Guidelines

The European Alliance of Associations for Rheumatology has updated its recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The 2022 revision – which was unveiled at the annual European Congress of Rheumatology – includes guidance on using new drugs, such as avacopan (Tavneos) and mepolizumab (Nucala), as well as revised recommendations on the use of rituximab and glucocorticosteroids.

EULAR

The overhaul also contains specific recommendations for treating eosinophilic granulomatosis with polyangiitis (EGPA), separating it out from granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) for the first time.

“Until now, EGPA has usually been managed in the same way as [the] other diseases,” Bernhard Hellmich, MD, of the University of Tübingen (Germany) said in an interview ahead of his presentation at the congress.

“But we now have data on each type specifically, so there is good reason to make separate recommendations,” he added.

Indeed, so much new data has become available in the past few years there are only three recommendations that remain unchanged from the previous iteration published in 2016.

Since then, “several high-impact studies in AAV have been published and the results of these studies required an update of the existing recommendations,” Dr. Hellmich said.

Developed in record time – just 7 months from start to finish – the process of updating the recommendations on AAV followed EULAR’s standard operating procedures. An important step in this process is to perform a systemic literature review. Perhaps crucially, and in contrast to the first U.S. vasculitis guidelines published only in 2021, the most recent literature search was able to include data on avacopan, which was approved for use in Europe in January as an adjunctive treatment for adults with severe active GPA and MPA.

The results of the literature review were reported separately at the EULAR 2022 Congress, with separate presentations highlighting the data behind the amended treatment and diagnostic and follow-up procedure recommendations.
 

Highlights of the changes

A key change is the introduction of four overarching principles, which weren’t included in the previous update, said Dr. Hellmich.

“We moved some of the existing recommendations with low level of evidence to overarching principles,” he added, stating that the first general principle was that all patients should be offered “the best care which must be based on shared decision-making between the patient and the physician considering efficacy, safety, and costs.”

The second principle states that patients should have access to education that covers the prognosis and impact of AAV, including recognizing warning symptoms and treatment options.

The third focuses on screening for adverse effects and comorbidities, recommending that patients are given appropriate prophylaxis and lifestyle advice.

Finally, the fourth general principle recognizes that AAV is a rare group of heterogenous and potentially life-threatening diseases that need multidisciplinary care, with access to specific vasculitis expertise.
 

New recommendations

Of the 17 recommendations made, 6 are completely new, including one on ANCA testing in patients who are suspected of having AAV.

“We recommend testing for both PR3- and MPO-ANCA using a high-quality antigen-specific assay as the primary method of testing,” Dr. Hellmich said. This is based on strong new evidence that antigen-specific assays have superior diagnostic accuracy, compared with indirect immunofluorescence.

“We also want to emphasize that ANCA testing should be done in patients with signs and symptoms in order to minimize the risk of false-positive results,” Dr. Hellmich said.

Also new is the recommendation to use oral steroids to induce remission in GPA/MPA, followed by a stepwise reduction in the dose, aiming for a dose of not more than 5 mg prednisolone per day by 4-5 months of treatment.

“Glucocorticoids are very effective, but also are the major trigger of infections in AAV,” said Dr. Hellmich. This is important since infections are a major driver of early mortality in AAV.

“Another possibility to reduce glucocorticoid exposure is avacopan,” he said. It’s recommended to be used in combination with rituximab or cyclophosphamide for remission induction in GPA/MPA as a strategy to basically “get rid of steroids.”

Indeed, “for patients who really have a high burden of glucocorticoid-associated adverse effects, especially relapsing patients, I think it would make sense just to give avacopan and no steroids,” Dr. Hellmich said.

Other new recommendations concern remission induction and maintenance therapy in new-onset EGPA. Regarding the latter, the choice of treatment depends on whether there is an organ- or life-threatening situation, with methotrexate, azathioprine, mepolizumab, or rituximab all recommended equally, or if there is no organ- or life-threatening situation, then mepolizumab is preferred.
 

Revised and unchanged recommendations

Eight of the recommendations have been revised, with rituximab being placed more prominently as a treatment in some. For remission induction in GPA and MPA with organ- or life threatening disease, rituximab is now the preferred option for relapsing disease. Rituximab also replaced methotrexate as the preferred option for maintaining remission, although methotrexate and azathioprine can still be considered as alternatives.

Another changed statement is on the duration of maintenance treatment in GPA and MPA, which now advocates 1-2 years of treatment after achieving remission. Longer therapy might be needed in relapsing cases, but the benefits and risks need to be carefully considered and patient preferences taken into account.

Prophylaxis against pneumonia and other infections is still recommended, with the revised guidance noting that patients receiving cyclophosphamide, rituximab, or high-dose steroids, should be treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

“There are retrospective data in the AAV population that the administration of co-trimoxazole reduces not only the incidence of pneumocystis, but also of other infections. So, this is important recommendation for clinical practice,” Dr. Hellmich said.
 

Summing up

“For a rare disease group, I think this is very good progress,” said Dr. Hellmich, but “there are still many open questions, so we have a long research agenda.”

There is purposefully no recommendation on COVID-19, however, as “the conditions that impact COVID outcomes change rapidly and any recommendation made now is likely to be outdated soon; the AAV recommendations are intended to last for at least a couple of years.”

In a press release issued by the German Society for Rheumatology, which was unrelated to Dr. Hellmich’s talk, experts commented on vasculitis guidelines generally, noting that there has been a move toward using biologic therapies such as rituximab and mepolizumab as a new standard of therapy.

DGRh President and chief physician at the Immanuel Hospital in Berlin Andreas Krause, MD, observed that “cyclophosphamide, which was used in the past and which inhibits blood formation in the bone marrow and can lead to infertility, can now often be dispensed with.”

Julia Holle, MD, of Rheumazentrum Schleswig-Holstein Mitte in Neumünster, Germany, was also quoted in the press release, saying that, “for patients, the successful use of biologics and the reduction in the glucocorticoid dose is important progress.”

Dr. Holle was involved in the development of revised European guidelines. She is also the lead author of a recent publication on treatment of vasculitis on available evidence. Dr. Hellmich acknowledged having ties to multiple pharma companies, acting as speaker, consultant, or both to Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, InflaRx, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Vifor.


 

The European Alliance of Associations for Rheumatology has updated its recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The 2022 revision – which was unveiled at the annual European Congress of Rheumatology – includes guidance on using new drugs, such as avacopan (Tavneos) and mepolizumab (Nucala), as well as revised recommendations on the use of rituximab and glucocorticosteroids.

EULAR

The overhaul also contains specific recommendations for treating eosinophilic granulomatosis with polyangiitis (EGPA), separating it out from granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) for the first time.

“Until now, EGPA has usually been managed in the same way as [the] other diseases,” Bernhard Hellmich, MD, of the University of Tübingen (Germany) said in an interview ahead of his presentation at the congress.

“But we now have data on each type specifically, so there is good reason to make separate recommendations,” he added.

Indeed, so much new data has become available in the past few years there are only three recommendations that remain unchanged from the previous iteration published in 2016.

Since then, “several high-impact studies in AAV have been published and the results of these studies required an update of the existing recommendations,” Dr. Hellmich said.

Developed in record time – just 7 months from start to finish – the process of updating the recommendations on AAV followed EULAR’s standard operating procedures. An important step in this process is to perform a systemic literature review. Perhaps crucially, and in contrast to the first U.S. vasculitis guidelines published only in 2021, the most recent literature search was able to include data on avacopan, which was approved for use in Europe in January as an adjunctive treatment for adults with severe active GPA and MPA.

The results of the literature review were reported separately at the EULAR 2022 Congress, with separate presentations highlighting the data behind the amended treatment and diagnostic and follow-up procedure recommendations.
 

Highlights of the changes

A key change is the introduction of four overarching principles, which weren’t included in the previous update, said Dr. Hellmich.

“We moved some of the existing recommendations with low level of evidence to overarching principles,” he added, stating that the first general principle was that all patients should be offered “the best care which must be based on shared decision-making between the patient and the physician considering efficacy, safety, and costs.”

The second principle states that patients should have access to education that covers the prognosis and impact of AAV, including recognizing warning symptoms and treatment options.

The third focuses on screening for adverse effects and comorbidities, recommending that patients are given appropriate prophylaxis and lifestyle advice.

Finally, the fourth general principle recognizes that AAV is a rare group of heterogenous and potentially life-threatening diseases that need multidisciplinary care, with access to specific vasculitis expertise.
 

New recommendations

Of the 17 recommendations made, 6 are completely new, including one on ANCA testing in patients who are suspected of having AAV.

“We recommend testing for both PR3- and MPO-ANCA using a high-quality antigen-specific assay as the primary method of testing,” Dr. Hellmich said. This is based on strong new evidence that antigen-specific assays have superior diagnostic accuracy, compared with indirect immunofluorescence.

“We also want to emphasize that ANCA testing should be done in patients with signs and symptoms in order to minimize the risk of false-positive results,” Dr. Hellmich said.

Also new is the recommendation to use oral steroids to induce remission in GPA/MPA, followed by a stepwise reduction in the dose, aiming for a dose of not more than 5 mg prednisolone per day by 4-5 months of treatment.

“Glucocorticoids are very effective, but also are the major trigger of infections in AAV,” said Dr. Hellmich. This is important since infections are a major driver of early mortality in AAV.

“Another possibility to reduce glucocorticoid exposure is avacopan,” he said. It’s recommended to be used in combination with rituximab or cyclophosphamide for remission induction in GPA/MPA as a strategy to basically “get rid of steroids.”

Indeed, “for patients who really have a high burden of glucocorticoid-associated adverse effects, especially relapsing patients, I think it would make sense just to give avacopan and no steroids,” Dr. Hellmich said.

Other new recommendations concern remission induction and maintenance therapy in new-onset EGPA. Regarding the latter, the choice of treatment depends on whether there is an organ- or life-threatening situation, with methotrexate, azathioprine, mepolizumab, or rituximab all recommended equally, or if there is no organ- or life-threatening situation, then mepolizumab is preferred.
 

Revised and unchanged recommendations

Eight of the recommendations have been revised, with rituximab being placed more prominently as a treatment in some. For remission induction in GPA and MPA with organ- or life threatening disease, rituximab is now the preferred option for relapsing disease. Rituximab also replaced methotrexate as the preferred option for maintaining remission, although methotrexate and azathioprine can still be considered as alternatives.

Another changed statement is on the duration of maintenance treatment in GPA and MPA, which now advocates 1-2 years of treatment after achieving remission. Longer therapy might be needed in relapsing cases, but the benefits and risks need to be carefully considered and patient preferences taken into account.

Prophylaxis against pneumonia and other infections is still recommended, with the revised guidance noting that patients receiving cyclophosphamide, rituximab, or high-dose steroids, should be treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

“There are retrospective data in the AAV population that the administration of co-trimoxazole reduces not only the incidence of pneumocystis, but also of other infections. So, this is important recommendation for clinical practice,” Dr. Hellmich said.
 

Summing up

“For a rare disease group, I think this is very good progress,” said Dr. Hellmich, but “there are still many open questions, so we have a long research agenda.”

There is purposefully no recommendation on COVID-19, however, as “the conditions that impact COVID outcomes change rapidly and any recommendation made now is likely to be outdated soon; the AAV recommendations are intended to last for at least a couple of years.”

In a press release issued by the German Society for Rheumatology, which was unrelated to Dr. Hellmich’s talk, experts commented on vasculitis guidelines generally, noting that there has been a move toward using biologic therapies such as rituximab and mepolizumab as a new standard of therapy.

DGRh President and chief physician at the Immanuel Hospital in Berlin Andreas Krause, MD, observed that “cyclophosphamide, which was used in the past and which inhibits blood formation in the bone marrow and can lead to infertility, can now often be dispensed with.”

Julia Holle, MD, of Rheumazentrum Schleswig-Holstein Mitte in Neumünster, Germany, was also quoted in the press release, saying that, “for patients, the successful use of biologics and the reduction in the glucocorticoid dose is important progress.”

Dr. Holle was involved in the development of revised European guidelines. She is also the lead author of a recent publication on treatment of vasculitis on available evidence. Dr. Hellmich acknowledged having ties to multiple pharma companies, acting as speaker, consultant, or both to Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, InflaRx, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Vifor.


 

The European Alliance of Associations for Rheumatology has updated its recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

The 2022 revision – which was unveiled at the annual European Congress of Rheumatology – includes guidance on using new drugs, such as avacopan (Tavneos) and mepolizumab (Nucala), as well as revised recommendations on the use of rituximab and glucocorticosteroids.

EULAR

The overhaul also contains specific recommendations for treating eosinophilic granulomatosis with polyangiitis (EGPA), separating it out from granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) for the first time.

“Until now, EGPA has usually been managed in the same way as [the] other diseases,” Bernhard Hellmich, MD, of the University of Tübingen (Germany) said in an interview ahead of his presentation at the congress.

“But we now have data on each type specifically, so there is good reason to make separate recommendations,” he added.

Indeed, so much new data has become available in the past few years there are only three recommendations that remain unchanged from the previous iteration published in 2016.

Since then, “several high-impact studies in AAV have been published and the results of these studies required an update of the existing recommendations,” Dr. Hellmich said.

Developed in record time – just 7 months from start to finish – the process of updating the recommendations on AAV followed EULAR’s standard operating procedures. An important step in this process is to perform a systemic literature review. Perhaps crucially, and in contrast to the first U.S. vasculitis guidelines published only in 2021, the most recent literature search was able to include data on avacopan, which was approved for use in Europe in January as an adjunctive treatment for adults with severe active GPA and MPA.

The results of the literature review were reported separately at the EULAR 2022 Congress, with separate presentations highlighting the data behind the amended treatment and diagnostic and follow-up procedure recommendations.
 

Highlights of the changes

A key change is the introduction of four overarching principles, which weren’t included in the previous update, said Dr. Hellmich.

“We moved some of the existing recommendations with low level of evidence to overarching principles,” he added, stating that the first general principle was that all patients should be offered “the best care which must be based on shared decision-making between the patient and the physician considering efficacy, safety, and costs.”

The second principle states that patients should have access to education that covers the prognosis and impact of AAV, including recognizing warning symptoms and treatment options.

The third focuses on screening for adverse effects and comorbidities, recommending that patients are given appropriate prophylaxis and lifestyle advice.

Finally, the fourth general principle recognizes that AAV is a rare group of heterogenous and potentially life-threatening diseases that need multidisciplinary care, with access to specific vasculitis expertise.
 

New recommendations

Of the 17 recommendations made, 6 are completely new, including one on ANCA testing in patients who are suspected of having AAV.

“We recommend testing for both PR3- and MPO-ANCA using a high-quality antigen-specific assay as the primary method of testing,” Dr. Hellmich said. This is based on strong new evidence that antigen-specific assays have superior diagnostic accuracy, compared with indirect immunofluorescence.

“We also want to emphasize that ANCA testing should be done in patients with signs and symptoms in order to minimize the risk of false-positive results,” Dr. Hellmich said.

Also new is the recommendation to use oral steroids to induce remission in GPA/MPA, followed by a stepwise reduction in the dose, aiming for a dose of not more than 5 mg prednisolone per day by 4-5 months of treatment.

“Glucocorticoids are very effective, but also are the major trigger of infections in AAV,” said Dr. Hellmich. This is important since infections are a major driver of early mortality in AAV.

“Another possibility to reduce glucocorticoid exposure is avacopan,” he said. It’s recommended to be used in combination with rituximab or cyclophosphamide for remission induction in GPA/MPA as a strategy to basically “get rid of steroids.”

Indeed, “for patients who really have a high burden of glucocorticoid-associated adverse effects, especially relapsing patients, I think it would make sense just to give avacopan and no steroids,” Dr. Hellmich said.

Other new recommendations concern remission induction and maintenance therapy in new-onset EGPA. Regarding the latter, the choice of treatment depends on whether there is an organ- or life-threatening situation, with methotrexate, azathioprine, mepolizumab, or rituximab all recommended equally, or if there is no organ- or life-threatening situation, then mepolizumab is preferred.
 

Revised and unchanged recommendations

Eight of the recommendations have been revised, with rituximab being placed more prominently as a treatment in some. For remission induction in GPA and MPA with organ- or life threatening disease, rituximab is now the preferred option for relapsing disease. Rituximab also replaced methotrexate as the preferred option for maintaining remission, although methotrexate and azathioprine can still be considered as alternatives.

Another changed statement is on the duration of maintenance treatment in GPA and MPA, which now advocates 1-2 years of treatment after achieving remission. Longer therapy might be needed in relapsing cases, but the benefits and risks need to be carefully considered and patient preferences taken into account.

Prophylaxis against pneumonia and other infections is still recommended, with the revised guidance noting that patients receiving cyclophosphamide, rituximab, or high-dose steroids, should be treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

“There are retrospective data in the AAV population that the administration of co-trimoxazole reduces not only the incidence of pneumocystis, but also of other infections. So, this is important recommendation for clinical practice,” Dr. Hellmich said.
 

Summing up

“For a rare disease group, I think this is very good progress,” said Dr. Hellmich, but “there are still many open questions, so we have a long research agenda.”

There is purposefully no recommendation on COVID-19, however, as “the conditions that impact COVID outcomes change rapidly and any recommendation made now is likely to be outdated soon; the AAV recommendations are intended to last for at least a couple of years.”

In a press release issued by the German Society for Rheumatology, which was unrelated to Dr. Hellmich’s talk, experts commented on vasculitis guidelines generally, noting that there has been a move toward using biologic therapies such as rituximab and mepolizumab as a new standard of therapy.

DGRh President and chief physician at the Immanuel Hospital in Berlin Andreas Krause, MD, observed that “cyclophosphamide, which was used in the past and which inhibits blood formation in the bone marrow and can lead to infertility, can now often be dispensed with.”

Julia Holle, MD, of Rheumazentrum Schleswig-Holstein Mitte in Neumünster, Germany, was also quoted in the press release, saying that, “for patients, the successful use of biologics and the reduction in the glucocorticoid dose is important progress.”

Dr. Holle was involved in the development of revised European guidelines. She is also the lead author of a recent publication on treatment of vasculitis on available evidence. Dr. Hellmich acknowledged having ties to multiple pharma companies, acting as speaker, consultant, or both to Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, InflaRx, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Vifor.


 

All U.S. patients with diabetes should undergo annual biomarker testing to allow for early diagnosis of progressive but presymptomatic heart failure, and treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class should expand among such patients to include everyone with stage B heart failure (“pre–heart failure”) or more advanced stages.

That’s a recommendation from an American Diabetes Association consensus report published June 1 in Diabetes Care.

The report notes that until now, “implementation of available strategies to detect asymptomatic heart failure [in patients with diabetes] has been suboptimal.” The remedy for this is that, “among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and to implement strategies to prevent transition to symptomatic heart failure.”

Written by a 10-member panel, chaired by Rodica Pop-Busui, MD, PhD, and endorsed by the American College of Cardiology, the document also set threshold for levels of these biomarkers that are diagnostic for a more advanced stage (stage B) of heart failure in patients with diabetes but without heart failure symptoms:

• A B-type natriuretic peptide (BNP) level of ≥50 pg/mL;
• An N-terminal pro-BNP level of ≥125 pg/mL; or
• Any high sensitivity cardiac troponin value that’s above the usual upper reference limit set at >99th percentile.

‘Inexpensive’ biomarker testing

“Addition of relatively inexpensive biomarker testing as part of the standard of care may help to refine heart failure risk prediction in individuals with diabetes,” the report says.

“Substantial data indicate the ability of these biomarkers to identify those in stage A or B [heart failure] at highest risk of progressing to symptomatic heart failure or death,” and this identification is useful because “the risk in such individuals may be lowered through targeted intervention or multidisciplinary care.”

It is “impossible to understate the importance of early recognition of heart failure” in patients with heart failure, the authors declare. However, the report also cautions that, “using biomarkers to identify and in turn reduce risk for heart failure should always be done within the context of a thoughtful clinical evaluation, supported by all information available.”

The report, written during March 2021 – March 2022, cites the high prevalence and increasing incidence of heart failure in patients with diabetes as the rationale for the new recommendations.

For a person with diabetes who receives a heart failure diagnosis, the report details several management steps, starting with an evaluation for obstructive coronary artery disease, given the strong link between diabetes and atherosclerotic cardiovascular disease.

It highlights the importance of interventions that involve nutrition, smoking avoidance, minimized alcohol intake, exercise, weight loss, and relevant social determinants of health, but focuses in greater detail on a range of pharmacologic interventions. These include treatment of hypertension for people with early-stage heart failure with an ACE inhibitor or an angiotensin receptor blocker, a thiazide-type diuretic, and a mineralocorticoid receptor antagonist, such as spironolactone or the newer, nonsteroidal agent finerenone for patients with diabetic kidney disease.

Dr. Busui of the division of metabolism, endocrinology, and diabetes at the University of Michigan, Ann Arbor, and colleagues cite recent recommendations for using guidelines-directed medical therapy to treat patients with more advanced, symptomatic stages of heart failure, including heart failure with reduced or with preserved ejection fraction.

‘Prioritize’ the SGLT2-inhibitor class

The consensus report also summarizes the roles for agents in the various classes of antidiabetes drugs now available, with particular emphasis on the role for the SGLT2-inhibitor class.

SGLT2 inhibitors “are recommended for all individuals with [diabetes and] heart failure,” it says. “This consensus recommends prioritizing the use of SGLT2 inhibitors in individuals with stage B heart failure, and that SGLT2 inhibitors be an expected element of care in all individuals with diabetes and symptomatic heart failure.”

Other agents for glycemic control that receive endorsement from the report are those in the glucagonlike peptide 1 receptor agonist class. “Despite the lack of conclusive evidence of direct heart failure risk reduction” with this class, it gets a “should be considered” designation, based on its positive effects on weight loss, blood pressure, and atherothrombotic disease.

Similar acknowledgment of potential benefit in a “should be considered” role goes to metformin. But the report turned a thumb down for both the class of dipeptidyl peptidase 4 inhibitors and the thiazolidinedione class, and said that agents from the insulin and sulfonylurea classes should be used “judiciously.”

The report did not identify any commercial funding. Several of the writing committee members listed personal commercial disclosures.

All U.S. patients with diabetes should undergo annual biomarker testing to allow for early diagnosis of progressive but presymptomatic heart failure, and treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class should expand among such patients to include everyone with stage B heart failure (“pre–heart failure”) or more advanced stages.

That’s a recommendation from an American Diabetes Association consensus report published June 1 in Diabetes Care.

The report notes that until now, “implementation of available strategies to detect asymptomatic heart failure [in patients with diabetes] has been suboptimal.” The remedy for this is that, “among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and to implement strategies to prevent transition to symptomatic heart failure.”

Written by a 10-member panel, chaired by Rodica Pop-Busui, MD, PhD, and endorsed by the American College of Cardiology, the document also set threshold for levels of these biomarkers that are diagnostic for a more advanced stage (stage B) of heart failure in patients with diabetes but without heart failure symptoms:

• A B-type natriuretic peptide (BNP) level of ≥50 pg/mL;
• An N-terminal pro-BNP level of ≥125 pg/mL; or
• Any high sensitivity cardiac troponin value that’s above the usual upper reference limit set at >99th percentile.

‘Inexpensive’ biomarker testing

“Addition of relatively inexpensive biomarker testing as part of the standard of care may help to refine heart failure risk prediction in individuals with diabetes,” the report says.

“Substantial data indicate the ability of these biomarkers to identify those in stage A or B [heart failure] at highest risk of progressing to symptomatic heart failure or death,” and this identification is useful because “the risk in such individuals may be lowered through targeted intervention or multidisciplinary care.”

It is “impossible to understate the importance of early recognition of heart failure” in patients with heart failure, the authors declare. However, the report also cautions that, “using biomarkers to identify and in turn reduce risk for heart failure should always be done within the context of a thoughtful clinical evaluation, supported by all information available.”

The report, written during March 2021 – March 2022, cites the high prevalence and increasing incidence of heart failure in patients with diabetes as the rationale for the new recommendations.

For a person with diabetes who receives a heart failure diagnosis, the report details several management steps, starting with an evaluation for obstructive coronary artery disease, given the strong link between diabetes and atherosclerotic cardiovascular disease.

It highlights the importance of interventions that involve nutrition, smoking avoidance, minimized alcohol intake, exercise, weight loss, and relevant social determinants of health, but focuses in greater detail on a range of pharmacologic interventions. These include treatment of hypertension for people with early-stage heart failure with an ACE inhibitor or an angiotensin receptor blocker, a thiazide-type diuretic, and a mineralocorticoid receptor antagonist, such as spironolactone or the newer, nonsteroidal agent finerenone for patients with diabetic kidney disease.

Dr. Busui of the division of metabolism, endocrinology, and diabetes at the University of Michigan, Ann Arbor, and colleagues cite recent recommendations for using guidelines-directed medical therapy to treat patients with more advanced, symptomatic stages of heart failure, including heart failure with reduced or with preserved ejection fraction.

‘Prioritize’ the SGLT2-inhibitor class

The consensus report also summarizes the roles for agents in the various classes of antidiabetes drugs now available, with particular emphasis on the role for the SGLT2-inhibitor class.

SGLT2 inhibitors “are recommended for all individuals with [diabetes and] heart failure,” it says. “This consensus recommends prioritizing the use of SGLT2 inhibitors in individuals with stage B heart failure, and that SGLT2 inhibitors be an expected element of care in all individuals with diabetes and symptomatic heart failure.”

Other agents for glycemic control that receive endorsement from the report are those in the glucagonlike peptide 1 receptor agonist class. “Despite the lack of conclusive evidence of direct heart failure risk reduction” with this class, it gets a “should be considered” designation, based on its positive effects on weight loss, blood pressure, and atherothrombotic disease.

Similar acknowledgment of potential benefit in a “should be considered” role goes to metformin. But the report turned a thumb down for both the class of dipeptidyl peptidase 4 inhibitors and the thiazolidinedione class, and said that agents from the insulin and sulfonylurea classes should be used “judiciously.”

The report did not identify any commercial funding. Several of the writing committee members listed personal commercial disclosures.

All U.S. patients with diabetes should undergo annual biomarker testing to allow for early diagnosis of progressive but presymptomatic heart failure, and treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class should expand among such patients to include everyone with stage B heart failure (“pre–heart failure”) or more advanced stages.

That’s a recommendation from an American Diabetes Association consensus report published June 1 in Diabetes Care.

The report notes that until now, “implementation of available strategies to detect asymptomatic heart failure [in patients with diabetes] has been suboptimal.” The remedy for this is that, “among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and to implement strategies to prevent transition to symptomatic heart failure.”

Written by a 10-member panel, chaired by Rodica Pop-Busui, MD, PhD, and endorsed by the American College of Cardiology, the document also set threshold for levels of these biomarkers that are diagnostic for a more advanced stage (stage B) of heart failure in patients with diabetes but without heart failure symptoms:

• A B-type natriuretic peptide (BNP) level of ≥50 pg/mL;
• An N-terminal pro-BNP level of ≥125 pg/mL; or
• Any high sensitivity cardiac troponin value that’s above the usual upper reference limit set at >99th percentile.

‘Inexpensive’ biomarker testing

“Addition of relatively inexpensive biomarker testing as part of the standard of care may help to refine heart failure risk prediction in individuals with diabetes,” the report says.

“Substantial data indicate the ability of these biomarkers to identify those in stage A or B [heart failure] at highest risk of progressing to symptomatic heart failure or death,” and this identification is useful because “the risk in such individuals may be lowered through targeted intervention or multidisciplinary care.”

It is “impossible to understate the importance of early recognition of heart failure” in patients with heart failure, the authors declare. However, the report also cautions that, “using biomarkers to identify and in turn reduce risk for heart failure should always be done within the context of a thoughtful clinical evaluation, supported by all information available.”

The report, written during March 2021 – March 2022, cites the high prevalence and increasing incidence of heart failure in patients with diabetes as the rationale for the new recommendations.

For a person with diabetes who receives a heart failure diagnosis, the report details several management steps, starting with an evaluation for obstructive coronary artery disease, given the strong link between diabetes and atherosclerotic cardiovascular disease.

It highlights the importance of interventions that involve nutrition, smoking avoidance, minimized alcohol intake, exercise, weight loss, and relevant social determinants of health, but focuses in greater detail on a range of pharmacologic interventions. These include treatment of hypertension for people with early-stage heart failure with an ACE inhibitor or an angiotensin receptor blocker, a thiazide-type diuretic, and a mineralocorticoid receptor antagonist, such as spironolactone or the newer, nonsteroidal agent finerenone for patients with diabetic kidney disease.

Dr. Busui of the division of metabolism, endocrinology, and diabetes at the University of Michigan, Ann Arbor, and colleagues cite recent recommendations for using guidelines-directed medical therapy to treat patients with more advanced, symptomatic stages of heart failure, including heart failure with reduced or with preserved ejection fraction.

‘Prioritize’ the SGLT2-inhibitor class

The consensus report also summarizes the roles for agents in the various classes of antidiabetes drugs now available, with particular emphasis on the role for the SGLT2-inhibitor class.

SGLT2 inhibitors “are recommended for all individuals with [diabetes and] heart failure,” it says. “This consensus recommends prioritizing the use of SGLT2 inhibitors in individuals with stage B heart failure, and that SGLT2 inhibitors be an expected element of care in all individuals with diabetes and symptomatic heart failure.”

Other agents for glycemic control that receive endorsement from the report are those in the glucagonlike peptide 1 receptor agonist class. “Despite the lack of conclusive evidence of direct heart failure risk reduction” with this class, it gets a “should be considered” designation, based on its positive effects on weight loss, blood pressure, and atherothrombotic disease.

Similar acknowledgment of potential benefit in a “should be considered” role goes to metformin. But the report turned a thumb down for both the class of dipeptidyl peptidase 4 inhibitors and the thiazolidinedione class, and said that agents from the insulin and sulfonylurea classes should be used “judiciously.”

The report did not identify any commercial funding. Several of the writing committee members listed personal commercial disclosures.

Many adults can achieve remission of type 2 diabetes with a primary intervention consisting of a diet that emphasizes whole, plant-based foods, according to a new publication from the American College of Lifestyle Medicine (ACLM).

The document was developed to assist clinicians treating adults with type 2 diabetes, with the goal of remission using diet as a primary intervention. A panel of 15 experts from seven societies reached consensus on 69 statements.

“A healthy diet is a foundational component of current lifestyle guidelines for treatment of type 2 diabetes, but it is often overlooked because of the lack of physician training and patient awareness,” Felice A. Caldarella, MD, president of the American Association of Clinical Endocrinology (AACE), said in a press release from ACLM.

“The consensus statements produced by this panel of experts are invaluable in bringing awareness to the value of diet for diabetes remission in addition to management,” he summarized.

The initiative was cosponsored by the Endocrine Society, endorsed by AACE, and supported by the Academy of Nutrition and Dietetics. The expert panel also included representatives from the American College of Cardiology, the American Heart Association, and the American Academy of Family Physicians. It was published in the American Journal of Lifestyle Medicine.

“I think many patients would do the challenging work of making lifestyle modifications if it meant remission of [type 2 diabetes] and sparing them the burden and cost of medications or surgery,” said Amy E. Rothberg, MD, PhD, who represented the Endocrine Society on the panel.

“By changing the course of the disease, i.e., if in remission, they are unlikely to get the complications related to [type 2 diabetes],” Dr. Rothberg, professor of nutritional sciences at the University of Michigan, Ann Arbor, told this news organization.
 

Consensus on 69 statements

The panel members used a modified Delphi process to develop the consensus statement. They identified 49 articles from the literature regarding dietary interventions in adults with type 2 diabetes. They reached consensus on 69 statements that cover seven topics: definitions and basic concepts; diet and remission of type 2 diabetes; dietary specifics and types of diets; adjuvant and alternative interventions; support, monitoring, and adherence to therapy; weight loss; and payment and policy.

Dr. Rothberg identified six key areas:

• Definition of remission: Type 2 diabetes remission is defined as A1c < 6.5% for at least 3 months with no surgery, devices, or active pharmacologic therapy for lowering blood glucose, consistent with the diabetes remission timeline published in 2021 by the American Diabetes Association. Remission does not exclude the possibility of recurrence. Remission is a realistic and achievable goal for some adults with type 2 diabetes.
• High-intensity diet, short duration of diabetes: Patients are more likely to attain remission with a high-intensity diet (e.g., high level of restrictions plus frequent patient contact or counseling) accompanied by physical activity and if the patient has had diabetes for 4 years or less. A high-fiber diet is essential.
• Fewer calories, focus on plant-based foods: Calorie reduction could be achieved by reducing food volume, portion sizes, or energy density, or by using liquid meal replacements, or by a combination of these approaches. It should mainly include whole, plant-based foods (whole grains, vegetables, legumes, fruits, nuts, and seeds) and avoid or minimize meat and other animal products, refined foods, ultra-processed foods, and foods with added fats.
• A very low energy diet as initial intervention is optional: There was consensus that this approach can achieve remission, but there was not agreement that low calorie content was essential for achieving remission, Dr. Rothberg noted.
• Beyond type 2 remission: Diet as a primary intervention can also lower the risk of cardiovascular disease and improve lipoprotein profile.
• Self-management, support, and monitoring: The group recognizes the importance of patient education and support. “This can play a vital role and should be part of any comprehensive lifestyle treatment,” said Dr. Rothberg. The diet and lifestyle strategies should be acceptable to most patients, easy to adhere to, accommodate patient preferences and values, and be culturally sensitive.

Intensive lifestyle change can equate to bariatric surgery

Also invited to comment, Yehuda Handelsman, MD, who coauthored a 2020 type 2 diabetes management algorithm by AACE and the American College of Endocrinology, and was not involved with the current initiative, agrees with the importance of lifestyle in the management of type 2 diabetes but takes issue with a few points.

Most clinicians and experts do not believe that diabetes can be reversed, as such, only controlled, noted Dr. Handelsman, medical director of the Metabolic Institute of America, Tarzana, Calif.

“We always have approached type 2 diabetes treatment with lifestyle – diet, exercise, and (as of late) sleep – as the mainstay of therapy,” he said.

However, most patients do not adhere to diet modifications by 6 months and especially by 1 year, which has led to universal recommendations to add medication to lifestyle from inception, he continued.

Most clinicians have not been trained in lifestyle modalities. And many patients with type 2 diabetes are not adherent to medications, which “led to the relative success of bariatric surgery leading to remission (at least for 3-5 years).”

“Remission, which in broad terms implies the disappearance of signs and symptoms, should be a top priority for individuals with type 2 diabetes,” the consensus statement authors wrote.

“While [bariatric surgery] can induce remission in 25% to 80% of targeted patients, it carries risk and its effectiveness wanes as subjects regain lost weight,” and “more dramatic and intensive [lifestyle] change produces remission rates equivalent to bariatric surgery,” they noted.

Need for more randomized trials

Dr. Handelsman also stressed that remission may be temporary. “Three months or 6 months cannot be a measure of success. We must have at least 1 year,” he added. “In fact, there are data to show that remission requires 3 years.”

Nevertheless, the consensus statement does highlight the importance of lifestyle in remission of diabetes, he agreed.

The expert panel also noted that patients can benefit from a healthy lifestyle, even if they do not attain remission, Dr. Rothberg pointed out. 

Moving forward, the statement concludes that “there is ... an ongoing need for additional randomized controlled trials to assess sustainable plant-based dietary interventions with whole or minimally processed foods, as a primary means of treating [type 2 diabetes] with the goal of remission, as well as factors that lead to successful patient adherence and effective dissemination and implementation of such interventions.”

This study was supported by the Lisa Wendel Memorial Foundation. Dr. Rothberg has disclosed being the medical director of  Rewind, a virtual platform created for weight control with the goal to “defeat” type 2 diabetes, and a consultant for a study for which Nestle provides product. Dr. Handelsman has disclosed receiving research grants and consultant and speaker honoraria from Amarin, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Esperion, Ionis, Mankind, Merck, Merck-Pfizer, Novartis, Novo Nordisk, Regor, Sanofi, and Vertis.

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

Many adults can achieve remission of type 2 diabetes with a primary intervention consisting of a diet that emphasizes whole, plant-based foods, according to a new publication from the American College of Lifestyle Medicine (ACLM).

The document was developed to assist clinicians treating adults with type 2 diabetes, with the goal of remission using diet as a primary intervention. A panel of 15 experts from seven societies reached consensus on 69 statements.

“A healthy diet is a foundational component of current lifestyle guidelines for treatment of type 2 diabetes, but it is often overlooked because of the lack of physician training and patient awareness,” Felice A. Caldarella, MD, president of the American Association of Clinical Endocrinology (AACE), said in a press release from ACLM.

“The consensus statements produced by this panel of experts are invaluable in bringing awareness to the value of diet for diabetes remission in addition to management,” he summarized.

The initiative was cosponsored by the Endocrine Society, endorsed by AACE, and supported by the Academy of Nutrition and Dietetics. The expert panel also included representatives from the American College of Cardiology, the American Heart Association, and the American Academy of Family Physicians. It was published in the American Journal of Lifestyle Medicine.

“I think many patients would do the challenging work of making lifestyle modifications if it meant remission of [type 2 diabetes] and sparing them the burden and cost of medications or surgery,” said Amy E. Rothberg, MD, PhD, who represented the Endocrine Society on the panel.

“By changing the course of the disease, i.e., if in remission, they are unlikely to get the complications related to [type 2 diabetes],” Dr. Rothberg, professor of nutritional sciences at the University of Michigan, Ann Arbor, told this news organization.
 

Consensus on 69 statements

The panel members used a modified Delphi process to develop the consensus statement. They identified 49 articles from the literature regarding dietary interventions in adults with type 2 diabetes. They reached consensus on 69 statements that cover seven topics: definitions and basic concepts; diet and remission of type 2 diabetes; dietary specifics and types of diets; adjuvant and alternative interventions; support, monitoring, and adherence to therapy; weight loss; and payment and policy.

Dr. Rothberg identified six key areas:

• Definition of remission: Type 2 diabetes remission is defined as A1c < 6.5% for at least 3 months with no surgery, devices, or active pharmacologic therapy for lowering blood glucose, consistent with the diabetes remission timeline published in 2021 by the American Diabetes Association. Remission does not exclude the possibility of recurrence. Remission is a realistic and achievable goal for some adults with type 2 diabetes.
• High-intensity diet, short duration of diabetes: Patients are more likely to attain remission with a high-intensity diet (e.g., high level of restrictions plus frequent patient contact or counseling) accompanied by physical activity and if the patient has had diabetes for 4 years or less. A high-fiber diet is essential.
• Fewer calories, focus on plant-based foods: Calorie reduction could be achieved by reducing food volume, portion sizes, or energy density, or by using liquid meal replacements, or by a combination of these approaches. It should mainly include whole, plant-based foods (whole grains, vegetables, legumes, fruits, nuts, and seeds) and avoid or minimize meat and other animal products, refined foods, ultra-processed foods, and foods with added fats.
• A very low energy diet as initial intervention is optional: There was consensus that this approach can achieve remission, but there was not agreement that low calorie content was essential for achieving remission, Dr. Rothberg noted.
• Beyond type 2 remission: Diet as a primary intervention can also lower the risk of cardiovascular disease and improve lipoprotein profile.
• Self-management, support, and monitoring: The group recognizes the importance of patient education and support. “This can play a vital role and should be part of any comprehensive lifestyle treatment,” said Dr. Rothberg. The diet and lifestyle strategies should be acceptable to most patients, easy to adhere to, accommodate patient preferences and values, and be culturally sensitive.

Intensive lifestyle change can equate to bariatric surgery

Also invited to comment, Yehuda Handelsman, MD, who coauthored a 2020 type 2 diabetes management algorithm by AACE and the American College of Endocrinology, and was not involved with the current initiative, agrees with the importance of lifestyle in the management of type 2 diabetes but takes issue with a few points.

Most clinicians and experts do not believe that diabetes can be reversed, as such, only controlled, noted Dr. Handelsman, medical director of the Metabolic Institute of America, Tarzana, Calif.

“We always have approached type 2 diabetes treatment with lifestyle – diet, exercise, and (as of late) sleep – as the mainstay of therapy,” he said.

However, most patients do not adhere to diet modifications by 6 months and especially by 1 year, which has led to universal recommendations to add medication to lifestyle from inception, he continued.

Most clinicians have not been trained in lifestyle modalities. And many patients with type 2 diabetes are not adherent to medications, which “led to the relative success of bariatric surgery leading to remission (at least for 3-5 years).”

“Remission, which in broad terms implies the disappearance of signs and symptoms, should be a top priority for individuals with type 2 diabetes,” the consensus statement authors wrote.

“While [bariatric surgery] can induce remission in 25% to 80% of targeted patients, it carries risk and its effectiveness wanes as subjects regain lost weight,” and “more dramatic and intensive [lifestyle] change produces remission rates equivalent to bariatric surgery,” they noted.

Need for more randomized trials

Dr. Handelsman also stressed that remission may be temporary. “Three months or 6 months cannot be a measure of success. We must have at least 1 year,” he added. “In fact, there are data to show that remission requires 3 years.”

Nevertheless, the consensus statement does highlight the importance of lifestyle in remission of diabetes, he agreed.

The expert panel also noted that patients can benefit from a healthy lifestyle, even if they do not attain remission, Dr. Rothberg pointed out. 

Moving forward, the statement concludes that “there is ... an ongoing need for additional randomized controlled trials to assess sustainable plant-based dietary interventions with whole or minimally processed foods, as a primary means of treating [type 2 diabetes] with the goal of remission, as well as factors that lead to successful patient adherence and effective dissemination and implementation of such interventions.”

This study was supported by the Lisa Wendel Memorial Foundation. Dr. Rothberg has disclosed being the medical director of  Rewind, a virtual platform created for weight control with the goal to “defeat” type 2 diabetes, and a consultant for a study for which Nestle provides product. Dr. Handelsman has disclosed receiving research grants and consultant and speaker honoraria from Amarin, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Esperion, Ionis, Mankind, Merck, Merck-Pfizer, Novartis, Novo Nordisk, Regor, Sanofi, and Vertis.

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

Many adults can achieve remission of type 2 diabetes with a primary intervention consisting of a diet that emphasizes whole, plant-based foods, according to a new publication from the American College of Lifestyle Medicine (ACLM).

The document was developed to assist clinicians treating adults with type 2 diabetes, with the goal of remission using diet as a primary intervention. A panel of 15 experts from seven societies reached consensus on 69 statements.

“A healthy diet is a foundational component of current lifestyle guidelines for treatment of type 2 diabetes, but it is often overlooked because of the lack of physician training and patient awareness,” Felice A. Caldarella, MD, president of the American Association of Clinical Endocrinology (AACE), said in a press release from ACLM.

“The consensus statements produced by this panel of experts are invaluable in bringing awareness to the value of diet for diabetes remission in addition to management,” he summarized.

The initiative was cosponsored by the Endocrine Society, endorsed by AACE, and supported by the Academy of Nutrition and Dietetics. The expert panel also included representatives from the American College of Cardiology, the American Heart Association, and the American Academy of Family Physicians. It was published in the American Journal of Lifestyle Medicine.

“I think many patients would do the challenging work of making lifestyle modifications if it meant remission of [type 2 diabetes] and sparing them the burden and cost of medications or surgery,” said Amy E. Rothberg, MD, PhD, who represented the Endocrine Society on the panel.

“By changing the course of the disease, i.e., if in remission, they are unlikely to get the complications related to [type 2 diabetes],” Dr. Rothberg, professor of nutritional sciences at the University of Michigan, Ann Arbor, told this news organization.
 

Consensus on 69 statements

The panel members used a modified Delphi process to develop the consensus statement. They identified 49 articles from the literature regarding dietary interventions in adults with type 2 diabetes. They reached consensus on 69 statements that cover seven topics: definitions and basic concepts; diet and remission of type 2 diabetes; dietary specifics and types of diets; adjuvant and alternative interventions; support, monitoring, and adherence to therapy; weight loss; and payment and policy.

Dr. Rothberg identified six key areas:

• Definition of remission: Type 2 diabetes remission is defined as A1c < 6.5% for at least 3 months with no surgery, devices, or active pharmacologic therapy for lowering blood glucose, consistent with the diabetes remission timeline published in 2021 by the American Diabetes Association. Remission does not exclude the possibility of recurrence. Remission is a realistic and achievable goal for some adults with type 2 diabetes.
• High-intensity diet, short duration of diabetes: Patients are more likely to attain remission with a high-intensity diet (e.g., high level of restrictions plus frequent patient contact or counseling) accompanied by physical activity and if the patient has had diabetes for 4 years or less. A high-fiber diet is essential.
• Fewer calories, focus on plant-based foods: Calorie reduction could be achieved by reducing food volume, portion sizes, or energy density, or by using liquid meal replacements, or by a combination of these approaches. It should mainly include whole, plant-based foods (whole grains, vegetables, legumes, fruits, nuts, and seeds) and avoid or minimize meat and other animal products, refined foods, ultra-processed foods, and foods with added fats.
• A very low energy diet as initial intervention is optional: There was consensus that this approach can achieve remission, but there was not agreement that low calorie content was essential for achieving remission, Dr. Rothberg noted.
• Beyond type 2 remission: Diet as a primary intervention can also lower the risk of cardiovascular disease and improve lipoprotein profile.
• Self-management, support, and monitoring: The group recognizes the importance of patient education and support. “This can play a vital role and should be part of any comprehensive lifestyle treatment,” said Dr. Rothberg. The diet and lifestyle strategies should be acceptable to most patients, easy to adhere to, accommodate patient preferences and values, and be culturally sensitive.

Intensive lifestyle change can equate to bariatric surgery

Also invited to comment, Yehuda Handelsman, MD, who coauthored a 2020 type 2 diabetes management algorithm by AACE and the American College of Endocrinology, and was not involved with the current initiative, agrees with the importance of lifestyle in the management of type 2 diabetes but takes issue with a few points.

Most clinicians and experts do not believe that diabetes can be reversed, as such, only controlled, noted Dr. Handelsman, medical director of the Metabolic Institute of America, Tarzana, Calif.

“We always have approached type 2 diabetes treatment with lifestyle – diet, exercise, and (as of late) sleep – as the mainstay of therapy,” he said.

However, most patients do not adhere to diet modifications by 6 months and especially by 1 year, which has led to universal recommendations to add medication to lifestyle from inception, he continued.

Most clinicians have not been trained in lifestyle modalities. And many patients with type 2 diabetes are not adherent to medications, which “led to the relative success of bariatric surgery leading to remission (at least for 3-5 years).”

“Remission, which in broad terms implies the disappearance of signs and symptoms, should be a top priority for individuals with type 2 diabetes,” the consensus statement authors wrote.

“While [bariatric surgery] can induce remission in 25% to 80% of targeted patients, it carries risk and its effectiveness wanes as subjects regain lost weight,” and “more dramatic and intensive [lifestyle] change produces remission rates equivalent to bariatric surgery,” they noted.

Need for more randomized trials

Dr. Handelsman also stressed that remission may be temporary. “Three months or 6 months cannot be a measure of success. We must have at least 1 year,” he added. “In fact, there are data to show that remission requires 3 years.”

Nevertheless, the consensus statement does highlight the importance of lifestyle in remission of diabetes, he agreed.

The expert panel also noted that patients can benefit from a healthy lifestyle, even if they do not attain remission, Dr. Rothberg pointed out. 

Moving forward, the statement concludes that “there is ... an ongoing need for additional randomized controlled trials to assess sustainable plant-based dietary interventions with whole or minimally processed foods, as a primary means of treating [type 2 diabetes] with the goal of remission, as well as factors that lead to successful patient adherence and effective dissemination and implementation of such interventions.”

This study was supported by the Lisa Wendel Memorial Foundation. Dr. Rothberg has disclosed being the medical director of  Rewind, a virtual platform created for weight control with the goal to “defeat” type 2 diabetes, and a consultant for a study for which Nestle provides product. Dr. Handelsman has disclosed receiving research grants and consultant and speaker honoraria from Amarin, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept, Esperion, Ionis, Mankind, Merck, Merck-Pfizer, Novartis, Novo Nordisk, Regor, Sanofi, and Vertis.

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

The first-ever guidelines for interventional cardiologists using percutaneous patent foramen ovale closure recommend expanding the use of the procedure beyond the Food and Drug Administration–approved indication following PFO-associated ischemic stroke, adding clarification about the use of PFO with anticoagulation and hedging against abuse and overuse of the procedure, said the chair of the guideline writing committee.

“The most important things surrounding these guidelines are to help clinicians and policymakers – third-party payers – to address PFO in patient subsets that were not included in the large randomized clinical trials that led to FDA approval,” said writing group chair Clifford J. Kavinsky, MD, PhD, chief of structural and interventional cardiology at Rush University Medical Center, Chicago.

The Society for Cardiovascular Angiography & Interventions issued the guidelines at its annual scientific sessions meeting in Atlanta and published them simultaneously in the society’s journal.

The guidelines issue strong and conditional recommendations. The former means clinicians should order the intervention for most patients; the latter means decisionmaking is more nuanced and should consider contributing factors.

The guidelines clarify patient selection for PFO closure outside the “pretty narrow” indication the FDA approved, Dr. Kavinsky said, which is for PFO-associated ischemic stroke in patients aged 18-60 years.

“So what about patients who are older than 60? What about patients who had their stroke 10 years ago?” Dr. Kavinsky asked. “Those are issues that were unanswered in the randomized clinical trials.”

The guidelines also refine recommendations about anticoagulation in these patients, including its use after PFO closure in selected patients, Dr. Kavinsky noted. “It’s the opinion of the panel that although anticoagulants may be effective, because of issues of noncompliance, because of issues of interruption of therapy by physicians for a variety of reasons, including surgery or noncompliance, that it is preferable to do a PFO device closure to giving anticoagulant therapy.”

Many of the recommendations cover PFO closure alongside antiplatelet or anticoagulation therapy. Key conditional recommendations for patients who haven’t had a PFO-related stroke are:

• Avoiding its routine use in patients with chronic migraines, prior decompression illness (DCI), thrombophilia, atrial septal aneurysm, transient ischemic attack (TIA), or deep vein thrombosis (DVT).
• Considering PFO closure in patients with platypnea-orthodeoxia syndrome (POS) with no other discernible cause of hypoxia or systemic embolism in whom other embolic causes have been ruled out.

In patients who’ve had a PFO-related stroke, the guidelines strongly recommend PFO closure versus antiplatelet therapy alone, but conditionally, not in patients with atrial fibrillation who’ve had an ischemic stroke. They also conditionally suggest PFO closure rather than long-term antiplatelet therapy alone in PFO stroke patients aged 60 and older, as well as those with thrombophilia already on antiplatelet therapy but not anticoagulation. However, the guidelines make no recommendation on PFO closure based on how much time has passed since the previous stroke.

“Furthermore,” Dr. Kavinsky said, “in patients who require lifelong anticoagulation because of recurrent DVT or recurrent pulmonary emboli or thrombopenia, if they’ve had a PFO-mediated stroke, then it’s our opinion that they should have their PFO closed in addition to taking lifelong anticoagulation because of the same issues of noncompliance and interruption of therapy.” Those are conditional recommendations.

The guideline also checks a box in the FDA labeling that mandated agreement between cardiology and neurology in patient selection. The American Academy of Neurology (AAN) issued its own guideline in 2020 for patients with stroke and PFO. In Europe, the European Society of Cardiology issued two position papers on expanded applications of PFO closure.

The recommendations on when PFO closure shouldn’t be done are noteworthy, Dr. Kavinsky said. “PFOs are present in 25% of the adult population, so the number of patients with PFO is huge and the indication for the FDA is really narrow: to reduce the risk of recurrent stroke in patients with PFO-mediated stroke. So, there’s the tremendous potential for abuse out there, of excessive procedures, of doing unnecessary procedures.”

The guidelines are a follow-up to the operator institutional requirements document SCAI issued in 2019 that set requirements for hospital offering and physicians performing PFO closure, Dr. Kavinsky added.

In an editorial accompanying the published guideline, Robert J. Sommer, MD, and Jamil A. Aboulhosn, MD, wrote that they support the recommendations “which help spotlight and clarify the growing list of potential indications for PFO closure.” They noted that the guidelines panel’s “strong” recommendations were for indications validated by randomized trials and that “conditional” recommendations were based on panelists’ experience and observational data.

“It is critical to recognize that most of these guidelines represent consensus opinion only,” wrote Dr. Sommer, who specializes in adult congenital and pediatric cardiology at Columbia University Irving Medical Center, New York, and Dr. Aboulhosn, an interventional cardiologist at Ronald Reagan University of California, Los Angeles, Medical Center. They emphasized the guidelines’ “heavy emphasis” on shared decisionmaking with patients.

Dr. Kavinsky is a principal investigator for Edwards Lifesciences, W.L. Gore and Associates, Medtronic, and Abbott. Dr. Sommer is a principal investigator and investigator in studies sponsored by W.L. Gore & Associates. Dr. Aboulhosn is a consultant to Abbott Medical.
 

The first-ever guidelines for interventional cardiologists using percutaneous patent foramen ovale closure recommend expanding the use of the procedure beyond the Food and Drug Administration–approved indication following PFO-associated ischemic stroke, adding clarification about the use of PFO with anticoagulation and hedging against abuse and overuse of the procedure, said the chair of the guideline writing committee.

“The most important things surrounding these guidelines are to help clinicians and policymakers – third-party payers – to address PFO in patient subsets that were not included in the large randomized clinical trials that led to FDA approval,” said writing group chair Clifford J. Kavinsky, MD, PhD, chief of structural and interventional cardiology at Rush University Medical Center, Chicago.

The Society for Cardiovascular Angiography & Interventions issued the guidelines at its annual scientific sessions meeting in Atlanta and published them simultaneously in the society’s journal.

The guidelines issue strong and conditional recommendations. The former means clinicians should order the intervention for most patients; the latter means decisionmaking is more nuanced and should consider contributing factors.

The guidelines clarify patient selection for PFO closure outside the “pretty narrow” indication the FDA approved, Dr. Kavinsky said, which is for PFO-associated ischemic stroke in patients aged 18-60 years.

“So what about patients who are older than 60? What about patients who had their stroke 10 years ago?” Dr. Kavinsky asked. “Those are issues that were unanswered in the randomized clinical trials.”

The guidelines also refine recommendations about anticoagulation in these patients, including its use after PFO closure in selected patients, Dr. Kavinsky noted. “It’s the opinion of the panel that although anticoagulants may be effective, because of issues of noncompliance, because of issues of interruption of therapy by physicians for a variety of reasons, including surgery or noncompliance, that it is preferable to do a PFO device closure to giving anticoagulant therapy.”

Many of the recommendations cover PFO closure alongside antiplatelet or anticoagulation therapy. Key conditional recommendations for patients who haven’t had a PFO-related stroke are:

• Avoiding its routine use in patients with chronic migraines, prior decompression illness (DCI), thrombophilia, atrial septal aneurysm, transient ischemic attack (TIA), or deep vein thrombosis (DVT).
• Considering PFO closure in patients with platypnea-orthodeoxia syndrome (POS) with no other discernible cause of hypoxia or systemic embolism in whom other embolic causes have been ruled out.

In patients who’ve had a PFO-related stroke, the guidelines strongly recommend PFO closure versus antiplatelet therapy alone, but conditionally, not in patients with atrial fibrillation who’ve had an ischemic stroke. They also conditionally suggest PFO closure rather than long-term antiplatelet therapy alone in PFO stroke patients aged 60 and older, as well as those with thrombophilia already on antiplatelet therapy but not anticoagulation. However, the guidelines make no recommendation on PFO closure based on how much time has passed since the previous stroke.

“Furthermore,” Dr. Kavinsky said, “in patients who require lifelong anticoagulation because of recurrent DVT or recurrent pulmonary emboli or thrombopenia, if they’ve had a PFO-mediated stroke, then it’s our opinion that they should have their PFO closed in addition to taking lifelong anticoagulation because of the same issues of noncompliance and interruption of therapy.” Those are conditional recommendations.

The guideline also checks a box in the FDA labeling that mandated agreement between cardiology and neurology in patient selection. The American Academy of Neurology (AAN) issued its own guideline in 2020 for patients with stroke and PFO. In Europe, the European Society of Cardiology issued two position papers on expanded applications of PFO closure.

The recommendations on when PFO closure shouldn’t be done are noteworthy, Dr. Kavinsky said. “PFOs are present in 25% of the adult population, so the number of patients with PFO is huge and the indication for the FDA is really narrow: to reduce the risk of recurrent stroke in patients with PFO-mediated stroke. So, there’s the tremendous potential for abuse out there, of excessive procedures, of doing unnecessary procedures.”

The guidelines are a follow-up to the operator institutional requirements document SCAI issued in 2019 that set requirements for hospital offering and physicians performing PFO closure, Dr. Kavinsky added.

In an editorial accompanying the published guideline, Robert J. Sommer, MD, and Jamil A. Aboulhosn, MD, wrote that they support the recommendations “which help spotlight and clarify the growing list of potential indications for PFO closure.” They noted that the guidelines panel’s “strong” recommendations were for indications validated by randomized trials and that “conditional” recommendations were based on panelists’ experience and observational data.

“It is critical to recognize that most of these guidelines represent consensus opinion only,” wrote Dr. Sommer, who specializes in adult congenital and pediatric cardiology at Columbia University Irving Medical Center, New York, and Dr. Aboulhosn, an interventional cardiologist at Ronald Reagan University of California, Los Angeles, Medical Center. They emphasized the guidelines’ “heavy emphasis” on shared decisionmaking with patients.

Dr. Kavinsky is a principal investigator for Edwards Lifesciences, W.L. Gore and Associates, Medtronic, and Abbott. Dr. Sommer is a principal investigator and investigator in studies sponsored by W.L. Gore & Associates. Dr. Aboulhosn is a consultant to Abbott Medical.
 

The first-ever guidelines for interventional cardiologists using percutaneous patent foramen ovale closure recommend expanding the use of the procedure beyond the Food and Drug Administration–approved indication following PFO-associated ischemic stroke, adding clarification about the use of PFO with anticoagulation and hedging against abuse and overuse of the procedure, said the chair of the guideline writing committee.

“The most important things surrounding these guidelines are to help clinicians and policymakers – third-party payers – to address PFO in patient subsets that were not included in the large randomized clinical trials that led to FDA approval,” said writing group chair Clifford J. Kavinsky, MD, PhD, chief of structural and interventional cardiology at Rush University Medical Center, Chicago.

The Society for Cardiovascular Angiography & Interventions issued the guidelines at its annual scientific sessions meeting in Atlanta and published them simultaneously in the society’s journal.

The guidelines issue strong and conditional recommendations. The former means clinicians should order the intervention for most patients; the latter means decisionmaking is more nuanced and should consider contributing factors.

The guidelines clarify patient selection for PFO closure outside the “pretty narrow” indication the FDA approved, Dr. Kavinsky said, which is for PFO-associated ischemic stroke in patients aged 18-60 years.

“So what about patients who are older than 60? What about patients who had their stroke 10 years ago?” Dr. Kavinsky asked. “Those are issues that were unanswered in the randomized clinical trials.”

The guidelines also refine recommendations about anticoagulation in these patients, including its use after PFO closure in selected patients, Dr. Kavinsky noted. “It’s the opinion of the panel that although anticoagulants may be effective, because of issues of noncompliance, because of issues of interruption of therapy by physicians for a variety of reasons, including surgery or noncompliance, that it is preferable to do a PFO device closure to giving anticoagulant therapy.”

Many of the recommendations cover PFO closure alongside antiplatelet or anticoagulation therapy. Key conditional recommendations for patients who haven’t had a PFO-related stroke are:

• Avoiding its routine use in patients with chronic migraines, prior decompression illness (DCI), thrombophilia, atrial septal aneurysm, transient ischemic attack (TIA), or deep vein thrombosis (DVT).
• Considering PFO closure in patients with platypnea-orthodeoxia syndrome (POS) with no other discernible cause of hypoxia or systemic embolism in whom other embolic causes have been ruled out.

In patients who’ve had a PFO-related stroke, the guidelines strongly recommend PFO closure versus antiplatelet therapy alone, but conditionally, not in patients with atrial fibrillation who’ve had an ischemic stroke. They also conditionally suggest PFO closure rather than long-term antiplatelet therapy alone in PFO stroke patients aged 60 and older, as well as those with thrombophilia already on antiplatelet therapy but not anticoagulation. However, the guidelines make no recommendation on PFO closure based on how much time has passed since the previous stroke.

“Furthermore,” Dr. Kavinsky said, “in patients who require lifelong anticoagulation because of recurrent DVT or recurrent pulmonary emboli or thrombopenia, if they’ve had a PFO-mediated stroke, then it’s our opinion that they should have their PFO closed in addition to taking lifelong anticoagulation because of the same issues of noncompliance and interruption of therapy.” Those are conditional recommendations.

The guideline also checks a box in the FDA labeling that mandated agreement between cardiology and neurology in patient selection. The American Academy of Neurology (AAN) issued its own guideline in 2020 for patients with stroke and PFO. In Europe, the European Society of Cardiology issued two position papers on expanded applications of PFO closure.

The recommendations on when PFO closure shouldn’t be done are noteworthy, Dr. Kavinsky said. “PFOs are present in 25% of the adult population, so the number of patients with PFO is huge and the indication for the FDA is really narrow: to reduce the risk of recurrent stroke in patients with PFO-mediated stroke. So, there’s the tremendous potential for abuse out there, of excessive procedures, of doing unnecessary procedures.”

The guidelines are a follow-up to the operator institutional requirements document SCAI issued in 2019 that set requirements for hospital offering and physicians performing PFO closure, Dr. Kavinsky added.

In an editorial accompanying the published guideline, Robert J. Sommer, MD, and Jamil A. Aboulhosn, MD, wrote that they support the recommendations “which help spotlight and clarify the growing list of potential indications for PFO closure.” They noted that the guidelines panel’s “strong” recommendations were for indications validated by randomized trials and that “conditional” recommendations were based on panelists’ experience and observational data.

“It is critical to recognize that most of these guidelines represent consensus opinion only,” wrote Dr. Sommer, who specializes in adult congenital and pediatric cardiology at Columbia University Irving Medical Center, New York, and Dr. Aboulhosn, an interventional cardiologist at Ronald Reagan University of California, Los Angeles, Medical Center. They emphasized the guidelines’ “heavy emphasis” on shared decisionmaking with patients.

Dr. Kavinsky is a principal investigator for Edwards Lifesciences, W.L. Gore and Associates, Medtronic, and Abbott. Dr. Sommer is a principal investigator and investigator in studies sponsored by W.L. Gore & Associates. Dr. Aboulhosn is a consultant to Abbott Medical.
 

Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).

Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.

The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online  in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.

“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.

“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.

“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.

Time-honored treatments no more?

Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.

For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.

Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.

“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.

The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.

In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.

The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.

For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.

It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.

For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.

However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
 

Multidisciplinary care

For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.

Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.

Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.

“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.

The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
 

Opportunity for prevention?

The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.

While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.

“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.

“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.

“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.

The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.

This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.

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

Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).

Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.

The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online  in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.

“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.

“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.

“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.

Time-honored treatments no more?

Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.

For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.

Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.

“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.

The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.

In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.

The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.

For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.

It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.

For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.

However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
 

Multidisciplinary care

For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.

Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.

Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.

“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.

The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
 

Opportunity for prevention?

The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.

While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.

“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.

“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.

“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.

The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.

This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.

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

Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).

Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.

The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online  in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.

“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.

“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.

“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.

Time-honored treatments no more?

Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.

For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.

Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.

“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.

The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.

In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.

The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.

For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.

It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.

For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.

However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
 

Multidisciplinary care

For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.

Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.

Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.

“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.

The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
 

Opportunity for prevention?

The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.

While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.

“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.

“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.

“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.

The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.

This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.

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

New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.

They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.

The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.

These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.

80 million Americans have NAFLD, but very few are aware

The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.

The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.

Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.

In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.

In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”

And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
 

Screening advised using new FIB-4 test

The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).

The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (10⁹/L) x ALT ½ (U/L).

Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.

“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.

The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.

For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.

Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.

“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
 

NAFLD treatment in endocrinology and primary care: CVD prevention

During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.

Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.

There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.  

The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.

In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”

To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”

Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.

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

New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.

They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.

The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.

These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.

80 million Americans have NAFLD, but very few are aware

The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.

The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.

Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.

In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.

In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”

And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
 

Screening advised using new FIB-4 test

The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).

The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (10⁹/L) x ALT ½ (U/L).

Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.

“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.

The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.

For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.

Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.

“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
 

NAFLD treatment in endocrinology and primary care: CVD prevention

During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.

Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.

There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.  

The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.

In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”

To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”

Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.

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

New clinical practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) are the first to be targeted specifically to primary care and endocrinology clinical settings.

They include 34 evidence-based clinical practice recommendations for screening, diagnosis, management, and referral, presented in a table and an algorithm flow chart as well as detailed text.

The new guidelines are by the American Association of Clinical Endocrinology and cosponsored by the American Association for the Study of Liver Diseases. They were presented at the annual scientific & clinical congress of the AACE and simultaneously published in Endocrine Practice.

These are “the first of this type for this field of medicine. The vast majority of patients with NAFLD are being seen in the primary care and endocrinology settings. Only when they get to the more advanced disease are they being referred to the liver specialists. So, we need to be the ones who are diagnosing and managing these patients because there just aren’t enough liver specialists to do that,” Scott Isaacs, MD, cochair of the writing panel for the guidelines, said in an interview.

80 million Americans have NAFLD, but very few are aware

The spectrum of NAFLD ranges from nonprogressive steatosis to the progressive conditions nonalcoholic steatohepatitis, fibrotic NASH, and end-stage NASH cirrhosis. And NASH, in turn, is a major cause of liver cancer. NAFLD is also strongly associated with insulin resistance, type 2 diabetes, atherogenesis, and myocardial dysfunction.

The global prevalence of NAFLD is about 25% and NASH, about 12%-14%. However, a recent study found that, among patients in endocrine and primary care clinics, more than 70% of patients with type 2 diabetes and more than 90% with type 2 diabetes who had a body mass index above 35 kg/m2 also had NAFLD, and more than 20% of those patients had significant liver fibrosis.

Problematically, very few people are aware they have either. “It’s so common. At least 80 million Americans have this but only about 6% know they have it. We talk about it a lot, but it’s not talked about enough,” said Dr. Isaacs, an endocrinologist who practices in Atlanta.

In fact, most cases of NAFLD are diagnosed incidentally when people undergo an ultrasound or a CT scan for another reason. And, in about 70% of cases the liver enzymes are normal, and those patients rarely undergo liver workups, Dr. Isaacs noted.

In an accompanying editorial, Suthat Liangpunsakul, MD, wrote: “In my perspective, as a hepatologist, this AACE guideline is very practical and easy to incorporate into routine practice in primary care and endocrinology settings. ... Early identification and risk stratification of patients with NAFLD, especially the degree of hepatic fibrosis, are required to reduce downstream health care costs and triage unwarranted specialty care referrals.”

And “an effective screening strategy may also identify those in primary care and endocrinology settings who may benefit from an appropriate referral to hepatologists before the development of portal hypertension complications, decompensated liver disease, and hepatocellular carcinoma,” added Dr. Liangpunsakul, professor of medicine in the division of gastroenterology and hepatology at Indiana University, Indianapolis.
 

Screening advised using new FIB-4 test

The guideline calls for screening all patients at high risk for NAFLD, including those with prediabetes, type 2 diabetes, obesity, and/or two or more cardiometabolic risk factors, or those with hepatic steatosis found on imaging, and/or persistently elevated plasma aminotransferase levels (that is, for more than 6 months).

The recommended screening test is the Fibrosis-4 (FIB-4) index, calculated using the patient’s age, AST level, platelet count, and ALT level: FIB-4 score = age (years) x AST (U/L)/PLT (10⁹/L) x ALT ½ (U/L).

Recently approved by the Food and Drug Administration, the FIB-4 has been demonstrated to help identify liver disease in primary care settings.

“We really want to encourage clinicians to do the screening. The first step is the FIB-4 test. It’s a mathematical calculation using blood tests that we do anyway,” Dr. Isaacs said in an interview.

The FIB-4 stratifies patients as being low, intermediate, or high risk for liver fibrosis. Those at low risk can be managed in primary care or endocrinology settings with a focus on obesity management and cardiovascular disease prevention. “Those at low risk on FIB-4 still have a high cardiovascular disease risk. They still need to be managed,” Dr. Isaacs observed.

For those at intermediate risk, a second noninvasive test – either a liver stiffness measurement by elastography or an enhanced liver fibrosis test – is advised. If the patient is found to be at high risk or is still indeterminant after two noninvasive tests, referral to a liver specialist for further testing, including possible biopsy, is advised.

Those found to be at high risk with the FIB-4 should also be referred to hepatology. In both the intermediate- and high-risk groups, management should be multidisciplinary, including a hepatologist, endocrinologist, and other professionals to prevent both cardiovascular disease and progression to cirrhosis, the guidelines say.

“The diagnosis isn’t about diagnosing liver fat. It’s about diagnosing fibrosis, or the risk for clinically significant fibrosis. That’s really where the challenge lies,” Dr. Isaacs commented.
 

NAFLD treatment in endocrinology and primary care: CVD prevention

During the presentation at the AACE meeting, guideline panel cochair Kenneth Cusi, MD, chief of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, summarized current and future treatments for NAFLD.

Lifestyle intervention, cardiovascular risk reduction, and weight loss for those who are overweight or obese are recommended for all patients with NAFLD, including structured weight-loss programs, antiobesity medications, and bariatric surgery if indicated.

There are currently no FDA-approved medications specifically for NASH, but pioglitazone, approved for type 2 diabetes, and glucagonlike peptide–1 agonists, approved for type 2 diabetes and weight loss, have been shown to be effective in treating the condition and preventing progression. Other treatments are in development, Dr. Cusi said.  

The guideline also includes a section on diagnosis and management of NAFLD in children and adolescents. Here, the FIB-4 is not recommended because it isn’t accurate due to the age part of the equation, so liver enzyme tests are used in pediatric patients considered at high risk because of clinical factors. Management is similar to adults, except not all medications used in adults are approved for use in children.

In the editorial, Dr. Liangpunsakul cautioned that “the level of uptake and usage of the guideline may be an obstacle.”

To remedy that, he advised that “the next effort should gear toward distributing this guideline to the targeted providers and developing the ‘feedback platforms’ on its execution in the real-world. ... The successful implementation of this AACE guideline by the primary care providers and endocrinologists, hopefully, will deescalate the future burden of NAFLD-related morbidity and mortality.”

Dr. Isaacs and Dr. Liangpunsakul have reported no relevant financial relationships. Dr. Cusi has reported receiving research support towards the University of Florida as principal investigator from the National Institute of Health, Echosens, Inventiva, Nordic Bioscience, Novo Nordisk, Poxel, Labcorp, and Zydus, and is a consultant for Altimmune, Akero, Arrowhead, AstraZeneca, 89Bio, Bristol-Myers Squibb, Coherus, Intercept, Lilly, Madrigal, Merck, Novo Nordisk, Quest, Sagimet, Sonic Incytes, Terns, and Thera Technologies.

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

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

All patients with idiopathic inflammatory myopathies (IIM) should be screened for swallowing difficulties, according to the first evidence-based guideline to be produced.

The guideline, which has been developed by a working group of the British Society for Rheumatology (BSR), also advises that all diagnosed patients should have their myositis antibody levels checked and have their overall well-being assessed. Other recommendations for all patients include the use of glucocorticoids to reduce muscle inflammation and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for long-term treatment.

“Finally, now, we’re able to standardize the way we treat adults and children with IIM,” senior guideline author Hector Chinoy, PhD, said at the society’s annual meeting.

It has been a long labor of love, however, taking 4 years to get the guideline published, said Dr. Chinoy, professor of rheumatology and neuromuscular disease at the University of Manchester (England), and a consultant at Salford (England) Royal Hospital.

“We’re not covering diagnosis, classification, or the investigation of suspected IIM,” said Dr. Chinoy. Inclusion body myositis also is not included.

Altogether, there are 13 recommendations that have been developed using a PICO (patient or population, intervention, comparison, outcome) format, graded based on the quality of the available evidence, and then voted on by the working group members to give a score of the strength of agreement. Dr. Chinoy noted that there was a checklist included in the Supplementary Data section of the guideline to help follow the recommendations.

“The target audience for the guideline reflects the variety of clinicians caring for patients with IIM,” Dr. Chinoy said. So that is not just pediatric and adult rheumatologists, but also neurologists, dermatologists, respiratory physicians, oncologists, gastroenterologists, cardiologists, and of course other health care professionals. This includes rheumatology and neurology nurses, psychologists, speech and language therapists, and podiatrists, as well as rheumatology specialist pharmacists, physiotherapists, and occupational therapists.

With reference to the latter, Liza McCann, MBBS, who co-led the development of the guideline, said in a statement released by the BSR that the guideline “highlights the importance of exercise, led and monitored by specialist physiotherapists and occupational therapists.”

Dr. McCann, a consultant pediatric rheumatologist at Alder Hey Hospital, Liverpool, England, and Honorary Clinical Lecturer at the University of Liverpool, added that the guidelines also cover “the need to address psychological wellbeing as an integral part of treatment, in parallel with pharmacological therapies.”

Recommendation highlights

Some of the highlights of the recommendations include the use of high-dose glucocorticoids to manage skeletal muscle inflammation at the time of treatment induction, with specific guidance on the different doses to use in adults and in children. There also is guidance on the use of csDMARDs in both populations and what to use if there is refractory disease – with the strongest evidence supporting the use of intravenous immunoglobulin (IVIG) or cyclophosphamide, and possibly rituximab and abatacept.

“There is insufficient evidence to recommend JAK inhibition,” Dr. Chinoy said. The data search used to develop the guideline had a cutoff of October 2020, but even now there is only anecdotal evidence from case studies, he added.

Importantly, the guidelines recognize that childhood IIM differs from adult disease and call for children to be managed by pediatric specialists.

“Routine assessment of dysphagia should be considered in all patients,” Dr. Chinoy said, “so ask the question.” The recommendation is that a swallowing assessment should involve a speech and language therapist or gastroenterologist, and that IVIG be considered for active disease and dysphagia that is resistant to other treatments.

There also are recommendations to screen adult patients for interstitial lung disease, consider fracture risk, and screen adult patients for cancer if they have specific risk factors that include older age at onset, male gender, dysphagia, and rapid disease onset, among others.
 

Separate cancer screening guidelines on cards

“Around one in four patients with myositis will develop cancer within the 3 years either before or after myositis onset,” Alexander Oldroyd, MBChB, PhD, said in a separate presentation at the BSR annual meeting.

“It’s a hugely increased risk compared to the general population, and a great worry for patients,” he added. Exactly why there is an increased risk is not known, but “there’s a big link between the biological onset of cancer and myositis.”

Dr. Oldroyd, who is an NIHR Academic Clinical Lecturer at the University of Manchester in England and a coauthor of the BSR myositis guideline, is part of a special interest group set up by the International Myositis Assessment and Clinical Studies Group (IMACS) that is in the process of developing separate guidelines for cancer screening in people newly diagnosed with IIM.

The aim was to produce evidence-based recommendations that were both “pragmatic and practical,” that could help clinicians answer patient’s questions on their risk and how best and how often to screen them, Dr. Oldroyd explained. Importantly, IMACS has endeavored to create recommendations that should be applicable across different countries and health care systems.

“We had to acknowledge that there’s not a lot of evidence base there,” Dr. Oldroyd said, noting that he and colleagues conducted a systematic literature review and meta-analysis and used a Delphi process to draft 20 recommendations. These cover identifying risk factors for cancer in people with myositis and categorizing people into low, medium, and high-risk categories. The recommendations also cover what should constitute basic and enhanced screening, and how often someone should be screened.

Moreover, the authors make recommendations on the use of imaging modalities such as PET and CT scans, as well as upper and lower gastrointestinal endoscopy and naso-endoscopy.

“As rheumatologists, we don’t talk about cancer a lot,” Dr. Oldroyd said. “We pick up a lot of incidental cancers, but we don’t usually talk about cancer screening with patients.” That’s something that needs to change, he said.

“It’s important – just get it out in the open, talk to people about it,” Dr. Oldroyd said.

“Tell them what you’re wanting to do, how you’re wanting to investigate for it, clearly communicate their risk,” he said. “But also acknowledge the limited evidence as well, and clearly communicate the results.”

Dr. Chinoy acknowledged he had received fees for presentations (UCB, Biogen), consultancy (Alexion, Novartis, Eli Lilly, Orphazyme, AstraZeneca), or grant support (Eli Lilly, UCB) that had been paid via his institution for the purpose of furthering myositis research. Dr. Oldroyd had no conflicts of interest to disclose.

The American Gastroenterological Association has published a clinical practice update on dietary interventions for patients with irritable bowel syndrome (IBS). The topics range from identification of suitable candidates for dietary interventions, to levels of evidence for specific diets, which are becoming increasingly recognized for their key role in managing patients with IBS, according to lead author William D. Chey, MD, of the University of Michigan, Ann Arbor, and colleagues.

“Most medical therapies for IBS improve global symptoms in fewer than one-half of patients, with a therapeutic gain of 7%-15% over placebo,” the researchers wrote in Gastroenterology. “Most patients with IBS associate their GI symptoms with eating food.”

According to Dr. Chey and colleagues, clinicians who are considering dietary modifications for treating IBS should first recognize the inherent challenges presented by this process and be aware that new diets won’t work for everyone.

“Specialty diets require planning and preparation, which may be impractical for some patients,” they wrote, noting that individuals with “decreased cognitive abilities and significant psychiatric disease” may be unable to follow diets or interpret their own responses to specific foods. Special diets may also be inappropriate for patients with financial constraints, and “should be avoided in patients with an eating disorder.”

Because of the challenges involved in dietary interventions, Dr. Chey and colleagues advised clinical support from a registered dietitian nutritionist or other resource.

Patients who are suitable candidates for intervention and willing to try a new diet should first provide information about their current eating habits. A food trial can then be personalized and implemented for a predetermined amount of time. If the patient does not respond, then the diet should be stopped and changed to a new diet or another intervention.

Dr. Chey and colleagues discussed three specific dietary interventions and their corresponding levels of evidence: soluble fiber; the low-fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet; and a gluten-free diet.

“Soluble fiber is efficacious in treating global symptoms of IBS,” they wrote, citing 15 randomized controlled trials. Soluble fiber is most suitable for patients with constipation-predominant IBS, and different soluble fibers may yield different outcomes based on characteristics such as rate of fermentation and viscosity. In contrast, insoluble fiber is unlikely to help with IBS, and may worsen abdominal pain and bloating.

The low-FODMAP diet is “currently the most evidence-based diet intervention for IBS,” especially for patients with diarrhea-predominant IBS. Dr. Chey and colleagues offered a clear roadmap for employing the diet. First, patients should eat only low-FODMAP foods for 4-6 weeks. If symptoms don’t improve, the diet should be stopped. If symptoms do improve, foods containing a single FODMAP should be reintroduced one at a time, each in increasing quantities over 3 days, alongside documentation of symptom responses. Finally, the diet should be personalized based on these responses. The majority of patients (close to 80%) “can liberalize” a low-FODMAP diet based on their responses.

In contrast with the low-FODMAP diet, which has a relatively solid body of supporting evidence, efficacy data are still limited for treating IBS with a gluten-free diet. “Although observational studies found that most patients with IBS improve with a gluten-free diet, randomized controlled trials have yielded mixed results,” Dr. Chey and colleagues explained.

Their report cited a recent monograph on the topic that concluded that gluten-free eating offered no significant benefit over placebo (relative risk, 0.46; 95% confidence interval, 0.16-1.28). While some studies have documented positive results with a gluten-free diet, Dr. Chey and colleagues suggested that confounding variables such as the nocebo effect and the impact of other dietary factors have yet to be ruled out. “At present, it remains unclear whether a gluten-free diet is of benefit to patients with IBS.”

Dr. Chey and colleagues also explored IBS biomarkers. While some early data have shown that biomarkers may predict dietary responses, “there is insufficient evidence to support their routine use in clinical practice. ... Further efforts to identify and validate biomarkers that predict response to dietary interventions are needed to deliver ‘personalized nutrition.’ ”

The clinical practice update was commissioned and approved by the AGA CPU Committee and the AGA Governing Board. The researchers disclosed relationships with Biomerica, Salix, Mauna Kea Technologies, and others.

This article was updated May 19, 2022.

The American Gastroenterological Association has published a clinical practice update on dietary interventions for patients with irritable bowel syndrome (IBS). The topics range from identification of suitable candidates for dietary interventions, to levels of evidence for specific diets, which are becoming increasingly recognized for their key role in managing patients with IBS, according to lead author William D. Chey, MD, of the University of Michigan, Ann Arbor, and colleagues.

“Most medical therapies for IBS improve global symptoms in fewer than one-half of patients, with a therapeutic gain of 7%-15% over placebo,” the researchers wrote in Gastroenterology. “Most patients with IBS associate their GI symptoms with eating food.”

According to Dr. Chey and colleagues, clinicians who are considering dietary modifications for treating IBS should first recognize the inherent challenges presented by this process and be aware that new diets won’t work for everyone.

“Specialty diets require planning and preparation, which may be impractical for some patients,” they wrote, noting that individuals with “decreased cognitive abilities and significant psychiatric disease” may be unable to follow diets or interpret their own responses to specific foods. Special diets may also be inappropriate for patients with financial constraints, and “should be avoided in patients with an eating disorder.”

Because of the challenges involved in dietary interventions, Dr. Chey and colleagues advised clinical support from a registered dietitian nutritionist or other resource.

Patients who are suitable candidates for intervention and willing to try a new diet should first provide information about their current eating habits. A food trial can then be personalized and implemented for a predetermined amount of time. If the patient does not respond, then the diet should be stopped and changed to a new diet or another intervention.

Dr. Chey and colleagues discussed three specific dietary interventions and their corresponding levels of evidence: soluble fiber; the low-fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet; and a gluten-free diet.

“Soluble fiber is efficacious in treating global symptoms of IBS,” they wrote, citing 15 randomized controlled trials. Soluble fiber is most suitable for patients with constipation-predominant IBS, and different soluble fibers may yield different outcomes based on characteristics such as rate of fermentation and viscosity. In contrast, insoluble fiber is unlikely to help with IBS, and may worsen abdominal pain and bloating.

The low-FODMAP diet is “currently the most evidence-based diet intervention for IBS,” especially for patients with diarrhea-predominant IBS. Dr. Chey and colleagues offered a clear roadmap for employing the diet. First, patients should eat only low-FODMAP foods for 4-6 weeks. If symptoms don’t improve, the diet should be stopped. If symptoms do improve, foods containing a single FODMAP should be reintroduced one at a time, each in increasing quantities over 3 days, alongside documentation of symptom responses. Finally, the diet should be personalized based on these responses. The majority of patients (close to 80%) “can liberalize” a low-FODMAP diet based on their responses.

In contrast with the low-FODMAP diet, which has a relatively solid body of supporting evidence, efficacy data are still limited for treating IBS with a gluten-free diet. “Although observational studies found that most patients with IBS improve with a gluten-free diet, randomized controlled trials have yielded mixed results,” Dr. Chey and colleagues explained.

Their report cited a recent monograph on the topic that concluded that gluten-free eating offered no significant benefit over placebo (relative risk, 0.46; 95% confidence interval, 0.16-1.28). While some studies have documented positive results with a gluten-free diet, Dr. Chey and colleagues suggested that confounding variables such as the nocebo effect and the impact of other dietary factors have yet to be ruled out. “At present, it remains unclear whether a gluten-free diet is of benefit to patients with IBS.”

Dr. Chey and colleagues also explored IBS biomarkers. While some early data have shown that biomarkers may predict dietary responses, “there is insufficient evidence to support their routine use in clinical practice. ... Further efforts to identify and validate biomarkers that predict response to dietary interventions are needed to deliver ‘personalized nutrition.’ ”

The clinical practice update was commissioned and approved by the AGA CPU Committee and the AGA Governing Board. The researchers disclosed relationships with Biomerica, Salix, Mauna Kea Technologies, and others.

This article was updated May 19, 2022.

The American Gastroenterological Association has published a clinical practice update on dietary interventions for patients with irritable bowel syndrome (IBS). The topics range from identification of suitable candidates for dietary interventions, to levels of evidence for specific diets, which are becoming increasingly recognized for their key role in managing patients with IBS, according to lead author William D. Chey, MD, of the University of Michigan, Ann Arbor, and colleagues.

“Most medical therapies for IBS improve global symptoms in fewer than one-half of patients, with a therapeutic gain of 7%-15% over placebo,” the researchers wrote in Gastroenterology. “Most patients with IBS associate their GI symptoms with eating food.”

According to Dr. Chey and colleagues, clinicians who are considering dietary modifications for treating IBS should first recognize the inherent challenges presented by this process and be aware that new diets won’t work for everyone.

“Specialty diets require planning and preparation, which may be impractical for some patients,” they wrote, noting that individuals with “decreased cognitive abilities and significant psychiatric disease” may be unable to follow diets or interpret their own responses to specific foods. Special diets may also be inappropriate for patients with financial constraints, and “should be avoided in patients with an eating disorder.”

Because of the challenges involved in dietary interventions, Dr. Chey and colleagues advised clinical support from a registered dietitian nutritionist or other resource.

Patients who are suitable candidates for intervention and willing to try a new diet should first provide information about their current eating habits. A food trial can then be personalized and implemented for a predetermined amount of time. If the patient does not respond, then the diet should be stopped and changed to a new diet or another intervention.

Dr. Chey and colleagues discussed three specific dietary interventions and their corresponding levels of evidence: soluble fiber; the low-fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet; and a gluten-free diet.

“Soluble fiber is efficacious in treating global symptoms of IBS,” they wrote, citing 15 randomized controlled trials. Soluble fiber is most suitable for patients with constipation-predominant IBS, and different soluble fibers may yield different outcomes based on characteristics such as rate of fermentation and viscosity. In contrast, insoluble fiber is unlikely to help with IBS, and may worsen abdominal pain and bloating.

The low-FODMAP diet is “currently the most evidence-based diet intervention for IBS,” especially for patients with diarrhea-predominant IBS. Dr. Chey and colleagues offered a clear roadmap for employing the diet. First, patients should eat only low-FODMAP foods for 4-6 weeks. If symptoms don’t improve, the diet should be stopped. If symptoms do improve, foods containing a single FODMAP should be reintroduced one at a time, each in increasing quantities over 3 days, alongside documentation of symptom responses. Finally, the diet should be personalized based on these responses. The majority of patients (close to 80%) “can liberalize” a low-FODMAP diet based on their responses.

In contrast with the low-FODMAP diet, which has a relatively solid body of supporting evidence, efficacy data are still limited for treating IBS with a gluten-free diet. “Although observational studies found that most patients with IBS improve with a gluten-free diet, randomized controlled trials have yielded mixed results,” Dr. Chey and colleagues explained.

Their report cited a recent monograph on the topic that concluded that gluten-free eating offered no significant benefit over placebo (relative risk, 0.46; 95% confidence interval, 0.16-1.28). While some studies have documented positive results with a gluten-free diet, Dr. Chey and colleagues suggested that confounding variables such as the nocebo effect and the impact of other dietary factors have yet to be ruled out. “At present, it remains unclear whether a gluten-free diet is of benefit to patients with IBS.”

Dr. Chey and colleagues also explored IBS biomarkers. While some early data have shown that biomarkers may predict dietary responses, “there is insufficient evidence to support their routine use in clinical practice. ... Further efforts to identify and validate biomarkers that predict response to dietary interventions are needed to deliver ‘personalized nutrition.’ ”

The clinical practice update was commissioned and approved by the AGA CPU Committee and the AGA Governing Board. The researchers disclosed relationships with Biomerica, Salix, Mauna Kea Technologies, and others.

This article was updated May 19, 2022.

The Society for Cardiovascular Angiography and Interventions (SCAI) has issued the first statement on best practices for percutaneous axillary arterial access and training.

The position statement helps fill a gap amid increasing use of transaxillary access as an alternative to the femoral route for large-bore transcatheter aortic valve replacement (TAVR), endovascular aortic repair (EVAR), and mechanical circulatory support.

“The need for alternative access has increased as we are using more and more TAVR for our elderly population, and EVAR has also increased,” writing committee chair Arnold H. Seto, MD, Long Beach VA Health Care System (California) said in an interview. “There’s also a set of patients who require balloon pumps for a prolonged period, and people were using balloon pumps from the axillary approach, which were not custom-designed for that purpose.”

He noted that the evidence base leans heavily on case reports and case series, and that they were approached for guidance by a vendor developing a balloon pump specific to axillary access. “So that helped spur all of us to get together and decide to write up something on this topic, which was developing, but was certainly picking up steam rapidly.”

The statement was published in the Journal of the Society for Cardiovascular Angiography and Interventions, and it reflects the consensus of experts in heart failure, interventional cardiology and radiology, and cardiothoracic and vascular surgery. It reviews anatomic considerations and risks for percutaneous axillary access and suggests techniques for insertion, closure, and complication management.

Although the femoral artery is the most frequent access site for percutaneous large-bore procedures, the document notes that this approach may be limited in 13%-20% of patients because of prior surgeries or severe aortoiliac and/or iliofemoral atherosclerotic disease, tortuosity, or calcification.

“Absolutely, the femoral should be the predominant access site,” Dr. Seto said. Whenever there is a compromised femoral artery, “the axillary artery, which is rarely involved with atherosclerosis, makes for the most optimal alternative access. Other forms of alternative access, including transcaval and transcarotid, are possible but have their own issues and difficulties.”

Axillary access has traditionally been done through an open surgical approach, which allows for direct puncture, primary arterial repair, or placement of a sidearm conduit. Percutaneous transaxillary access avoids a surgical incision and general anesthesia and, theoretically, reduces the risk of infection, he said. It also allows for better mobility for patients, for example, who may have a balloon pump in place for weeks or even a month when waiting for a bridge to transplant.

In terms of technique, key recommendations include:

• Gaining access preferably through the left axillary
• Inserting the needle directly through the pectoralis minor into the second segment of the axillary artery
• Using a shallow-needle angle of 25-30 degrees to improve access success and decrease sheath malformation, kinking, bleeding, or vessel perforation
• Using micropuncture needles to minimize trauma to adjacent tissues
• Abducting the patient’s arm to 45-90 degrees to reduce tortuosity
• Using angiographic and ultrasound techniques to optimize vascular access

The latter point was the one area of debate among the writing committee, Dr. Seto observed. “That is one of the controversies: Should we make ultrasound mandatory? ... Everybody agreed that it can be quite useful and was likely to be useful because of its success in every other access area,” he said. “But in the absence of randomized evidence, we couldn’t make it mandatory or a strong recommendation. We just had to make it one of several options for the operator.”

The document highlights the need for familiarity with potential axillary artery complications and their management, noting that the axillary is more fragile than the femoral artery and, thus, potentially more prone to complications during instrumentation.

Data from the ARMS study in 102 patients undergoing transaxillary access for mechanical hemodynamic support reported 17 procedural complications, including 10 minor access site bleeding events, one stroke, and one pseudoaneurysm. A small study of 25 complex EVAR procedures reported a perioperative access complication rate of 8%, including one axillary artery dissection and one stenosis.

“Despite the brachial plexus being around there, there’s actually rare reports of neurologic injury and certainly none that have been permanent,” Dr. Seto said. “Also, stroke risk is probably more related to your device size and type of device rather than the approach itself.”

A significant amount of the paper is also devoted to training and privileging suggestions with an emphasis on a multidisciplinary team. The writing group recommends graduate medical education programs develop training curricula in percutaneous axillary artery access.

Those already in practice should participate in a formal training program that focuses on axillary artery anatomy, training in large bore access and closure devices, and didactic training in imaging modalities as applied to the axillary artery. Training can occur hands-on or using online simulations.

They also recommend outlining the potential need or role for proctoring and call for ongoing formal professional monitoring programs to evaluate operator outcomes using local or registry data.

“From a privileging standpoint, it was important for hospitals to be equally fair, regardless of the specialty that a requesting practitioner came from,” Dr. Seto said. “In other words, treat the vascular surgeons and interventional cardiologists and radiologists equally in terms of who has the privilege to do transaxillary access.”

The SCAI position statement has been endorsed by the American College of Cardiology, the Heart Failure Society of America, the Society of Interventional Radiology, and the Vascular & Endovascular Surgery Society.

Dr. Seto reported receiving honoraria from Getinge prior to initiation of the document. Disclosures for the rest of the writing group are available with the original article.

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

The Society for Cardiovascular Angiography and Interventions (SCAI) has issued the first statement on best practices for percutaneous axillary arterial access and training.

The position statement helps fill a gap amid increasing use of transaxillary access as an alternative to the femoral route for large-bore transcatheter aortic valve replacement (TAVR), endovascular aortic repair (EVAR), and mechanical circulatory support.

“The need for alternative access has increased as we are using more and more TAVR for our elderly population, and EVAR has also increased,” writing committee chair Arnold H. Seto, MD, Long Beach VA Health Care System (California) said in an interview. “There’s also a set of patients who require balloon pumps for a prolonged period, and people were using balloon pumps from the axillary approach, which were not custom-designed for that purpose.”

He noted that the evidence base leans heavily on case reports and case series, and that they were approached for guidance by a vendor developing a balloon pump specific to axillary access. “So that helped spur all of us to get together and decide to write up something on this topic, which was developing, but was certainly picking up steam rapidly.”

The statement was published in the Journal of the Society for Cardiovascular Angiography and Interventions, and it reflects the consensus of experts in heart failure, interventional cardiology and radiology, and cardiothoracic and vascular surgery. It reviews anatomic considerations and risks for percutaneous axillary access and suggests techniques for insertion, closure, and complication management.

Although the femoral artery is the most frequent access site for percutaneous large-bore procedures, the document notes that this approach may be limited in 13%-20% of patients because of prior surgeries or severe aortoiliac and/or iliofemoral atherosclerotic disease, tortuosity, or calcification.

“Absolutely, the femoral should be the predominant access site,” Dr. Seto said. Whenever there is a compromised femoral artery, “the axillary artery, which is rarely involved with atherosclerosis, makes for the most optimal alternative access. Other forms of alternative access, including transcaval and transcarotid, are possible but have their own issues and difficulties.”

Axillary access has traditionally been done through an open surgical approach, which allows for direct puncture, primary arterial repair, or placement of a sidearm conduit. Percutaneous transaxillary access avoids a surgical incision and general anesthesia and, theoretically, reduces the risk of infection, he said. It also allows for better mobility for patients, for example, who may have a balloon pump in place for weeks or even a month when waiting for a bridge to transplant.

In terms of technique, key recommendations include:

• Gaining access preferably through the left axillary
• Inserting the needle directly through the pectoralis minor into the second segment of the axillary artery
• Using a shallow-needle angle of 25-30 degrees to improve access success and decrease sheath malformation, kinking, bleeding, or vessel perforation
• Using micropuncture needles to minimize trauma to adjacent tissues
• Abducting the patient’s arm to 45-90 degrees to reduce tortuosity
• Using angiographic and ultrasound techniques to optimize vascular access

The latter point was the one area of debate among the writing committee, Dr. Seto observed. “That is one of the controversies: Should we make ultrasound mandatory? ... Everybody agreed that it can be quite useful and was likely to be useful because of its success in every other access area,” he said. “But in the absence of randomized evidence, we couldn’t make it mandatory or a strong recommendation. We just had to make it one of several options for the operator.”

The document highlights the need for familiarity with potential axillary artery complications and their management, noting that the axillary is more fragile than the femoral artery and, thus, potentially more prone to complications during instrumentation.

Data from the ARMS study in 102 patients undergoing transaxillary access for mechanical hemodynamic support reported 17 procedural complications, including 10 minor access site bleeding events, one stroke, and one pseudoaneurysm. A small study of 25 complex EVAR procedures reported a perioperative access complication rate of 8%, including one axillary artery dissection and one stenosis.

“Despite the brachial plexus being around there, there’s actually rare reports of neurologic injury and certainly none that have been permanent,” Dr. Seto said. “Also, stroke risk is probably more related to your device size and type of device rather than the approach itself.”

A significant amount of the paper is also devoted to training and privileging suggestions with an emphasis on a multidisciplinary team. The writing group recommends graduate medical education programs develop training curricula in percutaneous axillary artery access.

Those already in practice should participate in a formal training program that focuses on axillary artery anatomy, training in large bore access and closure devices, and didactic training in imaging modalities as applied to the axillary artery. Training can occur hands-on or using online simulations.

They also recommend outlining the potential need or role for proctoring and call for ongoing formal professional monitoring programs to evaluate operator outcomes using local or registry data.

“From a privileging standpoint, it was important for hospitals to be equally fair, regardless of the specialty that a requesting practitioner came from,” Dr. Seto said. “In other words, treat the vascular surgeons and interventional cardiologists and radiologists equally in terms of who has the privilege to do transaxillary access.”

The SCAI position statement has been endorsed by the American College of Cardiology, the Heart Failure Society of America, the Society of Interventional Radiology, and the Vascular & Endovascular Surgery Society.

Dr. Seto reported receiving honoraria from Getinge prior to initiation of the document. Disclosures for the rest of the writing group are available with the original article.

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

The Society for Cardiovascular Angiography and Interventions (SCAI) has issued the first statement on best practices for percutaneous axillary arterial access and training.

The position statement helps fill a gap amid increasing use of transaxillary access as an alternative to the femoral route for large-bore transcatheter aortic valve replacement (TAVR), endovascular aortic repair (EVAR), and mechanical circulatory support.

“The need for alternative access has increased as we are using more and more TAVR for our elderly population, and EVAR has also increased,” writing committee chair Arnold H. Seto, MD, Long Beach VA Health Care System (California) said in an interview. “There’s also a set of patients who require balloon pumps for a prolonged period, and people were using balloon pumps from the axillary approach, which were not custom-designed for that purpose.”

He noted that the evidence base leans heavily on case reports and case series, and that they were approached for guidance by a vendor developing a balloon pump specific to axillary access. “So that helped spur all of us to get together and decide to write up something on this topic, which was developing, but was certainly picking up steam rapidly.”

The statement was published in the Journal of the Society for Cardiovascular Angiography and Interventions, and it reflects the consensus of experts in heart failure, interventional cardiology and radiology, and cardiothoracic and vascular surgery. It reviews anatomic considerations and risks for percutaneous axillary access and suggests techniques for insertion, closure, and complication management.

Although the femoral artery is the most frequent access site for percutaneous large-bore procedures, the document notes that this approach may be limited in 13%-20% of patients because of prior surgeries or severe aortoiliac and/or iliofemoral atherosclerotic disease, tortuosity, or calcification.

“Absolutely, the femoral should be the predominant access site,” Dr. Seto said. Whenever there is a compromised femoral artery, “the axillary artery, which is rarely involved with atherosclerosis, makes for the most optimal alternative access. Other forms of alternative access, including transcaval and transcarotid, are possible but have their own issues and difficulties.”

Axillary access has traditionally been done through an open surgical approach, which allows for direct puncture, primary arterial repair, or placement of a sidearm conduit. Percutaneous transaxillary access avoids a surgical incision and general anesthesia and, theoretically, reduces the risk of infection, he said. It also allows for better mobility for patients, for example, who may have a balloon pump in place for weeks or even a month when waiting for a bridge to transplant.

In terms of technique, key recommendations include:

• Gaining access preferably through the left axillary
• Inserting the needle directly through the pectoralis minor into the second segment of the axillary artery
• Using a shallow-needle angle of 25-30 degrees to improve access success and decrease sheath malformation, kinking, bleeding, or vessel perforation
• Using micropuncture needles to minimize trauma to adjacent tissues
• Abducting the patient’s arm to 45-90 degrees to reduce tortuosity
• Using angiographic and ultrasound techniques to optimize vascular access

The latter point was the one area of debate among the writing committee, Dr. Seto observed. “That is one of the controversies: Should we make ultrasound mandatory? ... Everybody agreed that it can be quite useful and was likely to be useful because of its success in every other access area,” he said. “But in the absence of randomized evidence, we couldn’t make it mandatory or a strong recommendation. We just had to make it one of several options for the operator.”

The document highlights the need for familiarity with potential axillary artery complications and their management, noting that the axillary is more fragile than the femoral artery and, thus, potentially more prone to complications during instrumentation.

Data from the ARMS study in 102 patients undergoing transaxillary access for mechanical hemodynamic support reported 17 procedural complications, including 10 minor access site bleeding events, one stroke, and one pseudoaneurysm. A small study of 25 complex EVAR procedures reported a perioperative access complication rate of 8%, including one axillary artery dissection and one stenosis.

“Despite the brachial plexus being around there, there’s actually rare reports of neurologic injury and certainly none that have been permanent,” Dr. Seto said. “Also, stroke risk is probably more related to your device size and type of device rather than the approach itself.”

A significant amount of the paper is also devoted to training and privileging suggestions with an emphasis on a multidisciplinary team. The writing group recommends graduate medical education programs develop training curricula in percutaneous axillary artery access.

Those already in practice should participate in a formal training program that focuses on axillary artery anatomy, training in large bore access and closure devices, and didactic training in imaging modalities as applied to the axillary artery. Training can occur hands-on or using online simulations.

They also recommend outlining the potential need or role for proctoring and call for ongoing formal professional monitoring programs to evaluate operator outcomes using local or registry data.

“From a privileging standpoint, it was important for hospitals to be equally fair, regardless of the specialty that a requesting practitioner came from,” Dr. Seto said. “In other words, treat the vascular surgeons and interventional cardiologists and radiologists equally in terms of who has the privilege to do transaxillary access.”

The SCAI position statement has been endorsed by the American College of Cardiology, the Heart Failure Society of America, the Society of Interventional Radiology, and the Vascular & Endovascular Surgery Society.

Dr. Seto reported receiving honoraria from Getinge prior to initiation of the document. Disclosures for the rest of the writing group are available with the original article.

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

A clinical practice guideline for the diagnosis and management of gastrointestinal hamartomatous polyposis syndromes has just been published by the U.S. Multi-Society Task Force on Colorectal Cancer, which is comprised of experts representing the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy.

Gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with intestinal and extraintestinal tumors. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,” lead author C. Richard Boland, MD, of the University of California, San Diego, and colleagues reported.

According to the investigators, “there are essentially no long-term prospective controlled studies of comparative effectiveness of management strategies for these syndromes.” As a result, their recommendations are based on “low-quality” evidence according to GRADE criteria.

Still, Dr. Boland and colleagues highlighted that “there has been tremendous progress in recent years, both in understanding the underlying genetics that underpin these disorders and in elucidating the biology of associated premalignant and malignant conditions.”

The guideline was published online in Gastroenterology .
 

Four syndromes reviewed

The investigators gathered these data to provide an overview of genetic and clinical features for each syndrome, as well as management strategies. Four disorders are included: juvenile polyposis syndrome; Peutz-Jeghers syndrome; hereditary mixed polyposis syndrome; and PTEN-hamartoma tumor syndrome, encompassing Bannayan-Riley-Ruvalcaba syndrome and Cowden’s syndrome.

Although all gastrointestinal hamartomatous polyposis syndromes are caused by germline alterations, Dr. Boland and colleagues pointed out that diagnoses are typically made based on clinical criteria, with germline results serving as confirmatory evidence.

The guideline recommends that any patient with a family history of hamartomatous polyps, or with a history of at least two hamartomatous polyps, should undergo genetic testing. The guideline also provides more nuanced genetic testing algorithms for each syndrome.

Among all the hamartomatous polyp disorders, Peutz-Jeghers syndrome is most understood, according to the investigators. It is caused by aberrations in the STK11 gene, and is characterized by polyps with “branching bands of smooth muscle covered by hyperplastic glandular mucosa” that may occur in the stomach, small intestine, and colon. Patients are also at risk of extraintestinal neoplasia.

For management of Peutz-Jeghers syndrome, the guideline advises frequent endoscopic surveillance to prevent mechanical obstruction and bleeding, as well as multidisciplinary surveillance of the breasts, pancreas, ovaries, testes, and lungs.

Juvenile polyposis syndrome is most often characterized by solitary, sporadic polyps in the colorectum (98% of patients affected), followed distantly by polyps in the stomach (14%), ileum (7%), jejunum (7%), and duodenum (7%). The condition is linked with abnormalities in BMPR1A or SMAD4 genes, with SMAD4 germline abnormalities more often leading to “massive” gastric polyps, gastrointestinal bleeding, protein-losing enteropathy, and a higher incidence of gastric cancer in adulthood. Most patients with SMAD4 mutations also have hereditary hemorrhagic telangiectasia, characterized by gastrointestinal bleeding from mucocutaneous telangiectasias, arteriovenous malformations, and epistaxis.

Management of juvenile polyposis syndrome depends on frequent colonoscopies with polypectomies beginning at 12-15 years.

“The goal of surveillance in juvenile polyposis syndrome is to mitigate symptoms related to the disorder and decrease the risk of complications from the manifestations, including cancer,” Dr. Boland and colleagues wrote.

PTEN-hamartoma tumor syndrome, which includes both Bannayan-Riley-Ruvalcaba syndrome and Cowden’s syndrome, is caused by abnormalities in the eponymous PTEN gene. Patients with the condition have an increased risk of colon cancer and polyposis, as well as extraintestinal cancers.

Diagnosis of PTEN-hamartoma tumor syndrome may be complex, involving “clinical examination, mammography and breast MRI, thyroid ultrasound, transvaginal ultrasound, upper gastrointestinal endoscopy, colonoscopy, and renal ultrasound,” according to the guideline.

After diagnosis, frequent colonoscopies are recommended, typically starting at age 35 years, as well as continued surveillance of other organs.

Hereditary mixed polyposis syndrome, which involves attenuated colonic polyposis, is the rarest of the four disorders, having been reported in only “a few families,” according to the guideline. The condition has been linked with “large duplications of the promoter region or entire GREM1 gene.”

Onset is typically in the late 20s, “which is when colonoscopic surveillance should begin,” the investigators wrote. More data are needed to determine appropriate surveillance intervals and if the condition is associated with increased risk of extraintestinal neoplasia.

This call for more research into gastrointestinal hamartomatous polyposis syndromes carried through to the conclusion of the guideline.

“Long-term prospective studies of mutation carriers are still needed to further clarify the risk of cancer and the role of surveillance in these syndromes,” Dr. Boland and colleagues wrote. “With increases in genetic testing and evaluation, future studies will be conducted with more robust cohorts of genetically characterized, less heterogeneous populations. However, there is also a need to study patients and families with unusual phenotypes where no genotype can be found.”

The investigators disclosed no conflicts of interest with the current guideline; however, they provided a list of industry relationships, including Salix Pharmaceuticals, Ferring Pharmaceuticals, and Pfizer, among others.

A clinical practice guideline for the diagnosis and management of gastrointestinal hamartomatous polyposis syndromes has just been published by the U.S. Multi-Society Task Force on Colorectal Cancer, which is comprised of experts representing the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy.

Gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with intestinal and extraintestinal tumors. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,” lead author C. Richard Boland, MD, of the University of California, San Diego, and colleagues reported.

According to the investigators, “there are essentially no long-term prospective controlled studies of comparative effectiveness of management strategies for these syndromes.” As a result, their recommendations are based on “low-quality” evidence according to GRADE criteria.

Still, Dr. Boland and colleagues highlighted that “there has been tremendous progress in recent years, both in understanding the underlying genetics that underpin these disorders and in elucidating the biology of associated premalignant and malignant conditions.”

The guideline was published online in Gastroenterology .
 

Four syndromes reviewed

The investigators gathered these data to provide an overview of genetic and clinical features for each syndrome, as well as management strategies. Four disorders are included: juvenile polyposis syndrome; Peutz-Jeghers syndrome; hereditary mixed polyposis syndrome; and PTEN-hamartoma tumor syndrome, encompassing Bannayan-Riley-Ruvalcaba syndrome and Cowden’s syndrome.

Although all gastrointestinal hamartomatous polyposis syndromes are caused by germline alterations, Dr. Boland and colleagues pointed out that diagnoses are typically made based on clinical criteria, with germline results serving as confirmatory evidence.

The guideline recommends that any patient with a family history of hamartomatous polyps, or with a history of at least two hamartomatous polyps, should undergo genetic testing. The guideline also provides more nuanced genetic testing algorithms for each syndrome.

Among all the hamartomatous polyp disorders, Peutz-Jeghers syndrome is most understood, according to the investigators. It is caused by aberrations in the STK11 gene, and is characterized by polyps with “branching bands of smooth muscle covered by hyperplastic glandular mucosa” that may occur in the stomach, small intestine, and colon. Patients are also at risk of extraintestinal neoplasia.

For management of Peutz-Jeghers syndrome, the guideline advises frequent endoscopic surveillance to prevent mechanical obstruction and bleeding, as well as multidisciplinary surveillance of the breasts, pancreas, ovaries, testes, and lungs.

Juvenile polyposis syndrome is most often characterized by solitary, sporadic polyps in the colorectum (98% of patients affected), followed distantly by polyps in the stomach (14%), ileum (7%), jejunum (7%), and duodenum (7%). The condition is linked with abnormalities in BMPR1A or SMAD4 genes, with SMAD4 germline abnormalities more often leading to “massive” gastric polyps, gastrointestinal bleeding, protein-losing enteropathy, and a higher incidence of gastric cancer in adulthood. Most patients with SMAD4 mutations also have hereditary hemorrhagic telangiectasia, characterized by gastrointestinal bleeding from mucocutaneous telangiectasias, arteriovenous malformations, and epistaxis.

Management of juvenile polyposis syndrome depends on frequent colonoscopies with polypectomies beginning at 12-15 years.

“The goal of surveillance in juvenile polyposis syndrome is to mitigate symptoms related to the disorder and decrease the risk of complications from the manifestations, including cancer,” Dr. Boland and colleagues wrote.

PTEN-hamartoma tumor syndrome, which includes both Bannayan-Riley-Ruvalcaba syndrome and Cowden’s syndrome, is caused by abnormalities in the eponymous PTEN gene. Patients with the condition have an increased risk of colon cancer and polyposis, as well as extraintestinal cancers.

Diagnosis of PTEN-hamartoma tumor syndrome may be complex, involving “clinical examination, mammography and breast MRI, thyroid ultrasound, transvaginal ultrasound, upper gastrointestinal endoscopy, colonoscopy, and renal ultrasound,” according to the guideline.

After diagnosis, frequent colonoscopies are recommended, typically starting at age 35 years, as well as continued surveillance of other organs.

Hereditary mixed polyposis syndrome, which involves attenuated colonic polyposis, is the rarest of the four disorders, having been reported in only “a few families,” according to the guideline. The condition has been linked with “large duplications of the promoter region or entire GREM1 gene.”

Onset is typically in the late 20s, “which is when colonoscopic surveillance should begin,” the investigators wrote. More data are needed to determine appropriate surveillance intervals and if the condition is associated with increased risk of extraintestinal neoplasia.

This call for more research into gastrointestinal hamartomatous polyposis syndromes carried through to the conclusion of the guideline.

“Long-term prospective studies of mutation carriers are still needed to further clarify the risk of cancer and the role of surveillance in these syndromes,” Dr. Boland and colleagues wrote. “With increases in genetic testing and evaluation, future studies will be conducted with more robust cohorts of genetically characterized, less heterogeneous populations. However, there is also a need to study patients and families with unusual phenotypes where no genotype can be found.”

The investigators disclosed no conflicts of interest with the current guideline; however, they provided a list of industry relationships, including Salix Pharmaceuticals, Ferring Pharmaceuticals, and Pfizer, among others.

A clinical practice guideline for the diagnosis and management of gastrointestinal hamartomatous polyposis syndromes has just been published by the U.S. Multi-Society Task Force on Colorectal Cancer, which is comprised of experts representing the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy.

Gastrointestinal hamartomatous polyposis syndromes are rare, autosomal dominant disorders associated with intestinal and extraintestinal tumors. Expert consensus statements have previously offered some recommendations for managing these syndromes, but clinical data are scarce, so the present review “is intended to establish a starting point for future research,” lead author C. Richard Boland, MD, of the University of California, San Diego, and colleagues reported.

According to the investigators, “there are essentially no long-term prospective controlled studies of comparative effectiveness of management strategies for these syndromes.” As a result, their recommendations are based on “low-quality” evidence according to GRADE criteria.

Still, Dr. Boland and colleagues highlighted that “there has been tremendous progress in recent years, both in understanding the underlying genetics that underpin these disorders and in elucidating the biology of associated premalignant and malignant conditions.”

The guideline was published online in Gastroenterology .
 

Four syndromes reviewed

The investigators gathered these data to provide an overview of genetic and clinical features for each syndrome, as well as management strategies. Four disorders are included: juvenile polyposis syndrome; Peutz-Jeghers syndrome; hereditary mixed polyposis syndrome; and PTEN-hamartoma tumor syndrome, encompassing Bannayan-Riley-Ruvalcaba syndrome and Cowden’s syndrome.

Although all gastrointestinal hamartomatous polyposis syndromes are caused by germline alterations, Dr. Boland and colleagues pointed out that diagnoses are typically made based on clinical criteria, with germline results serving as confirmatory evidence.

The guideline recommends that any patient with a family history of hamartomatous polyps, or with a history of at least two hamartomatous polyps, should undergo genetic testing. The guideline also provides more nuanced genetic testing algorithms for each syndrome.

Among all the hamartomatous polyp disorders, Peutz-Jeghers syndrome is most understood, according to the investigators. It is caused by aberrations in the STK11 gene, and is characterized by polyps with “branching bands of smooth muscle covered by hyperplastic glandular mucosa” that may occur in the stomach, small intestine, and colon. Patients are also at risk of extraintestinal neoplasia.

For management of Peutz-Jeghers syndrome, the guideline advises frequent endoscopic surveillance to prevent mechanical obstruction and bleeding, as well as multidisciplinary surveillance of the breasts, pancreas, ovaries, testes, and lungs.

Juvenile polyposis syndrome is most often characterized by solitary, sporadic polyps in the colorectum (98% of patients affected), followed distantly by polyps in the stomach (14%), ileum (7%), jejunum (7%), and duodenum (7%). The condition is linked with abnormalities in BMPR1A or SMAD4 genes, with SMAD4 germline abnormalities more often leading to “massive” gastric polyps, gastrointestinal bleeding, protein-losing enteropathy, and a higher incidence of gastric cancer in adulthood. Most patients with SMAD4 mutations also have hereditary hemorrhagic telangiectasia, characterized by gastrointestinal bleeding from mucocutaneous telangiectasias, arteriovenous malformations, and epistaxis.

Management of juvenile polyposis syndrome depends on frequent colonoscopies with polypectomies beginning at 12-15 years.

“The goal of surveillance in juvenile polyposis syndrome is to mitigate symptoms related to the disorder and decrease the risk of complications from the manifestations, including cancer,” Dr. Boland and colleagues wrote.

PTEN-hamartoma tumor syndrome, which includes both Bannayan-Riley-Ruvalcaba syndrome and Cowden’s syndrome, is caused by abnormalities in the eponymous PTEN gene. Patients with the condition have an increased risk of colon cancer and polyposis, as well as extraintestinal cancers.

Diagnosis of PTEN-hamartoma tumor syndrome may be complex, involving “clinical examination, mammography and breast MRI, thyroid ultrasound, transvaginal ultrasound, upper gastrointestinal endoscopy, colonoscopy, and renal ultrasound,” according to the guideline.

After diagnosis, frequent colonoscopies are recommended, typically starting at age 35 years, as well as continued surveillance of other organs.

Hereditary mixed polyposis syndrome, which involves attenuated colonic polyposis, is the rarest of the four disorders, having been reported in only “a few families,” according to the guideline. The condition has been linked with “large duplications of the promoter region or entire GREM1 gene.”

Onset is typically in the late 20s, “which is when colonoscopic surveillance should begin,” the investigators wrote. More data are needed to determine appropriate surveillance intervals and if the condition is associated with increased risk of extraintestinal neoplasia.

This call for more research into gastrointestinal hamartomatous polyposis syndromes carried through to the conclusion of the guideline.

“Long-term prospective studies of mutation carriers are still needed to further clarify the risk of cancer and the role of surveillance in these syndromes,” Dr. Boland and colleagues wrote. “With increases in genetic testing and evaluation, future studies will be conducted with more robust cohorts of genetically characterized, less heterogeneous populations. However, there is also a need to study patients and families with unusual phenotypes where no genotype can be found.”

The investigators disclosed no conflicts of interest with the current guideline; however, they provided a list of industry relationships, including Salix Pharmaceuticals, Ferring Pharmaceuticals, and Pfizer, among others.