A 26-year-old woman presented to our clinic with pruritic, hyperpigmented, symmetric edematous plaques on her upper flank, chest, and lower back (FIGURE) 3 weeks after starting a strict ketogenic (high fat/low carbohydrate) diet for postpartum weight loss. The patient was an otherwise healthy stay-at-home mother with an unremarkable medical history.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Prurigo pigmentosa

We recognized that this was a case of prurigo pigmentosa based on the characteristic pruritic rash that had developed after the patient started a strict ketogenic diet.

Prurigo pigmentosa is a benign, pruritic rash that most commonly presents with erythematous or hyperpigmented, symmetrically distributed urticarial papules and plaques on the chest and back. Females represent approximately 70% of cases with a predominant age range of 11 to 30.¹

While the pathophysiology remains unknown, the rash most often is reported in association with ketogenic diets.¹ Despite occurring in only a fraction of patients on the ketogenic diet, the characteristic presentation has led to the alternative name of the “keto rash” in online nutritional forums and blogs.

The characteristic presentation of prurigo pigmentosa has led to the alternative name of the “keto rash” in online nutritional forums.

Although prurigo pigmentosa is relatively uncommon (with an unknown incidence), primary care physicians may begin to encounter the characteristic rash more frequently, given the number of articles over the past 5 years in the primary care and nutritional literature highlighting the diet’s health benefits.² The ketogenic diet is a high-fat, low-carbohydrate diet with preliminary evidence of improved weight loss, cardiovascular health, and glycemic control suggested by a meta-analysis of 13 randomized controlled trials.³ Additionally, the popular press and general public’s rising interest are likely to increase the number of patients on this diet.

A clinical diagnosis

The diagnosis is made clinically, so the appearance of a symmetric pruritic, hyperpigmented rash on the chest and back should prompt the physician to ask about any recent changes in diet. Laboratory analysis is unnecessary, as a complete blood count, basic metabolic panel, and liver function panel are almost always normal. Urinary ketones are present in only 30% to 50% of patients; there is, however, an absence of blood ketones.^1,4

Continue to: Other conditions can mimic prurigo pigmentosa

 

 

Other conditions can mimic prurigo pigmentosa

Urticaria presents as individual lesions that often have a pale center. The lesions may occur anywhere on the body and generally last less than 24 hours. History may reveal a trigger including drugs, infection, food, or emotional stress in up to 50% of cases.⁵

Irritant contact dermatitis often is associated with a stinging or burning sensation. Irritant and allergic contact dermatitis may have a geometric, or “outside job,” distribution suggestive of external contact, potentially with plants, alkalis, acids, or solvents.⁵

Confluent and reticulated papillomatosis is a rare asymptomatic dermatosis of unknown etiology that presents as hyperpigmented papules on the upper trunk, neck, and axillae. Most patients lack associated pruritis which is in contrast to prurigo pigmentosa.⁶

Pityriasis rosea is a viral exanthem that may be associated with constitutional symptoms and often presents initially with a herald patch progressing to a classic “Christmas tree” distribution with a fine collarette of scale. It often is asymptomatic, although some cases may be pruritic.⁵

Treatment focuses on dietary modification

Primary treatment includes resumption of a normal diet. This often leads to rapid resolution of pruritis. Residual hyperpigmentation may take months to fade.

Continue to: Pharmaceutical intervention may be necessary

 

 

Pharmaceutical intervention may be necessary

If additional treatment is required, minocycline 100 to 200 mg/d has been reported most effective, likely due to its anti-inflammatory properties.^1,4 Topical corticosteroids and oral antihistamines provide symptomatic relief in some patients.^1,4

Our patient had resolution of the pruritis and urticarial lesions within 2 days of resuming a normal diet; however, residual asymptomatic hyperpigmentation persisted. A retrial of the ketogenic diet initiated a flare of the rash in the same distribution. It rapidly resolved with carbohydrate intake.

CORRESPONDENCE
Daniel Croom, MD, 34520 Bob Wilson Dr, Naval Medical Center San Diego, San Diego, CA 92134; daniel.l.croom.mil@mail.mil

A 26-year-old woman presented to our clinic with pruritic, hyperpigmented, symmetric edematous plaques on her upper flank, chest, and lower back (FIGURE) 3 weeks after starting a strict ketogenic (high fat/low carbohydrate) diet for postpartum weight loss. The patient was an otherwise healthy stay-at-home mother with an unremarkable medical history.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Prurigo pigmentosa

We recognized that this was a case of prurigo pigmentosa based on the characteristic pruritic rash that had developed after the patient started a strict ketogenic diet.

Prurigo pigmentosa is a benign, pruritic rash that most commonly presents with erythematous or hyperpigmented, symmetrically distributed urticarial papules and plaques on the chest and back. Females represent approximately 70% of cases with a predominant age range of 11 to 30.¹

While the pathophysiology remains unknown, the rash most often is reported in association with ketogenic diets.¹ Despite occurring in only a fraction of patients on the ketogenic diet, the characteristic presentation has led to the alternative name of the “keto rash” in online nutritional forums and blogs.

The characteristic presentation of prurigo pigmentosa has led to the alternative name of the “keto rash” in online nutritional forums.

Although prurigo pigmentosa is relatively uncommon (with an unknown incidence), primary care physicians may begin to encounter the characteristic rash more frequently, given the number of articles over the past 5 years in the primary care and nutritional literature highlighting the diet’s health benefits.² The ketogenic diet is a high-fat, low-carbohydrate diet with preliminary evidence of improved weight loss, cardiovascular health, and glycemic control suggested by a meta-analysis of 13 randomized controlled trials.³ Additionally, the popular press and general public’s rising interest are likely to increase the number of patients on this diet.

A clinical diagnosis

The diagnosis is made clinically, so the appearance of a symmetric pruritic, hyperpigmented rash on the chest and back should prompt the physician to ask about any recent changes in diet. Laboratory analysis is unnecessary, as a complete blood count, basic metabolic panel, and liver function panel are almost always normal. Urinary ketones are present in only 30% to 50% of patients; there is, however, an absence of blood ketones.^1,4

Continue to: Other conditions can mimic prurigo pigmentosa

 

 

Other conditions can mimic prurigo pigmentosa

Urticaria presents as individual lesions that often have a pale center. The lesions may occur anywhere on the body and generally last less than 24 hours. History may reveal a trigger including drugs, infection, food, or emotional stress in up to 50% of cases.⁵

Irritant contact dermatitis often is associated with a stinging or burning sensation. Irritant and allergic contact dermatitis may have a geometric, or “outside job,” distribution suggestive of external contact, potentially with plants, alkalis, acids, or solvents.⁵

Confluent and reticulated papillomatosis is a rare asymptomatic dermatosis of unknown etiology that presents as hyperpigmented papules on the upper trunk, neck, and axillae. Most patients lack associated pruritis which is in contrast to prurigo pigmentosa.⁶

Pityriasis rosea is a viral exanthem that may be associated with constitutional symptoms and often presents initially with a herald patch progressing to a classic “Christmas tree” distribution with a fine collarette of scale. It often is asymptomatic, although some cases may be pruritic.⁵

Treatment focuses on dietary modification

Primary treatment includes resumption of a normal diet. This often leads to rapid resolution of pruritis. Residual hyperpigmentation may take months to fade.

Continue to: Pharmaceutical intervention may be necessary

 

 

Pharmaceutical intervention may be necessary

If additional treatment is required, minocycline 100 to 200 mg/d has been reported most effective, likely due to its anti-inflammatory properties.^1,4 Topical corticosteroids and oral antihistamines provide symptomatic relief in some patients.^1,4

Our patient had resolution of the pruritis and urticarial lesions within 2 days of resuming a normal diet; however, residual asymptomatic hyperpigmentation persisted. A retrial of the ketogenic diet initiated a flare of the rash in the same distribution. It rapidly resolved with carbohydrate intake.

CORRESPONDENCE
Daniel Croom, MD, 34520 Bob Wilson Dr, Naval Medical Center San Diego, San Diego, CA 92134; daniel.l.croom.mil@mail.mil

A 26-year-old woman presented to our clinic with pruritic, hyperpigmented, symmetric edematous plaques on her upper flank, chest, and lower back (FIGURE) 3 weeks after starting a strict ketogenic (high fat/low carbohydrate) diet for postpartum weight loss. The patient was an otherwise healthy stay-at-home mother with an unremarkable medical history.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Prurigo pigmentosa

We recognized that this was a case of prurigo pigmentosa based on the characteristic pruritic rash that had developed after the patient started a strict ketogenic diet.

Prurigo pigmentosa is a benign, pruritic rash that most commonly presents with erythematous or hyperpigmented, symmetrically distributed urticarial papules and plaques on the chest and back. Females represent approximately 70% of cases with a predominant age range of 11 to 30.¹

While the pathophysiology remains unknown, the rash most often is reported in association with ketogenic diets.¹ Despite occurring in only a fraction of patients on the ketogenic diet, the characteristic presentation has led to the alternative name of the “keto rash” in online nutritional forums and blogs.

The characteristic presentation of prurigo pigmentosa has led to the alternative name of the “keto rash” in online nutritional forums.

Although prurigo pigmentosa is relatively uncommon (with an unknown incidence), primary care physicians may begin to encounter the characteristic rash more frequently, given the number of articles over the past 5 years in the primary care and nutritional literature highlighting the diet’s health benefits.² The ketogenic diet is a high-fat, low-carbohydrate diet with preliminary evidence of improved weight loss, cardiovascular health, and glycemic control suggested by a meta-analysis of 13 randomized controlled trials.³ Additionally, the popular press and general public’s rising interest are likely to increase the number of patients on this diet.

A clinical diagnosis

The diagnosis is made clinically, so the appearance of a symmetric pruritic, hyperpigmented rash on the chest and back should prompt the physician to ask about any recent changes in diet. Laboratory analysis is unnecessary, as a complete blood count, basic metabolic panel, and liver function panel are almost always normal. Urinary ketones are present in only 30% to 50% of patients; there is, however, an absence of blood ketones.^1,4

Continue to: Other conditions can mimic prurigo pigmentosa

 

 

Other conditions can mimic prurigo pigmentosa

Urticaria presents as individual lesions that often have a pale center. The lesions may occur anywhere on the body and generally last less than 24 hours. History may reveal a trigger including drugs, infection, food, or emotional stress in up to 50% of cases.⁵

Irritant contact dermatitis often is associated with a stinging or burning sensation. Irritant and allergic contact dermatitis may have a geometric, or “outside job,” distribution suggestive of external contact, potentially with plants, alkalis, acids, or solvents.⁵

Confluent and reticulated papillomatosis is a rare asymptomatic dermatosis of unknown etiology that presents as hyperpigmented papules on the upper trunk, neck, and axillae. Most patients lack associated pruritis which is in contrast to prurigo pigmentosa.⁶

Pityriasis rosea is a viral exanthem that may be associated with constitutional symptoms and often presents initially with a herald patch progressing to a classic “Christmas tree” distribution with a fine collarette of scale. It often is asymptomatic, although some cases may be pruritic.⁵

Treatment focuses on dietary modification

Primary treatment includes resumption of a normal diet. This often leads to rapid resolution of pruritis. Residual hyperpigmentation may take months to fade.

Continue to: Pharmaceutical intervention may be necessary

 

 

Pharmaceutical intervention may be necessary

If additional treatment is required, minocycline 100 to 200 mg/d has been reported most effective, likely due to its anti-inflammatory properties.^1,4 Topical corticosteroids and oral antihistamines provide symptomatic relief in some patients.^1,4

Our patient had resolution of the pruritis and urticarial lesions within 2 days of resuming a normal diet; however, residual asymptomatic hyperpigmentation persisted. A retrial of the ketogenic diet initiated a flare of the rash in the same distribution. It rapidly resolved with carbohydrate intake.

CORRESPONDENCE
Daniel Croom, MD, 34520 Bob Wilson Dr, Naval Medical Center San Diego, San Diego, CA 92134; daniel.l.croom.mil@mail.mil

A 58-year-old man presents to your office with a 2-day history of moderate (6/10) left lower quadrant pain, mild fever (none currently), 2 episodes of vomiting, no diarrhea, and no relief with OTC medications. You suspect diverticulitis and obtain an abdominal CT scan, which shows mild, uncomplicated (Hinchey stage 1a) diverticulitis. How would you treat this patient?

Diverticulitis is common; each year, about 200,000 people in the United States are admitted to the hospital because of it.^2,3 Health care providers typically treat diverticular disease with antibiotics and bowel rest.^2,3 While severe forms of diverticulitis often require parenteral antibiotics and/or surgery, practitioners are increasingly managing the condition with oral antibiotics.⁴

One previous randomized controlled trial (RCT; N = 623) found that antibiotic treatment for acute uncomplicated diverticulitis did not speed recovery or prevent complications (perforation or abscess formation) or recurrence at 12 months.⁵ The study’s strengths included limiting enrollment to people with CT-proven diverticulitis, using a good randomization and concealment process, and employing intention-to-treat analysis. The study was limited by the lack of a standardized antibiotic regimen across centers, previous diverticulitis diagnoses in 40% of patients, nonuniform follow-up processes to confirm anatomic resolution, and the lack of assessment to confirm resolution.⁵

STUDY SUMMARY

Watchful waiting just as effective as antibiotics

This newer study was a single-blind RCT that compared treatment with antibiotics to observation among 528 adults in the Netherlands. Patients were enrolled if they had CT-proven, primary, left-sided, uncomplicated acute diverticulitis (Hinchey stage 1a and 1b).¹ (The Hinchey classification is based on radiologic findings, with 0 for clinical diverticulitis only, 1a for confined pericolic inflammation or phlegmon, and 1b for pericolic or mesocolic abscess.⁶) Exclusion criteria included suspicion of colonic cancer by CT or ultrasound (US), previous CT/US-proven diverticulitis, sepsis, pregnancy, or antibiotic use in the previous 4 weeks.¹

Observational vs antibiotic treatment. Enrolled patients were randomly assigned to receive amoxicillin-clavulanate (1,200 mg by IV qid for at least 48 hours, followed by 625 mg po tid, for 10 total days; n = 266) or to be observed (n = 262). Randomization was performed by computer, with a random varying block size and stratification by Hinchey classification and center; allocation was concealed. The investigators were masked to the allocation until all analyses were completed.¹

The primary outcome was the time to functional recovery (resumption of pre-illness work activities) during a 6-month follow-up period. Secondary outcomes included hospital readmission rate; complicated, ongoing, and recurrent diverticulitis; sigmoid resection; other nonsurgical intervention; antibiotic adverse effects; and all-cause mortality.

Results. Median recovery time for observational treatment was not inferior to antibiotic treatment (14 d vs 12 d; hazard ratio for functional recovery, 0.91). Observation was not inferior to antibiotics for any of the secondary endpoints at 6 and 12 months of follow-up: complicated diverticulitis (3.8% vs 2.6%, respectively), recurrent diverticulitis (3.4% vs 3%), readmission (17.6% vs 12%), or adverse events (48.5% vs 54.5%). Initial hospitalization length of stay was shorter in the observation group (2 vs 3 d). The researchers conducted a 24-month telephone follow-up, but no differences from the 12-month follow-up were noted.¹

Continue to: WHAT'S NEW

WHAT’S NEW

Study looked at true patient-oriented ­outcome

Previous studies of treatment options for acute uncomplicated diverticulitis looked at short-term outcomes, or at readmission, recurrence, and surgical intervention rate or requirement for percutaneous drainage.^7,8 This study is the first to look at functional return to work (a true patient-oriented outcome). And it is the only study to follow up at 24 months to gauge long-term outcomes with observational treatment.

CAVEATS

Can’t generalize to worse cases

It is worth noting that the findings of this study apply only to the mildest form of CT-proven acute diverticulitis (those patients classified as having Hinchey 1a disease) and are not generalizable to patients with more severe forms. Not enough patients with Hinchey 1b acute diverticulitis were enrolled in the study to reach any conclusions about treatment.

Various guidelines issued outside the United States recommend antibiotics for uncomplicated diverticulitis; however, the American Gastroenterological Association (AGA) indicates that antibiotics should be used selectively.^1,9,10 This recommendation was based on an emerging understanding that diverticulitis may be more inflammatory than infectious in nature. The AGA guideline authors acknowledge that their conclusion was based on low-quality evidence.⁹

CHALLENGES TO IMPLEMENTATION

None to speak of

We see no challenges to implementing this recommendation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67[7]:435-436,438).

A 58-year-old man presents to your office with a 2-day history of moderate (6/10) left lower quadrant pain, mild fever (none currently), 2 episodes of vomiting, no diarrhea, and no relief with OTC medications. You suspect diverticulitis and obtain an abdominal CT scan, which shows mild, uncomplicated (Hinchey stage 1a) diverticulitis. How would you treat this patient?

Diverticulitis is common; each year, about 200,000 people in the United States are admitted to the hospital because of it.^2,3 Health care providers typically treat diverticular disease with antibiotics and bowel rest.^2,3 While severe forms of diverticulitis often require parenteral antibiotics and/or surgery, practitioners are increasingly managing the condition with oral antibiotics.⁴

One previous randomized controlled trial (RCT; N = 623) found that antibiotic treatment for acute uncomplicated diverticulitis did not speed recovery or prevent complications (perforation or abscess formation) or recurrence at 12 months.⁵ The study’s strengths included limiting enrollment to people with CT-proven diverticulitis, using a good randomization and concealment process, and employing intention-to-treat analysis. The study was limited by the lack of a standardized antibiotic regimen across centers, previous diverticulitis diagnoses in 40% of patients, nonuniform follow-up processes to confirm anatomic resolution, and the lack of assessment to confirm resolution.⁵

STUDY SUMMARY

Watchful waiting just as effective as antibiotics

This newer study was a single-blind RCT that compared treatment with antibiotics to observation among 528 adults in the Netherlands. Patients were enrolled if they had CT-proven, primary, left-sided, uncomplicated acute diverticulitis (Hinchey stage 1a and 1b).¹ (The Hinchey classification is based on radiologic findings, with 0 for clinical diverticulitis only, 1a for confined pericolic inflammation or phlegmon, and 1b for pericolic or mesocolic abscess.⁶) Exclusion criteria included suspicion of colonic cancer by CT or ultrasound (US), previous CT/US-proven diverticulitis, sepsis, pregnancy, or antibiotic use in the previous 4 weeks.¹

Observational vs antibiotic treatment. Enrolled patients were randomly assigned to receive amoxicillin-clavulanate (1,200 mg by IV qid for at least 48 hours, followed by 625 mg po tid, for 10 total days; n = 266) or to be observed (n = 262). Randomization was performed by computer, with a random varying block size and stratification by Hinchey classification and center; allocation was concealed. The investigators were masked to the allocation until all analyses were completed.¹

The primary outcome was the time to functional recovery (resumption of pre-illness work activities) during a 6-month follow-up period. Secondary outcomes included hospital readmission rate; complicated, ongoing, and recurrent diverticulitis; sigmoid resection; other nonsurgical intervention; antibiotic adverse effects; and all-cause mortality.

Results. Median recovery time for observational treatment was not inferior to antibiotic treatment (14 d vs 12 d; hazard ratio for functional recovery, 0.91). Observation was not inferior to antibiotics for any of the secondary endpoints at 6 and 12 months of follow-up: complicated diverticulitis (3.8% vs 2.6%, respectively), recurrent diverticulitis (3.4% vs 3%), readmission (17.6% vs 12%), or adverse events (48.5% vs 54.5%). Initial hospitalization length of stay was shorter in the observation group (2 vs 3 d). The researchers conducted a 24-month telephone follow-up, but no differences from the 12-month follow-up were noted.¹

Continue to: WHAT'S NEW

WHAT’S NEW

Study looked at true patient-oriented ­outcome

Previous studies of treatment options for acute uncomplicated diverticulitis looked at short-term outcomes, or at readmission, recurrence, and surgical intervention rate or requirement for percutaneous drainage.^7,8 This study is the first to look at functional return to work (a true patient-oriented outcome). And it is the only study to follow up at 24 months to gauge long-term outcomes with observational treatment.

CAVEATS

Can’t generalize to worse cases

It is worth noting that the findings of this study apply only to the mildest form of CT-proven acute diverticulitis (those patients classified as having Hinchey 1a disease) and are not generalizable to patients with more severe forms. Not enough patients with Hinchey 1b acute diverticulitis were enrolled in the study to reach any conclusions about treatment.

Various guidelines issued outside the United States recommend antibiotics for uncomplicated diverticulitis; however, the American Gastroenterological Association (AGA) indicates that antibiotics should be used selectively.^1,9,10 This recommendation was based on an emerging understanding that diverticulitis may be more inflammatory than infectious in nature. The AGA guideline authors acknowledge that their conclusion was based on low-quality evidence.⁹

CHALLENGES TO IMPLEMENTATION

None to speak of

We see no challenges to implementing this recommendation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67[7]:435-436,438).

A 58-year-old man presents to your office with a 2-day history of moderate (6/10) left lower quadrant pain, mild fever (none currently), 2 episodes of vomiting, no diarrhea, and no relief with OTC medications. You suspect diverticulitis and obtain an abdominal CT scan, which shows mild, uncomplicated (Hinchey stage 1a) diverticulitis. How would you treat this patient?

Diverticulitis is common; each year, about 200,000 people in the United States are admitted to the hospital because of it.^2,3 Health care providers typically treat diverticular disease with antibiotics and bowel rest.^2,3 While severe forms of diverticulitis often require parenteral antibiotics and/or surgery, practitioners are increasingly managing the condition with oral antibiotics.⁴

One previous randomized controlled trial (RCT; N = 623) found that antibiotic treatment for acute uncomplicated diverticulitis did not speed recovery or prevent complications (perforation or abscess formation) or recurrence at 12 months.⁵ The study’s strengths included limiting enrollment to people with CT-proven diverticulitis, using a good randomization and concealment process, and employing intention-to-treat analysis. The study was limited by the lack of a standardized antibiotic regimen across centers, previous diverticulitis diagnoses in 40% of patients, nonuniform follow-up processes to confirm anatomic resolution, and the lack of assessment to confirm resolution.⁵

STUDY SUMMARY

Watchful waiting just as effective as antibiotics

This newer study was a single-blind RCT that compared treatment with antibiotics to observation among 528 adults in the Netherlands. Patients were enrolled if they had CT-proven, primary, left-sided, uncomplicated acute diverticulitis (Hinchey stage 1a and 1b).¹ (The Hinchey classification is based on radiologic findings, with 0 for clinical diverticulitis only, 1a for confined pericolic inflammation or phlegmon, and 1b for pericolic or mesocolic abscess.⁶) Exclusion criteria included suspicion of colonic cancer by CT or ultrasound (US), previous CT/US-proven diverticulitis, sepsis, pregnancy, or antibiotic use in the previous 4 weeks.¹

Observational vs antibiotic treatment. Enrolled patients were randomly assigned to receive amoxicillin-clavulanate (1,200 mg by IV qid for at least 48 hours, followed by 625 mg po tid, for 10 total days; n = 266) or to be observed (n = 262). Randomization was performed by computer, with a random varying block size and stratification by Hinchey classification and center; allocation was concealed. The investigators were masked to the allocation until all analyses were completed.¹

The primary outcome was the time to functional recovery (resumption of pre-illness work activities) during a 6-month follow-up period. Secondary outcomes included hospital readmission rate; complicated, ongoing, and recurrent diverticulitis; sigmoid resection; other nonsurgical intervention; antibiotic adverse effects; and all-cause mortality.

Results. Median recovery time for observational treatment was not inferior to antibiotic treatment (14 d vs 12 d; hazard ratio for functional recovery, 0.91). Observation was not inferior to antibiotics for any of the secondary endpoints at 6 and 12 months of follow-up: complicated diverticulitis (3.8% vs 2.6%, respectively), recurrent diverticulitis (3.4% vs 3%), readmission (17.6% vs 12%), or adverse events (48.5% vs 54.5%). Initial hospitalization length of stay was shorter in the observation group (2 vs 3 d). The researchers conducted a 24-month telephone follow-up, but no differences from the 12-month follow-up were noted.¹

Continue to: WHAT'S NEW

WHAT’S NEW

Study looked at true patient-oriented ­outcome

Previous studies of treatment options for acute uncomplicated diverticulitis looked at short-term outcomes, or at readmission, recurrence, and surgical intervention rate or requirement for percutaneous drainage.^7,8 This study is the first to look at functional return to work (a true patient-oriented outcome). And it is the only study to follow up at 24 months to gauge long-term outcomes with observational treatment.

CAVEATS

Can’t generalize to worse cases

It is worth noting that the findings of this study apply only to the mildest form of CT-proven acute diverticulitis (those patients classified as having Hinchey 1a disease) and are not generalizable to patients with more severe forms. Not enough patients with Hinchey 1b acute diverticulitis were enrolled in the study to reach any conclusions about treatment.

Various guidelines issued outside the United States recommend antibiotics for uncomplicated diverticulitis; however, the American Gastroenterological Association (AGA) indicates that antibiotics should be used selectively.^1,9,10 This recommendation was based on an emerging understanding that diverticulitis may be more inflammatory than infectious in nature. The AGA guideline authors acknowledge that their conclusion was based on low-quality evidence.⁹

CHALLENGES TO IMPLEMENTATION

None to speak of

We see no challenges to implementing this recommendation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2018. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2018;67[7]:435-436,438).

HONOLULU – During the first month after a new cancer diagnosis, patients face a substantially elevated risk for an arterial thromboembolic event – an MI or stroke – consistent with the well-described increased risk newly diagnosed cancer patients face from venous thromboembolism, based on findings from a prospective study of more than 4,000 people.

In the new study, 836 patients newly diagnosed with cancer had a 480% increased rate of a fatal or nonfatal MI or stroke during the 30 days following their diagnosis, compared with 3,339 matched people without cancer and after adjustment for baseline differences in demographics and cardiovascular risk factors, Babak B. Navi, MD, said while presenting a poster at the International Stroke Conference sponsored by the American Heart Association.

An additional analysis that focused on 210 of the 836 patients with incident cancer who had any of seven of the cancers known to pose the highest venous thromboembolism risk (lymphoma; gynecologic cancer; or cancer of the pancreas, stomach, lung, bladder, or testes) showed an 1,750% greater rate of incident MI or stroke during the first 30 days after diagnosis, compared with matched people without cancer, reported Dr. Navi, chief of the stroke and hospital neurology at Weill Cornell Medicine, New York.

In contrast, during both the period 1-3 months after the cancer diagnosis and more than 3 months after, the rate of MI or stroke among recently diagnosed cancer patients was not significantly different from the rate in comparator individuals, although the data showed modest trends toward more arterial thromboembolic events after a month, and the lack of statistically significant differences may have been a power issue, Dr. Navi suggested.

Mitchel L. Zoler/MDedge News

Dr. Navi and his associates designed this study to validate previously reported findings of increased arterial thromboembolic events in newly diagnosed cancer patients from studies of insurance claims databases. Although the increased risk for venous thromboembolism in cancer patients is already well established, documenting a similar risk for arterial events is important because they are “generally more impactful for patients than venous thromboembolism,” Dr. Navi said.

REGARDS has received no commercial funding. Dr. Navi reported no disclosures.

mzoler@mdedge.com

SOURCE: Navi BB et al. Stroke. 2019 Feb;50(Suppl_1): Abstract WMP53.

HONOLULU – During the first month after a new cancer diagnosis, patients face a substantially elevated risk for an arterial thromboembolic event – an MI or stroke – consistent with the well-described increased risk newly diagnosed cancer patients face from venous thromboembolism, based on findings from a prospective study of more than 4,000 people.

In the new study, 836 patients newly diagnosed with cancer had a 480% increased rate of a fatal or nonfatal MI or stroke during the 30 days following their diagnosis, compared with 3,339 matched people without cancer and after adjustment for baseline differences in demographics and cardiovascular risk factors, Babak B. Navi, MD, said while presenting a poster at the International Stroke Conference sponsored by the American Heart Association.

An additional analysis that focused on 210 of the 836 patients with incident cancer who had any of seven of the cancers known to pose the highest venous thromboembolism risk (lymphoma; gynecologic cancer; or cancer of the pancreas, stomach, lung, bladder, or testes) showed an 1,750% greater rate of incident MI or stroke during the first 30 days after diagnosis, compared with matched people without cancer, reported Dr. Navi, chief of the stroke and hospital neurology at Weill Cornell Medicine, New York.

In contrast, during both the period 1-3 months after the cancer diagnosis and more than 3 months after, the rate of MI or stroke among recently diagnosed cancer patients was not significantly different from the rate in comparator individuals, although the data showed modest trends toward more arterial thromboembolic events after a month, and the lack of statistically significant differences may have been a power issue, Dr. Navi suggested.

Mitchel L. Zoler/MDedge News

Dr. Navi and his associates designed this study to validate previously reported findings of increased arterial thromboembolic events in newly diagnosed cancer patients from studies of insurance claims databases. Although the increased risk for venous thromboembolism in cancer patients is already well established, documenting a similar risk for arterial events is important because they are “generally more impactful for patients than venous thromboembolism,” Dr. Navi said.

REGARDS has received no commercial funding. Dr. Navi reported no disclosures.

mzoler@mdedge.com

SOURCE: Navi BB et al. Stroke. 2019 Feb;50(Suppl_1): Abstract WMP53.

HONOLULU – During the first month after a new cancer diagnosis, patients face a substantially elevated risk for an arterial thromboembolic event – an MI or stroke – consistent with the well-described increased risk newly diagnosed cancer patients face from venous thromboembolism, based on findings from a prospective study of more than 4,000 people.

In the new study, 836 patients newly diagnosed with cancer had a 480% increased rate of a fatal or nonfatal MI or stroke during the 30 days following their diagnosis, compared with 3,339 matched people without cancer and after adjustment for baseline differences in demographics and cardiovascular risk factors, Babak B. Navi, MD, said while presenting a poster at the International Stroke Conference sponsored by the American Heart Association.

An additional analysis that focused on 210 of the 836 patients with incident cancer who had any of seven of the cancers known to pose the highest venous thromboembolism risk (lymphoma; gynecologic cancer; or cancer of the pancreas, stomach, lung, bladder, or testes) showed an 1,750% greater rate of incident MI or stroke during the first 30 days after diagnosis, compared with matched people without cancer, reported Dr. Navi, chief of the stroke and hospital neurology at Weill Cornell Medicine, New York.

In contrast, during both the period 1-3 months after the cancer diagnosis and more than 3 months after, the rate of MI or stroke among recently diagnosed cancer patients was not significantly different from the rate in comparator individuals, although the data showed modest trends toward more arterial thromboembolic events after a month, and the lack of statistically significant differences may have been a power issue, Dr. Navi suggested.

Mitchel L. Zoler/MDedge News

Dr. Navi and his associates designed this study to validate previously reported findings of increased arterial thromboembolic events in newly diagnosed cancer patients from studies of insurance claims databases. Although the increased risk for venous thromboembolism in cancer patients is already well established, documenting a similar risk for arterial events is important because they are “generally more impactful for patients than venous thromboembolism,” Dr. Navi said.

REGARDS has received no commercial funding. Dr. Navi reported no disclosures.

mzoler@mdedge.com

SOURCE: Navi BB et al. Stroke. 2019 Feb;50(Suppl_1): Abstract WMP53.

SAN FRANCISCO – Antibiotic exposure in the month before cancer immunotherapy starts may hamper the efficacy of immune checkpoint inhibitors, investigators caution.

Neil Osterweil/MDedge News

A prospective study of 196 patients treated with immune checkpoint inhibitors for various cancers showed that the 29 patients who received antibiotics within 30 days of starting immunotherapy had significantly worse overall survival than patients without antibiotic exposure; this effect was seen across cancer types, reported David James Pinato, MD, PhD, from Imperial College London.

In contrast, concurrent antibiotic and checkpoint inhibitor use was not significantly associated with overall survival differences, he said at the American Society of Clinical Oncology (ASCO) – Society for Immunotherapy of Cancer (SITC): Clinical Immuno-Oncology Symposium.

“I think these data are quite interesting in showing an independent detrimental effect, both on response and survival, in unselected patients treated with immune checkpoint inhibitors in routine clinical practice,” Dr. Pinato said.

The data also suggest “the timing of antibiotic exposure is crucial,” he added. Antibiotic treatment concurrent with immunotherapy did not appear to affect prognosis. Alternatively, prior antibiotic therapy appeared to have “a sort of a priming effect towards the immune system.”

Broad-spectrum antibiotics can affect the diversity of the gut microbiome, which influences mucosal immunity, dendritic cell function, and antigen presentation. Alternatively, enrichment of the microbiome with several bacterial species can enhance the potency of checkpoint inhibitors by facilitating the process of tumor rejection, Dr. Pinato explained.

To see whether antibiotic disruption, or “dysbiosis” of the gut microbiome, could hinder responsiveness to checkpoint inhibitors regardless of the tumor site and whether there were time-dependent effects of antibiotic exposure on response to checkpoint inhibitors, the investigators conducted a prospective, observational study in 196 patients treated with checkpoint inhibitors for non–small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, head and neck cancer, transitional cell carcinoma of the bladder, and other cancers.

The researchers defined prior antibiotic exposure as more than 30 days before the start of checkpoint inhibitor therapy and concurrent exposure as antibiotics begun on the first day of the first cycle of checkpoint inhibitor dosing.

Of the 196 patients, 29 had previously received antibiotics, and 68 received them concurrently. The most frequently prescribed antibiotics were beta-lactam agents given in a single, short course. Other classes of drugs, used in eight or fewer patients each, included quinolones, macrolides, sulfonamides, tetracyclines, aminoglycosides, and nitroimidazole.

Median overall survival for the entire cohort, one of two primary outcomes, was 2 months for patients who had received prior antibiotics and 26 months for patients with no prior exposure. This difference was similar for patients with NSCLC (2.5 vs. 26 months), melanoma (3.9 vs. 14 months), and other cancers combined (1.1 vs. 11.0 months; log-rank P less than .01 for all comparisons).

In multivariate analysis, only response to checkpoints inhibitors (complete vs. partial response, stable disease, or progression) and prior antibiotic exposure were significantly associated with survival. The hazard ratio for survival for patients who had not previously received antibiotics was 3.5 (P less than .001).

In contrast, concurrent antibiotic and checkpoint inhibitor use did not have a significant effect on survival.

An analysis of radiologic responses also showed that patients with prior antibiotic exposure had a significantly higher probability of primary disease progression than those without (81% vs. 44%; P less than .001). There were no associations, however, between specific classes of antibiotics or corticosteroid use.

The findings indicate that “certainly, mechanistic studies are required here, not just to investigate the prognostic role of antibiotic-mediated dysbiosis, but perhaps transform this into an actual driver of antitumor immunity,” Dr. Pinato concluded.

The study was internally supported. Dr. Pinato reported receiving grant funding from Merck and Bristol-Myers Squibb unrelated to the study, as well as honoraria from ViiV Healthcare.

SOURCE: Pinato DJ et al. ASCO-SITC, Abstract 147.

SAN FRANCISCO – Antibiotic exposure in the month before cancer immunotherapy starts may hamper the efficacy of immune checkpoint inhibitors, investigators caution.

Neil Osterweil/MDedge News

A prospective study of 196 patients treated with immune checkpoint inhibitors for various cancers showed that the 29 patients who received antibiotics within 30 days of starting immunotherapy had significantly worse overall survival than patients without antibiotic exposure; this effect was seen across cancer types, reported David James Pinato, MD, PhD, from Imperial College London.

In contrast, concurrent antibiotic and checkpoint inhibitor use was not significantly associated with overall survival differences, he said at the American Society of Clinical Oncology (ASCO) – Society for Immunotherapy of Cancer (SITC): Clinical Immuno-Oncology Symposium.

“I think these data are quite interesting in showing an independent detrimental effect, both on response and survival, in unselected patients treated with immune checkpoint inhibitors in routine clinical practice,” Dr. Pinato said.

The data also suggest “the timing of antibiotic exposure is crucial,” he added. Antibiotic treatment concurrent with immunotherapy did not appear to affect prognosis. Alternatively, prior antibiotic therapy appeared to have “a sort of a priming effect towards the immune system.”

Broad-spectrum antibiotics can affect the diversity of the gut microbiome, which influences mucosal immunity, dendritic cell function, and antigen presentation. Alternatively, enrichment of the microbiome with several bacterial species can enhance the potency of checkpoint inhibitors by facilitating the process of tumor rejection, Dr. Pinato explained.

To see whether antibiotic disruption, or “dysbiosis” of the gut microbiome, could hinder responsiveness to checkpoint inhibitors regardless of the tumor site and whether there were time-dependent effects of antibiotic exposure on response to checkpoint inhibitors, the investigators conducted a prospective, observational study in 196 patients treated with checkpoint inhibitors for non–small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, head and neck cancer, transitional cell carcinoma of the bladder, and other cancers.

The researchers defined prior antibiotic exposure as more than 30 days before the start of checkpoint inhibitor therapy and concurrent exposure as antibiotics begun on the first day of the first cycle of checkpoint inhibitor dosing.

Of the 196 patients, 29 had previously received antibiotics, and 68 received them concurrently. The most frequently prescribed antibiotics were beta-lactam agents given in a single, short course. Other classes of drugs, used in eight or fewer patients each, included quinolones, macrolides, sulfonamides, tetracyclines, aminoglycosides, and nitroimidazole.

Median overall survival for the entire cohort, one of two primary outcomes, was 2 months for patients who had received prior antibiotics and 26 months for patients with no prior exposure. This difference was similar for patients with NSCLC (2.5 vs. 26 months), melanoma (3.9 vs. 14 months), and other cancers combined (1.1 vs. 11.0 months; log-rank P less than .01 for all comparisons).

In multivariate analysis, only response to checkpoints inhibitors (complete vs. partial response, stable disease, or progression) and prior antibiotic exposure were significantly associated with survival. The hazard ratio for survival for patients who had not previously received antibiotics was 3.5 (P less than .001).

In contrast, concurrent antibiotic and checkpoint inhibitor use did not have a significant effect on survival.

An analysis of radiologic responses also showed that patients with prior antibiotic exposure had a significantly higher probability of primary disease progression than those without (81% vs. 44%; P less than .001). There were no associations, however, between specific classes of antibiotics or corticosteroid use.

The findings indicate that “certainly, mechanistic studies are required here, not just to investigate the prognostic role of antibiotic-mediated dysbiosis, but perhaps transform this into an actual driver of antitumor immunity,” Dr. Pinato concluded.

The study was internally supported. Dr. Pinato reported receiving grant funding from Merck and Bristol-Myers Squibb unrelated to the study, as well as honoraria from ViiV Healthcare.

SOURCE: Pinato DJ et al. ASCO-SITC, Abstract 147.

SAN FRANCISCO – Antibiotic exposure in the month before cancer immunotherapy starts may hamper the efficacy of immune checkpoint inhibitors, investigators caution.

Neil Osterweil/MDedge News

A prospective study of 196 patients treated with immune checkpoint inhibitors for various cancers showed that the 29 patients who received antibiotics within 30 days of starting immunotherapy had significantly worse overall survival than patients without antibiotic exposure; this effect was seen across cancer types, reported David James Pinato, MD, PhD, from Imperial College London.

In contrast, concurrent antibiotic and checkpoint inhibitor use was not significantly associated with overall survival differences, he said at the American Society of Clinical Oncology (ASCO) – Society for Immunotherapy of Cancer (SITC): Clinical Immuno-Oncology Symposium.

“I think these data are quite interesting in showing an independent detrimental effect, both on response and survival, in unselected patients treated with immune checkpoint inhibitors in routine clinical practice,” Dr. Pinato said.

The data also suggest “the timing of antibiotic exposure is crucial,” he added. Antibiotic treatment concurrent with immunotherapy did not appear to affect prognosis. Alternatively, prior antibiotic therapy appeared to have “a sort of a priming effect towards the immune system.”

Broad-spectrum antibiotics can affect the diversity of the gut microbiome, which influences mucosal immunity, dendritic cell function, and antigen presentation. Alternatively, enrichment of the microbiome with several bacterial species can enhance the potency of checkpoint inhibitors by facilitating the process of tumor rejection, Dr. Pinato explained.

To see whether antibiotic disruption, or “dysbiosis” of the gut microbiome, could hinder responsiveness to checkpoint inhibitors regardless of the tumor site and whether there were time-dependent effects of antibiotic exposure on response to checkpoint inhibitors, the investigators conducted a prospective, observational study in 196 patients treated with checkpoint inhibitors for non–small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, head and neck cancer, transitional cell carcinoma of the bladder, and other cancers.

The researchers defined prior antibiotic exposure as more than 30 days before the start of checkpoint inhibitor therapy and concurrent exposure as antibiotics begun on the first day of the first cycle of checkpoint inhibitor dosing.

Of the 196 patients, 29 had previously received antibiotics, and 68 received them concurrently. The most frequently prescribed antibiotics were beta-lactam agents given in a single, short course. Other classes of drugs, used in eight or fewer patients each, included quinolones, macrolides, sulfonamides, tetracyclines, aminoglycosides, and nitroimidazole.

Median overall survival for the entire cohort, one of two primary outcomes, was 2 months for patients who had received prior antibiotics and 26 months for patients with no prior exposure. This difference was similar for patients with NSCLC (2.5 vs. 26 months), melanoma (3.9 vs. 14 months), and other cancers combined (1.1 vs. 11.0 months; log-rank P less than .01 for all comparisons).

In multivariate analysis, only response to checkpoints inhibitors (complete vs. partial response, stable disease, or progression) and prior antibiotic exposure were significantly associated with survival. The hazard ratio for survival for patients who had not previously received antibiotics was 3.5 (P less than .001).

In contrast, concurrent antibiotic and checkpoint inhibitor use did not have a significant effect on survival.

An analysis of radiologic responses also showed that patients with prior antibiotic exposure had a significantly higher probability of primary disease progression than those without (81% vs. 44%; P less than .001). There were no associations, however, between specific classes of antibiotics or corticosteroid use.

The findings indicate that “certainly, mechanistic studies are required here, not just to investigate the prognostic role of antibiotic-mediated dysbiosis, but perhaps transform this into an actual driver of antitumor immunity,” Dr. Pinato concluded.

The study was internally supported. Dr. Pinato reported receiving grant funding from Merck and Bristol-Myers Squibb unrelated to the study, as well as honoraria from ViiV Healthcare.

SOURCE: Pinato DJ et al. ASCO-SITC, Abstract 147.

HONOLULU – Acute ischemic stroke patients who underwent endovascular thrombectomy and then had a peak systolic blood pressure of greater than 158 mm Hg during the next 24 hours had worse 90-day outcomes than did patients whose peak systolic pressure remained at or below 158 mm Hg in a prospective, multicenter, observational study with 485 patients.

Mitchel L. Zoler/MDedge News

The results hint that maintaining a lower systolic blood pressure after thrombectomy in acute ischemic stroke patients may improve outcomes, but because the current study was observational, the hypothesis that patients benefit when treatment keeps their systolic pressure at or below 158 mm Hg must undergo testing in a prospective, randomized trial, Eva A. Mistry, MBBS, said at the International Stroke Conference, sponsored by the American Heart Association.

The finding from this study that 158 mm Hg provided the best dichotomous division between systolic blood pressures linked with good or bad outcomes is a first step toward trying to devise a more systematic and evidence-based approach to blood pressure management in acute ischemic stroke patients following endovascular thrombectomy, said Dr. Mistry, a neurologist at Vanderbilt University in Nashville, Tenn.

Neither Vanderbilt nor any of the other 11 major U.S. stroke centers that participated in the current study currently have an established protocol for blood pressure management after thrombectomy, Dr. Mistry said in an interview.

“We usually treat to reduce blood pressure, but we don’t have a [broadly agreed on] threshold” to trigger treatment. “It depends on a collective decision” by the various medical specialists who care for an individual acute stroke patient. In addition, no consensus yet exists for the best treatment strategy for blood pressure lowering in acute ischemic stroke patients. Intravenous nicardipine is often the top choice because it is fast-acting and easy to administer and control as an intravenous agent. Those same properties make the beta blocker labetalol a frequently used second drug, she said.

The BEST (Blood Pressure After Endovascular Stroke Therapy) study ran at 12 U.S. centers and enrolled 485 patients who underwent endovascular thrombectomy to treat an acute ischemic stroke. The patients averaged 69 years old, and 48% also underwent thrombolytic treatment. The study’s primary outcome was the percentage of patients with a modified Rankin Scale score of 0-2 at 90 days after their stroke, an outcome reached by 39% of all patients in the study.

Statistical analysis of the collected data showed that a peak systolic blood pressure of 158 mm Hg reached during the 24 hours following thrombectomy best divided patients with good 90-day outcomes from those with worse outcomes. Patients with a postthrombectomy peak systolic pressure above 158 mm Hg had a 2.2-fold increased rate of having a modified Rankin Scale score of 3 or higher after 90 days, a statistically significant relationship, Dr. Mistry reported. However, in an analysis that also adjusted for age, baseline stroke severity, glucose level, time to reperfusion, ASPECTS score, history of hypertension, and recanalization status, the elevated risk for a bad outcome linked with higher systolic pressure dropped to 39% greater than that for patients with systolic pressures that did not rise above 158 mm Hg, a difference that was not statistically significant. This suggests that these adjustments were unable to account for all confounders and further highlighted the need for a prospective, randomized trial to test the value of controlling blood pressure following thrombectomy, Dr. Mistry said. The unadjusted results confirmed a prior report from Dr. Mistry and her associates that found a link between higher blood pressure after stroke thrombectomy and worse outcomes (J Am Heart Assoc. 2017 May 18. doi: 10.1161/JAHA.117.006167).

The analysis also showed that patients who were successfully recanalized by thrombectomy, achieving a thrombolysis in cerebral infarction (TICI) score of 2b or 3, had lower peak systolic blood pressures than did patients who failed to get this level of restored cerebral blood flow from thrombectomy.

BEST received no commercial funding. Dr. Mistry had no disclosures.

mzoler@mdedge.com

SOURCE: Mistry EA et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 94.

HONOLULU – Acute ischemic stroke patients who underwent endovascular thrombectomy and then had a peak systolic blood pressure of greater than 158 mm Hg during the next 24 hours had worse 90-day outcomes than did patients whose peak systolic pressure remained at or below 158 mm Hg in a prospective, multicenter, observational study with 485 patients.

Mitchel L. Zoler/MDedge News

The results hint that maintaining a lower systolic blood pressure after thrombectomy in acute ischemic stroke patients may improve outcomes, but because the current study was observational, the hypothesis that patients benefit when treatment keeps their systolic pressure at or below 158 mm Hg must undergo testing in a prospective, randomized trial, Eva A. Mistry, MBBS, said at the International Stroke Conference, sponsored by the American Heart Association.

The finding from this study that 158 mm Hg provided the best dichotomous division between systolic blood pressures linked with good or bad outcomes is a first step toward trying to devise a more systematic and evidence-based approach to blood pressure management in acute ischemic stroke patients following endovascular thrombectomy, said Dr. Mistry, a neurologist at Vanderbilt University in Nashville, Tenn.

Neither Vanderbilt nor any of the other 11 major U.S. stroke centers that participated in the current study currently have an established protocol for blood pressure management after thrombectomy, Dr. Mistry said in an interview.

“We usually treat to reduce blood pressure, but we don’t have a [broadly agreed on] threshold” to trigger treatment. “It depends on a collective decision” by the various medical specialists who care for an individual acute stroke patient. In addition, no consensus yet exists for the best treatment strategy for blood pressure lowering in acute ischemic stroke patients. Intravenous nicardipine is often the top choice because it is fast-acting and easy to administer and control as an intravenous agent. Those same properties make the beta blocker labetalol a frequently used second drug, she said.

The BEST (Blood Pressure After Endovascular Stroke Therapy) study ran at 12 U.S. centers and enrolled 485 patients who underwent endovascular thrombectomy to treat an acute ischemic stroke. The patients averaged 69 years old, and 48% also underwent thrombolytic treatment. The study’s primary outcome was the percentage of patients with a modified Rankin Scale score of 0-2 at 90 days after their stroke, an outcome reached by 39% of all patients in the study.

Statistical analysis of the collected data showed that a peak systolic blood pressure of 158 mm Hg reached during the 24 hours following thrombectomy best divided patients with good 90-day outcomes from those with worse outcomes. Patients with a postthrombectomy peak systolic pressure above 158 mm Hg had a 2.2-fold increased rate of having a modified Rankin Scale score of 3 or higher after 90 days, a statistically significant relationship, Dr. Mistry reported. However, in an analysis that also adjusted for age, baseline stroke severity, glucose level, time to reperfusion, ASPECTS score, history of hypertension, and recanalization status, the elevated risk for a bad outcome linked with higher systolic pressure dropped to 39% greater than that for patients with systolic pressures that did not rise above 158 mm Hg, a difference that was not statistically significant. This suggests that these adjustments were unable to account for all confounders and further highlighted the need for a prospective, randomized trial to test the value of controlling blood pressure following thrombectomy, Dr. Mistry said. The unadjusted results confirmed a prior report from Dr. Mistry and her associates that found a link between higher blood pressure after stroke thrombectomy and worse outcomes (J Am Heart Assoc. 2017 May 18. doi: 10.1161/JAHA.117.006167).

The analysis also showed that patients who were successfully recanalized by thrombectomy, achieving a thrombolysis in cerebral infarction (TICI) score of 2b or 3, had lower peak systolic blood pressures than did patients who failed to get this level of restored cerebral blood flow from thrombectomy.

BEST received no commercial funding. Dr. Mistry had no disclosures.

mzoler@mdedge.com

SOURCE: Mistry EA et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 94.

HONOLULU – Acute ischemic stroke patients who underwent endovascular thrombectomy and then had a peak systolic blood pressure of greater than 158 mm Hg during the next 24 hours had worse 90-day outcomes than did patients whose peak systolic pressure remained at or below 158 mm Hg in a prospective, multicenter, observational study with 485 patients.

Mitchel L. Zoler/MDedge News

The results hint that maintaining a lower systolic blood pressure after thrombectomy in acute ischemic stroke patients may improve outcomes, but because the current study was observational, the hypothesis that patients benefit when treatment keeps their systolic pressure at or below 158 mm Hg must undergo testing in a prospective, randomized trial, Eva A. Mistry, MBBS, said at the International Stroke Conference, sponsored by the American Heart Association.

The finding from this study that 158 mm Hg provided the best dichotomous division between systolic blood pressures linked with good or bad outcomes is a first step toward trying to devise a more systematic and evidence-based approach to blood pressure management in acute ischemic stroke patients following endovascular thrombectomy, said Dr. Mistry, a neurologist at Vanderbilt University in Nashville, Tenn.

Neither Vanderbilt nor any of the other 11 major U.S. stroke centers that participated in the current study currently have an established protocol for blood pressure management after thrombectomy, Dr. Mistry said in an interview.

“We usually treat to reduce blood pressure, but we don’t have a [broadly agreed on] threshold” to trigger treatment. “It depends on a collective decision” by the various medical specialists who care for an individual acute stroke patient. In addition, no consensus yet exists for the best treatment strategy for blood pressure lowering in acute ischemic stroke patients. Intravenous nicardipine is often the top choice because it is fast-acting and easy to administer and control as an intravenous agent. Those same properties make the beta blocker labetalol a frequently used second drug, she said.

The BEST (Blood Pressure After Endovascular Stroke Therapy) study ran at 12 U.S. centers and enrolled 485 patients who underwent endovascular thrombectomy to treat an acute ischemic stroke. The patients averaged 69 years old, and 48% also underwent thrombolytic treatment. The study’s primary outcome was the percentage of patients with a modified Rankin Scale score of 0-2 at 90 days after their stroke, an outcome reached by 39% of all patients in the study.

Statistical analysis of the collected data showed that a peak systolic blood pressure of 158 mm Hg reached during the 24 hours following thrombectomy best divided patients with good 90-day outcomes from those with worse outcomes. Patients with a postthrombectomy peak systolic pressure above 158 mm Hg had a 2.2-fold increased rate of having a modified Rankin Scale score of 3 or higher after 90 days, a statistically significant relationship, Dr. Mistry reported. However, in an analysis that also adjusted for age, baseline stroke severity, glucose level, time to reperfusion, ASPECTS score, history of hypertension, and recanalization status, the elevated risk for a bad outcome linked with higher systolic pressure dropped to 39% greater than that for patients with systolic pressures that did not rise above 158 mm Hg, a difference that was not statistically significant. This suggests that these adjustments were unable to account for all confounders and further highlighted the need for a prospective, randomized trial to test the value of controlling blood pressure following thrombectomy, Dr. Mistry said. The unadjusted results confirmed a prior report from Dr. Mistry and her associates that found a link between higher blood pressure after stroke thrombectomy and worse outcomes (J Am Heart Assoc. 2017 May 18. doi: 10.1161/JAHA.117.006167).

The analysis also showed that patients who were successfully recanalized by thrombectomy, achieving a thrombolysis in cerebral infarction (TICI) score of 2b or 3, had lower peak systolic blood pressures than did patients who failed to get this level of restored cerebral blood flow from thrombectomy.

BEST received no commercial funding. Dr. Mistry had no disclosures.

mzoler@mdedge.com

SOURCE: Mistry EA et al. Stroke. 2019 Feb;50(Suppl_1): Abstract 94.

SNOWMASS, COLO. – Interventions that are simple and straightforward for other patients – such as therapeutic phlebotomy, bronchoscopy, anticoagulation, administration of IV antibiotics – can quickly have catastrophic results in patients with Eisenmenger syndrome, Carole A. Warnes, MD, cautioned at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

This is why the 2018 ACC/American Heart Association guidelines on the management of patients with adult congenital heart disease recommend as a Class I indication that most patients with ACHD, including all those with Eisenmenger syndrome, be managed in collaboration with a cardiologist at a specialized ACHD center (Circulation. 2018 Aug 16. doi: 10.1161/CIR.0000000000000603), noted Dr. Warnes, professor of medicine at the Mayo Clinic in Rochester, Minn., and director of the Snowmass conference.

“There are lots of mistakes in diagnosis and management because so many physicians are unfamiliar with the kinds of problems these patients face,” the cardiologist said.

She cited as a real-world example a patient with Eisenmenger syndrome admitted for pneumonia. Twenty minutes after being placed on intravenous antibiotics she had a stroke. Why?

“She didn’t have an air filter on her IV line. Any air going into a cyanotic’s blood stream will go to the head and give them a stroke. Something that is simple – routine for other patients – may kill a patient with cyanotic heart disease,” Dr. Warnes said.

Another illustrative case: a patient with Eisenmenger syndrome presents with hemoptysis, an infiltrate in her right lung, a hemoglobin of 19.8 g/dL, and anemia. Should she undergo therapeutic phlebotomy? How about urgent bronchoscopy?

No and no, Dr. Warnes emphasized.

“You do not phlebotomize cyanotic patients unless they have symptoms of hyperviscosity, meaning terrible headache or poor concentration, along with a hemoglobin greater than 20 g/dL. They need that high hemoglobin. They may be blue, and you need those red cells to carry the oxygen around. Otherwise you may make them worse. And if you give them iron for their anemia, you will increase their risk of stroke,” she explained.

Hemoptysis in patients with Eisenmenger syndrome is a life-threatening warning sign. By the time Eisenmenger syndrome patients reach age 40 years, nearly all of them have experienced episodes of hemoptysis. And more and more patients with the syndrome are moving well beyond that milestone and surviving into their 60s and beyond.

“Many Eisenmenger syndrome patients are not dying when they’re 20 or 30. We can get them to a good old age,” according to Dr. Warnes, who founded the ACHD center at the Mayo Clinic.

Most of the time the cause of hemoptysis in patients with Eisenmenger syndrome is an intrapulmonary hemorrhage. Anticoagulation can turn that hemorrhage catastrophic. So can bronchoscopy. Indeed, the cause of death in roughly 30% of patients with this form of congenital heart disease is catastrophic hemoptysis.

“You bar the door from your friendly pulmonologist who wants to bronchoscope these patients. Bronchoscopy never does any good unless the patient is so hypoxic that you need to suck the blood out of their lungs,” Dr. Warnes emphasized.

Anticoagulation is ordinarily to be avoided in patients with Eisenmenger syndrome because of their bleeding risk, even when pulmonary thrombosis is suspected, she added.

So, to summarize: These patients basically need stabilizing, with no anticoagulation, no bronchoscopy, and no phlebotomy, she said.

Another danger zone for patients with Eisenmenger syndrome is pregnancy. The condition is associated with a 30% maternal mortality rate.

Dr. Warnes noted that, even at the Mayo Clinic, which has had a pioneering ACHD center for decades, awareness of key elements of management of affected patients is low among nonspecialists.

“As I’ve done my hospital services in the last couple of months, I sort of felt I was on patrol, snatching these patients from problems,” she recalled.

Dr. Warnes reported having no financial conflicts regarding her presentation.
 

bjancin@mdedge.com

SNOWMASS, COLO. – Interventions that are simple and straightforward for other patients – such as therapeutic phlebotomy, bronchoscopy, anticoagulation, administration of IV antibiotics – can quickly have catastrophic results in patients with Eisenmenger syndrome, Carole A. Warnes, MD, cautioned at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

This is why the 2018 ACC/American Heart Association guidelines on the management of patients with adult congenital heart disease recommend as a Class I indication that most patients with ACHD, including all those with Eisenmenger syndrome, be managed in collaboration with a cardiologist at a specialized ACHD center (Circulation. 2018 Aug 16. doi: 10.1161/CIR.0000000000000603), noted Dr. Warnes, professor of medicine at the Mayo Clinic in Rochester, Minn., and director of the Snowmass conference.

“There are lots of mistakes in diagnosis and management because so many physicians are unfamiliar with the kinds of problems these patients face,” the cardiologist said.

She cited as a real-world example a patient with Eisenmenger syndrome admitted for pneumonia. Twenty minutes after being placed on intravenous antibiotics she had a stroke. Why?

“She didn’t have an air filter on her IV line. Any air going into a cyanotic’s blood stream will go to the head and give them a stroke. Something that is simple – routine for other patients – may kill a patient with cyanotic heart disease,” Dr. Warnes said.

Another illustrative case: a patient with Eisenmenger syndrome presents with hemoptysis, an infiltrate in her right lung, a hemoglobin of 19.8 g/dL, and anemia. Should she undergo therapeutic phlebotomy? How about urgent bronchoscopy?

No and no, Dr. Warnes emphasized.

“You do not phlebotomize cyanotic patients unless they have symptoms of hyperviscosity, meaning terrible headache or poor concentration, along with a hemoglobin greater than 20 g/dL. They need that high hemoglobin. They may be blue, and you need those red cells to carry the oxygen around. Otherwise you may make them worse. And if you give them iron for their anemia, you will increase their risk of stroke,” she explained.

Hemoptysis in patients with Eisenmenger syndrome is a life-threatening warning sign. By the time Eisenmenger syndrome patients reach age 40 years, nearly all of them have experienced episodes of hemoptysis. And more and more patients with the syndrome are moving well beyond that milestone and surviving into their 60s and beyond.

“Many Eisenmenger syndrome patients are not dying when they’re 20 or 30. We can get them to a good old age,” according to Dr. Warnes, who founded the ACHD center at the Mayo Clinic.

Most of the time the cause of hemoptysis in patients with Eisenmenger syndrome is an intrapulmonary hemorrhage. Anticoagulation can turn that hemorrhage catastrophic. So can bronchoscopy. Indeed, the cause of death in roughly 30% of patients with this form of congenital heart disease is catastrophic hemoptysis.

“You bar the door from your friendly pulmonologist who wants to bronchoscope these patients. Bronchoscopy never does any good unless the patient is so hypoxic that you need to suck the blood out of their lungs,” Dr. Warnes emphasized.

Anticoagulation is ordinarily to be avoided in patients with Eisenmenger syndrome because of their bleeding risk, even when pulmonary thrombosis is suspected, she added.

So, to summarize: These patients basically need stabilizing, with no anticoagulation, no bronchoscopy, and no phlebotomy, she said.

Another danger zone for patients with Eisenmenger syndrome is pregnancy. The condition is associated with a 30% maternal mortality rate.

Dr. Warnes noted that, even at the Mayo Clinic, which has had a pioneering ACHD center for decades, awareness of key elements of management of affected patients is low among nonspecialists.

“As I’ve done my hospital services in the last couple of months, I sort of felt I was on patrol, snatching these patients from problems,” she recalled.

Dr. Warnes reported having no financial conflicts regarding her presentation.
 

bjancin@mdedge.com

SNOWMASS, COLO. – Interventions that are simple and straightforward for other patients – such as therapeutic phlebotomy, bronchoscopy, anticoagulation, administration of IV antibiotics – can quickly have catastrophic results in patients with Eisenmenger syndrome, Carole A. Warnes, MD, cautioned at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

This is why the 2018 ACC/American Heart Association guidelines on the management of patients with adult congenital heart disease recommend as a Class I indication that most patients with ACHD, including all those with Eisenmenger syndrome, be managed in collaboration with a cardiologist at a specialized ACHD center (Circulation. 2018 Aug 16. doi: 10.1161/CIR.0000000000000603), noted Dr. Warnes, professor of medicine at the Mayo Clinic in Rochester, Minn., and director of the Snowmass conference.

“There are lots of mistakes in diagnosis and management because so many physicians are unfamiliar with the kinds of problems these patients face,” the cardiologist said.

She cited as a real-world example a patient with Eisenmenger syndrome admitted for pneumonia. Twenty minutes after being placed on intravenous antibiotics she had a stroke. Why?

“She didn’t have an air filter on her IV line. Any air going into a cyanotic’s blood stream will go to the head and give them a stroke. Something that is simple – routine for other patients – may kill a patient with cyanotic heart disease,” Dr. Warnes said.

Another illustrative case: a patient with Eisenmenger syndrome presents with hemoptysis, an infiltrate in her right lung, a hemoglobin of 19.8 g/dL, and anemia. Should she undergo therapeutic phlebotomy? How about urgent bronchoscopy?

No and no, Dr. Warnes emphasized.

“You do not phlebotomize cyanotic patients unless they have symptoms of hyperviscosity, meaning terrible headache or poor concentration, along with a hemoglobin greater than 20 g/dL. They need that high hemoglobin. They may be blue, and you need those red cells to carry the oxygen around. Otherwise you may make them worse. And if you give them iron for their anemia, you will increase their risk of stroke,” she explained.

Hemoptysis in patients with Eisenmenger syndrome is a life-threatening warning sign. By the time Eisenmenger syndrome patients reach age 40 years, nearly all of them have experienced episodes of hemoptysis. And more and more patients with the syndrome are moving well beyond that milestone and surviving into their 60s and beyond.

“Many Eisenmenger syndrome patients are not dying when they’re 20 or 30. We can get them to a good old age,” according to Dr. Warnes, who founded the ACHD center at the Mayo Clinic.

Most of the time the cause of hemoptysis in patients with Eisenmenger syndrome is an intrapulmonary hemorrhage. Anticoagulation can turn that hemorrhage catastrophic. So can bronchoscopy. Indeed, the cause of death in roughly 30% of patients with this form of congenital heart disease is catastrophic hemoptysis.

“You bar the door from your friendly pulmonologist who wants to bronchoscope these patients. Bronchoscopy never does any good unless the patient is so hypoxic that you need to suck the blood out of their lungs,” Dr. Warnes emphasized.

Anticoagulation is ordinarily to be avoided in patients with Eisenmenger syndrome because of their bleeding risk, even when pulmonary thrombosis is suspected, she added.

So, to summarize: These patients basically need stabilizing, with no anticoagulation, no bronchoscopy, and no phlebotomy, she said.

Another danger zone for patients with Eisenmenger syndrome is pregnancy. The condition is associated with a 30% maternal mortality rate.

Dr. Warnes noted that, even at the Mayo Clinic, which has had a pioneering ACHD center for decades, awareness of key elements of management of affected patients is low among nonspecialists.

“As I’ve done my hospital services in the last couple of months, I sort of felt I was on patrol, snatching these patients from problems,” she recalled.

Dr. Warnes reported having no financial conflicts regarding her presentation.
 

bjancin@mdedge.com

The two newer classes of antihyperglycemic drugs that lower cardiovascular risk have different effects on specific cardiovascular and kidney disease outcomes in patients with type 2 diabetes, results of a meta-analysis suggest. Sodium-glucose contransporter-2 (SGLT2) inhibitors significantly reduced hospitalization from heart failure, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not, according to the reported results.

The GLP-1–RA class reduced risk of kidney disease progression, largely driven by a reduction in macroalbuminuria, according to the authors, whereas only the SGLT2 inhibitors reduced adverse kidney disease outcomes in a composite excluding that biomarker.

“The prevention of heart failure and progression of kidney disease by SGLT2 [inhibitors] should be considered in the decision-making process when treating patients with type 2 diabetes,” study senior author Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital, Boston, and his coauthors wrote in a report on the study appearing in Circulation.

Both GLP-1 RAs and SGLT2 inhibitors significantly reduced major adverse cardiovascular events (MACE) and, as shown in other recent findings, their benefits were confined to patients with established atherosclerotic cardiovascular disease, Dr. Sabatine and his colleagues wrote.

The systematic review and meta-analysis of eight cardiovascular outcomes trials included 77,242 patients, of whom about 56% participated in GLP-1–RA studies and 44% in SGLT2-inhibitor trials. Just under three-quarters of the patients had established atherosclerotic cardiovascular disease, while the remainder had multiple risk factors for it.

Relative risk of hospitalization for heart failure was reduced by 31% with SGLT2 inhibitors, but it was not significantly reduced by GLP-1 RAs, the authors noted.

Risk of kidney disease progression was reduced by 38% with SGLT2 inhibitors and by 18% with GLP-1 RAs when the researchers used a broad composite endpoint including macroalbuminuria, estimated glomerular filtration rate (eGFR), end-stage kidney disease, and death due to renal causes.

By contrast, SGLT2 inhibitors reduced by 45% the relative risk of a narrower kidney outcome that excluded macroalbuminuria, whereas GLP-1 RAs had only a nonsignificant effect on the risk of doubling serum creatinine. That suggests the relative risk reduction of the kidney composite with GLP-1 RAs was driven mainly by a reduction in macroalbuminuria, the authors wrote.

Although albuminuria is an established biomarker for kidney and cardiovascular disease, it is a surrogate marker and can even be absent in patients with reduced eGFR, they said.

“Reduction in eGFR has emerged as a more meaningful endpoint of greater importance and is used in ongoing diabetes trials for kidney outcomes,” the authors said in a discussion of their results.

Relative risk of the composite MACE endpoint, including myocardial infarction, stroke, and cardiovascular death, was reduced by 12% for GLP-1 RAs and by 11% for SGLT2 [inhibitors], according to results of the analysis. However, the benefit was confined to patients with established cardiovascular disease, who had a 14% reduction of risk, compared with no treatment effect in patients who had multiple risk factors only.

Looking at individual MACE components, investigators found that both drug classes significantly reduced relative risk of myocardial infarction and of cardiovascular death, whereas only GLP-1 RAs significantly reduced relative risk of stroke.

Study authors provided disclosures related to AstraZeneca, Amgen, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, and Medimmune, among others.

SOURCE: Zelniker TA et al. Circulation. 2019 Feb 21. doi: 10.1161/CIRCULATIONAHA.118.038868.

The two newer classes of antihyperglycemic drugs that lower cardiovascular risk have different effects on specific cardiovascular and kidney disease outcomes in patients with type 2 diabetes, results of a meta-analysis suggest. Sodium-glucose contransporter-2 (SGLT2) inhibitors significantly reduced hospitalization from heart failure, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not, according to the reported results.

The GLP-1–RA class reduced risk of kidney disease progression, largely driven by a reduction in macroalbuminuria, according to the authors, whereas only the SGLT2 inhibitors reduced adverse kidney disease outcomes in a composite excluding that biomarker.

“The prevention of heart failure and progression of kidney disease by SGLT2 [inhibitors] should be considered in the decision-making process when treating patients with type 2 diabetes,” study senior author Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital, Boston, and his coauthors wrote in a report on the study appearing in Circulation.

Both GLP-1 RAs and SGLT2 inhibitors significantly reduced major adverse cardiovascular events (MACE) and, as shown in other recent findings, their benefits were confined to patients with established atherosclerotic cardiovascular disease, Dr. Sabatine and his colleagues wrote.

The systematic review and meta-analysis of eight cardiovascular outcomes trials included 77,242 patients, of whom about 56% participated in GLP-1–RA studies and 44% in SGLT2-inhibitor trials. Just under three-quarters of the patients had established atherosclerotic cardiovascular disease, while the remainder had multiple risk factors for it.

Relative risk of hospitalization for heart failure was reduced by 31% with SGLT2 inhibitors, but it was not significantly reduced by GLP-1 RAs, the authors noted.

Risk of kidney disease progression was reduced by 38% with SGLT2 inhibitors and by 18% with GLP-1 RAs when the researchers used a broad composite endpoint including macroalbuminuria, estimated glomerular filtration rate (eGFR), end-stage kidney disease, and death due to renal causes.

By contrast, SGLT2 inhibitors reduced by 45% the relative risk of a narrower kidney outcome that excluded macroalbuminuria, whereas GLP-1 RAs had only a nonsignificant effect on the risk of doubling serum creatinine. That suggests the relative risk reduction of the kidney composite with GLP-1 RAs was driven mainly by a reduction in macroalbuminuria, the authors wrote.

Although albuminuria is an established biomarker for kidney and cardiovascular disease, it is a surrogate marker and can even be absent in patients with reduced eGFR, they said.

“Reduction in eGFR has emerged as a more meaningful endpoint of greater importance and is used in ongoing diabetes trials for kidney outcomes,” the authors said in a discussion of their results.

Relative risk of the composite MACE endpoint, including myocardial infarction, stroke, and cardiovascular death, was reduced by 12% for GLP-1 RAs and by 11% for SGLT2 [inhibitors], according to results of the analysis. However, the benefit was confined to patients with established cardiovascular disease, who had a 14% reduction of risk, compared with no treatment effect in patients who had multiple risk factors only.

Looking at individual MACE components, investigators found that both drug classes significantly reduced relative risk of myocardial infarction and of cardiovascular death, whereas only GLP-1 RAs significantly reduced relative risk of stroke.

Study authors provided disclosures related to AstraZeneca, Amgen, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, and Medimmune, among others.

SOURCE: Zelniker TA et al. Circulation. 2019 Feb 21. doi: 10.1161/CIRCULATIONAHA.118.038868.

The two newer classes of antihyperglycemic drugs that lower cardiovascular risk have different effects on specific cardiovascular and kidney disease outcomes in patients with type 2 diabetes, results of a meta-analysis suggest. Sodium-glucose contransporter-2 (SGLT2) inhibitors significantly reduced hospitalization from heart failure, whereas glucagon-like peptide-1 receptor agonists (GLP-1 RAs) did not, according to the reported results.

The GLP-1–RA class reduced risk of kidney disease progression, largely driven by a reduction in macroalbuminuria, according to the authors, whereas only the SGLT2 inhibitors reduced adverse kidney disease outcomes in a composite excluding that biomarker.

“The prevention of heart failure and progression of kidney disease by SGLT2 [inhibitors] should be considered in the decision-making process when treating patients with type 2 diabetes,” study senior author Marc S. Sabatine, MD, MPH, of Brigham and Women’s Hospital, Boston, and his coauthors wrote in a report on the study appearing in Circulation.

Both GLP-1 RAs and SGLT2 inhibitors significantly reduced major adverse cardiovascular events (MACE) and, as shown in other recent findings, their benefits were confined to patients with established atherosclerotic cardiovascular disease, Dr. Sabatine and his colleagues wrote.

The systematic review and meta-analysis of eight cardiovascular outcomes trials included 77,242 patients, of whom about 56% participated in GLP-1–RA studies and 44% in SGLT2-inhibitor trials. Just under three-quarters of the patients had established atherosclerotic cardiovascular disease, while the remainder had multiple risk factors for it.

Relative risk of hospitalization for heart failure was reduced by 31% with SGLT2 inhibitors, but it was not significantly reduced by GLP-1 RAs, the authors noted.

Risk of kidney disease progression was reduced by 38% with SGLT2 inhibitors and by 18% with GLP-1 RAs when the researchers used a broad composite endpoint including macroalbuminuria, estimated glomerular filtration rate (eGFR), end-stage kidney disease, and death due to renal causes.

By contrast, SGLT2 inhibitors reduced by 45% the relative risk of a narrower kidney outcome that excluded macroalbuminuria, whereas GLP-1 RAs had only a nonsignificant effect on the risk of doubling serum creatinine. That suggests the relative risk reduction of the kidney composite with GLP-1 RAs was driven mainly by a reduction in macroalbuminuria, the authors wrote.

Although albuminuria is an established biomarker for kidney and cardiovascular disease, it is a surrogate marker and can even be absent in patients with reduced eGFR, they said.

“Reduction in eGFR has emerged as a more meaningful endpoint of greater importance and is used in ongoing diabetes trials for kidney outcomes,” the authors said in a discussion of their results.

Relative risk of the composite MACE endpoint, including myocardial infarction, stroke, and cardiovascular death, was reduced by 12% for GLP-1 RAs and by 11% for SGLT2 [inhibitors], according to results of the analysis. However, the benefit was confined to patients with established cardiovascular disease, who had a 14% reduction of risk, compared with no treatment effect in patients who had multiple risk factors only.

Looking at individual MACE components, investigators found that both drug classes significantly reduced relative risk of myocardial infarction and of cardiovascular death, whereas only GLP-1 RAs significantly reduced relative risk of stroke.

Study authors provided disclosures related to AstraZeneca, Amgen, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, and Medimmune, among others.

SOURCE: Zelniker TA et al. Circulation. 2019 Feb 21. doi: 10.1161/CIRCULATIONAHA.118.038868.

Patients with textured silicone gluteal implants could be at risk of anaplastic large cell lymphoma, based on a possible case of ALCL in a patient diagnosed 1 year after implant placement.

The 49-year-old woman was initially diagnosed with anaplastic lymphoma kinase–negative ALCL via a lung mass and pleural fluid before bilateral gluteal ulceration occurred 1 month later, reported Orr Shauly of the University of Southern California in Los Angeles, and his colleagues.

Soft-tissue disease and fluid accumulation around the gluteal implants suggested that the lung mass had metastasized from primary neoplasia in the gluteal region. If ALCL did originate at the site of the gluteal implants, it would represent a first for silicone implant–associated ALCL, which has historically been associated exclusively with breast implants.

“As many as 200 cases of [breast implant-associated ALCL] have been described worldwide, with a majority in the context of cosmetic primary breast augmentation or cancer-related breast reconstruction with the use of a textured implant (57% of all cases),” the investigators wrote in Aesthetic Surgery Journal. “Recently however, it has been hypothesized that the relationship of ALCL with the placement of textured silicone implants may not [be] limited to the breast due to its multifactorial nature and association with texturization of the implant surface.”

During the initial work-up, a CT showed fluid collection and enhancement around the gluteal implants. Following ALCL diagnosis via lung mass biopsy and histopathology, the patient was transferred to a different facility for chemotherapy. When the patient presented 1 month later to the original facility with gluteal ulceration, the oncology team suspected infection; however, all cultures from fluid around the implants were negative.

Because of the possibility of false-negative tests, the patient was started on a regimen of acyclovir, vancomycin, metronidazole, and isavuconazole. Explantation was planned, but before this could occur, the patient deteriorated rapidly and died of respiratory and renal failure.

ALCL was not confirmed via cytology or histopathology in the gluteal region, and the patient’s family did not consent to autopsy, so a definitive diagnosis of gluteal implant–associated ALCL remained elusive.

“In this instance, it can only be concluded that the patient’s condition may have been associated with placement of textured silicone gluteal implants, but [we] still lack evidence of causation,” the investigators wrote. “It should also be noted that ALCL does not typically present with skin ulceration, and this may be a unique disease process in this patient or as a result of her bedridden state given the late stage of her disease. Furthermore, this presentation was uniquely aggressive and presented extremely quickly after placement of the gluteal implants. In most patients, ALCL develops and presents approximately 10 years after implantation.”

The investigators cautioned that “care should be taken to avoid sensationalizing all implant-associated ALCL.”

The authors reported having no conflicts of interest and the study did not receive funding.

SOURCE: Shauly O et al. Aesthet Surg J. 2019 Feb 15. doi: 10.1093/asj/sjz044.

Patients with textured silicone gluteal implants could be at risk of anaplastic large cell lymphoma, based on a possible case of ALCL in a patient diagnosed 1 year after implant placement.

The 49-year-old woman was initially diagnosed with anaplastic lymphoma kinase–negative ALCL via a lung mass and pleural fluid before bilateral gluteal ulceration occurred 1 month later, reported Orr Shauly of the University of Southern California in Los Angeles, and his colleagues.

Soft-tissue disease and fluid accumulation around the gluteal implants suggested that the lung mass had metastasized from primary neoplasia in the gluteal region. If ALCL did originate at the site of the gluteal implants, it would represent a first for silicone implant–associated ALCL, which has historically been associated exclusively with breast implants.

“As many as 200 cases of [breast implant-associated ALCL] have been described worldwide, with a majority in the context of cosmetic primary breast augmentation or cancer-related breast reconstruction with the use of a textured implant (57% of all cases),” the investigators wrote in Aesthetic Surgery Journal. “Recently however, it has been hypothesized that the relationship of ALCL with the placement of textured silicone implants may not [be] limited to the breast due to its multifactorial nature and association with texturization of the implant surface.”

During the initial work-up, a CT showed fluid collection and enhancement around the gluteal implants. Following ALCL diagnosis via lung mass biopsy and histopathology, the patient was transferred to a different facility for chemotherapy. When the patient presented 1 month later to the original facility with gluteal ulceration, the oncology team suspected infection; however, all cultures from fluid around the implants were negative.

Because of the possibility of false-negative tests, the patient was started on a regimen of acyclovir, vancomycin, metronidazole, and isavuconazole. Explantation was planned, but before this could occur, the patient deteriorated rapidly and died of respiratory and renal failure.

ALCL was not confirmed via cytology or histopathology in the gluteal region, and the patient’s family did not consent to autopsy, so a definitive diagnosis of gluteal implant–associated ALCL remained elusive.

“In this instance, it can only be concluded that the patient’s condition may have been associated with placement of textured silicone gluteal implants, but [we] still lack evidence of causation,” the investigators wrote. “It should also be noted that ALCL does not typically present with skin ulceration, and this may be a unique disease process in this patient or as a result of her bedridden state given the late stage of her disease. Furthermore, this presentation was uniquely aggressive and presented extremely quickly after placement of the gluteal implants. In most patients, ALCL develops and presents approximately 10 years after implantation.”

The investigators cautioned that “care should be taken to avoid sensationalizing all implant-associated ALCL.”

The authors reported having no conflicts of interest and the study did not receive funding.

SOURCE: Shauly O et al. Aesthet Surg J. 2019 Feb 15. doi: 10.1093/asj/sjz044.

Patients with textured silicone gluteal implants could be at risk of anaplastic large cell lymphoma, based on a possible case of ALCL in a patient diagnosed 1 year after implant placement.

The 49-year-old woman was initially diagnosed with anaplastic lymphoma kinase–negative ALCL via a lung mass and pleural fluid before bilateral gluteal ulceration occurred 1 month later, reported Orr Shauly of the University of Southern California in Los Angeles, and his colleagues.

Soft-tissue disease and fluid accumulation around the gluteal implants suggested that the lung mass had metastasized from primary neoplasia in the gluteal region. If ALCL did originate at the site of the gluteal implants, it would represent a first for silicone implant–associated ALCL, which has historically been associated exclusively with breast implants.

“As many as 200 cases of [breast implant-associated ALCL] have been described worldwide, with a majority in the context of cosmetic primary breast augmentation or cancer-related breast reconstruction with the use of a textured implant (57% of all cases),” the investigators wrote in Aesthetic Surgery Journal. “Recently however, it has been hypothesized that the relationship of ALCL with the placement of textured silicone implants may not [be] limited to the breast due to its multifactorial nature and association with texturization of the implant surface.”

During the initial work-up, a CT showed fluid collection and enhancement around the gluteal implants. Following ALCL diagnosis via lung mass biopsy and histopathology, the patient was transferred to a different facility for chemotherapy. When the patient presented 1 month later to the original facility with gluteal ulceration, the oncology team suspected infection; however, all cultures from fluid around the implants were negative.

Because of the possibility of false-negative tests, the patient was started on a regimen of acyclovir, vancomycin, metronidazole, and isavuconazole. Explantation was planned, but before this could occur, the patient deteriorated rapidly and died of respiratory and renal failure.

ALCL was not confirmed via cytology or histopathology in the gluteal region, and the patient’s family did not consent to autopsy, so a definitive diagnosis of gluteal implant–associated ALCL remained elusive.

“In this instance, it can only be concluded that the patient’s condition may have been associated with placement of textured silicone gluteal implants, but [we] still lack evidence of causation,” the investigators wrote. “It should also be noted that ALCL does not typically present with skin ulceration, and this may be a unique disease process in this patient or as a result of her bedridden state given the late stage of her disease. Furthermore, this presentation was uniquely aggressive and presented extremely quickly after placement of the gluteal implants. In most patients, ALCL develops and presents approximately 10 years after implantation.”

The investigators cautioned that “care should be taken to avoid sensationalizing all implant-associated ALCL.”

The authors reported having no conflicts of interest and the study did not receive funding.

SOURCE: Shauly O et al. Aesthet Surg J. 2019 Feb 15. doi: 10.1093/asj/sjz044.

Weak evidence suggests that prophylactic use of mesenchymal stem cells (MSCs) may reduce the risk of chronic graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), according to a recent Cochrane review.

However, other uses of MSCs with HSCT – such as prophylaxis with MSCs for acute GVHD or treatment of GVHD – lack evidence of efficacy, reported lead author Sheila A. Fisher, PhD, of National Health Service Blood and Transplant in Oxford (England), and her colleagues.

The investigators noted that most studies included in the review had low-quality evidence.

“[R]andomization methods were poorly reported and several of the included studies were subject to a high risk of performance bias and reporting bias,” the investigators wrote in the Cochrane Database of Systematic Reviews. “One trial which started in 2008 has not been published and the progress of this trial is unknown, leading to potential publication bias. The quality of evidence was therefore low or very low for all outcomes due to a high risk of bias as well as imprecision due to the low number of overall participants, and in some cases, evidence based on a single study.”

The investigators identified 25 randomized, controlled trials (RCTs) involving MSCs for GVHD, of which 12 were completed (879 participants) and 13 were ongoing (1,532 planned participants). Out of the 12 completed trials, 2 compared different doses of MSCs, while 10 compared MSCs with no MSCs. Five trials investigated treatment with MSCs and seven investigated prophylactic use.

The one finding that was supportive of MSCs, albeit based on low-quality evidence, showed that prophylactic use reduced the risk of chronic GVHD, compared with no prophylaxis (risk ratio, 0.66). Other findings were less supportive or unsupportive of MSCs.

Prophylactic use of MSCs had little or no impact on risk of acute GVHD (RR, 0.86; low-quality evidence), risk of relapse of malignant disease (RR, 1.08; low-quality evidence), or all-cause mortality (hazard ratio, 0.85; low-quality evidence).

Treatment with MSCs was disappointing across the board. Risk of all-cause mortality was unaffected (HR, 1.12; very low–quality evidence) and a minimal impact was found for complete responses in acute GVHD (RR, 1.16; very low–quality evidence).

Although treatment of chronic GVHD with MSCs was associated with an improved complete response rate (RR, 5.00), the investigators noted that this finding came from a single trial with 40 participants that was deemed to have very low–quality evidence. The two trials comparing doses of MSCs found no differences between treatment groups.

“Despite a number of reports of positive outcomes from the use of MSCs for treating acute GVHD, the evidence to date from RCTs has not supported the conclusion that they are an effective therapy,” the investigators wrote.

The study was funded by NHS Blood and Transplant. Dr. Fischer reported having no financial disclosures. One coauthor reported research funding from the Leukemia and Lymphoma Research charity and the National Institute for Health Research.

SOURCE: Fisher SA et al. Cochrane Database Syst Rev. 2019 Jan 30. doi: 10.1002/14651858.CD009768.pub2.

Weak evidence suggests that prophylactic use of mesenchymal stem cells (MSCs) may reduce the risk of chronic graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), according to a recent Cochrane review.

However, other uses of MSCs with HSCT – such as prophylaxis with MSCs for acute GVHD or treatment of GVHD – lack evidence of efficacy, reported lead author Sheila A. Fisher, PhD, of National Health Service Blood and Transplant in Oxford (England), and her colleagues.

The investigators noted that most studies included in the review had low-quality evidence.

“[R]andomization methods were poorly reported and several of the included studies were subject to a high risk of performance bias and reporting bias,” the investigators wrote in the Cochrane Database of Systematic Reviews. “One trial which started in 2008 has not been published and the progress of this trial is unknown, leading to potential publication bias. The quality of evidence was therefore low or very low for all outcomes due to a high risk of bias as well as imprecision due to the low number of overall participants, and in some cases, evidence based on a single study.”

The investigators identified 25 randomized, controlled trials (RCTs) involving MSCs for GVHD, of which 12 were completed (879 participants) and 13 were ongoing (1,532 planned participants). Out of the 12 completed trials, 2 compared different doses of MSCs, while 10 compared MSCs with no MSCs. Five trials investigated treatment with MSCs and seven investigated prophylactic use.

The one finding that was supportive of MSCs, albeit based on low-quality evidence, showed that prophylactic use reduced the risk of chronic GVHD, compared with no prophylaxis (risk ratio, 0.66). Other findings were less supportive or unsupportive of MSCs.

Prophylactic use of MSCs had little or no impact on risk of acute GVHD (RR, 0.86; low-quality evidence), risk of relapse of malignant disease (RR, 1.08; low-quality evidence), or all-cause mortality (hazard ratio, 0.85; low-quality evidence).

Treatment with MSCs was disappointing across the board. Risk of all-cause mortality was unaffected (HR, 1.12; very low–quality evidence) and a minimal impact was found for complete responses in acute GVHD (RR, 1.16; very low–quality evidence).

Although treatment of chronic GVHD with MSCs was associated with an improved complete response rate (RR, 5.00), the investigators noted that this finding came from a single trial with 40 participants that was deemed to have very low–quality evidence. The two trials comparing doses of MSCs found no differences between treatment groups.

“Despite a number of reports of positive outcomes from the use of MSCs for treating acute GVHD, the evidence to date from RCTs has not supported the conclusion that they are an effective therapy,” the investigators wrote.

The study was funded by NHS Blood and Transplant. Dr. Fischer reported having no financial disclosures. One coauthor reported research funding from the Leukemia and Lymphoma Research charity and the National Institute for Health Research.

SOURCE: Fisher SA et al. Cochrane Database Syst Rev. 2019 Jan 30. doi: 10.1002/14651858.CD009768.pub2.

Weak evidence suggests that prophylactic use of mesenchymal stem cells (MSCs) may reduce the risk of chronic graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), according to a recent Cochrane review.

However, other uses of MSCs with HSCT – such as prophylaxis with MSCs for acute GVHD or treatment of GVHD – lack evidence of efficacy, reported lead author Sheila A. Fisher, PhD, of National Health Service Blood and Transplant in Oxford (England), and her colleagues.

The investigators noted that most studies included in the review had low-quality evidence.

“[R]andomization methods were poorly reported and several of the included studies were subject to a high risk of performance bias and reporting bias,” the investigators wrote in the Cochrane Database of Systematic Reviews. “One trial which started in 2008 has not been published and the progress of this trial is unknown, leading to potential publication bias. The quality of evidence was therefore low or very low for all outcomes due to a high risk of bias as well as imprecision due to the low number of overall participants, and in some cases, evidence based on a single study.”

The investigators identified 25 randomized, controlled trials (RCTs) involving MSCs for GVHD, of which 12 were completed (879 participants) and 13 were ongoing (1,532 planned participants). Out of the 12 completed trials, 2 compared different doses of MSCs, while 10 compared MSCs with no MSCs. Five trials investigated treatment with MSCs and seven investigated prophylactic use.

The one finding that was supportive of MSCs, albeit based on low-quality evidence, showed that prophylactic use reduced the risk of chronic GVHD, compared with no prophylaxis (risk ratio, 0.66). Other findings were less supportive or unsupportive of MSCs.

Prophylactic use of MSCs had little or no impact on risk of acute GVHD (RR, 0.86; low-quality evidence), risk of relapse of malignant disease (RR, 1.08; low-quality evidence), or all-cause mortality (hazard ratio, 0.85; low-quality evidence).

Treatment with MSCs was disappointing across the board. Risk of all-cause mortality was unaffected (HR, 1.12; very low–quality evidence) and a minimal impact was found for complete responses in acute GVHD (RR, 1.16; very low–quality evidence).

Although treatment of chronic GVHD with MSCs was associated with an improved complete response rate (RR, 5.00), the investigators noted that this finding came from a single trial with 40 participants that was deemed to have very low–quality evidence. The two trials comparing doses of MSCs found no differences between treatment groups.

“Despite a number of reports of positive outcomes from the use of MSCs for treating acute GVHD, the evidence to date from RCTs has not supported the conclusion that they are an effective therapy,” the investigators wrote.

The study was funded by NHS Blood and Transplant. Dr. Fischer reported having no financial disclosures. One coauthor reported research funding from the Leukemia and Lymphoma Research charity and the National Institute for Health Research.

SOURCE: Fisher SA et al. Cochrane Database Syst Rev. 2019 Jan 30. doi: 10.1002/14651858.CD009768.pub2.

Adding once-weekly treatment with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide helped most patients with type 2 diabetes already being treated with sodium-glucose cotransporter-2 (SGLT2) inhibitors meet their glycemic targets and lose weight, researchers reported.

“Combining the distinct modes of action of these two drug classes has beneficial effects on glucose and weight outcomes,” wrote Bernard Zinman, MD, of Mount Sinai Hospital, Toronto, and his coauthors. Their report is in Lancet Diabetes and Endocrinology.

In the international, double-blind, phase 3 SUSTAIN 9 trial, 302 patients with type 2 diabetes whose hemoglobin A_{1c (}HbA_1c) levels were 7.0% to 10.0% (53 to 86 mmol/mol) despite at least 90 days of SGLT2-inhibitor therapy (alone or with metformin or sulfonylurea) were randomly assigned to add either once-weekly semaglutide (1-mg injection) or placebo to their regimen.

A total of 294 patients completed the trial. After 30 weeks, those who had received adjunctive semaglutide had significantly greater reductions in their HbA_1c levels (estimated treatment difference, –1.42%; P less than .0001). They also lost about 3.81 kg more bodyweight than did patients in the placebo group and they had significantly greater reductions in mean body mass index, waist circumference, fasting and self-measured blood glucose, systolic blood pressure, pulse rate, total cholesterol, and low-density lipoprotein and triglyceride levels.

The most commonly reported adverse effects of semaglutide were nausea, diarrhea, vomiting, and constipation, which were usually mild in severity. Severe or blood-glucose–confirmed hypoglycemia occurred in 2.7% patients on semaglutide and none on placebo. However, most patients who received semaglutide achieved an HbA_1c of 7.0% (53 mmol/mol) or less without weight gain or severe or blood-glucose–confirmed hypoglycemia (P less than .0001 vs. placebo).

Novo Nordisk funded the study. Three of the authors were employees of Novo Nordisk at the time of the study, and the remaining authors reported that they and/or their institutions had received funding from the company.

SOURCE: Zinman B et al. Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587(19)30066-X.

Adding once-weekly treatment with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide helped most patients with type 2 diabetes already being treated with sodium-glucose cotransporter-2 (SGLT2) inhibitors meet their glycemic targets and lose weight, researchers reported.

“Combining the distinct modes of action of these two drug classes has beneficial effects on glucose and weight outcomes,” wrote Bernard Zinman, MD, of Mount Sinai Hospital, Toronto, and his coauthors. Their report is in Lancet Diabetes and Endocrinology.

In the international, double-blind, phase 3 SUSTAIN 9 trial, 302 patients with type 2 diabetes whose hemoglobin A_{1c (}HbA_1c) levels were 7.0% to 10.0% (53 to 86 mmol/mol) despite at least 90 days of SGLT2-inhibitor therapy (alone or with metformin or sulfonylurea) were randomly assigned to add either once-weekly semaglutide (1-mg injection) or placebo to their regimen.

A total of 294 patients completed the trial. After 30 weeks, those who had received adjunctive semaglutide had significantly greater reductions in their HbA_1c levels (estimated treatment difference, –1.42%; P less than .0001). They also lost about 3.81 kg more bodyweight than did patients in the placebo group and they had significantly greater reductions in mean body mass index, waist circumference, fasting and self-measured blood glucose, systolic blood pressure, pulse rate, total cholesterol, and low-density lipoprotein and triglyceride levels.

The most commonly reported adverse effects of semaglutide were nausea, diarrhea, vomiting, and constipation, which were usually mild in severity. Severe or blood-glucose–confirmed hypoglycemia occurred in 2.7% patients on semaglutide and none on placebo. However, most patients who received semaglutide achieved an HbA_1c of 7.0% (53 mmol/mol) or less without weight gain or severe or blood-glucose–confirmed hypoglycemia (P less than .0001 vs. placebo).

Novo Nordisk funded the study. Three of the authors were employees of Novo Nordisk at the time of the study, and the remaining authors reported that they and/or their institutions had received funding from the company.

SOURCE: Zinman B et al. Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587(19)30066-X.

Adding once-weekly treatment with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide helped most patients with type 2 diabetes already being treated with sodium-glucose cotransporter-2 (SGLT2) inhibitors meet their glycemic targets and lose weight, researchers reported.

“Combining the distinct modes of action of these two drug classes has beneficial effects on glucose and weight outcomes,” wrote Bernard Zinman, MD, of Mount Sinai Hospital, Toronto, and his coauthors. Their report is in Lancet Diabetes and Endocrinology.

In the international, double-blind, phase 3 SUSTAIN 9 trial, 302 patients with type 2 diabetes whose hemoglobin A_{1c (}HbA_1c) levels were 7.0% to 10.0% (53 to 86 mmol/mol) despite at least 90 days of SGLT2-inhibitor therapy (alone or with metformin or sulfonylurea) were randomly assigned to add either once-weekly semaglutide (1-mg injection) or placebo to their regimen.

A total of 294 patients completed the trial. After 30 weeks, those who had received adjunctive semaglutide had significantly greater reductions in their HbA_1c levels (estimated treatment difference, –1.42%; P less than .0001). They also lost about 3.81 kg more bodyweight than did patients in the placebo group and they had significantly greater reductions in mean body mass index, waist circumference, fasting and self-measured blood glucose, systolic blood pressure, pulse rate, total cholesterol, and low-density lipoprotein and triglyceride levels.

The most commonly reported adverse effects of semaglutide were nausea, diarrhea, vomiting, and constipation, which were usually mild in severity. Severe or blood-glucose–confirmed hypoglycemia occurred in 2.7% patients on semaglutide and none on placebo. However, most patients who received semaglutide achieved an HbA_1c of 7.0% (53 mmol/mol) or less without weight gain or severe or blood-glucose–confirmed hypoglycemia (P less than .0001 vs. placebo).

Novo Nordisk funded the study. Three of the authors were employees of Novo Nordisk at the time of the study, and the remaining authors reported that they and/or their institutions had received funding from the company.

SOURCE: Zinman B et al. Lancet Diabetes Endocrinol. 2019 Mar 1. doi: 10.1016/S2213-8587(19)30066-X.