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Psyllium cut frequency of abdominal pain in pediatric IBS trial
Consuming psyllium fiber significantly reduced the frequency, but not the severity, of abdominal pain in children with irritable bowel syndrome in a randomized, double-blind, placebo-controlled trial reported in the May issue of Clinical Gastroenterology and Hepatology (2016 Nov;14[11]:1667).
Psyllium therapy did not reduce the self-reported severity of abdominal pain, Robert J. Shulman, MD, of Baylor College of Medicine in Houston reported with his associates in Clinical Gastroenterology and Hepatology. Psyllium was associated with shifts in intestinal microbiota, compared with baseline, although the changes did not reach statistical significance when compared with placebo, the researchers added. “Further studies are needed to investigate the potential mechanism whereby psyllium decreases abdominal pain frequency in children with irritable bowel syndrome [IBS],” they wrote.
IBS affects up to 20% of school-aged children. Consuming psyllium is thought to improve abdominal pain and stooling symptoms in adults with IBS, but data are inconclusive, and few randomized trials have evaluated fiber in childhood IBS. Therefore, the investigators randomly assigned 103 children (average age, 13 years; standard deviation, 3 years) with IBS who had responded inadequately to an 8-day carbohydrate elimination diet to receive a single daily dose of either psyllium or placebo maltodextrin for 6 weeks. Children aged 7-11 years received 6 g of fiber, while those aged 12-18 years received 12 g of fiber. Patients filled out a daily pain and stool diary during a 2-week baseline assessment period and again during the final 2 weeks of the trial. They also underwent breath hydrogen and methane testing, gut permeability testing, and a stool microbiota assessment during the final weekend of treatment.
At baseline, the trial arms resembled each other in terms of frequency and severity of abdominal pain, psychological characteristics, percentage of normal stools, baseline hydrogen production, and gastrointestinal permeability, the researchers said. During the final 2 weeks of treatment, the psyllium arm reported an average of 8.2 (standard deviation, 1.2) fewer episodes of abdominal pain, compared with baseline, while the control arm reported a mean reduction of 4.1 (SD, 1.3) episodes of abdominal pain (P = .03). At the end of treatment, the arms did not significantly differ in percentage of breath hydrogen or methane production, gastrointestinal permeability, or percentage of normal stools or diarrhea. However, controls had a significantly greater reduction in constipation compared with the psyllium group (P = .048).
Stool microbiome assessments of 33 children revealed a trend toward a greater increase in Bacteroidetes and a greater decrease in Firmicutes bacteria in the fiber group, compared with the control group (P = .068). The fiber group was also “marginally enriched” in bacteria of class Bacteroidia, while the placebo group was enriched in bacteria of class Clostridia (P = .094). However, the groups did not differ at narrower taxonomic levels, the researchers said. A larger sample size might have facilitated better detection of differences between groups, such as in breath hydrogen production or interactions between abdominal pain and psychological symptoms, they added.
The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
Consuming psyllium fiber significantly reduced the frequency, but not the severity, of abdominal pain in children with irritable bowel syndrome in a randomized, double-blind, placebo-controlled trial reported in the May issue of Clinical Gastroenterology and Hepatology (2016 Nov;14[11]:1667).
Psyllium therapy did not reduce the self-reported severity of abdominal pain, Robert J. Shulman, MD, of Baylor College of Medicine in Houston reported with his associates in Clinical Gastroenterology and Hepatology. Psyllium was associated with shifts in intestinal microbiota, compared with baseline, although the changes did not reach statistical significance when compared with placebo, the researchers added. “Further studies are needed to investigate the potential mechanism whereby psyllium decreases abdominal pain frequency in children with irritable bowel syndrome [IBS],” they wrote.
IBS affects up to 20% of school-aged children. Consuming psyllium is thought to improve abdominal pain and stooling symptoms in adults with IBS, but data are inconclusive, and few randomized trials have evaluated fiber in childhood IBS. Therefore, the investigators randomly assigned 103 children (average age, 13 years; standard deviation, 3 years) with IBS who had responded inadequately to an 8-day carbohydrate elimination diet to receive a single daily dose of either psyllium or placebo maltodextrin for 6 weeks. Children aged 7-11 years received 6 g of fiber, while those aged 12-18 years received 12 g of fiber. Patients filled out a daily pain and stool diary during a 2-week baseline assessment period and again during the final 2 weeks of the trial. They also underwent breath hydrogen and methane testing, gut permeability testing, and a stool microbiota assessment during the final weekend of treatment.
At baseline, the trial arms resembled each other in terms of frequency and severity of abdominal pain, psychological characteristics, percentage of normal stools, baseline hydrogen production, and gastrointestinal permeability, the researchers said. During the final 2 weeks of treatment, the psyllium arm reported an average of 8.2 (standard deviation, 1.2) fewer episodes of abdominal pain, compared with baseline, while the control arm reported a mean reduction of 4.1 (SD, 1.3) episodes of abdominal pain (P = .03). At the end of treatment, the arms did not significantly differ in percentage of breath hydrogen or methane production, gastrointestinal permeability, or percentage of normal stools or diarrhea. However, controls had a significantly greater reduction in constipation compared with the psyllium group (P = .048).
Stool microbiome assessments of 33 children revealed a trend toward a greater increase in Bacteroidetes and a greater decrease in Firmicutes bacteria in the fiber group, compared with the control group (P = .068). The fiber group was also “marginally enriched” in bacteria of class Bacteroidia, while the placebo group was enriched in bacteria of class Clostridia (P = .094). However, the groups did not differ at narrower taxonomic levels, the researchers said. A larger sample size might have facilitated better detection of differences between groups, such as in breath hydrogen production or interactions between abdominal pain and psychological symptoms, they added.
The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
Consuming psyllium fiber significantly reduced the frequency, but not the severity, of abdominal pain in children with irritable bowel syndrome in a randomized, double-blind, placebo-controlled trial reported in the May issue of Clinical Gastroenterology and Hepatology (2016 Nov;14[11]:1667).
Psyllium therapy did not reduce the self-reported severity of abdominal pain, Robert J. Shulman, MD, of Baylor College of Medicine in Houston reported with his associates in Clinical Gastroenterology and Hepatology. Psyllium was associated with shifts in intestinal microbiota, compared with baseline, although the changes did not reach statistical significance when compared with placebo, the researchers added. “Further studies are needed to investigate the potential mechanism whereby psyllium decreases abdominal pain frequency in children with irritable bowel syndrome [IBS],” they wrote.
IBS affects up to 20% of school-aged children. Consuming psyllium is thought to improve abdominal pain and stooling symptoms in adults with IBS, but data are inconclusive, and few randomized trials have evaluated fiber in childhood IBS. Therefore, the investigators randomly assigned 103 children (average age, 13 years; standard deviation, 3 years) with IBS who had responded inadequately to an 8-day carbohydrate elimination diet to receive a single daily dose of either psyllium or placebo maltodextrin for 6 weeks. Children aged 7-11 years received 6 g of fiber, while those aged 12-18 years received 12 g of fiber. Patients filled out a daily pain and stool diary during a 2-week baseline assessment period and again during the final 2 weeks of the trial. They also underwent breath hydrogen and methane testing, gut permeability testing, and a stool microbiota assessment during the final weekend of treatment.
At baseline, the trial arms resembled each other in terms of frequency and severity of abdominal pain, psychological characteristics, percentage of normal stools, baseline hydrogen production, and gastrointestinal permeability, the researchers said. During the final 2 weeks of treatment, the psyllium arm reported an average of 8.2 (standard deviation, 1.2) fewer episodes of abdominal pain, compared with baseline, while the control arm reported a mean reduction of 4.1 (SD, 1.3) episodes of abdominal pain (P = .03). At the end of treatment, the arms did not significantly differ in percentage of breath hydrogen or methane production, gastrointestinal permeability, or percentage of normal stools or diarrhea. However, controls had a significantly greater reduction in constipation compared with the psyllium group (P = .048).
Stool microbiome assessments of 33 children revealed a trend toward a greater increase in Bacteroidetes and a greater decrease in Firmicutes bacteria in the fiber group, compared with the control group (P = .068). The fiber group was also “marginally enriched” in bacteria of class Bacteroidia, while the placebo group was enriched in bacteria of class Clostridia (P = .094). However, the groups did not differ at narrower taxonomic levels, the researchers said. A larger sample size might have facilitated better detection of differences between groups, such as in breath hydrogen production or interactions between abdominal pain and psychological symptoms, they added.
The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Compared with placebo maltodextrin, consuming psyllium fiber significantly reduced the self-reported frequency of abdominal pain in children with irritable bowel syndrome.
Major finding: Children who received psyllium reported an average of 8.2 fewer pain episodes, compared with baseline, while controls reported a mean reduction of 4.1 pain episodes (P = .03).
Data source: A randomized, double-blind trial of 103 children aged 12-18 years of age with irritable bowel syndrome.
Disclosures: The study was supported in part by the National Institutes of Health, the Daffy’s Foundation, and the USDA/ARS. The investigators reported having no conflicts of interest.
Aggressive HCC in males traced to higher serotonin
The greater frequency and aggressiveness of hepatocellular carcinoma (HCC) in men than in women might be attributable to greater synthesis and accumulation of serotonin in males, according to a report published online in Cellular and Molecular Gastroenterology and Hepatology (2017 May. doi: 10.1016/j.jcmgh.2017.01.002).
HCC is nearly five times more common in men than in women, and several molecular studies “have shown a more robust and active HCC tumor microenvironment” in men as well. For example, the density of infiltrating, tumor-associated macrophages is higher among males in a mouse model of the cancer, and human men have substantially higher amounts of intratumoral cluster-of-differentiation cells and neutrophils that indicate a poor prognosis, said Qiqi Yang, PhD, of the department of biological sciences at the National University of Singapore, and her associates.
The investigators developed several zebrafish models of HCC in which the cancer could be induced by transgenic expression of an oncogene in the animals’ hepatocytes. These models “allow the oncogene to be activated at a given and controlled timing in both sexes, providing an excellent platform to study the sex disparity in HCC initiation and progression,” they noted.
They also confirmed the zebrafish findings in human lab studies by analyzing tissue samples from 5 normal livers, 7 inflamed livers, 16 cirrhotic livers, and 30 livers affected with HCC.
The investigators found an increased level of serotonin production in male, compared with female, livers. They demonstrated that serotonin was necessary for the survival of hepatic stellate cells, which also are more abundant in males than in females and have recently been shown to promote tumorigenesis. Serotonin also was crucial for activating hepatic stellate cells during HCC carcinogenesis.
In addition, serotonin levels were significantly elevated in inflamed, cirrhotic, and cancerous livers, compared with normal livers, among men but not among women. “This is in line with the prevailing knowledge that men have a significantly higher rate of serotonin synthesis than do women,” Dr. Yang and her associates said.
Serotonin is a small molecule neurotransmitter with diverse functions such as modulation of mood, appetite, wound healing, gastrointestinal motility, and blood coagulation. It was shown that serotonin can promote liver regeneration in mice via a direct action on hepatocytes, the main building blocks of liver. However, other cell types such as liver stellate cells, the main liver fibrogenic cells, can also be influenced by serotonin. Serotonin action on liver stellate cells results in production of transforming growth factor–beta1 (TGF-beta1), a multifunctional cytokine. TGF-beta1 can then inhibit regeneration of hepatocytes and promote fibrosis. In a new study, scientists have shown that the same pathway is active during hepatic carcinogenesis and promotes development of cancer in a zebrafish model. They also discovered that hepatocytes can produce serotonin and increase TGF-beta1 synthesis in stellate cells. Interestingly, they uncovered a significant sexual dimorphism in both human and fish samples in components of this pathway (for example, more serotonin and TGF-beta1 in males). This study unravels underlying mechanisms of sex differences in liver cancer. Importantly, it can provide a therapeutic opportunity to treat human liver cancer by modulation of serotonin signaling. This approach is attractive since potent and selective pharmacologic agents for serotonin signaling are already available for other purposes such as modulation of gut motility or neurological disorders. Future studies using human cells or samples will pave the path toward clinical translation of these findings.
Mo Ebrahimkhani, MD, is an assistant professor in the school of biological and health systems engineering, Arizona State University, Tempe. He has no conflicts of interest.
Serotonin is a small molecule neurotransmitter with diverse functions such as modulation of mood, appetite, wound healing, gastrointestinal motility, and blood coagulation. It was shown that serotonin can promote liver regeneration in mice via a direct action on hepatocytes, the main building blocks of liver. However, other cell types such as liver stellate cells, the main liver fibrogenic cells, can also be influenced by serotonin. Serotonin action on liver stellate cells results in production of transforming growth factor–beta1 (TGF-beta1), a multifunctional cytokine. TGF-beta1 can then inhibit regeneration of hepatocytes and promote fibrosis. In a new study, scientists have shown that the same pathway is active during hepatic carcinogenesis and promotes development of cancer in a zebrafish model. They also discovered that hepatocytes can produce serotonin and increase TGF-beta1 synthesis in stellate cells. Interestingly, they uncovered a significant sexual dimorphism in both human and fish samples in components of this pathway (for example, more serotonin and TGF-beta1 in males). This study unravels underlying mechanisms of sex differences in liver cancer. Importantly, it can provide a therapeutic opportunity to treat human liver cancer by modulation of serotonin signaling. This approach is attractive since potent and selective pharmacologic agents for serotonin signaling are already available for other purposes such as modulation of gut motility or neurological disorders. Future studies using human cells or samples will pave the path toward clinical translation of these findings.
Mo Ebrahimkhani, MD, is an assistant professor in the school of biological and health systems engineering, Arizona State University, Tempe. He has no conflicts of interest.
Serotonin is a small molecule neurotransmitter with diverse functions such as modulation of mood, appetite, wound healing, gastrointestinal motility, and blood coagulation. It was shown that serotonin can promote liver regeneration in mice via a direct action on hepatocytes, the main building blocks of liver. However, other cell types such as liver stellate cells, the main liver fibrogenic cells, can also be influenced by serotonin. Serotonin action on liver stellate cells results in production of transforming growth factor–beta1 (TGF-beta1), a multifunctional cytokine. TGF-beta1 can then inhibit regeneration of hepatocytes and promote fibrosis. In a new study, scientists have shown that the same pathway is active during hepatic carcinogenesis and promotes development of cancer in a zebrafish model. They also discovered that hepatocytes can produce serotonin and increase TGF-beta1 synthesis in stellate cells. Interestingly, they uncovered a significant sexual dimorphism in both human and fish samples in components of this pathway (for example, more serotonin and TGF-beta1 in males). This study unravels underlying mechanisms of sex differences in liver cancer. Importantly, it can provide a therapeutic opportunity to treat human liver cancer by modulation of serotonin signaling. This approach is attractive since potent and selective pharmacologic agents for serotonin signaling are already available for other purposes such as modulation of gut motility or neurological disorders. Future studies using human cells or samples will pave the path toward clinical translation of these findings.
Mo Ebrahimkhani, MD, is an assistant professor in the school of biological and health systems engineering, Arizona State University, Tempe. He has no conflicts of interest.
The greater frequency and aggressiveness of hepatocellular carcinoma (HCC) in men than in women might be attributable to greater synthesis and accumulation of serotonin in males, according to a report published online in Cellular and Molecular Gastroenterology and Hepatology (2017 May. doi: 10.1016/j.jcmgh.2017.01.002).
HCC is nearly five times more common in men than in women, and several molecular studies “have shown a more robust and active HCC tumor microenvironment” in men as well. For example, the density of infiltrating, tumor-associated macrophages is higher among males in a mouse model of the cancer, and human men have substantially higher amounts of intratumoral cluster-of-differentiation cells and neutrophils that indicate a poor prognosis, said Qiqi Yang, PhD, of the department of biological sciences at the National University of Singapore, and her associates.
The investigators developed several zebrafish models of HCC in which the cancer could be induced by transgenic expression of an oncogene in the animals’ hepatocytes. These models “allow the oncogene to be activated at a given and controlled timing in both sexes, providing an excellent platform to study the sex disparity in HCC initiation and progression,” they noted.
They also confirmed the zebrafish findings in human lab studies by analyzing tissue samples from 5 normal livers, 7 inflamed livers, 16 cirrhotic livers, and 30 livers affected with HCC.
The investigators found an increased level of serotonin production in male, compared with female, livers. They demonstrated that serotonin was necessary for the survival of hepatic stellate cells, which also are more abundant in males than in females and have recently been shown to promote tumorigenesis. Serotonin also was crucial for activating hepatic stellate cells during HCC carcinogenesis.
In addition, serotonin levels were significantly elevated in inflamed, cirrhotic, and cancerous livers, compared with normal livers, among men but not among women. “This is in line with the prevailing knowledge that men have a significantly higher rate of serotonin synthesis than do women,” Dr. Yang and her associates said.
The greater frequency and aggressiveness of hepatocellular carcinoma (HCC) in men than in women might be attributable to greater synthesis and accumulation of serotonin in males, according to a report published online in Cellular and Molecular Gastroenterology and Hepatology (2017 May. doi: 10.1016/j.jcmgh.2017.01.002).
HCC is nearly five times more common in men than in women, and several molecular studies “have shown a more robust and active HCC tumor microenvironment” in men as well. For example, the density of infiltrating, tumor-associated macrophages is higher among males in a mouse model of the cancer, and human men have substantially higher amounts of intratumoral cluster-of-differentiation cells and neutrophils that indicate a poor prognosis, said Qiqi Yang, PhD, of the department of biological sciences at the National University of Singapore, and her associates.
The investigators developed several zebrafish models of HCC in which the cancer could be induced by transgenic expression of an oncogene in the animals’ hepatocytes. These models “allow the oncogene to be activated at a given and controlled timing in both sexes, providing an excellent platform to study the sex disparity in HCC initiation and progression,” they noted.
They also confirmed the zebrafish findings in human lab studies by analyzing tissue samples from 5 normal livers, 7 inflamed livers, 16 cirrhotic livers, and 30 livers affected with HCC.
The investigators found an increased level of serotonin production in male, compared with female, livers. They demonstrated that serotonin was necessary for the survival of hepatic stellate cells, which also are more abundant in males than in females and have recently been shown to promote tumorigenesis. Serotonin also was crucial for activating hepatic stellate cells during HCC carcinogenesis.
In addition, serotonin levels were significantly elevated in inflamed, cirrhotic, and cancerous livers, compared with normal livers, among men but not among women. “This is in line with the prevailing knowledge that men have a significantly higher rate of serotonin synthesis than do women,” Dr. Yang and her associates said.
FROM CELLULAR & MOLECULAR GASTROENTEROLOGY & HEPATOLOGY
Key clinical point: The greater frequency and aggressiveness of hepatocellular carcinoma in men than in women might be attributable to greater synthesis and accumulation of serotonin in males.
Major finding: Serotonin levels were significantly elevated in 7 inflamed, 16 cirrhotic, and 30 cancerous livers, compared with 5 normal livers, among men but not among women.
Data source: Laboratory studies involving a zebrafish model of HCC and tissue samples from 60 human livers.
Disclosures: This study was supported by the National Medical Research Council and the Ministry of Education of Singapore. Dr. Yang and her associates reported no relevant financial disclosures.
Open-capsule PPIs linked to faster ulcer healing after Roux-en-Y
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules.
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules.
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
Proton pump inhibitors (PPIs) are frequently employed to treat marginal ulcers after Roux-en-Y gastric bypass (RYGB). In a retrospective study, Schulman et al. compared intact vs. “open” PPI capsules.
They state that “this may be overcome by use of a soluble form of PPI,” but don’t state what is meant by “soluble PPI” or how the open-capsule PPI was delivered. Among the PPIs they reported using to compare intact vs. open capsules was Protonix [pantoprazole] which is not produced as a capsule, and soluble Prevacid [lansoprazole], which is an orally disintegrating tablet that should provide characteristics similar to an “open capsule.”
PPI capsules provide PPI in enteric-coated granules, which are designed to protect the PPI from acid degradation in the stomach of individuals with intact gastrointestinal tracts and allow more of the PPI dose to reach the small intestine where it is absorbed. If capsules really fail to release their enteric-coated granules until very distally in RYGB patients, bypassing this step to allow earlier release of PPI makes intuitive sense; formulations such as suspensions and rapidly disintegrating tablets that deliver enteric-coated granules without capsules are currently available.
However, if this is an issue, administering a suspension of uncoated PPI with bicarbonate potentially might be the most attractive option, given more rapid absorption than PPI delivered as enteric-coated granules.
Loren Laine, MD, AGAF, professor of medicine, digestive diseases, Yale University, New Haven, Conn. He has no conflicts of interest.
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed marginal ulcers after Roux-en-Y gastric bypass, in a single-center retrospective cohort study.
In contrast, the specific class of proton pump inhibitor (PPI) did not affect healing times, wrote Allison R. Schulman, MD, and her associates at Brigham and Women’s Hospital, Boston. The report is in the April issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.10.015). “Given these results and the high prevalence of marginal ulceration in this patient population, further study in a randomized controlled setting is warranted, and use of open-capsule PPIs should be considered as a low-risk, low-cost alternative,” they added.
Roux-en-Y gastric bypass is one of the most common types of gastric bypass surgeries in the world, and up to 16% of patients develop postsurgical ulcers at the gastrojejunal anastomosis, the investigators noted. Acidity is a prime suspect in these “marginal ulcerations” because bypassing the acid-buffering duodenum exposes the jejunum to acid from the stomach, they added. High-dose PPIs are the main treatment, but there is no consensus on the formulation or dose of therapy. Because Roux-en-Y creates a small gastric pouch and hastens small-bowel transit, closed capsules designed to break down in the stomach “even may make their way to the colon before breakdown occurs,” they wrote.
They reviewed medical charts from patients who developed marginal ulcerations after undergoing Roux-en-Y gastric bypass at their hospital from 2000 through 2015. A total of 115 patients received open-capsule PPIs and 49 received intact capsules. All were followed until their ulcers healed.
For the open-capsule group, median time to healing was 91 days, compared with 342 days for the closed-capsule group (P less than .001). Importantly, capsule type was the only independent predictor of healing time (hazard ratio, 6.0; 95% confidence interval, 3.7 to 9.8; P less than .001) in a Cox regression model that included other known correlates of ulcer healing, including age, smoking status, the use of nonsteroidal anti-inflammatory drugs, Helicobacter pylori infection, the length of the gastric pouch, and the presence of fistulae or foreign bodies such as sutures or staples.
The use of sucralfate also did not affect time to ulcer healing, reflecting “many previous studies showing a lack of definitive benefit to this medication,” the researchers said. The findings have “tremendous implications” for health care utilization, they added. Indeed, patients who received open-capsule PPIs needed significantly fewer endoscopic procedures (median, 1.2 versus 1.8; P = .02) and used fewer health care resources overall ($7,206 versus $11,009; P = .05) compared with those prescribed intact PPI capsules.
This study was limited to patients who developed ulcer symptoms and underwent repeated surveillance endoscopies after surgery, the researchers noted. Selection bias is always a concern with retrospective studies, but insurers always covered both types of therapy and the choice of capsule type was entirely up to providers, all of whom consistently prescribed either open- or closed-capsule PPI therapy, they added.
The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: The use of proton pump inhibitors in opened instead of closed capsules was associated with a nearly fourfold shorter median healing time among patients who developed ulcers at the gastrojejunal anastomosis after Roux-en-Y gastric bypass.
Major finding: The median time to ulcer healing was 91.0 versus 342.0 days for the open- and closed-capsule groups, respectively (P less than .001).
Data source: A single-center retrospective study of 162 patients.
Disclosures: The investigators did not acknowledge external funding sources. Dr. Schulman and four coinvestigators reported having no competing interests. One coinvestigator disclosed ties to Olympus, Boston Scientific, and Covidien.
VIDEO: Point-of-care assay caught acetaminophen toxicity
A rapid point-of-care assay for acetaminophen-related liver toxicity had a sensitivity of 100% and a specificity of 86%, compared with etiologic diagnosis, based on the results of a multicenter study published in the April issue of Clinical Gastroenterology and Hepatology.
The test might help guide treatment decisions for these patients in the emergency department and intensive care unit, said Dean W. Roberts, PhD, of the University of Arkansas, Little Rock, and his associates.
About 45% of acute liver failure cases in the United States stem from acetaminophen toxicity, but the diagnosis can be hard to confirm because the drug has a short half-life and patients often cannot or will not report an overdose, which also may consist of multiple exposures, limiting the interpretability of the Rumack nonogram. High-pressure liquid chromatography with electrochemical detection (HPLC-EC) accurately detects acetaminophen-protein adducts (3-[cysteine-S-yl] acetaminophen) released by lysed hepatocytes into the peripheral circulation, but this test requires specialized equipment and skilled personnel, the researchers noted (Clin Gastroenterol Hepatol. 2016 Sep 15. doi: 10.1016/j.cgh.2016.09.007).
The point-of-care assay was positive in all 33 patients diagnosed with acetaminophen toxicity, for a test sensitivity of 100%, the researchers reported. The median band amplitude for cases was 584 (range, 222-1,027), significantly lower than that for patients with nonacetaminophen acute liver failure (3,678; range, 394-8,289; P less than .001) or for controls (8,971; range, 5,151-11,108; P less than .001). Band amplitude correlated inversely with adduct levels because AcetaSTAT is a competitive immunoassay – the presence of adducts decreases reactions at the test band, the investigators reported.
AcetaSTAT results were negative for 25 of 29 patients who were initially diagnosed with nonacetaminophen liver failure, for a test specificity of 86%, a positive predictive value of 89%, and a negative predictive value of 100%. Among the remaining four “false positives,” three tested near or above the toxicity threshold on HPLC-EC and were considered positive after further review, the investigators said. The fourth false-positive case was HPLC-EC–negative autoimmune hepatitis.
AcetaSTAT might not catch cases very early after acetaminophen overdose or that have only mild toxicity, the researchers noted. Nonetheless, it can help guide treatment decisions “at the point of clinical care,” they said. “Because the survival rate of acetaminophen acute liver failure is more favorable than that of other causes of acute live failure, assay results could impact future physician referral patterns and reduce medical costs associated with additional tests to determine the etiology of liver injury.”
The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Roberts and two coinvestigators are part owners of Acetaminophen Toxicity Diagnostics and have submitted a patent application for the AcetaSTAT serum assay used in this study. There were no other disclosures.
Source: American Gastroenterological Association
A rapid point-of-care assay for acetaminophen-related liver toxicity had a sensitivity of 100% and a specificity of 86%, compared with etiologic diagnosis, based on the results of a multicenter study published in the April issue of Clinical Gastroenterology and Hepatology.
The test might help guide treatment decisions for these patients in the emergency department and intensive care unit, said Dean W. Roberts, PhD, of the University of Arkansas, Little Rock, and his associates.
About 45% of acute liver failure cases in the United States stem from acetaminophen toxicity, but the diagnosis can be hard to confirm because the drug has a short half-life and patients often cannot or will not report an overdose, which also may consist of multiple exposures, limiting the interpretability of the Rumack nonogram. High-pressure liquid chromatography with electrochemical detection (HPLC-EC) accurately detects acetaminophen-protein adducts (3-[cysteine-S-yl] acetaminophen) released by lysed hepatocytes into the peripheral circulation, but this test requires specialized equipment and skilled personnel, the researchers noted (Clin Gastroenterol Hepatol. 2016 Sep 15. doi: 10.1016/j.cgh.2016.09.007).
The point-of-care assay was positive in all 33 patients diagnosed with acetaminophen toxicity, for a test sensitivity of 100%, the researchers reported. The median band amplitude for cases was 584 (range, 222-1,027), significantly lower than that for patients with nonacetaminophen acute liver failure (3,678; range, 394-8,289; P less than .001) or for controls (8,971; range, 5,151-11,108; P less than .001). Band amplitude correlated inversely with adduct levels because AcetaSTAT is a competitive immunoassay – the presence of adducts decreases reactions at the test band, the investigators reported.
AcetaSTAT results were negative for 25 of 29 patients who were initially diagnosed with nonacetaminophen liver failure, for a test specificity of 86%, a positive predictive value of 89%, and a negative predictive value of 100%. Among the remaining four “false positives,” three tested near or above the toxicity threshold on HPLC-EC and were considered positive after further review, the investigators said. The fourth false-positive case was HPLC-EC–negative autoimmune hepatitis.
AcetaSTAT might not catch cases very early after acetaminophen overdose or that have only mild toxicity, the researchers noted. Nonetheless, it can help guide treatment decisions “at the point of clinical care,” they said. “Because the survival rate of acetaminophen acute liver failure is more favorable than that of other causes of acute live failure, assay results could impact future physician referral patterns and reduce medical costs associated with additional tests to determine the etiology of liver injury.”
The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Roberts and two coinvestigators are part owners of Acetaminophen Toxicity Diagnostics and have submitted a patent application for the AcetaSTAT serum assay used in this study. There were no other disclosures.
Source: American Gastroenterological Association
A rapid point-of-care assay for acetaminophen-related liver toxicity had a sensitivity of 100% and a specificity of 86%, compared with etiologic diagnosis, based on the results of a multicenter study published in the April issue of Clinical Gastroenterology and Hepatology.
The test might help guide treatment decisions for these patients in the emergency department and intensive care unit, said Dean W. Roberts, PhD, of the University of Arkansas, Little Rock, and his associates.
About 45% of acute liver failure cases in the United States stem from acetaminophen toxicity, but the diagnosis can be hard to confirm because the drug has a short half-life and patients often cannot or will not report an overdose, which also may consist of multiple exposures, limiting the interpretability of the Rumack nonogram. High-pressure liquid chromatography with electrochemical detection (HPLC-EC) accurately detects acetaminophen-protein adducts (3-[cysteine-S-yl] acetaminophen) released by lysed hepatocytes into the peripheral circulation, but this test requires specialized equipment and skilled personnel, the researchers noted (Clin Gastroenterol Hepatol. 2016 Sep 15. doi: 10.1016/j.cgh.2016.09.007).
The point-of-care assay was positive in all 33 patients diagnosed with acetaminophen toxicity, for a test sensitivity of 100%, the researchers reported. The median band amplitude for cases was 584 (range, 222-1,027), significantly lower than that for patients with nonacetaminophen acute liver failure (3,678; range, 394-8,289; P less than .001) or for controls (8,971; range, 5,151-11,108; P less than .001). Band amplitude correlated inversely with adduct levels because AcetaSTAT is a competitive immunoassay – the presence of adducts decreases reactions at the test band, the investigators reported.
AcetaSTAT results were negative for 25 of 29 patients who were initially diagnosed with nonacetaminophen liver failure, for a test specificity of 86%, a positive predictive value of 89%, and a negative predictive value of 100%. Among the remaining four “false positives,” three tested near or above the toxicity threshold on HPLC-EC and were considered positive after further review, the investigators said. The fourth false-positive case was HPLC-EC–negative autoimmune hepatitis.
AcetaSTAT might not catch cases very early after acetaminophen overdose or that have only mild toxicity, the researchers noted. Nonetheless, it can help guide treatment decisions “at the point of clinical care,” they said. “Because the survival rate of acetaminophen acute liver failure is more favorable than that of other causes of acute live failure, assay results could impact future physician referral patterns and reduce medical costs associated with additional tests to determine the etiology of liver injury.”
The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Roberts and two coinvestigators are part owners of Acetaminophen Toxicity Diagnostics and have submitted a patent application for the AcetaSTAT serum assay used in this study. There were no other disclosures.
Source: American Gastroenterological Association
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point:
Major finding: Compared with etiologic diagnosis, its sensitivity was 100%, specificity was 86%, positive predictive value was 89%, and negative predictive value was 100%.
Data source: Competitive immunoassays of serum samples from 19 healthy controls, 29 patients with nonacetaminophen acute liver failure, and 33 patients with acetaminophen-induced acute liver failure.
Disclosures: The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. Dr. Roberts and two coinvestigators are part owners of Acetaminophen Toxicity Diagnostics and have submitted a patent application for the AcetaSTAT serum assay used in this study. There were no other disclosures.
AGA Clinical Practice Update: Using FLIP to assess upper GI tract still murky territory
New clinical practice advice has been issued for use of the functional lumen imaging probe (FLIP) to assess disorders of the upper gastrointestinal tract, with the main takeaway being the device’s potency in diagnosing achalasia.
“Although the strongest data appear to be focused on the management of achalasia, emerging evidence supports the clinical relevance of FLIP in the assessment of disease severity and as an outcome measure in [eosinophilic esophagitis (EoE)] intervention trials,” wrote the authors of the update, led by John E. Pandolfino, MD, of Northwestern University, Chicago. The report is in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.
10.022).
In terms of evaluating the LES, however, FLIP can be used during laparoscopic Heller myotomy or peroral endoscopic myotomy (POEM) as a way of monitoring the LES. Using FLIP this way can help clinicians and surgeons personalize the procedure to each patient, even while it’s ongoing. FLIP also can be used with dilation balloons, with the balloon diameter allowing dilation measurement without the need to also use fluoroscopy.
For treating gastroesophageal reflux disease (GERD), the evidence found in existing literature points with less certainty toward use of FLIP.
“The role of FLIP for physiologic evaluation and management in GERD remains appealing; however, the level of evidence is low and currently FLIP should not be used in routine GERD management,” the authors explained. “Future outcome studies are needed to substantiate the utility of FLIP in GERD and to develop metrics that predict severity and treatment response after antireflux procedures.”
FLIP can be used in managing eosinophilic esophagitis, but is recommended only in certain scenarios. According to the authors, FLIP can be used to measure esophageal narrowing and the overall esophageal body. FLIP also can be used to measure esophageal distensibility, and, in the case of at least one study reviewed by the authors, allows “significantly greater accuracy and precision in estimating the effects of remodeling” in certain patients.
Dr. Pandolfino and his colleagues warned that “current recommendations are limited by the low level of evidence and lack of generalized availability of the analysis paradigms.” They noted the need for “further outcome studies that validate the distensibility plateau threshold and further refinements in software analyses to make this methodology more generalizable.”
Overall, the authors concluded, more study still needs to be done to ascertain exactly what FLIP is capable of and when it can be used to greatest effect. In addition to evaluating its benefit in patients with GERD, research should focus on how to make data obtained via FLIP easier to interpret and put to use.
“More work is needed [that] focuses on optimizing data analysis, standardizing protocols, and defining outcome metrics prior to the widespread adoption [of FLIP] into general clinical practice,” the authors wrote.
Dr. Pandolfino disclosed relationships with Medtronic and Sandhill Scientific. Other coauthors did not report any relevant financial disclosures.
*This story updated on 3/9/2017.
New clinical practice advice has been issued for use of the functional lumen imaging probe (FLIP) to assess disorders of the upper gastrointestinal tract, with the main takeaway being the device’s potency in diagnosing achalasia.
“Although the strongest data appear to be focused on the management of achalasia, emerging evidence supports the clinical relevance of FLIP in the assessment of disease severity and as an outcome measure in [eosinophilic esophagitis (EoE)] intervention trials,” wrote the authors of the update, led by John E. Pandolfino, MD, of Northwestern University, Chicago. The report is in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.
10.022).
In terms of evaluating the LES, however, FLIP can be used during laparoscopic Heller myotomy or peroral endoscopic myotomy (POEM) as a way of monitoring the LES. Using FLIP this way can help clinicians and surgeons personalize the procedure to each patient, even while it’s ongoing. FLIP also can be used with dilation balloons, with the balloon diameter allowing dilation measurement without the need to also use fluoroscopy.
For treating gastroesophageal reflux disease (GERD), the evidence found in existing literature points with less certainty toward use of FLIP.
“The role of FLIP for physiologic evaluation and management in GERD remains appealing; however, the level of evidence is low and currently FLIP should not be used in routine GERD management,” the authors explained. “Future outcome studies are needed to substantiate the utility of FLIP in GERD and to develop metrics that predict severity and treatment response after antireflux procedures.”
FLIP can be used in managing eosinophilic esophagitis, but is recommended only in certain scenarios. According to the authors, FLIP can be used to measure esophageal narrowing and the overall esophageal body. FLIP also can be used to measure esophageal distensibility, and, in the case of at least one study reviewed by the authors, allows “significantly greater accuracy and precision in estimating the effects of remodeling” in certain patients.
Dr. Pandolfino and his colleagues warned that “current recommendations are limited by the low level of evidence and lack of generalized availability of the analysis paradigms.” They noted the need for “further outcome studies that validate the distensibility plateau threshold and further refinements in software analyses to make this methodology more generalizable.”
Overall, the authors concluded, more study still needs to be done to ascertain exactly what FLIP is capable of and when it can be used to greatest effect. In addition to evaluating its benefit in patients with GERD, research should focus on how to make data obtained via FLIP easier to interpret and put to use.
“More work is needed [that] focuses on optimizing data analysis, standardizing protocols, and defining outcome metrics prior to the widespread adoption [of FLIP] into general clinical practice,” the authors wrote.
Dr. Pandolfino disclosed relationships with Medtronic and Sandhill Scientific. Other coauthors did not report any relevant financial disclosures.
*This story updated on 3/9/2017.
New clinical practice advice has been issued for use of the functional lumen imaging probe (FLIP) to assess disorders of the upper gastrointestinal tract, with the main takeaway being the device’s potency in diagnosing achalasia.
“Although the strongest data appear to be focused on the management of achalasia, emerging evidence supports the clinical relevance of FLIP in the assessment of disease severity and as an outcome measure in [eosinophilic esophagitis (EoE)] intervention trials,” wrote the authors of the update, led by John E. Pandolfino, MD, of Northwestern University, Chicago. The report is in the March issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2016.
10.022).
In terms of evaluating the LES, however, FLIP can be used during laparoscopic Heller myotomy or peroral endoscopic myotomy (POEM) as a way of monitoring the LES. Using FLIP this way can help clinicians and surgeons personalize the procedure to each patient, even while it’s ongoing. FLIP also can be used with dilation balloons, with the balloon diameter allowing dilation measurement without the need to also use fluoroscopy.
For treating gastroesophageal reflux disease (GERD), the evidence found in existing literature points with less certainty toward use of FLIP.
“The role of FLIP for physiologic evaluation and management in GERD remains appealing; however, the level of evidence is low and currently FLIP should not be used in routine GERD management,” the authors explained. “Future outcome studies are needed to substantiate the utility of FLIP in GERD and to develop metrics that predict severity and treatment response after antireflux procedures.”
FLIP can be used in managing eosinophilic esophagitis, but is recommended only in certain scenarios. According to the authors, FLIP can be used to measure esophageal narrowing and the overall esophageal body. FLIP also can be used to measure esophageal distensibility, and, in the case of at least one study reviewed by the authors, allows “significantly greater accuracy and precision in estimating the effects of remodeling” in certain patients.
Dr. Pandolfino and his colleagues warned that “current recommendations are limited by the low level of evidence and lack of generalized availability of the analysis paradigms.” They noted the need for “further outcome studies that validate the distensibility plateau threshold and further refinements in software analyses to make this methodology more generalizable.”
Overall, the authors concluded, more study still needs to be done to ascertain exactly what FLIP is capable of and when it can be used to greatest effect. In addition to evaluating its benefit in patients with GERD, research should focus on how to make data obtained via FLIP easier to interpret and put to use.
“More work is needed [that] focuses on optimizing data analysis, standardizing protocols, and defining outcome metrics prior to the widespread adoption [of FLIP] into general clinical practice,” the authors wrote.
Dr. Pandolfino disclosed relationships with Medtronic and Sandhill Scientific. Other coauthors did not report any relevant financial disclosures.
*This story updated on 3/9/2017.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA Clinical Practice Update: Best practice advice on EBT use released
The AGA Institute has released a series of new best practice statements that gastroenterologists should use when considering a patient for endoscopic bariatric treatments or surgeries (EBTs).
“There is a need for less-invasive weight loss therapies that are more effective and durable than lifestyle interventions alone, less invasive and risky than bariatric surgery, and easily performed at a lower expense than that of surgery, thereby allowing improved access and application to a larger segment of the population with moderate obesity,” wrote the authors of the expert review, led by Barham K. Abu Dayyeh, MD of the Mayo Clinic in Rochester, Minn. The report is in the March issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.035). “[EBTs] potentially meet these criteria and may provide an effective treatment approach to obesity in selected patients.”
The best practice statements come from a review of relevant studies in the Ovid, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus databases, among others, that were published between Jan. 1, 2000, and Sept. 30, 2016.
EBTs should be used on patients who have already been unable to lose weight despite lifestyle interventions and more traditional weight loss methods. However, patients that undergo EBTs should also be placed on a weight loss regimen that includes diet, exercise, and lifestyle changes.
In addition to being used for weight loss, they can also be used to transition a patient to traditional bariatric surgery, or to lower a patient’s weight so that they can undergo a different procedure unrelated to bariatric surgery. Anyone being considered for EBT, or a weight loss regimen involving EBT, should be thoroughly evaluated for comorbidities, behavior, or medical concerns that could lead to adverse effects.
Any patients who are placed on EBT regimens should be followed up regularly by their clinicians, to monitor their progress in terms of weight loss and the development of any adverse effects. Should any adverse outcomes arise, alternative therapies should be implemented as soon as possible. Clinicians are advised to know the ins and outs of risks, contraindications, and potential complications related to EBTs before ever implementing them in their practice, let alone recommending them to a patient.
Finally, it’s imperative that health care institutions with EBT programs make sure there are training protocols clinicians must stringently follow before being allowed to perform EBT procedures.
“Moving ahead, it will be important to better incorporate training in obesity management principles into the GI fellowship curriculum to have a more significant impact,” the authors wrote, adding that it’s important to study the “tandem and sequential use of a combination of EBTs and obesity pharmacotherapies in addition to a comprehensive life-style intervention program.”
Dr. Abu Dayyeh disclosed relationships with Apollo Endosurgery, Metamodix, Aspire Bariatric, and GI Dynamics. Other coauthors also disclosed potential conflicting interests.
The AGA Institute has released a series of new best practice statements that gastroenterologists should use when considering a patient for endoscopic bariatric treatments or surgeries (EBTs).
“There is a need for less-invasive weight loss therapies that are more effective and durable than lifestyle interventions alone, less invasive and risky than bariatric surgery, and easily performed at a lower expense than that of surgery, thereby allowing improved access and application to a larger segment of the population with moderate obesity,” wrote the authors of the expert review, led by Barham K. Abu Dayyeh, MD of the Mayo Clinic in Rochester, Minn. The report is in the March issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.035). “[EBTs] potentially meet these criteria and may provide an effective treatment approach to obesity in selected patients.”
The best practice statements come from a review of relevant studies in the Ovid, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus databases, among others, that were published between Jan. 1, 2000, and Sept. 30, 2016.
EBTs should be used on patients who have already been unable to lose weight despite lifestyle interventions and more traditional weight loss methods. However, patients that undergo EBTs should also be placed on a weight loss regimen that includes diet, exercise, and lifestyle changes.
In addition to being used for weight loss, they can also be used to transition a patient to traditional bariatric surgery, or to lower a patient’s weight so that they can undergo a different procedure unrelated to bariatric surgery. Anyone being considered for EBT, or a weight loss regimen involving EBT, should be thoroughly evaluated for comorbidities, behavior, or medical concerns that could lead to adverse effects.
Any patients who are placed on EBT regimens should be followed up regularly by their clinicians, to monitor their progress in terms of weight loss and the development of any adverse effects. Should any adverse outcomes arise, alternative therapies should be implemented as soon as possible. Clinicians are advised to know the ins and outs of risks, contraindications, and potential complications related to EBTs before ever implementing them in their practice, let alone recommending them to a patient.
Finally, it’s imperative that health care institutions with EBT programs make sure there are training protocols clinicians must stringently follow before being allowed to perform EBT procedures.
“Moving ahead, it will be important to better incorporate training in obesity management principles into the GI fellowship curriculum to have a more significant impact,” the authors wrote, adding that it’s important to study the “tandem and sequential use of a combination of EBTs and obesity pharmacotherapies in addition to a comprehensive life-style intervention program.”
Dr. Abu Dayyeh disclosed relationships with Apollo Endosurgery, Metamodix, Aspire Bariatric, and GI Dynamics. Other coauthors also disclosed potential conflicting interests.
The AGA Institute has released a series of new best practice statements that gastroenterologists should use when considering a patient for endoscopic bariatric treatments or surgeries (EBTs).
“There is a need for less-invasive weight loss therapies that are more effective and durable than lifestyle interventions alone, less invasive and risky than bariatric surgery, and easily performed at a lower expense than that of surgery, thereby allowing improved access and application to a larger segment of the population with moderate obesity,” wrote the authors of the expert review, led by Barham K. Abu Dayyeh, MD of the Mayo Clinic in Rochester, Minn. The report is in the March issue of Gastroenterology (doi: 10.1053/j.gastro.2017.01.035). “[EBTs] potentially meet these criteria and may provide an effective treatment approach to obesity in selected patients.”
The best practice statements come from a review of relevant studies in the Ovid, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus databases, among others, that were published between Jan. 1, 2000, and Sept. 30, 2016.
EBTs should be used on patients who have already been unable to lose weight despite lifestyle interventions and more traditional weight loss methods. However, patients that undergo EBTs should also be placed on a weight loss regimen that includes diet, exercise, and lifestyle changes.
In addition to being used for weight loss, they can also be used to transition a patient to traditional bariatric surgery, or to lower a patient’s weight so that they can undergo a different procedure unrelated to bariatric surgery. Anyone being considered for EBT, or a weight loss regimen involving EBT, should be thoroughly evaluated for comorbidities, behavior, or medical concerns that could lead to adverse effects.
Any patients who are placed on EBT regimens should be followed up regularly by their clinicians, to monitor their progress in terms of weight loss and the development of any adverse effects. Should any adverse outcomes arise, alternative therapies should be implemented as soon as possible. Clinicians are advised to know the ins and outs of risks, contraindications, and potential complications related to EBTs before ever implementing them in their practice, let alone recommending them to a patient.
Finally, it’s imperative that health care institutions with EBT programs make sure there are training protocols clinicians must stringently follow before being allowed to perform EBT procedures.
“Moving ahead, it will be important to better incorporate training in obesity management principles into the GI fellowship curriculum to have a more significant impact,” the authors wrote, adding that it’s important to study the “tandem and sequential use of a combination of EBTs and obesity pharmacotherapies in addition to a comprehensive life-style intervention program.”
Dr. Abu Dayyeh disclosed relationships with Apollo Endosurgery, Metamodix, Aspire Bariatric, and GI Dynamics. Other coauthors also disclosed potential conflicting interests.
FROM GASTROENTEROLOGY
AGA Clinical Practice Update: PPIs should be prescribed sparingly, carefully
Updated best practice statements regarding the use of proton pump inhibitors first detail what types of patients should be using short and long-term PPIs.
“When PPIs are appropriately prescribed, their benefits are likely to outweigh their risks [but] when PPIs are inappropriately prescribed, modest risks become important because there is no potential benefit,” wrote the authors of the updated guidance, published in the March issue of Gastroenterology.
“There is currently insufficient evidence to recommend specific strategies for mitigating PPI adverse effects,” noted Daniel E. Freedberg, MD, of Columbia University, New York, and his colleagues.
PPIs should be used on a short-term basis for individuals with gastroesophageal reflux disease (GERD) or conditions such as erosive esophagitis. These patients can also use PPIs for maintenance and occasional symptom management, but those with uncomplicated GERD should be weaned off PPIs if they respond favorably to them.
If a patient is unable to be weaned off PPIs, then ambulatory esophageal pH and impedance monitoring should be done, as this will allow clinicians to determine if the patient has a functional syndrome or GERD. Lifelong PPI treatment should not be considered until this step is taken, according to the new best practice statements.
“Short-term PPIs are highly effective for uncomplicated GERD [but] because patients who cannot reduce PPIs face lifelong therapy, we would consider testing for an acid-related disorder in this situation,” the authors explained. “However, there is no high-quality evidence on which to base this recommendation.”
Patients who have symptomatic GERD or Barrett’s esophagus, either symptomatic or asymptomatic, should be on long-term PPI treatment. Patients who are at a higher risk for NSAID-induced ulcer bleeding should be taking PPIs if they continue to take NSAIDs.
When recommending long-term PPI treatment for a patient, the patient need not use probiotics on a regular basis; there appears to be no need to routinely check the patient’s bone mineral density, serum creatinine, magnesium, or vitamin B12 level on a regular basis. In addition, they need not consume more than the Recommended Dietary Allowance of calcium, magnesium, or vitamin B12.
Finally, the authors state that “specific PPI formulations should not be selected based on potential risks.” This is because no evidence has been found indicating that PPI formulations can be ranked in any way based on risk.
These recommendations come from the AGA’s Clinical Practice Updates Committee, which pored through studies published through July 2016 in the PubMed, EMbase, and Cochrane library databases. Expert opinions and quality assessments on each study contributed to forming these best practice statements.
“In sum, the best current strategies for mitigating the potential risks of long-term PPIs are to avoid prescribing them when they are not indicated and to reduce them to their minimum dose when they are indicated,” Dr. Freedberg and his colleagues concluded.
The researchers did not report any relevant financial disclosures.
Updated best practice statements regarding the use of proton pump inhibitors first detail what types of patients should be using short and long-term PPIs.
“When PPIs are appropriately prescribed, their benefits are likely to outweigh their risks [but] when PPIs are inappropriately prescribed, modest risks become important because there is no potential benefit,” wrote the authors of the updated guidance, published in the March issue of Gastroenterology.
“There is currently insufficient evidence to recommend specific strategies for mitigating PPI adverse effects,” noted Daniel E. Freedberg, MD, of Columbia University, New York, and his colleagues.
PPIs should be used on a short-term basis for individuals with gastroesophageal reflux disease (GERD) or conditions such as erosive esophagitis. These patients can also use PPIs for maintenance and occasional symptom management, but those with uncomplicated GERD should be weaned off PPIs if they respond favorably to them.
If a patient is unable to be weaned off PPIs, then ambulatory esophageal pH and impedance monitoring should be done, as this will allow clinicians to determine if the patient has a functional syndrome or GERD. Lifelong PPI treatment should not be considered until this step is taken, according to the new best practice statements.
“Short-term PPIs are highly effective for uncomplicated GERD [but] because patients who cannot reduce PPIs face lifelong therapy, we would consider testing for an acid-related disorder in this situation,” the authors explained. “However, there is no high-quality evidence on which to base this recommendation.”
Patients who have symptomatic GERD or Barrett’s esophagus, either symptomatic or asymptomatic, should be on long-term PPI treatment. Patients who are at a higher risk for NSAID-induced ulcer bleeding should be taking PPIs if they continue to take NSAIDs.
When recommending long-term PPI treatment for a patient, the patient need not use probiotics on a regular basis; there appears to be no need to routinely check the patient’s bone mineral density, serum creatinine, magnesium, or vitamin B12 level on a regular basis. In addition, they need not consume more than the Recommended Dietary Allowance of calcium, magnesium, or vitamin B12.
Finally, the authors state that “specific PPI formulations should not be selected based on potential risks.” This is because no evidence has been found indicating that PPI formulations can be ranked in any way based on risk.
These recommendations come from the AGA’s Clinical Practice Updates Committee, which pored through studies published through July 2016 in the PubMed, EMbase, and Cochrane library databases. Expert opinions and quality assessments on each study contributed to forming these best practice statements.
“In sum, the best current strategies for mitigating the potential risks of long-term PPIs are to avoid prescribing them when they are not indicated and to reduce them to their minimum dose when they are indicated,” Dr. Freedberg and his colleagues concluded.
The researchers did not report any relevant financial disclosures.
Updated best practice statements regarding the use of proton pump inhibitors first detail what types of patients should be using short and long-term PPIs.
“When PPIs are appropriately prescribed, their benefits are likely to outweigh their risks [but] when PPIs are inappropriately prescribed, modest risks become important because there is no potential benefit,” wrote the authors of the updated guidance, published in the March issue of Gastroenterology.
“There is currently insufficient evidence to recommend specific strategies for mitigating PPI adverse effects,” noted Daniel E. Freedberg, MD, of Columbia University, New York, and his colleagues.
PPIs should be used on a short-term basis for individuals with gastroesophageal reflux disease (GERD) or conditions such as erosive esophagitis. These patients can also use PPIs for maintenance and occasional symptom management, but those with uncomplicated GERD should be weaned off PPIs if they respond favorably to them.
If a patient is unable to be weaned off PPIs, then ambulatory esophageal pH and impedance monitoring should be done, as this will allow clinicians to determine if the patient has a functional syndrome or GERD. Lifelong PPI treatment should not be considered until this step is taken, according to the new best practice statements.
“Short-term PPIs are highly effective for uncomplicated GERD [but] because patients who cannot reduce PPIs face lifelong therapy, we would consider testing for an acid-related disorder in this situation,” the authors explained. “However, there is no high-quality evidence on which to base this recommendation.”
Patients who have symptomatic GERD or Barrett’s esophagus, either symptomatic or asymptomatic, should be on long-term PPI treatment. Patients who are at a higher risk for NSAID-induced ulcer bleeding should be taking PPIs if they continue to take NSAIDs.
When recommending long-term PPI treatment for a patient, the patient need not use probiotics on a regular basis; there appears to be no need to routinely check the patient’s bone mineral density, serum creatinine, magnesium, or vitamin B12 level on a regular basis. In addition, they need not consume more than the Recommended Dietary Allowance of calcium, magnesium, or vitamin B12.
Finally, the authors state that “specific PPI formulations should not be selected based on potential risks.” This is because no evidence has been found indicating that PPI formulations can be ranked in any way based on risk.
These recommendations come from the AGA’s Clinical Practice Updates Committee, which pored through studies published through July 2016 in the PubMed, EMbase, and Cochrane library databases. Expert opinions and quality assessments on each study contributed to forming these best practice statements.
“In sum, the best current strategies for mitigating the potential risks of long-term PPIs are to avoid prescribing them when they are not indicated and to reduce them to their minimum dose when they are indicated,” Dr. Freedberg and his colleagues concluded.
The researchers did not report any relevant financial disclosures.
FROM GASTROENTEROLOGY
Unique, multi-omic profile found in children with autism and functional GI disorders
The gut microbiomes of children with autism spectrum disorder (ASD) and functional gastrointestinal disorders (FGID) had significantly higher levels of several Clostridium species and lower concentrations of other bacteria compared with neurotypical children with and without FGIDs, which correlated with increases in inflammatory cytokines, decreased tryptophan, and increased serotonin, according to a small, single-center, cross-sectional study.
This “unique multi-omic profile [was] specific to ASD-FGID and ASD-FGID with abdominal pain,” wrote Ruth Ann Luna, PhD, of Texas Children’s Microbiome Center at Texas Children’s Hospital, Houston, and her associates. The report was published online in Cellular and Molecular Gastroenterology and Hepatology (doi: 10.1016/j.jcmgh.2016.11.008).
Children with ASD are at increased risk for FGIDs such as functional constipation, nonretentive fecal incontinence, functional abdominal pain, abdominal migraines, and irritable bowel syndrome, compared with their neurotypical peers. Changes in the gut microbiome can affect immunologic pathways and the balance between tryptophan and serotonin. This altered “microbial-gut-brain axis” has been reported in both ASD and FGID, suggesting “that altered gut-brain communications not only may play a role in the increased occurrence of FGIDs in ASD individuals, but could advance our understanding of potential risk factors for FGID in the ASD community,” the researchers wrote.
Previous studies of stool specimens have found higher levels of several species of Clostridium in pediatric ASD compared with neurotypical children. To confirm and expand on that work, the investigators examined microbial and neuroimmune markers in rectal biopsies and blood specimens from 14 children with ASD-FGID, 15 neurotypical children with FGID, and 6 asymptomatic neurotypical children. Participants were recruited from Nationwide Children’s Hospital in Columbus, Ohio. The researchers quantified microbial 16S ribosomal DNA community signatures, cytokines, chemokines, and serotonergic metabolites, and correlated results with parental responses to the Questionnaire on Pediatric Gastrointestinal Symptoms–Rome III version.
The ASD-FGID group had significantly higher numbers for ribosomal DNA sequences for Clostridium lituseburense (P = .002), Lachnoclostridium bolteae (P = .02), Lachnoclostridium hathewayi (P = .03), Clostridium aldenense (P = .04), and Oscillospira plautii (P = .04), compared with neurotypical children with and without FGID. Children with ASD-FGID also had significantly lower levels of Dorea formicigenerans (P = .006), Blautia luti (P = .02), and Sutterella species (P = .03). “Overall, our identification of clostridial species aligns with previous autism studies that have identified microbiome alterations,” the researchers noted.
They also looked specifically at abdominal pain. Children with ASD-FGID and abdominal pain had significantly higher gut mucosal levels of Turicibacter sanguinis (P = .03), Clostridium aldenense (P = .004), Clostridium lituseburense (P = .003), Oscillospira plautii (P = .01), Clostridium disporicum (P = .049), and Clostridium tertium (P = .045) than did any other subgroup, the investigators found. Patients with both ASD-FGID and abdominal pain also had significantly higher levels of C. aldenense (P = .03), O. plautii (P = .04), Tyzzerella species (P = .045), and Parasutterella excrementihominis (P = .04) than did ASD-FGID patients without abdominal pain.
Both C. disporicum and C. tertium correlated with increases in the proinflammatory cytokines IL6 and interferon-gamma. Levels of these cytokines were highest in patients with ASD-FGID, and IL6 was highest of all among children with ASD-FGID with abdominal pain. Another proinflammatory cytokine, IL17A, also correlated with Clostridia species that were enriched in children with ASD-FGID. Both IL6 and IL17A have been implicated in autism-like phenotypes in rodents, the researchers noted. Several other cytokines also were linked to ASD-FGID, and abdominal pain correlated significantly with increases in MCP-1 (P = .03) and eotaxin (P = .03).
Gut mucosal levels of tryptophan were significantly lower among children with ASD-FGID compared with neurotypical children, either with (P = .006) or without (P = .009) FGID. In contrast, gut mucosal levels of 5-HIAA, the primary metabolite of serotonin, were significantly higher among children with ASD-FGID compared with neurotypical children (P = .01). Increased 5-HIAA also correlated significantly with abdominal pain (P = .04). Six species of bacteria correlated significantly with tryptophan or serotonin, implicating the gut microbiome in the serotonin pathway.
“Although these initial findings are correlative, these data form the framework for future studies targeting tryptophan-serotonin metabolism and inflammatory pathways in FGID in ASD,” the researchers concluded.
The U.S. Department of Health and Human Services funded the work. The investigators had no relevant disclosures.
Autism-spectrum disorder is a serious and increasingly prevalent developmental behavior disorder often accompanied and aggravated by a range of gastrointestinal and cognitive dysfunctions. Its etiology probably involves maternal diet and inflammatory events that alter central nervous system neurodevelopment critical to the cognition of social interaction. Candidate causal products of these events include the cytokines IL-6 and IL-17A, and certain bioactive amines, notably serotonin. Functional gastrointestinal disorders share these same molecules as biomarkers and disease modifiers, probably elicited in part by the intestinal microbiome. Hence, the comorbidity in ASD suggests these two disease processes are etiologically related.
The study by Luna and colleagues tightens the case for a microbial hub and serotonin and cytokine spokes in the gastrointestinal dysfunction of ASD: elevated mucosal tissue levels of select microbial taxa, mainly members of the genus Clostridium, and mucosal production of cytokines and serotonin-pathway bioamines associated with these and other select microbial species. Important and challenging questions loom ahead. What are the direct mucosal cell types and functions targeted of this network for the microbiota, and via what microbial products? Might they elicit epithelial or mucosal hematopoietic cell cytokine production that in turn causes mucosal bioamine secretion? And, what associated microbiota and products are just secondarily altered and not causally involved? The exciting study of Luna and colleagues raises confidence for this path ahead, and its promise for clarifying ASD pathogenesis and uncovering targetable elements for intervention.
Jonathan Braun, MD, PhD, is professor and chair of pathology and laboratory medicine, UCLA David Geffen School of Medicine, UCLA Health System, Los Angeles. He has no conflicts of interest.
Autism-spectrum disorder is a serious and increasingly prevalent developmental behavior disorder often accompanied and aggravated by a range of gastrointestinal and cognitive dysfunctions. Its etiology probably involves maternal diet and inflammatory events that alter central nervous system neurodevelopment critical to the cognition of social interaction. Candidate causal products of these events include the cytokines IL-6 and IL-17A, and certain bioactive amines, notably serotonin. Functional gastrointestinal disorders share these same molecules as biomarkers and disease modifiers, probably elicited in part by the intestinal microbiome. Hence, the comorbidity in ASD suggests these two disease processes are etiologically related.
The study by Luna and colleagues tightens the case for a microbial hub and serotonin and cytokine spokes in the gastrointestinal dysfunction of ASD: elevated mucosal tissue levels of select microbial taxa, mainly members of the genus Clostridium, and mucosal production of cytokines and serotonin-pathway bioamines associated with these and other select microbial species. Important and challenging questions loom ahead. What are the direct mucosal cell types and functions targeted of this network for the microbiota, and via what microbial products? Might they elicit epithelial or mucosal hematopoietic cell cytokine production that in turn causes mucosal bioamine secretion? And, what associated microbiota and products are just secondarily altered and not causally involved? The exciting study of Luna and colleagues raises confidence for this path ahead, and its promise for clarifying ASD pathogenesis and uncovering targetable elements for intervention.
Jonathan Braun, MD, PhD, is professor and chair of pathology and laboratory medicine, UCLA David Geffen School of Medicine, UCLA Health System, Los Angeles. He has no conflicts of interest.
Autism-spectrum disorder is a serious and increasingly prevalent developmental behavior disorder often accompanied and aggravated by a range of gastrointestinal and cognitive dysfunctions. Its etiology probably involves maternal diet and inflammatory events that alter central nervous system neurodevelopment critical to the cognition of social interaction. Candidate causal products of these events include the cytokines IL-6 and IL-17A, and certain bioactive amines, notably serotonin. Functional gastrointestinal disorders share these same molecules as biomarkers and disease modifiers, probably elicited in part by the intestinal microbiome. Hence, the comorbidity in ASD suggests these two disease processes are etiologically related.
The study by Luna and colleagues tightens the case for a microbial hub and serotonin and cytokine spokes in the gastrointestinal dysfunction of ASD: elevated mucosal tissue levels of select microbial taxa, mainly members of the genus Clostridium, and mucosal production of cytokines and serotonin-pathway bioamines associated with these and other select microbial species. Important and challenging questions loom ahead. What are the direct mucosal cell types and functions targeted of this network for the microbiota, and via what microbial products? Might they elicit epithelial or mucosal hematopoietic cell cytokine production that in turn causes mucosal bioamine secretion? And, what associated microbiota and products are just secondarily altered and not causally involved? The exciting study of Luna and colleagues raises confidence for this path ahead, and its promise for clarifying ASD pathogenesis and uncovering targetable elements for intervention.
Jonathan Braun, MD, PhD, is professor and chair of pathology and laboratory medicine, UCLA David Geffen School of Medicine, UCLA Health System, Los Angeles. He has no conflicts of interest.
The gut microbiomes of children with autism spectrum disorder (ASD) and functional gastrointestinal disorders (FGID) had significantly higher levels of several Clostridium species and lower concentrations of other bacteria compared with neurotypical children with and without FGIDs, which correlated with increases in inflammatory cytokines, decreased tryptophan, and increased serotonin, according to a small, single-center, cross-sectional study.
This “unique multi-omic profile [was] specific to ASD-FGID and ASD-FGID with abdominal pain,” wrote Ruth Ann Luna, PhD, of Texas Children’s Microbiome Center at Texas Children’s Hospital, Houston, and her associates. The report was published online in Cellular and Molecular Gastroenterology and Hepatology (doi: 10.1016/j.jcmgh.2016.11.008).
Children with ASD are at increased risk for FGIDs such as functional constipation, nonretentive fecal incontinence, functional abdominal pain, abdominal migraines, and irritable bowel syndrome, compared with their neurotypical peers. Changes in the gut microbiome can affect immunologic pathways and the balance between tryptophan and serotonin. This altered “microbial-gut-brain axis” has been reported in both ASD and FGID, suggesting “that altered gut-brain communications not only may play a role in the increased occurrence of FGIDs in ASD individuals, but could advance our understanding of potential risk factors for FGID in the ASD community,” the researchers wrote.
Previous studies of stool specimens have found higher levels of several species of Clostridium in pediatric ASD compared with neurotypical children. To confirm and expand on that work, the investigators examined microbial and neuroimmune markers in rectal biopsies and blood specimens from 14 children with ASD-FGID, 15 neurotypical children with FGID, and 6 asymptomatic neurotypical children. Participants were recruited from Nationwide Children’s Hospital in Columbus, Ohio. The researchers quantified microbial 16S ribosomal DNA community signatures, cytokines, chemokines, and serotonergic metabolites, and correlated results with parental responses to the Questionnaire on Pediatric Gastrointestinal Symptoms–Rome III version.
The ASD-FGID group had significantly higher numbers for ribosomal DNA sequences for Clostridium lituseburense (P = .002), Lachnoclostridium bolteae (P = .02), Lachnoclostridium hathewayi (P = .03), Clostridium aldenense (P = .04), and Oscillospira plautii (P = .04), compared with neurotypical children with and without FGID. Children with ASD-FGID also had significantly lower levels of Dorea formicigenerans (P = .006), Blautia luti (P = .02), and Sutterella species (P = .03). “Overall, our identification of clostridial species aligns with previous autism studies that have identified microbiome alterations,” the researchers noted.
They also looked specifically at abdominal pain. Children with ASD-FGID and abdominal pain had significantly higher gut mucosal levels of Turicibacter sanguinis (P = .03), Clostridium aldenense (P = .004), Clostridium lituseburense (P = .003), Oscillospira plautii (P = .01), Clostridium disporicum (P = .049), and Clostridium tertium (P = .045) than did any other subgroup, the investigators found. Patients with both ASD-FGID and abdominal pain also had significantly higher levels of C. aldenense (P = .03), O. plautii (P = .04), Tyzzerella species (P = .045), and Parasutterella excrementihominis (P = .04) than did ASD-FGID patients without abdominal pain.
Both C. disporicum and C. tertium correlated with increases in the proinflammatory cytokines IL6 and interferon-gamma. Levels of these cytokines were highest in patients with ASD-FGID, and IL6 was highest of all among children with ASD-FGID with abdominal pain. Another proinflammatory cytokine, IL17A, also correlated with Clostridia species that were enriched in children with ASD-FGID. Both IL6 and IL17A have been implicated in autism-like phenotypes in rodents, the researchers noted. Several other cytokines also were linked to ASD-FGID, and abdominal pain correlated significantly with increases in MCP-1 (P = .03) and eotaxin (P = .03).
Gut mucosal levels of tryptophan were significantly lower among children with ASD-FGID compared with neurotypical children, either with (P = .006) or without (P = .009) FGID. In contrast, gut mucosal levels of 5-HIAA, the primary metabolite of serotonin, were significantly higher among children with ASD-FGID compared with neurotypical children (P = .01). Increased 5-HIAA also correlated significantly with abdominal pain (P = .04). Six species of bacteria correlated significantly with tryptophan or serotonin, implicating the gut microbiome in the serotonin pathway.
“Although these initial findings are correlative, these data form the framework for future studies targeting tryptophan-serotonin metabolism and inflammatory pathways in FGID in ASD,” the researchers concluded.
The U.S. Department of Health and Human Services funded the work. The investigators had no relevant disclosures.
The gut microbiomes of children with autism spectrum disorder (ASD) and functional gastrointestinal disorders (FGID) had significantly higher levels of several Clostridium species and lower concentrations of other bacteria compared with neurotypical children with and without FGIDs, which correlated with increases in inflammatory cytokines, decreased tryptophan, and increased serotonin, according to a small, single-center, cross-sectional study.
This “unique multi-omic profile [was] specific to ASD-FGID and ASD-FGID with abdominal pain,” wrote Ruth Ann Luna, PhD, of Texas Children’s Microbiome Center at Texas Children’s Hospital, Houston, and her associates. The report was published online in Cellular and Molecular Gastroenterology and Hepatology (doi: 10.1016/j.jcmgh.2016.11.008).
Children with ASD are at increased risk for FGIDs such as functional constipation, nonretentive fecal incontinence, functional abdominal pain, abdominal migraines, and irritable bowel syndrome, compared with their neurotypical peers. Changes in the gut microbiome can affect immunologic pathways and the balance between tryptophan and serotonin. This altered “microbial-gut-brain axis” has been reported in both ASD and FGID, suggesting “that altered gut-brain communications not only may play a role in the increased occurrence of FGIDs in ASD individuals, but could advance our understanding of potential risk factors for FGID in the ASD community,” the researchers wrote.
Previous studies of stool specimens have found higher levels of several species of Clostridium in pediatric ASD compared with neurotypical children. To confirm and expand on that work, the investigators examined microbial and neuroimmune markers in rectal biopsies and blood specimens from 14 children with ASD-FGID, 15 neurotypical children with FGID, and 6 asymptomatic neurotypical children. Participants were recruited from Nationwide Children’s Hospital in Columbus, Ohio. The researchers quantified microbial 16S ribosomal DNA community signatures, cytokines, chemokines, and serotonergic metabolites, and correlated results with parental responses to the Questionnaire on Pediatric Gastrointestinal Symptoms–Rome III version.
The ASD-FGID group had significantly higher numbers for ribosomal DNA sequences for Clostridium lituseburense (P = .002), Lachnoclostridium bolteae (P = .02), Lachnoclostridium hathewayi (P = .03), Clostridium aldenense (P = .04), and Oscillospira plautii (P = .04), compared with neurotypical children with and without FGID. Children with ASD-FGID also had significantly lower levels of Dorea formicigenerans (P = .006), Blautia luti (P = .02), and Sutterella species (P = .03). “Overall, our identification of clostridial species aligns with previous autism studies that have identified microbiome alterations,” the researchers noted.
They also looked specifically at abdominal pain. Children with ASD-FGID and abdominal pain had significantly higher gut mucosal levels of Turicibacter sanguinis (P = .03), Clostridium aldenense (P = .004), Clostridium lituseburense (P = .003), Oscillospira plautii (P = .01), Clostridium disporicum (P = .049), and Clostridium tertium (P = .045) than did any other subgroup, the investigators found. Patients with both ASD-FGID and abdominal pain also had significantly higher levels of C. aldenense (P = .03), O. plautii (P = .04), Tyzzerella species (P = .045), and Parasutterella excrementihominis (P = .04) than did ASD-FGID patients without abdominal pain.
Both C. disporicum and C. tertium correlated with increases in the proinflammatory cytokines IL6 and interferon-gamma. Levels of these cytokines were highest in patients with ASD-FGID, and IL6 was highest of all among children with ASD-FGID with abdominal pain. Another proinflammatory cytokine, IL17A, also correlated with Clostridia species that were enriched in children with ASD-FGID. Both IL6 and IL17A have been implicated in autism-like phenotypes in rodents, the researchers noted. Several other cytokines also were linked to ASD-FGID, and abdominal pain correlated significantly with increases in MCP-1 (P = .03) and eotaxin (P = .03).
Gut mucosal levels of tryptophan were significantly lower among children with ASD-FGID compared with neurotypical children, either with (P = .006) or without (P = .009) FGID. In contrast, gut mucosal levels of 5-HIAA, the primary metabolite of serotonin, were significantly higher among children with ASD-FGID compared with neurotypical children (P = .01). Increased 5-HIAA also correlated significantly with abdominal pain (P = .04). Six species of bacteria correlated significantly with tryptophan or serotonin, implicating the gut microbiome in the serotonin pathway.
“Although these initial findings are correlative, these data form the framework for future studies targeting tryptophan-serotonin metabolism and inflammatory pathways in FGID in ASD,” the researchers concluded.
The U.S. Department of Health and Human Services funded the work. The investigators had no relevant disclosures.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: The mucosal microbiome of children with comorbid autism spectrum disorder and functional gastrointestinal disorders significantly differed from that of neurotypical children with and without FGIDs, and these differences correlated with altered levels of inflammatory cytokines, tryptophan, and serotonin.
Major finding: Children with ASD-FGID had significant increases in Clostridium lituseburense (P = .002), Lachnoclostridium bolteae (P = .02), Lachnoclostridium hathewayi (P = .03), Clostridium aldenense (P = .04), and Oscillospira plautii (P = .04), and significant decreases in Dorea formicigenerans (P = .006), Blautia luti (P = .020), and Sutterella species (P = .025). The ASD-FGID phenotype was characterized by significantly lower gut levels of tryptophan, with higher levels of the serotonin metabolite 5-HIAA, and with several proinflammatory cytokines. Several bacterial species correlated with tryptophan, serotonin, or proinflammatory cytokines.
Data source: A single-center cross-sectional study of 14 children with ASD-FGID and 21 neurotypical children, of whom 15 had FGIDs.
Disclosures: The U.S. Department of Health and Human Services funded the work. The investigators had no relevant disclosures.
VIDEO: Infectious enteritis quadrupled short-term risk of IBS
More than 10% of patients developed irritable bowel syndrome (IBS) within a year after infectious enteritis, which gave them a more than fourfold greater risk than that of controls, according to a systematic review and meta-analysis of 45 studies.
“Protozoal and bacterial enteritis confer the greatest overall risk, although the magnitude of increased risk diminishes with time since exposure,” Fabiane B. Klem, MD, and Akhilesh Wadhwa, MD, of Mayo Clinic in Rochester, Minn., and their associates wrote in the April issue of Gastroenterology. Other significant risk factors for postinfectious IBS (PI-IBS) included female sex, clinically severe infections, antibiotic therapy, and comorbid psychological distress, they said.
Postinfectious IBS can last at least a decade after resolution of campylobacteriosis, shigellosis, salmonellosis, giardiasis, and norovirus infections, even when patients have no other risk factors for IBS, the researchers noted. To update and expand the most recent meta-analysis of this topic (Aliment Pharmacol Ther. 2007;26:535-44), the investigators searched Ovid Medline, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews for studies published from 2006 through Aug. 31, 2015. This search yielded 45 studies, including 30 studies comparing infected patients with controls, who were usually matched by age, sex, and geographic location (Gastroenterology. 2017 Jan 6. doi: 10.1053/j.gastro.2016.12.039).
In all, 10.1% of patients with infectious enteritis developed IBS in the next 12 months (95% confidence interval, 7.2-14.1) – a 4.2-fold increase in risk, compared with that of controls (risk ratio, 4.2; 95% CI, 3.2-5.7). This risk subsequently dropped, but remained significantly elevated (RR, 2.3; 95% CI, 1.8-3.0), compared with controls. “Of patients with enteritis caused by protozoa or parasites, 41.9% developed IBS; of patients with enteritis caused by bacterial infection, 13.8% developed IBS,” the researchers emphasized. Patients with these infections remained at elevated risk of PI-IBS even after 1 year. Viral enteritis also significantly increased the risk of PI-IBS, but risk dropped to baseline levels after a year.
Among 10 pooled studies of IBS subtypes, 46% of patients had mixed IBS, 39% had diarrhea-predominant IBS, and 15% had constipation-predominant IBS. Female sex doubled the odds of PI-IBS (odds ratio, 2.2; 95% CI, 1.6-3.1) in 11 pooled studies. Significant clinical risk factors for PI-IBS included diarrhea lasting more than 7 days (eight studies; OR, 2.6; 95% CI, 1.5-4.6), bloody stool (four studies; OR, 1.9; 95% CI, 1.1-3.0), and antibiotic therapy during infectious enteritis (seven studies; OR, 1.7; 95% CI, 1.2-2.4).
Multiple reports linked PI-IBS to clinical psychological distress at the time of infectious enteritis. Specific risk factors included depression based on the Hospitalization Anxiety and Depression Scale (five studies; OR, 1.5; 95% CI, 1.2-1.9), anxiety based on the Hospital Anxiety and Depression Scale (four studies; OR, 2.0; 95% CI, 1.3-2.9), somatization (four studies; OR, 4.1; 95% CI, 2.7-6.0), and neuroticism (two studies; OR, 3.3; 95% CI, 1.6-6.6). Isolated studies also implicated hypochondriasis, extroversion, negative illness beliefs, stress, sleep disturbance, and adverse life events in the preceding year, the researchers said.
They found no evidence of publication bias, but noted a substantial amount of heterogeneity among studies. Also, some studies did not report multivariate analyses, so individual odds ratios might reflect “a conglomeration of factors,” they said.
The National Institutes of Health and the American Gastroenterological Association funded the work. The investigators reported having no conflicts of interest.
Source: American Gastroenterological Association
The phenomenon of IBS developing after a bout of gastroenteritis (postinfectious [PI]–IBS) was first reported in 1950 and subsequently elaborated by studies from Oxford (Q J Med. 1962;123:307-22), Sheffield (Gut. 1999;44:400-6), and Nottingham (BMJ 1997;314:779-82; Gut. 2000;47:804-11). It has proven to be a fertile area for research, which is the basis for this excellent meta-analysis.
The authors identified 45 studies, 29 in the last decade including a total of 21,421 participants with exposure to gastroenteritis. The pooled prevalence for PI-IBS was 11.5% (95% CI, 8.2%-15.8%) but with considerable heterogeneity, which the authors attempted to explain by a number of subgroup analyses. The authors report that protozoal infection seems to have a higher rate of PI-IBS than bacterial or viral infection, though some caution is warranted, since these figures rely on reports from just one outbreak of giardiasis in Bergen, Norway (Scand J Gastroenterol. 2012;47:956-61). However, if true, this might suggest that a different immune response could be responsible, a feature which others have suggested might predispose particular individuals to PI-IBS (Gut. 2016;65[8]1279-88).
The meta-analysis confirms the consistent increased risk in female patients (odds ratio, 1.69), anxiety (OR, 1.97), and somatization (greatest RR, 4.05), all common risks for the development of IBS but not specific to PI-IBS. Initial disease severity indicators, including bloody stool and more than 7 days of initial illness, which might indicate the severity of underlying damage to the gut, were shown to be significant risk factors. Animal studies of acute infection, particularly parasitic infestation, indicate that significant changes can be seen in both nerve and muscle, but routine histology in PI-IBS patients is normal. Infection produces a striking increase in gut permeability (Gut 2000;47:804-11), a feature of IBS whose molecular basis has been demonstrated by a series of elegant studies (Gut. 2017 Jan 12 [Epub ahead of print]; Gut. 2015;64:1379-88) demonstrating altered tight junctions and immune activation in IBS with diarrhea. The authors found treatment with antibiotics increased the risk of PI-IBS but whether this is attributable to confounding by indication is unclear.
This meta-analysis indicates that PI-IBS also potentially is the most common cause of IBS, given that both the Centers for Disease Control and Prevention in the United States and community surveys in the United Kingdom (BMJ. 1999;318:1046-50) indicate that gastroenteritis affects around 1 in 5 of the population each year. If the incidence of PI-IBS is around 10%, modeling suggests PI-IBS could account for the majority of new cases (J Neurogastroenterol Motil. 2012;18:200-4).
Dr. Robin Spiller is professor of gastroenterology, NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham Digestive Diseases Centre, University of Nottingham, England. He has no relevant conflicts of interest.
The phenomenon of IBS developing after a bout of gastroenteritis (postinfectious [PI]–IBS) was first reported in 1950 and subsequently elaborated by studies from Oxford (Q J Med. 1962;123:307-22), Sheffield (Gut. 1999;44:400-6), and Nottingham (BMJ 1997;314:779-82; Gut. 2000;47:804-11). It has proven to be a fertile area for research, which is the basis for this excellent meta-analysis.
The authors identified 45 studies, 29 in the last decade including a total of 21,421 participants with exposure to gastroenteritis. The pooled prevalence for PI-IBS was 11.5% (95% CI, 8.2%-15.8%) but with considerable heterogeneity, which the authors attempted to explain by a number of subgroup analyses. The authors report that protozoal infection seems to have a higher rate of PI-IBS than bacterial or viral infection, though some caution is warranted, since these figures rely on reports from just one outbreak of giardiasis in Bergen, Norway (Scand J Gastroenterol. 2012;47:956-61). However, if true, this might suggest that a different immune response could be responsible, a feature which others have suggested might predispose particular individuals to PI-IBS (Gut. 2016;65[8]1279-88).
The meta-analysis confirms the consistent increased risk in female patients (odds ratio, 1.69), anxiety (OR, 1.97), and somatization (greatest RR, 4.05), all common risks for the development of IBS but not specific to PI-IBS. Initial disease severity indicators, including bloody stool and more than 7 days of initial illness, which might indicate the severity of underlying damage to the gut, were shown to be significant risk factors. Animal studies of acute infection, particularly parasitic infestation, indicate that significant changes can be seen in both nerve and muscle, but routine histology in PI-IBS patients is normal. Infection produces a striking increase in gut permeability (Gut 2000;47:804-11), a feature of IBS whose molecular basis has been demonstrated by a series of elegant studies (Gut. 2017 Jan 12 [Epub ahead of print]; Gut. 2015;64:1379-88) demonstrating altered tight junctions and immune activation in IBS with diarrhea. The authors found treatment with antibiotics increased the risk of PI-IBS but whether this is attributable to confounding by indication is unclear.
This meta-analysis indicates that PI-IBS also potentially is the most common cause of IBS, given that both the Centers for Disease Control and Prevention in the United States and community surveys in the United Kingdom (BMJ. 1999;318:1046-50) indicate that gastroenteritis affects around 1 in 5 of the population each year. If the incidence of PI-IBS is around 10%, modeling suggests PI-IBS could account for the majority of new cases (J Neurogastroenterol Motil. 2012;18:200-4).
Dr. Robin Spiller is professor of gastroenterology, NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham Digestive Diseases Centre, University of Nottingham, England. He has no relevant conflicts of interest.
The phenomenon of IBS developing after a bout of gastroenteritis (postinfectious [PI]–IBS) was first reported in 1950 and subsequently elaborated by studies from Oxford (Q J Med. 1962;123:307-22), Sheffield (Gut. 1999;44:400-6), and Nottingham (BMJ 1997;314:779-82; Gut. 2000;47:804-11). It has proven to be a fertile area for research, which is the basis for this excellent meta-analysis.
The authors identified 45 studies, 29 in the last decade including a total of 21,421 participants with exposure to gastroenteritis. The pooled prevalence for PI-IBS was 11.5% (95% CI, 8.2%-15.8%) but with considerable heterogeneity, which the authors attempted to explain by a number of subgroup analyses. The authors report that protozoal infection seems to have a higher rate of PI-IBS than bacterial or viral infection, though some caution is warranted, since these figures rely on reports from just one outbreak of giardiasis in Bergen, Norway (Scand J Gastroenterol. 2012;47:956-61). However, if true, this might suggest that a different immune response could be responsible, a feature which others have suggested might predispose particular individuals to PI-IBS (Gut. 2016;65[8]1279-88).
The meta-analysis confirms the consistent increased risk in female patients (odds ratio, 1.69), anxiety (OR, 1.97), and somatization (greatest RR, 4.05), all common risks for the development of IBS but not specific to PI-IBS. Initial disease severity indicators, including bloody stool and more than 7 days of initial illness, which might indicate the severity of underlying damage to the gut, were shown to be significant risk factors. Animal studies of acute infection, particularly parasitic infestation, indicate that significant changes can be seen in both nerve and muscle, but routine histology in PI-IBS patients is normal. Infection produces a striking increase in gut permeability (Gut 2000;47:804-11), a feature of IBS whose molecular basis has been demonstrated by a series of elegant studies (Gut. 2017 Jan 12 [Epub ahead of print]; Gut. 2015;64:1379-88) demonstrating altered tight junctions and immune activation in IBS with diarrhea. The authors found treatment with antibiotics increased the risk of PI-IBS but whether this is attributable to confounding by indication is unclear.
This meta-analysis indicates that PI-IBS also potentially is the most common cause of IBS, given that both the Centers for Disease Control and Prevention in the United States and community surveys in the United Kingdom (BMJ. 1999;318:1046-50) indicate that gastroenteritis affects around 1 in 5 of the population each year. If the incidence of PI-IBS is around 10%, modeling suggests PI-IBS could account for the majority of new cases (J Neurogastroenterol Motil. 2012;18:200-4).
Dr. Robin Spiller is professor of gastroenterology, NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham Digestive Diseases Centre, University of Nottingham, England. He has no relevant conflicts of interest.
More than 10% of patients developed irritable bowel syndrome (IBS) within a year after infectious enteritis, which gave them a more than fourfold greater risk than that of controls, according to a systematic review and meta-analysis of 45 studies.
“Protozoal and bacterial enteritis confer the greatest overall risk, although the magnitude of increased risk diminishes with time since exposure,” Fabiane B. Klem, MD, and Akhilesh Wadhwa, MD, of Mayo Clinic in Rochester, Minn., and their associates wrote in the April issue of Gastroenterology. Other significant risk factors for postinfectious IBS (PI-IBS) included female sex, clinically severe infections, antibiotic therapy, and comorbid psychological distress, they said.
Postinfectious IBS can last at least a decade after resolution of campylobacteriosis, shigellosis, salmonellosis, giardiasis, and norovirus infections, even when patients have no other risk factors for IBS, the researchers noted. To update and expand the most recent meta-analysis of this topic (Aliment Pharmacol Ther. 2007;26:535-44), the investigators searched Ovid Medline, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews for studies published from 2006 through Aug. 31, 2015. This search yielded 45 studies, including 30 studies comparing infected patients with controls, who were usually matched by age, sex, and geographic location (Gastroenterology. 2017 Jan 6. doi: 10.1053/j.gastro.2016.12.039).
In all, 10.1% of patients with infectious enteritis developed IBS in the next 12 months (95% confidence interval, 7.2-14.1) – a 4.2-fold increase in risk, compared with that of controls (risk ratio, 4.2; 95% CI, 3.2-5.7). This risk subsequently dropped, but remained significantly elevated (RR, 2.3; 95% CI, 1.8-3.0), compared with controls. “Of patients with enteritis caused by protozoa or parasites, 41.9% developed IBS; of patients with enteritis caused by bacterial infection, 13.8% developed IBS,” the researchers emphasized. Patients with these infections remained at elevated risk of PI-IBS even after 1 year. Viral enteritis also significantly increased the risk of PI-IBS, but risk dropped to baseline levels after a year.
Among 10 pooled studies of IBS subtypes, 46% of patients had mixed IBS, 39% had diarrhea-predominant IBS, and 15% had constipation-predominant IBS. Female sex doubled the odds of PI-IBS (odds ratio, 2.2; 95% CI, 1.6-3.1) in 11 pooled studies. Significant clinical risk factors for PI-IBS included diarrhea lasting more than 7 days (eight studies; OR, 2.6; 95% CI, 1.5-4.6), bloody stool (four studies; OR, 1.9; 95% CI, 1.1-3.0), and antibiotic therapy during infectious enteritis (seven studies; OR, 1.7; 95% CI, 1.2-2.4).
Multiple reports linked PI-IBS to clinical psychological distress at the time of infectious enteritis. Specific risk factors included depression based on the Hospitalization Anxiety and Depression Scale (five studies; OR, 1.5; 95% CI, 1.2-1.9), anxiety based on the Hospital Anxiety and Depression Scale (four studies; OR, 2.0; 95% CI, 1.3-2.9), somatization (four studies; OR, 4.1; 95% CI, 2.7-6.0), and neuroticism (two studies; OR, 3.3; 95% CI, 1.6-6.6). Isolated studies also implicated hypochondriasis, extroversion, negative illness beliefs, stress, sleep disturbance, and adverse life events in the preceding year, the researchers said.
They found no evidence of publication bias, but noted a substantial amount of heterogeneity among studies. Also, some studies did not report multivariate analyses, so individual odds ratios might reflect “a conglomeration of factors,” they said.
The National Institutes of Health and the American Gastroenterological Association funded the work. The investigators reported having no conflicts of interest.
Source: American Gastroenterological Association
More than 10% of patients developed irritable bowel syndrome (IBS) within a year after infectious enteritis, which gave them a more than fourfold greater risk than that of controls, according to a systematic review and meta-analysis of 45 studies.
“Protozoal and bacterial enteritis confer the greatest overall risk, although the magnitude of increased risk diminishes with time since exposure,” Fabiane B. Klem, MD, and Akhilesh Wadhwa, MD, of Mayo Clinic in Rochester, Minn., and their associates wrote in the April issue of Gastroenterology. Other significant risk factors for postinfectious IBS (PI-IBS) included female sex, clinically severe infections, antibiotic therapy, and comorbid psychological distress, they said.
Postinfectious IBS can last at least a decade after resolution of campylobacteriosis, shigellosis, salmonellosis, giardiasis, and norovirus infections, even when patients have no other risk factors for IBS, the researchers noted. To update and expand the most recent meta-analysis of this topic (Aliment Pharmacol Ther. 2007;26:535-44), the investigators searched Ovid Medline, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews for studies published from 2006 through Aug. 31, 2015. This search yielded 45 studies, including 30 studies comparing infected patients with controls, who were usually matched by age, sex, and geographic location (Gastroenterology. 2017 Jan 6. doi: 10.1053/j.gastro.2016.12.039).
In all, 10.1% of patients with infectious enteritis developed IBS in the next 12 months (95% confidence interval, 7.2-14.1) – a 4.2-fold increase in risk, compared with that of controls (risk ratio, 4.2; 95% CI, 3.2-5.7). This risk subsequently dropped, but remained significantly elevated (RR, 2.3; 95% CI, 1.8-3.0), compared with controls. “Of patients with enteritis caused by protozoa or parasites, 41.9% developed IBS; of patients with enteritis caused by bacterial infection, 13.8% developed IBS,” the researchers emphasized. Patients with these infections remained at elevated risk of PI-IBS even after 1 year. Viral enteritis also significantly increased the risk of PI-IBS, but risk dropped to baseline levels after a year.
Among 10 pooled studies of IBS subtypes, 46% of patients had mixed IBS, 39% had diarrhea-predominant IBS, and 15% had constipation-predominant IBS. Female sex doubled the odds of PI-IBS (odds ratio, 2.2; 95% CI, 1.6-3.1) in 11 pooled studies. Significant clinical risk factors for PI-IBS included diarrhea lasting more than 7 days (eight studies; OR, 2.6; 95% CI, 1.5-4.6), bloody stool (four studies; OR, 1.9; 95% CI, 1.1-3.0), and antibiotic therapy during infectious enteritis (seven studies; OR, 1.7; 95% CI, 1.2-2.4).
Multiple reports linked PI-IBS to clinical psychological distress at the time of infectious enteritis. Specific risk factors included depression based on the Hospitalization Anxiety and Depression Scale (five studies; OR, 1.5; 95% CI, 1.2-1.9), anxiety based on the Hospital Anxiety and Depression Scale (four studies; OR, 2.0; 95% CI, 1.3-2.9), somatization (four studies; OR, 4.1; 95% CI, 2.7-6.0), and neuroticism (two studies; OR, 3.3; 95% CI, 1.6-6.6). Isolated studies also implicated hypochondriasis, extroversion, negative illness beliefs, stress, sleep disturbance, and adverse life events in the preceding year, the researchers said.
They found no evidence of publication bias, but noted a substantial amount of heterogeneity among studies. Also, some studies did not report multivariate analyses, so individual odds ratios might reflect “a conglomeration of factors,” they said.
The National Institutes of Health and the American Gastroenterological Association funded the work. The investigators reported having no conflicts of interest.
Source: American Gastroenterological Association
FROM GASTROENTEROLOGY
Key clinical point.
Major finding: A total of 10.1% of patients with infectious enteritis developed IBS in the next 12 months, a 4.2-fold increase in risk, compared with that of controls.
Data source: A systematic review and meta-analysis of 45 studies.
Disclosures: The National Institutes of Health and the American Gastroenterological Association funded the work. The investigators reported having no conflicts of interest.
AGA Clinical Practice Update: Clostridium difficile in IBD
Inflammatory bowel disease (IBD) increases the risk and severity of Clostridium difficile infection (CDI) while CDI tends to complicate and worsen the clinical course of IBD, experts note in a clinical practice update.
Thus, it is crucial that clinicians pursue stool testing for toxigenic C. difficile infection whenever a patient with IBD presents with a colitis flare, regardless of the recent antibiotic history, wrote Sahil Khanna, MBBS, of the Mayo Clinic, Rochester, Minn., and his associates (Clin Gastroenterol Hepatol. 2016 Feb. doi: 10.1016/j.cgh.2016.10.024). Clinicians should also test for recurrent CDI if symptoms of colitis persist or return after antibiotic therapy for CDI, they emphasized.
CDI can present atypically in IBD. Underlying colitis leads to colonic dysbiosis and loss of resistance to bacterial colonization, which permits CDI to develop even when patients have not recently received antibiotics. Patients with IBD also tend to develop CDI starting at younger ages, more often acquire it from community settings, and may lack the typical colonoscopic features of CDI. Simple colonization of C. difficile without infection also is more common in patients with IBD than in those without IBD, the experts note.
The authors contradict guidelines from both the American College of Gastroenterology and Infectious Diseases Society of America by recommending consideration of vancomycin over metronidazole for treatment of CDI. Not only are C. difficile treatment failures with metronidazole rising, but vancomycin was more effective than was metronidazole in a recent post hoc analysis (Clin Infect Dis. 2014;59[3]:345-54) of two large multicenter phase III trials. Furthermore, another phase III trial (N Engl J Med. 2011;364:422-31) found vancomycin noninferior to fidaxomicin for CDI.
The experts recommend “strong consideration” of hospitalization if patients with IBD and CDI present with profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other signs and symptoms of sepsis. Aggressive monitoring and treatment are especially important because it can be difficult to distinguish an IBD flare, which merits immunosuppression, from superimposed CDI, which might exacerbate the underlying infection, they noted. Few studies are available to help guide the decision about when to intensify steroids and other immunosuppressives in IBD patients with acute CDI. Thus, the experts suggest delaying this step until after starting therapy for CDI, but note that this decision should be individualized pending more robust data.
The authors emphasized the potential role of fecal microbiota transplantation (FMT), which has been shown to be very effective in both immunocompetent patients with CDI and those who are immunosuppressed, including because of IBD therapies. They recommend considering referral for FMT as early as the first recurrence of CDI in patients with IBD, particularly because of the strong safety and efficacy profile of FMT, the risk of complications from CDI in IBD patients, and scarce data on antibiotic therapy for recurrent CDI in the setting of IBD.
Dr. Khanna disclosed consulting relationships with Rebiotix. and Summit Pharmaceuticals. Senior author Ciaran P. Kelly, MD, disclosed serving as a consultant to Merck, Seres Therapeutics, Summit Pharmaceuticals, and Takeda Pharmaceuticals. The third author, Andrea Shin, MD, had no relevant disclosures.
Inflammatory bowel disease (IBD) increases the risk and severity of Clostridium difficile infection (CDI) while CDI tends to complicate and worsen the clinical course of IBD, experts note in a clinical practice update.
Thus, it is crucial that clinicians pursue stool testing for toxigenic C. difficile infection whenever a patient with IBD presents with a colitis flare, regardless of the recent antibiotic history, wrote Sahil Khanna, MBBS, of the Mayo Clinic, Rochester, Minn., and his associates (Clin Gastroenterol Hepatol. 2016 Feb. doi: 10.1016/j.cgh.2016.10.024). Clinicians should also test for recurrent CDI if symptoms of colitis persist or return after antibiotic therapy for CDI, they emphasized.
CDI can present atypically in IBD. Underlying colitis leads to colonic dysbiosis and loss of resistance to bacterial colonization, which permits CDI to develop even when patients have not recently received antibiotics. Patients with IBD also tend to develop CDI starting at younger ages, more often acquire it from community settings, and may lack the typical colonoscopic features of CDI. Simple colonization of C. difficile without infection also is more common in patients with IBD than in those without IBD, the experts note.
The authors contradict guidelines from both the American College of Gastroenterology and Infectious Diseases Society of America by recommending consideration of vancomycin over metronidazole for treatment of CDI. Not only are C. difficile treatment failures with metronidazole rising, but vancomycin was more effective than was metronidazole in a recent post hoc analysis (Clin Infect Dis. 2014;59[3]:345-54) of two large multicenter phase III trials. Furthermore, another phase III trial (N Engl J Med. 2011;364:422-31) found vancomycin noninferior to fidaxomicin for CDI.
The experts recommend “strong consideration” of hospitalization if patients with IBD and CDI present with profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other signs and symptoms of sepsis. Aggressive monitoring and treatment are especially important because it can be difficult to distinguish an IBD flare, which merits immunosuppression, from superimposed CDI, which might exacerbate the underlying infection, they noted. Few studies are available to help guide the decision about when to intensify steroids and other immunosuppressives in IBD patients with acute CDI. Thus, the experts suggest delaying this step until after starting therapy for CDI, but note that this decision should be individualized pending more robust data.
The authors emphasized the potential role of fecal microbiota transplantation (FMT), which has been shown to be very effective in both immunocompetent patients with CDI and those who are immunosuppressed, including because of IBD therapies. They recommend considering referral for FMT as early as the first recurrence of CDI in patients with IBD, particularly because of the strong safety and efficacy profile of FMT, the risk of complications from CDI in IBD patients, and scarce data on antibiotic therapy for recurrent CDI in the setting of IBD.
Dr. Khanna disclosed consulting relationships with Rebiotix. and Summit Pharmaceuticals. Senior author Ciaran P. Kelly, MD, disclosed serving as a consultant to Merck, Seres Therapeutics, Summit Pharmaceuticals, and Takeda Pharmaceuticals. The third author, Andrea Shin, MD, had no relevant disclosures.
Inflammatory bowel disease (IBD) increases the risk and severity of Clostridium difficile infection (CDI) while CDI tends to complicate and worsen the clinical course of IBD, experts note in a clinical practice update.
Thus, it is crucial that clinicians pursue stool testing for toxigenic C. difficile infection whenever a patient with IBD presents with a colitis flare, regardless of the recent antibiotic history, wrote Sahil Khanna, MBBS, of the Mayo Clinic, Rochester, Minn., and his associates (Clin Gastroenterol Hepatol. 2016 Feb. doi: 10.1016/j.cgh.2016.10.024). Clinicians should also test for recurrent CDI if symptoms of colitis persist or return after antibiotic therapy for CDI, they emphasized.
CDI can present atypically in IBD. Underlying colitis leads to colonic dysbiosis and loss of resistance to bacterial colonization, which permits CDI to develop even when patients have not recently received antibiotics. Patients with IBD also tend to develop CDI starting at younger ages, more often acquire it from community settings, and may lack the typical colonoscopic features of CDI. Simple colonization of C. difficile without infection also is more common in patients with IBD than in those without IBD, the experts note.
The authors contradict guidelines from both the American College of Gastroenterology and Infectious Diseases Society of America by recommending consideration of vancomycin over metronidazole for treatment of CDI. Not only are C. difficile treatment failures with metronidazole rising, but vancomycin was more effective than was metronidazole in a recent post hoc analysis (Clin Infect Dis. 2014;59[3]:345-54) of two large multicenter phase III trials. Furthermore, another phase III trial (N Engl J Med. 2011;364:422-31) found vancomycin noninferior to fidaxomicin for CDI.
The experts recommend “strong consideration” of hospitalization if patients with IBD and CDI present with profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other signs and symptoms of sepsis. Aggressive monitoring and treatment are especially important because it can be difficult to distinguish an IBD flare, which merits immunosuppression, from superimposed CDI, which might exacerbate the underlying infection, they noted. Few studies are available to help guide the decision about when to intensify steroids and other immunosuppressives in IBD patients with acute CDI. Thus, the experts suggest delaying this step until after starting therapy for CDI, but note that this decision should be individualized pending more robust data.
The authors emphasized the potential role of fecal microbiota transplantation (FMT), which has been shown to be very effective in both immunocompetent patients with CDI and those who are immunosuppressed, including because of IBD therapies. They recommend considering referral for FMT as early as the first recurrence of CDI in patients with IBD, particularly because of the strong safety and efficacy profile of FMT, the risk of complications from CDI in IBD patients, and scarce data on antibiotic therapy for recurrent CDI in the setting of IBD.
Dr. Khanna disclosed consulting relationships with Rebiotix. and Summit Pharmaceuticals. Senior author Ciaran P. Kelly, MD, disclosed serving as a consultant to Merck, Seres Therapeutics, Summit Pharmaceuticals, and Takeda Pharmaceuticals. The third author, Andrea Shin, MD, had no relevant disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY