The available evidence suggests that proton pump inhibitors (PPIs) do not cause gastric cancer, researchers say.

A new study could help resolve a controversy over one of the most serious side effects attributed to the widely used medications.

“Our findings are reassuring, especially to all those patients who have an indication for long-term PPI use and need persistent and effective gastric acid suppression to prevent serious health consequences,” said Daniele Piovani, MSc, PhD, an assistant professor of medical statistics at Humanitas University, Milan, in an email to this news organization.

Previous studies did not take into account the probability that the diseases for which the medications were prescribed might have caused the cancer, Dr. Piovani and colleagues write in Alimentary Pharmacology and Therapeutics.

Researchers have worried about the potential of PPIs to cause cancer after finding that they are associated with enterochromaffin-like cells, gastric atrophy, and changes in gut microbiota and gastric mucosal immunology.

Observational studies and meta-analyses showed a link between PPIs and an increased risk for gastric cancer.

“However, the underlying conditions for which PPIs are prescribed are associated with gastric cancer,” said Dr. Piovani. “This may result in an apparent association between PPIs and gastric cancer.”

Another potential confounding factor is that as-yet undiagnosed cancer might also cause symptoms that are treated with PPIs. Patient behavior also may play a role, she noted.

“Let’s imagine a patient with peptic ulcer who takes PPIs,” said Dr. Piovani. “He may not only have peptic ulcer but also be a heavy smoker. He may drink much more alcohol, have a different dietary pattern, be more likely to be exposed to high levels of stress, etc. in respect to a control [patient] who does not have peptic ulcer and does not take PPIs.”
 

Comparing two drug classes

More recent studies have compared people taking PPIs to people taking histamine-2 receptor antagonists (H2RAs). H2RAs are often used to treat the same conditions as PPIs, but they are not as strongly linked to hypergastrinemia and are not associated with gastric atrophy, so they might serve as good comparators.

Since results of these studies have been conflicting, Dr. Piovani and colleagues attempted to weigh them together in a systematic review and meta-analysis. They identified two randomized clinical trials and 12 observational studies with a total of over 6 million patients.

One randomized controlled trial involved Helicobacter pylori–negative patients with bleeding ulcers. Researchers assigned 138 to 20 mg daily rabeprazole (a PPI) and 132 to 40 mg famotidine (an H2RA). After a year, no cancer occurred.

The other randomized controlled trial involved H. pylori–negative patients with idiopathic peptic ulcers. Investigators assigned 114 to 30 mg lansoprazole (another PPI) and 114 to 40 mg famotidine. In 2 years, one patient receiving famotidine developed cancer.

The researchers found several methodological problems with these trials. One flaw is that the study periods were not long enough to accurately measure what effects the medications might have on gastric cancers, which are a rare outcome, they note. The evidence from these studies was so weak they could not draw conclusions from the results, the investigators conclude.

Pooling data from the 11 observational trials they were able to combine, the researchers found that PPI users had a one-third higher random relative risk of cancer than H2RA users (95% confidence interval, 1.11-1.59). However, these studies were heterogenous, and five of them did not adjust for age and sex, as well as other potentially confounding covariates.

The remaining six observational studies adjusted for age, sex, and at least two other covariates that could affect the risk for gastric cancer. These studies had a total of 2.5 million patients and 7,372 gastric cancers. Combined, these studies showed an RR of gastric cancer in PPI users, compared with H2RA users of 1.07, which was not statistically significant (95% CI, 0.97-1.19).

The researchers found no clear evidence of a dose-response or of an increased risk with longer-term use of PPIs.
 

Findings support practice guidance

“I found this relatively reassuring,” Mark Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare, Murray, Utah, told this news organization.

PPIs do dramatically increase the pH of the stomach, stimulating the stomach to try to compensate in a process that can sometimes give rise to tumors, Dr. Lewis said. But these tumors appear to be benign.

Other concerns about PPI use, such as reduction in bone density, remain under investigation, he said.

Some H2RA blockers might actually pose a greater cancer risk than PPIs, said Dr. Lewis, and many clinicians seem to favor PPIs. “I have seen a huge sea change where most patients are on PPIs. And I would say that H2RA blockers are older and increasingly the exception in terms of usage, not the rule.”

The investigators note that observational studies by their nature cannot prove cause and effect, but because gastric cancer is so rare, a randomized controlled trial of PPIs versus H2RAs that is large enough to be definitive may not be feasible.

They conclude that their findings support the American Gastroenterological Association recommendation that “the decision to discontinue PPIs should be based solely on the lack of an indication for use and not because of concern for PPI-associated adverse effects.”

Dr. Piovani and Dr. Lewis report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The available evidence suggests that proton pump inhibitors (PPIs) do not cause gastric cancer, researchers say.

A new study could help resolve a controversy over one of the most serious side effects attributed to the widely used medications.

“Our findings are reassuring, especially to all those patients who have an indication for long-term PPI use and need persistent and effective gastric acid suppression to prevent serious health consequences,” said Daniele Piovani, MSc, PhD, an assistant professor of medical statistics at Humanitas University, Milan, in an email to this news organization.

Previous studies did not take into account the probability that the diseases for which the medications were prescribed might have caused the cancer, Dr. Piovani and colleagues write in Alimentary Pharmacology and Therapeutics.

Researchers have worried about the potential of PPIs to cause cancer after finding that they are associated with enterochromaffin-like cells, gastric atrophy, and changes in gut microbiota and gastric mucosal immunology.

Observational studies and meta-analyses showed a link between PPIs and an increased risk for gastric cancer.

“However, the underlying conditions for which PPIs are prescribed are associated with gastric cancer,” said Dr. Piovani. “This may result in an apparent association between PPIs and gastric cancer.”

Another potential confounding factor is that as-yet undiagnosed cancer might also cause symptoms that are treated with PPIs. Patient behavior also may play a role, she noted.

“Let’s imagine a patient with peptic ulcer who takes PPIs,” said Dr. Piovani. “He may not only have peptic ulcer but also be a heavy smoker. He may drink much more alcohol, have a different dietary pattern, be more likely to be exposed to high levels of stress, etc. in respect to a control [patient] who does not have peptic ulcer and does not take PPIs.”
 

Comparing two drug classes

More recent studies have compared people taking PPIs to people taking histamine-2 receptor antagonists (H2RAs). H2RAs are often used to treat the same conditions as PPIs, but they are not as strongly linked to hypergastrinemia and are not associated with gastric atrophy, so they might serve as good comparators.

Since results of these studies have been conflicting, Dr. Piovani and colleagues attempted to weigh them together in a systematic review and meta-analysis. They identified two randomized clinical trials and 12 observational studies with a total of over 6 million patients.

One randomized controlled trial involved Helicobacter pylori–negative patients with bleeding ulcers. Researchers assigned 138 to 20 mg daily rabeprazole (a PPI) and 132 to 40 mg famotidine (an H2RA). After a year, no cancer occurred.

The other randomized controlled trial involved H. pylori–negative patients with idiopathic peptic ulcers. Investigators assigned 114 to 30 mg lansoprazole (another PPI) and 114 to 40 mg famotidine. In 2 years, one patient receiving famotidine developed cancer.

The researchers found several methodological problems with these trials. One flaw is that the study periods were not long enough to accurately measure what effects the medications might have on gastric cancers, which are a rare outcome, they note. The evidence from these studies was so weak they could not draw conclusions from the results, the investigators conclude.

Pooling data from the 11 observational trials they were able to combine, the researchers found that PPI users had a one-third higher random relative risk of cancer than H2RA users (95% confidence interval, 1.11-1.59). However, these studies were heterogenous, and five of them did not adjust for age and sex, as well as other potentially confounding covariates.

The remaining six observational studies adjusted for age, sex, and at least two other covariates that could affect the risk for gastric cancer. These studies had a total of 2.5 million patients and 7,372 gastric cancers. Combined, these studies showed an RR of gastric cancer in PPI users, compared with H2RA users of 1.07, which was not statistically significant (95% CI, 0.97-1.19).

The researchers found no clear evidence of a dose-response or of an increased risk with longer-term use of PPIs.
 

Findings support practice guidance

“I found this relatively reassuring,” Mark Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare, Murray, Utah, told this news organization.

PPIs do dramatically increase the pH of the stomach, stimulating the stomach to try to compensate in a process that can sometimes give rise to tumors, Dr. Lewis said. But these tumors appear to be benign.

Other concerns about PPI use, such as reduction in bone density, remain under investigation, he said.

Some H2RA blockers might actually pose a greater cancer risk than PPIs, said Dr. Lewis, and many clinicians seem to favor PPIs. “I have seen a huge sea change where most patients are on PPIs. And I would say that H2RA blockers are older and increasingly the exception in terms of usage, not the rule.”

The investigators note that observational studies by their nature cannot prove cause and effect, but because gastric cancer is so rare, a randomized controlled trial of PPIs versus H2RAs that is large enough to be definitive may not be feasible.

They conclude that their findings support the American Gastroenterological Association recommendation that “the decision to discontinue PPIs should be based solely on the lack of an indication for use and not because of concern for PPI-associated adverse effects.”

Dr. Piovani and Dr. Lewis report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The available evidence suggests that proton pump inhibitors (PPIs) do not cause gastric cancer, researchers say.

A new study could help resolve a controversy over one of the most serious side effects attributed to the widely used medications.

“Our findings are reassuring, especially to all those patients who have an indication for long-term PPI use and need persistent and effective gastric acid suppression to prevent serious health consequences,” said Daniele Piovani, MSc, PhD, an assistant professor of medical statistics at Humanitas University, Milan, in an email to this news organization.

Previous studies did not take into account the probability that the diseases for which the medications were prescribed might have caused the cancer, Dr. Piovani and colleagues write in Alimentary Pharmacology and Therapeutics.

Researchers have worried about the potential of PPIs to cause cancer after finding that they are associated with enterochromaffin-like cells, gastric atrophy, and changes in gut microbiota and gastric mucosal immunology.

Observational studies and meta-analyses showed a link between PPIs and an increased risk for gastric cancer.

“However, the underlying conditions for which PPIs are prescribed are associated with gastric cancer,” said Dr. Piovani. “This may result in an apparent association between PPIs and gastric cancer.”

Another potential confounding factor is that as-yet undiagnosed cancer might also cause symptoms that are treated with PPIs. Patient behavior also may play a role, she noted.

“Let’s imagine a patient with peptic ulcer who takes PPIs,” said Dr. Piovani. “He may not only have peptic ulcer but also be a heavy smoker. He may drink much more alcohol, have a different dietary pattern, be more likely to be exposed to high levels of stress, etc. in respect to a control [patient] who does not have peptic ulcer and does not take PPIs.”
 

Comparing two drug classes

More recent studies have compared people taking PPIs to people taking histamine-2 receptor antagonists (H2RAs). H2RAs are often used to treat the same conditions as PPIs, but they are not as strongly linked to hypergastrinemia and are not associated with gastric atrophy, so they might serve as good comparators.

Since results of these studies have been conflicting, Dr. Piovani and colleagues attempted to weigh them together in a systematic review and meta-analysis. They identified two randomized clinical trials and 12 observational studies with a total of over 6 million patients.

One randomized controlled trial involved Helicobacter pylori–negative patients with bleeding ulcers. Researchers assigned 138 to 20 mg daily rabeprazole (a PPI) and 132 to 40 mg famotidine (an H2RA). After a year, no cancer occurred.

The other randomized controlled trial involved H. pylori–negative patients with idiopathic peptic ulcers. Investigators assigned 114 to 30 mg lansoprazole (another PPI) and 114 to 40 mg famotidine. In 2 years, one patient receiving famotidine developed cancer.

The researchers found several methodological problems with these trials. One flaw is that the study periods were not long enough to accurately measure what effects the medications might have on gastric cancers, which are a rare outcome, they note. The evidence from these studies was so weak they could not draw conclusions from the results, the investigators conclude.

Pooling data from the 11 observational trials they were able to combine, the researchers found that PPI users had a one-third higher random relative risk of cancer than H2RA users (95% confidence interval, 1.11-1.59). However, these studies were heterogenous, and five of them did not adjust for age and sex, as well as other potentially confounding covariates.

The remaining six observational studies adjusted for age, sex, and at least two other covariates that could affect the risk for gastric cancer. These studies had a total of 2.5 million patients and 7,372 gastric cancers. Combined, these studies showed an RR of gastric cancer in PPI users, compared with H2RA users of 1.07, which was not statistically significant (95% CI, 0.97-1.19).

The researchers found no clear evidence of a dose-response or of an increased risk with longer-term use of PPIs.
 

Findings support practice guidance

“I found this relatively reassuring,” Mark Lewis, MD, director of gastrointestinal oncology at Intermountain Healthcare, Murray, Utah, told this news organization.

PPIs do dramatically increase the pH of the stomach, stimulating the stomach to try to compensate in a process that can sometimes give rise to tumors, Dr. Lewis said. But these tumors appear to be benign.

Other concerns about PPI use, such as reduction in bone density, remain under investigation, he said.

Some H2RA blockers might actually pose a greater cancer risk than PPIs, said Dr. Lewis, and many clinicians seem to favor PPIs. “I have seen a huge sea change where most patients are on PPIs. And I would say that H2RA blockers are older and increasingly the exception in terms of usage, not the rule.”

The investigators note that observational studies by their nature cannot prove cause and effect, but because gastric cancer is so rare, a randomized controlled trial of PPIs versus H2RAs that is large enough to be definitive may not be feasible.

They conclude that their findings support the American Gastroenterological Association recommendation that “the decision to discontinue PPIs should be based solely on the lack of an indication for use and not because of concern for PPI-associated adverse effects.”

Dr. Piovani and Dr. Lewis report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Granuloma annulare (GA) is a self-limiting condition, and is known as the most common noninfectious granulomatous disease. The prevalence and incidence is approximately 0.1%-0.4%. Although the condition is benign, it may be associated with more serious conditions such as HIV and malignancy. GA affects women more frequently than men but can affect any age group, although it most commonly presents in those ages 30 years and younger. While the exact etiology is unknown, GA has been most strongly associated with diabetes mellitus, hyperlipidemia, and autoimmune diseases.

Courtesy Lucas Shapiro and Dr. Bilu Martin

The disease presents as localized, annular erythematous plaques and papules on the dorsal hands and feet in approximately 75% of cases. However, eruptions may appear on the trunk and extremities and can be categorized into patchy, generalized, interstitial, subcutaneous, or perforating subtypes. The lesions are often asymptomatic and typically not associated with any other symptoms.

Courtesy Lucas Shapiro and Dr. Bilu Martin

The pathogenesis of GA is still under investigation, but recent studies suggest that a Th1-mediated dysregulation of the JAK-STAT pathway may contribute to the disease. Other hypotheses include a delayed hypersensitivity reaction or cell mediated immune response. The mechanism may be multifaceted, and epidemiologic research suggests a genetic predisposition in White individuals, but these findings may be associated with socioeconomic factors and disparities in health care.

GA presents on histology with palisading histiocytes surrounding focal collagen necrobiosis with mucin deposition. Tissue samples also display leukocytic infiltration of the dermis featuring multinucleated giant cells. There are defining features of the different subtypes, but focal collagen necrosis, the presence of histiocytes, and mucin deposition are consistent findings across all presentations.

GA lesions commonly regress on their own, but they tend to recur and can be functionally and visually unappealing to patients. The most common treatments for GA include topical corticosteroids, intralesional corticosteroid injections, and other anti-inflammatory drugs. These interventions can be administered in a variety of ways as the inflammation caused by GA exists on a spectrum, and less severe cases can be managed with topical or intralesional treatment. Systemic therapy may be necessary for severe and recalcitrant cases. Other interventions that have shown promise in smaller studies include phototherapy, hydroxychloroquine, and TNF-alpha inhibitors.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Joshi TP and Duvic M. Am J Clin Dermatol. 2022 Jan;23(1):37-50. doi: 10.1007/s40257-021-00636-1.

Muse M et al. Dermatol Online J. 2021 Apr 15;27(4):13030/qt0m50398n.

Schmieder SJ et al. Granuloma Annulare. NIH National Center for Biotechnology Information [Updated 2022 Nov 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. 7.

Granuloma annulare (GA) is a self-limiting condition, and is known as the most common noninfectious granulomatous disease. The prevalence and incidence is approximately 0.1%-0.4%. Although the condition is benign, it may be associated with more serious conditions such as HIV and malignancy. GA affects women more frequently than men but can affect any age group, although it most commonly presents in those ages 30 years and younger. While the exact etiology is unknown, GA has been most strongly associated with diabetes mellitus, hyperlipidemia, and autoimmune diseases.

Courtesy Lucas Shapiro and Dr. Bilu Martin

The disease presents as localized, annular erythematous plaques and papules on the dorsal hands and feet in approximately 75% of cases. However, eruptions may appear on the trunk and extremities and can be categorized into patchy, generalized, interstitial, subcutaneous, or perforating subtypes. The lesions are often asymptomatic and typically not associated with any other symptoms.

Courtesy Lucas Shapiro and Dr. Bilu Martin

The pathogenesis of GA is still under investigation, but recent studies suggest that a Th1-mediated dysregulation of the JAK-STAT pathway may contribute to the disease. Other hypotheses include a delayed hypersensitivity reaction or cell mediated immune response. The mechanism may be multifaceted, and epidemiologic research suggests a genetic predisposition in White individuals, but these findings may be associated with socioeconomic factors and disparities in health care.

GA presents on histology with palisading histiocytes surrounding focal collagen necrobiosis with mucin deposition. Tissue samples also display leukocytic infiltration of the dermis featuring multinucleated giant cells. There are defining features of the different subtypes, but focal collagen necrosis, the presence of histiocytes, and mucin deposition are consistent findings across all presentations.

GA lesions commonly regress on their own, but they tend to recur and can be functionally and visually unappealing to patients. The most common treatments for GA include topical corticosteroids, intralesional corticosteroid injections, and other anti-inflammatory drugs. These interventions can be administered in a variety of ways as the inflammation caused by GA exists on a spectrum, and less severe cases can be managed with topical or intralesional treatment. Systemic therapy may be necessary for severe and recalcitrant cases. Other interventions that have shown promise in smaller studies include phototherapy, hydroxychloroquine, and TNF-alpha inhibitors.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Joshi TP and Duvic M. Am J Clin Dermatol. 2022 Jan;23(1):37-50. doi: 10.1007/s40257-021-00636-1.

Muse M et al. Dermatol Online J. 2021 Apr 15;27(4):13030/qt0m50398n.

Schmieder SJ et al. Granuloma Annulare. NIH National Center for Biotechnology Information [Updated 2022 Nov 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. 7.

Granuloma annulare (GA) is a self-limiting condition, and is known as the most common noninfectious granulomatous disease. The prevalence and incidence is approximately 0.1%-0.4%. Although the condition is benign, it may be associated with more serious conditions such as HIV and malignancy. GA affects women more frequently than men but can affect any age group, although it most commonly presents in those ages 30 years and younger. While the exact etiology is unknown, GA has been most strongly associated with diabetes mellitus, hyperlipidemia, and autoimmune diseases.

Courtesy Lucas Shapiro and Dr. Bilu Martin

The disease presents as localized, annular erythematous plaques and papules on the dorsal hands and feet in approximately 75% of cases. However, eruptions may appear on the trunk and extremities and can be categorized into patchy, generalized, interstitial, subcutaneous, or perforating subtypes. The lesions are often asymptomatic and typically not associated with any other symptoms.

Courtesy Lucas Shapiro and Dr. Bilu Martin

The pathogenesis of GA is still under investigation, but recent studies suggest that a Th1-mediated dysregulation of the JAK-STAT pathway may contribute to the disease. Other hypotheses include a delayed hypersensitivity reaction or cell mediated immune response. The mechanism may be multifaceted, and epidemiologic research suggests a genetic predisposition in White individuals, but these findings may be associated with socioeconomic factors and disparities in health care.

GA presents on histology with palisading histiocytes surrounding focal collagen necrobiosis with mucin deposition. Tissue samples also display leukocytic infiltration of the dermis featuring multinucleated giant cells. There are defining features of the different subtypes, but focal collagen necrosis, the presence of histiocytes, and mucin deposition are consistent findings across all presentations.

GA lesions commonly regress on their own, but they tend to recur and can be functionally and visually unappealing to patients. The most common treatments for GA include topical corticosteroids, intralesional corticosteroid injections, and other anti-inflammatory drugs. These interventions can be administered in a variety of ways as the inflammation caused by GA exists on a spectrum, and less severe cases can be managed with topical or intralesional treatment. Systemic therapy may be necessary for severe and recalcitrant cases. Other interventions that have shown promise in smaller studies include phototherapy, hydroxychloroquine, and TNF-alpha inhibitors.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to dermnews@mdedge.com.

References

Joshi TP and Duvic M. Am J Clin Dermatol. 2022 Jan;23(1):37-50. doi: 10.1007/s40257-021-00636-1.

Muse M et al. Dermatol Online J. 2021 Apr 15;27(4):13030/qt0m50398n.

Schmieder SJ et al. Granuloma Annulare. NIH National Center for Biotechnology Information [Updated 2022 Nov 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan. 7.

COVID-19 remained the top-ranked cause of death among law enforcement officers last year. 

A new report says 70 officers died of COVID-related causes after getting the virus while on the job. The number is down dramatically from 2021, when 405 officer deaths were attributed to COVID.

The annual count was published Wednesday by the National Law Enforcement Officers Memorial Fund.

In total, 226 officers died in the line of duty in 2022, which is a decrease of 61% from 2021.

The decrease “is almost entirely related to the significant reduction in COVID-19 deaths,” the report stated. The authors said the decline was likely due to “reduced infection rates and the broad availability and use of vaccinations.”

Reported deaths included federal, state, tribal, and local law enforcement officers.

Firearms-related fatalities were the second-leading cause of death among officers, with 64 in 2022. That count sustains a 21% increase seen in 2021, up from the decade-long average of 53 firearms-related deaths annually from 2010 to 2020. 

Traffic-related causes ranked third for cause of death in 2022, accounting for 56 deaths. 

“While overall line-of-duty deaths are trending down, the continuing trend of greater-than-average firearms-related deaths continues to be a serious concern,” Marcia Ferranto, the organization’s chief executive officer, said in a news release. “Using and reporting on this data allows us to highlight the continuing cost of maintaining our democracy, regrettably measured in the lives of the many law enforcement professionals who sacrifice everything fulfilling their promise to serve and protect.”

A version of this article first appeared on WebMD.com.

COVID-19 remained the top-ranked cause of death among law enforcement officers last year. 

A new report says 70 officers died of COVID-related causes after getting the virus while on the job. The number is down dramatically from 2021, when 405 officer deaths were attributed to COVID.

The annual count was published Wednesday by the National Law Enforcement Officers Memorial Fund.

In total, 226 officers died in the line of duty in 2022, which is a decrease of 61% from 2021.

The decrease “is almost entirely related to the significant reduction in COVID-19 deaths,” the report stated. The authors said the decline was likely due to “reduced infection rates and the broad availability and use of vaccinations.”

Reported deaths included federal, state, tribal, and local law enforcement officers.

Firearms-related fatalities were the second-leading cause of death among officers, with 64 in 2022. That count sustains a 21% increase seen in 2021, up from the decade-long average of 53 firearms-related deaths annually from 2010 to 2020. 

Traffic-related causes ranked third for cause of death in 2022, accounting for 56 deaths. 

“While overall line-of-duty deaths are trending down, the continuing trend of greater-than-average firearms-related deaths continues to be a serious concern,” Marcia Ferranto, the organization’s chief executive officer, said in a news release. “Using and reporting on this data allows us to highlight the continuing cost of maintaining our democracy, regrettably measured in the lives of the many law enforcement professionals who sacrifice everything fulfilling their promise to serve and protect.”

A version of this article first appeared on WebMD.com.

COVID-19 remained the top-ranked cause of death among law enforcement officers last year. 

A new report says 70 officers died of COVID-related causes after getting the virus while on the job. The number is down dramatically from 2021, when 405 officer deaths were attributed to COVID.

The annual count was published Wednesday by the National Law Enforcement Officers Memorial Fund.

In total, 226 officers died in the line of duty in 2022, which is a decrease of 61% from 2021.

The decrease “is almost entirely related to the significant reduction in COVID-19 deaths,” the report stated. The authors said the decline was likely due to “reduced infection rates and the broad availability and use of vaccinations.”

Reported deaths included federal, state, tribal, and local law enforcement officers.

Firearms-related fatalities were the second-leading cause of death among officers, with 64 in 2022. That count sustains a 21% increase seen in 2021, up from the decade-long average of 53 firearms-related deaths annually from 2010 to 2020. 

Traffic-related causes ranked third for cause of death in 2022, accounting for 56 deaths. 

“While overall line-of-duty deaths are trending down, the continuing trend of greater-than-average firearms-related deaths continues to be a serious concern,” Marcia Ferranto, the organization’s chief executive officer, said in a news release. “Using and reporting on this data allows us to highlight the continuing cost of maintaining our democracy, regrettably measured in the lives of the many law enforcement professionals who sacrifice everything fulfilling their promise to serve and protect.”

A version of this article first appeared on WebMD.com.

Oramed Pharmaceuticals’ investigational oral insulin failed to achieve its primary endpoint in a phase 3 trial, according to top-line results announced by the company.

“Therefore, Oramed expects to discontinue its oral insulin clinical activities for [type 2 diabetes],” according to a company statement.

Top-line results were negative for the phase 3, randomized, double-blind, placebo-controlled, multicenter trial, ORA-D-013-1, comparing the efficacy of the insulin product ORMD-0801 to placebo in 710 people with type 2 diabetes with inadequate glycemic control on two or three oral glucose-lowering agents.

The participants were randomized 2:2:1:1 into ORMD-0801 dosed at 8 mg once or twice daily, or placebo dosed once or twice daily. They completed a 21-day screening period, followed by a 26-week double-blind treatment period.

The product didn’t achieve the primary endpoint comparing reduction in hemoglobin A1c from baseline to 26 weeks, or the secondary endpoint of mean change in fasting plasma glucose at 26 weeks. There were no serious adverse events.

Oramed Pharmaceuticals specializes in developing oral delivery formulations of drugs currently delivered via injection. The company has offices in the United States and Israel.

Oramed CEO Nadav Kidron commented in the statement, “Today’s outcome is very disappointing, given the positive results from prior trials. Once full data from the studies are available, we expect to share relevant learnings and future plans. We thank all the patients, families, and health care professionals who participated in the trial.”

Insulin manufacturer Novo Nordisk had also been developing an oral insulin product. Successful phase 2a results were presented at the American Diabetes Association’s 2017 Scientific Sessions and full phase 2 feasibility results were published in Lancet Diabetes & Endocrinology in 2019.

However, Novo Nordisk, which manufactures the oral glucagon-like peptide-1 receptor agonist semaglutide (Rybelsus), subsequently discontinued development of their oral insulin product. According to a statement, “Initial results raised questions about truly addressing patients’ unmet needs with insulin therapy. Therefore, we discontinued this work to focus on projects that could in fact improve cardiometabolic outcomes for people living with diabetes.”

A version of this article first appeared on Medscape.com.

Oramed Pharmaceuticals’ investigational oral insulin failed to achieve its primary endpoint in a phase 3 trial, according to top-line results announced by the company.

“Therefore, Oramed expects to discontinue its oral insulin clinical activities for [type 2 diabetes],” according to a company statement.

Top-line results were negative for the phase 3, randomized, double-blind, placebo-controlled, multicenter trial, ORA-D-013-1, comparing the efficacy of the insulin product ORMD-0801 to placebo in 710 people with type 2 diabetes with inadequate glycemic control on two or three oral glucose-lowering agents.

The participants were randomized 2:2:1:1 into ORMD-0801 dosed at 8 mg once or twice daily, or placebo dosed once or twice daily. They completed a 21-day screening period, followed by a 26-week double-blind treatment period.

The product didn’t achieve the primary endpoint comparing reduction in hemoglobin A1c from baseline to 26 weeks, or the secondary endpoint of mean change in fasting plasma glucose at 26 weeks. There were no serious adverse events.

Oramed Pharmaceuticals specializes in developing oral delivery formulations of drugs currently delivered via injection. The company has offices in the United States and Israel.

Oramed CEO Nadav Kidron commented in the statement, “Today’s outcome is very disappointing, given the positive results from prior trials. Once full data from the studies are available, we expect to share relevant learnings and future plans. We thank all the patients, families, and health care professionals who participated in the trial.”

Insulin manufacturer Novo Nordisk had also been developing an oral insulin product. Successful phase 2a results were presented at the American Diabetes Association’s 2017 Scientific Sessions and full phase 2 feasibility results were published in Lancet Diabetes & Endocrinology in 2019.

However, Novo Nordisk, which manufactures the oral glucagon-like peptide-1 receptor agonist semaglutide (Rybelsus), subsequently discontinued development of their oral insulin product. According to a statement, “Initial results raised questions about truly addressing patients’ unmet needs with insulin therapy. Therefore, we discontinued this work to focus on projects that could in fact improve cardiometabolic outcomes for people living with diabetes.”

A version of this article first appeared on Medscape.com.

Oramed Pharmaceuticals’ investigational oral insulin failed to achieve its primary endpoint in a phase 3 trial, according to top-line results announced by the company.

“Therefore, Oramed expects to discontinue its oral insulin clinical activities for [type 2 diabetes],” according to a company statement.

Top-line results were negative for the phase 3, randomized, double-blind, placebo-controlled, multicenter trial, ORA-D-013-1, comparing the efficacy of the insulin product ORMD-0801 to placebo in 710 people with type 2 diabetes with inadequate glycemic control on two or three oral glucose-lowering agents.

The participants were randomized 2:2:1:1 into ORMD-0801 dosed at 8 mg once or twice daily, or placebo dosed once or twice daily. They completed a 21-day screening period, followed by a 26-week double-blind treatment period.

The product didn’t achieve the primary endpoint comparing reduction in hemoglobin A1c from baseline to 26 weeks, or the secondary endpoint of mean change in fasting plasma glucose at 26 weeks. There were no serious adverse events.

Oramed Pharmaceuticals specializes in developing oral delivery formulations of drugs currently delivered via injection. The company has offices in the United States and Israel.

Oramed CEO Nadav Kidron commented in the statement, “Today’s outcome is very disappointing, given the positive results from prior trials. Once full data from the studies are available, we expect to share relevant learnings and future plans. We thank all the patients, families, and health care professionals who participated in the trial.”

Insulin manufacturer Novo Nordisk had also been developing an oral insulin product. Successful phase 2a results were presented at the American Diabetes Association’s 2017 Scientific Sessions and full phase 2 feasibility results were published in Lancet Diabetes & Endocrinology in 2019.

However, Novo Nordisk, which manufactures the oral glucagon-like peptide-1 receptor agonist semaglutide (Rybelsus), subsequently discontinued development of their oral insulin product. According to a statement, “Initial results raised questions about truly addressing patients’ unmet needs with insulin therapy. Therefore, we discontinued this work to focus on projects that could in fact improve cardiometabolic outcomes for people living with diabetes.”

A version of this article first appeared on Medscape.com.

Gestational diabetes is a significant health problem worldwide that is associated with immediate and lifelong consequences for the affected woman and her infant. Gestational diabetes increases the risk for pregnancy-related complications, such as induced labor, cesarean delivery, and preeclampsia. There is also an increased risk for neonatal complications, including large-for-gestational-age birth weight, shoulder dystocia, birth injuries, lung disease, jaundice, and hypoglycemia. Regardless of birth weight, neonates born to mothers with gestational diabetes have greater adiposity than do neonates born to mothers without obesity and with normal glucose tolerance, and they have a predilection toward obesity and obesity-related metabolic disorders, including T2D in childhood and adulthood. Similarly, women who develop gestational diabetes have an increased lifetime risk for T2D as well as an increased risk for cardiovascular disease even if they do not progress to T2D.

According to the International Diabetes Federation, 1 in 6 pregnancies is affected by gestational diabetes. Risk factors include higher age and BMI, previous history of gestational diabetes, a family history of T2D, and polycystic ovarian syndrome. Patients may have few, if any, symptoms of gestational diabetes, or they may mistake their symptoms for the normal side effects of pregnancy. Potential symptoms include blurred vision, tingling or numbness in the hands and/or feet, excessive thirst, frequent urination, sores that heal slowly, and excessive fatigue. 

The American Diabetes Association (ADA) states that the treatment of gestational diabetes should include medical nutrition therapy, physical activity, and weight management, depending on pregestational weight. Glucose monitoring is essential: Patients should aim for fasting glucose < 95 mg/dL (5.3 mmol/L) and either 1-hour postprandial glucose < 140 mg/dL (7.8 mmol/L) or 2-hour postprandial glucose < 120 mg/dL (6.7 mmol/L). According to the ADA, insulin should be added to lifestyle modifications if needed to achieve glycemic targets. Metformin and glyburide are not recommended as first-line agents because both cross the placenta to the fetus. Long-term safety data are not available for the use of other oral and noninsulin injectable glucose-lowering medications during pregnancy. 

Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.

Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Gestational diabetes is a significant health problem worldwide that is associated with immediate and lifelong consequences for the affected woman and her infant. Gestational diabetes increases the risk for pregnancy-related complications, such as induced labor, cesarean delivery, and preeclampsia. There is also an increased risk for neonatal complications, including large-for-gestational-age birth weight, shoulder dystocia, birth injuries, lung disease, jaundice, and hypoglycemia. Regardless of birth weight, neonates born to mothers with gestational diabetes have greater adiposity than do neonates born to mothers without obesity and with normal glucose tolerance, and they have a predilection toward obesity and obesity-related metabolic disorders, including T2D in childhood and adulthood. Similarly, women who develop gestational diabetes have an increased lifetime risk for T2D as well as an increased risk for cardiovascular disease even if they do not progress to T2D.

According to the International Diabetes Federation, 1 in 6 pregnancies is affected by gestational diabetes. Risk factors include higher age and BMI, previous history of gestational diabetes, a family history of T2D, and polycystic ovarian syndrome. Patients may have few, if any, symptoms of gestational diabetes, or they may mistake their symptoms for the normal side effects of pregnancy. Potential symptoms include blurred vision, tingling or numbness in the hands and/or feet, excessive thirst, frequent urination, sores that heal slowly, and excessive fatigue. 

The American Diabetes Association (ADA) states that the treatment of gestational diabetes should include medical nutrition therapy, physical activity, and weight management, depending on pregestational weight. Glucose monitoring is essential: Patients should aim for fasting glucose < 95 mg/dL (5.3 mmol/L) and either 1-hour postprandial glucose < 140 mg/dL (7.8 mmol/L) or 2-hour postprandial glucose < 120 mg/dL (6.7 mmol/L). According to the ADA, insulin should be added to lifestyle modifications if needed to achieve glycemic targets. Metformin and glyburide are not recommended as first-line agents because both cross the placenta to the fetus. Long-term safety data are not available for the use of other oral and noninsulin injectable glucose-lowering medications during pregnancy. 

Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.

Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Gestational diabetes is a significant health problem worldwide that is associated with immediate and lifelong consequences for the affected woman and her infant. Gestational diabetes increases the risk for pregnancy-related complications, such as induced labor, cesarean delivery, and preeclampsia. There is also an increased risk for neonatal complications, including large-for-gestational-age birth weight, shoulder dystocia, birth injuries, lung disease, jaundice, and hypoglycemia. Regardless of birth weight, neonates born to mothers with gestational diabetes have greater adiposity than do neonates born to mothers without obesity and with normal glucose tolerance, and they have a predilection toward obesity and obesity-related metabolic disorders, including T2D in childhood and adulthood. Similarly, women who develop gestational diabetes have an increased lifetime risk for T2D as well as an increased risk for cardiovascular disease even if they do not progress to T2D.

According to the International Diabetes Federation, 1 in 6 pregnancies is affected by gestational diabetes. Risk factors include higher age and BMI, previous history of gestational diabetes, a family history of T2D, and polycystic ovarian syndrome. Patients may have few, if any, symptoms of gestational diabetes, or they may mistake their symptoms for the normal side effects of pregnancy. Potential symptoms include blurred vision, tingling or numbness in the hands and/or feet, excessive thirst, frequent urination, sores that heal slowly, and excessive fatigue. 

The American Diabetes Association (ADA) states that the treatment of gestational diabetes should include medical nutrition therapy, physical activity, and weight management, depending on pregestational weight. Glucose monitoring is essential: Patients should aim for fasting glucose < 95 mg/dL (5.3 mmol/L) and either 1-hour postprandial glucose < 140 mg/dL (7.8 mmol/L) or 2-hour postprandial glucose < 120 mg/dL (6.7 mmol/L). According to the ADA, insulin should be added to lifestyle modifications if needed to achieve glycemic targets. Metformin and glyburide are not recommended as first-line agents because both cross the placenta to the fetus. Long-term safety data are not available for the use of other oral and noninsulin injectable glucose-lowering medications during pregnancy. 

Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.

Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Low levels of serum lactate dehydrogenase were significantly associated with depression and suicide attempts in adults with major depressive disorder, based on data from more than 300 individuals.

The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.

Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.

“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.

In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).

The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.

The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.

In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.

Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.

The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Low levels of serum lactate dehydrogenase were significantly associated with depression and suicide attempts in adults with major depressive disorder, based on data from more than 300 individuals.

The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.

Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.

“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.

In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).

The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.

The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.

In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.

Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.

The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Low levels of serum lactate dehydrogenase were significantly associated with depression and suicide attempts in adults with major depressive disorder, based on data from more than 300 individuals.

The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.

Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.

“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.

In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).

The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.

The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.

In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.

Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.

The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Gastroenterology

October 2022

Cryer B et al. Bridging the Racial, Ethnic, and Gender Gap in Gastroenterology. Gastroenterology. 2022 Oct;163(4):800-5. doi: 10.1053/j.gastro.2022.08.037. PMID: 36137708.



Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-51. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.



November 2022

Grunvald E et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology. 2022 Nov;163(5):1198-225. doi: 10.1053/j.gastro.2022.08.045. Epub 2022 Oct 20. PMID: 36273831.



December 2022

Blackett JW et al. Comparison of Anorectal Manometry, Rectal Balloon Expulsion Test, and Defecography for Diagnosing Defecatory Disorders. Gastroenterology. 2022 Dec;163(6):1582-92.e2. doi: 10.1053/j.gastro.2022.08.034. Epub 2022 Aug 19. PMID: 35995074; PMCID: PMC9691522.



de Voogd F et al. Intestinal Ultrasound Is Accurate to Determine Endoscopic Response and Remission in Patients With Moderate to Severe Ulcerative Colitis: A Longitudinal Prospective Cohort Study. Gastroenterology. 2022 Dec;163(6):1569-81. doi: 10.1053/j.gastro.2022.08.038. Epub 2022 Aug 24. PMID: 36030056.
 

Clinical Gastroenterology and Hepatology

October 2022

Bhavsar-Burke I et al. How to Promote Professional Identity Development and Support Fellows-In-Training Through Teaching, Coaching, Mentorship, and Sponsorship. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2166-9. doi: 10.1016/j.cgh.2022.05.043. Epub 2022 Aug 7. PMID: 35948073.



van Megen F et al. A Low FODMAP Diet Reduces Symptoms in Treated Celiac Patients With Ongoing Symptoms – A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2258-66.e3. doi: 10.1016/j.cgh.2022.01.011. Epub 2022 Jan 17. PMID: 35051648.



November 2022

Sharzehi K et al. AGA Clinical Practice Update on Management of Subepithelial Lesions Encountered During Routine Endoscopy: Expert Review. Clin Gastroenterol Hepatol. 2022 Nov;20(11):2435-43.e4. doi: 10.1016/j.cgh.2022.05.054. Epub 2022 Jul 13. PMID: 35842117.



December 2022

Kardashian A et al. Food Insecurity is Associated With Mortality Among U.S. Adults With Nonalcoholic Fatty Liver Disease and Advanced Fibrosis. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2790-9.e4. doi: 10.1016/j.cgh.2021.11.029. Epub 2021 Dec 16. PMID: 34958747.



Schuitenmaker JM et al. Sleep Positional Therapy for Nocturnal Gastroesophageal Reflux: A Double-Blind, Randomized, Sham-Controlled Trial. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2753-62.e2. doi: 10.1016/j.cgh.2022.02.058. Epub 2022 Mar 14. PMID: 35301135.
 

Techniques and Innovations in Gastrointestinal Endoscopy

Azizian JM et al. Yield of Post-Acute Diverticulitis Colonoscopy for Ruling Out Colorectal Cancer. Tech Innov Gastrointest Endosc. 2022;24(3):254-61. doi: 10.1016/j.tige.2022.04.001. Epub 2022 Apr 18. PMID: 36540108; PMCID: PMC9762736.
 

Gastro Hep Advances

Kim RW et al. Timely Albumin Improves Survival in Patients With Cirrhosis on Diuretic Therapy Who Develop Acute Kidney Injury: Real-World Evidence in the United States. Gastro Hep Advances. 2023;2(2):252-60. doi: 10.1016/j.gastha.2022.10.008.

Gastroenterology

October 2022

Cryer B et al. Bridging the Racial, Ethnic, and Gender Gap in Gastroenterology. Gastroenterology. 2022 Oct;163(4):800-5. doi: 10.1053/j.gastro.2022.08.037. PMID: 36137708.



Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-51. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.



November 2022

Grunvald E et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology. 2022 Nov;163(5):1198-225. doi: 10.1053/j.gastro.2022.08.045. Epub 2022 Oct 20. PMID: 36273831.



December 2022

Blackett JW et al. Comparison of Anorectal Manometry, Rectal Balloon Expulsion Test, and Defecography for Diagnosing Defecatory Disorders. Gastroenterology. 2022 Dec;163(6):1582-92.e2. doi: 10.1053/j.gastro.2022.08.034. Epub 2022 Aug 19. PMID: 35995074; PMCID: PMC9691522.



de Voogd F et al. Intestinal Ultrasound Is Accurate to Determine Endoscopic Response and Remission in Patients With Moderate to Severe Ulcerative Colitis: A Longitudinal Prospective Cohort Study. Gastroenterology. 2022 Dec;163(6):1569-81. doi: 10.1053/j.gastro.2022.08.038. Epub 2022 Aug 24. PMID: 36030056.
 

Clinical Gastroenterology and Hepatology

October 2022

Bhavsar-Burke I et al. How to Promote Professional Identity Development and Support Fellows-In-Training Through Teaching, Coaching, Mentorship, and Sponsorship. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2166-9. doi: 10.1016/j.cgh.2022.05.043. Epub 2022 Aug 7. PMID: 35948073.



van Megen F et al. A Low FODMAP Diet Reduces Symptoms in Treated Celiac Patients With Ongoing Symptoms – A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2258-66.e3. doi: 10.1016/j.cgh.2022.01.011. Epub 2022 Jan 17. PMID: 35051648.



November 2022

Sharzehi K et al. AGA Clinical Practice Update on Management of Subepithelial Lesions Encountered During Routine Endoscopy: Expert Review. Clin Gastroenterol Hepatol. 2022 Nov;20(11):2435-43.e4. doi: 10.1016/j.cgh.2022.05.054. Epub 2022 Jul 13. PMID: 35842117.



December 2022

Kardashian A et al. Food Insecurity is Associated With Mortality Among U.S. Adults With Nonalcoholic Fatty Liver Disease and Advanced Fibrosis. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2790-9.e4. doi: 10.1016/j.cgh.2021.11.029. Epub 2021 Dec 16. PMID: 34958747.



Schuitenmaker JM et al. Sleep Positional Therapy for Nocturnal Gastroesophageal Reflux: A Double-Blind, Randomized, Sham-Controlled Trial. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2753-62.e2. doi: 10.1016/j.cgh.2022.02.058. Epub 2022 Mar 14. PMID: 35301135.
 

Techniques and Innovations in Gastrointestinal Endoscopy

Azizian JM et al. Yield of Post-Acute Diverticulitis Colonoscopy for Ruling Out Colorectal Cancer. Tech Innov Gastrointest Endosc. 2022;24(3):254-61. doi: 10.1016/j.tige.2022.04.001. Epub 2022 Apr 18. PMID: 36540108; PMCID: PMC9762736.
 

Gastro Hep Advances

Kim RW et al. Timely Albumin Improves Survival in Patients With Cirrhosis on Diuretic Therapy Who Develop Acute Kidney Injury: Real-World Evidence in the United States. Gastro Hep Advances. 2023;2(2):252-60. doi: 10.1016/j.gastha.2022.10.008.

Gastroenterology

October 2022

Cryer B et al. Bridging the Racial, Ethnic, and Gender Gap in Gastroenterology. Gastroenterology. 2022 Oct;163(4):800-5. doi: 10.1053/j.gastro.2022.08.037. PMID: 36137708.



Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-51. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.



November 2022

Grunvald E et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology. 2022 Nov;163(5):1198-225. doi: 10.1053/j.gastro.2022.08.045. Epub 2022 Oct 20. PMID: 36273831.



December 2022

Blackett JW et al. Comparison of Anorectal Manometry, Rectal Balloon Expulsion Test, and Defecography for Diagnosing Defecatory Disorders. Gastroenterology. 2022 Dec;163(6):1582-92.e2. doi: 10.1053/j.gastro.2022.08.034. Epub 2022 Aug 19. PMID: 35995074; PMCID: PMC9691522.



de Voogd F et al. Intestinal Ultrasound Is Accurate to Determine Endoscopic Response and Remission in Patients With Moderate to Severe Ulcerative Colitis: A Longitudinal Prospective Cohort Study. Gastroenterology. 2022 Dec;163(6):1569-81. doi: 10.1053/j.gastro.2022.08.038. Epub 2022 Aug 24. PMID: 36030056.
 

Clinical Gastroenterology and Hepatology

October 2022

Bhavsar-Burke I et al. How to Promote Professional Identity Development and Support Fellows-In-Training Through Teaching, Coaching, Mentorship, and Sponsorship. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2166-9. doi: 10.1016/j.cgh.2022.05.043. Epub 2022 Aug 7. PMID: 35948073.



van Megen F et al. A Low FODMAP Diet Reduces Symptoms in Treated Celiac Patients With Ongoing Symptoms – A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2258-66.e3. doi: 10.1016/j.cgh.2022.01.011. Epub 2022 Jan 17. PMID: 35051648.



November 2022

Sharzehi K et al. AGA Clinical Practice Update on Management of Subepithelial Lesions Encountered During Routine Endoscopy: Expert Review. Clin Gastroenterol Hepatol. 2022 Nov;20(11):2435-43.e4. doi: 10.1016/j.cgh.2022.05.054. Epub 2022 Jul 13. PMID: 35842117.



December 2022

Kardashian A et al. Food Insecurity is Associated With Mortality Among U.S. Adults With Nonalcoholic Fatty Liver Disease and Advanced Fibrosis. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2790-9.e4. doi: 10.1016/j.cgh.2021.11.029. Epub 2021 Dec 16. PMID: 34958747.



Schuitenmaker JM et al. Sleep Positional Therapy for Nocturnal Gastroesophageal Reflux: A Double-Blind, Randomized, Sham-Controlled Trial. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2753-62.e2. doi: 10.1016/j.cgh.2022.02.058. Epub 2022 Mar 14. PMID: 35301135.
 

Techniques and Innovations in Gastrointestinal Endoscopy

Azizian JM et al. Yield of Post-Acute Diverticulitis Colonoscopy for Ruling Out Colorectal Cancer. Tech Innov Gastrointest Endosc. 2022;24(3):254-61. doi: 10.1016/j.tige.2022.04.001. Epub 2022 Apr 18. PMID: 36540108; PMCID: PMC9762736.
 

Gastro Hep Advances

Kim RW et al. Timely Albumin Improves Survival in Patients With Cirrhosis on Diuretic Therapy Who Develop Acute Kidney Injury: Real-World Evidence in the United States. Gastro Hep Advances. 2023;2(2):252-60. doi: 10.1016/j.gastha.2022.10.008.

A statewide quality initiative can improve severe maternal morbidity (SMM) and reduce the incidence of maternal morbidity and mortality from postpartum hemorrhage (PPH), a modeling analysis found. Such measures could potentially provide savings to birthing hospitals, according to the California cost-effectiveness study, published in Obstetrics & Gynecology.

A team led by Eric C. Wiesehan, MHA, MBA, a PhD candidate in health policy at Stanford (Calif.) University, examined the effects of the safety initiative of the California Maternal Quality Care Collaborative (CMQCC) in a theoretical cohort of 480,000 births across a mix of hospital settings and sizes. The CMQCC developed a PPH toolkit and quality-improvement protocol to increase recognition, measurement, and timely response to PPH.

Drawing retrospectively on a large 2017 California implementation study, the simulation estimated that collaborative implementation of the CMQCC added 182 quality-adjusted life-years (0.000379 per birth) by averting 913 cases of SMM, 28 emergency hysterectomies, and one maternal mortality. Additionally, it saved $9 million ($17.78 per birth) owing to avoided SMM costs.

According to the Centers for Disease Control and Prevention, pregnancy-related maternal deaths in the United States have increased from 7.2 per 100,000 live births to 16.9 per 100,000 live births over the past 20 years, making it the only country in the Organization for Economic Cooperation and Development with rising rates of maternal mortality. PPH accounts for 11% of maternal deaths.

As to the study’s broader applicability, Dr. Wiesehan said in an interview, “findings of effectiveness in terms of reducing PPH-related SMM are well known outside of California. In terms of costs, however, it is more of an unknown how much is generalizable. It would go a long way if another state quality care collaborative implementing such a project recorded costs prospectively. Prospective costing, particularly microcosting, would be optimal to precisely place where the most, or least, value of this quality improvement project is achieved.”

Studies of PPH safety programs in other U.S. jurisdictions showing reductions in blood transfusions and maternal morbidities suggest the current findings are relevant to a range of hospital settings and regions. “With state perinatal collaboratives already in 47 states, examination of implementation of the PPH-SMM reduction initiative within additional collaboratives would add further robustness to our findings,” the authors wrote.

In 2022, a New York City hospital study reported that learning collaboratives that optimize practice and raise staff awareness could be important tools for improving maternal outcomes.

Still to be answered, said Dr. Wiesehan, are questions about the long-term effectiveness and sustainability of the quality initiative project beyond the early pre/post periods. 

The authors indicated no specific funding for the study and had no conflicts of interest to disclose.

A statewide quality initiative can improve severe maternal morbidity (SMM) and reduce the incidence of maternal morbidity and mortality from postpartum hemorrhage (PPH), a modeling analysis found. Such measures could potentially provide savings to birthing hospitals, according to the California cost-effectiveness study, published in Obstetrics & Gynecology.

A team led by Eric C. Wiesehan, MHA, MBA, a PhD candidate in health policy at Stanford (Calif.) University, examined the effects of the safety initiative of the California Maternal Quality Care Collaborative (CMQCC) in a theoretical cohort of 480,000 births across a mix of hospital settings and sizes. The CMQCC developed a PPH toolkit and quality-improvement protocol to increase recognition, measurement, and timely response to PPH.

Drawing retrospectively on a large 2017 California implementation study, the simulation estimated that collaborative implementation of the CMQCC added 182 quality-adjusted life-years (0.000379 per birth) by averting 913 cases of SMM, 28 emergency hysterectomies, and one maternal mortality. Additionally, it saved $9 million ($17.78 per birth) owing to avoided SMM costs.

According to the Centers for Disease Control and Prevention, pregnancy-related maternal deaths in the United States have increased from 7.2 per 100,000 live births to 16.9 per 100,000 live births over the past 20 years, making it the only country in the Organization for Economic Cooperation and Development with rising rates of maternal mortality. PPH accounts for 11% of maternal deaths.

As to the study’s broader applicability, Dr. Wiesehan said in an interview, “findings of effectiveness in terms of reducing PPH-related SMM are well known outside of California. In terms of costs, however, it is more of an unknown how much is generalizable. It would go a long way if another state quality care collaborative implementing such a project recorded costs prospectively. Prospective costing, particularly microcosting, would be optimal to precisely place where the most, or least, value of this quality improvement project is achieved.”

Studies of PPH safety programs in other U.S. jurisdictions showing reductions in blood transfusions and maternal morbidities suggest the current findings are relevant to a range of hospital settings and regions. “With state perinatal collaboratives already in 47 states, examination of implementation of the PPH-SMM reduction initiative within additional collaboratives would add further robustness to our findings,” the authors wrote.

In 2022, a New York City hospital study reported that learning collaboratives that optimize practice and raise staff awareness could be important tools for improving maternal outcomes.

Still to be answered, said Dr. Wiesehan, are questions about the long-term effectiveness and sustainability of the quality initiative project beyond the early pre/post periods. 

The authors indicated no specific funding for the study and had no conflicts of interest to disclose.

A statewide quality initiative can improve severe maternal morbidity (SMM) and reduce the incidence of maternal morbidity and mortality from postpartum hemorrhage (PPH), a modeling analysis found. Such measures could potentially provide savings to birthing hospitals, according to the California cost-effectiveness study, published in Obstetrics & Gynecology.

A team led by Eric C. Wiesehan, MHA, MBA, a PhD candidate in health policy at Stanford (Calif.) University, examined the effects of the safety initiative of the California Maternal Quality Care Collaborative (CMQCC) in a theoretical cohort of 480,000 births across a mix of hospital settings and sizes. The CMQCC developed a PPH toolkit and quality-improvement protocol to increase recognition, measurement, and timely response to PPH.

Drawing retrospectively on a large 2017 California implementation study, the simulation estimated that collaborative implementation of the CMQCC added 182 quality-adjusted life-years (0.000379 per birth) by averting 913 cases of SMM, 28 emergency hysterectomies, and one maternal mortality. Additionally, it saved $9 million ($17.78 per birth) owing to avoided SMM costs.

According to the Centers for Disease Control and Prevention, pregnancy-related maternal deaths in the United States have increased from 7.2 per 100,000 live births to 16.9 per 100,000 live births over the past 20 years, making it the only country in the Organization for Economic Cooperation and Development with rising rates of maternal mortality. PPH accounts for 11% of maternal deaths.

As to the study’s broader applicability, Dr. Wiesehan said in an interview, “findings of effectiveness in terms of reducing PPH-related SMM are well known outside of California. In terms of costs, however, it is more of an unknown how much is generalizable. It would go a long way if another state quality care collaborative implementing such a project recorded costs prospectively. Prospective costing, particularly microcosting, would be optimal to precisely place where the most, or least, value of this quality improvement project is achieved.”

Studies of PPH safety programs in other U.S. jurisdictions showing reductions in blood transfusions and maternal morbidities suggest the current findings are relevant to a range of hospital settings and regions. “With state perinatal collaboratives already in 47 states, examination of implementation of the PPH-SMM reduction initiative within additional collaboratives would add further robustness to our findings,” the authors wrote.

In 2022, a New York City hospital study reported that learning collaboratives that optimize practice and raise staff awareness could be important tools for improving maternal outcomes.

Still to be answered, said Dr. Wiesehan, are questions about the long-term effectiveness and sustainability of the quality initiative project beyond the early pre/post periods. 

The authors indicated no specific funding for the study and had no conflicts of interest to disclose.

Bariatric surgery for severe obesity does not appear to raise the risk of esophageal and gastric cancer, a new study shows.

In fact, an analysis of close to 1 million French adults suggests that the weight-loss surgery may offer some protection against these cancers.

The study results present a “clinical paradox,” according to authors of a commentary published this week along with the study in JAMA Surgery. A procedure known to increase the risk of gastroesophageal reflux disease (GERD), and potentially adenocarcinoma of the distal esophagus and gastroesophageal junction, may help shield patients from esophagogastric cancer.

The study marks “an important step toward improving the understanding of potential lifetime risks of bariatric surgery and overall major health benefits of surgically induced weight loss,” commentary authors Piotr Gorecki, MD, and Michael Zenilman, MD, with Weill Cornell Medicine in New York, write.

Recent data indicate that excess body weight is associated with nearly 8% of cancer cases and 6.5% of cancer deaths. Studies also show that bariatric surgery can reduce the risk of some cancers, but whether this extends to esophageal and gastric cancer remains unclear.

To investigate, the researchers used French national data to compare the incidence of esophageal and gastric cancer in 303,709 mostly female patients with obesity who underwent bariatric surgery and a matched group of 605,140 patients with obesity who did not undergo the surgery.

The mean age of the cohort was about 40 years. The mean period of follow-up was 6 years for the surgery group and 5.6 years for the control arm. A total of 337 patients underwent esophagogastric cancer – 83 in the surgical group and 254 in the control group. Gastric cancer was about two times more common than esophageal cancer (225 vs. 112 patients).

The incidence rate of esophagogastric cancer was higher in the control group than in the surgery group – 6.9 vs. 4.9 cases per 100,000 population per year, for an incidence rate ratio of 1.42 (P = .005).

Bariatric surgery was associated with a significant 24% lower risk of esophagogastric cancer (hazard ratio, 0.76; P = .03) and a 40% lower risk of overall in-hospital mortality, defined as “any death occurring during a hospital stay regardless of the cause” (HR, 0.60; P < .001).

The authors also found no significant difference in cancer outcomes and type of bariatric procedure, which included sleeve gastrectomy, gastric bypass, and adjustable gastric banding.

They note that key study limitations include the retrospective design, limited follow-up period, and lack of histologic data on the specific cancers. In addition, the study population was relatively young, whereas esophageal cancer is more common in older people.

But overall, the findings suggest that bariatric surgery can be performed to treat severe obesity without increasing the risk of esophageal and gastric cancer, the authors conclude.

“It seems that the balance between protective factors (weight loss, metabolic effects, and eradication of H. pylori infection) and risk factors (GERD and bile reflux) for cancer after bariatric surgery is in favor of protective factors,” the authors, led by Andrea Lazzati, MD, PhD, of Centre Hospitalier Intercommunal de Créteil, France, explain.

Although the potential protective mechanisms remain unclear, in their commentary, Dr. Gorecki and Dr. Zenilman suggest that a reduction in chronic inflammation and immunosuppression following bariatric surgery could help explain the results.

Although the study provides “reassurance of the protective clinical benefits of weight loss surgery,” more large-scale studies are needed to “better identify, elucidate, and address the pathophysiological processes of bariatric procedure,” Dr. Gorecki and Dr. Zenilman conclude.

No specific funding for the study was reported. Dr. Lazzati has received personal fees from Johnson & Johnson, Medtronic, and Gore. Dr. Zenilman has received personal fees from Academic Medical Professionals Insurance and Mohamed & Obaid Almulla Group.

A version of this article first appeared on Medscape.com.

Bariatric surgery for severe obesity does not appear to raise the risk of esophageal and gastric cancer, a new study shows.

In fact, an analysis of close to 1 million French adults suggests that the weight-loss surgery may offer some protection against these cancers.

The study results present a “clinical paradox,” according to authors of a commentary published this week along with the study in JAMA Surgery. A procedure known to increase the risk of gastroesophageal reflux disease (GERD), and potentially adenocarcinoma of the distal esophagus and gastroesophageal junction, may help shield patients from esophagogastric cancer.

The study marks “an important step toward improving the understanding of potential lifetime risks of bariatric surgery and overall major health benefits of surgically induced weight loss,” commentary authors Piotr Gorecki, MD, and Michael Zenilman, MD, with Weill Cornell Medicine in New York, write.

Recent data indicate that excess body weight is associated with nearly 8% of cancer cases and 6.5% of cancer deaths. Studies also show that bariatric surgery can reduce the risk of some cancers, but whether this extends to esophageal and gastric cancer remains unclear.

To investigate, the researchers used French national data to compare the incidence of esophageal and gastric cancer in 303,709 mostly female patients with obesity who underwent bariatric surgery and a matched group of 605,140 patients with obesity who did not undergo the surgery.

The mean age of the cohort was about 40 years. The mean period of follow-up was 6 years for the surgery group and 5.6 years for the control arm. A total of 337 patients underwent esophagogastric cancer – 83 in the surgical group and 254 in the control group. Gastric cancer was about two times more common than esophageal cancer (225 vs. 112 patients).

The incidence rate of esophagogastric cancer was higher in the control group than in the surgery group – 6.9 vs. 4.9 cases per 100,000 population per year, for an incidence rate ratio of 1.42 (P = .005).

Bariatric surgery was associated with a significant 24% lower risk of esophagogastric cancer (hazard ratio, 0.76; P = .03) and a 40% lower risk of overall in-hospital mortality, defined as “any death occurring during a hospital stay regardless of the cause” (HR, 0.60; P < .001).

The authors also found no significant difference in cancer outcomes and type of bariatric procedure, which included sleeve gastrectomy, gastric bypass, and adjustable gastric banding.

They note that key study limitations include the retrospective design, limited follow-up period, and lack of histologic data on the specific cancers. In addition, the study population was relatively young, whereas esophageal cancer is more common in older people.

But overall, the findings suggest that bariatric surgery can be performed to treat severe obesity without increasing the risk of esophageal and gastric cancer, the authors conclude.

“It seems that the balance between protective factors (weight loss, metabolic effects, and eradication of H. pylori infection) and risk factors (GERD and bile reflux) for cancer after bariatric surgery is in favor of protective factors,” the authors, led by Andrea Lazzati, MD, PhD, of Centre Hospitalier Intercommunal de Créteil, France, explain.

Although the potential protective mechanisms remain unclear, in their commentary, Dr. Gorecki and Dr. Zenilman suggest that a reduction in chronic inflammation and immunosuppression following bariatric surgery could help explain the results.

Although the study provides “reassurance of the protective clinical benefits of weight loss surgery,” more large-scale studies are needed to “better identify, elucidate, and address the pathophysiological processes of bariatric procedure,” Dr. Gorecki and Dr. Zenilman conclude.

No specific funding for the study was reported. Dr. Lazzati has received personal fees from Johnson & Johnson, Medtronic, and Gore. Dr. Zenilman has received personal fees from Academic Medical Professionals Insurance and Mohamed & Obaid Almulla Group.

A version of this article first appeared on Medscape.com.

Bariatric surgery for severe obesity does not appear to raise the risk of esophageal and gastric cancer, a new study shows.

In fact, an analysis of close to 1 million French adults suggests that the weight-loss surgery may offer some protection against these cancers.

The study results present a “clinical paradox,” according to authors of a commentary published this week along with the study in JAMA Surgery. A procedure known to increase the risk of gastroesophageal reflux disease (GERD), and potentially adenocarcinoma of the distal esophagus and gastroesophageal junction, may help shield patients from esophagogastric cancer.

The study marks “an important step toward improving the understanding of potential lifetime risks of bariatric surgery and overall major health benefits of surgically induced weight loss,” commentary authors Piotr Gorecki, MD, and Michael Zenilman, MD, with Weill Cornell Medicine in New York, write.

Recent data indicate that excess body weight is associated with nearly 8% of cancer cases and 6.5% of cancer deaths. Studies also show that bariatric surgery can reduce the risk of some cancers, but whether this extends to esophageal and gastric cancer remains unclear.

To investigate, the researchers used French national data to compare the incidence of esophageal and gastric cancer in 303,709 mostly female patients with obesity who underwent bariatric surgery and a matched group of 605,140 patients with obesity who did not undergo the surgery.

The mean age of the cohort was about 40 years. The mean period of follow-up was 6 years for the surgery group and 5.6 years for the control arm. A total of 337 patients underwent esophagogastric cancer – 83 in the surgical group and 254 in the control group. Gastric cancer was about two times more common than esophageal cancer (225 vs. 112 patients).

The incidence rate of esophagogastric cancer was higher in the control group than in the surgery group – 6.9 vs. 4.9 cases per 100,000 population per year, for an incidence rate ratio of 1.42 (P = .005).

Bariatric surgery was associated with a significant 24% lower risk of esophagogastric cancer (hazard ratio, 0.76; P = .03) and a 40% lower risk of overall in-hospital mortality, defined as “any death occurring during a hospital stay regardless of the cause” (HR, 0.60; P < .001).

The authors also found no significant difference in cancer outcomes and type of bariatric procedure, which included sleeve gastrectomy, gastric bypass, and adjustable gastric banding.

They note that key study limitations include the retrospective design, limited follow-up period, and lack of histologic data on the specific cancers. In addition, the study population was relatively young, whereas esophageal cancer is more common in older people.

But overall, the findings suggest that bariatric surgery can be performed to treat severe obesity without increasing the risk of esophageal and gastric cancer, the authors conclude.

“It seems that the balance between protective factors (weight loss, metabolic effects, and eradication of H. pylori infection) and risk factors (GERD and bile reflux) for cancer after bariatric surgery is in favor of protective factors,” the authors, led by Andrea Lazzati, MD, PhD, of Centre Hospitalier Intercommunal de Créteil, France, explain.

Although the potential protective mechanisms remain unclear, in their commentary, Dr. Gorecki and Dr. Zenilman suggest that a reduction in chronic inflammation and immunosuppression following bariatric surgery could help explain the results.

Although the study provides “reassurance of the protective clinical benefits of weight loss surgery,” more large-scale studies are needed to “better identify, elucidate, and address the pathophysiological processes of bariatric procedure,” Dr. Gorecki and Dr. Zenilman conclude.

No specific funding for the study was reported. Dr. Lazzati has received personal fees from Johnson & Johnson, Medtronic, and Gore. Dr. Zenilman has received personal fees from Academic Medical Professionals Insurance and Mohamed & Obaid Almulla Group.

A version of this article first appeared on Medscape.com.

Patients with moderate to severe active ulcerative colitis (UC) who received induction therapy with either ritlecitinib or brepocitinib showed significant improvement across multiple outcome metrics in a phase 2b “umbrella” study of the two investigational agents.

The study by William J. Sandborn, MD, division of gastroenterology, University of California, San Diego, and colleagues was published online in Clinical Gastroenterology and Hepatology.

Ritlecitinib is a dual inhibitor that selectively inhibits Janus kinase 3 (JAK3) and the TEC family of tyrosine kinases, while brepocitinib is a dual tyrosine kinase 2 (TYK2) and JAK1 inhibitor.

Both agents have demonstrated efficacy and acceptable safety in the treatment of alopecia areata and rheumatoid arthritis and are being evaluated for treating vitiligo, Crohn’s disease, and UC.

The different JAK selectivity profiles of ritlecitinib (JAK3/TEC) and brepocitinib (TYK2/JAK1), compared with other JAK inhibitors, could further the understanding of the role these pathways play in UC, the investigators note.
 

The VIBRATO study

As part of the phase 2b VIBRATO study, 317 patients with moderate to severe active UC (total Mayo Score ≥ 6) were randomly assigned to an 8-week induction course of once-daily oral ritlecitinib (20, 70, or 200 mg), brepocitinib (10, 30, or 60 mg), or matching placebo.

At week 8, compared with placebo, treatment with ritlecitinib or brepocitinib was associated with significantly lower mean total Mayo Scores (the primary endpoint) and higher rates of clinical remission, endoscopic and histologic improvement, and mucosal healing.

For both drugs, improvement on most metrics was dose dependent, with greater benefit at the highest dose.

For example, the placebo-adjusted mean total Mayo Score at week 8 was −4.6 for ritlecitinib 200 mg (P < .001) and −3.2 for brepocitinib 60 mg (P < .001). Both agents showed a “rapid” onset of action, with significant effects on the partial Mayo Score seen after just 2 weeks of treatment, the authors report.

Modified clinical remission at week 8 (a key secondary endpoint) was achieved in 36% of patients taking ritlecitinib 200 mg and 25.5% of those taking brepocitinib 60 mg (vs. 0% for patients taking placebo).

Endoscopic and histologic improvement, clinical response, mucosal healing, and the patient-reported outcome on the Inflammatory Bowel Disease Questionnaire followed a similar pattern, with a dose-dependent increase in treatment effect observed in most parameters at week 8, compared with placebo.
 

Longer-term data needed

Both agents were well tolerated with “acceptable short-term safety profiles,” the authors say.

There were no clinically significant findings for any laboratory parameters evaluated. Adverse events were mostly mild.

Infections were observed in 8.7% of patients taking ritlecitinib and 16.9% of those taking brepocitinib, compared with 4% of patients taking placebo. No serious cases of herpes zoster occurred.

One patient taking ritlecitinib suffered myocardial infarction and died, and one patient taking brepocitinib had peripheral artery thrombosis (left tibial artery). Both cases were considered unrelated to the study drug.

“As JAK inhibitors are associated with increased risk of major cardiovascular events and venous thromboembolisms, larger studies are needed for ritlecitinib and brepocitinib to fully understand their safety profiles,” the investigators say.

Limitations of the study include the small sample size and short 8-week treatment period. Longer-term safety and efficacy of both agents are being investigated.

The study was sponsored by Pfizer, which is developing both drugs. Dr. Sandborn and several coauthors have disclosed financial relationships with the company.

A version of this article first appeared on Medscape.com.

Patients with moderate to severe active ulcerative colitis (UC) who received induction therapy with either ritlecitinib or brepocitinib showed significant improvement across multiple outcome metrics in a phase 2b “umbrella” study of the two investigational agents.

The study by William J. Sandborn, MD, division of gastroenterology, University of California, San Diego, and colleagues was published online in Clinical Gastroenterology and Hepatology.

Ritlecitinib is a dual inhibitor that selectively inhibits Janus kinase 3 (JAK3) and the TEC family of tyrosine kinases, while brepocitinib is a dual tyrosine kinase 2 (TYK2) and JAK1 inhibitor.

Both agents have demonstrated efficacy and acceptable safety in the treatment of alopecia areata and rheumatoid arthritis and are being evaluated for treating vitiligo, Crohn’s disease, and UC.

The different JAK selectivity profiles of ritlecitinib (JAK3/TEC) and brepocitinib (TYK2/JAK1), compared with other JAK inhibitors, could further the understanding of the role these pathways play in UC, the investigators note.
 

The VIBRATO study

As part of the phase 2b VIBRATO study, 317 patients with moderate to severe active UC (total Mayo Score ≥ 6) were randomly assigned to an 8-week induction course of once-daily oral ritlecitinib (20, 70, or 200 mg), brepocitinib (10, 30, or 60 mg), or matching placebo.

At week 8, compared with placebo, treatment with ritlecitinib or brepocitinib was associated with significantly lower mean total Mayo Scores (the primary endpoint) and higher rates of clinical remission, endoscopic and histologic improvement, and mucosal healing.

For both drugs, improvement on most metrics was dose dependent, with greater benefit at the highest dose.

For example, the placebo-adjusted mean total Mayo Score at week 8 was −4.6 for ritlecitinib 200 mg (P < .001) and −3.2 for brepocitinib 60 mg (P < .001). Both agents showed a “rapid” onset of action, with significant effects on the partial Mayo Score seen after just 2 weeks of treatment, the authors report.

Modified clinical remission at week 8 (a key secondary endpoint) was achieved in 36% of patients taking ritlecitinib 200 mg and 25.5% of those taking brepocitinib 60 mg (vs. 0% for patients taking placebo).

Endoscopic and histologic improvement, clinical response, mucosal healing, and the patient-reported outcome on the Inflammatory Bowel Disease Questionnaire followed a similar pattern, with a dose-dependent increase in treatment effect observed in most parameters at week 8, compared with placebo.
 

Longer-term data needed

Both agents were well tolerated with “acceptable short-term safety profiles,” the authors say.

There were no clinically significant findings for any laboratory parameters evaluated. Adverse events were mostly mild.

Infections were observed in 8.7% of patients taking ritlecitinib and 16.9% of those taking brepocitinib, compared with 4% of patients taking placebo. No serious cases of herpes zoster occurred.

One patient taking ritlecitinib suffered myocardial infarction and died, and one patient taking brepocitinib had peripheral artery thrombosis (left tibial artery). Both cases were considered unrelated to the study drug.

“As JAK inhibitors are associated with increased risk of major cardiovascular events and venous thromboembolisms, larger studies are needed for ritlecitinib and brepocitinib to fully understand their safety profiles,” the investigators say.

Limitations of the study include the small sample size and short 8-week treatment period. Longer-term safety and efficacy of both agents are being investigated.

The study was sponsored by Pfizer, which is developing both drugs. Dr. Sandborn and several coauthors have disclosed financial relationships with the company.

A version of this article first appeared on Medscape.com.

Patients with moderate to severe active ulcerative colitis (UC) who received induction therapy with either ritlecitinib or brepocitinib showed significant improvement across multiple outcome metrics in a phase 2b “umbrella” study of the two investigational agents.

The study by William J. Sandborn, MD, division of gastroenterology, University of California, San Diego, and colleagues was published online in Clinical Gastroenterology and Hepatology.

Ritlecitinib is a dual inhibitor that selectively inhibits Janus kinase 3 (JAK3) and the TEC family of tyrosine kinases, while brepocitinib is a dual tyrosine kinase 2 (TYK2) and JAK1 inhibitor.

Both agents have demonstrated efficacy and acceptable safety in the treatment of alopecia areata and rheumatoid arthritis and are being evaluated for treating vitiligo, Crohn’s disease, and UC.

The different JAK selectivity profiles of ritlecitinib (JAK3/TEC) and brepocitinib (TYK2/JAK1), compared with other JAK inhibitors, could further the understanding of the role these pathways play in UC, the investigators note.
 

The VIBRATO study

As part of the phase 2b VIBRATO study, 317 patients with moderate to severe active UC (total Mayo Score ≥ 6) were randomly assigned to an 8-week induction course of once-daily oral ritlecitinib (20, 70, or 200 mg), brepocitinib (10, 30, or 60 mg), or matching placebo.

At week 8, compared with placebo, treatment with ritlecitinib or brepocitinib was associated with significantly lower mean total Mayo Scores (the primary endpoint) and higher rates of clinical remission, endoscopic and histologic improvement, and mucosal healing.

For both drugs, improvement on most metrics was dose dependent, with greater benefit at the highest dose.

For example, the placebo-adjusted mean total Mayo Score at week 8 was −4.6 for ritlecitinib 200 mg (P < .001) and −3.2 for brepocitinib 60 mg (P < .001). Both agents showed a “rapid” onset of action, with significant effects on the partial Mayo Score seen after just 2 weeks of treatment, the authors report.

Modified clinical remission at week 8 (a key secondary endpoint) was achieved in 36% of patients taking ritlecitinib 200 mg and 25.5% of those taking brepocitinib 60 mg (vs. 0% for patients taking placebo).

Endoscopic and histologic improvement, clinical response, mucosal healing, and the patient-reported outcome on the Inflammatory Bowel Disease Questionnaire followed a similar pattern, with a dose-dependent increase in treatment effect observed in most parameters at week 8, compared with placebo.
 

Longer-term data needed

Both agents were well tolerated with “acceptable short-term safety profiles,” the authors say.

There were no clinically significant findings for any laboratory parameters evaluated. Adverse events were mostly mild.

Infections were observed in 8.7% of patients taking ritlecitinib and 16.9% of those taking brepocitinib, compared with 4% of patients taking placebo. No serious cases of herpes zoster occurred.

One patient taking ritlecitinib suffered myocardial infarction and died, and one patient taking brepocitinib had peripheral artery thrombosis (left tibial artery). Both cases were considered unrelated to the study drug.

“As JAK inhibitors are associated with increased risk of major cardiovascular events and venous thromboembolisms, larger studies are needed for ritlecitinib and brepocitinib to fully understand their safety profiles,” the investigators say.

Limitations of the study include the small sample size and short 8-week treatment period. Longer-term safety and efficacy of both agents are being investigated.

The study was sponsored by Pfizer, which is developing both drugs. Dr. Sandborn and several coauthors have disclosed financial relationships with the company.

A version of this article first appeared on Medscape.com.