From the AGA Journals

The role of probiotics in the management of gastrointestinal disorders remains largely unclear, according to a clinical practice guideline published by the American Gastroenterological Association (AGA).

Out of eight disorders reviewed by the guideline panel, four had enough relevant data to support conditional recommendations, while the other four were associated with knowledge gaps that precluded guidance, reported lead author Grace L. Su, MD, AGAF, of the University of Michigan, Ann Arbor, and colleagues.

“It is estimated that 3.9 million American adults used some form of probiotics or prebiotics ... in 2015, an amount which is four times that in 2007,” the guideline panelists wrote. Their report is in Gastroenterology. “Given widespread use and often biased sources of information, it is essential that clinicians have objective guidance for their patients about the appropriate use of and indications for probiotics.”

The creation of such guidance, however, proved a challenging task for the panel, who faced an “extremely varied” evidence base.

Dr. Su and colleagues, who were selected by the AGA Governing Board and Clinical Guidelines Committee, encountered “differences in the strain of microbe(s) used, dose, and route of administration.”

They noted that such differences can significantly affect clinical outcomes.

“Within species, different strains can have widely different activities and biologic effects,” they wrote. “Many immunologic, neurologic, and biochemical effects of gut microbiota are likely not only to be strain specific, but also dose specific. Furthermore, combinations of different microbial strains may also have widely different activity as some microbial activities are dependent on interactions between different strains.”

Beyond differences in treatments, the investigators also reported wide variability in endpoints and outcomes, as well as relatively small study populations compared with pharmacological trials.

Still, data were sufficient to provide some conditional recommendations.

The guideline supports probiotics for patients with pouchitis, those receiving antibiotic therapy, and preterm/low-birthweight infants. In contrast, the panel recommended against probiotics for children with acute infectious gastroenteritis, noting that this recommendation differs from those made by other medical organizations.

“While other society guidelines have previously recommended the use of probiotics in [children with acute infectious gastroenteritis], these guidelines were developed without utilizing GRADE methodology and also relied on data outside of North America which became available after the recommendations were made,” wrote Dr. Su and colleagues. They described a moderate quality of evidence relevant to this indication.

In comparison, the quality of evidence was very low for patients with pouchitis, low for those receiving antibiotics, and moderate/high for preterm/low-birthweight infants.

For Clostridioides difficile infection, Crohn’s disease, ulcerative colitis, and irritable bowel syndrome, the panel recommended probiotics only in the context of a clinical trial, citing knowledge gaps in these areas.

They also noted that probiotics may not be suitable for those at high risk of infection.

“[F]or patients who place a high value on avoidance of potential harms, particularly those with severe illnesses or immunosuppression, it would be reasonable to select not to use probiotics,” the panelists wrote.

Concluding their discussion, Dr. Su and colleagues called for more high-quality research.

“We identified that significant knowledge gaps exist in this very promising and important area of research due to the significant heterogeneity between studies and variability in the probiotic strains studied,” they wrote. “The lack of consistent harms reporting makes it difficult to assess true harms. The lack of product manufacturing details prohibits true comparisons and decreases the feasibility of obtaining certain products by patients. Future high-quality studies are urgently needed which address these pitfalls.”

According to the panelists, the probiotic guideline will be updated in 3-5 years, or possibly earlier if practice-altering findings are published.

The investigators disclosed relationships with Nestex, AbbVie, Takeda, and others.

The role of probiotics in the management of gastrointestinal disorders remains largely unclear, according to a clinical practice guideline published by the American Gastroenterological Association (AGA).

Out of eight disorders reviewed by the guideline panel, four had enough relevant data to support conditional recommendations, while the other four were associated with knowledge gaps that precluded guidance, reported lead author Grace L. Su, MD, AGAF, of the University of Michigan, Ann Arbor, and colleagues.

“It is estimated that 3.9 million American adults used some form of probiotics or prebiotics ... in 2015, an amount which is four times that in 2007,” the guideline panelists wrote. Their report is in Gastroenterology. “Given widespread use and often biased sources of information, it is essential that clinicians have objective guidance for their patients about the appropriate use of and indications for probiotics.”

The creation of such guidance, however, proved a challenging task for the panel, who faced an “extremely varied” evidence base.

Dr. Su and colleagues, who were selected by the AGA Governing Board and Clinical Guidelines Committee, encountered “differences in the strain of microbe(s) used, dose, and route of administration.”

They noted that such differences can significantly affect clinical outcomes.

“Within species, different strains can have widely different activities and biologic effects,” they wrote. “Many immunologic, neurologic, and biochemical effects of gut microbiota are likely not only to be strain specific, but also dose specific. Furthermore, combinations of different microbial strains may also have widely different activity as some microbial activities are dependent on interactions between different strains.”

Beyond differences in treatments, the investigators also reported wide variability in endpoints and outcomes, as well as relatively small study populations compared with pharmacological trials.

Still, data were sufficient to provide some conditional recommendations.

The guideline supports probiotics for patients with pouchitis, those receiving antibiotic therapy, and preterm/low-birthweight infants. In contrast, the panel recommended against probiotics for children with acute infectious gastroenteritis, noting that this recommendation differs from those made by other medical organizations.

“While other society guidelines have previously recommended the use of probiotics in [children with acute infectious gastroenteritis], these guidelines were developed without utilizing GRADE methodology and also relied on data outside of North America which became available after the recommendations were made,” wrote Dr. Su and colleagues. They described a moderate quality of evidence relevant to this indication.

In comparison, the quality of evidence was very low for patients with pouchitis, low for those receiving antibiotics, and moderate/high for preterm/low-birthweight infants.

For Clostridioides difficile infection, Crohn’s disease, ulcerative colitis, and irritable bowel syndrome, the panel recommended probiotics only in the context of a clinical trial, citing knowledge gaps in these areas.

They also noted that probiotics may not be suitable for those at high risk of infection.

“[F]or patients who place a high value on avoidance of potential harms, particularly those with severe illnesses or immunosuppression, it would be reasonable to select not to use probiotics,” the panelists wrote.

Concluding their discussion, Dr. Su and colleagues called for more high-quality research.

“We identified that significant knowledge gaps exist in this very promising and important area of research due to the significant heterogeneity between studies and variability in the probiotic strains studied,” they wrote. “The lack of consistent harms reporting makes it difficult to assess true harms. The lack of product manufacturing details prohibits true comparisons and decreases the feasibility of obtaining certain products by patients. Future high-quality studies are urgently needed which address these pitfalls.”

According to the panelists, the probiotic guideline will be updated in 3-5 years, or possibly earlier if practice-altering findings are published.

The investigators disclosed relationships with Nestex, AbbVie, Takeda, and others.

The role of probiotics in the management of gastrointestinal disorders remains largely unclear, according to a clinical practice guideline published by the American Gastroenterological Association (AGA).

Out of eight disorders reviewed by the guideline panel, four had enough relevant data to support conditional recommendations, while the other four were associated with knowledge gaps that precluded guidance, reported lead author Grace L. Su, MD, AGAF, of the University of Michigan, Ann Arbor, and colleagues.

“It is estimated that 3.9 million American adults used some form of probiotics or prebiotics ... in 2015, an amount which is four times that in 2007,” the guideline panelists wrote. Their report is in Gastroenterology. “Given widespread use and often biased sources of information, it is essential that clinicians have objective guidance for their patients about the appropriate use of and indications for probiotics.”

The creation of such guidance, however, proved a challenging task for the panel, who faced an “extremely varied” evidence base.

Dr. Su and colleagues, who were selected by the AGA Governing Board and Clinical Guidelines Committee, encountered “differences in the strain of microbe(s) used, dose, and route of administration.”

They noted that such differences can significantly affect clinical outcomes.

“Within species, different strains can have widely different activities and biologic effects,” they wrote. “Many immunologic, neurologic, and biochemical effects of gut microbiota are likely not only to be strain specific, but also dose specific. Furthermore, combinations of different microbial strains may also have widely different activity as some microbial activities are dependent on interactions between different strains.”

Beyond differences in treatments, the investigators also reported wide variability in endpoints and outcomes, as well as relatively small study populations compared with pharmacological trials.

Still, data were sufficient to provide some conditional recommendations.

The guideline supports probiotics for patients with pouchitis, those receiving antibiotic therapy, and preterm/low-birthweight infants. In contrast, the panel recommended against probiotics for children with acute infectious gastroenteritis, noting that this recommendation differs from those made by other medical organizations.

“While other society guidelines have previously recommended the use of probiotics in [children with acute infectious gastroenteritis], these guidelines were developed without utilizing GRADE methodology and also relied on data outside of North America which became available after the recommendations were made,” wrote Dr. Su and colleagues. They described a moderate quality of evidence relevant to this indication.

In comparison, the quality of evidence was very low for patients with pouchitis, low for those receiving antibiotics, and moderate/high for preterm/low-birthweight infants.

For Clostridioides difficile infection, Crohn’s disease, ulcerative colitis, and irritable bowel syndrome, the panel recommended probiotics only in the context of a clinical trial, citing knowledge gaps in these areas.

They also noted that probiotics may not be suitable for those at high risk of infection.

“[F]or patients who place a high value on avoidance of potential harms, particularly those with severe illnesses or immunosuppression, it would be reasonable to select not to use probiotics,” the panelists wrote.

Concluding their discussion, Dr. Su and colleagues called for more high-quality research.

“We identified that significant knowledge gaps exist in this very promising and important area of research due to the significant heterogeneity between studies and variability in the probiotic strains studied,” they wrote. “The lack of consistent harms reporting makes it difficult to assess true harms. The lack of product manufacturing details prohibits true comparisons and decreases the feasibility of obtaining certain products by patients. Future high-quality studies are urgently needed which address these pitfalls.”

According to the panelists, the probiotic guideline will be updated in 3-5 years, or possibly earlier if practice-altering findings are published.

The investigators disclosed relationships with Nestex, AbbVie, Takeda, and others.

For preterm, low-birth-weight infants, probiotic formulations containing Lactobacillus and Bifidobacterium strains appear to be superior to single-strain probiotics and to other multiple-strain formulations for reducing the risk of all-cause mortality, according to the findings of a network meta-analysis of randomized clinical trials.

The results of a prior Cochrane review indicated that probiotics can help prevent severe necrotizing enterocolitis and all-cause mortality in preterm infants, but the most effective formulations remained unclear. Therefore, Rebecca L. Morgan, PhD, MPH, and her associates searched MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through Jan. 1, 2019, to identify studies of single-strain and multistrain probiotic formulations in preterm, low-birth-weight neonates. A total of 63 studies involving 15,712 infants met inclusion criteria. “We used a frequentist approach for network meta-analysis and [a] GRADE approach to assess certainty of evidence,” they noted.

“High-certainty” evidence indicated that combination therapy with one or more Lactobacillus species and one or more Bifidobacterium species significantly reduced all-cause mortality, compared with placebo (odds ratio, 0.56; 95% confidence interval, 0.39-0.80), wrote Dr. Morgan, of McMaster University, Hamilton, Canada, and her coinvestigators. This was the only intervention to have moderate- or high-quality evidence for a reduction in mortality, the researchers wrote in Gastroenterology.

They added that, among the probiotic formulations with moderate- or high-quality evidence for efficacy, compared with placebo, those containing at least one species of Lactobacillus and at least one species of Bifidobacterium, and the single-strain probiotics containing Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced the risk of severe necrotizing enterocolitis (Bell stage II or higher), with statistically significant odds ratios of 0.35, 0.31, 0.55, and 0.44, respectively.

Three formulations were associated with “low-” or “very low-certainty” evidence for a reduction in risk for severe necrotizing enterocolitis, compared with placebo: Bacillus plus Enterococcus species, Lactobacillus plus Bifidobacterium plus Enterococcus species and Bifidobacterium plus Streptococcus salivarius subspecies thermophilus. Estimated odds ratios were 0.23 (risk difference, –4.9%), 0.28 (RD, –4.9%), and 0.38 (RD, –3.9%), respectively.

“The combinations of Bacillus species and Enterococcus species, and one or more Bifidobacterium species and S. salivarius subspecies thermophilus, might produce the largest reduction in necrotizing enterocolitis development,” the investigators wrote. “Further trials are needed.”

Compared with placebo, no probiotic formulation significantly improved the third primary outcome in the meta-analysis, culture-confirmed sepsis. However, several formulations were associated with moderate- or high-quality evidence for efficacy on secondary outcome measures. Compared with placebo, combinations of Lactobacillus and Bifidobacterium and Saccharomyces boulardii were associated with a significant decrease in the number of days to reach full feeding (mean reduction, 3.3 days; 95% CI, 5.9-0.7 days). Compared with placebo, single-strain therapy with B. animalis subspecies lactis or Lactobacillus reuteri was associated with a shorter duration of hospitalization, with mean reductions of 13.0 days (95% CI, 22.7-3.3 days) and 7.9 days (95% CI, 11.6-4.2 days), respectively.

“Multicenter and large randomized controlled trials should be prioritized to distinguish between the efficacy of single- and multiple-strain probiotics among preterm infants,” Dr. Morgan and her associates concluded. Such studies would further clarify the safety of probiotic formulations in this “fragile population,” they wrote. “Although the primary concern of live microbe administration, intestinal barrier translocation leading to sepsis, is decreased by several probiotic formulations, sound clinical judgement should be exercised.”

Partial support was provided by Mitacs Canada, in partnership with Nestlé Canada. The funder was not involved in designing or conducting the study or writing the manuscript. Dr. Morgan reported having no relevant conflicts of interest. One coinvestigator disclosed ties to AbbVie, Ferring, Janssen, and Takeda.

SOURCE: Morgan RL et al. Gastroenterology. 2020 Jun 24. doi: 10.1053/j.gastro.2020.05.096.

For preterm, low-birth-weight infants, probiotic formulations containing Lactobacillus and Bifidobacterium strains appear to be superior to single-strain probiotics and to other multiple-strain formulations for reducing the risk of all-cause mortality, according to the findings of a network meta-analysis of randomized clinical trials.

The results of a prior Cochrane review indicated that probiotics can help prevent severe necrotizing enterocolitis and all-cause mortality in preterm infants, but the most effective formulations remained unclear. Therefore, Rebecca L. Morgan, PhD, MPH, and her associates searched MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through Jan. 1, 2019, to identify studies of single-strain and multistrain probiotic formulations in preterm, low-birth-weight neonates. A total of 63 studies involving 15,712 infants met inclusion criteria. “We used a frequentist approach for network meta-analysis and [a] GRADE approach to assess certainty of evidence,” they noted.

“High-certainty” evidence indicated that combination therapy with one or more Lactobacillus species and one or more Bifidobacterium species significantly reduced all-cause mortality, compared with placebo (odds ratio, 0.56; 95% confidence interval, 0.39-0.80), wrote Dr. Morgan, of McMaster University, Hamilton, Canada, and her coinvestigators. This was the only intervention to have moderate- or high-quality evidence for a reduction in mortality, the researchers wrote in Gastroenterology.

They added that, among the probiotic formulations with moderate- or high-quality evidence for efficacy, compared with placebo, those containing at least one species of Lactobacillus and at least one species of Bifidobacterium, and the single-strain probiotics containing Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced the risk of severe necrotizing enterocolitis (Bell stage II or higher), with statistically significant odds ratios of 0.35, 0.31, 0.55, and 0.44, respectively.

Three formulations were associated with “low-” or “very low-certainty” evidence for a reduction in risk for severe necrotizing enterocolitis, compared with placebo: Bacillus plus Enterococcus species, Lactobacillus plus Bifidobacterium plus Enterococcus species and Bifidobacterium plus Streptococcus salivarius subspecies thermophilus. Estimated odds ratios were 0.23 (risk difference, –4.9%), 0.28 (RD, –4.9%), and 0.38 (RD, –3.9%), respectively.

“The combinations of Bacillus species and Enterococcus species, and one or more Bifidobacterium species and S. salivarius subspecies thermophilus, might produce the largest reduction in necrotizing enterocolitis development,” the investigators wrote. “Further trials are needed.”

Compared with placebo, no probiotic formulation significantly improved the third primary outcome in the meta-analysis, culture-confirmed sepsis. However, several formulations were associated with moderate- or high-quality evidence for efficacy on secondary outcome measures. Compared with placebo, combinations of Lactobacillus and Bifidobacterium and Saccharomyces boulardii were associated with a significant decrease in the number of days to reach full feeding (mean reduction, 3.3 days; 95% CI, 5.9-0.7 days). Compared with placebo, single-strain therapy with B. animalis subspecies lactis or Lactobacillus reuteri was associated with a shorter duration of hospitalization, with mean reductions of 13.0 days (95% CI, 22.7-3.3 days) and 7.9 days (95% CI, 11.6-4.2 days), respectively.

“Multicenter and large randomized controlled trials should be prioritized to distinguish between the efficacy of single- and multiple-strain probiotics among preterm infants,” Dr. Morgan and her associates concluded. Such studies would further clarify the safety of probiotic formulations in this “fragile population,” they wrote. “Although the primary concern of live microbe administration, intestinal barrier translocation leading to sepsis, is decreased by several probiotic formulations, sound clinical judgement should be exercised.”

Partial support was provided by Mitacs Canada, in partnership with Nestlé Canada. The funder was not involved in designing or conducting the study or writing the manuscript. Dr. Morgan reported having no relevant conflicts of interest. One coinvestigator disclosed ties to AbbVie, Ferring, Janssen, and Takeda.

SOURCE: Morgan RL et al. Gastroenterology. 2020 Jun 24. doi: 10.1053/j.gastro.2020.05.096.

For preterm, low-birth-weight infants, probiotic formulations containing Lactobacillus and Bifidobacterium strains appear to be superior to single-strain probiotics and to other multiple-strain formulations for reducing the risk of all-cause mortality, according to the findings of a network meta-analysis of randomized clinical trials.

The results of a prior Cochrane review indicated that probiotics can help prevent severe necrotizing enterocolitis and all-cause mortality in preterm infants, but the most effective formulations remained unclear. Therefore, Rebecca L. Morgan, PhD, MPH, and her associates searched MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through Jan. 1, 2019, to identify studies of single-strain and multistrain probiotic formulations in preterm, low-birth-weight neonates. A total of 63 studies involving 15,712 infants met inclusion criteria. “We used a frequentist approach for network meta-analysis and [a] GRADE approach to assess certainty of evidence,” they noted.

“High-certainty” evidence indicated that combination therapy with one or more Lactobacillus species and one or more Bifidobacterium species significantly reduced all-cause mortality, compared with placebo (odds ratio, 0.56; 95% confidence interval, 0.39-0.80), wrote Dr. Morgan, of McMaster University, Hamilton, Canada, and her coinvestigators. This was the only intervention to have moderate- or high-quality evidence for a reduction in mortality, the researchers wrote in Gastroenterology.

They added that, among the probiotic formulations with moderate- or high-quality evidence for efficacy, compared with placebo, those containing at least one species of Lactobacillus and at least one species of Bifidobacterium, and the single-strain probiotics containing Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced the risk of severe necrotizing enterocolitis (Bell stage II or higher), with statistically significant odds ratios of 0.35, 0.31, 0.55, and 0.44, respectively.

Three formulations were associated with “low-” or “very low-certainty” evidence for a reduction in risk for severe necrotizing enterocolitis, compared with placebo: Bacillus plus Enterococcus species, Lactobacillus plus Bifidobacterium plus Enterococcus species and Bifidobacterium plus Streptococcus salivarius subspecies thermophilus. Estimated odds ratios were 0.23 (risk difference, –4.9%), 0.28 (RD, –4.9%), and 0.38 (RD, –3.9%), respectively.

“The combinations of Bacillus species and Enterococcus species, and one or more Bifidobacterium species and S. salivarius subspecies thermophilus, might produce the largest reduction in necrotizing enterocolitis development,” the investigators wrote. “Further trials are needed.”

Compared with placebo, no probiotic formulation significantly improved the third primary outcome in the meta-analysis, culture-confirmed sepsis. However, several formulations were associated with moderate- or high-quality evidence for efficacy on secondary outcome measures. Compared with placebo, combinations of Lactobacillus and Bifidobacterium and Saccharomyces boulardii were associated with a significant decrease in the number of days to reach full feeding (mean reduction, 3.3 days; 95% CI, 5.9-0.7 days). Compared with placebo, single-strain therapy with B. animalis subspecies lactis or Lactobacillus reuteri was associated with a shorter duration of hospitalization, with mean reductions of 13.0 days (95% CI, 22.7-3.3 days) and 7.9 days (95% CI, 11.6-4.2 days), respectively.

“Multicenter and large randomized controlled trials should be prioritized to distinguish between the efficacy of single- and multiple-strain probiotics among preterm infants,” Dr. Morgan and her associates concluded. Such studies would further clarify the safety of probiotic formulations in this “fragile population,” they wrote. “Although the primary concern of live microbe administration, intestinal barrier translocation leading to sepsis, is decreased by several probiotic formulations, sound clinical judgement should be exercised.”

Partial support was provided by Mitacs Canada, in partnership with Nestlé Canada. The funder was not involved in designing or conducting the study or writing the manuscript. Dr. Morgan reported having no relevant conflicts of interest. One coinvestigator disclosed ties to AbbVie, Ferring, Janssen, and Takeda.

SOURCE: Morgan RL et al. Gastroenterology. 2020 Jun 24. doi: 10.1053/j.gastro.2020.05.096.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative-pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non–COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: use of N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no use of only surgical masks in confirmed COVID-19 patients or suspected cases; and use of reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area; minimizing the number of personnel in the room; avoiding change of personnel and keeping nonprocedural personnel out during the procedure; considering use of nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time-sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative-pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non–COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: use of N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no use of only surgical masks in confirmed COVID-19 patients or suspected cases; and use of reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area; minimizing the number of personnel in the room; avoiding change of personnel and keeping nonprocedural personnel out during the procedure; considering use of nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time-sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

Nausea, vomiting, and diarrhea are gastrointestinal symptoms that COVID-19 patients have had, and up to 30% have been reported to have liver symptoms. Because patients with these symptoms may require endoscopy, the American Gastroenterological Association has issued a rapid recommendation document that advises physicians and health care workers to use N95 masks, double gloves, and negative-pressure rooms when performing GI procedures during the COVID-19 pandemic.

The recommendations, published in Gastroenterology (2020. doi: 10.1053/j.gastro.2020.03.072), also cover non–COVID-19 patients and situations where N95 masks should be used, offer guidelines for triaging patients for endoscopy and timing of nonurgent procedures, and evaluate the latest evidence in the incidence of GI and liver manifestations of COVID-19. The guideline panel met in March.

The document includes seven recommendations for use of personal protective equipment by physicians and nurses performing GI procedures. The recommendations and the level of evidence supporting them fall under four categories:

1. Masks, comprising four recommendations: use of N95 masks for upper and lower GI procedures regardless of a patient’s COVID-19 status; no use of only surgical masks in confirmed COVID-19 patients or suspected cases; and use of reused N95 masks when fresh ones aren’t available instead of using a surgical mask only (very low to moderate level of evidence depending on the recommendation).

2. Double-gloving when performing any GI procedure regardless of the patient’s COVID-19 status (moderate quality evidence).

3. When available, a negative-pressure room for any COVID-19 patient or suspect rather than a regular endoscopy room (very low certainty of evidence).

4. Standard cleaning, endoscopic disinfection, and reprocessing protocols regardless of a patient’s COVID-19 status (good practice statement).

For decontamination, the panel noted that commonly used biocidal agents, such as hydrogen peroxide, alcohols, sodium hypochlorite, or benzalkonium chloride have proved effective for decontaminating of coronavirus.

For implementing the PPE recommendations, the panel stated that personnel still need to practice don and doff standard protocols, and that N95 masks should be fitted for each individual.

Other steps include banning personal belongings in the procedure area; minimizing the number of personnel in the room; avoiding change of personnel and keeping nonprocedural personnel out during the procedure; considering use of nursing teams that follow the patient through preprocedure, procedure, and recovery, and considering having endoscopy teams remain together during the day to minimize exposure.

The triage recommendations stated that “trained medical personnel” should review all procedures and categorize them as time-sensitive or not time-sensitive, based on a framework the recommendation includes. In “an open-access endoscopy system” when there isn’t enough information to determine timing for the procedure, the recommendation provides a three-step approach: a phone consult with the referring physician, a telehealth visit with the patient, or a multidisciplinary team approach or virtual disease/tumor board.

“The proposed framework of separating procedures into time-sensitive and non–time-sensitive cases may be useful in determining which procedures if delayed may negatively impact on patient-important outcomes,” wrote Shahnaz Sultan, MD, AGAF, of the University of Minnesota, Minneapolis, and colleagues. The panel noted decision-making should focus on “patient-important outcomes.”

For nonurgent procedures, the panel arrived at a consensus that 8 weeks was an appropriate window for reassessment of deferred procedures, depending on the availability of resources and if the time-sensitivity of the procedure changes.

The panel also attempted to determine the likelihood of GI and liver manifestations of COVID-19 by evaluating published cohort studies. They found that 2%-13.8% of patients had diarrhea, 1%-10.1% had nausea or vomiting, and one study reported 2% had abdominal pain (Am J Gastroenterol. 2020 May;115[5]766-73). What’s more, some studies have shown stool samples positive for SARS-CoV-2 RNA even after respiratory samples were negative.

The evidence on liver manifestations isn’t as robust, but one study reported that 20%-30% of patients had liver injury upon diagnosis of COVID-19 (Gastroenterology. 2020;158:1518-9), and that severe hepatitis has been reported but liver failure seems rare (Lancet. 2020 Feb 15;395[10223]:507-13). “The pattern of liver injury appears to be predominantly hepatocellular, and the etiology remains uncertain but may represent a secondary effect of the systemic inflammatory response observed with COVID-19 disease, although direct viral infection and drug-induced liver injury cannot be excluded,” Dr. Sultan and colleagues noted.

There were no relevant author conflicts of interest. The American Gastroenterological Association (AGA) Institute funded the study.

SOURCE: Sultan S et al. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.03.072.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

The American Gastroenterological Association has released a new guideline for consultative management of patients with COVID-19.

The recommendations, which were written by Shahnaz Sultan, MD, AGAF, chair of the AGA Clinical Guidelines Committee, of the University of Minnesota, Minneapolis, and colleagues, were based on a meta-analysis of data from 47 studies involving 10,890 unique patients.

“We seek to summarize international data on the GI and liver manifestations of COVID-19 infection and treatment,” the panelists wrote in Gastroenterology. “Additionally, this document provides evidence-based clinical guidance on clinical questions that gastroenterologists may be consulted for.”

The guideline includes seven best practice statements.

The first three statements relate to COVID-19–related GI symptoms, which are estimated to occur in less than 10% of patients, and rarely in the absence of other COVID-19–related symptoms, according to Dr. Sultan and her copanelists.

“The overall prevalence of GI symptoms in the context of COVID-19, including nausea, vomiting, abdominal pain, and diarrhea, is lower than estimated previously,” the panelists wrote, referencing a previous meta-analysis by Ka Shing Cheung, MBBS, and colleagues that showed a prevalence of 17.6%.

“It is important to note that the majority of studies were focused on hospitalized patients with COVID-19, and the prevalence of diarrhea in patients with mild symptoms who were not hospitalized is not known.”

Since GI issues may precede other symptoms of COVID-19, the guideline recommends questioning outpatients with new-onset GI symptoms about other symptoms of COVID-19, with viral testing recommended in areas of high prevalence. Conversely, the panelists recommended that patients with suspected or known COVID-19 should undergo thorough history taking for GI symptoms, “including onset, characteristics, duration, and severity.”

The fourth practice statement advises against COVID-19 stool testing in routine clinical practice, either for diagnostic or monitoring purposes.

Although Dr. Cheung and colleagues reported that 48.1% of fecal specimens from patients with COVID-19 contained viral RNA, the panelists concluded that the practical relevance of this finding remains unknown.

“Stool infectivity and transmission have not been confirmed,” the panelists wrote, citing a lack of evidence and conflicting findings.

The final three practice statements address liver concerns.

First, any patient with suspected or confirmed COVID-19 who has elevated liver function tests should be evaluated for alternative etiologies. Second, hospitalized patients with suspected or confirmed COVID-19 should undergo baseline liver function testing, followed by liver monitoring throughout their stay, “particularly in the context of drug treatment for COVID-19.” And third, any patient receiving drugs to treat COVID-19 should be monitored for treatment-related hepatic and GI adverse effects.

Dr. Sultan and colleagues found that approximately 15% of patients with COVID-19 included in their meta-analysis had abnormal liver function tests, more often because of secondary effects rather than virally induced liver injury.

Although liver function test abnormalities were inconsistently reported across studies, and when available, often lacked relevant contextual data, such as information about underlying liver disease, published data suggest that abnormal liver values could predict more severe COVID-19, supporting baseline and serial liver testing, the panelists wrote.

Following these recommendations, the guideline includes a discussion of GI and hepatic adverse effects related to specific COVID-19 treatments.

According to the panelists, chloroquine and hydroxychloroquine may infrequently lead to GI disturbances, and rarely, liver injury, with the latter thought to be a sequela of a hypersensitivity reaction; among antiviral medications, lopinavir/ritonavir and favipiravir may cause GI adverse effects in approximately 5%-15% of patients, with potentially higher rates in children and those receiving higher doses.

“In particular, GI adverse events are poorly understood for both favipiravir and remdesivir,” the panelists wrote.

Hepatic adverse effects, ranging from mild elevations in aminotransferases to acute liver failure, have been documented, albeit rarely, among patients receiving lopinavir/ritonavir, according to the panelists. For remdesivir, liver injury has also been reported, although frequency is unknown, and for favipiravir, hepatic adverse events may be seen in 3% of patients, although, again, the panelists noted a scarcity of relevant findings.

In their concluding remarks, Dr. Sultan and colleagues called for more high-quality data, and encouraged clinicians to contribute to international registries, as these could help guide COVID-19 recommendations for patient subgroups.

The article was funded by the American Gastroenterological Association Institute.

SOURCE: Sultan S et al. Gastroenterology. 2020 May 11. doi: 10.1053/j.gastro.2020.05.001.

The American Gastroenterological Association has released a new guideline for consultative management of patients with COVID-19.

The recommendations, which were written by Shahnaz Sultan, MD, AGAF, chair of the AGA Clinical Guidelines Committee, of the University of Minnesota, Minneapolis, and colleagues, were based on a meta-analysis of data from 47 studies involving 10,890 unique patients.

“We seek to summarize international data on the GI and liver manifestations of COVID-19 infection and treatment,” the panelists wrote in Gastroenterology. “Additionally, this document provides evidence-based clinical guidance on clinical questions that gastroenterologists may be consulted for.”

The guideline includes seven best practice statements.

The first three statements relate to COVID-19–related GI symptoms, which are estimated to occur in less than 10% of patients, and rarely in the absence of other COVID-19–related symptoms, according to Dr. Sultan and her copanelists.

“The overall prevalence of GI symptoms in the context of COVID-19, including nausea, vomiting, abdominal pain, and diarrhea, is lower than estimated previously,” the panelists wrote, referencing a previous meta-analysis by Ka Shing Cheung, MBBS, and colleagues that showed a prevalence of 17.6%.

“It is important to note that the majority of studies were focused on hospitalized patients with COVID-19, and the prevalence of diarrhea in patients with mild symptoms who were not hospitalized is not known.”

Since GI issues may precede other symptoms of COVID-19, the guideline recommends questioning outpatients with new-onset GI symptoms about other symptoms of COVID-19, with viral testing recommended in areas of high prevalence. Conversely, the panelists recommended that patients with suspected or known COVID-19 should undergo thorough history taking for GI symptoms, “including onset, characteristics, duration, and severity.”

The fourth practice statement advises against COVID-19 stool testing in routine clinical practice, either for diagnostic or monitoring purposes.

Although Dr. Cheung and colleagues reported that 48.1% of fecal specimens from patients with COVID-19 contained viral RNA, the panelists concluded that the practical relevance of this finding remains unknown.

“Stool infectivity and transmission have not been confirmed,” the panelists wrote, citing a lack of evidence and conflicting findings.

The final three practice statements address liver concerns.

First, any patient with suspected or confirmed COVID-19 who has elevated liver function tests should be evaluated for alternative etiologies. Second, hospitalized patients with suspected or confirmed COVID-19 should undergo baseline liver function testing, followed by liver monitoring throughout their stay, “particularly in the context of drug treatment for COVID-19.” And third, any patient receiving drugs to treat COVID-19 should be monitored for treatment-related hepatic and GI adverse effects.

Dr. Sultan and colleagues found that approximately 15% of patients with COVID-19 included in their meta-analysis had abnormal liver function tests, more often because of secondary effects rather than virally induced liver injury.

Although liver function test abnormalities were inconsistently reported across studies, and when available, often lacked relevant contextual data, such as information about underlying liver disease, published data suggest that abnormal liver values could predict more severe COVID-19, supporting baseline and serial liver testing, the panelists wrote.

Following these recommendations, the guideline includes a discussion of GI and hepatic adverse effects related to specific COVID-19 treatments.

According to the panelists, chloroquine and hydroxychloroquine may infrequently lead to GI disturbances, and rarely, liver injury, with the latter thought to be a sequela of a hypersensitivity reaction; among antiviral medications, lopinavir/ritonavir and favipiravir may cause GI adverse effects in approximately 5%-15% of patients, with potentially higher rates in children and those receiving higher doses.

“In particular, GI adverse events are poorly understood for both favipiravir and remdesivir,” the panelists wrote.

Hepatic adverse effects, ranging from mild elevations in aminotransferases to acute liver failure, have been documented, albeit rarely, among patients receiving lopinavir/ritonavir, according to the panelists. For remdesivir, liver injury has also been reported, although frequency is unknown, and for favipiravir, hepatic adverse events may be seen in 3% of patients, although, again, the panelists noted a scarcity of relevant findings.

In their concluding remarks, Dr. Sultan and colleagues called for more high-quality data, and encouraged clinicians to contribute to international registries, as these could help guide COVID-19 recommendations for patient subgroups.

The article was funded by the American Gastroenterological Association Institute.

SOURCE: Sultan S et al. Gastroenterology. 2020 May 11. doi: 10.1053/j.gastro.2020.05.001.

The American Gastroenterological Association has released a new guideline for consultative management of patients with COVID-19.

The recommendations, which were written by Shahnaz Sultan, MD, AGAF, chair of the AGA Clinical Guidelines Committee, of the University of Minnesota, Minneapolis, and colleagues, were based on a meta-analysis of data from 47 studies involving 10,890 unique patients.

“We seek to summarize international data on the GI and liver manifestations of COVID-19 infection and treatment,” the panelists wrote in Gastroenterology. “Additionally, this document provides evidence-based clinical guidance on clinical questions that gastroenterologists may be consulted for.”

The guideline includes seven best practice statements.

The first three statements relate to COVID-19–related GI symptoms, which are estimated to occur in less than 10% of patients, and rarely in the absence of other COVID-19–related symptoms, according to Dr. Sultan and her copanelists.

“The overall prevalence of GI symptoms in the context of COVID-19, including nausea, vomiting, abdominal pain, and diarrhea, is lower than estimated previously,” the panelists wrote, referencing a previous meta-analysis by Ka Shing Cheung, MBBS, and colleagues that showed a prevalence of 17.6%.

“It is important to note that the majority of studies were focused on hospitalized patients with COVID-19, and the prevalence of diarrhea in patients with mild symptoms who were not hospitalized is not known.”

Since GI issues may precede other symptoms of COVID-19, the guideline recommends questioning outpatients with new-onset GI symptoms about other symptoms of COVID-19, with viral testing recommended in areas of high prevalence. Conversely, the panelists recommended that patients with suspected or known COVID-19 should undergo thorough history taking for GI symptoms, “including onset, characteristics, duration, and severity.”

The fourth practice statement advises against COVID-19 stool testing in routine clinical practice, either for diagnostic or monitoring purposes.

Although Dr. Cheung and colleagues reported that 48.1% of fecal specimens from patients with COVID-19 contained viral RNA, the panelists concluded that the practical relevance of this finding remains unknown.

“Stool infectivity and transmission have not been confirmed,” the panelists wrote, citing a lack of evidence and conflicting findings.

The final three practice statements address liver concerns.

First, any patient with suspected or confirmed COVID-19 who has elevated liver function tests should be evaluated for alternative etiologies. Second, hospitalized patients with suspected or confirmed COVID-19 should undergo baseline liver function testing, followed by liver monitoring throughout their stay, “particularly in the context of drug treatment for COVID-19.” And third, any patient receiving drugs to treat COVID-19 should be monitored for treatment-related hepatic and GI adverse effects.

Dr. Sultan and colleagues found that approximately 15% of patients with COVID-19 included in their meta-analysis had abnormal liver function tests, more often because of secondary effects rather than virally induced liver injury.

Although liver function test abnormalities were inconsistently reported across studies, and when available, often lacked relevant contextual data, such as information about underlying liver disease, published data suggest that abnormal liver values could predict more severe COVID-19, supporting baseline and serial liver testing, the panelists wrote.

Following these recommendations, the guideline includes a discussion of GI and hepatic adverse effects related to specific COVID-19 treatments.

According to the panelists, chloroquine and hydroxychloroquine may infrequently lead to GI disturbances, and rarely, liver injury, with the latter thought to be a sequela of a hypersensitivity reaction; among antiviral medications, lopinavir/ritonavir and favipiravir may cause GI adverse effects in approximately 5%-15% of patients, with potentially higher rates in children and those receiving higher doses.

“In particular, GI adverse events are poorly understood for both favipiravir and remdesivir,” the panelists wrote.

Hepatic adverse effects, ranging from mild elevations in aminotransferases to acute liver failure, have been documented, albeit rarely, among patients receiving lopinavir/ritonavir, according to the panelists. For remdesivir, liver injury has also been reported, although frequency is unknown, and for favipiravir, hepatic adverse events may be seen in 3% of patients, although, again, the panelists noted a scarcity of relevant findings.

In their concluding remarks, Dr. Sultan and colleagues called for more high-quality data, and encouraged clinicians to contribute to international registries, as these could help guide COVID-19 recommendations for patient subgroups.

The article was funded by the American Gastroenterological Association Institute.

SOURCE: Sultan S et al. Gastroenterology. 2020 May 11. doi: 10.1053/j.gastro.2020.05.001.

Patients with COVID-19 develop a distinct subset of pancreatitis hallmarked by duodenal and periduodenal inflammation, according to a recent case series.

Although all five patients presented with multiple predictive markers of severe pancreatitis, the subsequent clinical pathway “was much more benign than anticipated,” reported lead author Peter Szatmary, MB, BChir, PhD, of the University of Liverpool (England) and colleagues. Still, they noted prolonged hospital stays because of persistent inflammation and poor diabetic control.

“As the global pandemic of SARS-CoV-2 continues, nuances of the disease it precipitates in humans continue to emerge,” the investigators wrote in Gastroenterology. “[A] group from Wuhan reported a series of 9 patients with purported pancreatic injury in the context of SARS-CoV-2 infection, but did not provide robust evidence for pancreatitis relying on mild hyperamylasemia alone.”

For the present series, Dr. Szatmary and colleagues restricted diagnosis of pancreatitis to international consensus guidelines, which require “abdominal pain consistent with pancreatitis, serum amylase/lipase greater than three times the upper limit of normal, and characteristic findings on cross-sectional imaging.”

From middle of March to late April, the investigators identified 35 patients with acute pancreatitis at Royal Liverpool (England) University Hospital, 25 of whom tested negative for SARS-CoV-2, which resulted in study exclusion. An additional five patients were excluded from the series as another etiology for pancreatitis was clearly present, such as gallstones.

“The remaining 5 patients, all with SARS-CoV-2, presented atypically yet homogenously with a distinct metabolic-pancreatitis phenotype,” the investigators wrote.

All five patients were obese or overweight young men with a median body mass index of 30 kg/m² and age of 42 years. On presentation, all patients had elevated, but nondiagnostic, levels of amylase (median, 149 U/L). Contrast-enhanced abdominal CT revealed moderate to severe hepatic steatosis (less than 104 HU), which rapidly regressed within a week among patients who underwent repeat imaging.

“The pattern of pancreatic inflammation was similarly unusual in these patients,” the investigators wrote, going on to describe “mild pancreatic edema without significant pancreatic or peripancreatic necrosis, with distinct duodenal/periduodenal inflammation involving the second and third part of the duodenum.”

According to Dr. Szatmary and colleagues, these findings were “accompanied by a profound systemic inflammatory response,” including 1-2 criteria for systemic inflammatory response syndrome that increased to 2-4 criteria within 48 hours. During hospitalization, patients also exhibited a “dramatic elevation” of C-reactive protein, from a median of 31 mg/L upon admission to 485 mg/L within 48 hours.

Although these markers predicted severe disease, all cases followed a clinical course similar to “a typical attack of moderate pancreatitis,” the investigators wrote.

All patients were treated with IV fluids, four out of five received broad-spectrum IV antibiotics for pneumonitis, three out of five received fibrate and/or insulin therapy, and two out of five received pancreatic enzyme replacement therapy. No patients required corticosteroids, organ support, or respiratory support beyond low-flow oxygen. Median hospital stay was 14 days.

“We ... propose the combination of male sex, abdominal pain, metabolic stress, and CT-findings of predominantly pancreatico-duodenal inflammation with steatosis represent a distinct subset of pancreatitis in patients infected with SARS-CoV-2,” the investigators wrote.

They suggested that the endocrine pancreas may be “particularly vulnerable to this infection,” citing prolonged hospital stays because of poor diabetic control.

“[T]ransient dyslipidemias and impaired glucose tolerance may be common in SARS-CoV-2 patients and warrant further investigation,” they concluded.

Oscar J. Hines, MD, chief of the division of general surgery at UCLA Medical Center and leader in the field of pancreatitis management, said that the case series has a limited impact.

“The findings are unlikely to change practice and only call attention for physicians to the possibility of pancreatitis in COVID-positive patients,” Dr. Hines said.

The investigators reported grants from NIHR, Wellcome Trust, Mylan, and others.

SOURCE: Szatmary P et al. Gastroenterology. 2020 Jun 1. doi: 10.1053/j.gastro.2020.05.069.

Patients with COVID-19 develop a distinct subset of pancreatitis hallmarked by duodenal and periduodenal inflammation, according to a recent case series.

Although all five patients presented with multiple predictive markers of severe pancreatitis, the subsequent clinical pathway “was much more benign than anticipated,” reported lead author Peter Szatmary, MB, BChir, PhD, of the University of Liverpool (England) and colleagues. Still, they noted prolonged hospital stays because of persistent inflammation and poor diabetic control.

“As the global pandemic of SARS-CoV-2 continues, nuances of the disease it precipitates in humans continue to emerge,” the investigators wrote in Gastroenterology. “[A] group from Wuhan reported a series of 9 patients with purported pancreatic injury in the context of SARS-CoV-2 infection, but did not provide robust evidence for pancreatitis relying on mild hyperamylasemia alone.”

For the present series, Dr. Szatmary and colleagues restricted diagnosis of pancreatitis to international consensus guidelines, which require “abdominal pain consistent with pancreatitis, serum amylase/lipase greater than three times the upper limit of normal, and characteristic findings on cross-sectional imaging.”

From middle of March to late April, the investigators identified 35 patients with acute pancreatitis at Royal Liverpool (England) University Hospital, 25 of whom tested negative for SARS-CoV-2, which resulted in study exclusion. An additional five patients were excluded from the series as another etiology for pancreatitis was clearly present, such as gallstones.

“The remaining 5 patients, all with SARS-CoV-2, presented atypically yet homogenously with a distinct metabolic-pancreatitis phenotype,” the investigators wrote.

All five patients were obese or overweight young men with a median body mass index of 30 kg/m² and age of 42 years. On presentation, all patients had elevated, but nondiagnostic, levels of amylase (median, 149 U/L). Contrast-enhanced abdominal CT revealed moderate to severe hepatic steatosis (less than 104 HU), which rapidly regressed within a week among patients who underwent repeat imaging.

“The pattern of pancreatic inflammation was similarly unusual in these patients,” the investigators wrote, going on to describe “mild pancreatic edema without significant pancreatic or peripancreatic necrosis, with distinct duodenal/periduodenal inflammation involving the second and third part of the duodenum.”

According to Dr. Szatmary and colleagues, these findings were “accompanied by a profound systemic inflammatory response,” including 1-2 criteria for systemic inflammatory response syndrome that increased to 2-4 criteria within 48 hours. During hospitalization, patients also exhibited a “dramatic elevation” of C-reactive protein, from a median of 31 mg/L upon admission to 485 mg/L within 48 hours.

Although these markers predicted severe disease, all cases followed a clinical course similar to “a typical attack of moderate pancreatitis,” the investigators wrote.

All patients were treated with IV fluids, four out of five received broad-spectrum IV antibiotics for pneumonitis, three out of five received fibrate and/or insulin therapy, and two out of five received pancreatic enzyme replacement therapy. No patients required corticosteroids, organ support, or respiratory support beyond low-flow oxygen. Median hospital stay was 14 days.

“We ... propose the combination of male sex, abdominal pain, metabolic stress, and CT-findings of predominantly pancreatico-duodenal inflammation with steatosis represent a distinct subset of pancreatitis in patients infected with SARS-CoV-2,” the investigators wrote.

They suggested that the endocrine pancreas may be “particularly vulnerable to this infection,” citing prolonged hospital stays because of poor diabetic control.

“[T]ransient dyslipidemias and impaired glucose tolerance may be common in SARS-CoV-2 patients and warrant further investigation,” they concluded.

Oscar J. Hines, MD, chief of the division of general surgery at UCLA Medical Center and leader in the field of pancreatitis management, said that the case series has a limited impact.

“The findings are unlikely to change practice and only call attention for physicians to the possibility of pancreatitis in COVID-positive patients,” Dr. Hines said.

The investigators reported grants from NIHR, Wellcome Trust, Mylan, and others.

SOURCE: Szatmary P et al. Gastroenterology. 2020 Jun 1. doi: 10.1053/j.gastro.2020.05.069.

Patients with COVID-19 develop a distinct subset of pancreatitis hallmarked by duodenal and periduodenal inflammation, according to a recent case series.

Although all five patients presented with multiple predictive markers of severe pancreatitis, the subsequent clinical pathway “was much more benign than anticipated,” reported lead author Peter Szatmary, MB, BChir, PhD, of the University of Liverpool (England) and colleagues. Still, they noted prolonged hospital stays because of persistent inflammation and poor diabetic control.

“As the global pandemic of SARS-CoV-2 continues, nuances of the disease it precipitates in humans continue to emerge,” the investigators wrote in Gastroenterology. “[A] group from Wuhan reported a series of 9 patients with purported pancreatic injury in the context of SARS-CoV-2 infection, but did not provide robust evidence for pancreatitis relying on mild hyperamylasemia alone.”

For the present series, Dr. Szatmary and colleagues restricted diagnosis of pancreatitis to international consensus guidelines, which require “abdominal pain consistent with pancreatitis, serum amylase/lipase greater than three times the upper limit of normal, and characteristic findings on cross-sectional imaging.”

From middle of March to late April, the investigators identified 35 patients with acute pancreatitis at Royal Liverpool (England) University Hospital, 25 of whom tested negative for SARS-CoV-2, which resulted in study exclusion. An additional five patients were excluded from the series as another etiology for pancreatitis was clearly present, such as gallstones.

“The remaining 5 patients, all with SARS-CoV-2, presented atypically yet homogenously with a distinct metabolic-pancreatitis phenotype,” the investigators wrote.

All five patients were obese or overweight young men with a median body mass index of 30 kg/m² and age of 42 years. On presentation, all patients had elevated, but nondiagnostic, levels of amylase (median, 149 U/L). Contrast-enhanced abdominal CT revealed moderate to severe hepatic steatosis (less than 104 HU), which rapidly regressed within a week among patients who underwent repeat imaging.

“The pattern of pancreatic inflammation was similarly unusual in these patients,” the investigators wrote, going on to describe “mild pancreatic edema without significant pancreatic or peripancreatic necrosis, with distinct duodenal/periduodenal inflammation involving the second and third part of the duodenum.”

According to Dr. Szatmary and colleagues, these findings were “accompanied by a profound systemic inflammatory response,” including 1-2 criteria for systemic inflammatory response syndrome that increased to 2-4 criteria within 48 hours. During hospitalization, patients also exhibited a “dramatic elevation” of C-reactive protein, from a median of 31 mg/L upon admission to 485 mg/L within 48 hours.

Although these markers predicted severe disease, all cases followed a clinical course similar to “a typical attack of moderate pancreatitis,” the investigators wrote.

All patients were treated with IV fluids, four out of five received broad-spectrum IV antibiotics for pneumonitis, three out of five received fibrate and/or insulin therapy, and two out of five received pancreatic enzyme replacement therapy. No patients required corticosteroids, organ support, or respiratory support beyond low-flow oxygen. Median hospital stay was 14 days.

“We ... propose the combination of male sex, abdominal pain, metabolic stress, and CT-findings of predominantly pancreatico-duodenal inflammation with steatosis represent a distinct subset of pancreatitis in patients infected with SARS-CoV-2,” the investigators wrote.

They suggested that the endocrine pancreas may be “particularly vulnerable to this infection,” citing prolonged hospital stays because of poor diabetic control.

“[T]ransient dyslipidemias and impaired glucose tolerance may be common in SARS-CoV-2 patients and warrant further investigation,” they concluded.

Oscar J. Hines, MD, chief of the division of general surgery at UCLA Medical Center and leader in the field of pancreatitis management, said that the case series has a limited impact.

“The findings are unlikely to change practice and only call attention for physicians to the possibility of pancreatitis in COVID-positive patients,” Dr. Hines said.

The investigators reported grants from NIHR, Wellcome Trust, Mylan, and others.

SOURCE: Szatmary P et al. Gastroenterology. 2020 Jun 1. doi: 10.1053/j.gastro.2020.05.069.

Exposure to Shiga toxin induces a complex intestinal response involving transcriptional changes, necrosis, apoptotic cell death, cellular proliferation, and cross-talk between epithelial and mesenchymal cells, according to investigators.

The study explored new territory in Shiga toxin research, enabled by the use of human intestinal organoids (HIOs), reported lead author Suman Pradhan, PhD, of the University of Cincinnati, and colleagues.

Each year, Shiga toxin–producing Escherichia coli infections cause approximately 3 million cases of bloody diarrheal disease, with about 4,000 of those patients developing the life-threatening complication of hemolytic uremic syndrome (HUS), the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

But little is known about the underlying biological processes driving Shiga-induced disease.

“Developing effective interventions for disease resulting from Shiga toxin is exacerbated by a lack of tractable model systems,” the investigators wrote. “Mice do not develop the symptoms characteristic of HUS, and the murine intestinal tract is resistant to Shiga toxin.”

To overcome this obstacle, Dr. Pradhan and colleagues turned to HIOs, which are grown in culture by directing differentiation of pluripotent stem cells. HIOs represent the small bowel, complete with a lumen surrounded by epithelial and mesenchymal layers that include typical cell types, such as goblet cells and myofibroblasts. The model is made more realistic by transplantation into mice, where it grows under the kidney capsule to form crypts, structured villi, and proliferating progenitor zones. And HIOs grown with neuronal precursors develop an enteric nervous system, complete with functional peristalsis.

For the present study, the investigators evaluated the effect of Shiga toxin on HIOs both in culture and after transplantation into mice.

First, they demonstrated that HIOs in culture expressed glycolipid Gb3, the Shiga toxin receptor. “Reports regarding expression of glycolipid Gb3 ... on human intestine have been inconsistent,” the investigators noted. “For negative reports, the inability to detect Gb3 could be owing to technical limitations.”

Next, Dr. Pradhan and colleagues showed that HIOs were susceptible to Shiga toxin whether it be delivered lumenally or basolaterally, which respectively represent intestinal exposure and exposure via circulating toxin or after breakdown of the epithelial barrier. Leakage from the lumen was observed with both Shiga toxin 1 (Stx1) and 2 (Stx2). Subsequent testing involved only Stx2, as this form is more relevant to human disease.

In addition to lumenal leakage, Stx2 exposure caused significant transcriptional up-regulation of multiple gene families, including those involved in cellular transport and metabolic processes. Increased expression also was observed for epithelial structural proteins, lineage-specific proteins, factors involved in mucus layer formation and stabilization, and cytokines interleukin-18 and CCL15.

In both epithelial and mesenchymal layers, transcriptional changes were accompanied by cellular necrosis and apoptosis, and, to a greater degree with interstitial exposure, cellular proliferation.

With lumenal exposure, mesenchymal necrosis was observed before loss of epithelial barrier function, indicating toxin access to mesenchymal cells. This phenomenon was explained by transcytosis, which the investigators observed in two-dimensional monolayers of enteroids grown in Transwells.

“[Shiga toxin] was transferred from the apical to the basolateral surface in the absence of loss of epithelial barrier function,” the investigators wrote, noting that this finding explains how Shiga toxin can quickly access the circulatory system, and from there damage the kidneys and brain, as seen in cases of HUS.

Mice with transplanted HIOs, and those receiving HIOs with an enteric nervous system (HIO + ENS), lost weight when organoids were injected with 10 ng of Stx2. Mice with HIO + ENS transplants developed more severe responses, prompting closer analysis.

Postmortem histologic examination of HIO + ENS transplants revealed epithelial damage and blood accumulation in the mesenchyme and villi. Additional staining showed signs of apoptosis and mesenchymal-epithelial transition.

Dr. Pradham and colleagues suggested that their findings could inform therapeutic research.

“If preventing cellular death is to be an effective intervention, it is likely that both necrosis and apoptosis need to be targeted,” the investigators wrote.

More generally, the study supports the use of HIOs as a disease model for future investigations.

“The advent of stem cell–derived human tissue models, both in vitro and in vivo, has a tremendous potential to increase our understanding of Shiga toxin disease and lead to development of therapeutic interventions,” the investigators concluded.

The study was funded by the National Institutes of Health, the Center for Clinical and Translational Science, the National Institute of Diabetes and Digestive and Kidney Diseases, and others. The investigators disclosed no conflicts of interest.

SOURCE: Pradhan S et al. Cell Mol Gastroenterol Hepatol. 2020 Mar 5. doi: 10.1016/j.jcmgh.2020.02.006.

Exposure to Shiga toxin induces a complex intestinal response involving transcriptional changes, necrosis, apoptotic cell death, cellular proliferation, and cross-talk between epithelial and mesenchymal cells, according to investigators.

The study explored new territory in Shiga toxin research, enabled by the use of human intestinal organoids (HIOs), reported lead author Suman Pradhan, PhD, of the University of Cincinnati, and colleagues.

Each year, Shiga toxin–producing Escherichia coli infections cause approximately 3 million cases of bloody diarrheal disease, with about 4,000 of those patients developing the life-threatening complication of hemolytic uremic syndrome (HUS), the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

But little is known about the underlying biological processes driving Shiga-induced disease.

“Developing effective interventions for disease resulting from Shiga toxin is exacerbated by a lack of tractable model systems,” the investigators wrote. “Mice do not develop the symptoms characteristic of HUS, and the murine intestinal tract is resistant to Shiga toxin.”

To overcome this obstacle, Dr. Pradhan and colleagues turned to HIOs, which are grown in culture by directing differentiation of pluripotent stem cells. HIOs represent the small bowel, complete with a lumen surrounded by epithelial and mesenchymal layers that include typical cell types, such as goblet cells and myofibroblasts. The model is made more realistic by transplantation into mice, where it grows under the kidney capsule to form crypts, structured villi, and proliferating progenitor zones. And HIOs grown with neuronal precursors develop an enteric nervous system, complete with functional peristalsis.

For the present study, the investigators evaluated the effect of Shiga toxin on HIOs both in culture and after transplantation into mice.

First, they demonstrated that HIOs in culture expressed glycolipid Gb3, the Shiga toxin receptor. “Reports regarding expression of glycolipid Gb3 ... on human intestine have been inconsistent,” the investigators noted. “For negative reports, the inability to detect Gb3 could be owing to technical limitations.”

Next, Dr. Pradhan and colleagues showed that HIOs were susceptible to Shiga toxin whether it be delivered lumenally or basolaterally, which respectively represent intestinal exposure and exposure via circulating toxin or after breakdown of the epithelial barrier. Leakage from the lumen was observed with both Shiga toxin 1 (Stx1) and 2 (Stx2). Subsequent testing involved only Stx2, as this form is more relevant to human disease.

In addition to lumenal leakage, Stx2 exposure caused significant transcriptional up-regulation of multiple gene families, including those involved in cellular transport and metabolic processes. Increased expression also was observed for epithelial structural proteins, lineage-specific proteins, factors involved in mucus layer formation and stabilization, and cytokines interleukin-18 and CCL15.

In both epithelial and mesenchymal layers, transcriptional changes were accompanied by cellular necrosis and apoptosis, and, to a greater degree with interstitial exposure, cellular proliferation.

With lumenal exposure, mesenchymal necrosis was observed before loss of epithelial barrier function, indicating toxin access to mesenchymal cells. This phenomenon was explained by transcytosis, which the investigators observed in two-dimensional monolayers of enteroids grown in Transwells.

“[Shiga toxin] was transferred from the apical to the basolateral surface in the absence of loss of epithelial barrier function,” the investigators wrote, noting that this finding explains how Shiga toxin can quickly access the circulatory system, and from there damage the kidneys and brain, as seen in cases of HUS.

Mice with transplanted HIOs, and those receiving HIOs with an enteric nervous system (HIO + ENS), lost weight when organoids were injected with 10 ng of Stx2. Mice with HIO + ENS transplants developed more severe responses, prompting closer analysis.

Postmortem histologic examination of HIO + ENS transplants revealed epithelial damage and blood accumulation in the mesenchyme and villi. Additional staining showed signs of apoptosis and mesenchymal-epithelial transition.

Dr. Pradham and colleagues suggested that their findings could inform therapeutic research.

“If preventing cellular death is to be an effective intervention, it is likely that both necrosis and apoptosis need to be targeted,” the investigators wrote.

More generally, the study supports the use of HIOs as a disease model for future investigations.

“The advent of stem cell–derived human tissue models, both in vitro and in vivo, has a tremendous potential to increase our understanding of Shiga toxin disease and lead to development of therapeutic interventions,” the investigators concluded.

The study was funded by the National Institutes of Health, the Center for Clinical and Translational Science, the National Institute of Diabetes and Digestive and Kidney Diseases, and others. The investigators disclosed no conflicts of interest.

SOURCE: Pradhan S et al. Cell Mol Gastroenterol Hepatol. 2020 Mar 5. doi: 10.1016/j.jcmgh.2020.02.006.

Exposure to Shiga toxin induces a complex intestinal response involving transcriptional changes, necrosis, apoptotic cell death, cellular proliferation, and cross-talk between epithelial and mesenchymal cells, according to investigators.

The study explored new territory in Shiga toxin research, enabled by the use of human intestinal organoids (HIOs), reported lead author Suman Pradhan, PhD, of the University of Cincinnati, and colleagues.

Each year, Shiga toxin–producing Escherichia coli infections cause approximately 3 million cases of bloody diarrheal disease, with about 4,000 of those patients developing the life-threatening complication of hemolytic uremic syndrome (HUS), the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

But little is known about the underlying biological processes driving Shiga-induced disease.

“Developing effective interventions for disease resulting from Shiga toxin is exacerbated by a lack of tractable model systems,” the investigators wrote. “Mice do not develop the symptoms characteristic of HUS, and the murine intestinal tract is resistant to Shiga toxin.”

To overcome this obstacle, Dr. Pradhan and colleagues turned to HIOs, which are grown in culture by directing differentiation of pluripotent stem cells. HIOs represent the small bowel, complete with a lumen surrounded by epithelial and mesenchymal layers that include typical cell types, such as goblet cells and myofibroblasts. The model is made more realistic by transplantation into mice, where it grows under the kidney capsule to form crypts, structured villi, and proliferating progenitor zones. And HIOs grown with neuronal precursors develop an enteric nervous system, complete with functional peristalsis.

For the present study, the investigators evaluated the effect of Shiga toxin on HIOs both in culture and after transplantation into mice.

First, they demonstrated that HIOs in culture expressed glycolipid Gb3, the Shiga toxin receptor. “Reports regarding expression of glycolipid Gb3 ... on human intestine have been inconsistent,” the investigators noted. “For negative reports, the inability to detect Gb3 could be owing to technical limitations.”

Next, Dr. Pradhan and colleagues showed that HIOs were susceptible to Shiga toxin whether it be delivered lumenally or basolaterally, which respectively represent intestinal exposure and exposure via circulating toxin or after breakdown of the epithelial barrier. Leakage from the lumen was observed with both Shiga toxin 1 (Stx1) and 2 (Stx2). Subsequent testing involved only Stx2, as this form is more relevant to human disease.

In addition to lumenal leakage, Stx2 exposure caused significant transcriptional up-regulation of multiple gene families, including those involved in cellular transport and metabolic processes. Increased expression also was observed for epithelial structural proteins, lineage-specific proteins, factors involved in mucus layer formation and stabilization, and cytokines interleukin-18 and CCL15.

In both epithelial and mesenchymal layers, transcriptional changes were accompanied by cellular necrosis and apoptosis, and, to a greater degree with interstitial exposure, cellular proliferation.

With lumenal exposure, mesenchymal necrosis was observed before loss of epithelial barrier function, indicating toxin access to mesenchymal cells. This phenomenon was explained by transcytosis, which the investigators observed in two-dimensional monolayers of enteroids grown in Transwells.

“[Shiga toxin] was transferred from the apical to the basolateral surface in the absence of loss of epithelial barrier function,” the investigators wrote, noting that this finding explains how Shiga toxin can quickly access the circulatory system, and from there damage the kidneys and brain, as seen in cases of HUS.

Mice with transplanted HIOs, and those receiving HIOs with an enteric nervous system (HIO + ENS), lost weight when organoids were injected with 10 ng of Stx2. Mice with HIO + ENS transplants developed more severe responses, prompting closer analysis.

Postmortem histologic examination of HIO + ENS transplants revealed epithelial damage and blood accumulation in the mesenchyme and villi. Additional staining showed signs of apoptosis and mesenchymal-epithelial transition.

Dr. Pradham and colleagues suggested that their findings could inform therapeutic research.

“If preventing cellular death is to be an effective intervention, it is likely that both necrosis and apoptosis need to be targeted,” the investigators wrote.

More generally, the study supports the use of HIOs as a disease model for future investigations.

“The advent of stem cell–derived human tissue models, both in vitro and in vivo, has a tremendous potential to increase our understanding of Shiga toxin disease and lead to development of therapeutic interventions,” the investigators concluded.

The study was funded by the National Institutes of Health, the Center for Clinical and Translational Science, the National Institute of Diabetes and Digestive and Kidney Diseases, and others. The investigators disclosed no conflicts of interest.

SOURCE: Pradhan S et al. Cell Mol Gastroenterol Hepatol. 2020 Mar 5. doi: 10.1016/j.jcmgh.2020.02.006.

Even without GI symptoms, many patients with COVID-19 shed viral RNA in feces, suggesting that stool testing and prevention of fecal-oral transmission may be needed to combat the ongoing pandemic, according to investigators.

A meta-analysis of 29 studies showed that 12% of patients with COVID-19 developed nausea, diarrhea, or vomiting, while 41% shed viral RNA in feces, reported lead author Sravanthi Parasa, MD, of Swedish Medical Center, Seattle.Writing in JAMA Network Open, Dr. Parasa and colleagues emphasized that respiratory symptoms remain the predominant form of disease; however, GI symptoms can occur.

“In fact, the first reported patient with COVID-19 in the U.S. reported GI symptoms of loose bowel movements and abdominal discomfort,” the investigators wrote, noting that the patient went on to test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in both respiratory and stool specimens.

“This raises the question of inadvertent human-to-human transmission via the fecal route despite public health emphasis on droplet transmission and precautions for contact with respiratory secretions,” the investigators wrote.

To address this question, the investigators conducted a systematic review and meta-analysis involving 23 published and 6 preprint studies involving a total of 4,805 patients, all of whom tested positive for SARS-CoV-2 based on PCR results from nasopharyngeal swabs. Dr. Parasa and colleagues noted that most of the studies “scored between 8 and 10 on the MINORS quality assessment,” suggesting moderate quality.

Pooled data from these studies showed that 4.6% of patients reported nausea or vomiting, while 7.4% reported diarrhea. Such symptoms may serve as an early warning flag for clinicians, the investigators noted.

“[T]he presence of GI symptoms may portend a worse outcome for patients infected with SARS-CoV-2,” they wrote, citing a study by Pan and colleagues, which found that GI symptoms were associated with lower rates of recovery and hospital discharge.

Regardless of GI symptoms, 40.5% of patients in the meta-analysis tested positive for viral RNA in feces (95% confidence interval, 27.4%-55.1%). Duration of viral shedding in feces lasted up to 11 days after symptom onset, or in a single-patient case study, 18 days after hospitalization.

The investigators called these duration figures “particularly concerning,” especially in light of a study published by Xiao and colleagues, which showed that 23.3% of patients with negative respiratory tests were still shedding live virus in feces.

“[T]he fecal-oral route of transmission could be an additional potential source of infection spread,” wrote Dr. Parasa and colleagues. “Our results also suggest that testing of the virus in feces ... could be helpful in disease monitoring and surveillance.”

David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, said that the findings confirm what has been suspected for some time: GI disease is relatively common with COVID-19.

“The evidence is clear now that a sizable percentage of patients have GI symptoms,” Dr. Johnson said in an interview.

GI issues may precede respiratory signs, he added, so clinicians should be aware that nausea, vomiting, or diarrhea could be early indicators of COVID-19, and possibly, a worse outcome.

“The other highlight of this study is that stool shedding may be extended beyond respiratory shedding,” Dr. Johnson said.

He suggested that this finding could influence current CDC criteria, which define absence of infectious risk by two consecutive, negative nasopharyngeal swabs. Instead, fecal testing may be needed, he said, along with measures to prevent fecal-oral transmission.

Dr. Johnson expressed particular concern for risk of infection via toilet plume, in which toilet flushing aerosolizes viral particles.

“As much as people try to social distance by 6 feet – you can do that when you walk into a store, or a building, but you can’t necessarily do that when you walk into a public toilet, where the plume may have been expansive for a period of time,” he said. “That toilet may never really get cleaned to a high level of disinfection, and those droplets set up potential for fecal-oral spread.”

Dr. Sharma disclosed relationships with Medtronic, Fujifilm, Boston Scientific, and others. Dr. Johnson disclosed no relevant conflicts of interest.

SOURCE: Parasa S et al. JAMA Network Open. 2020 Jun 11. doi: 10.1001/jamanetworkopen.2020.11335.

Even without GI symptoms, many patients with COVID-19 shed viral RNA in feces, suggesting that stool testing and prevention of fecal-oral transmission may be needed to combat the ongoing pandemic, according to investigators.

A meta-analysis of 29 studies showed that 12% of patients with COVID-19 developed nausea, diarrhea, or vomiting, while 41% shed viral RNA in feces, reported lead author Sravanthi Parasa, MD, of Swedish Medical Center, Seattle.Writing in JAMA Network Open, Dr. Parasa and colleagues emphasized that respiratory symptoms remain the predominant form of disease; however, GI symptoms can occur.

“In fact, the first reported patient with COVID-19 in the U.S. reported GI symptoms of loose bowel movements and abdominal discomfort,” the investigators wrote, noting that the patient went on to test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in both respiratory and stool specimens.

“This raises the question of inadvertent human-to-human transmission via the fecal route despite public health emphasis on droplet transmission and precautions for contact with respiratory secretions,” the investigators wrote.

To address this question, the investigators conducted a systematic review and meta-analysis involving 23 published and 6 preprint studies involving a total of 4,805 patients, all of whom tested positive for SARS-CoV-2 based on PCR results from nasopharyngeal swabs. Dr. Parasa and colleagues noted that most of the studies “scored between 8 and 10 on the MINORS quality assessment,” suggesting moderate quality.

Pooled data from these studies showed that 4.6% of patients reported nausea or vomiting, while 7.4% reported diarrhea. Such symptoms may serve as an early warning flag for clinicians, the investigators noted.

“[T]he presence of GI symptoms may portend a worse outcome for patients infected with SARS-CoV-2,” they wrote, citing a study by Pan and colleagues, which found that GI symptoms were associated with lower rates of recovery and hospital discharge.

Regardless of GI symptoms, 40.5% of patients in the meta-analysis tested positive for viral RNA in feces (95% confidence interval, 27.4%-55.1%). Duration of viral shedding in feces lasted up to 11 days after symptom onset, or in a single-patient case study, 18 days after hospitalization.

The investigators called these duration figures “particularly concerning,” especially in light of a study published by Xiao and colleagues, which showed that 23.3% of patients with negative respiratory tests were still shedding live virus in feces.

“[T]he fecal-oral route of transmission could be an additional potential source of infection spread,” wrote Dr. Parasa and colleagues. “Our results also suggest that testing of the virus in feces ... could be helpful in disease monitoring and surveillance.”

David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, said that the findings confirm what has been suspected for some time: GI disease is relatively common with COVID-19.

“The evidence is clear now that a sizable percentage of patients have GI symptoms,” Dr. Johnson said in an interview.

GI issues may precede respiratory signs, he added, so clinicians should be aware that nausea, vomiting, or diarrhea could be early indicators of COVID-19, and possibly, a worse outcome.

“The other highlight of this study is that stool shedding may be extended beyond respiratory shedding,” Dr. Johnson said.

He suggested that this finding could influence current CDC criteria, which define absence of infectious risk by two consecutive, negative nasopharyngeal swabs. Instead, fecal testing may be needed, he said, along with measures to prevent fecal-oral transmission.

Dr. Johnson expressed particular concern for risk of infection via toilet plume, in which toilet flushing aerosolizes viral particles.

“As much as people try to social distance by 6 feet – you can do that when you walk into a store, or a building, but you can’t necessarily do that when you walk into a public toilet, where the plume may have been expansive for a period of time,” he said. “That toilet may never really get cleaned to a high level of disinfection, and those droplets set up potential for fecal-oral spread.”

Dr. Sharma disclosed relationships with Medtronic, Fujifilm, Boston Scientific, and others. Dr. Johnson disclosed no relevant conflicts of interest.

SOURCE: Parasa S et al. JAMA Network Open. 2020 Jun 11. doi: 10.1001/jamanetworkopen.2020.11335.

Even without GI symptoms, many patients with COVID-19 shed viral RNA in feces, suggesting that stool testing and prevention of fecal-oral transmission may be needed to combat the ongoing pandemic, according to investigators.

A meta-analysis of 29 studies showed that 12% of patients with COVID-19 developed nausea, diarrhea, or vomiting, while 41% shed viral RNA in feces, reported lead author Sravanthi Parasa, MD, of Swedish Medical Center, Seattle.Writing in JAMA Network Open, Dr. Parasa and colleagues emphasized that respiratory symptoms remain the predominant form of disease; however, GI symptoms can occur.

“In fact, the first reported patient with COVID-19 in the U.S. reported GI symptoms of loose bowel movements and abdominal discomfort,” the investigators wrote, noting that the patient went on to test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in both respiratory and stool specimens.

“This raises the question of inadvertent human-to-human transmission via the fecal route despite public health emphasis on droplet transmission and precautions for contact with respiratory secretions,” the investigators wrote.

To address this question, the investigators conducted a systematic review and meta-analysis involving 23 published and 6 preprint studies involving a total of 4,805 patients, all of whom tested positive for SARS-CoV-2 based on PCR results from nasopharyngeal swabs. Dr. Parasa and colleagues noted that most of the studies “scored between 8 and 10 on the MINORS quality assessment,” suggesting moderate quality.

Pooled data from these studies showed that 4.6% of patients reported nausea or vomiting, while 7.4% reported diarrhea. Such symptoms may serve as an early warning flag for clinicians, the investigators noted.

“[T]he presence of GI symptoms may portend a worse outcome for patients infected with SARS-CoV-2,” they wrote, citing a study by Pan and colleagues, which found that GI symptoms were associated with lower rates of recovery and hospital discharge.

Regardless of GI symptoms, 40.5% of patients in the meta-analysis tested positive for viral RNA in feces (95% confidence interval, 27.4%-55.1%). Duration of viral shedding in feces lasted up to 11 days after symptom onset, or in a single-patient case study, 18 days after hospitalization.

The investigators called these duration figures “particularly concerning,” especially in light of a study published by Xiao and colleagues, which showed that 23.3% of patients with negative respiratory tests were still shedding live virus in feces.

“[T]he fecal-oral route of transmission could be an additional potential source of infection spread,” wrote Dr. Parasa and colleagues. “Our results also suggest that testing of the virus in feces ... could be helpful in disease monitoring and surveillance.”

David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, said that the findings confirm what has been suspected for some time: GI disease is relatively common with COVID-19.

“The evidence is clear now that a sizable percentage of patients have GI symptoms,” Dr. Johnson said in an interview.

GI issues may precede respiratory signs, he added, so clinicians should be aware that nausea, vomiting, or diarrhea could be early indicators of COVID-19, and possibly, a worse outcome.

“The other highlight of this study is that stool shedding may be extended beyond respiratory shedding,” Dr. Johnson said.

He suggested that this finding could influence current CDC criteria, which define absence of infectious risk by two consecutive, negative nasopharyngeal swabs. Instead, fecal testing may be needed, he said, along with measures to prevent fecal-oral transmission.

Dr. Johnson expressed particular concern for risk of infection via toilet plume, in which toilet flushing aerosolizes viral particles.

“As much as people try to social distance by 6 feet – you can do that when you walk into a store, or a building, but you can’t necessarily do that when you walk into a public toilet, where the plume may have been expansive for a period of time,” he said. “That toilet may never really get cleaned to a high level of disinfection, and those droplets set up potential for fecal-oral spread.”

Dr. Sharma disclosed relationships with Medtronic, Fujifilm, Boston Scientific, and others. Dr. Johnson disclosed no relevant conflicts of interest.

SOURCE: Parasa S et al. JAMA Network Open. 2020 Jun 11. doi: 10.1001/jamanetworkopen.2020.11335.

For endoscopists performing electrosurgical snare resection of large colorectal polyps, choosing between the blue foot pedal and the yellow foot pedal may be the least important step of the day, according to data from almost 1,000 patients.

Risks of severe adverse events and polyp recurrence were similar between cases in which blended current (yellow pedal) was used and those in which coagulation current (blue pedal) was used, reported lead author Heiko Pohl, MD, of Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“Although electrosurgical application is a fundamental aspect of polypectomy, various currents and settings are clinically used, and there are no accepted standards of practice,” the investigators wrote in Gastroenterology.

According to Dr. Pohl and colleagues, a 2004 study showed that the split between endoscopists using coagulation current and those using blended current was about 50-50 (46% vs. 46%), but no studies to date have tested the relative safety or efficacy of these approaches.

The investigators aimed to address this knowledge gap with a single-blinded study involving 928 patients who underwent endoscopic mucosal resection of nonpedunculated, large (20 mm or larger) colorectal polyps with an Erbe Vio^® 300D electrosurgical unit (Erbe USA Inc., Marietta, Ga.) at 18 medical centers.

Patients were randomized in 2x2 factorial design involving clip closure versus no clip closure, and blended current (Endocut Q) versus pure coagulation current (Forced Coagulation). Although electrosurgical setting was initially a secondary intervention in the trial, post hoc analysis showed that interaction between the interventions was not significant (P = .957), allowing for the present, independent analysis of current type.

For this analysis, the primary outcome was severe adverse event rate, both during the procedure, and after the procedure for up to 30 days. Secondary outcomes included proportion of polyps completely excised and recurrence rate at time of first surveillance endoscopy.

Out of 928 patients randomized, 919 completed 30-day follow-up, and 675 underwent first surveillance colonoscopy. Baseline characteristics were similar between groups, apart from the proportion of individuals with more than one large polyp, which was significantly greater in the Endocut Q group (8.6% vs. 4.5%; P = .012), although the investigators noted that this imbalance did not affect main outcomes.

Rates of severe adverse events were similar between groups: 7.2% for the Endocut Q group and 7.9% for the Forced Coagulation group (P = .762). Groups also had similar rates of intra- and postprocedure adverse events, and types of adverse events.

Efficacy measures also revealed high similarity between cutting techniques. Endoscopists using Endocut achieved complete polyp removal 96% of the time, compared with 95% of the time when using Forced Coagulation (P = .267). Piecemeal resection rates were similar, at 90% and 87% for Endocut Q and Forced Coagulation, respectively (P = .270).

Although Endocut Q less frequently resulted in small residual tissue islands after initial snare resection (35% vs. 41%; P = .041), it more often caused intraprocedural bleeding that required treatment (17% vs. 11%; P = .006).

According to Dr. Pohl and colleagues, previous discussions have included concerns that such bleeding may impair visualization and therefore lead to higher rates of polyp recurrence; but surveillance colonoscopy, which was performed in 79% of patients, revealed a polyp recurrence rate of 17% for each group.

“Although we did not find a difference in recurrence between the two groups, our study cannot completely exclude this possibility,” the investigators added.

They also noted that six perforations occurred in the Endocut Q group, compared with three in the Forced Coagulation group, and suggested that this risk may be real, yet statistically unsupported by the present analysis because of sample size.

“Endoscopists using Endocut should therefore be aware of this potential risk and [ensure] that no muscularis propria is entrapped in the snare before electrosurgery is applied,” the investigators wrote.

Still, the investigators’ final conclusion supported the existing method of decision-making: personal choice.

“Overall, polyp resection with Endocut or Forced Coagulation did not differ with respect to severe adverse events, complete resection rate, or polyp recurrence,” they wrote. “This study therefore supports an individual approach based on endoscopist preference.”

The study was funded by Boston Scientific and the American College of Gastroenterology. The investigators disclosed additional relationships with Medtronic, Olympus, Cook Endoscopy, and others.

SOURCE: Pohl H et al. Gastroenterology. 2020 Mar 12. doi: 10.1053/j.gastro.2020.03.014.

For endoscopists performing electrosurgical snare resection of large colorectal polyps, choosing between the blue foot pedal and the yellow foot pedal may be the least important step of the day, according to data from almost 1,000 patients.

Risks of severe adverse events and polyp recurrence were similar between cases in which blended current (yellow pedal) was used and those in which coagulation current (blue pedal) was used, reported lead author Heiko Pohl, MD, of Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“Although electrosurgical application is a fundamental aspect of polypectomy, various currents and settings are clinically used, and there are no accepted standards of practice,” the investigators wrote in Gastroenterology.

According to Dr. Pohl and colleagues, a 2004 study showed that the split between endoscopists using coagulation current and those using blended current was about 50-50 (46% vs. 46%), but no studies to date have tested the relative safety or efficacy of these approaches.

The investigators aimed to address this knowledge gap with a single-blinded study involving 928 patients who underwent endoscopic mucosal resection of nonpedunculated, large (20 mm or larger) colorectal polyps with an Erbe Vio^® 300D electrosurgical unit (Erbe USA Inc., Marietta, Ga.) at 18 medical centers.

Patients were randomized in 2x2 factorial design involving clip closure versus no clip closure, and blended current (Endocut Q) versus pure coagulation current (Forced Coagulation). Although electrosurgical setting was initially a secondary intervention in the trial, post hoc analysis showed that interaction between the interventions was not significant (P = .957), allowing for the present, independent analysis of current type.

For this analysis, the primary outcome was severe adverse event rate, both during the procedure, and after the procedure for up to 30 days. Secondary outcomes included proportion of polyps completely excised and recurrence rate at time of first surveillance endoscopy.

Out of 928 patients randomized, 919 completed 30-day follow-up, and 675 underwent first surveillance colonoscopy. Baseline characteristics were similar between groups, apart from the proportion of individuals with more than one large polyp, which was significantly greater in the Endocut Q group (8.6% vs. 4.5%; P = .012), although the investigators noted that this imbalance did not affect main outcomes.

Rates of severe adverse events were similar between groups: 7.2% for the Endocut Q group and 7.9% for the Forced Coagulation group (P = .762). Groups also had similar rates of intra- and postprocedure adverse events, and types of adverse events.

Efficacy measures also revealed high similarity between cutting techniques. Endoscopists using Endocut achieved complete polyp removal 96% of the time, compared with 95% of the time when using Forced Coagulation (P = .267). Piecemeal resection rates were similar, at 90% and 87% for Endocut Q and Forced Coagulation, respectively (P = .270).

Although Endocut Q less frequently resulted in small residual tissue islands after initial snare resection (35% vs. 41%; P = .041), it more often caused intraprocedural bleeding that required treatment (17% vs. 11%; P = .006).

According to Dr. Pohl and colleagues, previous discussions have included concerns that such bleeding may impair visualization and therefore lead to higher rates of polyp recurrence; but surveillance colonoscopy, which was performed in 79% of patients, revealed a polyp recurrence rate of 17% for each group.

“Although we did not find a difference in recurrence between the two groups, our study cannot completely exclude this possibility,” the investigators added.

They also noted that six perforations occurred in the Endocut Q group, compared with three in the Forced Coagulation group, and suggested that this risk may be real, yet statistically unsupported by the present analysis because of sample size.

“Endoscopists using Endocut should therefore be aware of this potential risk and [ensure] that no muscularis propria is entrapped in the snare before electrosurgery is applied,” the investigators wrote.

Still, the investigators’ final conclusion supported the existing method of decision-making: personal choice.

“Overall, polyp resection with Endocut or Forced Coagulation did not differ with respect to severe adverse events, complete resection rate, or polyp recurrence,” they wrote. “This study therefore supports an individual approach based on endoscopist preference.”

The study was funded by Boston Scientific and the American College of Gastroenterology. The investigators disclosed additional relationships with Medtronic, Olympus, Cook Endoscopy, and others.

SOURCE: Pohl H et al. Gastroenterology. 2020 Mar 12. doi: 10.1053/j.gastro.2020.03.014.

For endoscopists performing electrosurgical snare resection of large colorectal polyps, choosing between the blue foot pedal and the yellow foot pedal may be the least important step of the day, according to data from almost 1,000 patients.

Risks of severe adverse events and polyp recurrence were similar between cases in which blended current (yellow pedal) was used and those in which coagulation current (blue pedal) was used, reported lead author Heiko Pohl, MD, of Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“Although electrosurgical application is a fundamental aspect of polypectomy, various currents and settings are clinically used, and there are no accepted standards of practice,” the investigators wrote in Gastroenterology.

According to Dr. Pohl and colleagues, a 2004 study showed that the split between endoscopists using coagulation current and those using blended current was about 50-50 (46% vs. 46%), but no studies to date have tested the relative safety or efficacy of these approaches.

The investigators aimed to address this knowledge gap with a single-blinded study involving 928 patients who underwent endoscopic mucosal resection of nonpedunculated, large (20 mm or larger) colorectal polyps with an Erbe Vio^® 300D electrosurgical unit (Erbe USA Inc., Marietta, Ga.) at 18 medical centers.

Patients were randomized in 2x2 factorial design involving clip closure versus no clip closure, and blended current (Endocut Q) versus pure coagulation current (Forced Coagulation). Although electrosurgical setting was initially a secondary intervention in the trial, post hoc analysis showed that interaction between the interventions was not significant (P = .957), allowing for the present, independent analysis of current type.

For this analysis, the primary outcome was severe adverse event rate, both during the procedure, and after the procedure for up to 30 days. Secondary outcomes included proportion of polyps completely excised and recurrence rate at time of first surveillance endoscopy.

Out of 928 patients randomized, 919 completed 30-day follow-up, and 675 underwent first surveillance colonoscopy. Baseline characteristics were similar between groups, apart from the proportion of individuals with more than one large polyp, which was significantly greater in the Endocut Q group (8.6% vs. 4.5%; P = .012), although the investigators noted that this imbalance did not affect main outcomes.

Rates of severe adverse events were similar between groups: 7.2% for the Endocut Q group and 7.9% for the Forced Coagulation group (P = .762). Groups also had similar rates of intra- and postprocedure adverse events, and types of adverse events.

Efficacy measures also revealed high similarity between cutting techniques. Endoscopists using Endocut achieved complete polyp removal 96% of the time, compared with 95% of the time when using Forced Coagulation (P = .267). Piecemeal resection rates were similar, at 90% and 87% for Endocut Q and Forced Coagulation, respectively (P = .270).

Although Endocut Q less frequently resulted in small residual tissue islands after initial snare resection (35% vs. 41%; P = .041), it more often caused intraprocedural bleeding that required treatment (17% vs. 11%; P = .006).

According to Dr. Pohl and colleagues, previous discussions have included concerns that such bleeding may impair visualization and therefore lead to higher rates of polyp recurrence; but surveillance colonoscopy, which was performed in 79% of patients, revealed a polyp recurrence rate of 17% for each group.

“Although we did not find a difference in recurrence between the two groups, our study cannot completely exclude this possibility,” the investigators added.

They also noted that six perforations occurred in the Endocut Q group, compared with three in the Forced Coagulation group, and suggested that this risk may be real, yet statistically unsupported by the present analysis because of sample size.

“Endoscopists using Endocut should therefore be aware of this potential risk and [ensure] that no muscularis propria is entrapped in the snare before electrosurgery is applied,” the investigators wrote.

Still, the investigators’ final conclusion supported the existing method of decision-making: personal choice.

“Overall, polyp resection with Endocut or Forced Coagulation did not differ with respect to severe adverse events, complete resection rate, or polyp recurrence,” they wrote. “This study therefore supports an individual approach based on endoscopist preference.”

The study was funded by Boston Scientific and the American College of Gastroenterology. The investigators disclosed additional relationships with Medtronic, Olympus, Cook Endoscopy, and others.

SOURCE: Pohl H et al. Gastroenterology. 2020 Mar 12. doi: 10.1053/j.gastro.2020.03.014.

When performing transient elastography (FibroScan) to evaluate patients for hepatic steatosis, using an M probe instead of an XL probe may significantly underestimate hepatic fat content, according to investigators.

The findings, which were independent of body weight, suggest that probe-specific controlled attenuation parameter (CAP) thresholds are needed to accurately interpret FibroScan results, reported lead author Cyrielle Caussy, MD, PhD, of the University of California, San Diego, and colleagues.

“We have previously determined the optimal threshold of CAP using either [an] M or XL probe for the detection of ... nonalcoholic fatty liver disease (NAFLD),” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, head-to-head comparison of consecutive measurements of CAP with both the M and XL probes versus MRI-PDFF [proton density fat fraction] ... has not been reported yet.”

Dr. Caussy and colleagues set out to do just that. They enrolled 105 individuals with and without NAFLD who had a mean body mass index (BMI) of 30.6 kg/m², as this represented a typical population screened for NAFLD. After evaluation for other causes of hepatic steatosis and liver disease, participants underwent MRI-PDFF, which served as a gold standard, followed by FibroScan using both M and XL probes on the same day.

The primary outcome was hepatic steatosis (MRI-PDFF of at least 5%), while the secondary outcome was MRI-PDFF–detected hepatic fat content of at least 10%, the latter of which has been “used in several therapeutic trials as inclusion criteria,” the investigators noted.

A total of 100 participants were included in the final analysis, of whom two-thirds (66%) underwent MRI and FibroScan on the same day, with a mean interval between test types of 11 days. Most participants (68%) had an MRI-PDFF of at least 5%, while almost half (48%) exceeded an MRI-PDFF of 10%.

The mean CAP measurement with the M probe was 310 dB/m, which was significantly lower than the mean value detected by the XL probe, which was 317 dB/m (P = .007). In participants with hepatic steatosis, when the M probe was used for those with a BMI of less than 30, and the XL probe was used for those with a BMI of 30 or more, the M probe still provided a significantly lower measure of hepatic fat content (312 vs. 345 dB/m; P = .0035).

“[T]hese results have direct application in routine clinical practice,” the investigators wrote, “as [they] will help clinicians interpreting CAP measurements depending on the type of probe used.”

Dr. Caussy and colleagues went on to offer a diagnostic algorithm involving optimal probe-specific thresholds for CAP based on hepatic fat content. Individuals screened with an M probe who have a CAP of 294 dB/m or more should be considered positive for NAFLD, while patients screened with an XL probe need to have a CAP of at least 307 dB/m to be NAFLD positive.

For the XL probe, but not the M probe, diagnostic accuracy depended upon an interquartile range of less than 30 dB/m. The investigators noted that this finding should alter the interpretation of a 2019 study by Eddowes and colleagues, which concluded that interquartile range was unrelated to diagnostic accuracy.

“As Eddowes et al. did not perform head-to-head comparison of CAP measurement with both the M and XL probes, this important difference could not have been observed,” the investigators wrote, noting that “an interquartile range of CAP below 30 dB/m should be considered as a quality indicator that significantly improves the diagnostic performance of CAP using the XL probe for the detection of hepatic steatosis in NAFLD.”

The investigators concluded by suggesting that their findings will drive research forward.

“The use of these new thresholds will help to further assess the clinical utility of CAP for the detection of hepatic steatosis and its cost-effectiveness, compared with other modalities, to develop optimal strategies for the screening of NAFLD,” they wrote.

The study was funded by Atlantic Philanthropies, the John A. Hartford Foundation, the American Gastroenterological Association, and others. The investigators disclosed no conflicts of interest.

SOURCE: Caussy C et al. Clin Gastro Hepatol. 2019 Dec 13. doi: 10.1016/j.cgh.2019.11.060.

When performing transient elastography (FibroScan) to evaluate patients for hepatic steatosis, using an M probe instead of an XL probe may significantly underestimate hepatic fat content, according to investigators.

The findings, which were independent of body weight, suggest that probe-specific controlled attenuation parameter (CAP) thresholds are needed to accurately interpret FibroScan results, reported lead author Cyrielle Caussy, MD, PhD, of the University of California, San Diego, and colleagues.

“We have previously determined the optimal threshold of CAP using either [an] M or XL probe for the detection of ... nonalcoholic fatty liver disease (NAFLD),” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, head-to-head comparison of consecutive measurements of CAP with both the M and XL probes versus MRI-PDFF [proton density fat fraction] ... has not been reported yet.”

Dr. Caussy and colleagues set out to do just that. They enrolled 105 individuals with and without NAFLD who had a mean body mass index (BMI) of 30.6 kg/m², as this represented a typical population screened for NAFLD. After evaluation for other causes of hepatic steatosis and liver disease, participants underwent MRI-PDFF, which served as a gold standard, followed by FibroScan using both M and XL probes on the same day.

The primary outcome was hepatic steatosis (MRI-PDFF of at least 5%), while the secondary outcome was MRI-PDFF–detected hepatic fat content of at least 10%, the latter of which has been “used in several therapeutic trials as inclusion criteria,” the investigators noted.

A total of 100 participants were included in the final analysis, of whom two-thirds (66%) underwent MRI and FibroScan on the same day, with a mean interval between test types of 11 days. Most participants (68%) had an MRI-PDFF of at least 5%, while almost half (48%) exceeded an MRI-PDFF of 10%.

The mean CAP measurement with the M probe was 310 dB/m, which was significantly lower than the mean value detected by the XL probe, which was 317 dB/m (P = .007). In participants with hepatic steatosis, when the M probe was used for those with a BMI of less than 30, and the XL probe was used for those with a BMI of 30 or more, the M probe still provided a significantly lower measure of hepatic fat content (312 vs. 345 dB/m; P = .0035).

“[T]hese results have direct application in routine clinical practice,” the investigators wrote, “as [they] will help clinicians interpreting CAP measurements depending on the type of probe used.”

Dr. Caussy and colleagues went on to offer a diagnostic algorithm involving optimal probe-specific thresholds for CAP based on hepatic fat content. Individuals screened with an M probe who have a CAP of 294 dB/m or more should be considered positive for NAFLD, while patients screened with an XL probe need to have a CAP of at least 307 dB/m to be NAFLD positive.

For the XL probe, but not the M probe, diagnostic accuracy depended upon an interquartile range of less than 30 dB/m. The investigators noted that this finding should alter the interpretation of a 2019 study by Eddowes and colleagues, which concluded that interquartile range was unrelated to diagnostic accuracy.

“As Eddowes et al. did not perform head-to-head comparison of CAP measurement with both the M and XL probes, this important difference could not have been observed,” the investigators wrote, noting that “an interquartile range of CAP below 30 dB/m should be considered as a quality indicator that significantly improves the diagnostic performance of CAP using the XL probe for the detection of hepatic steatosis in NAFLD.”

The investigators concluded by suggesting that their findings will drive research forward.

“The use of these new thresholds will help to further assess the clinical utility of CAP for the detection of hepatic steatosis and its cost-effectiveness, compared with other modalities, to develop optimal strategies for the screening of NAFLD,” they wrote.

The study was funded by Atlantic Philanthropies, the John A. Hartford Foundation, the American Gastroenterological Association, and others. The investigators disclosed no conflicts of interest.

SOURCE: Caussy C et al. Clin Gastro Hepatol. 2019 Dec 13. doi: 10.1016/j.cgh.2019.11.060.

When performing transient elastography (FibroScan) to evaluate patients for hepatic steatosis, using an M probe instead of an XL probe may significantly underestimate hepatic fat content, according to investigators.

The findings, which were independent of body weight, suggest that probe-specific controlled attenuation parameter (CAP) thresholds are needed to accurately interpret FibroScan results, reported lead author Cyrielle Caussy, MD, PhD, of the University of California, San Diego, and colleagues.

“We have previously determined the optimal threshold of CAP using either [an] M or XL probe for the detection of ... nonalcoholic fatty liver disease (NAFLD),” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, head-to-head comparison of consecutive measurements of CAP with both the M and XL probes versus MRI-PDFF [proton density fat fraction] ... has not been reported yet.”

Dr. Caussy and colleagues set out to do just that. They enrolled 105 individuals with and without NAFLD who had a mean body mass index (BMI) of 30.6 kg/m², as this represented a typical population screened for NAFLD. After evaluation for other causes of hepatic steatosis and liver disease, participants underwent MRI-PDFF, which served as a gold standard, followed by FibroScan using both M and XL probes on the same day.

The primary outcome was hepatic steatosis (MRI-PDFF of at least 5%), while the secondary outcome was MRI-PDFF–detected hepatic fat content of at least 10%, the latter of which has been “used in several therapeutic trials as inclusion criteria,” the investigators noted.

A total of 100 participants were included in the final analysis, of whom two-thirds (66%) underwent MRI and FibroScan on the same day, with a mean interval between test types of 11 days. Most participants (68%) had an MRI-PDFF of at least 5%, while almost half (48%) exceeded an MRI-PDFF of 10%.

The mean CAP measurement with the M probe was 310 dB/m, which was significantly lower than the mean value detected by the XL probe, which was 317 dB/m (P = .007). In participants with hepatic steatosis, when the M probe was used for those with a BMI of less than 30, and the XL probe was used for those with a BMI of 30 or more, the M probe still provided a significantly lower measure of hepatic fat content (312 vs. 345 dB/m; P = .0035).

“[T]hese results have direct application in routine clinical practice,” the investigators wrote, “as [they] will help clinicians interpreting CAP measurements depending on the type of probe used.”

Dr. Caussy and colleagues went on to offer a diagnostic algorithm involving optimal probe-specific thresholds for CAP based on hepatic fat content. Individuals screened with an M probe who have a CAP of 294 dB/m or more should be considered positive for NAFLD, while patients screened with an XL probe need to have a CAP of at least 307 dB/m to be NAFLD positive.

For the XL probe, but not the M probe, diagnostic accuracy depended upon an interquartile range of less than 30 dB/m. The investigators noted that this finding should alter the interpretation of a 2019 study by Eddowes and colleagues, which concluded that interquartile range was unrelated to diagnostic accuracy.

“As Eddowes et al. did not perform head-to-head comparison of CAP measurement with both the M and XL probes, this important difference could not have been observed,” the investigators wrote, noting that “an interquartile range of CAP below 30 dB/m should be considered as a quality indicator that significantly improves the diagnostic performance of CAP using the XL probe for the detection of hepatic steatosis in NAFLD.”

The investigators concluded by suggesting that their findings will drive research forward.

“The use of these new thresholds will help to further assess the clinical utility of CAP for the detection of hepatic steatosis and its cost-effectiveness, compared with other modalities, to develop optimal strategies for the screening of NAFLD,” they wrote.

The study was funded by Atlantic Philanthropies, the John A. Hartford Foundation, the American Gastroenterological Association, and others. The investigators disclosed no conflicts of interest.

SOURCE: Caussy C et al. Clin Gastro Hepatol. 2019 Dec 13. doi: 10.1016/j.cgh.2019.11.060.

Prophylactically clipping large proximal colorectal lesions after resection may reduce risk of postprocedural bleeding, according to a meta-analysis involving nine randomized controlled trials.

Across all lesions, prophylactic clipping had no significant benefit, but when considering only large proximal lesions, clipping reduced bleeding risk by 63%, reported lead author Marco Spadaccini, MD, of Humanitas University, Rozzano, Italy, and colleagues.

According to the investigators, these findings emphasize the relevance of polyp size and location when assessing bleeding risk, which may influence future clinical guidance.

“Despite lack of high-quality evidence, prophylactic clipping has been advocated as a technique to reduce the risk of postprocedural bleeding,” the investigators wrote in Gastroenterology, referring to the European Society of Gastrointestinal Endoscopy recommendation that is based on patient risk factors.

Although previous meta-analyses reported that prophylactic clipping had no protective effect, these studies were “at high risk of bias” and predominantly evaluated lesions less than 20 mm in diameter, the investigators wrote.

Dr. Spadaccini and colleagues suggested that data from more recent, high-quality, randomized controlled trials could be used to identify subgroups that may benefit from clipping. This knowledge is particularly valuable considering the “costs and technical complexity” involved in the procedure, they noted.

The present meta-analysis comprised nine trials that included 7,197 colorectal lesions, of which 49.2% were proximally located and 22.5% were large (at least 20 mm in diameter).

Across all lesions, postprocedural bleeding occurred in 2.2% of clipped lesions and 3.3% of nonclipped lesions, a difference that was not statistically significant (P = .072). But for lesions 20 mm or larger, clipping was associated with a significantly lower rate of bleeding (4.3% vs. 7.6%; relative risk, 0.51; 95% CI, 0.33-0.78; P = .020). Similarly, clipping in the proximal location was independently associated with reduced bleeding risk (3.0% vs. 6.2%; RR, 0.53; 95% CI, 0.35-0.81; P less than .001). A multilevel meta-regression added further clarity by combining both size and location; it showed that clipping had a significant protective effect for large proximal lesions (RR, 0.37; 95% CI, 0.22-0.61; P = .021), but not for those that were small and proximal (RR, 0.88; 95% CI, 0.48-1.62; P = .581).

“According to our meta-analysis, routine practice of endoscopic clipping as a prophylactic intervention does not reduce the risk of postpolypectomy bleeding,” the investigators wrote. “However, clipping was effective in reducing the risk of postprocedural bleeding by nearly 50% for large lesions. If such lesions do not undergo endoscopic clipping, there was fourfold increase in the baseline risk of post-procedural bleeding as compared with those less than 20 mm.”

While the present analysis suggested that clipping was beneficial only for large lesions in the proximal colon, the investigators noted that the protective effect of clipping large lesions in the distal colon (RR, 0.70; 95% CI, 0.22-2.27) was “somewhat intermediate ... albeit not statistically significant” and driven by data from one trial.

“[T]his was not confirmed by other studies generating some uncertainty on the benefit of prophylactic clipping for large distal lesions,” the investigators wrote. “Thus, the decision for large and distal lesions should be tailored, especially taking into consideration other patient- and polyp-risk factors for postprocedural bleeding, such as the use of anti-thrombotic agents or intraprocedural bleeding.”

In contrast, the findings indicated that clipping is unnecessary for lesions less than 20 mm, the investigators wrote.

They went on to explain that clinical application of these findings could result in “significant cost savings” because one bleeding event would be prevented for every 23 large lesions clipped.

“Considering that clips are expensive and their placement might be technically demanding, prophylactic clipping tailored for a subgroup of higher-risk lesions/patients would decrease in parallel both adverse events and costs,” the investigators concluded.

The investigators reported no external funding or conflicts of interest.

[email protected]

SOURCE: Spadaccini M et al. Gastroenterology. 2020 Apr 1. doi: 10.1053/j.gastro.2020.03.051.

Prophylactically clipping large proximal colorectal lesions after resection may reduce risk of postprocedural bleeding, according to a meta-analysis involving nine randomized controlled trials.

Across all lesions, prophylactic clipping had no significant benefit, but when considering only large proximal lesions, clipping reduced bleeding risk by 63%, reported lead author Marco Spadaccini, MD, of Humanitas University, Rozzano, Italy, and colleagues.

According to the investigators, these findings emphasize the relevance of polyp size and location when assessing bleeding risk, which may influence future clinical guidance.

“Despite lack of high-quality evidence, prophylactic clipping has been advocated as a technique to reduce the risk of postprocedural bleeding,” the investigators wrote in Gastroenterology, referring to the European Society of Gastrointestinal Endoscopy recommendation that is based on patient risk factors.

Although previous meta-analyses reported that prophylactic clipping had no protective effect, these studies were “at high risk of bias” and predominantly evaluated lesions less than 20 mm in diameter, the investigators wrote.

Dr. Spadaccini and colleagues suggested that data from more recent, high-quality, randomized controlled trials could be used to identify subgroups that may benefit from clipping. This knowledge is particularly valuable considering the “costs and technical complexity” involved in the procedure, they noted.

The present meta-analysis comprised nine trials that included 7,197 colorectal lesions, of which 49.2% were proximally located and 22.5% were large (at least 20 mm in diameter).

Across all lesions, postprocedural bleeding occurred in 2.2% of clipped lesions and 3.3% of nonclipped lesions, a difference that was not statistically significant (P = .072). But for lesions 20 mm or larger, clipping was associated with a significantly lower rate of bleeding (4.3% vs. 7.6%; relative risk, 0.51; 95% CI, 0.33-0.78; P = .020). Similarly, clipping in the proximal location was independently associated with reduced bleeding risk (3.0% vs. 6.2%; RR, 0.53; 95% CI, 0.35-0.81; P less than .001). A multilevel meta-regression added further clarity by combining both size and location; it showed that clipping had a significant protective effect for large proximal lesions (RR, 0.37; 95% CI, 0.22-0.61; P = .021), but not for those that were small and proximal (RR, 0.88; 95% CI, 0.48-1.62; P = .581).

“According to our meta-analysis, routine practice of endoscopic clipping as a prophylactic intervention does not reduce the risk of postpolypectomy bleeding,” the investigators wrote. “However, clipping was effective in reducing the risk of postprocedural bleeding by nearly 50% for large lesions. If such lesions do not undergo endoscopic clipping, there was fourfold increase in the baseline risk of post-procedural bleeding as compared with those less than 20 mm.”

While the present analysis suggested that clipping was beneficial only for large lesions in the proximal colon, the investigators noted that the protective effect of clipping large lesions in the distal colon (RR, 0.70; 95% CI, 0.22-2.27) was “somewhat intermediate ... albeit not statistically significant” and driven by data from one trial.

“[T]his was not confirmed by other studies generating some uncertainty on the benefit of prophylactic clipping for large distal lesions,” the investigators wrote. “Thus, the decision for large and distal lesions should be tailored, especially taking into consideration other patient- and polyp-risk factors for postprocedural bleeding, such as the use of anti-thrombotic agents or intraprocedural bleeding.”

In contrast, the findings indicated that clipping is unnecessary for lesions less than 20 mm, the investigators wrote.

They went on to explain that clinical application of these findings could result in “significant cost savings” because one bleeding event would be prevented for every 23 large lesions clipped.

“Considering that clips are expensive and their placement might be technically demanding, prophylactic clipping tailored for a subgroup of higher-risk lesions/patients would decrease in parallel both adverse events and costs,” the investigators concluded.

The investigators reported no external funding or conflicts of interest.

[email protected]

SOURCE: Spadaccini M et al. Gastroenterology. 2020 Apr 1. doi: 10.1053/j.gastro.2020.03.051.

Prophylactically clipping large proximal colorectal lesions after resection may reduce risk of postprocedural bleeding, according to a meta-analysis involving nine randomized controlled trials.

Across all lesions, prophylactic clipping had no significant benefit, but when considering only large proximal lesions, clipping reduced bleeding risk by 63%, reported lead author Marco Spadaccini, MD, of Humanitas University, Rozzano, Italy, and colleagues.

According to the investigators, these findings emphasize the relevance of polyp size and location when assessing bleeding risk, which may influence future clinical guidance.

“Despite lack of high-quality evidence, prophylactic clipping has been advocated as a technique to reduce the risk of postprocedural bleeding,” the investigators wrote in Gastroenterology, referring to the European Society of Gastrointestinal Endoscopy recommendation that is based on patient risk factors.

Although previous meta-analyses reported that prophylactic clipping had no protective effect, these studies were “at high risk of bias” and predominantly evaluated lesions less than 20 mm in diameter, the investigators wrote.

Dr. Spadaccini and colleagues suggested that data from more recent, high-quality, randomized controlled trials could be used to identify subgroups that may benefit from clipping. This knowledge is particularly valuable considering the “costs and technical complexity” involved in the procedure, they noted.

The present meta-analysis comprised nine trials that included 7,197 colorectal lesions, of which 49.2% were proximally located and 22.5% were large (at least 20 mm in diameter).

Across all lesions, postprocedural bleeding occurred in 2.2% of clipped lesions and 3.3% of nonclipped lesions, a difference that was not statistically significant (P = .072). But for lesions 20 mm or larger, clipping was associated with a significantly lower rate of bleeding (4.3% vs. 7.6%; relative risk, 0.51; 95% CI, 0.33-0.78; P = .020). Similarly, clipping in the proximal location was independently associated with reduced bleeding risk (3.0% vs. 6.2%; RR, 0.53; 95% CI, 0.35-0.81; P less than .001). A multilevel meta-regression added further clarity by combining both size and location; it showed that clipping had a significant protective effect for large proximal lesions (RR, 0.37; 95% CI, 0.22-0.61; P = .021), but not for those that were small and proximal (RR, 0.88; 95% CI, 0.48-1.62; P = .581).

“According to our meta-analysis, routine practice of endoscopic clipping as a prophylactic intervention does not reduce the risk of postpolypectomy bleeding,” the investigators wrote. “However, clipping was effective in reducing the risk of postprocedural bleeding by nearly 50% for large lesions. If such lesions do not undergo endoscopic clipping, there was fourfold increase in the baseline risk of post-procedural bleeding as compared with those less than 20 mm.”

While the present analysis suggested that clipping was beneficial only for large lesions in the proximal colon, the investigators noted that the protective effect of clipping large lesions in the distal colon (RR, 0.70; 95% CI, 0.22-2.27) was “somewhat intermediate ... albeit not statistically significant” and driven by data from one trial.

“[T]his was not confirmed by other studies generating some uncertainty on the benefit of prophylactic clipping for large distal lesions,” the investigators wrote. “Thus, the decision for large and distal lesions should be tailored, especially taking into consideration other patient- and polyp-risk factors for postprocedural bleeding, such as the use of anti-thrombotic agents or intraprocedural bleeding.”

In contrast, the findings indicated that clipping is unnecessary for lesions less than 20 mm, the investigators wrote.

They went on to explain that clinical application of these findings could result in “significant cost savings” because one bleeding event would be prevented for every 23 large lesions clipped.

“Considering that clips are expensive and their placement might be technically demanding, prophylactic clipping tailored for a subgroup of higher-risk lesions/patients would decrease in parallel both adverse events and costs,” the investigators concluded.

The investigators reported no external funding or conflicts of interest.

[email protected]

SOURCE: Spadaccini M et al. Gastroenterology. 2020 Apr 1. doi: 10.1053/j.gastro.2020.03.051.