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IDSA updates infectious diarrhea guidelines
Molecular-based diagnostic tests for enteric pathogens are highly sensitive but may require expert input to assess their clinical and public health implications, according to new guidelines from the Infectious Diseases Society of America.
Among the specific areas on which the guidelines focus are assessment of the diagnostic needs of patients who have been traveling, those in health care settings, including long-term care facilities, and dealing with immunocompromised patients, especially those with acquired immune deficiency syndrome (AIDS).
“Differentiating colonization from active infection, obtaining antimicrobial susceptibility results, providing optimal management, and preventing transmission are areas in need of additional research as nonculture diagnostics replace traditional culture-based methods,” writes Andi L. Shane, MD, of Emory University and Children’s Healthcare in Atlanta, with her associates in Clinical Infectious Diseases. Performing a complete physical exam and taking a thorough exposure history remain crucial in this era of rapid molecular tests in order to identify and treat infectious diarrhea and interrupt the chain of transmission, the experts emphasize (Clin Infect Dis. 2017 Oct 19. doi: 10.1093/cid/cix669).
The rise of culture-independent diagnostic tests also has important public health implications, the experts state. Pulsed-field gel electrophoresis and whole-genome sequencing are essential for rapidly detecting outbreaks, but they must be performed on clinical isolates. “Continuing to detect and respond to such outbreaks is a vital part of making our food and water systems safer,” the authors add. “As culture-independent diagnostic panels become used more frequently, public health departments may request that specimens be cultured in public health laboratories if unable to be cultured in the clinical diagnostic laboratory.” Clinicians should continue submitting isolates for subtyping of notifiable pathogens, such as Salmonella, Shiga toxin–producing Escherichia coli, Shigella, and Listeria, according to the guidelines.
The guidelines also recommend a broad differential diagnosis in immunocompromised people with diarrhea, and people with AIDS who have persistent diarrhea should undergo additional testing for other organisms including, Cryptosporidium, Cyclospora, Cystoisospora, Microsporidia, Mycobacterium avium complex, and Cytomegalovirus.
The IDSA last updated its guidelines on infectious diarrhea in 2001. The current iteration includes 60 specific recommendations and five tables that stratify pathogens by exposures, clinical signs and symptoms, postinfectious sequelae, laboratory diagnostics, and antimicrobial therapy. Two additional tables list other sources of guidelines and provide detailed recommendations on rehydration therapy. Most patients with diarrhea do not need to be tested for infectious pathogens, with exceptions such as children younger than 5 years, the elderly, immunocompromised patients, and patients with bloody diarrhea, severe abdominal pain or tenderness, or signs of sepsis. Even when patients do not need to be tested, they should receive oral rehydration solution to correct mild to moderate dehydration or intravenous rehydration if they cannot tolerate oral therapy.
The World Health Organization defines diarrhea as loose or liquid stools occurring three or more times in 24 hours or more often than normal. Rapid molecular tests most often identify norovirus in these patients. Infectious diarrhea remains most common in children under age 5 years, but the advent of rotavirus vaccines over the past decade has decreased its incidence in this age group.
The work was funded by IDSA. Dr. Shane disclosed research grants from the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases, salary support from the Gerber Foundation, honoraria from SLACK, and travel support from International Scientific Association for Probiotics and Prebiotics.
This article was updated 11/3/17.
Molecular-based diagnostic tests for enteric pathogens are highly sensitive but may require expert input to assess their clinical and public health implications, according to new guidelines from the Infectious Diseases Society of America.
Among the specific areas on which the guidelines focus are assessment of the diagnostic needs of patients who have been traveling, those in health care settings, including long-term care facilities, and dealing with immunocompromised patients, especially those with acquired immune deficiency syndrome (AIDS).
“Differentiating colonization from active infection, obtaining antimicrobial susceptibility results, providing optimal management, and preventing transmission are areas in need of additional research as nonculture diagnostics replace traditional culture-based methods,” writes Andi L. Shane, MD, of Emory University and Children’s Healthcare in Atlanta, with her associates in Clinical Infectious Diseases. Performing a complete physical exam and taking a thorough exposure history remain crucial in this era of rapid molecular tests in order to identify and treat infectious diarrhea and interrupt the chain of transmission, the experts emphasize (Clin Infect Dis. 2017 Oct 19. doi: 10.1093/cid/cix669).
The rise of culture-independent diagnostic tests also has important public health implications, the experts state. Pulsed-field gel electrophoresis and whole-genome sequencing are essential for rapidly detecting outbreaks, but they must be performed on clinical isolates. “Continuing to detect and respond to such outbreaks is a vital part of making our food and water systems safer,” the authors add. “As culture-independent diagnostic panels become used more frequently, public health departments may request that specimens be cultured in public health laboratories if unable to be cultured in the clinical diagnostic laboratory.” Clinicians should continue submitting isolates for subtyping of notifiable pathogens, such as Salmonella, Shiga toxin–producing Escherichia coli, Shigella, and Listeria, according to the guidelines.
The guidelines also recommend a broad differential diagnosis in immunocompromised people with diarrhea, and people with AIDS who have persistent diarrhea should undergo additional testing for other organisms including, Cryptosporidium, Cyclospora, Cystoisospora, Microsporidia, Mycobacterium avium complex, and Cytomegalovirus.
The IDSA last updated its guidelines on infectious diarrhea in 2001. The current iteration includes 60 specific recommendations and five tables that stratify pathogens by exposures, clinical signs and symptoms, postinfectious sequelae, laboratory diagnostics, and antimicrobial therapy. Two additional tables list other sources of guidelines and provide detailed recommendations on rehydration therapy. Most patients with diarrhea do not need to be tested for infectious pathogens, with exceptions such as children younger than 5 years, the elderly, immunocompromised patients, and patients with bloody diarrhea, severe abdominal pain or tenderness, or signs of sepsis. Even when patients do not need to be tested, they should receive oral rehydration solution to correct mild to moderate dehydration or intravenous rehydration if they cannot tolerate oral therapy.
The World Health Organization defines diarrhea as loose or liquid stools occurring three or more times in 24 hours or more often than normal. Rapid molecular tests most often identify norovirus in these patients. Infectious diarrhea remains most common in children under age 5 years, but the advent of rotavirus vaccines over the past decade has decreased its incidence in this age group.
The work was funded by IDSA. Dr. Shane disclosed research grants from the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases, salary support from the Gerber Foundation, honoraria from SLACK, and travel support from International Scientific Association for Probiotics and Prebiotics.
This article was updated 11/3/17.
Molecular-based diagnostic tests for enteric pathogens are highly sensitive but may require expert input to assess their clinical and public health implications, according to new guidelines from the Infectious Diseases Society of America.
Among the specific areas on which the guidelines focus are assessment of the diagnostic needs of patients who have been traveling, those in health care settings, including long-term care facilities, and dealing with immunocompromised patients, especially those with acquired immune deficiency syndrome (AIDS).
“Differentiating colonization from active infection, obtaining antimicrobial susceptibility results, providing optimal management, and preventing transmission are areas in need of additional research as nonculture diagnostics replace traditional culture-based methods,” writes Andi L. Shane, MD, of Emory University and Children’s Healthcare in Atlanta, with her associates in Clinical Infectious Diseases. Performing a complete physical exam and taking a thorough exposure history remain crucial in this era of rapid molecular tests in order to identify and treat infectious diarrhea and interrupt the chain of transmission, the experts emphasize (Clin Infect Dis. 2017 Oct 19. doi: 10.1093/cid/cix669).
The rise of culture-independent diagnostic tests also has important public health implications, the experts state. Pulsed-field gel electrophoresis and whole-genome sequencing are essential for rapidly detecting outbreaks, but they must be performed on clinical isolates. “Continuing to detect and respond to such outbreaks is a vital part of making our food and water systems safer,” the authors add. “As culture-independent diagnostic panels become used more frequently, public health departments may request that specimens be cultured in public health laboratories if unable to be cultured in the clinical diagnostic laboratory.” Clinicians should continue submitting isolates for subtyping of notifiable pathogens, such as Salmonella, Shiga toxin–producing Escherichia coli, Shigella, and Listeria, according to the guidelines.
The guidelines also recommend a broad differential diagnosis in immunocompromised people with diarrhea, and people with AIDS who have persistent diarrhea should undergo additional testing for other organisms including, Cryptosporidium, Cyclospora, Cystoisospora, Microsporidia, Mycobacterium avium complex, and Cytomegalovirus.
The IDSA last updated its guidelines on infectious diarrhea in 2001. The current iteration includes 60 specific recommendations and five tables that stratify pathogens by exposures, clinical signs and symptoms, postinfectious sequelae, laboratory diagnostics, and antimicrobial therapy. Two additional tables list other sources of guidelines and provide detailed recommendations on rehydration therapy. Most patients with diarrhea do not need to be tested for infectious pathogens, with exceptions such as children younger than 5 years, the elderly, immunocompromised patients, and patients with bloody diarrhea, severe abdominal pain or tenderness, or signs of sepsis. Even when patients do not need to be tested, they should receive oral rehydration solution to correct mild to moderate dehydration or intravenous rehydration if they cannot tolerate oral therapy.
The World Health Organization defines diarrhea as loose or liquid stools occurring three or more times in 24 hours or more often than normal. Rapid molecular tests most often identify norovirus in these patients. Infectious diarrhea remains most common in children under age 5 years, but the advent of rotavirus vaccines over the past decade has decreased its incidence in this age group.
The work was funded by IDSA. Dr. Shane disclosed research grants from the Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases, salary support from the Gerber Foundation, honoraria from SLACK, and travel support from International Scientific Association for Probiotics and Prebiotics.
This article was updated 11/3/17.
FROM CLINICAL INFECTIOUS DISEASES
Biofeedback significantly improves abdominal distension in small study
An electromyographic biofeedback program significantly improved abdominothoracic muscle control and abdominal distension compared with placebo in a randomized trial of patients fulfilling Rome III criteria for functional intestinal disorders.
Sensations of abdominal distension improved by 56% with biofeedback (standard deviation, 1%) versus 13% (SD, 8%) with placebo, wrote Elizabeth Barba, MD, of University Hospital Vall d’Hebron in Barcelona, and her associates. The study was published in the December issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.06.052). Biofeedback also led to a doubling of anterior wall muscle activity (101%; SD, 10%) compared with a 4% (SD, 2%) improvement with placebo. Finally, biofeedback lowered intercostal muscle activity by a mean of 45% (SD, 3%) compared with 5% (SD, 2%) with placebo (all P values less than .001).
“Biofeedback in this trial was applied using a complex technique that provided effective guidance to patients and allowed close control of the mechanistic effects of the intervention on postural tone,” the researchers noted. “Having proved the [efficacy] of this treatment, the next steps are to develop and then to properly validate a simpler technique for widespread application.”
Episodic abdominal distension is a primary reason for visiting gastroenterology clinics. Patients typically experience an objective, visible increase in girth with no detectable cause, although they often have irritable bowel syndrome, functional dyspepsia, or both. Past work has linked abdominal distension with increased diaphragmatic tone and ventral protrusion and decreased muscle tone of the abdominal wall, the researchers noted.
Therefore, they developed an electromyography (EMG) biofeedback program to help patients learn to correct abdominothoracic muscular dystony. The trial comprised 48 patients (47 women and 1 man) ranging in age from 21 to 74 years. During each 30-minute session, patients sat upright in a quiet room while EMG recorded the activity of the intercostal muscles, anterior abdominal wall (external oblique, upper rectus, lower rectus, and internal oblique muscles), and diaphragm. Patients reported their sensation of abdominal distension on a visual rating scale ranging from 0 (no distension) to 6 (extreme distension). Those in the intervention group watched the EMG readout and were taught to reduce their intercostal and diaphragm activity while increasing the activity of the anterior abdominal muscles. Three training sessions occurred over 10 days and patients performed similar exercises at home for 5 minutes before each meal. Patients in the placebo group underwent the same instrumental interventions but did not watch the EMG recording, received no instructions about muscle control, and were given oral simethicone.
Symptoms associated with abdominal distension lessened by 57% (SD, 9%) in the biofeedback group and by 23% (4%) in the placebo group (P = .02). Treatment outcomes did not vary based on symptoms and there were no adverse effects of treatment, the researchers said. Furthermore, 19 patients in the placebo group who did not improve underwent biofeedback training and experienced benefits similar to those of the original intervention group. Sensations of abdominal distension and associated symptoms improved significantly immediately after biofeedback compared with baseline and continued to improve significantly over 6 months of follow-up.
The researchers described the complexity of the intervention, which, they acknowledged, would need to be simplified before it could be deployed widely. They measured the activity of the external oblique, upper rectus, lower rectus, and internal oblique muscles with bipolar leads, and recorded intercostal muscle activity by placing a monopolar electrode at the second intercostal space on the right midclavicular line, with a ground electrode over the central sternum. To verify correct placement, they recorded EMG responses to a Valsalva maneuver and a deep inhalation. They measured diaphragmatic activity by mounting electrodes on a polyvinyl tube, performing nasal intubation, and positioning the electrodes across the diaphragmatic hiatus under fluoroscopic control.
Funders included the Spanish Ministry of Economy and Competitiveness and the Instituto de Salud Carlos III. The researchers reported having no conflicts of interest.
An electromyographic biofeedback program significantly improved abdominothoracic muscle control and abdominal distension compared with placebo in a randomized trial of patients fulfilling Rome III criteria for functional intestinal disorders.
Sensations of abdominal distension improved by 56% with biofeedback (standard deviation, 1%) versus 13% (SD, 8%) with placebo, wrote Elizabeth Barba, MD, of University Hospital Vall d’Hebron in Barcelona, and her associates. The study was published in the December issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.06.052). Biofeedback also led to a doubling of anterior wall muscle activity (101%; SD, 10%) compared with a 4% (SD, 2%) improvement with placebo. Finally, biofeedback lowered intercostal muscle activity by a mean of 45% (SD, 3%) compared with 5% (SD, 2%) with placebo (all P values less than .001).
“Biofeedback in this trial was applied using a complex technique that provided effective guidance to patients and allowed close control of the mechanistic effects of the intervention on postural tone,” the researchers noted. “Having proved the [efficacy] of this treatment, the next steps are to develop and then to properly validate a simpler technique for widespread application.”
Episodic abdominal distension is a primary reason for visiting gastroenterology clinics. Patients typically experience an objective, visible increase in girth with no detectable cause, although they often have irritable bowel syndrome, functional dyspepsia, or both. Past work has linked abdominal distension with increased diaphragmatic tone and ventral protrusion and decreased muscle tone of the abdominal wall, the researchers noted.
Therefore, they developed an electromyography (EMG) biofeedback program to help patients learn to correct abdominothoracic muscular dystony. The trial comprised 48 patients (47 women and 1 man) ranging in age from 21 to 74 years. During each 30-minute session, patients sat upright in a quiet room while EMG recorded the activity of the intercostal muscles, anterior abdominal wall (external oblique, upper rectus, lower rectus, and internal oblique muscles), and diaphragm. Patients reported their sensation of abdominal distension on a visual rating scale ranging from 0 (no distension) to 6 (extreme distension). Those in the intervention group watched the EMG readout and were taught to reduce their intercostal and diaphragm activity while increasing the activity of the anterior abdominal muscles. Three training sessions occurred over 10 days and patients performed similar exercises at home for 5 minutes before each meal. Patients in the placebo group underwent the same instrumental interventions but did not watch the EMG recording, received no instructions about muscle control, and were given oral simethicone.
Symptoms associated with abdominal distension lessened by 57% (SD, 9%) in the biofeedback group and by 23% (4%) in the placebo group (P = .02). Treatment outcomes did not vary based on symptoms and there were no adverse effects of treatment, the researchers said. Furthermore, 19 patients in the placebo group who did not improve underwent biofeedback training and experienced benefits similar to those of the original intervention group. Sensations of abdominal distension and associated symptoms improved significantly immediately after biofeedback compared with baseline and continued to improve significantly over 6 months of follow-up.
The researchers described the complexity of the intervention, which, they acknowledged, would need to be simplified before it could be deployed widely. They measured the activity of the external oblique, upper rectus, lower rectus, and internal oblique muscles with bipolar leads, and recorded intercostal muscle activity by placing a monopolar electrode at the second intercostal space on the right midclavicular line, with a ground electrode over the central sternum. To verify correct placement, they recorded EMG responses to a Valsalva maneuver and a deep inhalation. They measured diaphragmatic activity by mounting electrodes on a polyvinyl tube, performing nasal intubation, and positioning the electrodes across the diaphragmatic hiatus under fluoroscopic control.
Funders included the Spanish Ministry of Economy and Competitiveness and the Instituto de Salud Carlos III. The researchers reported having no conflicts of interest.
An electromyographic biofeedback program significantly improved abdominothoracic muscle control and abdominal distension compared with placebo in a randomized trial of patients fulfilling Rome III criteria for functional intestinal disorders.
Sensations of abdominal distension improved by 56% with biofeedback (standard deviation, 1%) versus 13% (SD, 8%) with placebo, wrote Elizabeth Barba, MD, of University Hospital Vall d’Hebron in Barcelona, and her associates. The study was published in the December issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.06.052). Biofeedback also led to a doubling of anterior wall muscle activity (101%; SD, 10%) compared with a 4% (SD, 2%) improvement with placebo. Finally, biofeedback lowered intercostal muscle activity by a mean of 45% (SD, 3%) compared with 5% (SD, 2%) with placebo (all P values less than .001).
“Biofeedback in this trial was applied using a complex technique that provided effective guidance to patients and allowed close control of the mechanistic effects of the intervention on postural tone,” the researchers noted. “Having proved the [efficacy] of this treatment, the next steps are to develop and then to properly validate a simpler technique for widespread application.”
Episodic abdominal distension is a primary reason for visiting gastroenterology clinics. Patients typically experience an objective, visible increase in girth with no detectable cause, although they often have irritable bowel syndrome, functional dyspepsia, or both. Past work has linked abdominal distension with increased diaphragmatic tone and ventral protrusion and decreased muscle tone of the abdominal wall, the researchers noted.
Therefore, they developed an electromyography (EMG) biofeedback program to help patients learn to correct abdominothoracic muscular dystony. The trial comprised 48 patients (47 women and 1 man) ranging in age from 21 to 74 years. During each 30-minute session, patients sat upright in a quiet room while EMG recorded the activity of the intercostal muscles, anterior abdominal wall (external oblique, upper rectus, lower rectus, and internal oblique muscles), and diaphragm. Patients reported their sensation of abdominal distension on a visual rating scale ranging from 0 (no distension) to 6 (extreme distension). Those in the intervention group watched the EMG readout and were taught to reduce their intercostal and diaphragm activity while increasing the activity of the anterior abdominal muscles. Three training sessions occurred over 10 days and patients performed similar exercises at home for 5 minutes before each meal. Patients in the placebo group underwent the same instrumental interventions but did not watch the EMG recording, received no instructions about muscle control, and were given oral simethicone.
Symptoms associated with abdominal distension lessened by 57% (SD, 9%) in the biofeedback group and by 23% (4%) in the placebo group (P = .02). Treatment outcomes did not vary based on symptoms and there were no adverse effects of treatment, the researchers said. Furthermore, 19 patients in the placebo group who did not improve underwent biofeedback training and experienced benefits similar to those of the original intervention group. Sensations of abdominal distension and associated symptoms improved significantly immediately after biofeedback compared with baseline and continued to improve significantly over 6 months of follow-up.
The researchers described the complexity of the intervention, which, they acknowledged, would need to be simplified before it could be deployed widely. They measured the activity of the external oblique, upper rectus, lower rectus, and internal oblique muscles with bipolar leads, and recorded intercostal muscle activity by placing a monopolar electrode at the second intercostal space on the right midclavicular line, with a ground electrode over the central sternum. To verify correct placement, they recorded EMG responses to a Valsalva maneuver and a deep inhalation. They measured diaphragmatic activity by mounting electrodes on a polyvinyl tube, performing nasal intubation, and positioning the electrodes across the diaphragmatic hiatus under fluoroscopic control.
Funders included the Spanish Ministry of Economy and Competitiveness and the Instituto de Salud Carlos III. The researchers reported having no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Biofeedback training significantly improved abdominal distension in patients with functional intestinal disorders.
Major finding: Subjective abdominal distension improved by 56% in the intervention group and by 13% in the placebo group (P less than .001).
Data source: A randomized, placebo-controlled trial of 48 patients meeting Rome III criteria for functional intestinal disorders.
Disclosures: Funders included the Spanish Ministry of Economy and Competitiveness and Instituto de Salud Carlos III. The researchers reported having no conflicts of interest.
ADMIRE CD trial: Stem cells promote long-term fistula remission
ORLANDO – A single treatment with a suspension of allogeneic expanded adipose-derived mesenchymal stem cells, or Cx601, promotes long-term combined remission of complex perianal fistulas in patients with Crohn’s disease, according to 52-week results from the phase 3 ADMIRE CD trial.
Combined remission – a stringent endpoint consisting of closure of all treated external openings that were draining at baseline and of an absence of collections more than 2 cm of treated perianal fistulas as confirmed by blinded central MRI – was achieved in 56.3% of 103 treated patients, compared with 38.6% of 101 patients who received placebo (P = .010), Daniel C. Baumgart, MD, reported at the World Congress of Gastroenterology at ACG 2017.
This parallel-group, double-blind, multicenter study included patients who had draining, treatment-refractory, complex perianal fistulas and inactive or mildly active luminal Crohn’s disease (Crohn’s Disease Activity Index scores of 220 or less) at baseline. Those randomized to the Cx601 group received a single intralesional injection of 120 million expanded adipose-derived stem cells and standard of care. Those in the control arm received a placebo injection plus standard of care, said Dr. Baumgart of Charité Medical School, which is affiliated with both Humboldt University in Berlin and the Free University of Berlin.
Prior to receiving treatment or placebo, the patients underwent fistula curettage and, if indicated, seton placement and subsequent removal, he noted, adding that baseline concomitant medications, including immunosuppressants and anti–tumor necrosis factors, were continued without dose or regimen modification and that antibiotics were allowed for up to 4 weeks.
The 52-week findings were evaluated in the modified intention-to-treat population of patients who were randomized, were treated, and had at least one postbaseline efficacy assessment (61.8% of the study population). These findings showed that Cx601 is associated with even better outcomes at 1 year than those reported at 24 weeks; those prior results, published in The Lancet in July 2016, showed combined remission rates in the modified intention-to-treat population of 51% vs. 36% for placebo.
Furthermore, 75% of treated patients who achieved combined remission at 24 weeks maintained that remission at 52 weeks, compared with 55.9% of those in the placebo group (P = .052), Dr. Baumgart said.
Sensitivity analyses in this long-term assessment supported the long-term effectiveness of Cx601 over that of the control treatment, which provided evidence on the robustness of its advantage, he said, noting that safety results were also encouraging.
“The safety profile was similar to week 24; there were no new safety signals there at all,” he said.
The findings are of note because existing therapies for complex perianal fistulas in Crohn’s disease are often ineffective, he said, adding that fistulas occur in up to 50% of Crohn’s disease patients and that 70%-80% are complex and difficult to treat. Most are refractory to conventional anti–tumor necrosis factor therapies, and 60%-70% of patients relapse, he explained.
“If we’re honest, very few medications have been properly studied,” he said, adding that fistula patients often are excluded from industry trials.
“So [the ADMIRE CD trial] is new, design-wise, and has addressed a true medical need,” he said.
He attributed the good placebo response in this trial to the ongoing standard of care treatment in both groups, as well as to the team approach to care used in the trial. He also noted that a number of questions regarding the use of Cx601 remain to be answered, including the when the ideal retreatment time point should be, whether the treatment can be used for rectovaginal fistulas, and which patients should not receive treatment.
“So there is a lot to learn still, but I think it’s a revolutionary step forward, compared to what we have today, due to the trial design, which I think is robust, and also the encouraging outcomes,” he said.
The ADMIRE CD trial was sponsored by TiGenix SAU. Dr. Baumgart has received consulting fees and nonfinancial support from AbbVie, Biogen, and BMS.
ORLANDO – A single treatment with a suspension of allogeneic expanded adipose-derived mesenchymal stem cells, or Cx601, promotes long-term combined remission of complex perianal fistulas in patients with Crohn’s disease, according to 52-week results from the phase 3 ADMIRE CD trial.
Combined remission – a stringent endpoint consisting of closure of all treated external openings that were draining at baseline and of an absence of collections more than 2 cm of treated perianal fistulas as confirmed by blinded central MRI – was achieved in 56.3% of 103 treated patients, compared with 38.6% of 101 patients who received placebo (P = .010), Daniel C. Baumgart, MD, reported at the World Congress of Gastroenterology at ACG 2017.
This parallel-group, double-blind, multicenter study included patients who had draining, treatment-refractory, complex perianal fistulas and inactive or mildly active luminal Crohn’s disease (Crohn’s Disease Activity Index scores of 220 or less) at baseline. Those randomized to the Cx601 group received a single intralesional injection of 120 million expanded adipose-derived stem cells and standard of care. Those in the control arm received a placebo injection plus standard of care, said Dr. Baumgart of Charité Medical School, which is affiliated with both Humboldt University in Berlin and the Free University of Berlin.
Prior to receiving treatment or placebo, the patients underwent fistula curettage and, if indicated, seton placement and subsequent removal, he noted, adding that baseline concomitant medications, including immunosuppressants and anti–tumor necrosis factors, were continued without dose or regimen modification and that antibiotics were allowed for up to 4 weeks.
The 52-week findings were evaluated in the modified intention-to-treat population of patients who were randomized, were treated, and had at least one postbaseline efficacy assessment (61.8% of the study population). These findings showed that Cx601 is associated with even better outcomes at 1 year than those reported at 24 weeks; those prior results, published in The Lancet in July 2016, showed combined remission rates in the modified intention-to-treat population of 51% vs. 36% for placebo.
Furthermore, 75% of treated patients who achieved combined remission at 24 weeks maintained that remission at 52 weeks, compared with 55.9% of those in the placebo group (P = .052), Dr. Baumgart said.
Sensitivity analyses in this long-term assessment supported the long-term effectiveness of Cx601 over that of the control treatment, which provided evidence on the robustness of its advantage, he said, noting that safety results were also encouraging.
“The safety profile was similar to week 24; there were no new safety signals there at all,” he said.
The findings are of note because existing therapies for complex perianal fistulas in Crohn’s disease are often ineffective, he said, adding that fistulas occur in up to 50% of Crohn’s disease patients and that 70%-80% are complex and difficult to treat. Most are refractory to conventional anti–tumor necrosis factor therapies, and 60%-70% of patients relapse, he explained.
“If we’re honest, very few medications have been properly studied,” he said, adding that fistula patients often are excluded from industry trials.
“So [the ADMIRE CD trial] is new, design-wise, and has addressed a true medical need,” he said.
He attributed the good placebo response in this trial to the ongoing standard of care treatment in both groups, as well as to the team approach to care used in the trial. He also noted that a number of questions regarding the use of Cx601 remain to be answered, including the when the ideal retreatment time point should be, whether the treatment can be used for rectovaginal fistulas, and which patients should not receive treatment.
“So there is a lot to learn still, but I think it’s a revolutionary step forward, compared to what we have today, due to the trial design, which I think is robust, and also the encouraging outcomes,” he said.
The ADMIRE CD trial was sponsored by TiGenix SAU. Dr. Baumgart has received consulting fees and nonfinancial support from AbbVie, Biogen, and BMS.
ORLANDO – A single treatment with a suspension of allogeneic expanded adipose-derived mesenchymal stem cells, or Cx601, promotes long-term combined remission of complex perianal fistulas in patients with Crohn’s disease, according to 52-week results from the phase 3 ADMIRE CD trial.
Combined remission – a stringent endpoint consisting of closure of all treated external openings that were draining at baseline and of an absence of collections more than 2 cm of treated perianal fistulas as confirmed by blinded central MRI – was achieved in 56.3% of 103 treated patients, compared with 38.6% of 101 patients who received placebo (P = .010), Daniel C. Baumgart, MD, reported at the World Congress of Gastroenterology at ACG 2017.
This parallel-group, double-blind, multicenter study included patients who had draining, treatment-refractory, complex perianal fistulas and inactive or mildly active luminal Crohn’s disease (Crohn’s Disease Activity Index scores of 220 or less) at baseline. Those randomized to the Cx601 group received a single intralesional injection of 120 million expanded adipose-derived stem cells and standard of care. Those in the control arm received a placebo injection plus standard of care, said Dr. Baumgart of Charité Medical School, which is affiliated with both Humboldt University in Berlin and the Free University of Berlin.
Prior to receiving treatment or placebo, the patients underwent fistula curettage and, if indicated, seton placement and subsequent removal, he noted, adding that baseline concomitant medications, including immunosuppressants and anti–tumor necrosis factors, were continued without dose or regimen modification and that antibiotics were allowed for up to 4 weeks.
The 52-week findings were evaluated in the modified intention-to-treat population of patients who were randomized, were treated, and had at least one postbaseline efficacy assessment (61.8% of the study population). These findings showed that Cx601 is associated with even better outcomes at 1 year than those reported at 24 weeks; those prior results, published in The Lancet in July 2016, showed combined remission rates in the modified intention-to-treat population of 51% vs. 36% for placebo.
Furthermore, 75% of treated patients who achieved combined remission at 24 weeks maintained that remission at 52 weeks, compared with 55.9% of those in the placebo group (P = .052), Dr. Baumgart said.
Sensitivity analyses in this long-term assessment supported the long-term effectiveness of Cx601 over that of the control treatment, which provided evidence on the robustness of its advantage, he said, noting that safety results were also encouraging.
“The safety profile was similar to week 24; there were no new safety signals there at all,” he said.
The findings are of note because existing therapies for complex perianal fistulas in Crohn’s disease are often ineffective, he said, adding that fistulas occur in up to 50% of Crohn’s disease patients and that 70%-80% are complex and difficult to treat. Most are refractory to conventional anti–tumor necrosis factor therapies, and 60%-70% of patients relapse, he explained.
“If we’re honest, very few medications have been properly studied,” he said, adding that fistula patients often are excluded from industry trials.
“So [the ADMIRE CD trial] is new, design-wise, and has addressed a true medical need,” he said.
He attributed the good placebo response in this trial to the ongoing standard of care treatment in both groups, as well as to the team approach to care used in the trial. He also noted that a number of questions regarding the use of Cx601 remain to be answered, including the when the ideal retreatment time point should be, whether the treatment can be used for rectovaginal fistulas, and which patients should not receive treatment.
“So there is a lot to learn still, but I think it’s a revolutionary step forward, compared to what we have today, due to the trial design, which I think is robust, and also the encouraging outcomes,” he said.
The ADMIRE CD trial was sponsored by TiGenix SAU. Dr. Baumgart has received consulting fees and nonfinancial support from AbbVie, Biogen, and BMS.
AT THE WORLD CONGRESS OF GASTROENTEROLOGY
Key clinical point:
Major finding: Combined remission was achieved in 56.3% of treated patients, compared with 38.6% of controls.
Data source: The phase 3 ADMIRE CD trial of 204 patients.
Disclosures: The ADMIRE CD trial was sponsored by TiGenix SAU. Dr. Baumgart has received consulting fees and nonfinancial support from AbbVie, Biogen, and Bristol-Myers Squibb.
Autoimmune endocrinopathies spike after celiac disease diagnosis
ORLANDO – Patients diagnosed with celiac disease subsequently showed a high incidence of autoimmune endocrinopathies in a review of 249 patients in a longitudinal, population-based database.
The finding that celiac disease patients developed autoimmune endocrinopathies (AE) at a rate of 9.14 cases per person-year of follow-up suggests that “screening for AEs is recommended in treated celiac disease patients,” Imad Absah, MD, said at the World Congress of Gastroenterology at ACG 2017.
Autoimmune thyroid disorders are the screening focus, and Dr. Asbah recommended a screening interval of every 2 years. Among the 14 patients in the review who developed an AE following a diagnosis of celiac disease, the two most common conditions were Hashimoto’s thyroiditis (4 patients) and hypothyroidism (4 patients), said Dr. Absah, a pediatric gastroenterologist at the Mayo Clinic in Rochester, Minn. One additional patient developed Graves disease.
He also suggested screening for type 1 diabetes in patients who show symptoms of diabetes. In the review, one patient developed type 1 diabetes following an index diagnosis of celiac disease.
His study used data collected in the Rochester Epidemiology Project on residents of Olmsted County, Minn. during 1997-2015. The database included 90 children and 159 adults less than 80 years old diagnosed with celiac disease after they entered the study. The children averaged 9 years old, and the adults averaged 32 years old; about two-thirds were girls or women.
Fifty-four of these people (22%) had been diagnosed with an AE prior to developing celiac disease, and then an additional 20 people (8%) had an incident AE during an average 5.7 years of follow-up for the children and an average 8.5 years of follow-up among the adults. Six of these 20 patients also had a different AE prior to their celiac disease diagnosis. Dr. Absah censored out these six patients and focused his analysis on the 14 patients with no AE prior to developing celiac disease. The incidence rate in both subgroups was 7%, which worked out to an overall incidence rate of 9.14 cases of AE for every person-year of follow-up in newly diagnosed patients with celiac disease.
Finding similar incidence rates among both children and adults suggests that “the length of gluten exposure prior to celiac disease did not affect the risk for an AE,” Dr. Absah said.
Dr. Absah had no relevant disclosures.
This article was updated 10/30/17.
[email protected]
On Twitter @mitchelzoler
ORLANDO – Patients diagnosed with celiac disease subsequently showed a high incidence of autoimmune endocrinopathies in a review of 249 patients in a longitudinal, population-based database.
The finding that celiac disease patients developed autoimmune endocrinopathies (AE) at a rate of 9.14 cases per person-year of follow-up suggests that “screening for AEs is recommended in treated celiac disease patients,” Imad Absah, MD, said at the World Congress of Gastroenterology at ACG 2017.
Autoimmune thyroid disorders are the screening focus, and Dr. Asbah recommended a screening interval of every 2 years. Among the 14 patients in the review who developed an AE following a diagnosis of celiac disease, the two most common conditions were Hashimoto’s thyroiditis (4 patients) and hypothyroidism (4 patients), said Dr. Absah, a pediatric gastroenterologist at the Mayo Clinic in Rochester, Minn. One additional patient developed Graves disease.
He also suggested screening for type 1 diabetes in patients who show symptoms of diabetes. In the review, one patient developed type 1 diabetes following an index diagnosis of celiac disease.
His study used data collected in the Rochester Epidemiology Project on residents of Olmsted County, Minn. during 1997-2015. The database included 90 children and 159 adults less than 80 years old diagnosed with celiac disease after they entered the study. The children averaged 9 years old, and the adults averaged 32 years old; about two-thirds were girls or women.
Fifty-four of these people (22%) had been diagnosed with an AE prior to developing celiac disease, and then an additional 20 people (8%) had an incident AE during an average 5.7 years of follow-up for the children and an average 8.5 years of follow-up among the adults. Six of these 20 patients also had a different AE prior to their celiac disease diagnosis. Dr. Absah censored out these six patients and focused his analysis on the 14 patients with no AE prior to developing celiac disease. The incidence rate in both subgroups was 7%, which worked out to an overall incidence rate of 9.14 cases of AE for every person-year of follow-up in newly diagnosed patients with celiac disease.
Finding similar incidence rates among both children and adults suggests that “the length of gluten exposure prior to celiac disease did not affect the risk for an AE,” Dr. Absah said.
Dr. Absah had no relevant disclosures.
This article was updated 10/30/17.
[email protected]
On Twitter @mitchelzoler
ORLANDO – Patients diagnosed with celiac disease subsequently showed a high incidence of autoimmune endocrinopathies in a review of 249 patients in a longitudinal, population-based database.
The finding that celiac disease patients developed autoimmune endocrinopathies (AE) at a rate of 9.14 cases per person-year of follow-up suggests that “screening for AEs is recommended in treated celiac disease patients,” Imad Absah, MD, said at the World Congress of Gastroenterology at ACG 2017.
Autoimmune thyroid disorders are the screening focus, and Dr. Asbah recommended a screening interval of every 2 years. Among the 14 patients in the review who developed an AE following a diagnosis of celiac disease, the two most common conditions were Hashimoto’s thyroiditis (4 patients) and hypothyroidism (4 patients), said Dr. Absah, a pediatric gastroenterologist at the Mayo Clinic in Rochester, Minn. One additional patient developed Graves disease.
He also suggested screening for type 1 diabetes in patients who show symptoms of diabetes. In the review, one patient developed type 1 diabetes following an index diagnosis of celiac disease.
His study used data collected in the Rochester Epidemiology Project on residents of Olmsted County, Minn. during 1997-2015. The database included 90 children and 159 adults less than 80 years old diagnosed with celiac disease after they entered the study. The children averaged 9 years old, and the adults averaged 32 years old; about two-thirds were girls or women.
Fifty-four of these people (22%) had been diagnosed with an AE prior to developing celiac disease, and then an additional 20 people (8%) had an incident AE during an average 5.7 years of follow-up for the children and an average 8.5 years of follow-up among the adults. Six of these 20 patients also had a different AE prior to their celiac disease diagnosis. Dr. Absah censored out these six patients and focused his analysis on the 14 patients with no AE prior to developing celiac disease. The incidence rate in both subgroups was 7%, which worked out to an overall incidence rate of 9.14 cases of AE for every person-year of follow-up in newly diagnosed patients with celiac disease.
Finding similar incidence rates among both children and adults suggests that “the length of gluten exposure prior to celiac disease did not affect the risk for an AE,” Dr. Absah said.
Dr. Absah had no relevant disclosures.
This article was updated 10/30/17.
[email protected]
On Twitter @mitchelzoler
AT THE WORLD CONGRESS OF GASTROENTEROLOGY
Key clinical point:
Major finding: Following celiac disease diagnosis, the annual incidence of autoimmune endocrinopathies was 0.9%.
Data source: Review of 249 patients diagnosed with celiac disease in the Rochester Epidemiology Project database.
Disclosures: Dr. Absah had no disclosures.
Biosimilars poised to save $54 billion over the next decade
Biosimilars could reduce overall spending on biologic products by $54 billion from 2017 to 2026, according to new research from the Rand Corp.
Given the level of uncertainty surrounding the biosimilars market, however, the range of savings could be as low at $24 billion or as high as $150 billion.
“Because of limited U.S. experience with biosimilars, the key assumptions on market share and biosimilar prices are ‘best guesses’ based on anecdotes or professional opinion,” Andrew Mulcahy, PhD, a health policy researcher at Rand, and his colleagues, wrote in a perspective report.
“Whether actual cost savings end up above or below our baseline estimate hinges in large part on whether manufacturers continue to have a business case to invest in developing and marketing biosimilars,” the authors noted, citing a number of areas, including intellectual property litigation, payment, price competition, nonprice competition from reference biologic manufacturers, naming convention, and interchangeability.
Getting over these hurdles could require legislative or regulatory solutions.
“The pervasive uncertainty in the U.S. biosimilar market – including questions as to whether the market will be sustainable and lead to cost savings, as intended – presents two choices for policymakers,” Dr. Mulcahy and his colleagues wrote. “One strategy is to let the market continue to develop under current policies,” with stability coming from experience.
The alternative could be policy levers to “help steer the U.S. biosimilar market more quickly to a sustainable, competitive state,” they continued. “For example, regulators at the FDA could experiment with new approaches to provide stronger, earlier signals through guidance documents or other mechanisms on expectations surrounding interchangeability and other topics.”
The FDA appears to be moving on the latter. In an Oct. 23 blog post, FDA Commissioner Scott Gottlieb, MD, and Leah Christl, PhD, associate director for therapeutic biologics in the office of new drugs at the FDA’s Center for Drug Evaluation and Research, outlined a number of recent tools to help biosimilar adoption. The resources provide basics such as the basic definition associated with biosimilars (i.e., what is a biosimilar and a reference product, and what it means to be interchangeable), the standards of approval that biosimilars must go through, and easily accessible information on what the FDA is using to review biosimilarity.
“Next, FDA plans to embark on additional research with health care professionals to learn more about the types of information prescribers need to properly communicate with their patients about biosimilars,” Commissioner Gottlieb and Dr. Christl wrote. “An increase in market competition, offered by a growing complement of biosimilars, may lead to meaningfully reduced costs for both patients and our health care system.”
The Centers for Medicare & Medicaid Services also plays a role in developing policy to spur biosimilar adoption, Dr. Mulcahy and his colleagues wrote. They note work being done by the Medicare Payment Advisory Commission on recommendations that could address payment for physician-administered biosimilars under Part B, as well as incentives in the Part D prescription drug program to steer patients and providers toward lower cost biosimilars when appropriate. CMS changed current payment policy for biosimilars for 2018, which may have an effect.
“Beyond FDA regulation, payment, and coverage, both government and industry could play a role in educating patients and providers about the potential cost savings from biosimilars, much like both groups have done for generic drugs,” they stated. “While our study does not address whether policy action is needed now, it is likely that the answer will become clearer over the next 1 to 3 years as the market continues to develop.”
Biosimilars could reduce overall spending on biologic products by $54 billion from 2017 to 2026, according to new research from the Rand Corp.
Given the level of uncertainty surrounding the biosimilars market, however, the range of savings could be as low at $24 billion or as high as $150 billion.
“Because of limited U.S. experience with biosimilars, the key assumptions on market share and biosimilar prices are ‘best guesses’ based on anecdotes or professional opinion,” Andrew Mulcahy, PhD, a health policy researcher at Rand, and his colleagues, wrote in a perspective report.
“Whether actual cost savings end up above or below our baseline estimate hinges in large part on whether manufacturers continue to have a business case to invest in developing and marketing biosimilars,” the authors noted, citing a number of areas, including intellectual property litigation, payment, price competition, nonprice competition from reference biologic manufacturers, naming convention, and interchangeability.
Getting over these hurdles could require legislative or regulatory solutions.
“The pervasive uncertainty in the U.S. biosimilar market – including questions as to whether the market will be sustainable and lead to cost savings, as intended – presents two choices for policymakers,” Dr. Mulcahy and his colleagues wrote. “One strategy is to let the market continue to develop under current policies,” with stability coming from experience.
The alternative could be policy levers to “help steer the U.S. biosimilar market more quickly to a sustainable, competitive state,” they continued. “For example, regulators at the FDA could experiment with new approaches to provide stronger, earlier signals through guidance documents or other mechanisms on expectations surrounding interchangeability and other topics.”
The FDA appears to be moving on the latter. In an Oct. 23 blog post, FDA Commissioner Scott Gottlieb, MD, and Leah Christl, PhD, associate director for therapeutic biologics in the office of new drugs at the FDA’s Center for Drug Evaluation and Research, outlined a number of recent tools to help biosimilar adoption. The resources provide basics such as the basic definition associated with biosimilars (i.e., what is a biosimilar and a reference product, and what it means to be interchangeable), the standards of approval that biosimilars must go through, and easily accessible information on what the FDA is using to review biosimilarity.
“Next, FDA plans to embark on additional research with health care professionals to learn more about the types of information prescribers need to properly communicate with their patients about biosimilars,” Commissioner Gottlieb and Dr. Christl wrote. “An increase in market competition, offered by a growing complement of biosimilars, may lead to meaningfully reduced costs for both patients and our health care system.”
The Centers for Medicare & Medicaid Services also plays a role in developing policy to spur biosimilar adoption, Dr. Mulcahy and his colleagues wrote. They note work being done by the Medicare Payment Advisory Commission on recommendations that could address payment for physician-administered biosimilars under Part B, as well as incentives in the Part D prescription drug program to steer patients and providers toward lower cost biosimilars when appropriate. CMS changed current payment policy for biosimilars for 2018, which may have an effect.
“Beyond FDA regulation, payment, and coverage, both government and industry could play a role in educating patients and providers about the potential cost savings from biosimilars, much like both groups have done for generic drugs,” they stated. “While our study does not address whether policy action is needed now, it is likely that the answer will become clearer over the next 1 to 3 years as the market continues to develop.”
Biosimilars could reduce overall spending on biologic products by $54 billion from 2017 to 2026, according to new research from the Rand Corp.
Given the level of uncertainty surrounding the biosimilars market, however, the range of savings could be as low at $24 billion or as high as $150 billion.
“Because of limited U.S. experience with biosimilars, the key assumptions on market share and biosimilar prices are ‘best guesses’ based on anecdotes or professional opinion,” Andrew Mulcahy, PhD, a health policy researcher at Rand, and his colleagues, wrote in a perspective report.
“Whether actual cost savings end up above or below our baseline estimate hinges in large part on whether manufacturers continue to have a business case to invest in developing and marketing biosimilars,” the authors noted, citing a number of areas, including intellectual property litigation, payment, price competition, nonprice competition from reference biologic manufacturers, naming convention, and interchangeability.
Getting over these hurdles could require legislative or regulatory solutions.
“The pervasive uncertainty in the U.S. biosimilar market – including questions as to whether the market will be sustainable and lead to cost savings, as intended – presents two choices for policymakers,” Dr. Mulcahy and his colleagues wrote. “One strategy is to let the market continue to develop under current policies,” with stability coming from experience.
The alternative could be policy levers to “help steer the U.S. biosimilar market more quickly to a sustainable, competitive state,” they continued. “For example, regulators at the FDA could experiment with new approaches to provide stronger, earlier signals through guidance documents or other mechanisms on expectations surrounding interchangeability and other topics.”
The FDA appears to be moving on the latter. In an Oct. 23 blog post, FDA Commissioner Scott Gottlieb, MD, and Leah Christl, PhD, associate director for therapeutic biologics in the office of new drugs at the FDA’s Center for Drug Evaluation and Research, outlined a number of recent tools to help biosimilar adoption. The resources provide basics such as the basic definition associated with biosimilars (i.e., what is a biosimilar and a reference product, and what it means to be interchangeable), the standards of approval that biosimilars must go through, and easily accessible information on what the FDA is using to review biosimilarity.
“Next, FDA plans to embark on additional research with health care professionals to learn more about the types of information prescribers need to properly communicate with their patients about biosimilars,” Commissioner Gottlieb and Dr. Christl wrote. “An increase in market competition, offered by a growing complement of biosimilars, may lead to meaningfully reduced costs for both patients and our health care system.”
The Centers for Medicare & Medicaid Services also plays a role in developing policy to spur biosimilar adoption, Dr. Mulcahy and his colleagues wrote. They note work being done by the Medicare Payment Advisory Commission on recommendations that could address payment for physician-administered biosimilars under Part B, as well as incentives in the Part D prescription drug program to steer patients and providers toward lower cost biosimilars when appropriate. CMS changed current payment policy for biosimilars for 2018, which may have an effect.
“Beyond FDA regulation, payment, and coverage, both government and industry could play a role in educating patients and providers about the potential cost savings from biosimilars, much like both groups have done for generic drugs,” they stated. “While our study does not address whether policy action is needed now, it is likely that the answer will become clearer over the next 1 to 3 years as the market continues to develop.”
Session highlights controversies in diverticulitis management
SAN DIEGO – During the annual clinical congress of the American College of Surgeons, a panel of experts discussed a wide range of evolving controversies in the management of complicated diverticulitis.
John Migaly, MD, kicked off the session by exploring the current evidence for laparoscopic lavage versus primary resection for Hinchey III diverticulitis. “Over the past two decades there has been a growing utilization of primary resection and reanastomoses with or without the use of ileostomy,” said Dr. Migaly, director of the general surgery residency program at Duke University, Durham, N.C. “And most recently over the last 5 or 10 years there’s been growing enthusiasm for laparoscopic lavage for Hinchey III diverticulitis. The enthusiasm for this procedure is based on [its accessibility] to all of us who operate on the colon in the acute setting.”
The DILALA trial makes the best case for laparoscopic lavage, “but it doesn’t make a very good one,” he commented. The trial was conducted in nine surgical departments in Sweden and Denmark (Ann Surg. 2016;263[1]:117-22). Hinchey III patients were randomized 1:1 to laparoscopic lavage or the Hartmann procedure. The primary outcome was reoperations within 12 months. An early analysis of the short-term outcomes in 83 patients found similar 30-day and 90-day mortality and morbidity. Its authors concluded that laparoscopic lavage had equivalent morbidity and mortality compared with radical resection, shorter operative time, shorter time in the recovery unit, a shorter hospital stay, but no difference in the rate of reoperation.
“It was found to be safe and feasible,” Dr. Migaly said. One year later, the researchers presented their 12-month outcomes and came to the same conclusions. Limitations of the data are that it was conducted in nine centers “but they enrolled only 83 patients, so it seems underpowered,” he said. “And there was no mention of the incidence of abdominal abscess requiring percutaneous drainage or episodes of diverticulitis. The data seem a little less granular than the LADIES trial.”
The SCANDIV trial is the largest study on the topic to date, a randomized clinical superiority trial conducted at 21 centers in Sweden and Norway (JAMA 2015;314[13]:1364-75). Of the 509 patients screened, 415 were eligible and 199 were enrolled: 101 to laparoscopic lavage, 98 to colon resection. The primary endpoint was severe postoperative complications within 90 days, defined as a Clavien-Dindo score of over 3. The researchers found no difference in major complications nor in 90-day mortality between the two groups. The rate of reoperation was significantly higher in the lavage group, compared with the resection group (20.3% vs. 5.7%, respectively). Four sigmoid cancers were missed in the lavage group and, while the length of operation was significantly shorter in the lavage group, there were no differences between the two groups in hospital length of stay or quality of life.
A meta-analysis of the three randomized controlled trials that Dr. Migaly reviewed concluded that laparoscopic lavage, compared with resection, for Hinchey III diverticulitis increased the rate of total reoperations, the rate of reoperation for infection, and the rate of subsequent percutaneous drainage (J Gastrointest Surg 2017;21[9]:1491-99). A larger, more recent meta-analysis of 589 patients, including the three randomized controlled trials that Dr. Migaly discussed, concluded that laparoscopic lavage patients, compared with resection patients, had three times the risk of persistent peritonitis, intra-abdominal abscess, and emergency reoperative surgery. “Therefore, a reasonable conclusion would be that data at this point does not support the use of laparoscopic lavage,” he said.
The initial procedure of choice for most patients is abscess drainage via CT-guided percutaneous drainage. “There are some patients who are not candidates for percutaneous drainage, [such as] if the abscess is not accessible to the radiologist, if the patient is anticoagulated, and if the patient requires emergent surgical intervention irrespective of the abscess,” said Dr. Maron, a colorectal surgeon who practices at Cleveland Clinic Florida, Weston. “There is also a question of cavity size. Most authors in the literature use a cut-off of 3-4 cm.”
The goal is complete drainage of the abscess, and sometimes multiple catheters will be required. One study found that predictors of successful abscess drainage included having a well-defined, unilocular abscess. The success rate fell to 63% for patients who presented with more complex abscesses, including those that were loculated, poorly defined, associated with a fistula, and contained feces or semisolid material (Dis Colon Rectum. 1997;40:1009-13).
The 2014 ASCRS Practice Parameters includes the recommendation that elective colectomy should typically be considered after the patient recovers from an episode of complicated diverticulitis, “but some of the data may be calling that into question,” Dr. Maron said. In one series of 18 patients with an abscess treated percutaneously, 11 refused surgery and 7 had significant comorbidity (Dis Colon Rectum. 2014;57:331-6). Three patients died of a pre-existing condition and 7 of the 15 surviving patients had recurrent diverticulitis. Three underwent surgery and four were treated medically. The authors found no association between long-term failure and abscess location or previous episodes of diverticulitis.
In a larger study, researchers identified 218 patients who were initially treated with intravenous antibiotics and percutaneous drain (Dis Colon Rectum. 2013;56:622-6). About 10% of the patients required an urgent operation, while most of the other patients underwent elective resection, but 15% of patients did not undergo a subsequent colectomy. “Most of these patients were medically unfit to undergo surgery,” he noted. Abscess location was more commonly paracolic than pelvic. The mean abscess size was 4.2 cm, and the drain was left in for a median of 20 days. The recurrence rate in this series was only 30%, but none of the recurrences required surgery. The authors found that abscesses greater than 5 cm in size were associated with a greater risk of recurrence (P = .003). They concluded that observation after percutaneous drainage is safe in selected patients.
Based on results from this and other more recent studies, Dr. Maron said that it remains unclear whether surgeons should wait and watch or operate after successful percutaneous drainage of diverticular abscess. The data are “not as robust as we’d like … most of these are retrospective studies,” he said. “There’s quite a bit of inherent selection bias, and there is no standardization with regard to length of time of percutaneous drain, rationale for nonoperative management versus elective colectomy. What we do know is that there are some patients who can be managed safely without surgery. Unfortunately, there is no good algorithm I can offer you: Perhaps larger abscesses can portend a higher recurrence. I don’t think we’ll have a good answer to this until we perform a prospective randomized trial. However, we may learn some data from patients managed by peritoneal lavage and drain placement.”
Next, consider how to perform the procedure: laparoscopic or open? “But again, you’re going to look at how stable your patient is, what your skill set is, what equipment is available, and if the patient has had previous abdominal surgeries,” she advised. “In the traditional Hartmann procedure, you resect the perforated segment. You try not to open any tissue planes that you don’t have to. You do just enough so you can bring up a colostomy; you close the rectum or you make a mucous fistula. The problem with this operation is that up to 80% of these patients have their colostomy closed. That is why there is all this controversy. If there is any question, this [procedure] is always the safest option; there’s no anastomosis.”
What about a performing resection and a colorectal anastomosis? This is usually done more commonly in the elective situation, “when things are perfect, when you have healthy tissue,” Dr. Hull said. “If you do it in the emergent situation you have to think to yourself, ‘Could my patient tolerate a leak?’ You won’t want to do this operation on a 72-year-old who’s on steroids for chronic pulmonary disease and has coronary artery disease, because if they had a leak, they’d probably die.”
The third procedural option is to resect bowel (usually sigmoid) with colorectal anastomosis and diversion (loop ileostomy). “This is always my preferred choice,” Dr. Hull said. “I always am thinking, ‘Why can’t I do this?’ The reason is, closure of ileostomy is much easier than a Hartmann reversal, and 90% of these patients get reversed.” In a multicenter trial conducted by Swedish researchers, 62 patients were randomized to Hartmann’s procedure versus primary anastomosis with diverting ileostomy for perforated left-sided diverticulitis (Ann Surg. 2012;256[5]:819-27). The mortality and complications were similar, but the number of patients who got their stoma reversed was significantly less in the Hartmann’s group, compared with the primary anastomosis group (57% vs. 90%, respectively), and the serious complications were much higher in the Hartmann’s group (20% vs. 0). She cited an article from the World Journal of Emergency Surgery as one of the most comprehensive reviews of the subject.
So what is a surgeon to do? For an anastomosis after resection, “consider patient factors: Are they stable?” Dr. Hull said. “What are their comorbid conditions? You have to think, ‘What is my preference? Am I comfortable putting this back together?’ But a primary anastomosis is feasible, even in the acute setting with or without diverting ileostomy. The laparoscopic approach is typically preferred, but if that’s not in your armamentarium, the open [approach] is just fine. You should always perform a leak test. You can also do on table colonic lavage if feasible, especially if you have a large stool burden.”
None of the speakers reported having financial disclosures.
SAN DIEGO – During the annual clinical congress of the American College of Surgeons, a panel of experts discussed a wide range of evolving controversies in the management of complicated diverticulitis.
John Migaly, MD, kicked off the session by exploring the current evidence for laparoscopic lavage versus primary resection for Hinchey III diverticulitis. “Over the past two decades there has been a growing utilization of primary resection and reanastomoses with or without the use of ileostomy,” said Dr. Migaly, director of the general surgery residency program at Duke University, Durham, N.C. “And most recently over the last 5 or 10 years there’s been growing enthusiasm for laparoscopic lavage for Hinchey III diverticulitis. The enthusiasm for this procedure is based on [its accessibility] to all of us who operate on the colon in the acute setting.”
The DILALA trial makes the best case for laparoscopic lavage, “but it doesn’t make a very good one,” he commented. The trial was conducted in nine surgical departments in Sweden and Denmark (Ann Surg. 2016;263[1]:117-22). Hinchey III patients were randomized 1:1 to laparoscopic lavage or the Hartmann procedure. The primary outcome was reoperations within 12 months. An early analysis of the short-term outcomes in 83 patients found similar 30-day and 90-day mortality and morbidity. Its authors concluded that laparoscopic lavage had equivalent morbidity and mortality compared with radical resection, shorter operative time, shorter time in the recovery unit, a shorter hospital stay, but no difference in the rate of reoperation.
“It was found to be safe and feasible,” Dr. Migaly said. One year later, the researchers presented their 12-month outcomes and came to the same conclusions. Limitations of the data are that it was conducted in nine centers “but they enrolled only 83 patients, so it seems underpowered,” he said. “And there was no mention of the incidence of abdominal abscess requiring percutaneous drainage or episodes of diverticulitis. The data seem a little less granular than the LADIES trial.”
The SCANDIV trial is the largest study on the topic to date, a randomized clinical superiority trial conducted at 21 centers in Sweden and Norway (JAMA 2015;314[13]:1364-75). Of the 509 patients screened, 415 were eligible and 199 were enrolled: 101 to laparoscopic lavage, 98 to colon resection. The primary endpoint was severe postoperative complications within 90 days, defined as a Clavien-Dindo score of over 3. The researchers found no difference in major complications nor in 90-day mortality between the two groups. The rate of reoperation was significantly higher in the lavage group, compared with the resection group (20.3% vs. 5.7%, respectively). Four sigmoid cancers were missed in the lavage group and, while the length of operation was significantly shorter in the lavage group, there were no differences between the two groups in hospital length of stay or quality of life.
A meta-analysis of the three randomized controlled trials that Dr. Migaly reviewed concluded that laparoscopic lavage, compared with resection, for Hinchey III diverticulitis increased the rate of total reoperations, the rate of reoperation for infection, and the rate of subsequent percutaneous drainage (J Gastrointest Surg 2017;21[9]:1491-99). A larger, more recent meta-analysis of 589 patients, including the three randomized controlled trials that Dr. Migaly discussed, concluded that laparoscopic lavage patients, compared with resection patients, had three times the risk of persistent peritonitis, intra-abdominal abscess, and emergency reoperative surgery. “Therefore, a reasonable conclusion would be that data at this point does not support the use of laparoscopic lavage,” he said.
The initial procedure of choice for most patients is abscess drainage via CT-guided percutaneous drainage. “There are some patients who are not candidates for percutaneous drainage, [such as] if the abscess is not accessible to the radiologist, if the patient is anticoagulated, and if the patient requires emergent surgical intervention irrespective of the abscess,” said Dr. Maron, a colorectal surgeon who practices at Cleveland Clinic Florida, Weston. “There is also a question of cavity size. Most authors in the literature use a cut-off of 3-4 cm.”
The goal is complete drainage of the abscess, and sometimes multiple catheters will be required. One study found that predictors of successful abscess drainage included having a well-defined, unilocular abscess. The success rate fell to 63% for patients who presented with more complex abscesses, including those that were loculated, poorly defined, associated with a fistula, and contained feces or semisolid material (Dis Colon Rectum. 1997;40:1009-13).
The 2014 ASCRS Practice Parameters includes the recommendation that elective colectomy should typically be considered after the patient recovers from an episode of complicated diverticulitis, “but some of the data may be calling that into question,” Dr. Maron said. In one series of 18 patients with an abscess treated percutaneously, 11 refused surgery and 7 had significant comorbidity (Dis Colon Rectum. 2014;57:331-6). Three patients died of a pre-existing condition and 7 of the 15 surviving patients had recurrent diverticulitis. Three underwent surgery and four were treated medically. The authors found no association between long-term failure and abscess location or previous episodes of diverticulitis.
In a larger study, researchers identified 218 patients who were initially treated with intravenous antibiotics and percutaneous drain (Dis Colon Rectum. 2013;56:622-6). About 10% of the patients required an urgent operation, while most of the other patients underwent elective resection, but 15% of patients did not undergo a subsequent colectomy. “Most of these patients were medically unfit to undergo surgery,” he noted. Abscess location was more commonly paracolic than pelvic. The mean abscess size was 4.2 cm, and the drain was left in for a median of 20 days. The recurrence rate in this series was only 30%, but none of the recurrences required surgery. The authors found that abscesses greater than 5 cm in size were associated with a greater risk of recurrence (P = .003). They concluded that observation after percutaneous drainage is safe in selected patients.
Based on results from this and other more recent studies, Dr. Maron said that it remains unclear whether surgeons should wait and watch or operate after successful percutaneous drainage of diverticular abscess. The data are “not as robust as we’d like … most of these are retrospective studies,” he said. “There’s quite a bit of inherent selection bias, and there is no standardization with regard to length of time of percutaneous drain, rationale for nonoperative management versus elective colectomy. What we do know is that there are some patients who can be managed safely without surgery. Unfortunately, there is no good algorithm I can offer you: Perhaps larger abscesses can portend a higher recurrence. I don’t think we’ll have a good answer to this until we perform a prospective randomized trial. However, we may learn some data from patients managed by peritoneal lavage and drain placement.”
Next, consider how to perform the procedure: laparoscopic or open? “But again, you’re going to look at how stable your patient is, what your skill set is, what equipment is available, and if the patient has had previous abdominal surgeries,” she advised. “In the traditional Hartmann procedure, you resect the perforated segment. You try not to open any tissue planes that you don’t have to. You do just enough so you can bring up a colostomy; you close the rectum or you make a mucous fistula. The problem with this operation is that up to 80% of these patients have their colostomy closed. That is why there is all this controversy. If there is any question, this [procedure] is always the safest option; there’s no anastomosis.”
What about a performing resection and a colorectal anastomosis? This is usually done more commonly in the elective situation, “when things are perfect, when you have healthy tissue,” Dr. Hull said. “If you do it in the emergent situation you have to think to yourself, ‘Could my patient tolerate a leak?’ You won’t want to do this operation on a 72-year-old who’s on steroids for chronic pulmonary disease and has coronary artery disease, because if they had a leak, they’d probably die.”
The third procedural option is to resect bowel (usually sigmoid) with colorectal anastomosis and diversion (loop ileostomy). “This is always my preferred choice,” Dr. Hull said. “I always am thinking, ‘Why can’t I do this?’ The reason is, closure of ileostomy is much easier than a Hartmann reversal, and 90% of these patients get reversed.” In a multicenter trial conducted by Swedish researchers, 62 patients were randomized to Hartmann’s procedure versus primary anastomosis with diverting ileostomy for perforated left-sided diverticulitis (Ann Surg. 2012;256[5]:819-27). The mortality and complications were similar, but the number of patients who got their stoma reversed was significantly less in the Hartmann’s group, compared with the primary anastomosis group (57% vs. 90%, respectively), and the serious complications were much higher in the Hartmann’s group (20% vs. 0). She cited an article from the World Journal of Emergency Surgery as one of the most comprehensive reviews of the subject.
So what is a surgeon to do? For an anastomosis after resection, “consider patient factors: Are they stable?” Dr. Hull said. “What are their comorbid conditions? You have to think, ‘What is my preference? Am I comfortable putting this back together?’ But a primary anastomosis is feasible, even in the acute setting with or without diverting ileostomy. The laparoscopic approach is typically preferred, but if that’s not in your armamentarium, the open [approach] is just fine. You should always perform a leak test. You can also do on table colonic lavage if feasible, especially if you have a large stool burden.”
None of the speakers reported having financial disclosures.
SAN DIEGO – During the annual clinical congress of the American College of Surgeons, a panel of experts discussed a wide range of evolving controversies in the management of complicated diverticulitis.
John Migaly, MD, kicked off the session by exploring the current evidence for laparoscopic lavage versus primary resection for Hinchey III diverticulitis. “Over the past two decades there has been a growing utilization of primary resection and reanastomoses with or without the use of ileostomy,” said Dr. Migaly, director of the general surgery residency program at Duke University, Durham, N.C. “And most recently over the last 5 or 10 years there’s been growing enthusiasm for laparoscopic lavage for Hinchey III diverticulitis. The enthusiasm for this procedure is based on [its accessibility] to all of us who operate on the colon in the acute setting.”
The DILALA trial makes the best case for laparoscopic lavage, “but it doesn’t make a very good one,” he commented. The trial was conducted in nine surgical departments in Sweden and Denmark (Ann Surg. 2016;263[1]:117-22). Hinchey III patients were randomized 1:1 to laparoscopic lavage or the Hartmann procedure. The primary outcome was reoperations within 12 months. An early analysis of the short-term outcomes in 83 patients found similar 30-day and 90-day mortality and morbidity. Its authors concluded that laparoscopic lavage had equivalent morbidity and mortality compared with radical resection, shorter operative time, shorter time in the recovery unit, a shorter hospital stay, but no difference in the rate of reoperation.
“It was found to be safe and feasible,” Dr. Migaly said. One year later, the researchers presented their 12-month outcomes and came to the same conclusions. Limitations of the data are that it was conducted in nine centers “but they enrolled only 83 patients, so it seems underpowered,” he said. “And there was no mention of the incidence of abdominal abscess requiring percutaneous drainage or episodes of diverticulitis. The data seem a little less granular than the LADIES trial.”
The SCANDIV trial is the largest study on the topic to date, a randomized clinical superiority trial conducted at 21 centers in Sweden and Norway (JAMA 2015;314[13]:1364-75). Of the 509 patients screened, 415 were eligible and 199 were enrolled: 101 to laparoscopic lavage, 98 to colon resection. The primary endpoint was severe postoperative complications within 90 days, defined as a Clavien-Dindo score of over 3. The researchers found no difference in major complications nor in 90-day mortality between the two groups. The rate of reoperation was significantly higher in the lavage group, compared with the resection group (20.3% vs. 5.7%, respectively). Four sigmoid cancers were missed in the lavage group and, while the length of operation was significantly shorter in the lavage group, there were no differences between the two groups in hospital length of stay or quality of life.
A meta-analysis of the three randomized controlled trials that Dr. Migaly reviewed concluded that laparoscopic lavage, compared with resection, for Hinchey III diverticulitis increased the rate of total reoperations, the rate of reoperation for infection, and the rate of subsequent percutaneous drainage (J Gastrointest Surg 2017;21[9]:1491-99). A larger, more recent meta-analysis of 589 patients, including the three randomized controlled trials that Dr. Migaly discussed, concluded that laparoscopic lavage patients, compared with resection patients, had three times the risk of persistent peritonitis, intra-abdominal abscess, and emergency reoperative surgery. “Therefore, a reasonable conclusion would be that data at this point does not support the use of laparoscopic lavage,” he said.
The initial procedure of choice for most patients is abscess drainage via CT-guided percutaneous drainage. “There are some patients who are not candidates for percutaneous drainage, [such as] if the abscess is not accessible to the radiologist, if the patient is anticoagulated, and if the patient requires emergent surgical intervention irrespective of the abscess,” said Dr. Maron, a colorectal surgeon who practices at Cleveland Clinic Florida, Weston. “There is also a question of cavity size. Most authors in the literature use a cut-off of 3-4 cm.”
The goal is complete drainage of the abscess, and sometimes multiple catheters will be required. One study found that predictors of successful abscess drainage included having a well-defined, unilocular abscess. The success rate fell to 63% for patients who presented with more complex abscesses, including those that were loculated, poorly defined, associated with a fistula, and contained feces or semisolid material (Dis Colon Rectum. 1997;40:1009-13).
The 2014 ASCRS Practice Parameters includes the recommendation that elective colectomy should typically be considered after the patient recovers from an episode of complicated diverticulitis, “but some of the data may be calling that into question,” Dr. Maron said. In one series of 18 patients with an abscess treated percutaneously, 11 refused surgery and 7 had significant comorbidity (Dis Colon Rectum. 2014;57:331-6). Three patients died of a pre-existing condition and 7 of the 15 surviving patients had recurrent diverticulitis. Three underwent surgery and four were treated medically. The authors found no association between long-term failure and abscess location or previous episodes of diverticulitis.
In a larger study, researchers identified 218 patients who were initially treated with intravenous antibiotics and percutaneous drain (Dis Colon Rectum. 2013;56:622-6). About 10% of the patients required an urgent operation, while most of the other patients underwent elective resection, but 15% of patients did not undergo a subsequent colectomy. “Most of these patients were medically unfit to undergo surgery,” he noted. Abscess location was more commonly paracolic than pelvic. The mean abscess size was 4.2 cm, and the drain was left in for a median of 20 days. The recurrence rate in this series was only 30%, but none of the recurrences required surgery. The authors found that abscesses greater than 5 cm in size were associated with a greater risk of recurrence (P = .003). They concluded that observation after percutaneous drainage is safe in selected patients.
Based on results from this and other more recent studies, Dr. Maron said that it remains unclear whether surgeons should wait and watch or operate after successful percutaneous drainage of diverticular abscess. The data are “not as robust as we’d like … most of these are retrospective studies,” he said. “There’s quite a bit of inherent selection bias, and there is no standardization with regard to length of time of percutaneous drain, rationale for nonoperative management versus elective colectomy. What we do know is that there are some patients who can be managed safely without surgery. Unfortunately, there is no good algorithm I can offer you: Perhaps larger abscesses can portend a higher recurrence. I don’t think we’ll have a good answer to this until we perform a prospective randomized trial. However, we may learn some data from patients managed by peritoneal lavage and drain placement.”
Next, consider how to perform the procedure: laparoscopic or open? “But again, you’re going to look at how stable your patient is, what your skill set is, what equipment is available, and if the patient has had previous abdominal surgeries,” she advised. “In the traditional Hartmann procedure, you resect the perforated segment. You try not to open any tissue planes that you don’t have to. You do just enough so you can bring up a colostomy; you close the rectum or you make a mucous fistula. The problem with this operation is that up to 80% of these patients have their colostomy closed. That is why there is all this controversy. If there is any question, this [procedure] is always the safest option; there’s no anastomosis.”
What about a performing resection and a colorectal anastomosis? This is usually done more commonly in the elective situation, “when things are perfect, when you have healthy tissue,” Dr. Hull said. “If you do it in the emergent situation you have to think to yourself, ‘Could my patient tolerate a leak?’ You won’t want to do this operation on a 72-year-old who’s on steroids for chronic pulmonary disease and has coronary artery disease, because if they had a leak, they’d probably die.”
The third procedural option is to resect bowel (usually sigmoid) with colorectal anastomosis and diversion (loop ileostomy). “This is always my preferred choice,” Dr. Hull said. “I always am thinking, ‘Why can’t I do this?’ The reason is, closure of ileostomy is much easier than a Hartmann reversal, and 90% of these patients get reversed.” In a multicenter trial conducted by Swedish researchers, 62 patients were randomized to Hartmann’s procedure versus primary anastomosis with diverting ileostomy for perforated left-sided diverticulitis (Ann Surg. 2012;256[5]:819-27). The mortality and complications were similar, but the number of patients who got their stoma reversed was significantly less in the Hartmann’s group, compared with the primary anastomosis group (57% vs. 90%, respectively), and the serious complications were much higher in the Hartmann’s group (20% vs. 0). She cited an article from the World Journal of Emergency Surgery as one of the most comprehensive reviews of the subject.
So what is a surgeon to do? For an anastomosis after resection, “consider patient factors: Are they stable?” Dr. Hull said. “What are their comorbid conditions? You have to think, ‘What is my preference? Am I comfortable putting this back together?’ But a primary anastomosis is feasible, even in the acute setting with or without diverting ileostomy. The laparoscopic approach is typically preferred, but if that’s not in your armamentarium, the open [approach] is just fine. You should always perform a leak test. You can also do on table colonic lavage if feasible, especially if you have a large stool burden.”
None of the speakers reported having financial disclosures.
AT THE ACS CLINICAL CONGRESS
Ribaxamase reduced new CDI by 71%
SAN DIEGO – , results from a phase 2b study showed.
At an annual scientific meeting on infectious diseases, lead investigator John F. Kokai-Kun, PhD, said that the finding represents a paradigm shift in the use of intravenous beta-lactam antibiotics to prevent opportunistic infections. “We currently treat Clostridium difficile infection (CDI) with antibiotics, which attack the vegetative cells,” said Dr. Kokai-Kun, vice president of nonclinical affairs for Rockville, Md.–based Synthetic Biologics, which is developing ribaxamase. “Since C. diff. is primarily a toxin-mediated disease, certain products seem to neutralize the toxin. There’s also been work with probiotics and prebiotics to try to strengthen and repair the dysbiotic colon. Fecal replacement therapy has been shown to be fairly effective for treatment of recurrent C. diff. infection. What if we could simply block the initial insult that leads to this cascade? That’s the damage caused to the gut microbiome by the antibiotic that’s excreted to the intestine.”
That’s where ribaxamase comes in, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. Ribaxamase is an orally administered beta-lac-tamase designed to degrade penicillin and cephalosporins in the intestinal lumen. It’s formulated for release in the proximal small intestine and is expected to be given during or a short time after administration of IV beta-lactam antibiotics such as ceftriaxone. “This is expected to degrade the excess antibiotics that are excreted into the small intestine via the bile,” Dr. Kokai-Kun explained. “It’s designed to prevent disruption of the gut microbiome and thus protect from opportunistic GI infections like CDI.”
Early-stage clinical studies demonstrated that ribaxamase was well tolerated and that it is not systemically absorbed, while phase 2 studies showed that ribaxamase degrades ceftriaxone in the intestine to below the level of detection while not affecting the pharmacokinetics of ceftriaxone in the plasma.
For the current study, 412 patients were enrolled at 84 multinational clinical sites. These patients were admitted to the hospital for treatment of a lower respiratory tract infection and were randomized 1:1 to receive ceftriaxone plus 150 mg ribaxamase or ceftriaxone plus placebo. Patients in both groups could also receive an oral macrolide at the discretion of the clinical investigator.
The researchers also obtained fecal samples at screening, 72 hours post antibiotic treatment, and at the end of a 4-week follow-up visit, to determine colonization by opportunistic pathogens and to examine changes in the gut microbiome.
Patients were monitored for 6 weeks for diarrhea and CDI. Diarrhea was defined as three or more loose or watery stools in a 24-hour period. “If that occurred, then we collected a sample, which was sent to the local lab to determine the presence of C. difficile toxins,” Dr. Kokai-Kun said.
The average age of study participants was 70 years, and about one-third in each arm received oral macrolides. The number of adverse events and serious adverse events were similar between active and placebo arms, and there was no trend associated with ribaxamase use. The lower respiratory tract infection cure rate to the ceftriaxone treatment was about 99% in both arms at 72 hours post treatment and at 2 weeks post treatment.
To analyze changes in the gut microbiome, the researchers conducted 16S rRNA sequencing of DNA extracted from fecal samples. In all, 652 samples were sequenced from 229 patients. Results from that analysis suggests that ribaxamase “appears to protect the gut microbiome from the onslaught of the ceftriaxone,” he said.
Ribaxamase reduced the incidence of new-onset CDI by 71%, compared with placebo (P = .045). “It apparently did this by protecting the integrity of the gut microbiome,” Dr. Kokai-Kun said. “There was also a significant reduction of new colonization by vancomycin-resistant enterococci at 72 hours and 4 weeks (P = .0001 and P = .0002, respectively) which is an opportunistic pathogen that is known to be able to inhabit gut microbiome when there is dysbiosis.”
The study was sponsored by Synthetic Biologics. Dr. Kokai-Kun is an employee of the company.
AGA Resource
Help your patients better understand C. difficile by using AGA’s patient education materials available here.
[email protected]
SAN DIEGO – , results from a phase 2b study showed.
At an annual scientific meeting on infectious diseases, lead investigator John F. Kokai-Kun, PhD, said that the finding represents a paradigm shift in the use of intravenous beta-lactam antibiotics to prevent opportunistic infections. “We currently treat Clostridium difficile infection (CDI) with antibiotics, which attack the vegetative cells,” said Dr. Kokai-Kun, vice president of nonclinical affairs for Rockville, Md.–based Synthetic Biologics, which is developing ribaxamase. “Since C. diff. is primarily a toxin-mediated disease, certain products seem to neutralize the toxin. There’s also been work with probiotics and prebiotics to try to strengthen and repair the dysbiotic colon. Fecal replacement therapy has been shown to be fairly effective for treatment of recurrent C. diff. infection. What if we could simply block the initial insult that leads to this cascade? That’s the damage caused to the gut microbiome by the antibiotic that’s excreted to the intestine.”
That’s where ribaxamase comes in, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. Ribaxamase is an orally administered beta-lac-tamase designed to degrade penicillin and cephalosporins in the intestinal lumen. It’s formulated for release in the proximal small intestine and is expected to be given during or a short time after administration of IV beta-lactam antibiotics such as ceftriaxone. “This is expected to degrade the excess antibiotics that are excreted into the small intestine via the bile,” Dr. Kokai-Kun explained. “It’s designed to prevent disruption of the gut microbiome and thus protect from opportunistic GI infections like CDI.”
Early-stage clinical studies demonstrated that ribaxamase was well tolerated and that it is not systemically absorbed, while phase 2 studies showed that ribaxamase degrades ceftriaxone in the intestine to below the level of detection while not affecting the pharmacokinetics of ceftriaxone in the plasma.
For the current study, 412 patients were enrolled at 84 multinational clinical sites. These patients were admitted to the hospital for treatment of a lower respiratory tract infection and were randomized 1:1 to receive ceftriaxone plus 150 mg ribaxamase or ceftriaxone plus placebo. Patients in both groups could also receive an oral macrolide at the discretion of the clinical investigator.
The researchers also obtained fecal samples at screening, 72 hours post antibiotic treatment, and at the end of a 4-week follow-up visit, to determine colonization by opportunistic pathogens and to examine changes in the gut microbiome.
Patients were monitored for 6 weeks for diarrhea and CDI. Diarrhea was defined as three or more loose or watery stools in a 24-hour period. “If that occurred, then we collected a sample, which was sent to the local lab to determine the presence of C. difficile toxins,” Dr. Kokai-Kun said.
The average age of study participants was 70 years, and about one-third in each arm received oral macrolides. The number of adverse events and serious adverse events were similar between active and placebo arms, and there was no trend associated with ribaxamase use. The lower respiratory tract infection cure rate to the ceftriaxone treatment was about 99% in both arms at 72 hours post treatment and at 2 weeks post treatment.
To analyze changes in the gut microbiome, the researchers conducted 16S rRNA sequencing of DNA extracted from fecal samples. In all, 652 samples were sequenced from 229 patients. Results from that analysis suggests that ribaxamase “appears to protect the gut microbiome from the onslaught of the ceftriaxone,” he said.
Ribaxamase reduced the incidence of new-onset CDI by 71%, compared with placebo (P = .045). “It apparently did this by protecting the integrity of the gut microbiome,” Dr. Kokai-Kun said. “There was also a significant reduction of new colonization by vancomycin-resistant enterococci at 72 hours and 4 weeks (P = .0001 and P = .0002, respectively) which is an opportunistic pathogen that is known to be able to inhabit gut microbiome when there is dysbiosis.”
The study was sponsored by Synthetic Biologics. Dr. Kokai-Kun is an employee of the company.
AGA Resource
Help your patients better understand C. difficile by using AGA’s patient education materials available here.
[email protected]
SAN DIEGO – , results from a phase 2b study showed.
At an annual scientific meeting on infectious diseases, lead investigator John F. Kokai-Kun, PhD, said that the finding represents a paradigm shift in the use of intravenous beta-lactam antibiotics to prevent opportunistic infections. “We currently treat Clostridium difficile infection (CDI) with antibiotics, which attack the vegetative cells,” said Dr. Kokai-Kun, vice president of nonclinical affairs for Rockville, Md.–based Synthetic Biologics, which is developing ribaxamase. “Since C. diff. is primarily a toxin-mediated disease, certain products seem to neutralize the toxin. There’s also been work with probiotics and prebiotics to try to strengthen and repair the dysbiotic colon. Fecal replacement therapy has been shown to be fairly effective for treatment of recurrent C. diff. infection. What if we could simply block the initial insult that leads to this cascade? That’s the damage caused to the gut microbiome by the antibiotic that’s excreted to the intestine.”
That’s where ribaxamase comes in, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. Ribaxamase is an orally administered beta-lac-tamase designed to degrade penicillin and cephalosporins in the intestinal lumen. It’s formulated for release in the proximal small intestine and is expected to be given during or a short time after administration of IV beta-lactam antibiotics such as ceftriaxone. “This is expected to degrade the excess antibiotics that are excreted into the small intestine via the bile,” Dr. Kokai-Kun explained. “It’s designed to prevent disruption of the gut microbiome and thus protect from opportunistic GI infections like CDI.”
Early-stage clinical studies demonstrated that ribaxamase was well tolerated and that it is not systemically absorbed, while phase 2 studies showed that ribaxamase degrades ceftriaxone in the intestine to below the level of detection while not affecting the pharmacokinetics of ceftriaxone in the plasma.
For the current study, 412 patients were enrolled at 84 multinational clinical sites. These patients were admitted to the hospital for treatment of a lower respiratory tract infection and were randomized 1:1 to receive ceftriaxone plus 150 mg ribaxamase or ceftriaxone plus placebo. Patients in both groups could also receive an oral macrolide at the discretion of the clinical investigator.
The researchers also obtained fecal samples at screening, 72 hours post antibiotic treatment, and at the end of a 4-week follow-up visit, to determine colonization by opportunistic pathogens and to examine changes in the gut microbiome.
Patients were monitored for 6 weeks for diarrhea and CDI. Diarrhea was defined as three or more loose or watery stools in a 24-hour period. “If that occurred, then we collected a sample, which was sent to the local lab to determine the presence of C. difficile toxins,” Dr. Kokai-Kun said.
The average age of study participants was 70 years, and about one-third in each arm received oral macrolides. The number of adverse events and serious adverse events were similar between active and placebo arms, and there was no trend associated with ribaxamase use. The lower respiratory tract infection cure rate to the ceftriaxone treatment was about 99% in both arms at 72 hours post treatment and at 2 weeks post treatment.
To analyze changes in the gut microbiome, the researchers conducted 16S rRNA sequencing of DNA extracted from fecal samples. In all, 652 samples were sequenced from 229 patients. Results from that analysis suggests that ribaxamase “appears to protect the gut microbiome from the onslaught of the ceftriaxone,” he said.
Ribaxamase reduced the incidence of new-onset CDI by 71%, compared with placebo (P = .045). “It apparently did this by protecting the integrity of the gut microbiome,” Dr. Kokai-Kun said. “There was also a significant reduction of new colonization by vancomycin-resistant enterococci at 72 hours and 4 weeks (P = .0001 and P = .0002, respectively) which is an opportunistic pathogen that is known to be able to inhabit gut microbiome when there is dysbiosis.”
The study was sponsored by Synthetic Biologics. Dr. Kokai-Kun is an employee of the company.
AGA Resource
Help your patients better understand C. difficile by using AGA’s patient education materials available here.
[email protected]
VIDEO: Celiac disease runs ninefold higher in eosinophilic esophagitis
ORLANDO – Patients with eosinophilic esophagitis had a ninefold increased prevalence of celiac disease, compared with the general public, in a review of more than 35 million U.S. residents.
This finding, which corresponded to a 2% overall prevalence rate of celiac disease in patients diagnosed with eosinophilic esophagitis, suggests that routine screening for celiac disease in eosinophilic esophagitis patients is warranted, Emad Mansoor, MD, said at the World Congress of Gastroenterology at ACG 2017.
This high prevalence level “has great implications for how we screen, treat, and manage” patients with either disorder, Dr. Mansoor said in a video interview. He hypothesized that celiac disease and eosinophilic esophagitis could share genetic etiologies or environmental or autoimmune triggers that produce the high level of overlap that the results showed.
The same analysis also found high rates of celiac disease in patients with either eosinophilic gastroenteritis or colitis, but because these are both much less prevalent than eosiniphillic esophagitis the absolute number of patients with either of these eosinophilic disorders who also had celiac disease was much lower.
It’s very possible that the prevalence of eosinophilic esophagitis among patients with celiac disease is also significantly elevated, compared with the general population, but he and his associates have not run this analysis.
Their study included diagnostic records for 35,795,250 people in the Explorys database during May 2012 to May 2017, with entries from 317,000 providers at 360 U.S. hospitals. The review identified 84,040 patients with a diagnosis of celiac disease, 15,360 with eosinophilic esophagitis, 1,440 with eosinophilic gastritis, and 800 with eosinophilic colitis. This worked out to a 5-year prevalence rate of 234.8 cases of celiac disease per 100,000 patients (0.235%), an eosinophilic esophagitis prevalence of 43.7 per 100,000, an eosinophilic gastroenteritis rate of 4.0 per 100,000, and an eosinophilic colitis rate of 2.2 per 100,000, said Dr. Mansoor, a gastroenterologist at University Hospitals Cleveland Medical Center.
The prevalence of celiac disease among patients with eosinophilic gastroenteritis or colitis was higher than in the eosinophilic esophagitis patients, with rates of 3.5% and 3.7%, respectively, that translated into odds ratios about 16-fold higher than the prevalence rates in the general population for both of these eosionophilic disorders.
The analyses reported by Dr. Mansoor also showed that the prevalence of celiac disease among patients with eosinophilic esophagitis was nearly twice as high in children (not more than 18 years old) as in adults and 50% higher in women than in men. These age and sex differences were both statistically significant.
Dr. Mansoor had no disclosures.
[email protected]
On Twitter @mitchelzoler
ORLANDO – Patients with eosinophilic esophagitis had a ninefold increased prevalence of celiac disease, compared with the general public, in a review of more than 35 million U.S. residents.
This finding, which corresponded to a 2% overall prevalence rate of celiac disease in patients diagnosed with eosinophilic esophagitis, suggests that routine screening for celiac disease in eosinophilic esophagitis patients is warranted, Emad Mansoor, MD, said at the World Congress of Gastroenterology at ACG 2017.
This high prevalence level “has great implications for how we screen, treat, and manage” patients with either disorder, Dr. Mansoor said in a video interview. He hypothesized that celiac disease and eosinophilic esophagitis could share genetic etiologies or environmental or autoimmune triggers that produce the high level of overlap that the results showed.
The same analysis also found high rates of celiac disease in patients with either eosinophilic gastroenteritis or colitis, but because these are both much less prevalent than eosiniphillic esophagitis the absolute number of patients with either of these eosinophilic disorders who also had celiac disease was much lower.
It’s very possible that the prevalence of eosinophilic esophagitis among patients with celiac disease is also significantly elevated, compared with the general population, but he and his associates have not run this analysis.
Their study included diagnostic records for 35,795,250 people in the Explorys database during May 2012 to May 2017, with entries from 317,000 providers at 360 U.S. hospitals. The review identified 84,040 patients with a diagnosis of celiac disease, 15,360 with eosinophilic esophagitis, 1,440 with eosinophilic gastritis, and 800 with eosinophilic colitis. This worked out to a 5-year prevalence rate of 234.8 cases of celiac disease per 100,000 patients (0.235%), an eosinophilic esophagitis prevalence of 43.7 per 100,000, an eosinophilic gastroenteritis rate of 4.0 per 100,000, and an eosinophilic colitis rate of 2.2 per 100,000, said Dr. Mansoor, a gastroenterologist at University Hospitals Cleveland Medical Center.
The prevalence of celiac disease among patients with eosinophilic gastroenteritis or colitis was higher than in the eosinophilic esophagitis patients, with rates of 3.5% and 3.7%, respectively, that translated into odds ratios about 16-fold higher than the prevalence rates in the general population for both of these eosionophilic disorders.
The analyses reported by Dr. Mansoor also showed that the prevalence of celiac disease among patients with eosinophilic esophagitis was nearly twice as high in children (not more than 18 years old) as in adults and 50% higher in women than in men. These age and sex differences were both statistically significant.
Dr. Mansoor had no disclosures.
[email protected]
On Twitter @mitchelzoler
ORLANDO – Patients with eosinophilic esophagitis had a ninefold increased prevalence of celiac disease, compared with the general public, in a review of more than 35 million U.S. residents.
This finding, which corresponded to a 2% overall prevalence rate of celiac disease in patients diagnosed with eosinophilic esophagitis, suggests that routine screening for celiac disease in eosinophilic esophagitis patients is warranted, Emad Mansoor, MD, said at the World Congress of Gastroenterology at ACG 2017.
This high prevalence level “has great implications for how we screen, treat, and manage” patients with either disorder, Dr. Mansoor said in a video interview. He hypothesized that celiac disease and eosinophilic esophagitis could share genetic etiologies or environmental or autoimmune triggers that produce the high level of overlap that the results showed.
The same analysis also found high rates of celiac disease in patients with either eosinophilic gastroenteritis or colitis, but because these are both much less prevalent than eosiniphillic esophagitis the absolute number of patients with either of these eosinophilic disorders who also had celiac disease was much lower.
It’s very possible that the prevalence of eosinophilic esophagitis among patients with celiac disease is also significantly elevated, compared with the general population, but he and his associates have not run this analysis.
Their study included diagnostic records for 35,795,250 people in the Explorys database during May 2012 to May 2017, with entries from 317,000 providers at 360 U.S. hospitals. The review identified 84,040 patients with a diagnosis of celiac disease, 15,360 with eosinophilic esophagitis, 1,440 with eosinophilic gastritis, and 800 with eosinophilic colitis. This worked out to a 5-year prevalence rate of 234.8 cases of celiac disease per 100,000 patients (0.235%), an eosinophilic esophagitis prevalence of 43.7 per 100,000, an eosinophilic gastroenteritis rate of 4.0 per 100,000, and an eosinophilic colitis rate of 2.2 per 100,000, said Dr. Mansoor, a gastroenterologist at University Hospitals Cleveland Medical Center.
The prevalence of celiac disease among patients with eosinophilic gastroenteritis or colitis was higher than in the eosinophilic esophagitis patients, with rates of 3.5% and 3.7%, respectively, that translated into odds ratios about 16-fold higher than the prevalence rates in the general population for both of these eosionophilic disorders.
The analyses reported by Dr. Mansoor also showed that the prevalence of celiac disease among patients with eosinophilic esophagitis was nearly twice as high in children (not more than 18 years old) as in adults and 50% higher in women than in men. These age and sex differences were both statistically significant.
Dr. Mansoor had no disclosures.
[email protected]
On Twitter @mitchelzoler
AT THE WORLD CONGRESS OF GASTROENTEROLOGY
Key clinical point:
Major finding: Among patients with eosinophilic esophagitis, the celiac disease prevalence was ninefold higher than in the general population.
Data source: Review of more than 35 million U.S. patients during 2012-2017.
Disclosures: Dr. Mansoor had no disclosures.
Low risk of bariatric surgery complications in IBD
Bariatric surgery is safe and feasible in patients with inflammatory bowel disease (IBD), with a low risk of postoperative complications vs. controls, according to results of a recent cohort study.
Besides a significantly higher risk of perioperative small-bowel obstruction and a 1-day increase in hospital stay, outcomes were comparable between patients with IBD and controls (Obes Surg. 2017 Oct 10. doi: 10.1007/s11695-017-2955-4).
Limitations of the retrospective study, according to the authors, included a potential underestimation of short-term postoperative complications, since the data set used in the study was limited to in-hospital stays and would not include events occurring after discharge.
Nevertheless, “our data show that it is reasonable to carefully proceed with bariatric interventions in obese IBD patients, especially those who are at higher risk of cardiovascular mortality and drastic need for weight reduction, to accrue benefits of weight loss,” wrote Fateh Bazerbachi, MD, of the Mayo Clinic, Rochester, Minn. and his coauthors.
Bariatric surgery is the “most effective solution” for obesity, and “appropriate candidates should not be deprived of this important, potentially life-saving procedure, if the intervention is deemed acceptably safe,” Dr. Bazerbachi and his colleagues noted.
Their cohort study included data for 314,864 adult patients in the Nationwide Inpatient Sample who underwent bariatric surgery between 2011 and 2013. Of that group, 790 patients had underlying IBD (459 Crohn’s disease, 331 ulcerative colitis). Remaining patients made up the comparator group.
The primary outcomes evaluated in the study included risks of systemic and technical complications. Risk of perioperative small-bowel obstruction was significantly higher in the IBD group (adjusted odds ratio, 4.0; 95% confidence interval, 2.2-7.4). However, the rates of other complications were similar between the two groups, data show.
Secondary outcomes in the study included length of hospital stay and mortality. Mean length of hospital stay was 3.4 days for IBD patients, vs. 2.5 days for the comparison group (P = .01), according to the report. Mortality was 0.25% for controls, while no deaths were reported in the IBD group.
In the future, bariatric surgeons may face increasing demand to treat IBD patients, given the increasing prevalence of obesity in the IBD patient population, Dr. Bazerbachi and his colleagues said.
Some surgeons may believe that bariatric intervention is more challenging in IBD patients, in part because of the underlying inflammatory state that might interfere with healing of wounds and recovery of bowel motility, they said. Bariatric surgery, however, can reduce body mass index, which in turn might make future IBD surgeries less challenging.
Another potential advantage is reduction in cardiovascular risk, which is elevated in IBD patients both due to obesity as well as the IBD condition, they added.
“Further studies are certainly needed to examine long-term outcomes of bariatric surgery on IBD and to determine whether cardiovascular mortality is reduced from these interventions in this susceptible cohort of obese IBD patients,” Dr. Bazerbachi and his colleagues wrote.
The authors declared that they had no conflicts of interest.
Bariatric surgery is safe and feasible in patients with inflammatory bowel disease (IBD), with a low risk of postoperative complications vs. controls, according to results of a recent cohort study.
Besides a significantly higher risk of perioperative small-bowel obstruction and a 1-day increase in hospital stay, outcomes were comparable between patients with IBD and controls (Obes Surg. 2017 Oct 10. doi: 10.1007/s11695-017-2955-4).
Limitations of the retrospective study, according to the authors, included a potential underestimation of short-term postoperative complications, since the data set used in the study was limited to in-hospital stays and would not include events occurring after discharge.
Nevertheless, “our data show that it is reasonable to carefully proceed with bariatric interventions in obese IBD patients, especially those who are at higher risk of cardiovascular mortality and drastic need for weight reduction, to accrue benefits of weight loss,” wrote Fateh Bazerbachi, MD, of the Mayo Clinic, Rochester, Minn. and his coauthors.
Bariatric surgery is the “most effective solution” for obesity, and “appropriate candidates should not be deprived of this important, potentially life-saving procedure, if the intervention is deemed acceptably safe,” Dr. Bazerbachi and his colleagues noted.
Their cohort study included data for 314,864 adult patients in the Nationwide Inpatient Sample who underwent bariatric surgery between 2011 and 2013. Of that group, 790 patients had underlying IBD (459 Crohn’s disease, 331 ulcerative colitis). Remaining patients made up the comparator group.
The primary outcomes evaluated in the study included risks of systemic and technical complications. Risk of perioperative small-bowel obstruction was significantly higher in the IBD group (adjusted odds ratio, 4.0; 95% confidence interval, 2.2-7.4). However, the rates of other complications were similar between the two groups, data show.
Secondary outcomes in the study included length of hospital stay and mortality. Mean length of hospital stay was 3.4 days for IBD patients, vs. 2.5 days for the comparison group (P = .01), according to the report. Mortality was 0.25% for controls, while no deaths were reported in the IBD group.
In the future, bariatric surgeons may face increasing demand to treat IBD patients, given the increasing prevalence of obesity in the IBD patient population, Dr. Bazerbachi and his colleagues said.
Some surgeons may believe that bariatric intervention is more challenging in IBD patients, in part because of the underlying inflammatory state that might interfere with healing of wounds and recovery of bowel motility, they said. Bariatric surgery, however, can reduce body mass index, which in turn might make future IBD surgeries less challenging.
Another potential advantage is reduction in cardiovascular risk, which is elevated in IBD patients both due to obesity as well as the IBD condition, they added.
“Further studies are certainly needed to examine long-term outcomes of bariatric surgery on IBD and to determine whether cardiovascular mortality is reduced from these interventions in this susceptible cohort of obese IBD patients,” Dr. Bazerbachi and his colleagues wrote.
The authors declared that they had no conflicts of interest.
Bariatric surgery is safe and feasible in patients with inflammatory bowel disease (IBD), with a low risk of postoperative complications vs. controls, according to results of a recent cohort study.
Besides a significantly higher risk of perioperative small-bowel obstruction and a 1-day increase in hospital stay, outcomes were comparable between patients with IBD and controls (Obes Surg. 2017 Oct 10. doi: 10.1007/s11695-017-2955-4).
Limitations of the retrospective study, according to the authors, included a potential underestimation of short-term postoperative complications, since the data set used in the study was limited to in-hospital stays and would not include events occurring after discharge.
Nevertheless, “our data show that it is reasonable to carefully proceed with bariatric interventions in obese IBD patients, especially those who are at higher risk of cardiovascular mortality and drastic need for weight reduction, to accrue benefits of weight loss,” wrote Fateh Bazerbachi, MD, of the Mayo Clinic, Rochester, Minn. and his coauthors.
Bariatric surgery is the “most effective solution” for obesity, and “appropriate candidates should not be deprived of this important, potentially life-saving procedure, if the intervention is deemed acceptably safe,” Dr. Bazerbachi and his colleagues noted.
Their cohort study included data for 314,864 adult patients in the Nationwide Inpatient Sample who underwent bariatric surgery between 2011 and 2013. Of that group, 790 patients had underlying IBD (459 Crohn’s disease, 331 ulcerative colitis). Remaining patients made up the comparator group.
The primary outcomes evaluated in the study included risks of systemic and technical complications. Risk of perioperative small-bowel obstruction was significantly higher in the IBD group (adjusted odds ratio, 4.0; 95% confidence interval, 2.2-7.4). However, the rates of other complications were similar between the two groups, data show.
Secondary outcomes in the study included length of hospital stay and mortality. Mean length of hospital stay was 3.4 days for IBD patients, vs. 2.5 days for the comparison group (P = .01), according to the report. Mortality was 0.25% for controls, while no deaths were reported in the IBD group.
In the future, bariatric surgeons may face increasing demand to treat IBD patients, given the increasing prevalence of obesity in the IBD patient population, Dr. Bazerbachi and his colleagues said.
Some surgeons may believe that bariatric intervention is more challenging in IBD patients, in part because of the underlying inflammatory state that might interfere with healing of wounds and recovery of bowel motility, they said. Bariatric surgery, however, can reduce body mass index, which in turn might make future IBD surgeries less challenging.
Another potential advantage is reduction in cardiovascular risk, which is elevated in IBD patients both due to obesity as well as the IBD condition, they added.
“Further studies are certainly needed to examine long-term outcomes of bariatric surgery on IBD and to determine whether cardiovascular mortality is reduced from these interventions in this susceptible cohort of obese IBD patients,” Dr. Bazerbachi and his colleagues wrote.
The authors declared that they had no conflicts of interest.
FROM OBESITY SURGERY
Key clinical point: Watch for perioperative small-bowel obstruction in IBD patients undergoing bariatric surgery.
Major finding: IBD patients had a higher risk of perioperative small bowel obstruction (adjusted odds ratio, 4.0; 95% confidence interval, 2.2-7.4) and a 1-day increase in hospital stay (P = .01), compared with controls.
Data source: Retrospective cohort study of Nationwide Inpatient Sample data including 790 patients with underlying IBD.
Disclosures: The authors declared that they had no conflicts of interest.
Fungi and bacteria cooperate to form inflammatory gut biofilms
Fungi and bacteria in the gastrointestinal tract collaboratively form biofilms that may exacerbate inflammation in patients with inflammatory bowel disease (IBD), a review article concluded.
In particular, the investigators found compared with healthy family members.
Furthermore, these three organisms “worked together to form robust biofilms capable of exacerbating intestinal inflammation,” wrote authors Christopher L. Hager, MD, and Mahmoud A. Ghannoum, PhD, of the center for medical mycology at Case Western Reserve University, Cleveland, and University Hospitals Cleveland Medical Center.
This “interkingdom interaction” suggests a potential role for antifungals combined with probiotics as a treatment strategy for patients with IBD, they said in their review article discussing both their own studies to date and those by other research groups.
“These studies clearly demonstrate that mycobiome/bacteriome interactions play an important role in the perpetuation of GI inflammation,” they wrote (Dig Liver Dis. 2017 Nov;49[11]:1171-6). “Not only have we shown that fungi are important for overall GI tract health, we have also shown that overgrowth of the fungus due to imbalance has deleterious effects on the gastric mucosa.”
Dr. Ghannoum and his colleagues first highlighted the importance of the mycobiome in a 2010 study that used deep sequencing to characterize the human oral fungal community (PLOS Pathogens. 2010 Jan 8. doi: 10.1371/journal.ppat.1000713). They found that humans were colonized with Candida, as was expected, but also with species including Aspergillus, Cryptococcus, and Fusarium, which was unexpected, Dr. Hager and Dr. Ghannoum wrote in their review.
In their more recent work, Dr. Ghannoum, Dr. Hager, and their coinvestigators compared CD patients with their healthy relatives and found increased levels of E. coli, S. marcescens, and the fungus C. tropicalis in the gastrointestinal tract (mBio. 2016 Sep 20. doi: 10.1128/mBio.01250-16). In vitro, those three organisms cooperate to form biofilms that could activate the host immune response, they said.
“These findings suggest a possible role of these pathogenic organisms in the initiation and perpetuation of chronic intestinal inflammation, such as that observed in patients with inflammatory bowel disease,” they wrote. “Not only has this opened up the possibility of new therapeutic approaches in patients with IBD (i.e., antifungals/antibiotics), it has also paved the way for groundbreaking research on probiotic development aimed at disrupting GI biofilm formation, thus ending a vicious cycle of chronic intestinal inflammation.”
Developing new probiotic therapies that leverage mycobiome-level observations could help overcome some limitations of current treatment options for IBD, such as biologic therapies and antibiotics, the authors wrote.
Biologics can block immune pathways implicated in mucosal inflammation and lead to potentially deleterious secondary infections, they explained. Likewise, antibiotics can be effective in controlling inflammatory symptoms but raise the concern of potentially increasing antibiotic resistance.
Although new probiotic research could provide a new avenue of treatment, development of clinical studies could be limited in part, they said, because probiotics are considered to be food supplements rather than drugs regulated by the Food and Drug Administration.
“Conducting such trials is challenging due to the lack of funding, leaving companies with very little impetus to perform long, expensive, placebo-controlled studies,” the authors wrote.
The authors declared no conflicts of interest.
Fungi and bacteria in the gastrointestinal tract collaboratively form biofilms that may exacerbate inflammation in patients with inflammatory bowel disease (IBD), a review article concluded.
In particular, the investigators found compared with healthy family members.
Furthermore, these three organisms “worked together to form robust biofilms capable of exacerbating intestinal inflammation,” wrote authors Christopher L. Hager, MD, and Mahmoud A. Ghannoum, PhD, of the center for medical mycology at Case Western Reserve University, Cleveland, and University Hospitals Cleveland Medical Center.
This “interkingdom interaction” suggests a potential role for antifungals combined with probiotics as a treatment strategy for patients with IBD, they said in their review article discussing both their own studies to date and those by other research groups.
“These studies clearly demonstrate that mycobiome/bacteriome interactions play an important role in the perpetuation of GI inflammation,” they wrote (Dig Liver Dis. 2017 Nov;49[11]:1171-6). “Not only have we shown that fungi are important for overall GI tract health, we have also shown that overgrowth of the fungus due to imbalance has deleterious effects on the gastric mucosa.”
Dr. Ghannoum and his colleagues first highlighted the importance of the mycobiome in a 2010 study that used deep sequencing to characterize the human oral fungal community (PLOS Pathogens. 2010 Jan 8. doi: 10.1371/journal.ppat.1000713). They found that humans were colonized with Candida, as was expected, but also with species including Aspergillus, Cryptococcus, and Fusarium, which was unexpected, Dr. Hager and Dr. Ghannoum wrote in their review.
In their more recent work, Dr. Ghannoum, Dr. Hager, and their coinvestigators compared CD patients with their healthy relatives and found increased levels of E. coli, S. marcescens, and the fungus C. tropicalis in the gastrointestinal tract (mBio. 2016 Sep 20. doi: 10.1128/mBio.01250-16). In vitro, those three organisms cooperate to form biofilms that could activate the host immune response, they said.
“These findings suggest a possible role of these pathogenic organisms in the initiation and perpetuation of chronic intestinal inflammation, such as that observed in patients with inflammatory bowel disease,” they wrote. “Not only has this opened up the possibility of new therapeutic approaches in patients with IBD (i.e., antifungals/antibiotics), it has also paved the way for groundbreaking research on probiotic development aimed at disrupting GI biofilm formation, thus ending a vicious cycle of chronic intestinal inflammation.”
Developing new probiotic therapies that leverage mycobiome-level observations could help overcome some limitations of current treatment options for IBD, such as biologic therapies and antibiotics, the authors wrote.
Biologics can block immune pathways implicated in mucosal inflammation and lead to potentially deleterious secondary infections, they explained. Likewise, antibiotics can be effective in controlling inflammatory symptoms but raise the concern of potentially increasing antibiotic resistance.
Although new probiotic research could provide a new avenue of treatment, development of clinical studies could be limited in part, they said, because probiotics are considered to be food supplements rather than drugs regulated by the Food and Drug Administration.
“Conducting such trials is challenging due to the lack of funding, leaving companies with very little impetus to perform long, expensive, placebo-controlled studies,” the authors wrote.
The authors declared no conflicts of interest.
Fungi and bacteria in the gastrointestinal tract collaboratively form biofilms that may exacerbate inflammation in patients with inflammatory bowel disease (IBD), a review article concluded.
In particular, the investigators found compared with healthy family members.
Furthermore, these three organisms “worked together to form robust biofilms capable of exacerbating intestinal inflammation,” wrote authors Christopher L. Hager, MD, and Mahmoud A. Ghannoum, PhD, of the center for medical mycology at Case Western Reserve University, Cleveland, and University Hospitals Cleveland Medical Center.
This “interkingdom interaction” suggests a potential role for antifungals combined with probiotics as a treatment strategy for patients with IBD, they said in their review article discussing both their own studies to date and those by other research groups.
“These studies clearly demonstrate that mycobiome/bacteriome interactions play an important role in the perpetuation of GI inflammation,” they wrote (Dig Liver Dis. 2017 Nov;49[11]:1171-6). “Not only have we shown that fungi are important for overall GI tract health, we have also shown that overgrowth of the fungus due to imbalance has deleterious effects on the gastric mucosa.”
Dr. Ghannoum and his colleagues first highlighted the importance of the mycobiome in a 2010 study that used deep sequencing to characterize the human oral fungal community (PLOS Pathogens. 2010 Jan 8. doi: 10.1371/journal.ppat.1000713). They found that humans were colonized with Candida, as was expected, but also with species including Aspergillus, Cryptococcus, and Fusarium, which was unexpected, Dr. Hager and Dr. Ghannoum wrote in their review.
In their more recent work, Dr. Ghannoum, Dr. Hager, and their coinvestigators compared CD patients with their healthy relatives and found increased levels of E. coli, S. marcescens, and the fungus C. tropicalis in the gastrointestinal tract (mBio. 2016 Sep 20. doi: 10.1128/mBio.01250-16). In vitro, those three organisms cooperate to form biofilms that could activate the host immune response, they said.
“These findings suggest a possible role of these pathogenic organisms in the initiation and perpetuation of chronic intestinal inflammation, such as that observed in patients with inflammatory bowel disease,” they wrote. “Not only has this opened up the possibility of new therapeutic approaches in patients with IBD (i.e., antifungals/antibiotics), it has also paved the way for groundbreaking research on probiotic development aimed at disrupting GI biofilm formation, thus ending a vicious cycle of chronic intestinal inflammation.”
Developing new probiotic therapies that leverage mycobiome-level observations could help overcome some limitations of current treatment options for IBD, such as biologic therapies and antibiotics, the authors wrote.
Biologics can block immune pathways implicated in mucosal inflammation and lead to potentially deleterious secondary infections, they explained. Likewise, antibiotics can be effective in controlling inflammatory symptoms but raise the concern of potentially increasing antibiotic resistance.
Although new probiotic research could provide a new avenue of treatment, development of clinical studies could be limited in part, they said, because probiotics are considered to be food supplements rather than drugs regulated by the Food and Drug Administration.
“Conducting such trials is challenging due to the lack of funding, leaving companies with very little impetus to perform long, expensive, placebo-controlled studies,” the authors wrote.
The authors declared no conflicts of interest.
FROM DIGESTIVE AND LIVER DISEASE
Key clinical point: Fungi and bacteria interact in the gastrointestinal tract to form biofilms that may exacerbate inflammation, suggesting a potential role for antifungals combined with probiotics as a treatment strategy for patients with inflammatory bowel disease.
Major finding: Compared with healthy family members, patients with Crohn’s disease in one key study had higher levels of the fungus Candida tropicalis and of two bacteria, Escherichia coli and Serratia marcescens, all of which worked together to form robust biofilms.
Data source: A review article summarizing the limited number of investigations to date, most published in 2010 or later.
Disclosures: The authors declared no conflicts of interest.