing PD after pesticide exposure by increasing oxidative stress in the brain, leading to the degeneration of dopaminergic neurons, Dr. Wu said in an interview.

Pesticide exposure was an independent risk factor for PD. Only the GSTP1 Val 105 polymorphism, which occurred in about 20% of the patients, significantly increased the risk for the development of PD. This polymorphism raised the odds of developing PD by a factor of 2.2. The risk for PD was greatest among patients who had been exposed to pesticides for more than 35 years.

Those who carried the GSTP1 Val 105 polymorphism and were exposed to pesticides had even higher risk of developing PD. There was a trend for increasing PD risk that became stronger and more significant in pesticide-exposed patients who carried an additional putative high-risk GST genotype.

None of the investigators in either study had any conflicts of interest to declare.

The odds of developing Parkinson's disease rose with the number of years of professional use of pesticides.©LOOK PHOTO/

SARASOTA, FLA. — Preexisting conditions may be better predictors of the outcomes of intra-abdominal infections than are the source or type of infection, according to a single-center, retrospective study.

The results suggest that interventions for intra-abdominal infections (IAIs) should focus on treating the burden of chronic disease in patients rather than on preventing specific sources or types of IAIs, Tazo Inui said at the annual meeting of the Central Surgical Association.

Community-acquired IAIs (CIAIs) tend to occur most frequently with complicated appendicitis, but nosocomial IAIs (NIAIs) have been reported to have worse outcomes, said Mr. Inui, a fourth-year medical student at Case Western Reserve University, Cleveland.

In a review of 452 patients with IAIs during 1999-2007 at MetroHealth Medical Center, Cleveland, Mr. Inui and his associates, led by Dr. Mark Malagoni, compared 234 patients with a CIAI and 218 with an NIAI. An NIAI was defined as an infection diagnosed 48 hours or more after admission for an unrelated diagnosis or within 4 weeks of an operation or intervention for an IAI.

The investigators reviewed patients' scores on the Charlson Comorbidity Index, which is designed to predict mortality based on the burden of a patient's comorbid disease, as well as their multiorgan dysfunction (MOD) score, which is intended to measure dysfunction in six organ systems and has been shown to correlate strongly with mortality, particularly in ICU patients, Mr. Inui said.

Patients with CIAI most often presented with complicated appendicitis (52%), followed by colonic (26%) or small bowel (11%) sources of infection. NIAIs were associated most frequently with postoperative infection (44%), then colonic (29%) or small bowel sources (17%). NIAI patients also were significantly older than those with CIAI (53 vs. 50 years).

Patients were excluded from the study if they had been treated within 24 hours for a gastroduodenal perforation or within 12 hours for a traumatic intestinal perforation.

The investigators found that the 122 CIAI patients with complicated appendicitis were younger, had lower Charlson scores, and had lower preoperative MOD scores than did CIAI patients without complicated appendicitis. However, when they excluded CIAI patients with complicated appendicitis from the analysis, there were no differences in preoperative characteristics between NIAI patients and CIAI patients without appendicitis.

Mr. Inui and his colleagues excluded patients with complicated appendicitis from further analyses because no one with that condition died, and only 7% of such patients required reintervention (surgery or percutaneous drainage).

Thus, among patients without appendicitis in the CIAI and NIAI groups, comparable rates of treatment failure—defined as death (8% vs. 9%, respectively) or the need for reintervention (21% vs. 21%)—and postoperative complications were seen.

“This observation suggests that patients with community-acquired and nosocomial infections are, in fact, more alike than previously reported,” Mr. Inui said.

Mortality was independently predicted by the presence of catheter-related bloodstream infections, postoperative myocardial infarctions or arrhythmias, and an age of 65 years or older.

Even though Charlson scores of 2 or higher did not independently predict mortality, Mr. Inui noted that there was a stepwise increase in mortality according to Charlson score, such that mortality was less than 5% in patients with a score of 0, 10% with a score of 1-2, 12% with a score of 3-4, and 20% with a score of 5 or higher.

However, when patients with appendicitis were included in the analysis, treatment failure was independently associated with a nonappendiceal source of infection and a Charlson score of 2 or greater. Reintervention also was independently associated with a nonappendiceal source of infection, as well as a MOD score of 4 or greater on postoperative day 7.

Mr. Inui noted that he and his coinvestigators did not evaluate the results of cultures or the attempts to control the sources of infection.

SARASOTA, FLA. — Preexisting conditions may be better predictors of the outcomes of intra-abdominal infections than are the source or type of infection, according to a single-center, retrospective study.

The results suggest that interventions for intra-abdominal infections (IAIs) should focus on treating the burden of chronic disease in patients rather than on preventing specific sources or types of IAIs, Tazo Inui said at the annual meeting of the Central Surgical Association.

Community-acquired IAIs (CIAIs) tend to occur most frequently with complicated appendicitis, but nosocomial IAIs (NIAIs) have been reported to have worse outcomes, said Mr. Inui, a fourth-year medical student at Case Western Reserve University, Cleveland.

In a review of 452 patients with IAIs during 1999-2007 at MetroHealth Medical Center, Cleveland, Mr. Inui and his associates, led by Dr. Mark Malagoni, compared 234 patients with a CIAI and 218 with an NIAI. An NIAI was defined as an infection diagnosed 48 hours or more after admission for an unrelated diagnosis or within 4 weeks of an operation or intervention for an IAI.

The investigators reviewed patients' scores on the Charlson Comorbidity Index, which is designed to predict mortality based on the burden of a patient's comorbid disease, as well as their multiorgan dysfunction (MOD) score, which is intended to measure dysfunction in six organ systems and has been shown to correlate strongly with mortality, particularly in ICU patients, Mr. Inui said.

Patients with CIAI most often presented with complicated appendicitis (52%), followed by colonic (26%) or small bowel (11%) sources of infection. NIAIs were associated most frequently with postoperative infection (44%), then colonic (29%) or small bowel sources (17%). NIAI patients also were significantly older than those with CIAI (53 vs. 50 years).

Patients were excluded from the study if they had been treated within 24 hours for a gastroduodenal perforation or within 12 hours for a traumatic intestinal perforation.

The investigators found that the 122 CIAI patients with complicated appendicitis were younger, had lower Charlson scores, and had lower preoperative MOD scores than did CIAI patients without complicated appendicitis. However, when they excluded CIAI patients with complicated appendicitis from the analysis, there were no differences in preoperative characteristics between NIAI patients and CIAI patients without appendicitis.

Mr. Inui and his colleagues excluded patients with complicated appendicitis from further analyses because no one with that condition died, and only 7% of such patients required reintervention (surgery or percutaneous drainage).

Thus, among patients without appendicitis in the CIAI and NIAI groups, comparable rates of treatment failure—defined as death (8% vs. 9%, respectively) or the need for reintervention (21% vs. 21%)—and postoperative complications were seen.

“This observation suggests that patients with community-acquired and nosocomial infections are, in fact, more alike than previously reported,” Mr. Inui said.

Mortality was independently predicted by the presence of catheter-related bloodstream infections, postoperative myocardial infarctions or arrhythmias, and an age of 65 years or older.

Even though Charlson scores of 2 or higher did not independently predict mortality, Mr. Inui noted that there was a stepwise increase in mortality according to Charlson score, such that mortality was less than 5% in patients with a score of 0, 10% with a score of 1-2, 12% with a score of 3-4, and 20% with a score of 5 or higher.

However, when patients with appendicitis were included in the analysis, treatment failure was independently associated with a nonappendiceal source of infection and a Charlson score of 2 or greater. Reintervention also was independently associated with a nonappendiceal source of infection, as well as a MOD score of 4 or greater on postoperative day 7.

Mr. Inui noted that he and his coinvestigators did not evaluate the results of cultures or the attempts to control the sources of infection.

SARASOTA, FLA. — Preexisting conditions may be better predictors of the outcomes of intra-abdominal infections than are the source or type of infection, according to a single-center, retrospective study.

The results suggest that interventions for intra-abdominal infections (IAIs) should focus on treating the burden of chronic disease in patients rather than on preventing specific sources or types of IAIs, Tazo Inui said at the annual meeting of the Central Surgical Association.

Community-acquired IAIs (CIAIs) tend to occur most frequently with complicated appendicitis, but nosocomial IAIs (NIAIs) have been reported to have worse outcomes, said Mr. Inui, a fourth-year medical student at Case Western Reserve University, Cleveland.

In a review of 452 patients with IAIs during 1999-2007 at MetroHealth Medical Center, Cleveland, Mr. Inui and his associates, led by Dr. Mark Malagoni, compared 234 patients with a CIAI and 218 with an NIAI. An NIAI was defined as an infection diagnosed 48 hours or more after admission for an unrelated diagnosis or within 4 weeks of an operation or intervention for an IAI.

The investigators reviewed patients' scores on the Charlson Comorbidity Index, which is designed to predict mortality based on the burden of a patient's comorbid disease, as well as their multiorgan dysfunction (MOD) score, which is intended to measure dysfunction in six organ systems and has been shown to correlate strongly with mortality, particularly in ICU patients, Mr. Inui said.

Patients with CIAI most often presented with complicated appendicitis (52%), followed by colonic (26%) or small bowel (11%) sources of infection. NIAIs were associated most frequently with postoperative infection (44%), then colonic (29%) or small bowel sources (17%). NIAI patients also were significantly older than those with CIAI (53 vs. 50 years).

Patients were excluded from the study if they had been treated within 24 hours for a gastroduodenal perforation or within 12 hours for a traumatic intestinal perforation.

The investigators found that the 122 CIAI patients with complicated appendicitis were younger, had lower Charlson scores, and had lower preoperative MOD scores than did CIAI patients without complicated appendicitis. However, when they excluded CIAI patients with complicated appendicitis from the analysis, there were no differences in preoperative characteristics between NIAI patients and CIAI patients without appendicitis.

Mr. Inui and his colleagues excluded patients with complicated appendicitis from further analyses because no one with that condition died, and only 7% of such patients required reintervention (surgery or percutaneous drainage).

Thus, among patients without appendicitis in the CIAI and NIAI groups, comparable rates of treatment failure—defined as death (8% vs. 9%, respectively) or the need for reintervention (21% vs. 21%)—and postoperative complications were seen.

“This observation suggests that patients with community-acquired and nosocomial infections are, in fact, more alike than previously reported,” Mr. Inui said.

Mortality was independently predicted by the presence of catheter-related bloodstream infections, postoperative myocardial infarctions or arrhythmias, and an age of 65 years or older.

Even though Charlson scores of 2 or higher did not independently predict mortality, Mr. Inui noted that there was a stepwise increase in mortality according to Charlson score, such that mortality was less than 5% in patients with a score of 0, 10% with a score of 1-2, 12% with a score of 3-4, and 20% with a score of 5 or higher.

However, when patients with appendicitis were included in the analysis, treatment failure was independently associated with a nonappendiceal source of infection and a Charlson score of 2 or greater. Reintervention also was independently associated with a nonappendiceal source of infection, as well as a MOD score of 4 or greater on postoperative day 7.

Mr. Inui noted that he and his coinvestigators did not evaluate the results of cultures or the attempts to control the sources of infection.