Selective use of antibiotics based on birth circumstances may reduce unnecessary antibiotic exposure for preterm infants at risk of early-onset sepsis, based on data from 340 preterm infants at a single center.

Preterm infants born because of preterm labor, premature rupture of membranes, and/or intraamniotic infection (IAI) are considered at increased risk for early-onset sepsis, and current management strategies include a blood culture and initiation of empirical antibiotics, said Kirtan Patel, MD, of Texas A&M University, Dallas, and colleagues in a poster (# 1720) presented at the Pediatric Academic Societies annual meeting.

However, this blanket approach “may increase the unnecessary early antibiotic exposure in preterm infants possibly leading to future adverse health outcomes,” and physicians are advised to review the risks and benefits, Dr. Patel said.

Data from previous studies suggest that preterm infants born as a result of preterm labor and/or premature rupture of membranes with adequate Group B Streptococcus (GBS) intrapartum antibiotic prophylaxis and no indication of IAI may be managed without empiric antibiotics because the early-onset sepsis risk in these infants is much lower than the ones born through IAI and inadequate GBS intrapartum antibiotic prophylaxis.

To better identify preterm birth circumstances in which antibiotics might be avoided, the researchers conducted a retrospective cohort study of preterm infants born at 28-34 weeks’ gestation during the period from Jan. 1, 2015, to Dec. 31, 2018. These infants were in the low-risk category of preterm birth because of preterm labor or premature rupture of membranes, with no IAI and adequate GBS intrapartum antibiotic prophylaxis, and no signs of cardiovascular or respiratory instability after birth. Of these, 157 (46.2%) received empiric antibiotics soon after birth and 183 infants (53.8%) did not receive empiric antibiotics.

The mean gestational age and birth weight were significantly lower in the empiric antibiotic group, but after correcting for these variables, the factors with the greatest influence on the initiation of antibiotics were maternal intrapartum antibiotic prophylaxis (odds ratio, 3.13); premature rupture of membranes (OR, 3.75); use of continuous positive airway pressure (CPAP) in the delivery room (OR, 1.84); CPAP on admission to the neonatal intensive care unit (OR, 1.94); drawing a blood culture (OR, 13.72); and a complete blood count with immature to total neutrophil ratio greater than 0.2 (OR, 3.84).

Three infants (2%) in the antibiotics group had culture-positive early-onset sepsis with Escherichia coli, compared with no infants in the no-antibiotics group. No differences in short-term hospital outcomes appeared between the two groups. The study was limited in part by the retrospective design and sample size, the researchers noted.

However, the results support a selective approach to antibiotics for preterm infants, taking various birth circumstances into account, they said.
 

Further risk factor identification could curb antibiotic use

In this study, empiric antibiotics were cast as a wide net to avoid missing serious infections in a few patients, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.

“It is interesting in this retrospective review of 340 preterm infants that the three newborns that did have serious bacterial infection were correctly given empiric antibiotics from the start,” Dr. Joos noted. “The authors were very effective at elucidating the possible factors that go into starting or not starting empiric antibiotics, although there may be other factors in the clinician’s judgment that are being missed. … More studies are needed on this topic,” Dr. Joos said. “Further research examining how the septic newborns differ from the nonseptic ones could help to even further narrow the use of empiric antibiotics,” he added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.

Selective use of antibiotics based on birth circumstances may reduce unnecessary antibiotic exposure for preterm infants at risk of early-onset sepsis, based on data from 340 preterm infants at a single center.

Preterm infants born because of preterm labor, premature rupture of membranes, and/or intraamniotic infection (IAI) are considered at increased risk for early-onset sepsis, and current management strategies include a blood culture and initiation of empirical antibiotics, said Kirtan Patel, MD, of Texas A&M University, Dallas, and colleagues in a poster (# 1720) presented at the Pediatric Academic Societies annual meeting.

However, this blanket approach “may increase the unnecessary early antibiotic exposure in preterm infants possibly leading to future adverse health outcomes,” and physicians are advised to review the risks and benefits, Dr. Patel said.

Data from previous studies suggest that preterm infants born as a result of preterm labor and/or premature rupture of membranes with adequate Group B Streptococcus (GBS) intrapartum antibiotic prophylaxis and no indication of IAI may be managed without empiric antibiotics because the early-onset sepsis risk in these infants is much lower than the ones born through IAI and inadequate GBS intrapartum antibiotic prophylaxis.

To better identify preterm birth circumstances in which antibiotics might be avoided, the researchers conducted a retrospective cohort study of preterm infants born at 28-34 weeks’ gestation during the period from Jan. 1, 2015, to Dec. 31, 2018. These infants were in the low-risk category of preterm birth because of preterm labor or premature rupture of membranes, with no IAI and adequate GBS intrapartum antibiotic prophylaxis, and no signs of cardiovascular or respiratory instability after birth. Of these, 157 (46.2%) received empiric antibiotics soon after birth and 183 infants (53.8%) did not receive empiric antibiotics.

The mean gestational age and birth weight were significantly lower in the empiric antibiotic group, but after correcting for these variables, the factors with the greatest influence on the initiation of antibiotics were maternal intrapartum antibiotic prophylaxis (odds ratio, 3.13); premature rupture of membranes (OR, 3.75); use of continuous positive airway pressure (CPAP) in the delivery room (OR, 1.84); CPAP on admission to the neonatal intensive care unit (OR, 1.94); drawing a blood culture (OR, 13.72); and a complete blood count with immature to total neutrophil ratio greater than 0.2 (OR, 3.84).

Three infants (2%) in the antibiotics group had culture-positive early-onset sepsis with Escherichia coli, compared with no infants in the no-antibiotics group. No differences in short-term hospital outcomes appeared between the two groups. The study was limited in part by the retrospective design and sample size, the researchers noted.

However, the results support a selective approach to antibiotics for preterm infants, taking various birth circumstances into account, they said.
 

Further risk factor identification could curb antibiotic use

In this study, empiric antibiotics were cast as a wide net to avoid missing serious infections in a few patients, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.

“It is interesting in this retrospective review of 340 preterm infants that the three newborns that did have serious bacterial infection were correctly given empiric antibiotics from the start,” Dr. Joos noted. “The authors were very effective at elucidating the possible factors that go into starting or not starting empiric antibiotics, although there may be other factors in the clinician’s judgment that are being missed. … More studies are needed on this topic,” Dr. Joos said. “Further research examining how the septic newborns differ from the nonseptic ones could help to even further narrow the use of empiric antibiotics,” he added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.

Selective use of antibiotics based on birth circumstances may reduce unnecessary antibiotic exposure for preterm infants at risk of early-onset sepsis, based on data from 340 preterm infants at a single center.

Preterm infants born because of preterm labor, premature rupture of membranes, and/or intraamniotic infection (IAI) are considered at increased risk for early-onset sepsis, and current management strategies include a blood culture and initiation of empirical antibiotics, said Kirtan Patel, MD, of Texas A&M University, Dallas, and colleagues in a poster (# 1720) presented at the Pediatric Academic Societies annual meeting.

However, this blanket approach “may increase the unnecessary early antibiotic exposure in preterm infants possibly leading to future adverse health outcomes,” and physicians are advised to review the risks and benefits, Dr. Patel said.

Data from previous studies suggest that preterm infants born as a result of preterm labor and/or premature rupture of membranes with adequate Group B Streptococcus (GBS) intrapartum antibiotic prophylaxis and no indication of IAI may be managed without empiric antibiotics because the early-onset sepsis risk in these infants is much lower than the ones born through IAI and inadequate GBS intrapartum antibiotic prophylaxis.

To better identify preterm birth circumstances in which antibiotics might be avoided, the researchers conducted a retrospective cohort study of preterm infants born at 28-34 weeks’ gestation during the period from Jan. 1, 2015, to Dec. 31, 2018. These infants were in the low-risk category of preterm birth because of preterm labor or premature rupture of membranes, with no IAI and adequate GBS intrapartum antibiotic prophylaxis, and no signs of cardiovascular or respiratory instability after birth. Of these, 157 (46.2%) received empiric antibiotics soon after birth and 183 infants (53.8%) did not receive empiric antibiotics.

The mean gestational age and birth weight were significantly lower in the empiric antibiotic group, but after correcting for these variables, the factors with the greatest influence on the initiation of antibiotics were maternal intrapartum antibiotic prophylaxis (odds ratio, 3.13); premature rupture of membranes (OR, 3.75); use of continuous positive airway pressure (CPAP) in the delivery room (OR, 1.84); CPAP on admission to the neonatal intensive care unit (OR, 1.94); drawing a blood culture (OR, 13.72); and a complete blood count with immature to total neutrophil ratio greater than 0.2 (OR, 3.84).

Three infants (2%) in the antibiotics group had culture-positive early-onset sepsis with Escherichia coli, compared with no infants in the no-antibiotics group. No differences in short-term hospital outcomes appeared between the two groups. The study was limited in part by the retrospective design and sample size, the researchers noted.

However, the results support a selective approach to antibiotics for preterm infants, taking various birth circumstances into account, they said.
 

Further risk factor identification could curb antibiotic use

In this study, empiric antibiotics were cast as a wide net to avoid missing serious infections in a few patients, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.

“It is interesting in this retrospective review of 340 preterm infants that the three newborns that did have serious bacterial infection were correctly given empiric antibiotics from the start,” Dr. Joos noted. “The authors were very effective at elucidating the possible factors that go into starting or not starting empiric antibiotics, although there may be other factors in the clinician’s judgment that are being missed. … More studies are needed on this topic,” Dr. Joos said. “Further research examining how the septic newborns differ from the nonseptic ones could help to even further narrow the use of empiric antibiotics,” he added.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.

Two experts scoured the medical journals for the practice-changing research most relevant to hospital medicine in 2020 at a recent session at SHM Converge, the annual conference of the Society of Hospital Medicine.

The presenters chose findings they considered either practice changing or practice confirming, and in areas over which hospitalists have at least some control. Here is what they highlighted:
 

IV iron administration before hospital discharge

In a randomized double-blind, placebo-controlled trial across 121 centers in Europe, South America, and Singapore, 1,108 patients hospitalized with acute heart failure and iron deficiency were randomized to receive intravenous ferric carboxymaltose or placebo, with a first dose before discharge and a second at 6 weeks.

Those in the intravenous iron group had a significant reduction in hospitalizations for heart failure up to 52 weeks after randomization, but there was no significant reduction in deaths because of heart failure. There was no difference in serious adverse events.

Anthony Breu, MD, assistant professor of medicine at Harvard Medical School, Boston, said the findings should alter hospitalist practice.

“In patients hospitalized with acute heart failure and left ventricular ejection fraction of less than 50%, check iron studies and start IV iron prior to discharge if they have iron deficiency, with or without anemia,” he said.
 

Apixaban versus dalteparin for venous thromboembolism in cancer

This noninferiority trial involved 1,155 adults with cancer who had symptomatic or incidental acute proximal deep vein thrombosis or pulmonary embolism. The patients were randomized to receive oral apixaban or subcutaneous dalteparin for 6 months.

Patients in the apixaban group had a significantly lower rate of recurrent venous thromboembolism (P = .09), with no increase in major bleeds, Dr. Breu said. He noted that those with brain cancer and leukemia were excluded.

“In patients with cancer and acute venous thromboembolism, consider apixaban as your first-line treatment, with some caveats,” he said.
 

Clinical decision rule for penicillin allergy

With fewer than 10% of patients who report a penicillin allergy actually testing positive on a standard allergy test, a simpler way to predict an allergy would help clinicians, said Shoshana Herzig, MD, MPH, associate professor of medicine at Harvard Medical School.

A 622-patient cohort that had undergone penicillin allergy testing was used to identify factors that could help predict an allergy. A scoring system called PEN-FAST was developed based on five factors – a penicillin allergy reported by the patient, 5 years or less since the last reaction (2 points); anaphylaxis or angioedema, or severe cutaneous adverse reaction (2 points); and treatment being required for the reaction (1 point).

Researchers, after validation at three sites, found that a score below a threshold identified a group that had a 96% negative predictive value for penicillin allergy skin testing.

“A PEN-FAST score of less than 3 can be used to identify patients with reported penicillin allergy who can likely proceed safely to oral challenge,” Dr. Herzig said. She said the findings would benefit from validation in an inpatient setting.
 

Prehydration before contrast-enhanced computed tomography in CKD

Previous studies have found that omitting prehydration was noninferior to volume expansion with isotonic saline, and this trial looked at omission versus sodium bicarbonate hydration.

Participants were 523 adults with stage 3 chronic kidney disease who were getting elective outpatient CT with contrast. They were randomized to either no prehydration or prehydration with 250 mL of 1.4% sodium bicarbonate an hour before CT.

Researchers found that postcontrast acute kidney injury was rare even in this high-risk patient population overall, and that withholding prehydration was noninferior to prehydration with sodium bicarbonate, Dr. Herzig said.
 

Gabapentin for alcohol use disorder in those with alcohol withdrawal symptoms

Dr. Breu noted that only about one in five patients with alcohol use disorder receive medications to help preserve abstinence or to reduce drinking, and many medications target cravings but not symptoms of withdrawal.

In a double-blind, randomized, placebo-controlled trial at a single academic outpatient medical center in South Carolina, 90 patients were randomized to receive titrated gabapentin or placebo for 16 weeks.

Researchers found that, among those with abstinence of at least 2 days, gabapentin reduced the number of days of heavy drinking and the days of any drinking, especially in those with high symptoms of withdrawal.

“In patients with alcohol use disorder and high alcohol withdrawal symptoms, consider gabapentin to help reduce heavy drinking or maintain abstinence,” Dr. Breu said.
 

Hospitalist continuity of care and patient outcomes

In a retrospective study examining all medical admissions of Medicare patients with a 3- to 6-day length of stay, and in which all general medical care was provided by hospitalists, researchers examined the effects of continuity of care. Nearly 115,000 patient stays were included in the study, which covered 229 Texas hospitals.

The stays were grouped into quartiles of continuity of care, based on the number of hospitalists involved in a patient’s stay. Greater continuity was associated with lower 30-day mortality, with a linear relationship between the two. Researchers also found costs to be lower as continuity increased.

“Efforts by hospitals and hospitalist groups to promote working schedules with more continuity,” Dr. Herzig said, “could lead to improved postdischarge outcomes.”


 

Two experts scoured the medical journals for the practice-changing research most relevant to hospital medicine in 2020 at a recent session at SHM Converge, the annual conference of the Society of Hospital Medicine.

The presenters chose findings they considered either practice changing or practice confirming, and in areas over which hospitalists have at least some control. Here is what they highlighted:
 

IV iron administration before hospital discharge

In a randomized double-blind, placebo-controlled trial across 121 centers in Europe, South America, and Singapore, 1,108 patients hospitalized with acute heart failure and iron deficiency were randomized to receive intravenous ferric carboxymaltose or placebo, with a first dose before discharge and a second at 6 weeks.

Those in the intravenous iron group had a significant reduction in hospitalizations for heart failure up to 52 weeks after randomization, but there was no significant reduction in deaths because of heart failure. There was no difference in serious adverse events.

Anthony Breu, MD, assistant professor of medicine at Harvard Medical School, Boston, said the findings should alter hospitalist practice.

“In patients hospitalized with acute heart failure and left ventricular ejection fraction of less than 50%, check iron studies and start IV iron prior to discharge if they have iron deficiency, with or without anemia,” he said.
 

Apixaban versus dalteparin for venous thromboembolism in cancer

This noninferiority trial involved 1,155 adults with cancer who had symptomatic or incidental acute proximal deep vein thrombosis or pulmonary embolism. The patients were randomized to receive oral apixaban or subcutaneous dalteparin for 6 months.

Patients in the apixaban group had a significantly lower rate of recurrent venous thromboembolism (P = .09), with no increase in major bleeds, Dr. Breu said. He noted that those with brain cancer and leukemia were excluded.

“In patients with cancer and acute venous thromboembolism, consider apixaban as your first-line treatment, with some caveats,” he said.
 

Clinical decision rule for penicillin allergy

With fewer than 10% of patients who report a penicillin allergy actually testing positive on a standard allergy test, a simpler way to predict an allergy would help clinicians, said Shoshana Herzig, MD, MPH, associate professor of medicine at Harvard Medical School.

A 622-patient cohort that had undergone penicillin allergy testing was used to identify factors that could help predict an allergy. A scoring system called PEN-FAST was developed based on five factors – a penicillin allergy reported by the patient, 5 years or less since the last reaction (2 points); anaphylaxis or angioedema, or severe cutaneous adverse reaction (2 points); and treatment being required for the reaction (1 point).

Researchers, after validation at three sites, found that a score below a threshold identified a group that had a 96% negative predictive value for penicillin allergy skin testing.

“A PEN-FAST score of less than 3 can be used to identify patients with reported penicillin allergy who can likely proceed safely to oral challenge,” Dr. Herzig said. She said the findings would benefit from validation in an inpatient setting.
 

Prehydration before contrast-enhanced computed tomography in CKD

Previous studies have found that omitting prehydration was noninferior to volume expansion with isotonic saline, and this trial looked at omission versus sodium bicarbonate hydration.

Participants were 523 adults with stage 3 chronic kidney disease who were getting elective outpatient CT with contrast. They were randomized to either no prehydration or prehydration with 250 mL of 1.4% sodium bicarbonate an hour before CT.

Researchers found that postcontrast acute kidney injury was rare even in this high-risk patient population overall, and that withholding prehydration was noninferior to prehydration with sodium bicarbonate, Dr. Herzig said.
 

Gabapentin for alcohol use disorder in those with alcohol withdrawal symptoms

Dr. Breu noted that only about one in five patients with alcohol use disorder receive medications to help preserve abstinence or to reduce drinking, and many medications target cravings but not symptoms of withdrawal.

In a double-blind, randomized, placebo-controlled trial at a single academic outpatient medical center in South Carolina, 90 patients were randomized to receive titrated gabapentin or placebo for 16 weeks.

Researchers found that, among those with abstinence of at least 2 days, gabapentin reduced the number of days of heavy drinking and the days of any drinking, especially in those with high symptoms of withdrawal.

“In patients with alcohol use disorder and high alcohol withdrawal symptoms, consider gabapentin to help reduce heavy drinking or maintain abstinence,” Dr. Breu said.
 

Hospitalist continuity of care and patient outcomes

In a retrospective study examining all medical admissions of Medicare patients with a 3- to 6-day length of stay, and in which all general medical care was provided by hospitalists, researchers examined the effects of continuity of care. Nearly 115,000 patient stays were included in the study, which covered 229 Texas hospitals.

The stays were grouped into quartiles of continuity of care, based on the number of hospitalists involved in a patient’s stay. Greater continuity was associated with lower 30-day mortality, with a linear relationship between the two. Researchers also found costs to be lower as continuity increased.

“Efforts by hospitals and hospitalist groups to promote working schedules with more continuity,” Dr. Herzig said, “could lead to improved postdischarge outcomes.”


 

Two experts scoured the medical journals for the practice-changing research most relevant to hospital medicine in 2020 at a recent session at SHM Converge, the annual conference of the Society of Hospital Medicine.

The presenters chose findings they considered either practice changing or practice confirming, and in areas over which hospitalists have at least some control. Here is what they highlighted:
 

IV iron administration before hospital discharge

In a randomized double-blind, placebo-controlled trial across 121 centers in Europe, South America, and Singapore, 1,108 patients hospitalized with acute heart failure and iron deficiency were randomized to receive intravenous ferric carboxymaltose or placebo, with a first dose before discharge and a second at 6 weeks.

Those in the intravenous iron group had a significant reduction in hospitalizations for heart failure up to 52 weeks after randomization, but there was no significant reduction in deaths because of heart failure. There was no difference in serious adverse events.

Anthony Breu, MD, assistant professor of medicine at Harvard Medical School, Boston, said the findings should alter hospitalist practice.

“In patients hospitalized with acute heart failure and left ventricular ejection fraction of less than 50%, check iron studies and start IV iron prior to discharge if they have iron deficiency, with or without anemia,” he said.
 

Apixaban versus dalteparin for venous thromboembolism in cancer

This noninferiority trial involved 1,155 adults with cancer who had symptomatic or incidental acute proximal deep vein thrombosis or pulmonary embolism. The patients were randomized to receive oral apixaban or subcutaneous dalteparin for 6 months.

Patients in the apixaban group had a significantly lower rate of recurrent venous thromboembolism (P = .09), with no increase in major bleeds, Dr. Breu said. He noted that those with brain cancer and leukemia were excluded.

“In patients with cancer and acute venous thromboembolism, consider apixaban as your first-line treatment, with some caveats,” he said.
 

Clinical decision rule for penicillin allergy

With fewer than 10% of patients who report a penicillin allergy actually testing positive on a standard allergy test, a simpler way to predict an allergy would help clinicians, said Shoshana Herzig, MD, MPH, associate professor of medicine at Harvard Medical School.

A 622-patient cohort that had undergone penicillin allergy testing was used to identify factors that could help predict an allergy. A scoring system called PEN-FAST was developed based on five factors – a penicillin allergy reported by the patient, 5 years or less since the last reaction (2 points); anaphylaxis or angioedema, or severe cutaneous adverse reaction (2 points); and treatment being required for the reaction (1 point).

Researchers, after validation at three sites, found that a score below a threshold identified a group that had a 96% negative predictive value for penicillin allergy skin testing.

“A PEN-FAST score of less than 3 can be used to identify patients with reported penicillin allergy who can likely proceed safely to oral challenge,” Dr. Herzig said. She said the findings would benefit from validation in an inpatient setting.
 

Prehydration before contrast-enhanced computed tomography in CKD

Previous studies have found that omitting prehydration was noninferior to volume expansion with isotonic saline, and this trial looked at omission versus sodium bicarbonate hydration.

Participants were 523 adults with stage 3 chronic kidney disease who were getting elective outpatient CT with contrast. They were randomized to either no prehydration or prehydration with 250 mL of 1.4% sodium bicarbonate an hour before CT.

Researchers found that postcontrast acute kidney injury was rare even in this high-risk patient population overall, and that withholding prehydration was noninferior to prehydration with sodium bicarbonate, Dr. Herzig said.
 

Gabapentin for alcohol use disorder in those with alcohol withdrawal symptoms

Dr. Breu noted that only about one in five patients with alcohol use disorder receive medications to help preserve abstinence or to reduce drinking, and many medications target cravings but not symptoms of withdrawal.

In a double-blind, randomized, placebo-controlled trial at a single academic outpatient medical center in South Carolina, 90 patients were randomized to receive titrated gabapentin or placebo for 16 weeks.

Researchers found that, among those with abstinence of at least 2 days, gabapentin reduced the number of days of heavy drinking and the days of any drinking, especially in those with high symptoms of withdrawal.

“In patients with alcohol use disorder and high alcohol withdrawal symptoms, consider gabapentin to help reduce heavy drinking or maintain abstinence,” Dr. Breu said.
 

Hospitalist continuity of care and patient outcomes

In a retrospective study examining all medical admissions of Medicare patients with a 3- to 6-day length of stay, and in which all general medical care was provided by hospitalists, researchers examined the effects of continuity of care. Nearly 115,000 patient stays were included in the study, which covered 229 Texas hospitals.

The stays were grouped into quartiles of continuity of care, based on the number of hospitalists involved in a patient’s stay. Greater continuity was associated with lower 30-day mortality, with a linear relationship between the two. Researchers also found costs to be lower as continuity increased.

“Efforts by hospitals and hospitalist groups to promote working schedules with more continuity,” Dr. Herzig said, “could lead to improved postdischarge outcomes.”


 

My first thought on this column was maybe Pediatric News has written sufficiently about SARS-CoV-2 infection, and it is time to move on. However, the agenda for the May 12th Advisory Committee on Immunization Practice includes a review of the Pfizer-BioNTech COVID-19 vaccine safety and immunogenicity data for the 12- to 15-year-old age cohort that suggests the potential for vaccine availability and roll out for early adolescents in the near future and the need for up-to-date knowledge about the incidence, severity, and long-term outcome of COVID-19 in the pediatric population.

Updating and summarizing the pediatric experience for the pediatric community on what children and adolescents have experienced because of SARS-CoV-2 infection is critical to address the myriad of questions that will come from colleagues, parents, and adolescents themselves. A great resource, published weekly, is the joint report from the American Academy of Pediatrics and the Children’s Hospital Association.¹ As of April 29, 2021, 3,782,724 total child COVID-19 cases have been reported from 49 states, New York City (NYC), the District of Columbia, Guam, and Puerto Rico. Children represent approximately 14% of cases in the United States and not surprisingly are an increasing proportion of total cases as vaccine impact reduces cases among older age groups. Nearly 5% of the pediatric population has already been infected with SARS-CoV-2. Fortunately, compared with adults, hospitalization, severe disease, and mortality remain far lower both in number and proportion than in the adult population. Cumulative hospitalizations from 24 states and NYC total 15,456 (0.8%) among those infected, with 303 deaths reported (from 43 states, NYC, Guam, and Puerto Rico). Case fatality rate approximates 0.01% in the most recent summary of state reports. One of the limitations of this report is that each state decides how to report the age distribution of COVID-19 cases resulting in variation in age range; another is the data are limited to those details individual states chose to make publicly available.

Although children do not commonly develop severe disease, and the case fatality is low, there are still insights to be learned from understanding risk features for severe disease. Preston et al. reviewed discharge data from 869 medical facilities to describe patients 18 years or younger who had an inpatient or emergency department encounter with a primary or secondary COVID-19 discharge diagnosis from March 1 through October 31, 2020.² They reported that approximately 2,430 (11.7%) children were hospitalized and 746, nearly 31% of those hospitalized, had severe COVID disease. Those at greatest risk for severe disease were children with comorbid conditions and those less than 12 years, compared with the 12- to 18-year age group. They did not identify race as a risk for severe disease in this study. Moreira et al. described risk factors for morbidity and death from COVID in children less than 18 years of age³ using CDC COVID-NET, the Centers for Disease Control and Prevention COVID-19–associated hospitalization surveillance network. They reported a hospitalization rate of 4.7% among 27,045 cases. They identified three risk factors for hospitalization – age, race/ethnicity, and comorbid conditions. Thirty-nine children (0.19%) died; children who were black, non-Hispanic, and those with an underlying medical condition had a significantly increased risk of death. Thirty-three (85%) children who died had a comorbidity, and 27 (69%) were African American or Hispanic/Latino. The U.S. experience in children is also consistent with reports from the United Kingdom, Italy, Spain, Germany, France, and South Korea.⁴ Deaths from COVID-19 were uncommon but relatively more frequent in older children, compared with younger age groups among children less than 18 years of age in these countries.

Acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) do not predominantly target the neurologic systems; however, neurologic complications have been reported, some of which appear to result in long-lasting disability. LaRovere et al. identified 354 (22%) of 1,695 patients less than 21 years of age with acute COVID or MIS-C who had neurologic signs or symptoms during their illness. Among those with neurologic involvement, most children had prior neurologic deficits, mild symptoms, that resolved by the time of discharge. Forty-three (12%) were considered life threatening and included severe encephalopathy, stroke, central nervous system infection/demyelination, Guillain-Barre syndrome or variant, or acute cerebral edema. Several children, including some who were previously healthy prior to COVID, had persistent neurologic deficits at discharge. In addition to neurologic morbidity, long COVID – a syndrome of persistent symptoms following acute COVID that lasts for more than 12 weeks without alternative diagnosis – has also been described in children. Buonsenso et al. assessed 129 children diagnosed with COVID-19 between March and November 2020 in Rome, Italy.⁵ Persisting symptoms after 120 days were reported by more than 50%. Symptoms like fatigue, muscle and joint pain, headache, insomnia, respiratory problems, and palpitations were most common. Clearly, further follow-up of the long-term outcomes is necessary to understand the full spectrum of morbidity resulting from COVID-19 disease in children and its natural history.

The current picture of COVID infection in children younger than 18 reinforces that children are part of the pandemic. Although deaths in children have now exceeded 300 cases, severe disease remains uncommon in both the United States and western Europe. Risk factors for severe disease include comorbid illness and race/ethnicity with a disproportionate number of severe cases in children with underlying comorbidity and in African American and Hispanic/Latino children. Ongoing surveillance is critical as changes are likely to be observed over time as viral evolution affects disease burden and characteristics.
 

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Children and COVID-19: State-Level Data Report. Services AAP.org.

2. Preston LE et al. JAMA Network Open. 2021;4(4):e215298. doi:10.1001/jamanetworkopen.2021.5298

3. Moreira A et al. Eur J Pediatr. 2021;180:1659-63.

4. SS Bhopal et al. Lancet 2021. doi: 10.1016/ S2352-4642(21)00066-3.

5. Buonsenso D et al. medRxiv preprint. doi: 10.1101/2021.01.23.21250375.

My first thought on this column was maybe Pediatric News has written sufficiently about SARS-CoV-2 infection, and it is time to move on. However, the agenda for the May 12th Advisory Committee on Immunization Practice includes a review of the Pfizer-BioNTech COVID-19 vaccine safety and immunogenicity data for the 12- to 15-year-old age cohort that suggests the potential for vaccine availability and roll out for early adolescents in the near future and the need for up-to-date knowledge about the incidence, severity, and long-term outcome of COVID-19 in the pediatric population.

Updating and summarizing the pediatric experience for the pediatric community on what children and adolescents have experienced because of SARS-CoV-2 infection is critical to address the myriad of questions that will come from colleagues, parents, and adolescents themselves. A great resource, published weekly, is the joint report from the American Academy of Pediatrics and the Children’s Hospital Association.¹ As of April 29, 2021, 3,782,724 total child COVID-19 cases have been reported from 49 states, New York City (NYC), the District of Columbia, Guam, and Puerto Rico. Children represent approximately 14% of cases in the United States and not surprisingly are an increasing proportion of total cases as vaccine impact reduces cases among older age groups. Nearly 5% of the pediatric population has already been infected with SARS-CoV-2. Fortunately, compared with adults, hospitalization, severe disease, and mortality remain far lower both in number and proportion than in the adult population. Cumulative hospitalizations from 24 states and NYC total 15,456 (0.8%) among those infected, with 303 deaths reported (from 43 states, NYC, Guam, and Puerto Rico). Case fatality rate approximates 0.01% in the most recent summary of state reports. One of the limitations of this report is that each state decides how to report the age distribution of COVID-19 cases resulting in variation in age range; another is the data are limited to those details individual states chose to make publicly available.

Although children do not commonly develop severe disease, and the case fatality is low, there are still insights to be learned from understanding risk features for severe disease. Preston et al. reviewed discharge data from 869 medical facilities to describe patients 18 years or younger who had an inpatient or emergency department encounter with a primary or secondary COVID-19 discharge diagnosis from March 1 through October 31, 2020.² They reported that approximately 2,430 (11.7%) children were hospitalized and 746, nearly 31% of those hospitalized, had severe COVID disease. Those at greatest risk for severe disease were children with comorbid conditions and those less than 12 years, compared with the 12- to 18-year age group. They did not identify race as a risk for severe disease in this study. Moreira et al. described risk factors for morbidity and death from COVID in children less than 18 years of age³ using CDC COVID-NET, the Centers for Disease Control and Prevention COVID-19–associated hospitalization surveillance network. They reported a hospitalization rate of 4.7% among 27,045 cases. They identified three risk factors for hospitalization – age, race/ethnicity, and comorbid conditions. Thirty-nine children (0.19%) died; children who were black, non-Hispanic, and those with an underlying medical condition had a significantly increased risk of death. Thirty-three (85%) children who died had a comorbidity, and 27 (69%) were African American or Hispanic/Latino. The U.S. experience in children is also consistent with reports from the United Kingdom, Italy, Spain, Germany, France, and South Korea.⁴ Deaths from COVID-19 were uncommon but relatively more frequent in older children, compared with younger age groups among children less than 18 years of age in these countries.

Acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) do not predominantly target the neurologic systems; however, neurologic complications have been reported, some of which appear to result in long-lasting disability. LaRovere et al. identified 354 (22%) of 1,695 patients less than 21 years of age with acute COVID or MIS-C who had neurologic signs or symptoms during their illness. Among those with neurologic involvement, most children had prior neurologic deficits, mild symptoms, that resolved by the time of discharge. Forty-three (12%) were considered life threatening and included severe encephalopathy, stroke, central nervous system infection/demyelination, Guillain-Barre syndrome or variant, or acute cerebral edema. Several children, including some who were previously healthy prior to COVID, had persistent neurologic deficits at discharge. In addition to neurologic morbidity, long COVID – a syndrome of persistent symptoms following acute COVID that lasts for more than 12 weeks without alternative diagnosis – has also been described in children. Buonsenso et al. assessed 129 children diagnosed with COVID-19 between March and November 2020 in Rome, Italy.⁵ Persisting symptoms after 120 days were reported by more than 50%. Symptoms like fatigue, muscle and joint pain, headache, insomnia, respiratory problems, and palpitations were most common. Clearly, further follow-up of the long-term outcomes is necessary to understand the full spectrum of morbidity resulting from COVID-19 disease in children and its natural history.

The current picture of COVID infection in children younger than 18 reinforces that children are part of the pandemic. Although deaths in children have now exceeded 300 cases, severe disease remains uncommon in both the United States and western Europe. Risk factors for severe disease include comorbid illness and race/ethnicity with a disproportionate number of severe cases in children with underlying comorbidity and in African American and Hispanic/Latino children. Ongoing surveillance is critical as changes are likely to be observed over time as viral evolution affects disease burden and characteristics.
 

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Children and COVID-19: State-Level Data Report. Services AAP.org.

2. Preston LE et al. JAMA Network Open. 2021;4(4):e215298. doi:10.1001/jamanetworkopen.2021.5298

3. Moreira A et al. Eur J Pediatr. 2021;180:1659-63.

4. SS Bhopal et al. Lancet 2021. doi: 10.1016/ S2352-4642(21)00066-3.

5. Buonsenso D et al. medRxiv preprint. doi: 10.1101/2021.01.23.21250375.

My first thought on this column was maybe Pediatric News has written sufficiently about SARS-CoV-2 infection, and it is time to move on. However, the agenda for the May 12th Advisory Committee on Immunization Practice includes a review of the Pfizer-BioNTech COVID-19 vaccine safety and immunogenicity data for the 12- to 15-year-old age cohort that suggests the potential for vaccine availability and roll out for early adolescents in the near future and the need for up-to-date knowledge about the incidence, severity, and long-term outcome of COVID-19 in the pediatric population.

Updating and summarizing the pediatric experience for the pediatric community on what children and adolescents have experienced because of SARS-CoV-2 infection is critical to address the myriad of questions that will come from colleagues, parents, and adolescents themselves. A great resource, published weekly, is the joint report from the American Academy of Pediatrics and the Children’s Hospital Association.¹ As of April 29, 2021, 3,782,724 total child COVID-19 cases have been reported from 49 states, New York City (NYC), the District of Columbia, Guam, and Puerto Rico. Children represent approximately 14% of cases in the United States and not surprisingly are an increasing proportion of total cases as vaccine impact reduces cases among older age groups. Nearly 5% of the pediatric population has already been infected with SARS-CoV-2. Fortunately, compared with adults, hospitalization, severe disease, and mortality remain far lower both in number and proportion than in the adult population. Cumulative hospitalizations from 24 states and NYC total 15,456 (0.8%) among those infected, with 303 deaths reported (from 43 states, NYC, Guam, and Puerto Rico). Case fatality rate approximates 0.01% in the most recent summary of state reports. One of the limitations of this report is that each state decides how to report the age distribution of COVID-19 cases resulting in variation in age range; another is the data are limited to those details individual states chose to make publicly available.

Although children do not commonly develop severe disease, and the case fatality is low, there are still insights to be learned from understanding risk features for severe disease. Preston et al. reviewed discharge data from 869 medical facilities to describe patients 18 years or younger who had an inpatient or emergency department encounter with a primary or secondary COVID-19 discharge diagnosis from March 1 through October 31, 2020.² They reported that approximately 2,430 (11.7%) children were hospitalized and 746, nearly 31% of those hospitalized, had severe COVID disease. Those at greatest risk for severe disease were children with comorbid conditions and those less than 12 years, compared with the 12- to 18-year age group. They did not identify race as a risk for severe disease in this study. Moreira et al. described risk factors for morbidity and death from COVID in children less than 18 years of age³ using CDC COVID-NET, the Centers for Disease Control and Prevention COVID-19–associated hospitalization surveillance network. They reported a hospitalization rate of 4.7% among 27,045 cases. They identified three risk factors for hospitalization – age, race/ethnicity, and comorbid conditions. Thirty-nine children (0.19%) died; children who were black, non-Hispanic, and those with an underlying medical condition had a significantly increased risk of death. Thirty-three (85%) children who died had a comorbidity, and 27 (69%) were African American or Hispanic/Latino. The U.S. experience in children is also consistent with reports from the United Kingdom, Italy, Spain, Germany, France, and South Korea.⁴ Deaths from COVID-19 were uncommon but relatively more frequent in older children, compared with younger age groups among children less than 18 years of age in these countries.

Acute COVID-19 and multisystem inflammatory syndrome in children (MIS-C) do not predominantly target the neurologic systems; however, neurologic complications have been reported, some of which appear to result in long-lasting disability. LaRovere et al. identified 354 (22%) of 1,695 patients less than 21 years of age with acute COVID or MIS-C who had neurologic signs or symptoms during their illness. Among those with neurologic involvement, most children had prior neurologic deficits, mild symptoms, that resolved by the time of discharge. Forty-three (12%) were considered life threatening and included severe encephalopathy, stroke, central nervous system infection/demyelination, Guillain-Barre syndrome or variant, or acute cerebral edema. Several children, including some who were previously healthy prior to COVID, had persistent neurologic deficits at discharge. In addition to neurologic morbidity, long COVID – a syndrome of persistent symptoms following acute COVID that lasts for more than 12 weeks without alternative diagnosis – has also been described in children. Buonsenso et al. assessed 129 children diagnosed with COVID-19 between March and November 2020 in Rome, Italy.⁵ Persisting symptoms after 120 days were reported by more than 50%. Symptoms like fatigue, muscle and joint pain, headache, insomnia, respiratory problems, and palpitations were most common. Clearly, further follow-up of the long-term outcomes is necessary to understand the full spectrum of morbidity resulting from COVID-19 disease in children and its natural history.

The current picture of COVID infection in children younger than 18 reinforces that children are part of the pandemic. Although deaths in children have now exceeded 300 cases, severe disease remains uncommon in both the United States and western Europe. Risk factors for severe disease include comorbid illness and race/ethnicity with a disproportionate number of severe cases in children with underlying comorbidity and in African American and Hispanic/Latino children. Ongoing surveillance is critical as changes are likely to be observed over time as viral evolution affects disease burden and characteristics.
 

Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and senior attending physician in pediatric infectious diseases, Boston Medical Center. Email him at [email protected].

References

1. Children and COVID-19: State-Level Data Report. Services AAP.org.

2. Preston LE et al. JAMA Network Open. 2021;4(4):e215298. doi:10.1001/jamanetworkopen.2021.5298

3. Moreira A et al. Eur J Pediatr. 2021;180:1659-63.

4. SS Bhopal et al. Lancet 2021. doi: 10.1016/ S2352-4642(21)00066-3.

5. Buonsenso D et al. medRxiv preprint. doi: 10.1101/2021.01.23.21250375.

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

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

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

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

People who are fully vaccinated against COVID-19 are no longer required to wear masks or physically distance, regardless of location or size of the gathering, the CDC announced on May 13.

“Anyone who is fully vaccinated can participate in indoor and outdoor activities, large or small, without wearing a mask or physically distancing,” CDC director Rochelle Walensky, MD, said at a press briefing. “We have all longed for this moment when we can get back to some sense of normalcy.

“This is an exciting and powerful moment,” she added, “It could only happen because of the work from so many who made sure we had the rapid administration of three safe and effective vaccines.”

Dr. Walensky cited three large studies on the effectiveness of COVID-19 vaccines against the original virus and its variants. One study from Israel found the vaccine to be 97% effective against symptomatic infection.

Those who are symptomatic should still wear masks, Dr. Walensky said, and those who are immunocompromised should talk to their doctors for further guidance. The CDC still advises travelers to wear masks while on airplanes or trains.

The COVID-19 death rates are now the lowest they have been since April 2020.

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

The history of a brownish to pink patch with color change and rapid growth within the first year combined with the exam findings, are suggestive of a tufted angioma, though the findings presented may be nonspecific.

A tufted angioma is a rare vascular tumor of infancy or early childhood, that is present at birth in approximately half of cases. It may initially present as a faint pink to brown plaque, but develops as a firm, red to violaceous nodule or plaque, usually with “lumpiness” or nodularity.^1-3 Lesions usually are infiltrative with indistinct borders. They are named for their histologic appearance, with lobules of capillaries which appear as “tufts” in the dermis and subdermis with “cannonball” appearance, and are considered to be on a spectrum with another vascular tumor called kaposiform hemangioendothelioma (KHE).⁴ These vascular tumors can trigger Kasabach-Merritt syndrome, a disease process in which vascular tumors trap platelets and clotting factors, resulting in a life-threatening thrombocytopenia and consumptive coagulopathy with a high risk of bleeding and high-output heart failure.⁵
 

What’s the differential diagnosis?

The differential diagnosis of tufted angioma includes other potentially large vascular lesions including infantile hemangioma, congenital hemangioma, port-wine birth marks (capillary malformations), hemangioendotheliomas, and rhabdomyosarcomas.

Infantile hemangiomas (IH) are common vascular tumors of infancy seen in 4%-5% of infants that are characterized by a growth and involution phase. Classically, lesions can be absent or minimally evident at birth, becoming noticeable within the first months of life with a rapid growth phase and typical progression to bright red papules, nodules, or plaques. Deeper hemangiomas may appear more skin colored on the surface with a bluish coloration underneath. They are usually more discreet, with relatively defined borders. Diagnosis is typically clinical and many IHs self-resolve, albeit with residual findings including skin atrophy, scarring, and telangiectasia. Observation or topical timolol are first-line treatment options for more superficial lesions while systemic propranolol is the treatment of choice for deeper IHs or those resulting in possible airway or vision compromise.

Congenital hemangiomas (CH) are another type of vascular growth characterized by a solitary erythematous to violaceous plaque or nodule present at birth with overlying telangiectasia. CHs can be subdivided into categories including rapidly involuting (RICH), partially involuting (PICH), and noninvoluting (NICH). Diagnosis is usually clinical and, depending on the subtype, treatment can involve watchful waiting (for RICHs) or more active intervention such as pulse dye laser or surgical resection (for PICHs or NICHs). The growing nature of this patient’s mass makes a diagnosis of CH unlikely.

Port-wine birth mark, also known as nevus flammeus, is a vascular malformation that appears at birth as a nonpalpable irregular erythematous to violaceous macular plaque. Port-wine stains may be isolated birthmarks, or associated with Sturge-Weber syndrome, complex vascular malformations, or soft-tissue overgrowth. Klippel-Trenauny syndrome (KTS) describes capillary-venous malformations with limb overgrowth, with or without lymphatic malformations, and many are associated with somatic mutations in the PIK3CA gene. While KTS could be considered in this patient, the nodular appearance with lumpy texture and rapid growth makes a vascular tumor more likely.

Rhabdomyosarcoma is a malignancy of skeletal muscle lineage and the most common soft tissue tumor in pediatrics. Cutaneous rhabdomyosarcomas present as erythematous nodules, markedly firm, often “fixed” to deep tissue. A rapidly growing atypical, firm tumor of infancy should raise the consideration of rhabdomyosarcoma and imaging and biopsy are appropriate for evaluation.
 

What should the evaluation and management of this patient be?

Initial workup should include a complete blood count with platelet count as well as coagulation studies including D-dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time, to assess for any thrombocytopenia or coagulopathy.⁶ Ultrasound and/or MRI may also be performed to determine lesion extent. While typical MRI findings might be suggestive of a tufted angioma or hemangioendothelioma, biopsy for histologic examination is usually the approach to diagnosis, which will demonstrate stereotypic round lobules of capillaries in a “tufted” distribution.^2,7 Biopsy may be performed by a surgeon or dermatologist but bleeding at time of biopsy needs to be considered before moving forward with the procedure.

Tufted angiomas of early life may regress spontaneously, though lesions with symptoms, with functional significance, or associated with KHE may require therapy. Surgical excision is one option, but it may be difficult to execute given that these lesions often have poorly defined margins.¹ Other treatment choices include but are not limited to aspirin, systemic corticosteroids, vincristine, interferon-alpha, embolization, and sirolimus.⁸ No specific expert-directed consensus guidelines exist for these lesions, and suspicion of this lesion should prompt urgent referral to a pediatric dermatologist. Concern for Kasabach-Merritt syndrome should trigger immediate referral for rapid evaluation and management.

Complete blood count with platelet count and coagulation studies were normal in our patient. This infant underwent biopsy to confirm the diagnosis of tufted angioma and MRI to determine lesion extent. The lesion slowly involuted spontaneously without recurrence.
 

Mr. Haft is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. He is MS4 at the University of Rochester, N.Y. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Mr. Haft nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Herron MD et al. Pediatr Dermatol. 2002;19(5):394-401.

2. Jones EW and Orkin M. J Am Acad Dermatol. 1989;20(2 Pt 1):214-25.

3. Wong SN and Tay YK. Pediatr Dermatol. 2002;19(5):388-93.

4. Croteau SE and Gupta D. Semin Cutan Med Surg. 2016;35(3):147-52.

5. Kelly M. Pediatr Clin North Am. 2010;57(5):1085-9.

6. Osio A et al. Arch Dermatol. 2010;146(7):758-63.

7. Padilla RS et al. Am J Dermatopathol. 1987;9(4):292-300.

8. Liu XH et al. Int J Cancer. 2016;139(7):1658-66.

The history of a brownish to pink patch with color change and rapid growth within the first year combined with the exam findings, are suggestive of a tufted angioma, though the findings presented may be nonspecific.

A tufted angioma is a rare vascular tumor of infancy or early childhood, that is present at birth in approximately half of cases. It may initially present as a faint pink to brown plaque, but develops as a firm, red to violaceous nodule or plaque, usually with “lumpiness” or nodularity.^1-3 Lesions usually are infiltrative with indistinct borders. They are named for their histologic appearance, with lobules of capillaries which appear as “tufts” in the dermis and subdermis with “cannonball” appearance, and are considered to be on a spectrum with another vascular tumor called kaposiform hemangioendothelioma (KHE).⁴ These vascular tumors can trigger Kasabach-Merritt syndrome, a disease process in which vascular tumors trap platelets and clotting factors, resulting in a life-threatening thrombocytopenia and consumptive coagulopathy with a high risk of bleeding and high-output heart failure.⁵
 

What’s the differential diagnosis?

The differential diagnosis of tufted angioma includes other potentially large vascular lesions including infantile hemangioma, congenital hemangioma, port-wine birth marks (capillary malformations), hemangioendotheliomas, and rhabdomyosarcomas.

Infantile hemangiomas (IH) are common vascular tumors of infancy seen in 4%-5% of infants that are characterized by a growth and involution phase. Classically, lesions can be absent or minimally evident at birth, becoming noticeable within the first months of life with a rapid growth phase and typical progression to bright red papules, nodules, or plaques. Deeper hemangiomas may appear more skin colored on the surface with a bluish coloration underneath. They are usually more discreet, with relatively defined borders. Diagnosis is typically clinical and many IHs self-resolve, albeit with residual findings including skin atrophy, scarring, and telangiectasia. Observation or topical timolol are first-line treatment options for more superficial lesions while systemic propranolol is the treatment of choice for deeper IHs or those resulting in possible airway or vision compromise.

Congenital hemangiomas (CH) are another type of vascular growth characterized by a solitary erythematous to violaceous plaque or nodule present at birth with overlying telangiectasia. CHs can be subdivided into categories including rapidly involuting (RICH), partially involuting (PICH), and noninvoluting (NICH). Diagnosis is usually clinical and, depending on the subtype, treatment can involve watchful waiting (for RICHs) or more active intervention such as pulse dye laser or surgical resection (for PICHs or NICHs). The growing nature of this patient’s mass makes a diagnosis of CH unlikely.

Port-wine birth mark, also known as nevus flammeus, is a vascular malformation that appears at birth as a nonpalpable irregular erythematous to violaceous macular plaque. Port-wine stains may be isolated birthmarks, or associated with Sturge-Weber syndrome, complex vascular malformations, or soft-tissue overgrowth. Klippel-Trenauny syndrome (KTS) describes capillary-venous malformations with limb overgrowth, with or without lymphatic malformations, and many are associated with somatic mutations in the PIK3CA gene. While KTS could be considered in this patient, the nodular appearance with lumpy texture and rapid growth makes a vascular tumor more likely.

Rhabdomyosarcoma is a malignancy of skeletal muscle lineage and the most common soft tissue tumor in pediatrics. Cutaneous rhabdomyosarcomas present as erythematous nodules, markedly firm, often “fixed” to deep tissue. A rapidly growing atypical, firm tumor of infancy should raise the consideration of rhabdomyosarcoma and imaging and biopsy are appropriate for evaluation.
 

What should the evaluation and management of this patient be?

Initial workup should include a complete blood count with platelet count as well as coagulation studies including D-dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time, to assess for any thrombocytopenia or coagulopathy.⁶ Ultrasound and/or MRI may also be performed to determine lesion extent. While typical MRI findings might be suggestive of a tufted angioma or hemangioendothelioma, biopsy for histologic examination is usually the approach to diagnosis, which will demonstrate stereotypic round lobules of capillaries in a “tufted” distribution.^2,7 Biopsy may be performed by a surgeon or dermatologist but bleeding at time of biopsy needs to be considered before moving forward with the procedure.

Tufted angiomas of early life may regress spontaneously, though lesions with symptoms, with functional significance, or associated with KHE may require therapy. Surgical excision is one option, but it may be difficult to execute given that these lesions often have poorly defined margins.¹ Other treatment choices include but are not limited to aspirin, systemic corticosteroids, vincristine, interferon-alpha, embolization, and sirolimus.⁸ No specific expert-directed consensus guidelines exist for these lesions, and suspicion of this lesion should prompt urgent referral to a pediatric dermatologist. Concern for Kasabach-Merritt syndrome should trigger immediate referral for rapid evaluation and management.

Complete blood count with platelet count and coagulation studies were normal in our patient. This infant underwent biopsy to confirm the diagnosis of tufted angioma and MRI to determine lesion extent. The lesion slowly involuted spontaneously without recurrence.
 

Mr. Haft is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. He is MS4 at the University of Rochester, N.Y. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Mr. Haft nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Herron MD et al. Pediatr Dermatol. 2002;19(5):394-401.

2. Jones EW and Orkin M. J Am Acad Dermatol. 1989;20(2 Pt 1):214-25.

3. Wong SN and Tay YK. Pediatr Dermatol. 2002;19(5):388-93.

4. Croteau SE and Gupta D. Semin Cutan Med Surg. 2016;35(3):147-52.

5. Kelly M. Pediatr Clin North Am. 2010;57(5):1085-9.

6. Osio A et al. Arch Dermatol. 2010;146(7):758-63.

7. Padilla RS et al. Am J Dermatopathol. 1987;9(4):292-300.

8. Liu XH et al. Int J Cancer. 2016;139(7):1658-66.

The history of a brownish to pink patch with color change and rapid growth within the first year combined with the exam findings, are suggestive of a tufted angioma, though the findings presented may be nonspecific.

A tufted angioma is a rare vascular tumor of infancy or early childhood, that is present at birth in approximately half of cases. It may initially present as a faint pink to brown plaque, but develops as a firm, red to violaceous nodule or plaque, usually with “lumpiness” or nodularity.^1-3 Lesions usually are infiltrative with indistinct borders. They are named for their histologic appearance, with lobules of capillaries which appear as “tufts” in the dermis and subdermis with “cannonball” appearance, and are considered to be on a spectrum with another vascular tumor called kaposiform hemangioendothelioma (KHE).⁴ These vascular tumors can trigger Kasabach-Merritt syndrome, a disease process in which vascular tumors trap platelets and clotting factors, resulting in a life-threatening thrombocytopenia and consumptive coagulopathy with a high risk of bleeding and high-output heart failure.⁵
 

What’s the differential diagnosis?

The differential diagnosis of tufted angioma includes other potentially large vascular lesions including infantile hemangioma, congenital hemangioma, port-wine birth marks (capillary malformations), hemangioendotheliomas, and rhabdomyosarcomas.

Infantile hemangiomas (IH) are common vascular tumors of infancy seen in 4%-5% of infants that are characterized by a growth and involution phase. Classically, lesions can be absent or minimally evident at birth, becoming noticeable within the first months of life with a rapid growth phase and typical progression to bright red papules, nodules, or plaques. Deeper hemangiomas may appear more skin colored on the surface with a bluish coloration underneath. They are usually more discreet, with relatively defined borders. Diagnosis is typically clinical and many IHs self-resolve, albeit with residual findings including skin atrophy, scarring, and telangiectasia. Observation or topical timolol are first-line treatment options for more superficial lesions while systemic propranolol is the treatment of choice for deeper IHs or those resulting in possible airway or vision compromise.

Congenital hemangiomas (CH) are another type of vascular growth characterized by a solitary erythematous to violaceous plaque or nodule present at birth with overlying telangiectasia. CHs can be subdivided into categories including rapidly involuting (RICH), partially involuting (PICH), and noninvoluting (NICH). Diagnosis is usually clinical and, depending on the subtype, treatment can involve watchful waiting (for RICHs) or more active intervention such as pulse dye laser or surgical resection (for PICHs or NICHs). The growing nature of this patient’s mass makes a diagnosis of CH unlikely.

Port-wine birth mark, also known as nevus flammeus, is a vascular malformation that appears at birth as a nonpalpable irregular erythematous to violaceous macular plaque. Port-wine stains may be isolated birthmarks, or associated with Sturge-Weber syndrome, complex vascular malformations, or soft-tissue overgrowth. Klippel-Trenauny syndrome (KTS) describes capillary-venous malformations with limb overgrowth, with or without lymphatic malformations, and many are associated with somatic mutations in the PIK3CA gene. While KTS could be considered in this patient, the nodular appearance with lumpy texture and rapid growth makes a vascular tumor more likely.

Rhabdomyosarcoma is a malignancy of skeletal muscle lineage and the most common soft tissue tumor in pediatrics. Cutaneous rhabdomyosarcomas present as erythematous nodules, markedly firm, often “fixed” to deep tissue. A rapidly growing atypical, firm tumor of infancy should raise the consideration of rhabdomyosarcoma and imaging and biopsy are appropriate for evaluation.
 

What should the evaluation and management of this patient be?

Initial workup should include a complete blood count with platelet count as well as coagulation studies including D-dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time, to assess for any thrombocytopenia or coagulopathy.⁶ Ultrasound and/or MRI may also be performed to determine lesion extent. While typical MRI findings might be suggestive of a tufted angioma or hemangioendothelioma, biopsy for histologic examination is usually the approach to diagnosis, which will demonstrate stereotypic round lobules of capillaries in a “tufted” distribution.^2,7 Biopsy may be performed by a surgeon or dermatologist but bleeding at time of biopsy needs to be considered before moving forward with the procedure.

Tufted angiomas of early life may regress spontaneously, though lesions with symptoms, with functional significance, or associated with KHE may require therapy. Surgical excision is one option, but it may be difficult to execute given that these lesions often have poorly defined margins.¹ Other treatment choices include but are not limited to aspirin, systemic corticosteroids, vincristine, interferon-alpha, embolization, and sirolimus.⁸ No specific expert-directed consensus guidelines exist for these lesions, and suspicion of this lesion should prompt urgent referral to a pediatric dermatologist. Concern for Kasabach-Merritt syndrome should trigger immediate referral for rapid evaluation and management.

Complete blood count with platelet count and coagulation studies were normal in our patient. This infant underwent biopsy to confirm the diagnosis of tufted angioma and MRI to determine lesion extent. The lesion slowly involuted spontaneously without recurrence.
 

Mr. Haft is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. He is MS4 at the University of Rochester, N.Y. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Mr. Haft nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Herron MD et al. Pediatr Dermatol. 2002;19(5):394-401.

2. Jones EW and Orkin M. J Am Acad Dermatol. 1989;20(2 Pt 1):214-25.

3. Wong SN and Tay YK. Pediatr Dermatol. 2002;19(5):388-93.

4. Croteau SE and Gupta D. Semin Cutan Med Surg. 2016;35(3):147-52.

5. Kelly M. Pediatr Clin North Am. 2010;57(5):1085-9.

6. Osio A et al. Arch Dermatol. 2010;146(7):758-63.

7. Padilla RS et al. Am J Dermatopathol. 1987;9(4):292-300.

8. Liu XH et al. Int J Cancer. 2016;139(7):1658-66.

You’ve successfully resected a skin cancer lesion, leaving clear margins. Now what?

That’s the question the authors of an evidence-based guideline on reconstruction after skin cancer resection set out to answer.

The guideline – a joint effort of the American Society of Plastic Surgeons, American Society for Dermatologic Surgery, American Academy of Dermatology, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology – Head and Neck Surgery Foundation, American College of Mohs Surgery, American Society for Mohs Surgery, and American Society of Ophthalmic Plastic and Reconstructive Surgery – was published online in the Journal of the American Academy of Dermatology.

From the outset, the panel members realized that to keep the guideline manageable they had to limit recommendations to the practice of reconstruction defined as “cutaneous closure that requires a flap, graft, or tissue rearrangement.”

Other wound closure methods, such as secondary intention healing; simple closures; and complex closures that do not involve flaps, grafts, muscle, or bone, were not covered in the recommendations.

As with similar guidelines, the developers selected seven clinical questions to be addressed, and attempted to find consensus through literature searches, appraisal of the evidence, grading of recommendations, peer review, and public comment.

“We had a very heterogeneous set of things that we were trying to comment on, so we had to keep things somewhat generic,” lead author Andrew Chen, MD, chief of the division of plastic surgery, at the University of Connecticut Health Center, Farmington, said in an interview.

“Skin cancer and reconstruction affect different body areas and areas of different sizes. When we were creating the guidelines, we had to tailor the questions we could ask based on things that would make sense to answer, because obviously we couldn’t ask a question such as: ‘What’s better, a skin graft or a flap?’ Well, there are some things you can’t put a skin graft on – it won’t last, so we couldn’t ask that kind of question,” Dr. Chen said.

Curtis Cetrulo, MD, a plastic and reconstructive surgeon at Massachusetts General Hospital, Boston, who was not involved in the guideline process, said in an interview that the broad recommendations are in keeping with his practice and experience. He also acknowledged, however, the difficulty in creating a guideline that covers the complexity and heterogeneity of reconstructive surgery.

“These are generally good recommendations, but they’re recommendations only, with generally weak levels of evidence. What we really need are clinical trials that can give us definitive answers to some of these questions,” he said.

Recommendations
 

The seven key recommendations, based on the clinical questions raised, are summarized below:

• Delayed (asynchronous) reconstruction is acceptable. Although the quality of the evidence is low and the recommendations are listed as an option, the guideline authors said that depending on the situation, reconstruction can be performed either immediately after resection or delayed by days, weeks, “or even months.”
• Systemic antibiotics should not be routinely prescribed in the interim between resection and reconstruction in adults. Here too, the evidence is low and the recommendation strength is weak, but in “the absence of data showing convincing benefits, systemic antibiotic therapy does not appear necessary or desirable in most cases when there is an interval between cancer resection and reconstruction,” the work group wrote.
• Clinicians may administer perioperative systemic antibiotics in a facility-based setting for adults undergoing reconstruction (3a), but antibiotics should not be routinely prescribed in an office-based setting (3b). The rationale for these recommendations, supported by a moderate level of evidence, is that the risk of surgical-site infection is generally higher in facilities, compared with an office-based setting. Patients who undergo reconstruction in hospitals or surgical centers are more likely to have complex reconstructions or have risks that may make them suitable candidates for antibiotics, but patients in office-based setting may often be spared from the additional costs, side effects, and possible drug interactions from antibiotic use. “There is no evidence in either setting that long-term antibiotic prophylaxis provides infection risk reduction, compared with short-term prophylaxis,” the guideline working group wrote.
• Continue anticoagulant, antithrombotic, and antiplatelet medications for adult patients undergoing reconstruction after skin cancer resection in the office-based setting (4a), and in the facility-based setting should coordinate with the physician managing anticoagulation before modifying the medication prior to surgery (4b). Evidence quality and recommendation strength are both moderate.
• The guideline authors recommend against routine prescription of narcotics as first-line treatment for pain in adults undergoing skin reconstruction (5a), favoring instead acetaminophen and NSAIDs as first-line therapy (5b). Evidence quality and recommendation strength are both moderate.
• In the absence of standardized protocols for the management of pain medications, oral antibiotics, and/or anticoagulants in the perioperative period, clinicians should discuss possible approaches with adult patients. “Educating patients about their perioperative treatment through discussion of treatment strategies may help alleviate anxiety, improve communication, increase patient satisfaction, and maximize patient compliance with the postoperative orders,” the guideline authors wrote.
• The authors suggest that adult patients may be offered follow-up assessments to discuss functional and cosmetic outcomes. “The return of the patient for follow-up visits is an excellent opportunity to better understand and measure these outcomes, improve patient-physician communication, and foster quality improvement. Postoperative follow-up can lead to increased communication between the patient and physician, thereby empowering patients to comment on satisfaction and other important outcomes measures,” they wrote.

What’s next

The guideline developers acknowledged that data are limited regarding reconstructive surgery following skin cancer resection, and that higher-quality studies would help to improve future guidelines. Dr. Chen said that greater use of prospective surgical databases and more systematic collection of patient-reported outcomes could inform further efforts.

The guideline development process was supported by the various groups represented. Dr. Chen and Dr. Cetrulo reported no relevant disclosures.

You’ve successfully resected a skin cancer lesion, leaving clear margins. Now what?

That’s the question the authors of an evidence-based guideline on reconstruction after skin cancer resection set out to answer.

The guideline – a joint effort of the American Society of Plastic Surgeons, American Society for Dermatologic Surgery, American Academy of Dermatology, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology – Head and Neck Surgery Foundation, American College of Mohs Surgery, American Society for Mohs Surgery, and American Society of Ophthalmic Plastic and Reconstructive Surgery – was published online in the Journal of the American Academy of Dermatology.

From the outset, the panel members realized that to keep the guideline manageable they had to limit recommendations to the practice of reconstruction defined as “cutaneous closure that requires a flap, graft, or tissue rearrangement.”

Other wound closure methods, such as secondary intention healing; simple closures; and complex closures that do not involve flaps, grafts, muscle, or bone, were not covered in the recommendations.

As with similar guidelines, the developers selected seven clinical questions to be addressed, and attempted to find consensus through literature searches, appraisal of the evidence, grading of recommendations, peer review, and public comment.

“We had a very heterogeneous set of things that we were trying to comment on, so we had to keep things somewhat generic,” lead author Andrew Chen, MD, chief of the division of plastic surgery, at the University of Connecticut Health Center, Farmington, said in an interview.

“Skin cancer and reconstruction affect different body areas and areas of different sizes. When we were creating the guidelines, we had to tailor the questions we could ask based on things that would make sense to answer, because obviously we couldn’t ask a question such as: ‘What’s better, a skin graft or a flap?’ Well, there are some things you can’t put a skin graft on – it won’t last, so we couldn’t ask that kind of question,” Dr. Chen said.

Curtis Cetrulo, MD, a plastic and reconstructive surgeon at Massachusetts General Hospital, Boston, who was not involved in the guideline process, said in an interview that the broad recommendations are in keeping with his practice and experience. He also acknowledged, however, the difficulty in creating a guideline that covers the complexity and heterogeneity of reconstructive surgery.

“These are generally good recommendations, but they’re recommendations only, with generally weak levels of evidence. What we really need are clinical trials that can give us definitive answers to some of these questions,” he said.

Recommendations
 

The seven key recommendations, based on the clinical questions raised, are summarized below:

• Delayed (asynchronous) reconstruction is acceptable. Although the quality of the evidence is low and the recommendations are listed as an option, the guideline authors said that depending on the situation, reconstruction can be performed either immediately after resection or delayed by days, weeks, “or even months.”
• Systemic antibiotics should not be routinely prescribed in the interim between resection and reconstruction in adults. Here too, the evidence is low and the recommendation strength is weak, but in “the absence of data showing convincing benefits, systemic antibiotic therapy does not appear necessary or desirable in most cases when there is an interval between cancer resection and reconstruction,” the work group wrote.
• Clinicians may administer perioperative systemic antibiotics in a facility-based setting for adults undergoing reconstruction (3a), but antibiotics should not be routinely prescribed in an office-based setting (3b). The rationale for these recommendations, supported by a moderate level of evidence, is that the risk of surgical-site infection is generally higher in facilities, compared with an office-based setting. Patients who undergo reconstruction in hospitals or surgical centers are more likely to have complex reconstructions or have risks that may make them suitable candidates for antibiotics, but patients in office-based setting may often be spared from the additional costs, side effects, and possible drug interactions from antibiotic use. “There is no evidence in either setting that long-term antibiotic prophylaxis provides infection risk reduction, compared with short-term prophylaxis,” the guideline working group wrote.
• Continue anticoagulant, antithrombotic, and antiplatelet medications for adult patients undergoing reconstruction after skin cancer resection in the office-based setting (4a), and in the facility-based setting should coordinate with the physician managing anticoagulation before modifying the medication prior to surgery (4b). Evidence quality and recommendation strength are both moderate.
• The guideline authors recommend against routine prescription of narcotics as first-line treatment for pain in adults undergoing skin reconstruction (5a), favoring instead acetaminophen and NSAIDs as first-line therapy (5b). Evidence quality and recommendation strength are both moderate.
• In the absence of standardized protocols for the management of pain medications, oral antibiotics, and/or anticoagulants in the perioperative period, clinicians should discuss possible approaches with adult patients. “Educating patients about their perioperative treatment through discussion of treatment strategies may help alleviate anxiety, improve communication, increase patient satisfaction, and maximize patient compliance with the postoperative orders,” the guideline authors wrote.
• The authors suggest that adult patients may be offered follow-up assessments to discuss functional and cosmetic outcomes. “The return of the patient for follow-up visits is an excellent opportunity to better understand and measure these outcomes, improve patient-physician communication, and foster quality improvement. Postoperative follow-up can lead to increased communication between the patient and physician, thereby empowering patients to comment on satisfaction and other important outcomes measures,” they wrote.

What’s next

The guideline developers acknowledged that data are limited regarding reconstructive surgery following skin cancer resection, and that higher-quality studies would help to improve future guidelines. Dr. Chen said that greater use of prospective surgical databases and more systematic collection of patient-reported outcomes could inform further efforts.

The guideline development process was supported by the various groups represented. Dr. Chen and Dr. Cetrulo reported no relevant disclosures.

You’ve successfully resected a skin cancer lesion, leaving clear margins. Now what?

That’s the question the authors of an evidence-based guideline on reconstruction after skin cancer resection set out to answer.

The guideline – a joint effort of the American Society of Plastic Surgeons, American Society for Dermatologic Surgery, American Academy of Dermatology, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology – Head and Neck Surgery Foundation, American College of Mohs Surgery, American Society for Mohs Surgery, and American Society of Ophthalmic Plastic and Reconstructive Surgery – was published online in the Journal of the American Academy of Dermatology.

From the outset, the panel members realized that to keep the guideline manageable they had to limit recommendations to the practice of reconstruction defined as “cutaneous closure that requires a flap, graft, or tissue rearrangement.”

Other wound closure methods, such as secondary intention healing; simple closures; and complex closures that do not involve flaps, grafts, muscle, or bone, were not covered in the recommendations.

As with similar guidelines, the developers selected seven clinical questions to be addressed, and attempted to find consensus through literature searches, appraisal of the evidence, grading of recommendations, peer review, and public comment.

“We had a very heterogeneous set of things that we were trying to comment on, so we had to keep things somewhat generic,” lead author Andrew Chen, MD, chief of the division of plastic surgery, at the University of Connecticut Health Center, Farmington, said in an interview.

“Skin cancer and reconstruction affect different body areas and areas of different sizes. When we were creating the guidelines, we had to tailor the questions we could ask based on things that would make sense to answer, because obviously we couldn’t ask a question such as: ‘What’s better, a skin graft or a flap?’ Well, there are some things you can’t put a skin graft on – it won’t last, so we couldn’t ask that kind of question,” Dr. Chen said.

Curtis Cetrulo, MD, a plastic and reconstructive surgeon at Massachusetts General Hospital, Boston, who was not involved in the guideline process, said in an interview that the broad recommendations are in keeping with his practice and experience. He also acknowledged, however, the difficulty in creating a guideline that covers the complexity and heterogeneity of reconstructive surgery.

“These are generally good recommendations, but they’re recommendations only, with generally weak levels of evidence. What we really need are clinical trials that can give us definitive answers to some of these questions,” he said.

Recommendations
 

The seven key recommendations, based on the clinical questions raised, are summarized below:

• Delayed (asynchronous) reconstruction is acceptable. Although the quality of the evidence is low and the recommendations are listed as an option, the guideline authors said that depending on the situation, reconstruction can be performed either immediately after resection or delayed by days, weeks, “or even months.”
• Systemic antibiotics should not be routinely prescribed in the interim between resection and reconstruction in adults. Here too, the evidence is low and the recommendation strength is weak, but in “the absence of data showing convincing benefits, systemic antibiotic therapy does not appear necessary or desirable in most cases when there is an interval between cancer resection and reconstruction,” the work group wrote.
• Clinicians may administer perioperative systemic antibiotics in a facility-based setting for adults undergoing reconstruction (3a), but antibiotics should not be routinely prescribed in an office-based setting (3b). The rationale for these recommendations, supported by a moderate level of evidence, is that the risk of surgical-site infection is generally higher in facilities, compared with an office-based setting. Patients who undergo reconstruction in hospitals or surgical centers are more likely to have complex reconstructions or have risks that may make them suitable candidates for antibiotics, but patients in office-based setting may often be spared from the additional costs, side effects, and possible drug interactions from antibiotic use. “There is no evidence in either setting that long-term antibiotic prophylaxis provides infection risk reduction, compared with short-term prophylaxis,” the guideline working group wrote.
• Continue anticoagulant, antithrombotic, and antiplatelet medications for adult patients undergoing reconstruction after skin cancer resection in the office-based setting (4a), and in the facility-based setting should coordinate with the physician managing anticoagulation before modifying the medication prior to surgery (4b). Evidence quality and recommendation strength are both moderate.
• The guideline authors recommend against routine prescription of narcotics as first-line treatment for pain in adults undergoing skin reconstruction (5a), favoring instead acetaminophen and NSAIDs as first-line therapy (5b). Evidence quality and recommendation strength are both moderate.
• In the absence of standardized protocols for the management of pain medications, oral antibiotics, and/or anticoagulants in the perioperative period, clinicians should discuss possible approaches with adult patients. “Educating patients about their perioperative treatment through discussion of treatment strategies may help alleviate anxiety, improve communication, increase patient satisfaction, and maximize patient compliance with the postoperative orders,” the guideline authors wrote.
• The authors suggest that adult patients may be offered follow-up assessments to discuss functional and cosmetic outcomes. “The return of the patient for follow-up visits is an excellent opportunity to better understand and measure these outcomes, improve patient-physician communication, and foster quality improvement. Postoperative follow-up can lead to increased communication between the patient and physician, thereby empowering patients to comment on satisfaction and other important outcomes measures,” they wrote.

What’s next

The guideline developers acknowledged that data are limited regarding reconstructive surgery following skin cancer resection, and that higher-quality studies would help to improve future guidelines. Dr. Chen said that greater use of prospective surgical databases and more systematic collection of patient-reported outcomes could inform further efforts.

The guideline development process was supported by the various groups represented. Dr. Chen and Dr. Cetrulo reported no relevant disclosures.

Vegetarians have more favorable levels of a number of biomarkers including cardiovascular-linked ones – total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A and B – than meat eaters, according to results of the largest study of its kind to date.

Results of the cross-sectional, observational study of 178,000 participants were presented as an electronic poster at this year’s online European Congress on Obesity by Jirapitcha Boonpor of the Institute of Cardiovascular & Medical Sciences, University of Glasgow (Scotland).

“We found that the health benefits of becoming a vegetarian were independent of adiposity and other sociodemographic and lifestyle-related confounding factors,” senior author Carlos Celis-Morales, PhD, also from the University of Glasgow, said in an interview.

Total cholesterol and LDL cholesterol concentrations for vegetarians were 21% and 16.4% lower than in meat eaters. But some biomarkers considered beneficial – including vitamin D concentrations – were lower in vegetarians, while some considered unhealthy – including triglycerides and cystatin-C levels – were higher.  

Vegetarian diets have recently become much more popular, but there is insufficient information about the health benefits. Prior reports of associations between biomarkers and a vegetarian diet were unclear, including evidence of any metabolic benefits, noted Dr. Celis-Morales.

Importantly, participants in the study had followed a vegetarian or meat-eater diet for at least 5 years before their biomarkers in blood and urine were assessed.

“If you modify your diet, then, 2 weeks later, you can see changes in some metabolic markers, but changes in markers of cardiovascular disease will take 5-10 years,” he explained.
 

No single biomarker can assess health

Asked to comment on the findings, John C. Mathers, PhD, noted that they clearly confirm the importance of not reading any biomarker result in isolation.

Health is complex and individual markers tell you just part of the story,” said Dr. Mathers of the Human Nutrition Research Centre, Newcastle (England) University.

He says a vegetarian diet can be nourishing but cautioned that “just because someone excludes meat from their diet does not mean necessarily that they will be eating a healthy diet.”

“Some of the biomarker differences seen in this work – such as the lower concentrations of total cholesterol and LDL cholesterol, GGT [gamma-glutamyl transferase], and ALT [alanine transaminase] – are indicators that the vegetarians were healthier than the meat eaters. However, other differences were less encouraging, including the lower concentrations of vitamin D and higher concentrations of triglycerides and cystatin-C.”

Also reflecting on the results, Jose Lara Gallegos, PhD, senior lecturer in human nutrition at Northumbria University, Newcastle upon Tyne, England, said they support previous evidence from large studies such as the European Prospective Investigation into Cancer and Nutrition (EPIC), which showed that a vegetarian diet is associated with a lower risk of heart disease.

“A vegetarian diet might also be associated with lower risk for liver diseases such as nonalcoholic fatty liver disease,” Dr. Gallegos said, but added that some levels of biomarkers considered to be “healthy” were lower in the vegetarians, and it is important to remember that strictly restricted diets might be associated with potential risks of nutritional inadequacies.

“Other, less restrictive dietary patterns, such as a Mediterranean diet, are also associated with ... health benefits,” he observed.
 

Large data sample from the UK Biobank study

“Specifically, we wanted to know if vegetarians were healthier because they are generally leaner and lead healthier lives, or whether their diet specifically was responsible for their improved metabolic and cardiovascular health,” Dr. Celis-Morales explained.

Data were included from 177,723 healthy participants from the UK Biobank study who were aged 37-73 years and had reported no major dietary changes over the last 5 years. In total, 4,111 participants were self-reported vegetarians who followed a diet without red meat, poultry, or fish, and 166,516 participants were meat eaters.

Nineteen biomarkers related to diabetes, hypertension, cardiovascular diseases, cancer, and liver and renal function were included, and the associations between vegetarian diet and biomarkers, compared with meat eaters, were examined.

To minimize confounding, the findings were adjusted for age, sex, deprivation, education, ethnicity, smoking, total sedentary time, type of physical activity, alcohol intake, body mass index, and waist circumference.

Compared with meat eaters, vegetarians had significantly lower concentrations of 14 biomarkers, including total cholesterol (21% lower); LDL (16% lower); lipoprotein A (1% lower), lipoprotein B (4% lower), and liver function markers (GGT: 354% lower, and ALT: 153% lower), IGF-1 (134% lower), urate (122% lower), total protein (29% lower), creatinine (607% lower), and C-reactive protein (10% lower).

However, the researchers found that, compared with meat eaters, vegetarians had significantly higher concentrations of some unhealthy biomarkers, including triglycerides (15% higher) and cystatin-C (4% higher), and lower levels of some beneficial biomarkers including high-density lipoprotein (HDL) cholesterol (5% lower), vitamin D (635% lower), and calcium (0.7% lower).

No associations were found for hemoglobin A1c, systolic blood pressure, and aminotransferase.

“Some biomarkers, for example urate, were very low in vegetarians, and this served to verify our results because we expected meat eaters to have higher levels of urate,” remarked Dr. Celis-Morales.
 

Diet commitment and cardiovascular outcomes

Many people, whether vegetarians or meat-eaters, follow short-term diets, for example, the Atkins or the 5:2 diet, and often lack continuity switching from one diet to the next, or back to regular eating.  

“They are healthy, but they do not commit for long enough to make a difference to metabolic markers or potentially long-term health. In contrast, vegetarians are usually fully committed but the reasons behind this commitment might be a concern for the environment or animal welfare, for example,” Dr. Celis-Morales pointed out.

However, he added that many vegetarians replace the meat in their diet with unhealthy alternatives. “They often eat too much pasta or potatoes, or other high-energy food with low nutritional value.”

Having identified metabolic markers specific to long-term vegetarian diets, Dr. Celis-Morales wanted to know what happens to vegetarians’ long-term cardiovascular health. He analyzed and published these outcomes in a separate study published in December 2020.

“Over 9 years of follow-up, we have found that vegetarians have a lower risk in terms of myocardial infarction in the long-term, as well as other cardiovascular disease,” he reported.

Asked whether there was an optimum age or time in life to become a vegetarian to improve health, Dr. Celis-Morales explained that the healthier you are, the less likely you will reap the health benefits of dietary changes – for example to being a vegetarian.

“It is more likely that those people who have unhealthy lifestyle risk factors, such as smoking, and high consumption of high-energy foods or processed meat are more likely to see positive health effects,” he said.  

Lifestyle changes to improve cardiovascular outcomes are usually more likely to be required at 40 or 50 years old than at younger ages. He also noted that metabolic markers tend to show clear improvement at around 3 months after adopting a particular diet but improvements in disease outcomes take a lot longer to become evident.

Dr. Celis-Morales and his team are currently conducting a further analysis to understand if the vegetarian diet is also associated with a lower risk of cancer, depression, and dementia, compared with meat-eaters.

Dr. Celis-Morales, Dr. Mathers, and Dr. Gallegos have reported no relevant financial relationships.

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

Vegetarians have more favorable levels of a number of biomarkers including cardiovascular-linked ones – total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A and B – than meat eaters, according to results of the largest study of its kind to date.

Results of the cross-sectional, observational study of 178,000 participants were presented as an electronic poster at this year’s online European Congress on Obesity by Jirapitcha Boonpor of the Institute of Cardiovascular & Medical Sciences, University of Glasgow (Scotland).

“We found that the health benefits of becoming a vegetarian were independent of adiposity and other sociodemographic and lifestyle-related confounding factors,” senior author Carlos Celis-Morales, PhD, also from the University of Glasgow, said in an interview.

Total cholesterol and LDL cholesterol concentrations for vegetarians were 21% and 16.4% lower than in meat eaters. But some biomarkers considered beneficial – including vitamin D concentrations – were lower in vegetarians, while some considered unhealthy – including triglycerides and cystatin-C levels – were higher.  

Vegetarian diets have recently become much more popular, but there is insufficient information about the health benefits. Prior reports of associations between biomarkers and a vegetarian diet were unclear, including evidence of any metabolic benefits, noted Dr. Celis-Morales.

Importantly, participants in the study had followed a vegetarian or meat-eater diet for at least 5 years before their biomarkers in blood and urine were assessed.

“If you modify your diet, then, 2 weeks later, you can see changes in some metabolic markers, but changes in markers of cardiovascular disease will take 5-10 years,” he explained.
 

No single biomarker can assess health

Asked to comment on the findings, John C. Mathers, PhD, noted that they clearly confirm the importance of not reading any biomarker result in isolation.

Health is complex and individual markers tell you just part of the story,” said Dr. Mathers of the Human Nutrition Research Centre, Newcastle (England) University.

He says a vegetarian diet can be nourishing but cautioned that “just because someone excludes meat from their diet does not mean necessarily that they will be eating a healthy diet.”

“Some of the biomarker differences seen in this work – such as the lower concentrations of total cholesterol and LDL cholesterol, GGT [gamma-glutamyl transferase], and ALT [alanine transaminase] – are indicators that the vegetarians were healthier than the meat eaters. However, other differences were less encouraging, including the lower concentrations of vitamin D and higher concentrations of triglycerides and cystatin-C.”

Also reflecting on the results, Jose Lara Gallegos, PhD, senior lecturer in human nutrition at Northumbria University, Newcastle upon Tyne, England, said they support previous evidence from large studies such as the European Prospective Investigation into Cancer and Nutrition (EPIC), which showed that a vegetarian diet is associated with a lower risk of heart disease.

“A vegetarian diet might also be associated with lower risk for liver diseases such as nonalcoholic fatty liver disease,” Dr. Gallegos said, but added that some levels of biomarkers considered to be “healthy” were lower in the vegetarians, and it is important to remember that strictly restricted diets might be associated with potential risks of nutritional inadequacies.

“Other, less restrictive dietary patterns, such as a Mediterranean diet, are also associated with ... health benefits,” he observed.
 

Large data sample from the UK Biobank study

“Specifically, we wanted to know if vegetarians were healthier because they are generally leaner and lead healthier lives, or whether their diet specifically was responsible for their improved metabolic and cardiovascular health,” Dr. Celis-Morales explained.

Data were included from 177,723 healthy participants from the UK Biobank study who were aged 37-73 years and had reported no major dietary changes over the last 5 years. In total, 4,111 participants were self-reported vegetarians who followed a diet without red meat, poultry, or fish, and 166,516 participants were meat eaters.

Nineteen biomarkers related to diabetes, hypertension, cardiovascular diseases, cancer, and liver and renal function were included, and the associations between vegetarian diet and biomarkers, compared with meat eaters, were examined.

To minimize confounding, the findings were adjusted for age, sex, deprivation, education, ethnicity, smoking, total sedentary time, type of physical activity, alcohol intake, body mass index, and waist circumference.

Compared with meat eaters, vegetarians had significantly lower concentrations of 14 biomarkers, including total cholesterol (21% lower); LDL (16% lower); lipoprotein A (1% lower), lipoprotein B (4% lower), and liver function markers (GGT: 354% lower, and ALT: 153% lower), IGF-1 (134% lower), urate (122% lower), total protein (29% lower), creatinine (607% lower), and C-reactive protein (10% lower).

However, the researchers found that, compared with meat eaters, vegetarians had significantly higher concentrations of some unhealthy biomarkers, including triglycerides (15% higher) and cystatin-C (4% higher), and lower levels of some beneficial biomarkers including high-density lipoprotein (HDL) cholesterol (5% lower), vitamin D (635% lower), and calcium (0.7% lower).

No associations were found for hemoglobin A1c, systolic blood pressure, and aminotransferase.

“Some biomarkers, for example urate, were very low in vegetarians, and this served to verify our results because we expected meat eaters to have higher levels of urate,” remarked Dr. Celis-Morales.
 

Diet commitment and cardiovascular outcomes

Many people, whether vegetarians or meat-eaters, follow short-term diets, for example, the Atkins or the 5:2 diet, and often lack continuity switching from one diet to the next, or back to regular eating.  

“They are healthy, but they do not commit for long enough to make a difference to metabolic markers or potentially long-term health. In contrast, vegetarians are usually fully committed but the reasons behind this commitment might be a concern for the environment or animal welfare, for example,” Dr. Celis-Morales pointed out.

However, he added that many vegetarians replace the meat in their diet with unhealthy alternatives. “They often eat too much pasta or potatoes, or other high-energy food with low nutritional value.”

Having identified metabolic markers specific to long-term vegetarian diets, Dr. Celis-Morales wanted to know what happens to vegetarians’ long-term cardiovascular health. He analyzed and published these outcomes in a separate study published in December 2020.

“Over 9 years of follow-up, we have found that vegetarians have a lower risk in terms of myocardial infarction in the long-term, as well as other cardiovascular disease,” he reported.

Asked whether there was an optimum age or time in life to become a vegetarian to improve health, Dr. Celis-Morales explained that the healthier you are, the less likely you will reap the health benefits of dietary changes – for example to being a vegetarian.

“It is more likely that those people who have unhealthy lifestyle risk factors, such as smoking, and high consumption of high-energy foods or processed meat are more likely to see positive health effects,” he said.  

Lifestyle changes to improve cardiovascular outcomes are usually more likely to be required at 40 or 50 years old than at younger ages. He also noted that metabolic markers tend to show clear improvement at around 3 months after adopting a particular diet but improvements in disease outcomes take a lot longer to become evident.

Dr. Celis-Morales and his team are currently conducting a further analysis to understand if the vegetarian diet is also associated with a lower risk of cancer, depression, and dementia, compared with meat-eaters.

Dr. Celis-Morales, Dr. Mathers, and Dr. Gallegos have reported no relevant financial relationships.

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

Vegetarians have more favorable levels of a number of biomarkers including cardiovascular-linked ones – total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein A and B – than meat eaters, according to results of the largest study of its kind to date.

Results of the cross-sectional, observational study of 178,000 participants were presented as an electronic poster at this year’s online European Congress on Obesity by Jirapitcha Boonpor of the Institute of Cardiovascular & Medical Sciences, University of Glasgow (Scotland).

“We found that the health benefits of becoming a vegetarian were independent of adiposity and other sociodemographic and lifestyle-related confounding factors,” senior author Carlos Celis-Morales, PhD, also from the University of Glasgow, said in an interview.

Total cholesterol and LDL cholesterol concentrations for vegetarians were 21% and 16.4% lower than in meat eaters. But some biomarkers considered beneficial – including vitamin D concentrations – were lower in vegetarians, while some considered unhealthy – including triglycerides and cystatin-C levels – were higher.  

Vegetarian diets have recently become much more popular, but there is insufficient information about the health benefits. Prior reports of associations between biomarkers and a vegetarian diet were unclear, including evidence of any metabolic benefits, noted Dr. Celis-Morales.

Importantly, participants in the study had followed a vegetarian or meat-eater diet for at least 5 years before their biomarkers in blood and urine were assessed.

“If you modify your diet, then, 2 weeks later, you can see changes in some metabolic markers, but changes in markers of cardiovascular disease will take 5-10 years,” he explained.
 

No single biomarker can assess health

Asked to comment on the findings, John C. Mathers, PhD, noted that they clearly confirm the importance of not reading any biomarker result in isolation.

Health is complex and individual markers tell you just part of the story,” said Dr. Mathers of the Human Nutrition Research Centre, Newcastle (England) University.

He says a vegetarian diet can be nourishing but cautioned that “just because someone excludes meat from their diet does not mean necessarily that they will be eating a healthy diet.”

“Some of the biomarker differences seen in this work – such as the lower concentrations of total cholesterol and LDL cholesterol, GGT [gamma-glutamyl transferase], and ALT [alanine transaminase] – are indicators that the vegetarians were healthier than the meat eaters. However, other differences were less encouraging, including the lower concentrations of vitamin D and higher concentrations of triglycerides and cystatin-C.”

Also reflecting on the results, Jose Lara Gallegos, PhD, senior lecturer in human nutrition at Northumbria University, Newcastle upon Tyne, England, said they support previous evidence from large studies such as the European Prospective Investigation into Cancer and Nutrition (EPIC), which showed that a vegetarian diet is associated with a lower risk of heart disease.

“A vegetarian diet might also be associated with lower risk for liver diseases such as nonalcoholic fatty liver disease,” Dr. Gallegos said, but added that some levels of biomarkers considered to be “healthy” were lower in the vegetarians, and it is important to remember that strictly restricted diets might be associated with potential risks of nutritional inadequacies.

“Other, less restrictive dietary patterns, such as a Mediterranean diet, are also associated with ... health benefits,” he observed.
 

Large data sample from the UK Biobank study

“Specifically, we wanted to know if vegetarians were healthier because they are generally leaner and lead healthier lives, or whether their diet specifically was responsible for their improved metabolic and cardiovascular health,” Dr. Celis-Morales explained.

Data were included from 177,723 healthy participants from the UK Biobank study who were aged 37-73 years and had reported no major dietary changes over the last 5 years. In total, 4,111 participants were self-reported vegetarians who followed a diet without red meat, poultry, or fish, and 166,516 participants were meat eaters.

Nineteen biomarkers related to diabetes, hypertension, cardiovascular diseases, cancer, and liver and renal function were included, and the associations between vegetarian diet and biomarkers, compared with meat eaters, were examined.

To minimize confounding, the findings were adjusted for age, sex, deprivation, education, ethnicity, smoking, total sedentary time, type of physical activity, alcohol intake, body mass index, and waist circumference.

Compared with meat eaters, vegetarians had significantly lower concentrations of 14 biomarkers, including total cholesterol (21% lower); LDL (16% lower); lipoprotein A (1% lower), lipoprotein B (4% lower), and liver function markers (GGT: 354% lower, and ALT: 153% lower), IGF-1 (134% lower), urate (122% lower), total protein (29% lower), creatinine (607% lower), and C-reactive protein (10% lower).

However, the researchers found that, compared with meat eaters, vegetarians had significantly higher concentrations of some unhealthy biomarkers, including triglycerides (15% higher) and cystatin-C (4% higher), and lower levels of some beneficial biomarkers including high-density lipoprotein (HDL) cholesterol (5% lower), vitamin D (635% lower), and calcium (0.7% lower).

No associations were found for hemoglobin A1c, systolic blood pressure, and aminotransferase.

“Some biomarkers, for example urate, were very low in vegetarians, and this served to verify our results because we expected meat eaters to have higher levels of urate,” remarked Dr. Celis-Morales.
 

Diet commitment and cardiovascular outcomes

Many people, whether vegetarians or meat-eaters, follow short-term diets, for example, the Atkins or the 5:2 diet, and often lack continuity switching from one diet to the next, or back to regular eating.  

“They are healthy, but they do not commit for long enough to make a difference to metabolic markers or potentially long-term health. In contrast, vegetarians are usually fully committed but the reasons behind this commitment might be a concern for the environment or animal welfare, for example,” Dr. Celis-Morales pointed out.

However, he added that many vegetarians replace the meat in their diet with unhealthy alternatives. “They often eat too much pasta or potatoes, or other high-energy food with low nutritional value.”

Having identified metabolic markers specific to long-term vegetarian diets, Dr. Celis-Morales wanted to know what happens to vegetarians’ long-term cardiovascular health. He analyzed and published these outcomes in a separate study published in December 2020.

“Over 9 years of follow-up, we have found that vegetarians have a lower risk in terms of myocardial infarction in the long-term, as well as other cardiovascular disease,” he reported.

Asked whether there was an optimum age or time in life to become a vegetarian to improve health, Dr. Celis-Morales explained that the healthier you are, the less likely you will reap the health benefits of dietary changes – for example to being a vegetarian.

“It is more likely that those people who have unhealthy lifestyle risk factors, such as smoking, and high consumption of high-energy foods or processed meat are more likely to see positive health effects,” he said.  

Lifestyle changes to improve cardiovascular outcomes are usually more likely to be required at 40 or 50 years old than at younger ages. He also noted that metabolic markers tend to show clear improvement at around 3 months after adopting a particular diet but improvements in disease outcomes take a lot longer to become evident.

Dr. Celis-Morales and his team are currently conducting a further analysis to understand if the vegetarian diet is also associated with a lower risk of cancer, depression, and dementia, compared with meat-eaters.

Dr. Celis-Morales, Dr. Mathers, and Dr. Gallegos have reported no relevant financial relationships.

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

The American Medical Association has released a 3-year strategic plan to counter longstanding health inequities that hurt marginalized communities and to improve the AMA’s own performance in this regard.

The 82-page report, which was created by the association’s Center for Health Equity, argues for both internal changes at the AMA and changes in how the association addresses race-based inequities in general.

The report was released just 2 months after this news organization reported that a podcast hosted by AMA’s top journal was lambasted as racist and out of touch. In the podcast – entitled “Stuctural Racism for Doctors – What Is It?” – one JAMA editor argued that structural racism doesn’t exist. He eventually resigned and the journal’s top editor was placed on administration leave.

The new AMA report’s strategic framework “is driven by the immense need for equity-centered solutions to confront harms produced by systemic racism and other forms of oppression for Black, Latinx, Indigenous, Asian, and other people of color, as well as people who identify as LGBTQ+ and people with disabilities,” the AMA said in a news release. “Its urgency is underscored by ongoing circumstances including inequities exacerbated by the COVID-19 pandemic, ongoing police brutality, and hate crimes targeting Asian, Black, and Brown communities.”

The plan includes five main approaches to addressing inequities in health care and the AMA:

• Implement antiracist equity strategies through AMA practices, programming, policies, and culture.
• Build alliances with marginalized doctors and other stakeholders to elevate the experiences and ideas of historically marginalized and minority health care leaders.
• Strengthen, empower, and equip doctors with the knowledge and tools to dismantle structural and social health inequities.
• Ensure equitable opportunities in innovation.
• Foster truth, racial healing, reconciliation, and transformation for AMA’s past by accounting for how policies and processes excluded, discriminated, and harmed communities.

As the report acknowledges, the AMA has a long history of exclusion of and discrimination against Black physicians, for which the association publicly apologized in 2008. Within the past year, the AMA has reaffirmed its commitment to addressing this legacy and to be proactive on health equity.

Among other things, the association has described racism as a public health crisis, stated that race has nothing to do with biology, said police brutality is a product of structural racism, and called on the federal government to collect and release COVID-19 race/ethnicity data. It also removed the name of AMA founder Nathan Davis, MD, from an annual award and display because of his contribution to explicit racist practices.
 

Equity-centered solutions

The AMA launched its Center for Health Equity in 2019 with a mandate “to embed health equity across the organization.” Aletha Maybank, MD, was named the AMA’s chief health equity officer to lead the center.

In the report that Dr. Maybank helped write, the AMA discusses the consequences of individual and systemic injustice toward minorities. Among these consequences, the report said, is “segregated and inequitable health care systems.”

The “equity-centered solutions” listed in the report include:

• End segregated health care.
• Establish national health care equity and racial justice standards.
• End the use of race-based clinical decision models.
• Eliminate all forms of discrimination, exclusion and oppression in medical and physician education, training, hiring, and promotion.
• Prevent exclusion of and ensure equal representation of Black, Indigenous and Latinx people in medical school admissions as well as medical school and hospital leadership ranks.
• Ensure equity in innovation, including design, development, implementation along with support for equitable innovation opportunities and entrepreneurship.
• Solidify connections and coordination between health care and public health.
• Acknowledge and repair past harms committed by institutions.
•  

Changing medical education

In an exclusive interview, Gerald E. Harmon, MD, president-elect of the AMA, singled out medical education as an area that is ripe for change. “One of the most threatened phenotypes on the planet is the Black male physician,” he said. “Their numbers among medical school applicants continue to drop. We have increasing numbers of women in medical schools – over 50% of trainees are women – and more Black women are entering medical school, but Black men in medical school are an endangered species.

“We’re trying to get the physician workforce to look like the patient workforce.”

Dr. Harmon cited the “pipeline program” at the Morehouse School of Medicine in Atlanta and the AMA’s “doctors back to school” program as examples of efforts to attract minority high school students to health care careers. Much more needs to be done, he added. “We have to put equity and representation into our medical workforce so we can provide better high quality, more reliable care for underrepresented patients.”
 

Putting the AMA’s house in order

In its report, the AMA also makes recommendations about how it can improve equity within its own organization. Over the next 3 years, among other things, the association plans to improve the diversity of leadership at the AMA and its journal, JAMA; train all staff on equity requirements; and develop a plan to recruit more racial and ethnic minorities, LGBTQ+ people, and disabled people.

Dr. Maybank, the AMA’s chief health equity officer, said in an interview that she wouldn’t describe these efforts as affirmative action. “This is beyond affirmative action. It’s about intentional activity and action to ensure equity and justice within the AMA.”

The AMA has to thoroughly examine its own processes and determine “how inequity shows up on a day-to-day basis,” she said. “Whether it’s through hiring, innovation, publishing or communications, everybody needs to know how inequity shows up and how their own mental models can exacerbate inequities. People need tools to challenge themselves and ask themselves critical questions about racism in their processes and what they can do to mitigate those.”

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

The American Medical Association has released a 3-year strategic plan to counter longstanding health inequities that hurt marginalized communities and to improve the AMA’s own performance in this regard.

The 82-page report, which was created by the association’s Center for Health Equity, argues for both internal changes at the AMA and changes in how the association addresses race-based inequities in general.

The report was released just 2 months after this news organization reported that a podcast hosted by AMA’s top journal was lambasted as racist and out of touch. In the podcast – entitled “Stuctural Racism for Doctors – What Is It?” – one JAMA editor argued that structural racism doesn’t exist. He eventually resigned and the journal’s top editor was placed on administration leave.

The new AMA report’s strategic framework “is driven by the immense need for equity-centered solutions to confront harms produced by systemic racism and other forms of oppression for Black, Latinx, Indigenous, Asian, and other people of color, as well as people who identify as LGBTQ+ and people with disabilities,” the AMA said in a news release. “Its urgency is underscored by ongoing circumstances including inequities exacerbated by the COVID-19 pandemic, ongoing police brutality, and hate crimes targeting Asian, Black, and Brown communities.”

The plan includes five main approaches to addressing inequities in health care and the AMA:

• Implement antiracist equity strategies through AMA practices, programming, policies, and culture.
• Build alliances with marginalized doctors and other stakeholders to elevate the experiences and ideas of historically marginalized and minority health care leaders.
• Strengthen, empower, and equip doctors with the knowledge and tools to dismantle structural and social health inequities.
• Ensure equitable opportunities in innovation.
• Foster truth, racial healing, reconciliation, and transformation for AMA’s past by accounting for how policies and processes excluded, discriminated, and harmed communities.

As the report acknowledges, the AMA has a long history of exclusion of and discrimination against Black physicians, for which the association publicly apologized in 2008. Within the past year, the AMA has reaffirmed its commitment to addressing this legacy and to be proactive on health equity.

Among other things, the association has described racism as a public health crisis, stated that race has nothing to do with biology, said police brutality is a product of structural racism, and called on the federal government to collect and release COVID-19 race/ethnicity data. It also removed the name of AMA founder Nathan Davis, MD, from an annual award and display because of his contribution to explicit racist practices.
 

Equity-centered solutions

The AMA launched its Center for Health Equity in 2019 with a mandate “to embed health equity across the organization.” Aletha Maybank, MD, was named the AMA’s chief health equity officer to lead the center.

In the report that Dr. Maybank helped write, the AMA discusses the consequences of individual and systemic injustice toward minorities. Among these consequences, the report said, is “segregated and inequitable health care systems.”

The “equity-centered solutions” listed in the report include:

• End segregated health care.
• Establish national health care equity and racial justice standards.
• End the use of race-based clinical decision models.
• Eliminate all forms of discrimination, exclusion and oppression in medical and physician education, training, hiring, and promotion.
• Prevent exclusion of and ensure equal representation of Black, Indigenous and Latinx people in medical school admissions as well as medical school and hospital leadership ranks.
• Ensure equity in innovation, including design, development, implementation along with support for equitable innovation opportunities and entrepreneurship.
• Solidify connections and coordination between health care and public health.
• Acknowledge and repair past harms committed by institutions.
•  

Changing medical education

In an exclusive interview, Gerald E. Harmon, MD, president-elect of the AMA, singled out medical education as an area that is ripe for change. “One of the most threatened phenotypes on the planet is the Black male physician,” he said. “Their numbers among medical school applicants continue to drop. We have increasing numbers of women in medical schools – over 50% of trainees are women – and more Black women are entering medical school, but Black men in medical school are an endangered species.

“We’re trying to get the physician workforce to look like the patient workforce.”

Dr. Harmon cited the “pipeline program” at the Morehouse School of Medicine in Atlanta and the AMA’s “doctors back to school” program as examples of efforts to attract minority high school students to health care careers. Much more needs to be done, he added. “We have to put equity and representation into our medical workforce so we can provide better high quality, more reliable care for underrepresented patients.”
 

Putting the AMA’s house in order

In its report, the AMA also makes recommendations about how it can improve equity within its own organization. Over the next 3 years, among other things, the association plans to improve the diversity of leadership at the AMA and its journal, JAMA; train all staff on equity requirements; and develop a plan to recruit more racial and ethnic minorities, LGBTQ+ people, and disabled people.

Dr. Maybank, the AMA’s chief health equity officer, said in an interview that she wouldn’t describe these efforts as affirmative action. “This is beyond affirmative action. It’s about intentional activity and action to ensure equity and justice within the AMA.”

The AMA has to thoroughly examine its own processes and determine “how inequity shows up on a day-to-day basis,” she said. “Whether it’s through hiring, innovation, publishing or communications, everybody needs to know how inequity shows up and how their own mental models can exacerbate inequities. People need tools to challenge themselves and ask themselves critical questions about racism in their processes and what they can do to mitigate those.”

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

The American Medical Association has released a 3-year strategic plan to counter longstanding health inequities that hurt marginalized communities and to improve the AMA’s own performance in this regard.

The 82-page report, which was created by the association’s Center for Health Equity, argues for both internal changes at the AMA and changes in how the association addresses race-based inequities in general.

The report was released just 2 months after this news organization reported that a podcast hosted by AMA’s top journal was lambasted as racist and out of touch. In the podcast – entitled “Stuctural Racism for Doctors – What Is It?” – one JAMA editor argued that structural racism doesn’t exist. He eventually resigned and the journal’s top editor was placed on administration leave.

The new AMA report’s strategic framework “is driven by the immense need for equity-centered solutions to confront harms produced by systemic racism and other forms of oppression for Black, Latinx, Indigenous, Asian, and other people of color, as well as people who identify as LGBTQ+ and people with disabilities,” the AMA said in a news release. “Its urgency is underscored by ongoing circumstances including inequities exacerbated by the COVID-19 pandemic, ongoing police brutality, and hate crimes targeting Asian, Black, and Brown communities.”

The plan includes five main approaches to addressing inequities in health care and the AMA:

• Implement antiracist equity strategies through AMA practices, programming, policies, and culture.
• Build alliances with marginalized doctors and other stakeholders to elevate the experiences and ideas of historically marginalized and minority health care leaders.
• Strengthen, empower, and equip doctors with the knowledge and tools to dismantle structural and social health inequities.
• Ensure equitable opportunities in innovation.
• Foster truth, racial healing, reconciliation, and transformation for AMA’s past by accounting for how policies and processes excluded, discriminated, and harmed communities.

As the report acknowledges, the AMA has a long history of exclusion of and discrimination against Black physicians, for which the association publicly apologized in 2008. Within the past year, the AMA has reaffirmed its commitment to addressing this legacy and to be proactive on health equity.

Among other things, the association has described racism as a public health crisis, stated that race has nothing to do with biology, said police brutality is a product of structural racism, and called on the federal government to collect and release COVID-19 race/ethnicity data. It also removed the name of AMA founder Nathan Davis, MD, from an annual award and display because of his contribution to explicit racist practices.
 

Equity-centered solutions

The AMA launched its Center for Health Equity in 2019 with a mandate “to embed health equity across the organization.” Aletha Maybank, MD, was named the AMA’s chief health equity officer to lead the center.

In the report that Dr. Maybank helped write, the AMA discusses the consequences of individual and systemic injustice toward minorities. Among these consequences, the report said, is “segregated and inequitable health care systems.”

The “equity-centered solutions” listed in the report include:

• End segregated health care.
• Establish national health care equity and racial justice standards.
• End the use of race-based clinical decision models.
• Eliminate all forms of discrimination, exclusion and oppression in medical and physician education, training, hiring, and promotion.
• Prevent exclusion of and ensure equal representation of Black, Indigenous and Latinx people in medical school admissions as well as medical school and hospital leadership ranks.
• Ensure equity in innovation, including design, development, implementation along with support for equitable innovation opportunities and entrepreneurship.
• Solidify connections and coordination between health care and public health.
• Acknowledge and repair past harms committed by institutions.
•  

Changing medical education

In an exclusive interview, Gerald E. Harmon, MD, president-elect of the AMA, singled out medical education as an area that is ripe for change. “One of the most threatened phenotypes on the planet is the Black male physician,” he said. “Their numbers among medical school applicants continue to drop. We have increasing numbers of women in medical schools – over 50% of trainees are women – and more Black women are entering medical school, but Black men in medical school are an endangered species.

“We’re trying to get the physician workforce to look like the patient workforce.”

Dr. Harmon cited the “pipeline program” at the Morehouse School of Medicine in Atlanta and the AMA’s “doctors back to school” program as examples of efforts to attract minority high school students to health care careers. Much more needs to be done, he added. “We have to put equity and representation into our medical workforce so we can provide better high quality, more reliable care for underrepresented patients.”
 

Putting the AMA’s house in order

In its report, the AMA also makes recommendations about how it can improve equity within its own organization. Over the next 3 years, among other things, the association plans to improve the diversity of leadership at the AMA and its journal, JAMA; train all staff on equity requirements; and develop a plan to recruit more racial and ethnic minorities, LGBTQ+ people, and disabled people.

Dr. Maybank, the AMA’s chief health equity officer, said in an interview that she wouldn’t describe these efforts as affirmative action. “This is beyond affirmative action. It’s about intentional activity and action to ensure equity and justice within the AMA.”

The AMA has to thoroughly examine its own processes and determine “how inequity shows up on a day-to-day basis,” she said. “Whether it’s through hiring, innovation, publishing or communications, everybody needs to know how inequity shows up and how their own mental models can exacerbate inequities. People need tools to challenge themselves and ask themselves critical questions about racism in their processes and what they can do to mitigate those.”

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

Dual HER2 blockade with pertuzumab (Perjeta) and trastuzumab (Herceptin) on top of anthracycline-based neoadjuvant chemotherapy for early-stage breast cancer was associated with a low rate of clinically relevant cardiac events in the final follow-up of the BERENICE study.

After more than 5 years, 1.0%-1.5% of patients who had locally advanced, inflammatory, or early-stage breast cancer developed heart failure, and around 12%-13% showed any significant changes in left ventricular ejection fraction (LVEF).

Importantly, “there were no new safety concerns that arose during long-term follow-up,” study investigator Chau Dang, MD, said in presenting the findings at the European Society for Medical Oncology: Breast Cancer virtual meeting.

Dr. Dang, a medical oncologist at Memorial Sloan Kettering Cancer Centre in New York, reported that the most common cause of death was disease progression.

BERENICE was designed as a cardiac safety study and so not powered to look at long-term efficacy, which Dr. Dang was clear in reporting. Nevertheless event-free survival (EFS), invasive disease-free survival (IDFS), and overall survival (OS) rates at 5 years were all high, at least a respective 89.2%, 91%, and 93.8%, she said. “The medians have not been reached,” she observed.

“These data support the use of dual HER2 blockade with pertuzumab-trastuzumab–based regimens, including in combination with dose-dense, anthracycline-based chemotherapy, across the neoadjuvant and adjuvant treatment settings for the complete treatment of patients with HER2-positive early-stage breast cancer,” Dr. Dang said.

Evandro de Azambuja, MD, PhD, the invited discussant for the trial agreed that the regimens tested appeared “safe from a cardiac standpoint.” However, “you cannot forget that today we are using much less anthracyclines in our patient population.”

Patients in trials are also very different from those treated in clinical practice, often being younger and much fitter, he said. Therefore, it may be important to look at the baseline cardiac medications and comorbidities, Dr. de Azambuja, a medical oncologist at the Institut Jules Bordet in Brussels, Belgium, suggested.

That said, the BERENICE findings sit well with other trials that have been conducted, Dr. de Azambuja pointed out.

“If we look at other trials that have also tested dual HER2 blockade with anthracycline or nonanthracycline regimens, all of them reassure that dual blockade is not more cardiotoxic than single blockade,” he said. This includes trials such as TRYPHAENA, APHINITY, KRISTINE, NeoSphere and PEONY.

The 3-year IDFS rate of 91% in BERENICE also compares well to that seen in APHINITY (94%), Dr. de Azambuja said.
 

BERENICE study design

BERENICE was a multicenter, open-label, nonrandomized and noncomparative phase 2 trial that recruited 400 patients across 75 centers in 12 countries.

Eligibility criteria were that participants had to have been centrally confirmed HER2-positive locally advanced, inflammatory or early breast cancer, with the latter defined as tumors bigger than 2 cm or greater than 5 mm in size, and be node-positive. Patients also had to have a starting LVEF of 55% or higher.

Patients were allocated to one of two neoadjuvant chemotherapy regimens depending on the choice of their physician. One group received a regimen of dose-dense doxorubicin and cyclophosphamide (ddAC) given every 2 weeks for four cycles and then paclitaxel every week for 12 cycles. The other group received 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) every 3 weeks for four cycles and then docetaxel every 3 weeks for four cycles.

Pertuzumab and trastuzumab were started at the same time as the taxanes in both groups and given every 3 weeks for four cycles. Patients then underwent surgery and continued pertuzumab/trastuzumab treatment alone for a further 13 cycles.

The co-primary endpoints were the incidence of New York Heart Association class III or IV heart failure and incidence of symptomatic and asymptomatic LVEF decline of 10% or more.

The primary analysis of the trial was published in 2018 and, at that time, it was reported that three patients in the ddAC cohort and none in the FEC cohort experienced heart failure. LVEF decline was observed in a respective 6.5% and 2% of patients.
 

Discussion points

Dr. de Azambuja noted that the contribution of the chemotherapy to the efficacy cannot be assessed because of the nonrandomized trial design. That should not matter, pointed out Sybille Loibl, MD, PhD, during discussion.

“I think it compares nicely to other trials that looked at dose-dense chemotherapy,” said Dr. Loibl, who is an associate professor at the University of Frankfurt in Germany. “It seems that, in the light of what we consider today probably one of the best anti-HER2 treatments, the chemotherapy is less relevant, and that’s why a dose-dense regimen doesn’t add so much on a standard anthracycline taxane-containing regimen.”

Dr. de Azambuja also commented on the assessment of cardiotoxicity and the use of reduced LVEF as a measure: LVEF decline is a late effect of cardiotoxicity, he observed, and he suggested a different approach in future trials.

“If you use Global Longitudinal Strain, this could be an optimal parameter to detect early subclinical LVEF dysfunction and you should consider it for the next trials looking for cardiac safety. Also, cardiac biomarkers. This was not implemented in this trial, and I strongly recommend this should be for the next trial.”

The BERENICE trial was funded by F. Hoffmann-La Roche. Dr. Dang disclosed receiving consultancy fees from F. Hoffmann-La Roche, Genentech, Daiichi Sankyo, Lilly, and Puma Biotechnology. Dr. de Azambuja was not involved in the study but disclosed receiving honoraria, travel grants, research grants from Roche and Genentech as well as from other companies. Dr. Loibl was one of the cochairs of the session and, among disclosures regarding many other companies, has been an invited speaker for Roche and received reimbursement via her institution for a writing engagement.

Dual HER2 blockade with pertuzumab (Perjeta) and trastuzumab (Herceptin) on top of anthracycline-based neoadjuvant chemotherapy for early-stage breast cancer was associated with a low rate of clinically relevant cardiac events in the final follow-up of the BERENICE study.

After more than 5 years, 1.0%-1.5% of patients who had locally advanced, inflammatory, or early-stage breast cancer developed heart failure, and around 12%-13% showed any significant changes in left ventricular ejection fraction (LVEF).

Importantly, “there were no new safety concerns that arose during long-term follow-up,” study investigator Chau Dang, MD, said in presenting the findings at the European Society for Medical Oncology: Breast Cancer virtual meeting.

Dr. Dang, a medical oncologist at Memorial Sloan Kettering Cancer Centre in New York, reported that the most common cause of death was disease progression.

BERENICE was designed as a cardiac safety study and so not powered to look at long-term efficacy, which Dr. Dang was clear in reporting. Nevertheless event-free survival (EFS), invasive disease-free survival (IDFS), and overall survival (OS) rates at 5 years were all high, at least a respective 89.2%, 91%, and 93.8%, she said. “The medians have not been reached,” she observed.

“These data support the use of dual HER2 blockade with pertuzumab-trastuzumab–based regimens, including in combination with dose-dense, anthracycline-based chemotherapy, across the neoadjuvant and adjuvant treatment settings for the complete treatment of patients with HER2-positive early-stage breast cancer,” Dr. Dang said.

Evandro de Azambuja, MD, PhD, the invited discussant for the trial agreed that the regimens tested appeared “safe from a cardiac standpoint.” However, “you cannot forget that today we are using much less anthracyclines in our patient population.”

Patients in trials are also very different from those treated in clinical practice, often being younger and much fitter, he said. Therefore, it may be important to look at the baseline cardiac medications and comorbidities, Dr. de Azambuja, a medical oncologist at the Institut Jules Bordet in Brussels, Belgium, suggested.

That said, the BERENICE findings sit well with other trials that have been conducted, Dr. de Azambuja pointed out.

“If we look at other trials that have also tested dual HER2 blockade with anthracycline or nonanthracycline regimens, all of them reassure that dual blockade is not more cardiotoxic than single blockade,” he said. This includes trials such as TRYPHAENA, APHINITY, KRISTINE, NeoSphere and PEONY.

The 3-year IDFS rate of 91% in BERENICE also compares well to that seen in APHINITY (94%), Dr. de Azambuja said.
 

BERENICE study design

BERENICE was a multicenter, open-label, nonrandomized and noncomparative phase 2 trial that recruited 400 patients across 75 centers in 12 countries.

Eligibility criteria were that participants had to have been centrally confirmed HER2-positive locally advanced, inflammatory or early breast cancer, with the latter defined as tumors bigger than 2 cm or greater than 5 mm in size, and be node-positive. Patients also had to have a starting LVEF of 55% or higher.

Patients were allocated to one of two neoadjuvant chemotherapy regimens depending on the choice of their physician. One group received a regimen of dose-dense doxorubicin and cyclophosphamide (ddAC) given every 2 weeks for four cycles and then paclitaxel every week for 12 cycles. The other group received 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) every 3 weeks for four cycles and then docetaxel every 3 weeks for four cycles.

Pertuzumab and trastuzumab were started at the same time as the taxanes in both groups and given every 3 weeks for four cycles. Patients then underwent surgery and continued pertuzumab/trastuzumab treatment alone for a further 13 cycles.

The co-primary endpoints were the incidence of New York Heart Association class III or IV heart failure and incidence of symptomatic and asymptomatic LVEF decline of 10% or more.

The primary analysis of the trial was published in 2018 and, at that time, it was reported that three patients in the ddAC cohort and none in the FEC cohort experienced heart failure. LVEF decline was observed in a respective 6.5% and 2% of patients.
 

Discussion points

Dr. de Azambuja noted that the contribution of the chemotherapy to the efficacy cannot be assessed because of the nonrandomized trial design. That should not matter, pointed out Sybille Loibl, MD, PhD, during discussion.

“I think it compares nicely to other trials that looked at dose-dense chemotherapy,” said Dr. Loibl, who is an associate professor at the University of Frankfurt in Germany. “It seems that, in the light of what we consider today probably one of the best anti-HER2 treatments, the chemotherapy is less relevant, and that’s why a dose-dense regimen doesn’t add so much on a standard anthracycline taxane-containing regimen.”

Dr. de Azambuja also commented on the assessment of cardiotoxicity and the use of reduced LVEF as a measure: LVEF decline is a late effect of cardiotoxicity, he observed, and he suggested a different approach in future trials.

“If you use Global Longitudinal Strain, this could be an optimal parameter to detect early subclinical LVEF dysfunction and you should consider it for the next trials looking for cardiac safety. Also, cardiac biomarkers. This was not implemented in this trial, and I strongly recommend this should be for the next trial.”

The BERENICE trial was funded by F. Hoffmann-La Roche. Dr. Dang disclosed receiving consultancy fees from F. Hoffmann-La Roche, Genentech, Daiichi Sankyo, Lilly, and Puma Biotechnology. Dr. de Azambuja was not involved in the study but disclosed receiving honoraria, travel grants, research grants from Roche and Genentech as well as from other companies. Dr. Loibl was one of the cochairs of the session and, among disclosures regarding many other companies, has been an invited speaker for Roche and received reimbursement via her institution for a writing engagement.

Dual HER2 blockade with pertuzumab (Perjeta) and trastuzumab (Herceptin) on top of anthracycline-based neoadjuvant chemotherapy for early-stage breast cancer was associated with a low rate of clinically relevant cardiac events in the final follow-up of the BERENICE study.

After more than 5 years, 1.0%-1.5% of patients who had locally advanced, inflammatory, or early-stage breast cancer developed heart failure, and around 12%-13% showed any significant changes in left ventricular ejection fraction (LVEF).

Importantly, “there were no new safety concerns that arose during long-term follow-up,” study investigator Chau Dang, MD, said in presenting the findings at the European Society for Medical Oncology: Breast Cancer virtual meeting.

Dr. Dang, a medical oncologist at Memorial Sloan Kettering Cancer Centre in New York, reported that the most common cause of death was disease progression.

BERENICE was designed as a cardiac safety study and so not powered to look at long-term efficacy, which Dr. Dang was clear in reporting. Nevertheless event-free survival (EFS), invasive disease-free survival (IDFS), and overall survival (OS) rates at 5 years were all high, at least a respective 89.2%, 91%, and 93.8%, she said. “The medians have not been reached,” she observed.

“These data support the use of dual HER2 blockade with pertuzumab-trastuzumab–based regimens, including in combination with dose-dense, anthracycline-based chemotherapy, across the neoadjuvant and adjuvant treatment settings for the complete treatment of patients with HER2-positive early-stage breast cancer,” Dr. Dang said.

Evandro de Azambuja, MD, PhD, the invited discussant for the trial agreed that the regimens tested appeared “safe from a cardiac standpoint.” However, “you cannot forget that today we are using much less anthracyclines in our patient population.”

Patients in trials are also very different from those treated in clinical practice, often being younger and much fitter, he said. Therefore, it may be important to look at the baseline cardiac medications and comorbidities, Dr. de Azambuja, a medical oncologist at the Institut Jules Bordet in Brussels, Belgium, suggested.

That said, the BERENICE findings sit well with other trials that have been conducted, Dr. de Azambuja pointed out.

“If we look at other trials that have also tested dual HER2 blockade with anthracycline or nonanthracycline regimens, all of them reassure that dual blockade is not more cardiotoxic than single blockade,” he said. This includes trials such as TRYPHAENA, APHINITY, KRISTINE, NeoSphere and PEONY.

The 3-year IDFS rate of 91% in BERENICE also compares well to that seen in APHINITY (94%), Dr. de Azambuja said.
 

BERENICE study design

BERENICE was a multicenter, open-label, nonrandomized and noncomparative phase 2 trial that recruited 400 patients across 75 centers in 12 countries.

Eligibility criteria were that participants had to have been centrally confirmed HER2-positive locally advanced, inflammatory or early breast cancer, with the latter defined as tumors bigger than 2 cm or greater than 5 mm in size, and be node-positive. Patients also had to have a starting LVEF of 55% or higher.

Patients were allocated to one of two neoadjuvant chemotherapy regimens depending on the choice of their physician. One group received a regimen of dose-dense doxorubicin and cyclophosphamide (ddAC) given every 2 weeks for four cycles and then paclitaxel every week for 12 cycles. The other group received 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) every 3 weeks for four cycles and then docetaxel every 3 weeks for four cycles.

Pertuzumab and trastuzumab were started at the same time as the taxanes in both groups and given every 3 weeks for four cycles. Patients then underwent surgery and continued pertuzumab/trastuzumab treatment alone for a further 13 cycles.

The co-primary endpoints were the incidence of New York Heart Association class III or IV heart failure and incidence of symptomatic and asymptomatic LVEF decline of 10% or more.

The primary analysis of the trial was published in 2018 and, at that time, it was reported that three patients in the ddAC cohort and none in the FEC cohort experienced heart failure. LVEF decline was observed in a respective 6.5% and 2% of patients.
 

Discussion points

Dr. de Azambuja noted that the contribution of the chemotherapy to the efficacy cannot be assessed because of the nonrandomized trial design. That should not matter, pointed out Sybille Loibl, MD, PhD, during discussion.

“I think it compares nicely to other trials that looked at dose-dense chemotherapy,” said Dr. Loibl, who is an associate professor at the University of Frankfurt in Germany. “It seems that, in the light of what we consider today probably one of the best anti-HER2 treatments, the chemotherapy is less relevant, and that’s why a dose-dense regimen doesn’t add so much on a standard anthracycline taxane-containing regimen.”

Dr. de Azambuja also commented on the assessment of cardiotoxicity and the use of reduced LVEF as a measure: LVEF decline is a late effect of cardiotoxicity, he observed, and he suggested a different approach in future trials.

“If you use Global Longitudinal Strain, this could be an optimal parameter to detect early subclinical LVEF dysfunction and you should consider it for the next trials looking for cardiac safety. Also, cardiac biomarkers. This was not implemented in this trial, and I strongly recommend this should be for the next trial.”

The BERENICE trial was funded by F. Hoffmann-La Roche. Dr. Dang disclosed receiving consultancy fees from F. Hoffmann-La Roche, Genentech, Daiichi Sankyo, Lilly, and Puma Biotechnology. Dr. de Azambuja was not involved in the study but disclosed receiving honoraria, travel grants, research grants from Roche and Genentech as well as from other companies. Dr. Loibl was one of the cochairs of the session and, among disclosures regarding many other companies, has been an invited speaker for Roche and received reimbursement via her institution for a writing engagement.