Will Pass

Altering the gut microbiome may reduce the tumor-promoting effects of cigarette smoking, based on a preclinical study.

Mice treated with microbiome-depleting antibiotics or genetically modified to lack an adaptive immune response did not show increased rates of cancer growth when exposed to cigarette smoke, reported lead author Prateek Sharma, MBBS, of the University of Miami, and colleagues.

Although previous research has shown that the gut microbiome plays a role in the progression of cancer and that smoking alters the gut microbiome, the collective effects of these changes have not been studied, the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.

“There is information that smoking changes the gut microbiome ... but the impact of this change is not known,” Dr. Sharma said in a virtual press conference.

To learn more, the investigators first performed an experiment using wild-type mice. All mice were injected with a cancer cell line from the pancreas, colon, or bladder. Mice were then sorted into four groups, in which they were given microbiome-depleting antibiotics and exposed to smoke, given antibiotics alone, exposed to smoke alone, or left untreated and unexposed to serve as controls. Tumor size was then measured over the course of 2 months.

The experiment revealed that mice exposed to smoke but not treated with antibiotics had increased rates of tumor growth regardless of cancer type. But in mice treated with antibiotics, the tumor-promoting effects of smoke exposure were completely lost; the mice had rates of tumor growth even lower than controls.

This experiment was repeated with mice genetically engineered to lack an adaptive immune response. Regardless of smoke or antibiotic exposure, all mice had comparable rates of tumor growth.

Dr. Sharma offered a summary of the findings and their possible implications for human medicine.

“Cigarette smoking changes the gut microbiome, and this changed gut microbiome interacts with the immune system to affect cancer progression,” he said. “If we can target this changed microbiome with modulation strategies like antibiotics, probiotics, or administration of good bacteria, we can alter this process. And if the same results are found in human studies, it could go a long way to affect cancer outcomes in smokers.”

In addition to human studies, Dr. Sharma said that future research should aim to uncover the underlying mechanisms involved in this process, including the types of bacteria that play a role.

When asked if the study might lessen concerns about the negative impacts of smoking among cancer patients, Dr. Sharma suggested that, even if the findings do translate to humans, smoking would still carry significant health risks.

“Even if gut microbiome modulation strategies do work in these patients, it may help a little, but it’s not going to bring it down to the level of nonsmokers, so it’s no way an excuse to not fear or continue [smoking],” he said.

The study was funded by the Florida Department of Health. The investigators reported no conflicts of interest.

Altering the gut microbiome may reduce the tumor-promoting effects of cigarette smoking, based on a preclinical study.

Mice treated with microbiome-depleting antibiotics or genetically modified to lack an adaptive immune response did not show increased rates of cancer growth when exposed to cigarette smoke, reported lead author Prateek Sharma, MBBS, of the University of Miami, and colleagues.

Although previous research has shown that the gut microbiome plays a role in the progression of cancer and that smoking alters the gut microbiome, the collective effects of these changes have not been studied, the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.

“There is information that smoking changes the gut microbiome ... but the impact of this change is not known,” Dr. Sharma said in a virtual press conference.

To learn more, the investigators first performed an experiment using wild-type mice. All mice were injected with a cancer cell line from the pancreas, colon, or bladder. Mice were then sorted into four groups, in which they were given microbiome-depleting antibiotics and exposed to smoke, given antibiotics alone, exposed to smoke alone, or left untreated and unexposed to serve as controls. Tumor size was then measured over the course of 2 months.

The experiment revealed that mice exposed to smoke but not treated with antibiotics had increased rates of tumor growth regardless of cancer type. But in mice treated with antibiotics, the tumor-promoting effects of smoke exposure were completely lost; the mice had rates of tumor growth even lower than controls.

This experiment was repeated with mice genetically engineered to lack an adaptive immune response. Regardless of smoke or antibiotic exposure, all mice had comparable rates of tumor growth.

Dr. Sharma offered a summary of the findings and their possible implications for human medicine.

“Cigarette smoking changes the gut microbiome, and this changed gut microbiome interacts with the immune system to affect cancer progression,” he said. “If we can target this changed microbiome with modulation strategies like antibiotics, probiotics, or administration of good bacteria, we can alter this process. And if the same results are found in human studies, it could go a long way to affect cancer outcomes in smokers.”

In addition to human studies, Dr. Sharma said that future research should aim to uncover the underlying mechanisms involved in this process, including the types of bacteria that play a role.

When asked if the study might lessen concerns about the negative impacts of smoking among cancer patients, Dr. Sharma suggested that, even if the findings do translate to humans, smoking would still carry significant health risks.

“Even if gut microbiome modulation strategies do work in these patients, it may help a little, but it’s not going to bring it down to the level of nonsmokers, so it’s no way an excuse to not fear or continue [smoking],” he said.

The study was funded by the Florida Department of Health. The investigators reported no conflicts of interest.

Altering the gut microbiome may reduce the tumor-promoting effects of cigarette smoking, based on a preclinical study.

Mice treated with microbiome-depleting antibiotics or genetically modified to lack an adaptive immune response did not show increased rates of cancer growth when exposed to cigarette smoke, reported lead author Prateek Sharma, MBBS, of the University of Miami, and colleagues.

Although previous research has shown that the gut microbiome plays a role in the progression of cancer and that smoking alters the gut microbiome, the collective effects of these changes have not been studied, the investigators wrote in an abstract released as part of the annual Digestive Disease Week, which was canceled because of COVID-19.

“There is information that smoking changes the gut microbiome ... but the impact of this change is not known,” Dr. Sharma said in a virtual press conference.

To learn more, the investigators first performed an experiment using wild-type mice. All mice were injected with a cancer cell line from the pancreas, colon, or bladder. Mice were then sorted into four groups, in which they were given microbiome-depleting antibiotics and exposed to smoke, given antibiotics alone, exposed to smoke alone, or left untreated and unexposed to serve as controls. Tumor size was then measured over the course of 2 months.

The experiment revealed that mice exposed to smoke but not treated with antibiotics had increased rates of tumor growth regardless of cancer type. But in mice treated with antibiotics, the tumor-promoting effects of smoke exposure were completely lost; the mice had rates of tumor growth even lower than controls.

This experiment was repeated with mice genetically engineered to lack an adaptive immune response. Regardless of smoke or antibiotic exposure, all mice had comparable rates of tumor growth.

Dr. Sharma offered a summary of the findings and their possible implications for human medicine.

“Cigarette smoking changes the gut microbiome, and this changed gut microbiome interacts with the immune system to affect cancer progression,” he said. “If we can target this changed microbiome with modulation strategies like antibiotics, probiotics, or administration of good bacteria, we can alter this process. And if the same results are found in human studies, it could go a long way to affect cancer outcomes in smokers.”

In addition to human studies, Dr. Sharma said that future research should aim to uncover the underlying mechanisms involved in this process, including the types of bacteria that play a role.

When asked if the study might lessen concerns about the negative impacts of smoking among cancer patients, Dr. Sharma suggested that, even if the findings do translate to humans, smoking would still carry significant health risks.

“Even if gut microbiome modulation strategies do work in these patients, it may help a little, but it’s not going to bring it down to the level of nonsmokers, so it’s no way an excuse to not fear or continue [smoking],” he said.

The study was funded by the Florida Department of Health. The investigators reported no conflicts of interest.

First responders to the site of the 2001 World Trade Center attack may have an elevated risk of nonalcoholic fatty liver disease (NAFLD), according to investigators.

In a retrospective look at 236 first responders presenting with gastrointestinal symptoms to the World Trade Center Health Program, 195 (82.6%) had NAFLD, compared with 24%-45% of the general population, reported lead author Mishal Reja, MD, of Robert Wood Johnson University Hospital, New Brunswick, N.J.

The increased rate of NAFLD among first responders is likely because of toxin exposure at ground zero, which can cause a subtype of NAFLD known as toxin-associated fatty liver disease (TAFLD), Dr. Reja wrote in an abstract released as part of the annual Digestive Disease Week^®, which was canceled because of COVID-19.

“I was not surprised [by these findings],” Dr. Reja said during a virtual press conference. “In the prior literature that did examine TAFLD, it did show that populations exposed to these specific chemicals ... at the ground zero site had extremely high rates – consistent with the rates we found in our study – of fatty liver disease.”

Dr. Reja said that 9/11 first responders were exposed to “many common toxins that are consistently in occupational and environmental toxicant literature.” In particular, he named polycyclic aromatic hydrocarbons and vinyl chloride.

“A lot of these toxins are ... included in industrial solvents as well as building demolition,” Dr. Reja said. “So they’ve been around for so long, and they’ve been studied for so long, [that we have] literature that shows these toxins are associated with fatty liver disease, which is how we arrived at the hypothesis in the first place.”

The first responders were stratified by roles, which were associated with varying levels of exposure. About 40% of individuals in the study were involved in moving debris from the site, a small group (4%) were involved in clean-up and maintenance, while approximately 30%-40% worked in more protected, administrative roles.

Comparing individuals in the study with TAFLD versus those without TAFLD revealed additional risk factors. Multivariate logistical regression analysis showed that obese individuals had a significantly increased risk of fatty liver disease, suggesting a synergistic effect.

“If you were exposed to these toxins in the World Trade Center, and you were obese, [then] you are actually between two to three times more likely to get [TAFLD],” Dr. Reja said, noting that hypertension and diabetes were also identified as independent risk factors.

Dr. Reja and colleagues are planning a prospective trial to investigate further. The study will likely involve 100-200 first responders with TAFLD, a similar number of individuals with NAFLD, and another group without liver disease.

The investigators reported no outside funding or conflicts of interest.

SOURCE: Reja M et al. DDW 2020, Abstracts available online May 2.

First responders to the site of the 2001 World Trade Center attack may have an elevated risk of nonalcoholic fatty liver disease (NAFLD), according to investigators.

In a retrospective look at 236 first responders presenting with gastrointestinal symptoms to the World Trade Center Health Program, 195 (82.6%) had NAFLD, compared with 24%-45% of the general population, reported lead author Mishal Reja, MD, of Robert Wood Johnson University Hospital, New Brunswick, N.J.

The increased rate of NAFLD among first responders is likely because of toxin exposure at ground zero, which can cause a subtype of NAFLD known as toxin-associated fatty liver disease (TAFLD), Dr. Reja wrote in an abstract released as part of the annual Digestive Disease Week^®, which was canceled because of COVID-19.

“I was not surprised [by these findings],” Dr. Reja said during a virtual press conference. “In the prior literature that did examine TAFLD, it did show that populations exposed to these specific chemicals ... at the ground zero site had extremely high rates – consistent with the rates we found in our study – of fatty liver disease.”

Dr. Reja said that 9/11 first responders were exposed to “many common toxins that are consistently in occupational and environmental toxicant literature.” In particular, he named polycyclic aromatic hydrocarbons and vinyl chloride.

“A lot of these toxins are ... included in industrial solvents as well as building demolition,” Dr. Reja said. “So they’ve been around for so long, and they’ve been studied for so long, [that we have] literature that shows these toxins are associated with fatty liver disease, which is how we arrived at the hypothesis in the first place.”

The first responders were stratified by roles, which were associated with varying levels of exposure. About 40% of individuals in the study were involved in moving debris from the site, a small group (4%) were involved in clean-up and maintenance, while approximately 30%-40% worked in more protected, administrative roles.

Comparing individuals in the study with TAFLD versus those without TAFLD revealed additional risk factors. Multivariate logistical regression analysis showed that obese individuals had a significantly increased risk of fatty liver disease, suggesting a synergistic effect.

“If you were exposed to these toxins in the World Trade Center, and you were obese, [then] you are actually between two to three times more likely to get [TAFLD],” Dr. Reja said, noting that hypertension and diabetes were also identified as independent risk factors.

Dr. Reja and colleagues are planning a prospective trial to investigate further. The study will likely involve 100-200 first responders with TAFLD, a similar number of individuals with NAFLD, and another group without liver disease.

The investigators reported no outside funding or conflicts of interest.

SOURCE: Reja M et al. DDW 2020, Abstracts available online May 2.

First responders to the site of the 2001 World Trade Center attack may have an elevated risk of nonalcoholic fatty liver disease (NAFLD), according to investigators.

In a retrospective look at 236 first responders presenting with gastrointestinal symptoms to the World Trade Center Health Program, 195 (82.6%) had NAFLD, compared with 24%-45% of the general population, reported lead author Mishal Reja, MD, of Robert Wood Johnson University Hospital, New Brunswick, N.J.

The increased rate of NAFLD among first responders is likely because of toxin exposure at ground zero, which can cause a subtype of NAFLD known as toxin-associated fatty liver disease (TAFLD), Dr. Reja wrote in an abstract released as part of the annual Digestive Disease Week^®, which was canceled because of COVID-19.

“I was not surprised [by these findings],” Dr. Reja said during a virtual press conference. “In the prior literature that did examine TAFLD, it did show that populations exposed to these specific chemicals ... at the ground zero site had extremely high rates – consistent with the rates we found in our study – of fatty liver disease.”

Dr. Reja said that 9/11 first responders were exposed to “many common toxins that are consistently in occupational and environmental toxicant literature.” In particular, he named polycyclic aromatic hydrocarbons and vinyl chloride.

“A lot of these toxins are ... included in industrial solvents as well as building demolition,” Dr. Reja said. “So they’ve been around for so long, and they’ve been studied for so long, [that we have] literature that shows these toxins are associated with fatty liver disease, which is how we arrived at the hypothesis in the first place.”

The first responders were stratified by roles, which were associated with varying levels of exposure. About 40% of individuals in the study were involved in moving debris from the site, a small group (4%) were involved in clean-up and maintenance, while approximately 30%-40% worked in more protected, administrative roles.

Comparing individuals in the study with TAFLD versus those without TAFLD revealed additional risk factors. Multivariate logistical regression analysis showed that obese individuals had a significantly increased risk of fatty liver disease, suggesting a synergistic effect.

“If you were exposed to these toxins in the World Trade Center, and you were obese, [then] you are actually between two to three times more likely to get [TAFLD],” Dr. Reja said, noting that hypertension and diabetes were also identified as independent risk factors.

Dr. Reja and colleagues are planning a prospective trial to investigate further. The study will likely involve 100-200 first responders with TAFLD, a similar number of individuals with NAFLD, and another group without liver disease.

The investigators reported no outside funding or conflicts of interest.

SOURCE: Reja M et al. DDW 2020, Abstracts available online May 2.

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

Help your patients understand their Crohn’s disease treatment options by sharing AGA patient education content at https://www.gastro.org/practice-guidance/gi-patient-center/topic/crohn-s-disease.  

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

Help your patients understand their Crohn’s disease treatment options by sharing AGA patient education content at https://www.gastro.org/practice-guidance/gi-patient-center/topic/crohn-s-disease.  

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

Help your patients understand their Crohn’s disease treatment options by sharing AGA patient education content at https://www.gastro.org/practice-guidance/gi-patient-center/topic/crohn-s-disease.  

Risk models that incorporate genetic and circulating biomarker data in addition to established risk factors may improve risk modeling for pancreatic cancer in the general population, according to investigators.

Identifying high-risk individuals could facilitate earlier disease detection, which is essential for curing pancreatic cancer, reported lead author Jihye Kim, PhD, of Harvard School of Public Health, Boston, and colleagues.

“Given the late stage at presentation for most patients with pancreatic cancer, earlier detection approaches are worthy of significant investment as a critical means to reduce mortality from pancreatic cancer, soon to be the second-leading cause of cancer death in the United States,” the investigators wrote in Cancer Epidemiology, Biomarkers & Prevention.

According to the investigators, a variety of risk factors for pancreatic cancer are well established and include clinical, demographic, and lifestyle factors, while recent studies have reported associations with genetic and circulating biomarkers.

“Although risk factors have been investigated individually, their joint contribution to risk discrimination remains largely unknown,” the investigators wrote.

To learn more, Dr. Kim and colleagues performed a nested case-control study in which 500 patients with primary pancreatic adenocarcinoma were matched with 1,091 healthy controls. Data were drawn from four prospective studies: the Nurses’ Health Study, the Health Professionals Follow-up Study, the Women’s Health Initiative Observational Study, and the Physicians’ Health Study I. Via these studies, cases provided blood samples prior to diagnosis with pancreatic cancer.

“Importantly, because all our subjects were enrolled in prospective cohorts, all risk factor data and circulating markers were measured before the cases’ diagnosis of pancreatic cancer,” the investigators wrote. “This design faithfully recapitulates the situation faced by primary care physicians, where decisions related to disease screening are made in the prediagnostic setting using data collected in the several years prior to cancer diagnosis.”

In the present study, the investigators collected patient data for a variety of risk factors, including clinical and lifestyle characteristics, circulating biomarkers such as interleukin-6 and proinsulin, and 22 single-nucleotide polymorphisms. Frequencies and distributions of these factors were used to develop three multivariate risk models: a clinical model, a clinical/genetic model, and a clinical/genetic/biomarker model. To determine absolute risk of pancreatic cancer, these three models were combined with U.S. epidemiologic data, including incidence and mortality rates.

Cross-validation showed that the risk models became increasingly accurate with each added dataset; the area under the curve increased from 0.55 for the clinical model to 0.61 for the clinical/genetic model and ultimately to 0.62 for the clinical/genetic/biomarker model. Consequently, each model identified a greater number of individuals with at least a threefold risk of pancreatic cancer over a 10-year period. For example, the clinical model identified 1.5% of women and 0.2% of men with at least threefold risk, whereas the model that also included genetic and biomarker data identified 2.6% of women and 3.7% of men.

Absolute risk modeling allowed for generation of risk stratification percentiles by age. Women in the 99th risk percentile had a 1.7% risk of developing pancreatic cancer by age 70 years, and a 3.6% risk by age 80. For men, the highest-risk group had a 2.0% risk of pancreatic cancer by age 70 years and a 3.8% risk by age 80. Conversely, both men and women in the 10th risk percentile had a 0.2% risk by age 70 years and a 0.4% risk by age 80.

“[T]he addition of genetic variants and circulating markers added discriminatory ability beyond clinical factors that could be solicited in a physician’s office,” the investigators wrote.

“Further refinement and validation in independent samples will be necessary to make these models clinically actionable and impact survival of patients with pancreatic cancer,” they concluded.

The study was supported by the National Institutes of Health. The investigators reported additional relationships with Bayer, Celgene, Eli Lilly, and others.

SOURCE: Kim J et al. Cancer Epidemiol Biomarkers Prev. 2020 Apr 22. doi: 10.1158/1055-9965.EPI-19-1389.

Risk models that incorporate genetic and circulating biomarker data in addition to established risk factors may improve risk modeling for pancreatic cancer in the general population, according to investigators.

Identifying high-risk individuals could facilitate earlier disease detection, which is essential for curing pancreatic cancer, reported lead author Jihye Kim, PhD, of Harvard School of Public Health, Boston, and colleagues.

“Given the late stage at presentation for most patients with pancreatic cancer, earlier detection approaches are worthy of significant investment as a critical means to reduce mortality from pancreatic cancer, soon to be the second-leading cause of cancer death in the United States,” the investigators wrote in Cancer Epidemiology, Biomarkers & Prevention.

According to the investigators, a variety of risk factors for pancreatic cancer are well established and include clinical, demographic, and lifestyle factors, while recent studies have reported associations with genetic and circulating biomarkers.

“Although risk factors have been investigated individually, their joint contribution to risk discrimination remains largely unknown,” the investigators wrote.

To learn more, Dr. Kim and colleagues performed a nested case-control study in which 500 patients with primary pancreatic adenocarcinoma were matched with 1,091 healthy controls. Data were drawn from four prospective studies: the Nurses’ Health Study, the Health Professionals Follow-up Study, the Women’s Health Initiative Observational Study, and the Physicians’ Health Study I. Via these studies, cases provided blood samples prior to diagnosis with pancreatic cancer.

“Importantly, because all our subjects were enrolled in prospective cohorts, all risk factor data and circulating markers were measured before the cases’ diagnosis of pancreatic cancer,” the investigators wrote. “This design faithfully recapitulates the situation faced by primary care physicians, where decisions related to disease screening are made in the prediagnostic setting using data collected in the several years prior to cancer diagnosis.”

In the present study, the investigators collected patient data for a variety of risk factors, including clinical and lifestyle characteristics, circulating biomarkers such as interleukin-6 and proinsulin, and 22 single-nucleotide polymorphisms. Frequencies and distributions of these factors were used to develop three multivariate risk models: a clinical model, a clinical/genetic model, and a clinical/genetic/biomarker model. To determine absolute risk of pancreatic cancer, these three models were combined with U.S. epidemiologic data, including incidence and mortality rates.

Cross-validation showed that the risk models became increasingly accurate with each added dataset; the area under the curve increased from 0.55 for the clinical model to 0.61 for the clinical/genetic model and ultimately to 0.62 for the clinical/genetic/biomarker model. Consequently, each model identified a greater number of individuals with at least a threefold risk of pancreatic cancer over a 10-year period. For example, the clinical model identified 1.5% of women and 0.2% of men with at least threefold risk, whereas the model that also included genetic and biomarker data identified 2.6% of women and 3.7% of men.

Absolute risk modeling allowed for generation of risk stratification percentiles by age. Women in the 99th risk percentile had a 1.7% risk of developing pancreatic cancer by age 70 years, and a 3.6% risk by age 80. For men, the highest-risk group had a 2.0% risk of pancreatic cancer by age 70 years and a 3.8% risk by age 80. Conversely, both men and women in the 10th risk percentile had a 0.2% risk by age 70 years and a 0.4% risk by age 80.

“[T]he addition of genetic variants and circulating markers added discriminatory ability beyond clinical factors that could be solicited in a physician’s office,” the investigators wrote.

“Further refinement and validation in independent samples will be necessary to make these models clinically actionable and impact survival of patients with pancreatic cancer,” they concluded.

The study was supported by the National Institutes of Health. The investigators reported additional relationships with Bayer, Celgene, Eli Lilly, and others.

SOURCE: Kim J et al. Cancer Epidemiol Biomarkers Prev. 2020 Apr 22. doi: 10.1158/1055-9965.EPI-19-1389.

Risk models that incorporate genetic and circulating biomarker data in addition to established risk factors may improve risk modeling for pancreatic cancer in the general population, according to investigators.

Identifying high-risk individuals could facilitate earlier disease detection, which is essential for curing pancreatic cancer, reported lead author Jihye Kim, PhD, of Harvard School of Public Health, Boston, and colleagues.

“Given the late stage at presentation for most patients with pancreatic cancer, earlier detection approaches are worthy of significant investment as a critical means to reduce mortality from pancreatic cancer, soon to be the second-leading cause of cancer death in the United States,” the investigators wrote in Cancer Epidemiology, Biomarkers & Prevention.

According to the investigators, a variety of risk factors for pancreatic cancer are well established and include clinical, demographic, and lifestyle factors, while recent studies have reported associations with genetic and circulating biomarkers.

“Although risk factors have been investigated individually, their joint contribution to risk discrimination remains largely unknown,” the investigators wrote.

To learn more, Dr. Kim and colleagues performed a nested case-control study in which 500 patients with primary pancreatic adenocarcinoma were matched with 1,091 healthy controls. Data were drawn from four prospective studies: the Nurses’ Health Study, the Health Professionals Follow-up Study, the Women’s Health Initiative Observational Study, and the Physicians’ Health Study I. Via these studies, cases provided blood samples prior to diagnosis with pancreatic cancer.

“Importantly, because all our subjects were enrolled in prospective cohorts, all risk factor data and circulating markers were measured before the cases’ diagnosis of pancreatic cancer,” the investigators wrote. “This design faithfully recapitulates the situation faced by primary care physicians, where decisions related to disease screening are made in the prediagnostic setting using data collected in the several years prior to cancer diagnosis.”

In the present study, the investigators collected patient data for a variety of risk factors, including clinical and lifestyle characteristics, circulating biomarkers such as interleukin-6 and proinsulin, and 22 single-nucleotide polymorphisms. Frequencies and distributions of these factors were used to develop three multivariate risk models: a clinical model, a clinical/genetic model, and a clinical/genetic/biomarker model. To determine absolute risk of pancreatic cancer, these three models were combined with U.S. epidemiologic data, including incidence and mortality rates.

Cross-validation showed that the risk models became increasingly accurate with each added dataset; the area under the curve increased from 0.55 for the clinical model to 0.61 for the clinical/genetic model and ultimately to 0.62 for the clinical/genetic/biomarker model. Consequently, each model identified a greater number of individuals with at least a threefold risk of pancreatic cancer over a 10-year period. For example, the clinical model identified 1.5% of women and 0.2% of men with at least threefold risk, whereas the model that also included genetic and biomarker data identified 2.6% of women and 3.7% of men.

Absolute risk modeling allowed for generation of risk stratification percentiles by age. Women in the 99th risk percentile had a 1.7% risk of developing pancreatic cancer by age 70 years, and a 3.6% risk by age 80. For men, the highest-risk group had a 2.0% risk of pancreatic cancer by age 70 years and a 3.8% risk by age 80. Conversely, both men and women in the 10th risk percentile had a 0.2% risk by age 70 years and a 0.4% risk by age 80.

“[T]he addition of genetic variants and circulating markers added discriminatory ability beyond clinical factors that could be solicited in a physician’s office,” the investigators wrote.

“Further refinement and validation in independent samples will be necessary to make these models clinically actionable and impact survival of patients with pancreatic cancer,” they concluded.

The study was supported by the National Institutes of Health. The investigators reported additional relationships with Bayer, Celgene, Eli Lilly, and others.

SOURCE: Kim J et al. Cancer Epidemiol Biomarkers Prev. 2020 Apr 22. doi: 10.1158/1055-9965.EPI-19-1389.

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

A novel biomarker may predict early responses to anti–tumor necrosis factor (TNF) therapy in patients with Crohn’s disease, according to investigators.

After 1 week of therapy with adalimumab, serum levels of citrullinated and matrix metalloproteinase-degraded vimentin (VICM) predicted early responses to treatment with an odds ratio of 42.5, reported lead author Joachim H. Mortensen, PhD, of Nordic Bioscience, Herlev, Denmark, and colleagues.

“VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients,” the investigators wrote in the Journal of Clinical Gastroenterology.This is an area of particular need, the investigators explained because 10%-40% of patients with Crohn’s disease have an inadequate response to anti-TNF therapy, yet early detection of treatment failure remains challenging.

According to the investigators, C-reactive protein (CRP) may serve as a reliable biomarker for acute inflammation, but intestinal tissue remodeling in Crohn’s disease is largely caused by chronic inflammation, which is driven by proteases. As these proteases degrade intestinal tissue, protein fragments called neo-epitopes are released into circulation, offering a potential biomarker of disease activity. Previous research showed that VICM, a neo-epitope that correlates with macrophage activity, was highly associated with Crohn’s disease.

“Because anti-TNF reduces the number of activated macrophages, we hypothesized that changes in VICM levels can be applied to monitor the outcome of early response to anti-TNF treatment in Crohn’s disease,” the investigators wrote.

To test this hypothesis, the investigators retrospectively analyzed clinical data and serum samples from 42 patients with Crohn’s disease, of whom 21 were treated with adalimumab at University Medical Center Groningen (the Netherlands) and 21 were treated with infliximab at Aarhus (Denmark) University Hospital. In both cohorts, disease activity was measured by the Harvey-Bradshaw Index, with responders defined by a score of less than 5, which indicates clinical remission. Harvey-Bradshaw Index scores were evaluated at week 8 and week 14 for the adalimumab and infliximab groups, respectively. In the adalimumab group, serum VICM and CRP levels were evaluated at baseline, then at weeks 1 and 8. In the infliximab group, VICM and CRP were measured at baseline, then at weeks 2, 6, and 14.

Patients responding to adalimumab had significantly lower levels of VICM than did nonresponders at week 1 (P = .007) and week 8 (P = .048). Although infliximab responders showed numerical differences in VICM, compared with nonresponders, at week 2 (P = .48), these differences lacked statistical significance until week 6 (P = .046), then lost significance again at week 14 (P = .23). No significant differences in CRP levels between responders and nonresponders were detected at any timepoints.

Using a receiver operating characteristic–curve analysis, the investigators identified a clinically relevant cutoff value for VICM at 12.5 ng/mL. With this cutoff, responders were identifiable as early as week 6 in the infliximab group with an area under the curve (AUC) of 0.89 (specificity, 75%; sensitivity, 88%; P less than .01). In the adalimumab group, responders were identifiable as early as week 1, with an AUC of 0.91 (specificity, 87%; sensitivity, 100%; P less than .01).

In the infliximab group, patients with a serum VICM level less than 12.5 ng/mL at week 6 were 22.5 times more likely to be responders (odds ratio, 22.5). Patients treated with adalimumab were 42 times more likely to be responders if their VICM level fell below the cutoff at week 1. A similar analysis involving CRP had no predictive value.

“In conclusion, the reduction in VICM serum levels, but not reduction in CRP levels, was associated with early response to [anti–TNF-alpha] treatment in patients with Crohn’s disease,” the investigators concluded. “Thus, VICM may help to facilitate early decision-making of the best possible treatment option for Crohn’s disease patients.”

The study was funded by the Danish Research Foundation. The investigators disclosed additional relationships with Nordic Bioscience.

SOURCE: Mortensen JH et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001341.

For patients diagnosed with mild acute pancreatitis (AP) in the ED, an observation pathway may significantly reduce hospitalization rate and associated costs without compromising patient safety or quality of care, according to investigators.

Over a 2-year period, the observation pathway at Beth Israel Deaconess Medical Center, Boston, reduced hospitalizations by 31.2%, reported lead author Awais Ahmed, MD, of Harvard Medical School, Boston, and colleagues.

“AP carries a significant burden on the health care system, accounting for the third most common reason for gastrointestinal-related admissions in the United States,” the investigators wrote in the Journal of Clinical Gastroenterology. “As such, streamlining care for AP patients to reduce admissions can reduce the associated financial burden.”

The investigators’ efforts to reduce admissions for patients with AP began in 2016, when they first implemented an observation pathway at Beth Israel. This 6-month pilot study demonstrated proof of concept because it reduced admissions by 22.2% and shortened average length of stay without negatively affecting rates of mortality or readmission.

Based on these encouraging results, the hospital implemented the observation pathway as a standard of care. The present study analyzed 2 years of data from patients diagnosed with AP following the end of the pilot study. The primary outcome was hospitalization rate. Secondary outcomes included health care utilization, 30-day mortality rate, 30-day readmission rate, and median length of stay.

Patients with mild AP entered the observation pathway at the discretion of the supervising clinician, as well as based on absence of exclusion criteria, such as end organ damage, chronic pancreatitis, cholangitis, and other considerations.

Over 2 years, 165 patients were diagnosed with AP in the ED, of whom 118 (71.5%) had mild AP. From this latter group, 54 (45.8%) entered the observation pathway, while 64 (54.2%) were admitted as inpatients, primarily (n = 58) because of exclusion criteria. Within the observation group, 45 out of 54 patients (83.3%) successfully completed the pathway and were discharged. Six of these patients were readmitted within 30 days. Among the 9 patients who did not complete the pathway, 6 failed to meet discharge criteria, resulting in admission, whereas 3 patients left the hospital against medical advice.

Combining data from this 2-year period and the pilot study, the hospitalization rate for mild AP was reduced by 31.2%. In the present study, hospitalization was reduced by 27% for patients with AP of any severity. This figure was steady over a 3-year period, at 25.8%.

Median length of stay for patients with mild AP was significantly shorter in the present study’s observation pathway than in a historical cohort (19.9 vs. 72.0 hours); this remained significant when also including patients from the pilot study (21.2 vs. 72.0 hours). Compared with the historic cohort, patients in the observation had significantly fewer radiographic studies, and more patients were discharged in less than 24 hours. Meanwhile, 30-day readmission and mortality rates remained unchanged.

“In summary, our long-term data of a single center emergency department–based observation management pathway for mild AP demonstrates durability over more than 2 years in maintaining its objective of reducing hospitalization,” the investigators concluded. “This is associated with a [shorter] length of stay, and reduced health care resource utilization, suggesting a possible decrease in financial cost of managing mild AP, without affecting readmission rates or mortality.”

These findings encourage further research, the investigators suggested, while noting that the observation pathway may not be appropriate for all treatment centers.

“The generalizability of the pathway is limited, given its single center location, and tertiary environment,” the investigators wrote. “Smaller hospitals, lacking multidisciplinary support for complications of AP, may find it challenging to implement such a pathway, and thus triage these patients for inpatient admission at their facility or to nearby tertiary centers.”The investigators reported no conflicts of interest.

SOURCE: Ahmed A et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001354.

Visit the AGA GI Patient Center for information on pancreatitis to share with your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

For patients diagnosed with mild acute pancreatitis (AP) in the ED, an observation pathway may significantly reduce hospitalization rate and associated costs without compromising patient safety or quality of care, according to investigators.

Over a 2-year period, the observation pathway at Beth Israel Deaconess Medical Center, Boston, reduced hospitalizations by 31.2%, reported lead author Awais Ahmed, MD, of Harvard Medical School, Boston, and colleagues.

“AP carries a significant burden on the health care system, accounting for the third most common reason for gastrointestinal-related admissions in the United States,” the investigators wrote in the Journal of Clinical Gastroenterology. “As such, streamlining care for AP patients to reduce admissions can reduce the associated financial burden.”

The investigators’ efforts to reduce admissions for patients with AP began in 2016, when they first implemented an observation pathway at Beth Israel. This 6-month pilot study demonstrated proof of concept because it reduced admissions by 22.2% and shortened average length of stay without negatively affecting rates of mortality or readmission.

Based on these encouraging results, the hospital implemented the observation pathway as a standard of care. The present study analyzed 2 years of data from patients diagnosed with AP following the end of the pilot study. The primary outcome was hospitalization rate. Secondary outcomes included health care utilization, 30-day mortality rate, 30-day readmission rate, and median length of stay.

Patients with mild AP entered the observation pathway at the discretion of the supervising clinician, as well as based on absence of exclusion criteria, such as end organ damage, chronic pancreatitis, cholangitis, and other considerations.

Over 2 years, 165 patients were diagnosed with AP in the ED, of whom 118 (71.5%) had mild AP. From this latter group, 54 (45.8%) entered the observation pathway, while 64 (54.2%) were admitted as inpatients, primarily (n = 58) because of exclusion criteria. Within the observation group, 45 out of 54 patients (83.3%) successfully completed the pathway and were discharged. Six of these patients were readmitted within 30 days. Among the 9 patients who did not complete the pathway, 6 failed to meet discharge criteria, resulting in admission, whereas 3 patients left the hospital against medical advice.

Combining data from this 2-year period and the pilot study, the hospitalization rate for mild AP was reduced by 31.2%. In the present study, hospitalization was reduced by 27% for patients with AP of any severity. This figure was steady over a 3-year period, at 25.8%.

Median length of stay for patients with mild AP was significantly shorter in the present study’s observation pathway than in a historical cohort (19.9 vs. 72.0 hours); this remained significant when also including patients from the pilot study (21.2 vs. 72.0 hours). Compared with the historic cohort, patients in the observation had significantly fewer radiographic studies, and more patients were discharged in less than 24 hours. Meanwhile, 30-day readmission and mortality rates remained unchanged.

“In summary, our long-term data of a single center emergency department–based observation management pathway for mild AP demonstrates durability over more than 2 years in maintaining its objective of reducing hospitalization,” the investigators concluded. “This is associated with a [shorter] length of stay, and reduced health care resource utilization, suggesting a possible decrease in financial cost of managing mild AP, without affecting readmission rates or mortality.”

These findings encourage further research, the investigators suggested, while noting that the observation pathway may not be appropriate for all treatment centers.

“The generalizability of the pathway is limited, given its single center location, and tertiary environment,” the investigators wrote. “Smaller hospitals, lacking multidisciplinary support for complications of AP, may find it challenging to implement such a pathway, and thus triage these patients for inpatient admission at their facility or to nearby tertiary centers.”The investigators reported no conflicts of interest.

SOURCE: Ahmed A et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001354.

Visit the AGA GI Patient Center for information on pancreatitis to share with your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

For patients diagnosed with mild acute pancreatitis (AP) in the ED, an observation pathway may significantly reduce hospitalization rate and associated costs without compromising patient safety or quality of care, according to investigators.

Over a 2-year period, the observation pathway at Beth Israel Deaconess Medical Center, Boston, reduced hospitalizations by 31.2%, reported lead author Awais Ahmed, MD, of Harvard Medical School, Boston, and colleagues.

“AP carries a significant burden on the health care system, accounting for the third most common reason for gastrointestinal-related admissions in the United States,” the investigators wrote in the Journal of Clinical Gastroenterology. “As such, streamlining care for AP patients to reduce admissions can reduce the associated financial burden.”

The investigators’ efforts to reduce admissions for patients with AP began in 2016, when they first implemented an observation pathway at Beth Israel. This 6-month pilot study demonstrated proof of concept because it reduced admissions by 22.2% and shortened average length of stay without negatively affecting rates of mortality or readmission.

Based on these encouraging results, the hospital implemented the observation pathway as a standard of care. The present study analyzed 2 years of data from patients diagnosed with AP following the end of the pilot study. The primary outcome was hospitalization rate. Secondary outcomes included health care utilization, 30-day mortality rate, 30-day readmission rate, and median length of stay.

Patients with mild AP entered the observation pathway at the discretion of the supervising clinician, as well as based on absence of exclusion criteria, such as end organ damage, chronic pancreatitis, cholangitis, and other considerations.

Over 2 years, 165 patients were diagnosed with AP in the ED, of whom 118 (71.5%) had mild AP. From this latter group, 54 (45.8%) entered the observation pathway, while 64 (54.2%) were admitted as inpatients, primarily (n = 58) because of exclusion criteria. Within the observation group, 45 out of 54 patients (83.3%) successfully completed the pathway and were discharged. Six of these patients were readmitted within 30 days. Among the 9 patients who did not complete the pathway, 6 failed to meet discharge criteria, resulting in admission, whereas 3 patients left the hospital against medical advice.

Combining data from this 2-year period and the pilot study, the hospitalization rate for mild AP was reduced by 31.2%. In the present study, hospitalization was reduced by 27% for patients with AP of any severity. This figure was steady over a 3-year period, at 25.8%.

Median length of stay for patients with mild AP was significantly shorter in the present study’s observation pathway than in a historical cohort (19.9 vs. 72.0 hours); this remained significant when also including patients from the pilot study (21.2 vs. 72.0 hours). Compared with the historic cohort, patients in the observation had significantly fewer radiographic studies, and more patients were discharged in less than 24 hours. Meanwhile, 30-day readmission and mortality rates remained unchanged.

“In summary, our long-term data of a single center emergency department–based observation management pathway for mild AP demonstrates durability over more than 2 years in maintaining its objective of reducing hospitalization,” the investigators concluded. “This is associated with a [shorter] length of stay, and reduced health care resource utilization, suggesting a possible decrease in financial cost of managing mild AP, without affecting readmission rates or mortality.”

These findings encourage further research, the investigators suggested, while noting that the observation pathway may not be appropriate for all treatment centers.

“The generalizability of the pathway is limited, given its single center location, and tertiary environment,” the investigators wrote. “Smaller hospitals, lacking multidisciplinary support for complications of AP, may find it challenging to implement such a pathway, and thus triage these patients for inpatient admission at their facility or to nearby tertiary centers.”The investigators reported no conflicts of interest.

SOURCE: Ahmed A et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001354.

Visit the AGA GI Patient Center for information on pancreatitis to share with your patients at https://www.gastro.org/practice-guidance/gi-patient-center/topic/pancreatitis.

For patients diagnosed with mild acute pancreatitis (AP) in the ED, an observation pathway may significantly reduce hospitalization rate and associated costs without compromising patient safety or quality of care, according to investigators.

Over a 2-year period, the observation pathway at Beth Israel Deaconess Medical Center, Boston, reduced hospitalizations by 31.2%, reported lead author Awais Ahmed, MD, of Harvard Medical School, Boston, and colleagues.

“AP carries a significant burden on the health care system, accounting for the third most common reason for gastrointestinal-related admissions in the United States,” the investigators wrote in the Journal of Clinical Gastroenterology. “As such, streamlining care for AP patients to reduce admissions can reduce the associated financial burden.”

The investigators’ efforts to reduce admissions for patients with AP began in 2016, when they first implemented an observation pathway at Beth Israel. This 6-month pilot study demonstrated proof of concept because it reduced admissions by 22.2% and shortened average length of stay without negatively affecting rates of mortality or readmission.

Based on these encouraging results, the hospital implemented the observation pathway as a standard of care. The present study analyzed 2 years of data from patients diagnosed with AP following the end of the pilot study. The primary outcome was hospitalization rate. Secondary outcomes included health care utilization, 30-day mortality rate, 30-day readmission rate, and median length of stay.

Patients with mild AP entered the observation pathway at the discretion of the supervising clinician, as well as based on absence of exclusion criteria, such as end organ damage, chronic pancreatitis, cholangitis, and other considerations.

Over 2 years, 165 patients were diagnosed with AP in the ED, of whom 118 (71.5%) had mild AP. From this latter group, 54 (45.8%) entered the observation pathway, while 64 (54.2%) were admitted as inpatients, primarily (n = 58) because of exclusion criteria. Within the observation group, 45 out of 54 patients (83.3%) successfully completed the pathway and were discharged. Six of these patients were readmitted within 30 days. Among the 9 patients who did not complete the pathway, 6 failed to meet discharge criteria, resulting in admission, whereas 3 patients left the hospital against medical advice.

Combining data from this 2-year period and the pilot study, the hospitalization rate for mild AP was reduced by 31.2%. In the present study, hospitalization was reduced by 27% for patients with AP of any severity. This figure was steady over a 3-year period, at 25.8%.

Median length of stay for patients with mild AP was significantly shorter in the present study’s observation pathway than in a historical cohort (19.9 vs. 72.0 hours); this remained significant when also including patients from the pilot study (21.2 vs. 72.0 hours). Compared with the historic cohort, patients in the observation had significantly fewer radiographic studies, and more patients were discharged in less than 24 hours. Meanwhile, 30-day readmission and mortality rates remained unchanged.

“In summary, our long-term data of a single center emergency department–based observation management pathway for mild AP demonstrates durability over more than 2 years in maintaining its objective of reducing hospitalization,” the investigators concluded. “This is associated with a [shorter] length of stay, and reduced health care resource utilization, suggesting a possible decrease in financial cost of managing mild AP, without affecting readmission rates or mortality.”

These findings encourage further research, the investigators suggested, while noting that the observation pathway may not be appropriate for all treatment centers.

“The generalizability of the pathway is limited, given its single center location, and tertiary environment,” the investigators wrote. “Smaller hospitals, lacking multidisciplinary support for complications of AP, may find it challenging to implement such a pathway, and thus triage these patients for inpatient admission at their facility or to nearby tertiary centers.”The investigators reported no conflicts of interest.

SOURCE: Ahmed A et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001354.

For patients diagnosed with mild acute pancreatitis (AP) in the ED, an observation pathway may significantly reduce hospitalization rate and associated costs without compromising patient safety or quality of care, according to investigators.

Over a 2-year period, the observation pathway at Beth Israel Deaconess Medical Center, Boston, reduced hospitalizations by 31.2%, reported lead author Awais Ahmed, MD, of Harvard Medical School, Boston, and colleagues.

“AP carries a significant burden on the health care system, accounting for the third most common reason for gastrointestinal-related admissions in the United States,” the investigators wrote in the Journal of Clinical Gastroenterology. “As such, streamlining care for AP patients to reduce admissions can reduce the associated financial burden.”

The investigators’ efforts to reduce admissions for patients with AP began in 2016, when they first implemented an observation pathway at Beth Israel. This 6-month pilot study demonstrated proof of concept because it reduced admissions by 22.2% and shortened average length of stay without negatively affecting rates of mortality or readmission.

Based on these encouraging results, the hospital implemented the observation pathway as a standard of care. The present study analyzed 2 years of data from patients diagnosed with AP following the end of the pilot study. The primary outcome was hospitalization rate. Secondary outcomes included health care utilization, 30-day mortality rate, 30-day readmission rate, and median length of stay.

Patients with mild AP entered the observation pathway at the discretion of the supervising clinician, as well as based on absence of exclusion criteria, such as end organ damage, chronic pancreatitis, cholangitis, and other considerations.

Over 2 years, 165 patients were diagnosed with AP in the ED, of whom 118 (71.5%) had mild AP. From this latter group, 54 (45.8%) entered the observation pathway, while 64 (54.2%) were admitted as inpatients, primarily (n = 58) because of exclusion criteria. Within the observation group, 45 out of 54 patients (83.3%) successfully completed the pathway and were discharged. Six of these patients were readmitted within 30 days. Among the 9 patients who did not complete the pathway, 6 failed to meet discharge criteria, resulting in admission, whereas 3 patients left the hospital against medical advice.

Combining data from this 2-year period and the pilot study, the hospitalization rate for mild AP was reduced by 31.2%. In the present study, hospitalization was reduced by 27% for patients with AP of any severity. This figure was steady over a 3-year period, at 25.8%.

Median length of stay for patients with mild AP was significantly shorter in the present study’s observation pathway than in a historical cohort (19.9 vs. 72.0 hours); this remained significant when also including patients from the pilot study (21.2 vs. 72.0 hours). Compared with the historic cohort, patients in the observation had significantly fewer radiographic studies, and more patients were discharged in less than 24 hours. Meanwhile, 30-day readmission and mortality rates remained unchanged.

“In summary, our long-term data of a single center emergency department–based observation management pathway for mild AP demonstrates durability over more than 2 years in maintaining its objective of reducing hospitalization,” the investigators concluded. “This is associated with a [shorter] length of stay, and reduced health care resource utilization, suggesting a possible decrease in financial cost of managing mild AP, without affecting readmission rates or mortality.”

These findings encourage further research, the investigators suggested, while noting that the observation pathway may not be appropriate for all treatment centers.

“The generalizability of the pathway is limited, given its single center location, and tertiary environment,” the investigators wrote. “Smaller hospitals, lacking multidisciplinary support for complications of AP, may find it challenging to implement such a pathway, and thus triage these patients for inpatient admission at their facility or to nearby tertiary centers.”The investigators reported no conflicts of interest.

SOURCE: Ahmed A et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001354.

For patients diagnosed with mild acute pancreatitis (AP) in the ED, an observation pathway may significantly reduce hospitalization rate and associated costs without compromising patient safety or quality of care, according to investigators.

Over a 2-year period, the observation pathway at Beth Israel Deaconess Medical Center, Boston, reduced hospitalizations by 31.2%, reported lead author Awais Ahmed, MD, of Harvard Medical School, Boston, and colleagues.

“AP carries a significant burden on the health care system, accounting for the third most common reason for gastrointestinal-related admissions in the United States,” the investigators wrote in the Journal of Clinical Gastroenterology. “As such, streamlining care for AP patients to reduce admissions can reduce the associated financial burden.”

The investigators’ efforts to reduce admissions for patients with AP began in 2016, when they first implemented an observation pathway at Beth Israel. This 6-month pilot study demonstrated proof of concept because it reduced admissions by 22.2% and shortened average length of stay without negatively affecting rates of mortality or readmission.

Based on these encouraging results, the hospital implemented the observation pathway as a standard of care. The present study analyzed 2 years of data from patients diagnosed with AP following the end of the pilot study. The primary outcome was hospitalization rate. Secondary outcomes included health care utilization, 30-day mortality rate, 30-day readmission rate, and median length of stay.

Patients with mild AP entered the observation pathway at the discretion of the supervising clinician, as well as based on absence of exclusion criteria, such as end organ damage, chronic pancreatitis, cholangitis, and other considerations.

Over 2 years, 165 patients were diagnosed with AP in the ED, of whom 118 (71.5%) had mild AP. From this latter group, 54 (45.8%) entered the observation pathway, while 64 (54.2%) were admitted as inpatients, primarily (n = 58) because of exclusion criteria. Within the observation group, 45 out of 54 patients (83.3%) successfully completed the pathway and were discharged. Six of these patients were readmitted within 30 days. Among the 9 patients who did not complete the pathway, 6 failed to meet discharge criteria, resulting in admission, whereas 3 patients left the hospital against medical advice.

Combining data from this 2-year period and the pilot study, the hospitalization rate for mild AP was reduced by 31.2%. In the present study, hospitalization was reduced by 27% for patients with AP of any severity. This figure was steady over a 3-year period, at 25.8%.

Median length of stay for patients with mild AP was significantly shorter in the present study’s observation pathway than in a historical cohort (19.9 vs. 72.0 hours); this remained significant when also including patients from the pilot study (21.2 vs. 72.0 hours). Compared with the historic cohort, patients in the observation had significantly fewer radiographic studies, and more patients were discharged in less than 24 hours. Meanwhile, 30-day readmission and mortality rates remained unchanged.

“In summary, our long-term data of a single center emergency department–based observation management pathway for mild AP demonstrates durability over more than 2 years in maintaining its objective of reducing hospitalization,” the investigators concluded. “This is associated with a [shorter] length of stay, and reduced health care resource utilization, suggesting a possible decrease in financial cost of managing mild AP, without affecting readmission rates or mortality.”

These findings encourage further research, the investigators suggested, while noting that the observation pathway may not be appropriate for all treatment centers.

“The generalizability of the pathway is limited, given its single center location, and tertiary environment,” the investigators wrote. “Smaller hospitals, lacking multidisciplinary support for complications of AP, may find it challenging to implement such a pathway, and thus triage these patients for inpatient admission at their facility or to nearby tertiary centers.”The investigators reported no conflicts of interest.

SOURCE: Ahmed A et al. J Clin Gastroenterol. 2020 Apr 14. doi: 10.1097/MCG.0000000000001354.

The European Society for Medical Oncology (ESMO) has published guidelines for managing patients with gastrointestinal cancers during the COVID-19 pandemic, helping clinicians identify patients who require immediate care and those for whom treatment can wait.

The guidelines are part of an ESMO-led initiative to address pandemic-related clinical issues. ESMO has released recommendations for solid tumors and hematologic malignancies that were drafted by leading experts representing almost 60 research centers.

According to Florian Lordick, MD, PhD, ESMO director of education and professor of oncology at the University of Leipzig Medical Center, Germany, the effort was a response to clinician requests from around the world.

“Many physicians … in their centers, in their countries, would appreciate some guidance [regarding] how to act and how to react in this crisis,” Dr. Lordick said in an interview.

“This situation is very heterogenous,” he noted. “Even within Europe, even within some countries, some [health care providers] have very limited resources. ... Others can almost do their job as usual, so it’s not easy to give recommendations today that are exactly valid for everyone.”
 

Prioritizing patients and interventions

To account for disparities across countries, the ESMO guidelines are categorized by patient tiers, including low, medium, and high priority, as determined by the Cancer Care Ontario, Huntsman Cancer Institute and Magnitude of Clinical Benefit Scale. The scale incorporates both patient factors and benefits of intervention.

High-priority patients are in life-threatening condition, and delaying care would jeopardize their survival and/or quality of life. Medium-priority patients are noncritical, but delaying intervention beyond 6 weeks could affect outcomes. Low-priority patients are clinically stable, and delaying intervention would not affect their quality of life and/or survival.

ESMO’s guidelines for gastrointestinal cancers include recommendations for colorectal cancer, hepatocellular carcinoma, gastroesophageal tumors, and pancreatic cancer. The recommendations encompass outpatient visits, imaging and radiological/endoscopic interventions, surgical procedures, medical oncology, and radiotherapy.

According to Dr. Lordick, many patients with pancreatic cancer or gastroesophageal tumors have clinical needs that cannot wait, and the guidelines reflect that.

“We are dealing here with two cancer types that are highly aggressive, that have high mortality if not treated adequately,” Dr. Lordick said. “So we have to say that whenever there is a suspicion for one of these cancers, we put the diagnosis and staging – including imaging of these cancers – into high priority. We think, with these cancers, people cannot wait. We know that it may be difficult in some systems, but if there is a suspicion [of a pancreatic tumor], then it’s not a situation where you could wait for 6 or 8 weeks.”

Radiological diagnostic workup of suspected hepatocellular carcinoma is also a high priority, according to the guidelines. However, diagnostic imaging and endoscopy are considered medium-priority interventions for clinically suspected colorectal cancer or for patients at high risk of colorectal cancer.

The lowest-priority patients are those in the survivorship group without symptoms, Dr. Lordick said, noting that these patients are eligible for delayed or remote consultation.
 

Professionalism, preparedness, and patient empowerment

More generally, Dr. Lordick urged oncologists to maintain a high level of professionalism and preparedness during the pandemic.

“I think a good center really tries to create areas that are COVID-free for their cancer patients,” he said. “They try to see as soon as possible if someone is at risk of having an infection, to test these patients early, to isolate them from the other patients.”

Dr. Lordick also emphasized the importance of patient empowerment.

“Really give [patients] all the information – what they can do to protect themselves from infection, including all the things that are usually recommended, like hygiene of the hands, avoiding social contact, reporting quickly if they have symptoms,” he said. “That is something we find really important – the patient empowerment.”

To that end, the ESMO team also created a comprehensive patient guide to help those with cancer navigate the pandemic.

All of these resources are the result of a major collaboration by guideline experts from around the world, Dr. Lordick said. He expressed gratitude for their work, which was performed without pay, under a tight deadline, and often following a full day in the clinic. From concept to publication, the recommendations were completed in 14 days.“To be honest, I’m a bit surprised, even a bit proud of what people did in a short period of time,” Dr. Lordick said.He reported no conflicts of interest.

SOURCE: ESMO. April 2020. Cancer Patient Management During the COVID-19 Pandemic

The European Society for Medical Oncology (ESMO) has published guidelines for managing patients with gastrointestinal cancers during the COVID-19 pandemic, helping clinicians identify patients who require immediate care and those for whom treatment can wait.

The guidelines are part of an ESMO-led initiative to address pandemic-related clinical issues. ESMO has released recommendations for solid tumors and hematologic malignancies that were drafted by leading experts representing almost 60 research centers.

According to Florian Lordick, MD, PhD, ESMO director of education and professor of oncology at the University of Leipzig Medical Center, Germany, the effort was a response to clinician requests from around the world.

“Many physicians … in their centers, in their countries, would appreciate some guidance [regarding] how to act and how to react in this crisis,” Dr. Lordick said in an interview.

“This situation is very heterogenous,” he noted. “Even within Europe, even within some countries, some [health care providers] have very limited resources. ... Others can almost do their job as usual, so it’s not easy to give recommendations today that are exactly valid for everyone.”
 

Prioritizing patients and interventions

To account for disparities across countries, the ESMO guidelines are categorized by patient tiers, including low, medium, and high priority, as determined by the Cancer Care Ontario, Huntsman Cancer Institute and Magnitude of Clinical Benefit Scale. The scale incorporates both patient factors and benefits of intervention.

High-priority patients are in life-threatening condition, and delaying care would jeopardize their survival and/or quality of life. Medium-priority patients are noncritical, but delaying intervention beyond 6 weeks could affect outcomes. Low-priority patients are clinically stable, and delaying intervention would not affect their quality of life and/or survival.

ESMO’s guidelines for gastrointestinal cancers include recommendations for colorectal cancer, hepatocellular carcinoma, gastroesophageal tumors, and pancreatic cancer. The recommendations encompass outpatient visits, imaging and radiological/endoscopic interventions, surgical procedures, medical oncology, and radiotherapy.

According to Dr. Lordick, many patients with pancreatic cancer or gastroesophageal tumors have clinical needs that cannot wait, and the guidelines reflect that.

“We are dealing here with two cancer types that are highly aggressive, that have high mortality if not treated adequately,” Dr. Lordick said. “So we have to say that whenever there is a suspicion for one of these cancers, we put the diagnosis and staging – including imaging of these cancers – into high priority. We think, with these cancers, people cannot wait. We know that it may be difficult in some systems, but if there is a suspicion [of a pancreatic tumor], then it’s not a situation where you could wait for 6 or 8 weeks.”

Radiological diagnostic workup of suspected hepatocellular carcinoma is also a high priority, according to the guidelines. However, diagnostic imaging and endoscopy are considered medium-priority interventions for clinically suspected colorectal cancer or for patients at high risk of colorectal cancer.

The lowest-priority patients are those in the survivorship group without symptoms, Dr. Lordick said, noting that these patients are eligible for delayed or remote consultation.
 

Professionalism, preparedness, and patient empowerment

More generally, Dr. Lordick urged oncologists to maintain a high level of professionalism and preparedness during the pandemic.

“I think a good center really tries to create areas that are COVID-free for their cancer patients,” he said. “They try to see as soon as possible if someone is at risk of having an infection, to test these patients early, to isolate them from the other patients.”

Dr. Lordick also emphasized the importance of patient empowerment.

“Really give [patients] all the information – what they can do to protect themselves from infection, including all the things that are usually recommended, like hygiene of the hands, avoiding social contact, reporting quickly if they have symptoms,” he said. “That is something we find really important – the patient empowerment.”

To that end, the ESMO team also created a comprehensive patient guide to help those with cancer navigate the pandemic.

All of these resources are the result of a major collaboration by guideline experts from around the world, Dr. Lordick said. He expressed gratitude for their work, which was performed without pay, under a tight deadline, and often following a full day in the clinic. From concept to publication, the recommendations were completed in 14 days.“To be honest, I’m a bit surprised, even a bit proud of what people did in a short period of time,” Dr. Lordick said.He reported no conflicts of interest.

SOURCE: ESMO. April 2020. Cancer Patient Management During the COVID-19 Pandemic

The European Society for Medical Oncology (ESMO) has published guidelines for managing patients with gastrointestinal cancers during the COVID-19 pandemic, helping clinicians identify patients who require immediate care and those for whom treatment can wait.

The guidelines are part of an ESMO-led initiative to address pandemic-related clinical issues. ESMO has released recommendations for solid tumors and hematologic malignancies that were drafted by leading experts representing almost 60 research centers.

According to Florian Lordick, MD, PhD, ESMO director of education and professor of oncology at the University of Leipzig Medical Center, Germany, the effort was a response to clinician requests from around the world.

“Many physicians … in their centers, in their countries, would appreciate some guidance [regarding] how to act and how to react in this crisis,” Dr. Lordick said in an interview.

“This situation is very heterogenous,” he noted. “Even within Europe, even within some countries, some [health care providers] have very limited resources. ... Others can almost do their job as usual, so it’s not easy to give recommendations today that are exactly valid for everyone.”
 

Prioritizing patients and interventions

To account for disparities across countries, the ESMO guidelines are categorized by patient tiers, including low, medium, and high priority, as determined by the Cancer Care Ontario, Huntsman Cancer Institute and Magnitude of Clinical Benefit Scale. The scale incorporates both patient factors and benefits of intervention.

High-priority patients are in life-threatening condition, and delaying care would jeopardize their survival and/or quality of life. Medium-priority patients are noncritical, but delaying intervention beyond 6 weeks could affect outcomes. Low-priority patients are clinically stable, and delaying intervention would not affect their quality of life and/or survival.

ESMO’s guidelines for gastrointestinal cancers include recommendations for colorectal cancer, hepatocellular carcinoma, gastroesophageal tumors, and pancreatic cancer. The recommendations encompass outpatient visits, imaging and radiological/endoscopic interventions, surgical procedures, medical oncology, and radiotherapy.

According to Dr. Lordick, many patients with pancreatic cancer or gastroesophageal tumors have clinical needs that cannot wait, and the guidelines reflect that.

“We are dealing here with two cancer types that are highly aggressive, that have high mortality if not treated adequately,” Dr. Lordick said. “So we have to say that whenever there is a suspicion for one of these cancers, we put the diagnosis and staging – including imaging of these cancers – into high priority. We think, with these cancers, people cannot wait. We know that it may be difficult in some systems, but if there is a suspicion [of a pancreatic tumor], then it’s not a situation where you could wait for 6 or 8 weeks.”

Radiological diagnostic workup of suspected hepatocellular carcinoma is also a high priority, according to the guidelines. However, diagnostic imaging and endoscopy are considered medium-priority interventions for clinically suspected colorectal cancer or for patients at high risk of colorectal cancer.

The lowest-priority patients are those in the survivorship group without symptoms, Dr. Lordick said, noting that these patients are eligible for delayed or remote consultation.
 

Professionalism, preparedness, and patient empowerment

More generally, Dr. Lordick urged oncologists to maintain a high level of professionalism and preparedness during the pandemic.

“I think a good center really tries to create areas that are COVID-free for their cancer patients,” he said. “They try to see as soon as possible if someone is at risk of having an infection, to test these patients early, to isolate them from the other patients.”

Dr. Lordick also emphasized the importance of patient empowerment.

“Really give [patients] all the information – what they can do to protect themselves from infection, including all the things that are usually recommended, like hygiene of the hands, avoiding social contact, reporting quickly if they have symptoms,” he said. “That is something we find really important – the patient empowerment.”

To that end, the ESMO team also created a comprehensive patient guide to help those with cancer navigate the pandemic.

All of these resources are the result of a major collaboration by guideline experts from around the world, Dr. Lordick said. He expressed gratitude for their work, which was performed without pay, under a tight deadline, and often following a full day in the clinic. From concept to publication, the recommendations were completed in 14 days.“To be honest, I’m a bit surprised, even a bit proud of what people did in a short period of time,” Dr. Lordick said.He reported no conflicts of interest.

SOURCE: ESMO. April 2020. Cancer Patient Management During the COVID-19 Pandemic

Patients with inflammatory bowel disease (IBD) may benefit from biotin supplementation, according to a preclinical study.

In mice, biotin supplementation delayed onset of colitis, minimized pathology, and accelerated healing, reported lead author Jonathan Skupsky, MD, of the University of California, Irvine, and colleagues.

“Biotin deficiency often is overlooked in the setting of IBD and there have been several reports of biotin deficiency in patients with IBD,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

In addition to these clinical reports, Dr. Skupsky and colleagues were motivated by their previous research, which showed that, in mice, knockout of the sodium-dependent multivitamin transporter (SMVT) for intestinal biotin uptake led to intestinal inflammation and dysplasia, thereby adding evidence that IBD and biotin could be linked.

In the present study, the investigators first compared mice fed a biotin-deficient diet with those fed a biotin-rich diet. Mice lacking biotin developed alopecia and weight loss within 7 weeks, and over time, stool that was soft and bloody. At week 14, mice fed the biotin-deficient diet had intestinal inflammation, based on elevated fecal calprotectin levels. In contrast, mice fed a biotin-rich diet had no gastrointestinal pathology.

“Although no mouse model entirely recapitulates patients with IBD, this model reproduces many of the findings including weight loss, bloody diarrhea, increased fecal calprotectin, altered crypt architecture, and infiltration of neutrophils and lymphocytes to the mucosa and submucosa,” the investigators wrote.

After this experiment, another group of mice were given drinking water with 3% dextran sodium sulfate (DSS), which induced severe colitis within 7 days. The distal colons of these mice had reduced expression of SMVT, the biotin transporter. This finding was also observed in biopsy samples from patients with ulcerative colitis, suggesting a shared pathway.

“This raises the possibility that [the biotin transport pathway] could be a target for therapy,” the investigators wrote.

Next the investigators tested the effect of prophylactic biotin supplementation in mice receiving 1.5% DSS in drinking water. Compared with mice that went without biotin, those that received a week of supplementation before DSS challenge had delayed, milder colitis, with histologic findings and fecal calprotectin levels that approximated those of healthy controls.

In a similar experiment, two groups of mice were given DSS for 7 days, then water or water plus biotin. Those in the biotin group recovered faster and more completely, again with clinical and histologic findings that was close to controls.

According to the investigators, these findings suggest that biotin may be able to protect against development of colitis and speed healing during early remission.

Further experiments dove deeper into cellular processes and molecular mechanisms, ultimately revealing that biotin supplementation reduced activation of NF-kappaB, which led to decreased intestinal permeability and inflammatory cytokines.

“The specific mechanism(s) linking biotin and NF-kappaB is unclear but could be mediated via the different cellular pathways that are affected by biotin availability,” the investigators wrote.

They noted that IBD is a complex condition, which can make it difficult to accurately model the disease; however, they also suggested that the findings are compelling enough to prompt further investigation in human patients because biotin could be a convenient therapeutic add-on.

“We are optimistic that the data presented here will serve as the foundation for future clinical studies to determine if biotin supplementation should be used as adjunct therapy in IBD,” the investigators wrote. “Biotin is available over the counter, is affordable, and it has minimal side effects, making it an ideal therapeutic if clinical trials can show similar efficacy to what we have seen in this preclinical model.

The study was funded by the Veteran’s Administration and the National Institutes of Health. The investigators reported no conflicts of interest.

SOURCE: Skupsky J et al. Cell Mol Gastroenterol Hepatol. 2019 Nov 28. doi: 10.1016/j.jcmgh.2019.11.011.

Patients with inflammatory bowel disease (IBD) may benefit from biotin supplementation, according to a preclinical study.

In mice, biotin supplementation delayed onset of colitis, minimized pathology, and accelerated healing, reported lead author Jonathan Skupsky, MD, of the University of California, Irvine, and colleagues.

“Biotin deficiency often is overlooked in the setting of IBD and there have been several reports of biotin deficiency in patients with IBD,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

In addition to these clinical reports, Dr. Skupsky and colleagues were motivated by their previous research, which showed that, in mice, knockout of the sodium-dependent multivitamin transporter (SMVT) for intestinal biotin uptake led to intestinal inflammation and dysplasia, thereby adding evidence that IBD and biotin could be linked.

In the present study, the investigators first compared mice fed a biotin-deficient diet with those fed a biotin-rich diet. Mice lacking biotin developed alopecia and weight loss within 7 weeks, and over time, stool that was soft and bloody. At week 14, mice fed the biotin-deficient diet had intestinal inflammation, based on elevated fecal calprotectin levels. In contrast, mice fed a biotin-rich diet had no gastrointestinal pathology.

“Although no mouse model entirely recapitulates patients with IBD, this model reproduces many of the findings including weight loss, bloody diarrhea, increased fecal calprotectin, altered crypt architecture, and infiltration of neutrophils and lymphocytes to the mucosa and submucosa,” the investigators wrote.

After this experiment, another group of mice were given drinking water with 3% dextran sodium sulfate (DSS), which induced severe colitis within 7 days. The distal colons of these mice had reduced expression of SMVT, the biotin transporter. This finding was also observed in biopsy samples from patients with ulcerative colitis, suggesting a shared pathway.

“This raises the possibility that [the biotin transport pathway] could be a target for therapy,” the investigators wrote.

Next the investigators tested the effect of prophylactic biotin supplementation in mice receiving 1.5% DSS in drinking water. Compared with mice that went without biotin, those that received a week of supplementation before DSS challenge had delayed, milder colitis, with histologic findings and fecal calprotectin levels that approximated those of healthy controls.

In a similar experiment, two groups of mice were given DSS for 7 days, then water or water plus biotin. Those in the biotin group recovered faster and more completely, again with clinical and histologic findings that was close to controls.

According to the investigators, these findings suggest that biotin may be able to protect against development of colitis and speed healing during early remission.

Further experiments dove deeper into cellular processes and molecular mechanisms, ultimately revealing that biotin supplementation reduced activation of NF-kappaB, which led to decreased intestinal permeability and inflammatory cytokines.

“The specific mechanism(s) linking biotin and NF-kappaB is unclear but could be mediated via the different cellular pathways that are affected by biotin availability,” the investigators wrote.

They noted that IBD is a complex condition, which can make it difficult to accurately model the disease; however, they also suggested that the findings are compelling enough to prompt further investigation in human patients because biotin could be a convenient therapeutic add-on.

“We are optimistic that the data presented here will serve as the foundation for future clinical studies to determine if biotin supplementation should be used as adjunct therapy in IBD,” the investigators wrote. “Biotin is available over the counter, is affordable, and it has minimal side effects, making it an ideal therapeutic if clinical trials can show similar efficacy to what we have seen in this preclinical model.

The study was funded by the Veteran’s Administration and the National Institutes of Health. The investigators reported no conflicts of interest.

SOURCE: Skupsky J et al. Cell Mol Gastroenterol Hepatol. 2019 Nov 28. doi: 10.1016/j.jcmgh.2019.11.011.

Patients with inflammatory bowel disease (IBD) may benefit from biotin supplementation, according to a preclinical study.

In mice, biotin supplementation delayed onset of colitis, minimized pathology, and accelerated healing, reported lead author Jonathan Skupsky, MD, of the University of California, Irvine, and colleagues.

“Biotin deficiency often is overlooked in the setting of IBD and there have been several reports of biotin deficiency in patients with IBD,” the investigators wrote in Cellular and Molecular Gastroenterology and Hepatology.

In addition to these clinical reports, Dr. Skupsky and colleagues were motivated by their previous research, which showed that, in mice, knockout of the sodium-dependent multivitamin transporter (SMVT) for intestinal biotin uptake led to intestinal inflammation and dysplasia, thereby adding evidence that IBD and biotin could be linked.

In the present study, the investigators first compared mice fed a biotin-deficient diet with those fed a biotin-rich diet. Mice lacking biotin developed alopecia and weight loss within 7 weeks, and over time, stool that was soft and bloody. At week 14, mice fed the biotin-deficient diet had intestinal inflammation, based on elevated fecal calprotectin levels. In contrast, mice fed a biotin-rich diet had no gastrointestinal pathology.

“Although no mouse model entirely recapitulates patients with IBD, this model reproduces many of the findings including weight loss, bloody diarrhea, increased fecal calprotectin, altered crypt architecture, and infiltration of neutrophils and lymphocytes to the mucosa and submucosa,” the investigators wrote.

After this experiment, another group of mice were given drinking water with 3% dextran sodium sulfate (DSS), which induced severe colitis within 7 days. The distal colons of these mice had reduced expression of SMVT, the biotin transporter. This finding was also observed in biopsy samples from patients with ulcerative colitis, suggesting a shared pathway.

“This raises the possibility that [the biotin transport pathway] could be a target for therapy,” the investigators wrote.

Next the investigators tested the effect of prophylactic biotin supplementation in mice receiving 1.5% DSS in drinking water. Compared with mice that went without biotin, those that received a week of supplementation before DSS challenge had delayed, milder colitis, with histologic findings and fecal calprotectin levels that approximated those of healthy controls.

In a similar experiment, two groups of mice were given DSS for 7 days, then water or water plus biotin. Those in the biotin group recovered faster and more completely, again with clinical and histologic findings that was close to controls.

According to the investigators, these findings suggest that biotin may be able to protect against development of colitis and speed healing during early remission.

Further experiments dove deeper into cellular processes and molecular mechanisms, ultimately revealing that biotin supplementation reduced activation of NF-kappaB, which led to decreased intestinal permeability and inflammatory cytokines.

“The specific mechanism(s) linking biotin and NF-kappaB is unclear but could be mediated via the different cellular pathways that are affected by biotin availability,” the investigators wrote.

They noted that IBD is a complex condition, which can make it difficult to accurately model the disease; however, they also suggested that the findings are compelling enough to prompt further investigation in human patients because biotin could be a convenient therapeutic add-on.

“We are optimistic that the data presented here will serve as the foundation for future clinical studies to determine if biotin supplementation should be used as adjunct therapy in IBD,” the investigators wrote. “Biotin is available over the counter, is affordable, and it has minimal side effects, making it an ideal therapeutic if clinical trials can show similar efficacy to what we have seen in this preclinical model.

The study was funded by the Veteran’s Administration and the National Institutes of Health. The investigators reported no conflicts of interest.

SOURCE: Skupsky J et al. Cell Mol Gastroenterol Hepatol. 2019 Nov 28. doi: 10.1016/j.jcmgh.2019.11.011.

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.