Key clinical point: Tralokinumab is well tolerated and effective in older adults with moderate-to-severe atopic dermatitis (AD).

Major finding: Compared with the placebo group, a significantly higher proportion of patients in ECZTRA 1 and 2 achieved ≥ 75% improvement in the Eczema Area and Severity Index score (33.9% vs 4.76%; P < .001) and an Investigator’s Global Assessment 0 or 1 score (16.95% vs 0%; P < .001) in the tralokinumab group at week 16. The adverse event (AE) rate was comparable between the groups; however, fewer patients discontinued treatment due to AE in the tralokinumab vs placebo group (5.3% vs 6.9%).

Study details: Findings are from a post hoc analysis of ECZTRA 1, 2, and 3 trials and included 104 older patients (≥65 years) with AD who received tralokinumab (n = 75) or placebo (n = 29).

Disclosures: This study was supported by LEO Pharma. Two authors declared being employees of LEO Pharma. Some authors declared receiving grants, personal fees, or consulting fees from LEO Pharma and other sources.

Source: Merola JF et al. Safety and efficacy of tralokinumab in older adults with moderate-to-severe atopic dermatitis: A secondary analysis. JAMA Dermatol. 2023 (Aug 23). doi: 10.1001/jamadermatol.2023.2626

Key clinical point: Tralokinumab is well tolerated and effective in older adults with moderate-to-severe atopic dermatitis (AD).

Major finding: Compared with the placebo group, a significantly higher proportion of patients in ECZTRA 1 and 2 achieved ≥ 75% improvement in the Eczema Area and Severity Index score (33.9% vs 4.76%; P < .001) and an Investigator’s Global Assessment 0 or 1 score (16.95% vs 0%; P < .001) in the tralokinumab group at week 16. The adverse event (AE) rate was comparable between the groups; however, fewer patients discontinued treatment due to AE in the tralokinumab vs placebo group (5.3% vs 6.9%).

Study details: Findings are from a post hoc analysis of ECZTRA 1, 2, and 3 trials and included 104 older patients (≥65 years) with AD who received tralokinumab (n = 75) or placebo (n = 29).

Disclosures: This study was supported by LEO Pharma. Two authors declared being employees of LEO Pharma. Some authors declared receiving grants, personal fees, or consulting fees from LEO Pharma and other sources.

Source: Merola JF et al. Safety and efficacy of tralokinumab in older adults with moderate-to-severe atopic dermatitis: A secondary analysis. JAMA Dermatol. 2023 (Aug 23). doi: 10.1001/jamadermatol.2023.2626

Key clinical point: Tralokinumab is well tolerated and effective in older adults with moderate-to-severe atopic dermatitis (AD).

Major finding: Compared with the placebo group, a significantly higher proportion of patients in ECZTRA 1 and 2 achieved ≥ 75% improvement in the Eczema Area and Severity Index score (33.9% vs 4.76%; P < .001) and an Investigator’s Global Assessment 0 or 1 score (16.95% vs 0%; P < .001) in the tralokinumab group at week 16. The adverse event (AE) rate was comparable between the groups; however, fewer patients discontinued treatment due to AE in the tralokinumab vs placebo group (5.3% vs 6.9%).

Study details: Findings are from a post hoc analysis of ECZTRA 1, 2, and 3 trials and included 104 older patients (≥65 years) with AD who received tralokinumab (n = 75) or placebo (n = 29).

Disclosures: This study was supported by LEO Pharma. Two authors declared being employees of LEO Pharma. Some authors declared receiving grants, personal fees, or consulting fees from LEO Pharma and other sources.

Source: Merola JF et al. Safety and efficacy of tralokinumab in older adults with moderate-to-severe atopic dermatitis: A secondary analysis. JAMA Dermatol. 2023 (Aug 23). doi: 10.1001/jamadermatol.2023.2626

Key clinical point: Children and adults with atopic dermatitis (AD) have a significantly increased risk of developing inflammatory bowel disease (IBD), including Crohn’s disease (CD).

Major finding: Children with vs without AD had a significantly higher risk for IBD (adjusted HR [aHR] 1.44; 95% CI 1.31-1.58) and CD (aHR 1.74; 95% CI 1.54-1.97), but the risk for ulcerative colitis (UC; aHR 1.65; 95% CI 1.02-2.67) was higher only in children with severe AD. Adults with vs without AD had a significantly increased risk for IBD (aHR 1.34; 95% CI 1.27-1.40), CD (aHR 1.36; 95% CI 1.26-1.47), and UC (aHR 1.32; 95% CI 1.24-1.41).

Study details: This population-based cohort study matched children (n = 409,431; age < 18 years) and adults (n = 625,083) with AD with control children (n = 1,809,029) and adults (n = 2,678,888) without AD, respectively.

Disclosures: This study was supported by a contract from Pfizer Inc. Five authors declared receiving grants, personal fees, and fellowship funding from various sources, including Pfizer Inc.

Source: Chiesa Fuxench ZC et al. Risk of inflammatory bowel disease in patients with atopic dermatitis. JAMA Dermatol. 2023 (Aug 30). doi: 10.1001/jamadermatol.2023.2875

Key clinical point: Children and adults with atopic dermatitis (AD) have a significantly increased risk of developing inflammatory bowel disease (IBD), including Crohn’s disease (CD).

Major finding: Children with vs without AD had a significantly higher risk for IBD (adjusted HR [aHR] 1.44; 95% CI 1.31-1.58) and CD (aHR 1.74; 95% CI 1.54-1.97), but the risk for ulcerative colitis (UC; aHR 1.65; 95% CI 1.02-2.67) was higher only in children with severe AD. Adults with vs without AD had a significantly increased risk for IBD (aHR 1.34; 95% CI 1.27-1.40), CD (aHR 1.36; 95% CI 1.26-1.47), and UC (aHR 1.32; 95% CI 1.24-1.41).

Study details: This population-based cohort study matched children (n = 409,431; age < 18 years) and adults (n = 625,083) with AD with control children (n = 1,809,029) and adults (n = 2,678,888) without AD, respectively.

Disclosures: This study was supported by a contract from Pfizer Inc. Five authors declared receiving grants, personal fees, and fellowship funding from various sources, including Pfizer Inc.

Source: Chiesa Fuxench ZC et al. Risk of inflammatory bowel disease in patients with atopic dermatitis. JAMA Dermatol. 2023 (Aug 30). doi: 10.1001/jamadermatol.2023.2875

Key clinical point: Children and adults with atopic dermatitis (AD) have a significantly increased risk of developing inflammatory bowel disease (IBD), including Crohn’s disease (CD).

Major finding: Children with vs without AD had a significantly higher risk for IBD (adjusted HR [aHR] 1.44; 95% CI 1.31-1.58) and CD (aHR 1.74; 95% CI 1.54-1.97), but the risk for ulcerative colitis (UC; aHR 1.65; 95% CI 1.02-2.67) was higher only in children with severe AD. Adults with vs without AD had a significantly increased risk for IBD (aHR 1.34; 95% CI 1.27-1.40), CD (aHR 1.36; 95% CI 1.26-1.47), and UC (aHR 1.32; 95% CI 1.24-1.41).

Study details: This population-based cohort study matched children (n = 409,431; age < 18 years) and adults (n = 625,083) with AD with control children (n = 1,809,029) and adults (n = 2,678,888) without AD, respectively.

Disclosures: This study was supported by a contract from Pfizer Inc. Five authors declared receiving grants, personal fees, and fellowship funding from various sources, including Pfizer Inc.

Source: Chiesa Fuxench ZC et al. Risk of inflammatory bowel disease in patients with atopic dermatitis. JAMA Dermatol. 2023 (Aug 30). doi: 10.1001/jamadermatol.2023.2875

Key clinical point: Dupilumab significantly improved the overall sleep continuity and quality, itch, and other signs and symptoms of atopic dermatitis (AD) in patients with moderate-to-severe AD.

Major finding: At week 12, dupilumab vs placebo led to a significant improvement in the sleep Numeric Rating Scale (NRS), peak pruritus NRS, SCORing Atopic Dermatitis (SCORAD), SCORAD sleep visual analog scale, Eczema Area and Severity Index, Epworth Sleepiness Scale, and sleep-related impairment T-scores (all P < .001) and a lower overall treatment-emergent adverse event rate (56.7% vs 67.2%).

Study details: Findings are from the prospective phase 4 DUPISTAD study including patients with moderate-to-severe AD who were randomly assigned to receive 300 mg dupilumab every 2 weeks (n = 127) or placebo (n = 61).

Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Three authors declared being employees of and holding stocks or stock options in Sanofi or Regeneron. Other authors declared receiving grant support, travel grants, or speaker fees from or serving as principal investigators, advisory board members, or consultants for various sources.

Source: Merola JF et al. Dupilumab significantly improves sleep in adults with atopic dermatitis: Results from the 12-week placebo-controlled period of the 24-week phase 4 randomized double-blinded placebo-controlled DUPISTAD study. Br J Dermatol. 2023 (Aug 10). doi: 10.1093/bjd/ljad284

Key clinical point: Dupilumab significantly improved the overall sleep continuity and quality, itch, and other signs and symptoms of atopic dermatitis (AD) in patients with moderate-to-severe AD.

Major finding: At week 12, dupilumab vs placebo led to a significant improvement in the sleep Numeric Rating Scale (NRS), peak pruritus NRS, SCORing Atopic Dermatitis (SCORAD), SCORAD sleep visual analog scale, Eczema Area and Severity Index, Epworth Sleepiness Scale, and sleep-related impairment T-scores (all P < .001) and a lower overall treatment-emergent adverse event rate (56.7% vs 67.2%).

Study details: Findings are from the prospective phase 4 DUPISTAD study including patients with moderate-to-severe AD who were randomly assigned to receive 300 mg dupilumab every 2 weeks (n = 127) or placebo (n = 61).

Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Three authors declared being employees of and holding stocks or stock options in Sanofi or Regeneron. Other authors declared receiving grant support, travel grants, or speaker fees from or serving as principal investigators, advisory board members, or consultants for various sources.

Source: Merola JF et al. Dupilumab significantly improves sleep in adults with atopic dermatitis: Results from the 12-week placebo-controlled period of the 24-week phase 4 randomized double-blinded placebo-controlled DUPISTAD study. Br J Dermatol. 2023 (Aug 10). doi: 10.1093/bjd/ljad284

Key clinical point: Dupilumab significantly improved the overall sleep continuity and quality, itch, and other signs and symptoms of atopic dermatitis (AD) in patients with moderate-to-severe AD.

Major finding: At week 12, dupilumab vs placebo led to a significant improvement in the sleep Numeric Rating Scale (NRS), peak pruritus NRS, SCORing Atopic Dermatitis (SCORAD), SCORAD sleep visual analog scale, Eczema Area and Severity Index, Epworth Sleepiness Scale, and sleep-related impairment T-scores (all P < .001) and a lower overall treatment-emergent adverse event rate (56.7% vs 67.2%).

Study details: Findings are from the prospective phase 4 DUPISTAD study including patients with moderate-to-severe AD who were randomly assigned to receive 300 mg dupilumab every 2 weeks (n = 127) or placebo (n = 61).

Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals Inc. Three authors declared being employees of and holding stocks or stock options in Sanofi or Regeneron. Other authors declared receiving grant support, travel grants, or speaker fees from or serving as principal investigators, advisory board members, or consultants for various sources.

Source: Merola JF et al. Dupilumab significantly improves sleep in adults with atopic dermatitis: Results from the 12-week placebo-controlled period of the 24-week phase 4 randomized double-blinded placebo-controlled DUPISTAD study. Br J Dermatol. 2023 (Aug 10). doi: 10.1093/bjd/ljad284

In June 2023, a multisociety group agreed to change the name of the disease formerly known as nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction–associated steatotic liver disease (MASLD).

In the week leading up to this, Intercept Pharmaceuticals announced that their program to develop obeticholic acid (OCA) as a first-to-market, long-awaited potential drug therapy for metabolic dysfunction–associated steatohepatitis (MASH), the more pathogenic form of this disease, was being abandoned after the Food and Drug Administration Gastrointestinal Drugs Advisory Committee voted against accelerated approval of the drug. This decision was made in large part owing to data showing modest efficacy coupled with multiple drug-related side effects, including worsening metabolic dysfunction.

The juxtaposition of these two events highlights what could be a fundamental change in perspective when it comes to the management of patients with MASLD and the development of therapies for this disease.
 

A more precise nomenclature for a broad-spectrum disease

The updating of the NAFLD nomenclature to MASLD represents an important change in the way that the medical community is being asked to view and approach the disease of “fatty liver.”

The previous nomenclature clarified that pathogenic liver steatosis can exist in the absence of alcohol. However, it failed to define the primary drivers of the most common form of NAFLD: that is, metabolic syndrome diseases. The new nomenclature not only better defines the broad spectrum of steatotic liver diseases (alcohol, metabolic, drug/genetic, cryptogenic) but also refocuses the attention of providers on the fundamental basis of MASLD as a critical member of the metabolic syndrome spectrum of diseases.

This is in line with the recently updated American Association for the Study of Liver Disease Practice Guidelines for NAFLD (now MASLD), which focus on active screening to identify patients at risk for advanced MASLD, in particular those with medically complicated obesity or high-risk metabolic characteristics such as diabetes. This is a change from previous versions of the guidelines that were cautious to recommend broad screening guidelines in part owing to the lack of “available therapies.”

The increasing clinical burden of MASH has led to the recognition that patients do not have the luxury of waiting for “anticipated therapies” that have frequently shown only marginal or insignificant efficacy. As a result, some providers have refocused their efforts on the development of care pathways that can efficiently provide comprehensive lifestyle interventions to treat MASH and related metabolic comorbidities within hepatology or other subspecialty clinics.
 

Learning from OCA’s limitations

The approach to drug development for MASH seems to be shifting in a similar, metabolic syndrome–focused way.

The risk-benefit analysis from the FDA advisory committee evaluating OCA noted that the drug provided only modest (albeit statistically significant) benefits over placebo in achieving one of two primary clinical endpoints (improvement in fibrosis by one stage without worsening of NASH), but was associated with toxicity as well as significant drug-related side effects, including new or worsening dyslipidemia, accelerated progression to prediabetes or diabetes, and worsening glycemic control in patients with diabetes.

Worsening clinical markers of metabolic health were an important factor in the advisory committee’s decision to not provide accelerated approval of OCA. This informs the criteria upon which future MASH therapies will be evaluated for approval: that an ideal agent for MASH not only will have a significant impact on MASH pathophysiology but will also provide benefit for (or at least not worsen) the metabolic comorbidities associated with MASH.
 

New treatments on the horizon

Fortunately, several new MASH therapeutics in development seem to have promising metabolic profiles.

In the phase 3 MAESTRO-NASH biopsy trial, treatment with resmetirom, a thyroid hormone receptor–beta selective agonist versus placebo resulted in a clinically significant improvement in liver fibrosis by one stage or more (26% vs. 14%) and NASH resolution (30% vs. 10%). Unlike OCA, resmetirom was associated with a clinically significant reduction in LDL cholesterol (–16% compared with placebo).

Resmetirom has received a breakthrough therapy designation, and Madrigal Pharmaceuticals recently completed submission of a new drug application for accelerated approval of this agent to the FDA.

Semaglutide is a glucagonlike peptide–1 receptor agonist that is already FDA approved for treatment of diabetes and obesity and is being studied in a phase 3 analysis for NASH.

In a phase 2 trial, daily dosing of semaglutide vs placebo led to clinically significant improvement in NASH resolution (59% vs. 17%) but not significant improvement in fibrosis (43% vs 33%). Although it is impossible to make a meaningful comparison in outcomes between clinical trials, it should be noted that the absolute rate of response in this trial was higher than is routinely seen in other NASH trials and that the placebo rate for improvement in fibrosis was higher than expected, a common problem with NASH trials.

As expected, treatment with semaglutide was associated with dose-dependent reduction in body weight and hemoglobin A1c, highlighting the global metabolic benefit of this agent.

Another major class of agents being studied for NASH treatment are the fibroblast growth factor (FGF) 21 analogs.

In the recently published phase 2b ENLIVEN trial, treatment with the FGF21 analog pegozafermin versus placebo led to a statistically significant improvement in liver fibrosis by one stage (27% vs. 7%) and a numerical improvement in NASH resolution (26% vs. 2%).

In addition to its effects directly in the liver, FGF21 has been associated with promoting positive global metabolic effects, including improved peripheral insulin sensitivity and amelioration of dyslipidemia. Consistent with this, treatment with pegozafermin resulted in a decrease in serum triglycerides and an increase in serum HDL cholesterol and adiponectin levels.

Ultimately, the best therapeutic strategy for MASH may be one that uses combination therapy to maximize liver-directed effects and also ameliorate concomitant or contributing metabolic dysfunction. This approach is already being investigated. What seems clear, however, is that MASH therapy without concurrent treatment of metabolic comorbidities is probably destined to be ineffective, if not counterproductive.

So, what’s in a name? When it comes to MASLD, it seems quite a bit.
 

Dr. Janardhan is an assistant professor, department of internal medicine, at Rush University Medical Center, Chicago. Dr. Reau is a professor, department of internal medicine, Rush University. Dr. Janardhan reported conflicts of interest with Target RWE, Novo Nordisk, Intercept, and Enanta. Dr. Reau reported conflicts of interest with AbbVie, Gilead, and AASLD.

A version of this article appeared on Medscape.com.

In June 2023, a multisociety group agreed to change the name of the disease formerly known as nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction–associated steatotic liver disease (MASLD).

In the week leading up to this, Intercept Pharmaceuticals announced that their program to develop obeticholic acid (OCA) as a first-to-market, long-awaited potential drug therapy for metabolic dysfunction–associated steatohepatitis (MASH), the more pathogenic form of this disease, was being abandoned after the Food and Drug Administration Gastrointestinal Drugs Advisory Committee voted against accelerated approval of the drug. This decision was made in large part owing to data showing modest efficacy coupled with multiple drug-related side effects, including worsening metabolic dysfunction.

The juxtaposition of these two events highlights what could be a fundamental change in perspective when it comes to the management of patients with MASLD and the development of therapies for this disease.
 

A more precise nomenclature for a broad-spectrum disease

The updating of the NAFLD nomenclature to MASLD represents an important change in the way that the medical community is being asked to view and approach the disease of “fatty liver.”

The previous nomenclature clarified that pathogenic liver steatosis can exist in the absence of alcohol. However, it failed to define the primary drivers of the most common form of NAFLD: that is, metabolic syndrome diseases. The new nomenclature not only better defines the broad spectrum of steatotic liver diseases (alcohol, metabolic, drug/genetic, cryptogenic) but also refocuses the attention of providers on the fundamental basis of MASLD as a critical member of the metabolic syndrome spectrum of diseases.

This is in line with the recently updated American Association for the Study of Liver Disease Practice Guidelines for NAFLD (now MASLD), which focus on active screening to identify patients at risk for advanced MASLD, in particular those with medically complicated obesity or high-risk metabolic characteristics such as diabetes. This is a change from previous versions of the guidelines that were cautious to recommend broad screening guidelines in part owing to the lack of “available therapies.”

The increasing clinical burden of MASH has led to the recognition that patients do not have the luxury of waiting for “anticipated therapies” that have frequently shown only marginal or insignificant efficacy. As a result, some providers have refocused their efforts on the development of care pathways that can efficiently provide comprehensive lifestyle interventions to treat MASH and related metabolic comorbidities within hepatology or other subspecialty clinics.
 

Learning from OCA’s limitations

The approach to drug development for MASH seems to be shifting in a similar, metabolic syndrome–focused way.

The risk-benefit analysis from the FDA advisory committee evaluating OCA noted that the drug provided only modest (albeit statistically significant) benefits over placebo in achieving one of two primary clinical endpoints (improvement in fibrosis by one stage without worsening of NASH), but was associated with toxicity as well as significant drug-related side effects, including new or worsening dyslipidemia, accelerated progression to prediabetes or diabetes, and worsening glycemic control in patients with diabetes.

Worsening clinical markers of metabolic health were an important factor in the advisory committee’s decision to not provide accelerated approval of OCA. This informs the criteria upon which future MASH therapies will be evaluated for approval: that an ideal agent for MASH not only will have a significant impact on MASH pathophysiology but will also provide benefit for (or at least not worsen) the metabolic comorbidities associated with MASH.
 

New treatments on the horizon

Fortunately, several new MASH therapeutics in development seem to have promising metabolic profiles.

In the phase 3 MAESTRO-NASH biopsy trial, treatment with resmetirom, a thyroid hormone receptor–beta selective agonist versus placebo resulted in a clinically significant improvement in liver fibrosis by one stage or more (26% vs. 14%) and NASH resolution (30% vs. 10%). Unlike OCA, resmetirom was associated with a clinically significant reduction in LDL cholesterol (–16% compared with placebo).

Resmetirom has received a breakthrough therapy designation, and Madrigal Pharmaceuticals recently completed submission of a new drug application for accelerated approval of this agent to the FDA.

Semaglutide is a glucagonlike peptide–1 receptor agonist that is already FDA approved for treatment of diabetes and obesity and is being studied in a phase 3 analysis for NASH.

In a phase 2 trial, daily dosing of semaglutide vs placebo led to clinically significant improvement in NASH resolution (59% vs. 17%) but not significant improvement in fibrosis (43% vs 33%). Although it is impossible to make a meaningful comparison in outcomes between clinical trials, it should be noted that the absolute rate of response in this trial was higher than is routinely seen in other NASH trials and that the placebo rate for improvement in fibrosis was higher than expected, a common problem with NASH trials.

As expected, treatment with semaglutide was associated with dose-dependent reduction in body weight and hemoglobin A1c, highlighting the global metabolic benefit of this agent.

Another major class of agents being studied for NASH treatment are the fibroblast growth factor (FGF) 21 analogs.

In the recently published phase 2b ENLIVEN trial, treatment with the FGF21 analog pegozafermin versus placebo led to a statistically significant improvement in liver fibrosis by one stage (27% vs. 7%) and a numerical improvement in NASH resolution (26% vs. 2%).

In addition to its effects directly in the liver, FGF21 has been associated with promoting positive global metabolic effects, including improved peripheral insulin sensitivity and amelioration of dyslipidemia. Consistent with this, treatment with pegozafermin resulted in a decrease in serum triglycerides and an increase in serum HDL cholesterol and adiponectin levels.

Ultimately, the best therapeutic strategy for MASH may be one that uses combination therapy to maximize liver-directed effects and also ameliorate concomitant or contributing metabolic dysfunction. This approach is already being investigated. What seems clear, however, is that MASH therapy without concurrent treatment of metabolic comorbidities is probably destined to be ineffective, if not counterproductive.

So, what’s in a name? When it comes to MASLD, it seems quite a bit.
 

Dr. Janardhan is an assistant professor, department of internal medicine, at Rush University Medical Center, Chicago. Dr. Reau is a professor, department of internal medicine, Rush University. Dr. Janardhan reported conflicts of interest with Target RWE, Novo Nordisk, Intercept, and Enanta. Dr. Reau reported conflicts of interest with AbbVie, Gilead, and AASLD.

A version of this article appeared on Medscape.com.

In June 2023, a multisociety group agreed to change the name of the disease formerly known as nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction–associated steatotic liver disease (MASLD).

In the week leading up to this, Intercept Pharmaceuticals announced that their program to develop obeticholic acid (OCA) as a first-to-market, long-awaited potential drug therapy for metabolic dysfunction–associated steatohepatitis (MASH), the more pathogenic form of this disease, was being abandoned after the Food and Drug Administration Gastrointestinal Drugs Advisory Committee voted against accelerated approval of the drug. This decision was made in large part owing to data showing modest efficacy coupled with multiple drug-related side effects, including worsening metabolic dysfunction.

The juxtaposition of these two events highlights what could be a fundamental change in perspective when it comes to the management of patients with MASLD and the development of therapies for this disease.
 

A more precise nomenclature for a broad-spectrum disease

The updating of the NAFLD nomenclature to MASLD represents an important change in the way that the medical community is being asked to view and approach the disease of “fatty liver.”

The previous nomenclature clarified that pathogenic liver steatosis can exist in the absence of alcohol. However, it failed to define the primary drivers of the most common form of NAFLD: that is, metabolic syndrome diseases. The new nomenclature not only better defines the broad spectrum of steatotic liver diseases (alcohol, metabolic, drug/genetic, cryptogenic) but also refocuses the attention of providers on the fundamental basis of MASLD as a critical member of the metabolic syndrome spectrum of diseases.

This is in line with the recently updated American Association for the Study of Liver Disease Practice Guidelines for NAFLD (now MASLD), which focus on active screening to identify patients at risk for advanced MASLD, in particular those with medically complicated obesity or high-risk metabolic characteristics such as diabetes. This is a change from previous versions of the guidelines that were cautious to recommend broad screening guidelines in part owing to the lack of “available therapies.”

The increasing clinical burden of MASH has led to the recognition that patients do not have the luxury of waiting for “anticipated therapies” that have frequently shown only marginal or insignificant efficacy. As a result, some providers have refocused their efforts on the development of care pathways that can efficiently provide comprehensive lifestyle interventions to treat MASH and related metabolic comorbidities within hepatology or other subspecialty clinics.
 

Learning from OCA’s limitations

The approach to drug development for MASH seems to be shifting in a similar, metabolic syndrome–focused way.

The risk-benefit analysis from the FDA advisory committee evaluating OCA noted that the drug provided only modest (albeit statistically significant) benefits over placebo in achieving one of two primary clinical endpoints (improvement in fibrosis by one stage without worsening of NASH), but was associated with toxicity as well as significant drug-related side effects, including new or worsening dyslipidemia, accelerated progression to prediabetes or diabetes, and worsening glycemic control in patients with diabetes.

Worsening clinical markers of metabolic health were an important factor in the advisory committee’s decision to not provide accelerated approval of OCA. This informs the criteria upon which future MASH therapies will be evaluated for approval: that an ideal agent for MASH not only will have a significant impact on MASH pathophysiology but will also provide benefit for (or at least not worsen) the metabolic comorbidities associated with MASH.
 

New treatments on the horizon

Fortunately, several new MASH therapeutics in development seem to have promising metabolic profiles.

In the phase 3 MAESTRO-NASH biopsy trial, treatment with resmetirom, a thyroid hormone receptor–beta selective agonist versus placebo resulted in a clinically significant improvement in liver fibrosis by one stage or more (26% vs. 14%) and NASH resolution (30% vs. 10%). Unlike OCA, resmetirom was associated with a clinically significant reduction in LDL cholesterol (–16% compared with placebo).

Resmetirom has received a breakthrough therapy designation, and Madrigal Pharmaceuticals recently completed submission of a new drug application for accelerated approval of this agent to the FDA.

Semaglutide is a glucagonlike peptide–1 receptor agonist that is already FDA approved for treatment of diabetes and obesity and is being studied in a phase 3 analysis for NASH.

In a phase 2 trial, daily dosing of semaglutide vs placebo led to clinically significant improvement in NASH resolution (59% vs. 17%) but not significant improvement in fibrosis (43% vs 33%). Although it is impossible to make a meaningful comparison in outcomes between clinical trials, it should be noted that the absolute rate of response in this trial was higher than is routinely seen in other NASH trials and that the placebo rate for improvement in fibrosis was higher than expected, a common problem with NASH trials.

As expected, treatment with semaglutide was associated with dose-dependent reduction in body weight and hemoglobin A1c, highlighting the global metabolic benefit of this agent.

Another major class of agents being studied for NASH treatment are the fibroblast growth factor (FGF) 21 analogs.

In the recently published phase 2b ENLIVEN trial, treatment with the FGF21 analog pegozafermin versus placebo led to a statistically significant improvement in liver fibrosis by one stage (27% vs. 7%) and a numerical improvement in NASH resolution (26% vs. 2%).

In addition to its effects directly in the liver, FGF21 has been associated with promoting positive global metabolic effects, including improved peripheral insulin sensitivity and amelioration of dyslipidemia. Consistent with this, treatment with pegozafermin resulted in a decrease in serum triglycerides and an increase in serum HDL cholesterol and adiponectin levels.

Ultimately, the best therapeutic strategy for MASH may be one that uses combination therapy to maximize liver-directed effects and also ameliorate concomitant or contributing metabolic dysfunction. This approach is already being investigated. What seems clear, however, is that MASH therapy without concurrent treatment of metabolic comorbidities is probably destined to be ineffective, if not counterproductive.

So, what’s in a name? When it comes to MASLD, it seems quite a bit.
 

Dr. Janardhan is an assistant professor, department of internal medicine, at Rush University Medical Center, Chicago. Dr. Reau is a professor, department of internal medicine, Rush University. Dr. Janardhan reported conflicts of interest with Target RWE, Novo Nordisk, Intercept, and Enanta. Dr. Reau reported conflicts of interest with AbbVie, Gilead, and AASLD.

A version of this article appeared on Medscape.com.

Fear and a lack of health-related knowledge pose significant barriers to preventative cancer care access and effectiveness, recent survey data from The Harris Poll suggests.

The survey, commissioned by Bayer U.S. to identify patient behaviors and care barriers, indicates that more than one in four adults in the United States (27%) would rather not know if they have cancer, and nearly a third (31%) – particularly younger patients aged 18-44 years – avoid going to the doctor because they are afraid of what they might learn.

Similarly, 26% of 2,079 respondents said that fear and anxiety are the main reasons why they don’t make or keep doctor appointments. Those with lower household income and education levels, those with children under age 18 years, and Hispanic adults were most likely to cite this reason.

Almost half (up to 49%) lacked knowledge about certain cancers and risk factors.

For example, 48% of respondents were unaware that breast density affects breast cancer risk and diagnosis, and 38% said they were not very knowledgeable about breast cancer.

Regarding prostate cancer, 49% were unaware that race impacts risk and 49% said they were not knowledgeable about the disease.

The survey highlighted a lack of trust in treatments and health care processes among most adults, especially those with lower income and education levels. Overall, 53% said they have little or no trust in treatments developed by pharmaceutical companies, and 31% said they have little or no trust in medical tests, test results, and other medical processes.

The findings of the survey, which was conducted online June 6-8, 2023, among U.S. adults aged 18 years and older, underscore the need to better educate individuals about cancer risk factors and the benefits of preventative care.

“The increase of fear and anxiety, heightened by a lack of education and in some cases trust barriers, creates an environment where people may not access basic preventative care to ensure early diagnosis,” Sebastian Guth, president of Bayer U.S. and Pharmaceuticals North America, stated in a press release. “This is compounded by the fact that around 27.4 million people of all ages (8.3%) don’t have access to health insurance.

“Companies like Bayer have a responsibility to provide resources that increase health education on the importance of understanding disease risks, early disease screenings, and preventative health care,” Mr. Guth added, noting that the company is partnering with multiple patient advocacy groups to increase trust, awareness, and knowledge “to help individuals understand the resources available to them and their risks for a specific disease.”

Public health initiatives have had mixed results with respect to changing patient behaviors over time, but Breast Cancer Awareness Month (BCAM) in October of each year is a stand-out initiative that could serve as a model for other patient education initiatives, according to a 2022 study.

The Google trends analysis showed that from 2012 to 2021, BCAM was associated with improved public awareness of breast cancer, whereas Lung Cancer Awareness Month and Prostate Cancer Awareness Month had no impact on lung and prostate cancer awareness, respectively, over time, reported Yoshita Nishimura, MD, of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences in Japan, and Jared D. Acoba, MD, of the University of Hawaii, Honolulu.

Dr. Nishimura and Dr. Acoba concluded that the success of BCAM, which was launched in 1985 and is now led by the National Breast Cancer Foundation, is likely a result of “the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol.”

As for the role of physicians in raising awareness and increasing knowledge at the patient level, various guidelines focus on assessing patient needs and readiness to learn, communicating clearly, and identifying barriers, such as a lack of support and low health literacy.

An American Society of Clinical Oncology consensus guideline for physician-patient communication, for example, provides guidance on core communication skills that apply across the continuum of care, as well as specific topics to address, such as patient goals, treatment options, and support systems – all with an eye toward using “effective communication to optimize the patient-clinician relationship, patient and clinician well-being and family well-being.”

Fear and a lack of health-related knowledge pose significant barriers to preventative cancer care access and effectiveness, recent survey data from The Harris Poll suggests.

The survey, commissioned by Bayer U.S. to identify patient behaviors and care barriers, indicates that more than one in four adults in the United States (27%) would rather not know if they have cancer, and nearly a third (31%) – particularly younger patients aged 18-44 years – avoid going to the doctor because they are afraid of what they might learn.

Similarly, 26% of 2,079 respondents said that fear and anxiety are the main reasons why they don’t make or keep doctor appointments. Those with lower household income and education levels, those with children under age 18 years, and Hispanic adults were most likely to cite this reason.

Almost half (up to 49%) lacked knowledge about certain cancers and risk factors.

For example, 48% of respondents were unaware that breast density affects breast cancer risk and diagnosis, and 38% said they were not very knowledgeable about breast cancer.

Regarding prostate cancer, 49% were unaware that race impacts risk and 49% said they were not knowledgeable about the disease.

The survey highlighted a lack of trust in treatments and health care processes among most adults, especially those with lower income and education levels. Overall, 53% said they have little or no trust in treatments developed by pharmaceutical companies, and 31% said they have little or no trust in medical tests, test results, and other medical processes.

The findings of the survey, which was conducted online June 6-8, 2023, among U.S. adults aged 18 years and older, underscore the need to better educate individuals about cancer risk factors and the benefits of preventative care.

“The increase of fear and anxiety, heightened by a lack of education and in some cases trust barriers, creates an environment where people may not access basic preventative care to ensure early diagnosis,” Sebastian Guth, president of Bayer U.S. and Pharmaceuticals North America, stated in a press release. “This is compounded by the fact that around 27.4 million people of all ages (8.3%) don’t have access to health insurance.

“Companies like Bayer have a responsibility to provide resources that increase health education on the importance of understanding disease risks, early disease screenings, and preventative health care,” Mr. Guth added, noting that the company is partnering with multiple patient advocacy groups to increase trust, awareness, and knowledge “to help individuals understand the resources available to them and their risks for a specific disease.”

Public health initiatives have had mixed results with respect to changing patient behaviors over time, but Breast Cancer Awareness Month (BCAM) in October of each year is a stand-out initiative that could serve as a model for other patient education initiatives, according to a 2022 study.

The Google trends analysis showed that from 2012 to 2021, BCAM was associated with improved public awareness of breast cancer, whereas Lung Cancer Awareness Month and Prostate Cancer Awareness Month had no impact on lung and prostate cancer awareness, respectively, over time, reported Yoshita Nishimura, MD, of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences in Japan, and Jared D. Acoba, MD, of the University of Hawaii, Honolulu.

Dr. Nishimura and Dr. Acoba concluded that the success of BCAM, which was launched in 1985 and is now led by the National Breast Cancer Foundation, is likely a result of “the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol.”

As for the role of physicians in raising awareness and increasing knowledge at the patient level, various guidelines focus on assessing patient needs and readiness to learn, communicating clearly, and identifying barriers, such as a lack of support and low health literacy.

An American Society of Clinical Oncology consensus guideline for physician-patient communication, for example, provides guidance on core communication skills that apply across the continuum of care, as well as specific topics to address, such as patient goals, treatment options, and support systems – all with an eye toward using “effective communication to optimize the patient-clinician relationship, patient and clinician well-being and family well-being.”

Fear and a lack of health-related knowledge pose significant barriers to preventative cancer care access and effectiveness, recent survey data from The Harris Poll suggests.

The survey, commissioned by Bayer U.S. to identify patient behaviors and care barriers, indicates that more than one in four adults in the United States (27%) would rather not know if they have cancer, and nearly a third (31%) – particularly younger patients aged 18-44 years – avoid going to the doctor because they are afraid of what they might learn.

Similarly, 26% of 2,079 respondents said that fear and anxiety are the main reasons why they don’t make or keep doctor appointments. Those with lower household income and education levels, those with children under age 18 years, and Hispanic adults were most likely to cite this reason.

Almost half (up to 49%) lacked knowledge about certain cancers and risk factors.

For example, 48% of respondents were unaware that breast density affects breast cancer risk and diagnosis, and 38% said they were not very knowledgeable about breast cancer.

Regarding prostate cancer, 49% were unaware that race impacts risk and 49% said they were not knowledgeable about the disease.

The survey highlighted a lack of trust in treatments and health care processes among most adults, especially those with lower income and education levels. Overall, 53% said they have little or no trust in treatments developed by pharmaceutical companies, and 31% said they have little or no trust in medical tests, test results, and other medical processes.

The findings of the survey, which was conducted online June 6-8, 2023, among U.S. adults aged 18 years and older, underscore the need to better educate individuals about cancer risk factors and the benefits of preventative care.

“The increase of fear and anxiety, heightened by a lack of education and in some cases trust barriers, creates an environment where people may not access basic preventative care to ensure early diagnosis,” Sebastian Guth, president of Bayer U.S. and Pharmaceuticals North America, stated in a press release. “This is compounded by the fact that around 27.4 million people of all ages (8.3%) don’t have access to health insurance.

“Companies like Bayer have a responsibility to provide resources that increase health education on the importance of understanding disease risks, early disease screenings, and preventative health care,” Mr. Guth added, noting that the company is partnering with multiple patient advocacy groups to increase trust, awareness, and knowledge “to help individuals understand the resources available to them and their risks for a specific disease.”

Public health initiatives have had mixed results with respect to changing patient behaviors over time, but Breast Cancer Awareness Month (BCAM) in October of each year is a stand-out initiative that could serve as a model for other patient education initiatives, according to a 2022 study.

The Google trends analysis showed that from 2012 to 2021, BCAM was associated with improved public awareness of breast cancer, whereas Lung Cancer Awareness Month and Prostate Cancer Awareness Month had no impact on lung and prostate cancer awareness, respectively, over time, reported Yoshita Nishimura, MD, of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences in Japan, and Jared D. Acoba, MD, of the University of Hawaii, Honolulu.

Dr. Nishimura and Dr. Acoba concluded that the success of BCAM, which was launched in 1985 and is now led by the National Breast Cancer Foundation, is likely a result of “the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol.”

As for the role of physicians in raising awareness and increasing knowledge at the patient level, various guidelines focus on assessing patient needs and readiness to learn, communicating clearly, and identifying barriers, such as a lack of support and low health literacy.

An American Society of Clinical Oncology consensus guideline for physician-patient communication, for example, provides guidance on core communication skills that apply across the continuum of care, as well as specific topics to address, such as patient goals, treatment options, and support systems – all with an eye toward using “effective communication to optimize the patient-clinician relationship, patient and clinician well-being and family well-being.”

In the United States this year, approximately 288,300 men will be newly diagnosed with prostate cancer and about 34,700 men will die from this disease. It is the second leading cause of cancer in men, and one out of every eight men will be diagnosed with this cancer at some point in their lives.

As primary care physicians, a large part of our role is to prevent or detect cancers early. Patients look to us for this guidance. However, prostate cancer screening has long been a controversial issue. Earlier this year, the American Urological Association along with the Society of Urologic Oncology published updated guidelines.

Clear recommendations that come from this set of guidelines that are relevant to primary care physicians include:

• using PSA as the screening test of choice.
• repeating PSA in patients with newly elevated results before moving on to other test.
• offering PSA screening every 2-4 years in patients aged 50-69 years.
• offering baseline screening in those between 45-50 years of age.

In high-risk patients, screening can be initiated at 40-45 years of age. All of these recommendations come with the caveat that we give the patient all the pros and cons and leave it up to their “values and preferences.”

The guidelines make recommendations regarding PSA screening and biopsy standards. These guidelines are very specific in their recommendations; however, the question about whether to do PSA screening in the first place is left open to debate. While shared decision-making is important with any testing, it is more difficult with prostate cancer screening. Patients need to understand that there are possible adverse events that can result because of an elevated PSA, such as unneeded biopsies that may come with complications.

The authors of this set of guidelines suggest that physicians talk to patients more often about the benefits of the screening than they do about the negative consequences. This assumes that a negative biopsy result is an unnecessary test, which is not a fair assessment. Negative test results can provide useful clinical information. While a PSA result may lead to a biopsy that could have possibly been avoided, we don’t have any better screening tests available. Missing a prostate cancer that could have been detected by PSA screening is also very harmful. Deciding whether to do PSA screening for any given patient then becomes a difficult question.

More research into biomarkers to detect prostate cancer is needed, as suggested by the guideline authors. As primary care doctors, we’re the first ones to order these tests and make decisions regarding the results. While we may not be the ones to do the biopsies, we do need to know when to refer the patients to specialists or when we can just repeat the test.

Population health is often the benchmark used when looking at screening guidelines. But in the primary care setting, we are responsible for individual patients. Applying guidelines that take whole populations into consideration often doesn’t translate well to single patients. We do need to make them responsible for their own health care decisions but, at the same time, we need to offer them some guidance. If the guidelines are clear, this is easy. When they suggest giving patients all the pros and cons and letting them make their own decision, this is hard. Some of them want us to tell them what to do.

Additionally, patients in the primary care setting develop close relationships with their physicians. They are not an elevated PSA test or a negative biopsy result. They have concerns and fears. When they are high risk, the advice is easy. Keeping in mind that prostate cancer is the second leading cause of cancer in men in the United States, we should have clear screening guidelines, such as we do with mammograms in women. Yes, shared decision-making is important, but we also need to know the answer when our patients ask us whether or not they should have a PSA test done.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.

In the United States this year, approximately 288,300 men will be newly diagnosed with prostate cancer and about 34,700 men will die from this disease. It is the second leading cause of cancer in men, and one out of every eight men will be diagnosed with this cancer at some point in their lives.

As primary care physicians, a large part of our role is to prevent or detect cancers early. Patients look to us for this guidance. However, prostate cancer screening has long been a controversial issue. Earlier this year, the American Urological Association along with the Society of Urologic Oncology published updated guidelines.

Clear recommendations that come from this set of guidelines that are relevant to primary care physicians include:

• using PSA as the screening test of choice.
• repeating PSA in patients with newly elevated results before moving on to other test.
• offering PSA screening every 2-4 years in patients aged 50-69 years.
• offering baseline screening in those between 45-50 years of age.

In high-risk patients, screening can be initiated at 40-45 years of age. All of these recommendations come with the caveat that we give the patient all the pros and cons and leave it up to their “values and preferences.”

The guidelines make recommendations regarding PSA screening and biopsy standards. These guidelines are very specific in their recommendations; however, the question about whether to do PSA screening in the first place is left open to debate. While shared decision-making is important with any testing, it is more difficult with prostate cancer screening. Patients need to understand that there are possible adverse events that can result because of an elevated PSA, such as unneeded biopsies that may come with complications.

The authors of this set of guidelines suggest that physicians talk to patients more often about the benefits of the screening than they do about the negative consequences. This assumes that a negative biopsy result is an unnecessary test, which is not a fair assessment. Negative test results can provide useful clinical information. While a PSA result may lead to a biopsy that could have possibly been avoided, we don’t have any better screening tests available. Missing a prostate cancer that could have been detected by PSA screening is also very harmful. Deciding whether to do PSA screening for any given patient then becomes a difficult question.

More research into biomarkers to detect prostate cancer is needed, as suggested by the guideline authors. As primary care doctors, we’re the first ones to order these tests and make decisions regarding the results. While we may not be the ones to do the biopsies, we do need to know when to refer the patients to specialists or when we can just repeat the test.

Population health is often the benchmark used when looking at screening guidelines. But in the primary care setting, we are responsible for individual patients. Applying guidelines that take whole populations into consideration often doesn’t translate well to single patients. We do need to make them responsible for their own health care decisions but, at the same time, we need to offer them some guidance. If the guidelines are clear, this is easy. When they suggest giving patients all the pros and cons and letting them make their own decision, this is hard. Some of them want us to tell them what to do.

Additionally, patients in the primary care setting develop close relationships with their physicians. They are not an elevated PSA test or a negative biopsy result. They have concerns and fears. When they are high risk, the advice is easy. Keeping in mind that prostate cancer is the second leading cause of cancer in men in the United States, we should have clear screening guidelines, such as we do with mammograms in women. Yes, shared decision-making is important, but we also need to know the answer when our patients ask us whether or not they should have a PSA test done.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.

In the United States this year, approximately 288,300 men will be newly diagnosed with prostate cancer and about 34,700 men will die from this disease. It is the second leading cause of cancer in men, and one out of every eight men will be diagnosed with this cancer at some point in their lives.

As primary care physicians, a large part of our role is to prevent or detect cancers early. Patients look to us for this guidance. However, prostate cancer screening has long been a controversial issue. Earlier this year, the American Urological Association along with the Society of Urologic Oncology published updated guidelines.

Clear recommendations that come from this set of guidelines that are relevant to primary care physicians include:

• using PSA as the screening test of choice.
• repeating PSA in patients with newly elevated results before moving on to other test.
• offering PSA screening every 2-4 years in patients aged 50-69 years.
• offering baseline screening in those between 45-50 years of age.

In high-risk patients, screening can be initiated at 40-45 years of age. All of these recommendations come with the caveat that we give the patient all the pros and cons and leave it up to their “values and preferences.”

The guidelines make recommendations regarding PSA screening and biopsy standards. These guidelines are very specific in their recommendations; however, the question about whether to do PSA screening in the first place is left open to debate. While shared decision-making is important with any testing, it is more difficult with prostate cancer screening. Patients need to understand that there are possible adverse events that can result because of an elevated PSA, such as unneeded biopsies that may come with complications.

The authors of this set of guidelines suggest that physicians talk to patients more often about the benefits of the screening than they do about the negative consequences. This assumes that a negative biopsy result is an unnecessary test, which is not a fair assessment. Negative test results can provide useful clinical information. While a PSA result may lead to a biopsy that could have possibly been avoided, we don’t have any better screening tests available. Missing a prostate cancer that could have been detected by PSA screening is also very harmful. Deciding whether to do PSA screening for any given patient then becomes a difficult question.

More research into biomarkers to detect prostate cancer is needed, as suggested by the guideline authors. As primary care doctors, we’re the first ones to order these tests and make decisions regarding the results. While we may not be the ones to do the biopsies, we do need to know when to refer the patients to specialists or when we can just repeat the test.

Population health is often the benchmark used when looking at screening guidelines. But in the primary care setting, we are responsible for individual patients. Applying guidelines that take whole populations into consideration often doesn’t translate well to single patients. We do need to make them responsible for their own health care decisions but, at the same time, we need to offer them some guidance. If the guidelines are clear, this is easy. When they suggest giving patients all the pros and cons and letting them make their own decision, this is hard. Some of them want us to tell them what to do.

Additionally, patients in the primary care setting develop close relationships with their physicians. They are not an elevated PSA test or a negative biopsy result. They have concerns and fears. When they are high risk, the advice is easy. Keeping in mind that prostate cancer is the second leading cause of cancer in men in the United States, we should have clear screening guidelines, such as we do with mammograms in women. Yes, shared decision-making is important, but we also need to know the answer when our patients ask us whether or not they should have a PSA test done.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J.

New research hints at the possibility that cerebral amyloid angiopathy (CAA), a cause of spontaneous brain hemorrhage, can be transmitted via blood transfusion, raising the risk for spontaneous intracerebral hemorrhage (ICH) in transfusion recipients.

In an exploratory analysis, patients receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs, and were assumed to have CAA, were at a significantly increased risk of developing spontaneous ICH themselves.

“This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of CAA might explain this association,” the investigators noted.

“We do not think that the findings motivate a change in practice, and we should not let these results discourage otherwise indicated blood transfusion,” said lead author Jingcheng Zhao, MD, PhD, with Karolinska University Hospital Solna, Stockholm.

The study was published online  in the Journal of the American Medical Association.
 

Novel finding

Recent evidence suggests that CAA exhibits “prion-like” transmissivity, with reports of transmission through cadaveric pituitary hormone contaminated with amyloid-beta and tau protein, dura mater grafts, and possibly neurosurgical instruments.

CAA, which is characterized by the deposition of amyloid protein in the brain, is the second most common cause of spontaneous ICH. 

The researchers hypothesized that transfusion transmission of CAA may manifest through an increased risk for spontaneous ICH among transfusion recipients given blood from a donor with spontaneous ICH. To explore this hypothesis, they analyzed national registry data from Sweden and Denmark for ICH in recipients of red blood cell transfusion from donors who themselves had ICH over the years after their blood donations, with the assumption that donors with two or more ICHs would likely have CAA.

The cohort included nearly 760,000 individuals in Sweden (median age, 65 years; 59% women) and 330,000 in Denmark (median age, 64 years; 58% women), with a median follow-up of 5.8 and 6.1 years, respectively.

Receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs was associated with a greater than twofold increased risk of developing spontaneous ICH, compared with receiving a transfusion from donors without subsequent ICH (hazard ratio, 2.73; P < .001 in the Swedish cohort and HR, 2.32; P = .04 in the Danish cohort).

“The observed increased risk of spontaneous ICH associated with receiving a red blood cell transfusion from a donor who later developed multiple spontaneous ICHs, corresponding to a 30-year cumulative incidence difference of 2.3%, is a novel finding,” the researchers wrote.

There was no increase in post-transfusion ICH risk among recipients whose donors had a single post–blood-donation ICH.

The findings were robust to several of the sensitivity analyses.

A “negative” control analysis of post-transfusion ischemic stroke (instead of ICH) found no increased risk among recipients of blood from donors who had single or multiple ICHs.

This study provides “exploratory evidence of possible transfusion-transmission of a factor that causes ICHs, but more research is needed to confirm and to understand the mechanism,” said Dr. Zhao.

The researchers noted that they did not directly assess CAA but expect it would be more common among donors who develop multiple spontaneous ICHs, “as CAA-related ICH has been reported to have a 7-fold increase for recurrent ICHs, compared with non–CAA-related ICH.”
 

Worrisome finding or false alarm?

In an accompanying editorial, Steven Greenberg, MD, PhD, with the department of neurology, Harvard Medical School, Boston, said there are “good reasons to treat the possibility of CAA transmission via blood transfusion seriously – and good reasons to remain skeptical, at least for the present.”

“Powerful” arguments in support of the findings include the robust study methodology and the “striking” similarity in results from the two registries, which argues against a chance finding. Another is the negative control with ischemic stroke as the outcome, which argues against unsuspected confounding-causing associations with all types of stroke, Dr. Greenberg noted.

Arguments for remaining “unconvinced” of the association center on the weakness of evidence for a plausible biological mechanism for the finding, he points out. Another is the short-time course of ICHs after blood transfusion, which is “quite challenging to explain,” Dr. Greenberg said. Nearly half of the ICHs among blood recipients occurred within 5 years of transfusion, which is “dramatically” faster than the 30- to 40-year interval reported between neurosurgical exposure to cadaveric tissue and first ICH, he added.

Another related “mechanistic reservation” is the plausibility that a transmissible species of amyloid-beta could travel from blood to brain in sufficient quantities to trigger advanced CAA or Alzheimer disease pathology, he wrote.

He added the current study leaves him “squarely at the corner of anxiety and skepticism.”

With more than 10 million units of blood transfused in the United States each year, even a modest increase in risk for future brain hemorrhages or dementia conferred by “an uncommon – but as of now undetectable – donor trait would represent a substantial public health concern,” Dr. Greenberg wrote.

“From the standpoint of scientific plausibility, however, even this well-conducted analysis is at risk of representing a false alarm,” he cautioned.

Looking ahead, Dr. Greenberg said one clear direction is independent replication, ideally with datasets in which donor and recipient dementia can be reliably ascertained to assess the possibility of Alzheimer’s disease as well as CAA transmissibility.

“The other challenge is for experimental biologists to consider the alternative possibility of transfusion-related acceleration of downstream steps in the CAA-ICH pathway, such as the vessel remodeling by which amyloid beta–laden vessels proceed to rupture and bleed.”

“The current study is not yet a reason for alarm, certainly not a reason to avoid otherwise indicated blood transfusion, but it is a strong call for more scientific digging,” Dr. Greenberg concluded.

The study was funded by grants from the Karolinska Institute, the Swedish Research Council, and Region Stockholm. Dr. Zhao and Dr. Greenberg report no relevant financial relationships.

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

New research hints at the possibility that cerebral amyloid angiopathy (CAA), a cause of spontaneous brain hemorrhage, can be transmitted via blood transfusion, raising the risk for spontaneous intracerebral hemorrhage (ICH) in transfusion recipients.

In an exploratory analysis, patients receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs, and were assumed to have CAA, were at a significantly increased risk of developing spontaneous ICH themselves.

“This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of CAA might explain this association,” the investigators noted.

“We do not think that the findings motivate a change in practice, and we should not let these results discourage otherwise indicated blood transfusion,” said lead author Jingcheng Zhao, MD, PhD, with Karolinska University Hospital Solna, Stockholm.

The study was published online  in the Journal of the American Medical Association.
 

Novel finding

Recent evidence suggests that CAA exhibits “prion-like” transmissivity, with reports of transmission through cadaveric pituitary hormone contaminated with amyloid-beta and tau protein, dura mater grafts, and possibly neurosurgical instruments.

CAA, which is characterized by the deposition of amyloid protein in the brain, is the second most common cause of spontaneous ICH. 

The researchers hypothesized that transfusion transmission of CAA may manifest through an increased risk for spontaneous ICH among transfusion recipients given blood from a donor with spontaneous ICH. To explore this hypothesis, they analyzed national registry data from Sweden and Denmark for ICH in recipients of red blood cell transfusion from donors who themselves had ICH over the years after their blood donations, with the assumption that donors with two or more ICHs would likely have CAA.

The cohort included nearly 760,000 individuals in Sweden (median age, 65 years; 59% women) and 330,000 in Denmark (median age, 64 years; 58% women), with a median follow-up of 5.8 and 6.1 years, respectively.

Receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs was associated with a greater than twofold increased risk of developing spontaneous ICH, compared with receiving a transfusion from donors without subsequent ICH (hazard ratio, 2.73; P < .001 in the Swedish cohort and HR, 2.32; P = .04 in the Danish cohort).

“The observed increased risk of spontaneous ICH associated with receiving a red blood cell transfusion from a donor who later developed multiple spontaneous ICHs, corresponding to a 30-year cumulative incidence difference of 2.3%, is a novel finding,” the researchers wrote.

There was no increase in post-transfusion ICH risk among recipients whose donors had a single post–blood-donation ICH.

The findings were robust to several of the sensitivity analyses.

A “negative” control analysis of post-transfusion ischemic stroke (instead of ICH) found no increased risk among recipients of blood from donors who had single or multiple ICHs.

This study provides “exploratory evidence of possible transfusion-transmission of a factor that causes ICHs, but more research is needed to confirm and to understand the mechanism,” said Dr. Zhao.

The researchers noted that they did not directly assess CAA but expect it would be more common among donors who develop multiple spontaneous ICHs, “as CAA-related ICH has been reported to have a 7-fold increase for recurrent ICHs, compared with non–CAA-related ICH.”
 

Worrisome finding or false alarm?

In an accompanying editorial, Steven Greenberg, MD, PhD, with the department of neurology, Harvard Medical School, Boston, said there are “good reasons to treat the possibility of CAA transmission via blood transfusion seriously – and good reasons to remain skeptical, at least for the present.”

“Powerful” arguments in support of the findings include the robust study methodology and the “striking” similarity in results from the two registries, which argues against a chance finding. Another is the negative control with ischemic stroke as the outcome, which argues against unsuspected confounding-causing associations with all types of stroke, Dr. Greenberg noted.

Arguments for remaining “unconvinced” of the association center on the weakness of evidence for a plausible biological mechanism for the finding, he points out. Another is the short-time course of ICHs after blood transfusion, which is “quite challenging to explain,” Dr. Greenberg said. Nearly half of the ICHs among blood recipients occurred within 5 years of transfusion, which is “dramatically” faster than the 30- to 40-year interval reported between neurosurgical exposure to cadaveric tissue and first ICH, he added.

Another related “mechanistic reservation” is the plausibility that a transmissible species of amyloid-beta could travel from blood to brain in sufficient quantities to trigger advanced CAA or Alzheimer disease pathology, he wrote.

He added the current study leaves him “squarely at the corner of anxiety and skepticism.”

With more than 10 million units of blood transfused in the United States each year, even a modest increase in risk for future brain hemorrhages or dementia conferred by “an uncommon – but as of now undetectable – donor trait would represent a substantial public health concern,” Dr. Greenberg wrote.

“From the standpoint of scientific plausibility, however, even this well-conducted analysis is at risk of representing a false alarm,” he cautioned.

Looking ahead, Dr. Greenberg said one clear direction is independent replication, ideally with datasets in which donor and recipient dementia can be reliably ascertained to assess the possibility of Alzheimer’s disease as well as CAA transmissibility.

“The other challenge is for experimental biologists to consider the alternative possibility of transfusion-related acceleration of downstream steps in the CAA-ICH pathway, such as the vessel remodeling by which amyloid beta–laden vessels proceed to rupture and bleed.”

“The current study is not yet a reason for alarm, certainly not a reason to avoid otherwise indicated blood transfusion, but it is a strong call for more scientific digging,” Dr. Greenberg concluded.

The study was funded by grants from the Karolinska Institute, the Swedish Research Council, and Region Stockholm. Dr. Zhao and Dr. Greenberg report no relevant financial relationships.

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

New research hints at the possibility that cerebral amyloid angiopathy (CAA), a cause of spontaneous brain hemorrhage, can be transmitted via blood transfusion, raising the risk for spontaneous intracerebral hemorrhage (ICH) in transfusion recipients.

In an exploratory analysis, patients receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs, and were assumed to have CAA, were at a significantly increased risk of developing spontaneous ICH themselves.

“This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of CAA might explain this association,” the investigators noted.

“We do not think that the findings motivate a change in practice, and we should not let these results discourage otherwise indicated blood transfusion,” said lead author Jingcheng Zhao, MD, PhD, with Karolinska University Hospital Solna, Stockholm.

The study was published online  in the Journal of the American Medical Association.
 

Novel finding

Recent evidence suggests that CAA exhibits “prion-like” transmissivity, with reports of transmission through cadaveric pituitary hormone contaminated with amyloid-beta and tau protein, dura mater grafts, and possibly neurosurgical instruments.

CAA, which is characterized by the deposition of amyloid protein in the brain, is the second most common cause of spontaneous ICH. 

The researchers hypothesized that transfusion transmission of CAA may manifest through an increased risk for spontaneous ICH among transfusion recipients given blood from a donor with spontaneous ICH. To explore this hypothesis, they analyzed national registry data from Sweden and Denmark for ICH in recipients of red blood cell transfusion from donors who themselves had ICH over the years after their blood donations, with the assumption that donors with two or more ICHs would likely have CAA.

The cohort included nearly 760,000 individuals in Sweden (median age, 65 years; 59% women) and 330,000 in Denmark (median age, 64 years; 58% women), with a median follow-up of 5.8 and 6.1 years, respectively.

Receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs was associated with a greater than twofold increased risk of developing spontaneous ICH, compared with receiving a transfusion from donors without subsequent ICH (hazard ratio, 2.73; P < .001 in the Swedish cohort and HR, 2.32; P = .04 in the Danish cohort).

“The observed increased risk of spontaneous ICH associated with receiving a red blood cell transfusion from a donor who later developed multiple spontaneous ICHs, corresponding to a 30-year cumulative incidence difference of 2.3%, is a novel finding,” the researchers wrote.

There was no increase in post-transfusion ICH risk among recipients whose donors had a single post–blood-donation ICH.

The findings were robust to several of the sensitivity analyses.

A “negative” control analysis of post-transfusion ischemic stroke (instead of ICH) found no increased risk among recipients of blood from donors who had single or multiple ICHs.

This study provides “exploratory evidence of possible transfusion-transmission of a factor that causes ICHs, but more research is needed to confirm and to understand the mechanism,” said Dr. Zhao.

The researchers noted that they did not directly assess CAA but expect it would be more common among donors who develop multiple spontaneous ICHs, “as CAA-related ICH has been reported to have a 7-fold increase for recurrent ICHs, compared with non–CAA-related ICH.”
 

Worrisome finding or false alarm?

In an accompanying editorial, Steven Greenberg, MD, PhD, with the department of neurology, Harvard Medical School, Boston, said there are “good reasons to treat the possibility of CAA transmission via blood transfusion seriously – and good reasons to remain skeptical, at least for the present.”

“Powerful” arguments in support of the findings include the robust study methodology and the “striking” similarity in results from the two registries, which argues against a chance finding. Another is the negative control with ischemic stroke as the outcome, which argues against unsuspected confounding-causing associations with all types of stroke, Dr. Greenberg noted.

Arguments for remaining “unconvinced” of the association center on the weakness of evidence for a plausible biological mechanism for the finding, he points out. Another is the short-time course of ICHs after blood transfusion, which is “quite challenging to explain,” Dr. Greenberg said. Nearly half of the ICHs among blood recipients occurred within 5 years of transfusion, which is “dramatically” faster than the 30- to 40-year interval reported between neurosurgical exposure to cadaveric tissue and first ICH, he added.

Another related “mechanistic reservation” is the plausibility that a transmissible species of amyloid-beta could travel from blood to brain in sufficient quantities to trigger advanced CAA or Alzheimer disease pathology, he wrote.

He added the current study leaves him “squarely at the corner of anxiety and skepticism.”

With more than 10 million units of blood transfused in the United States each year, even a modest increase in risk for future brain hemorrhages or dementia conferred by “an uncommon – but as of now undetectable – donor trait would represent a substantial public health concern,” Dr. Greenberg wrote.

“From the standpoint of scientific plausibility, however, even this well-conducted analysis is at risk of representing a false alarm,” he cautioned.

Looking ahead, Dr. Greenberg said one clear direction is independent replication, ideally with datasets in which donor and recipient dementia can be reliably ascertained to assess the possibility of Alzheimer’s disease as well as CAA transmissibility.

“The other challenge is for experimental biologists to consider the alternative possibility of transfusion-related acceleration of downstream steps in the CAA-ICH pathway, such as the vessel remodeling by which amyloid beta–laden vessels proceed to rupture and bleed.”

“The current study is not yet a reason for alarm, certainly not a reason to avoid otherwise indicated blood transfusion, but it is a strong call for more scientific digging,” Dr. Greenberg concluded.

The study was funded by grants from the Karolinska Institute, the Swedish Research Council, and Region Stockholm. Dr. Zhao and Dr. Greenberg report no relevant financial relationships.

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

Key clinical point: Compared with paclitaxel chemotherapy, treatment with first-line cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) demonstrated better survival outcomes and a similar speed of improvement in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who had a visceral crisis (VC) or impending VC (IVC).

Major finding: CDK4/6i vs paclitaxel improved time-to-treatment failure (hazard ratio [HR] 0.33; P  =  .0002), progression-free survival (HR 0.38; P  =  .002), and overall survival (HR 0.37; P  =  .002) outcomes. The median time to first improvement in IVC/VC was comparable between the treatment groups (P  =  .773).

Study details: Findings are from a retrospective study including 59 patients with ER+/HER2− advanced BC who had either VC or IVC, of whom 27 patients received first-line treatment with CDK4/6i + endocrine therapy and 32 patients who were treated with weekly paclitaxel.

Disclosures: This study did not receive any funding. Two authors declared having joint working agreements with or receiving honoraria, conference fees, travel expenses, or research funding from various sources.

Source: Behrouzi R et al. CDK4/6 inhibitors versus weekly paclitaxel for treatment of ER+/HER2− advanced breast cancer with impending or established visceral crisis. Breast Cancer Res Treat. 2023 (Aug 16). doi: 10.1007/s10549-023-07035-6

Key clinical point: Compared with paclitaxel chemotherapy, treatment with first-line cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) demonstrated better survival outcomes and a similar speed of improvement in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who had a visceral crisis (VC) or impending VC (IVC).

Major finding: CDK4/6i vs paclitaxel improved time-to-treatment failure (hazard ratio [HR] 0.33; P  =  .0002), progression-free survival (HR 0.38; P  =  .002), and overall survival (HR 0.37; P  =  .002) outcomes. The median time to first improvement in IVC/VC was comparable between the treatment groups (P  =  .773).

Study details: Findings are from a retrospective study including 59 patients with ER+/HER2− advanced BC who had either VC or IVC, of whom 27 patients received first-line treatment with CDK4/6i + endocrine therapy and 32 patients who were treated with weekly paclitaxel.

Disclosures: This study did not receive any funding. Two authors declared having joint working agreements with or receiving honoraria, conference fees, travel expenses, or research funding from various sources.

Source: Behrouzi R et al. CDK4/6 inhibitors versus weekly paclitaxel for treatment of ER+/HER2− advanced breast cancer with impending or established visceral crisis. Breast Cancer Res Treat. 2023 (Aug 16). doi: 10.1007/s10549-023-07035-6

Key clinical point: Compared with paclitaxel chemotherapy, treatment with first-line cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) demonstrated better survival outcomes and a similar speed of improvement in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC) who had a visceral crisis (VC) or impending VC (IVC).

Major finding: CDK4/6i vs paclitaxel improved time-to-treatment failure (hazard ratio [HR] 0.33; P  =  .0002), progression-free survival (HR 0.38; P  =  .002), and overall survival (HR 0.37; P  =  .002) outcomes. The median time to first improvement in IVC/VC was comparable between the treatment groups (P  =  .773).

Study details: Findings are from a retrospective study including 59 patients with ER+/HER2− advanced BC who had either VC or IVC, of whom 27 patients received first-line treatment with CDK4/6i + endocrine therapy and 32 patients who were treated with weekly paclitaxel.

Disclosures: This study did not receive any funding. Two authors declared having joint working agreements with or receiving honoraria, conference fees, travel expenses, or research funding from various sources.

Source: Behrouzi R et al. CDK4/6 inhibitors versus weekly paclitaxel for treatment of ER+/HER2− advanced breast cancer with impending or established visceral crisis. Breast Cancer Res Treat. 2023 (Aug 16). doi: 10.1007/s10549-023-07035-6

Key clinical point: Patients who survive breast cancer (BC) may have an elevated risk of developing type 2 diabetes mellitus (T2D), especially after receiving tamoxifen therapy.

Major finding: The risk for incident T2D was elevated in patients with BC (effect estimate [EE] 1.23; 95% CI 1.13-1.33), particularly those who received endocrine therapy (EE 1.23; 95% CI 1.16-1.32), compared with individuals without BC. Moreover, the risk of developing T2D was higher among patients with BC who did vs did not receive tamoxifen (EE 1.28; 95% CI 1.18-1.38).

Study details: Findings are from a meta-analysis of 15 observational studies.

Disclosures: This study was funded by the Novo Nordisk Foundation and other sources. The authors declared no conflicts of interest.

Source: Jordt N et al. Breast cancer and incidence of type 2 diabetes mellitus: A systematic review and meta-analysis. Breast Cancer Res Treat. 2023 (Sep 1). doi: 10.1007/s10549-023-07043-6

Key clinical point: Patients who survive breast cancer (BC) may have an elevated risk of developing type 2 diabetes mellitus (T2D), especially after receiving tamoxifen therapy.

Major finding: The risk for incident T2D was elevated in patients with BC (effect estimate [EE] 1.23; 95% CI 1.13-1.33), particularly those who received endocrine therapy (EE 1.23; 95% CI 1.16-1.32), compared with individuals without BC. Moreover, the risk of developing T2D was higher among patients with BC who did vs did not receive tamoxifen (EE 1.28; 95% CI 1.18-1.38).

Study details: Findings are from a meta-analysis of 15 observational studies.

Disclosures: This study was funded by the Novo Nordisk Foundation and other sources. The authors declared no conflicts of interest.

Source: Jordt N et al. Breast cancer and incidence of type 2 diabetes mellitus: A systematic review and meta-analysis. Breast Cancer Res Treat. 2023 (Sep 1). doi: 10.1007/s10549-023-07043-6

Key clinical point: Patients who survive breast cancer (BC) may have an elevated risk of developing type 2 diabetes mellitus (T2D), especially after receiving tamoxifen therapy.

Major finding: The risk for incident T2D was elevated in patients with BC (effect estimate [EE] 1.23; 95% CI 1.13-1.33), particularly those who received endocrine therapy (EE 1.23; 95% CI 1.16-1.32), compared with individuals without BC. Moreover, the risk of developing T2D was higher among patients with BC who did vs did not receive tamoxifen (EE 1.28; 95% CI 1.18-1.38).

Study details: Findings are from a meta-analysis of 15 observational studies.

Disclosures: This study was funded by the Novo Nordisk Foundation and other sources. The authors declared no conflicts of interest.

Source: Jordt N et al. Breast cancer and incidence of type 2 diabetes mellitus: A systematic review and meta-analysis. Breast Cancer Res Treat. 2023 (Sep 1). doi: 10.1007/s10549-023-07043-6

Key clinical point: Certain preoperative clinicopathological factors can predict the presence of ≥4 pathologically positive lymph nodes in postmenopausal women with clinically node-negative (cN0) breast cancer (BC) who underwent sentinel lymph node biopsy (SLNB) with or without completion axillary lymph node dissection (cALND).

Major finding: Only 2.5% of the evaluated patients reported having ≥4 positive lymph nodes, with the factors serving as independent predictors of ≥4 positive nodes being larger tumor size (odds ratio [OR] 1.42; P < .0001), invasive lobular carcinoma (ILC) or mixed invasive ductal carcinoma/ILC histology (OR 3.03 or 1.99, respectively; P  =  .008), multifocality (OR 3.58; P < .0001), and the presence of lymphovascular invasion (OR 4.77; P < .0001).

Study details: This retrospective review included 2532 postmenopausal women with cN0 BC who underwent SLNB, of whom 24.3% underwent cALND.

Disclosures: This study was supported by an US National Institutes of Health/National Cancer Institute Cancer Center Support Grant. Some authors declared serving on medical or scientific advisory boards of, receiving research funding or support for clinical trials from, or having other ties with various sources.

Source: Farley C et al. To dissect or not to dissect: Can we predict the presence of four or more axillary lymph node metastases in postmenopausal women with clinically node-negative breast cancer? Ann Surg Oncol. 2023 (Sep 5). doi: 10.1245/s10434-023-14245-1

Key clinical point: Certain preoperative clinicopathological factors can predict the presence of ≥4 pathologically positive lymph nodes in postmenopausal women with clinically node-negative (cN0) breast cancer (BC) who underwent sentinel lymph node biopsy (SLNB) with or without completion axillary lymph node dissection (cALND).

Major finding: Only 2.5% of the evaluated patients reported having ≥4 positive lymph nodes, with the factors serving as independent predictors of ≥4 positive nodes being larger tumor size (odds ratio [OR] 1.42; P < .0001), invasive lobular carcinoma (ILC) or mixed invasive ductal carcinoma/ILC histology (OR 3.03 or 1.99, respectively; P  =  .008), multifocality (OR 3.58; P < .0001), and the presence of lymphovascular invasion (OR 4.77; P < .0001).

Study details: This retrospective review included 2532 postmenopausal women with cN0 BC who underwent SLNB, of whom 24.3% underwent cALND.

Disclosures: This study was supported by an US National Institutes of Health/National Cancer Institute Cancer Center Support Grant. Some authors declared serving on medical or scientific advisory boards of, receiving research funding or support for clinical trials from, or having other ties with various sources.

Source: Farley C et al. To dissect or not to dissect: Can we predict the presence of four or more axillary lymph node metastases in postmenopausal women with clinically node-negative breast cancer? Ann Surg Oncol. 2023 (Sep 5). doi: 10.1245/s10434-023-14245-1

Key clinical point: Certain preoperative clinicopathological factors can predict the presence of ≥4 pathologically positive lymph nodes in postmenopausal women with clinically node-negative (cN0) breast cancer (BC) who underwent sentinel lymph node biopsy (SLNB) with or without completion axillary lymph node dissection (cALND).

Major finding: Only 2.5% of the evaluated patients reported having ≥4 positive lymph nodes, with the factors serving as independent predictors of ≥4 positive nodes being larger tumor size (odds ratio [OR] 1.42; P < .0001), invasive lobular carcinoma (ILC) or mixed invasive ductal carcinoma/ILC histology (OR 3.03 or 1.99, respectively; P  =  .008), multifocality (OR 3.58; P < .0001), and the presence of lymphovascular invasion (OR 4.77; P < .0001).

Study details: This retrospective review included 2532 postmenopausal women with cN0 BC who underwent SLNB, of whom 24.3% underwent cALND.

Disclosures: This study was supported by an US National Institutes of Health/National Cancer Institute Cancer Center Support Grant. Some authors declared serving on medical or scientific advisory boards of, receiving research funding or support for clinical trials from, or having other ties with various sources.

Source: Farley C et al. To dissect or not to dissect: Can we predict the presence of four or more axillary lymph node metastases in postmenopausal women with clinically node-negative breast cancer? Ann Surg Oncol. 2023 (Sep 5). doi: 10.1245/s10434-023-14245-1