News

Childhood autism rates have ticked up once again, according to the latest data from Centers for Disease Control and Prevention.

According to the CDC, 1 in 36 (2.8%) 8-year-old children have been identified with autism spectrum disorder (ASD) – up from the previous 2018 estimate of 1 in 44 (2.3%).

The updated data come from 11 communities in the Autism and Developmental Disabilities Monitoring (ADDM) network and were published online in Morbidity and Mortality Weekly Report.

A separate report in the MMWR on 4-year-old children in the same 11 communities highlights the impact of COVID-19, showing disruptions in progress in early autism detection.

In the early months of the pandemic, 4-year-old children were less likely to have an evaluation or be identified with ASD than 8-year-old children when they were the same age. This coincides with interruptions in childcare and health care services during the COVID-19 pandemic.

“Disruptions due to the pandemic in the timely evaluation of children and delays in connecting children to the services and support they need could have long-lasting effects,” Karen Remley, MD, director of CDC’s National Center on Birth Defects and Developmental Disabilities, said in a statement.

“The data in this report can help communities better understand how the pandemic impacted early identification of autism in young children and anticipate future needs as these children get older,” Dr. Remley noted.
 

Shifting demographics

The latest data also show that ASD prevalence among Asian, Black, and Hispanic children was at least 30% higher in 2020 than in 2018, and ASD prevalence among White children was 14.6% higher than in 2018.

For the first time, according to the CDC, the percentage of 8-year-old Asian/Pacific Islander (3.3%), Hispanic (3.2%) and Black (2.9%) children identified with autism was higher than the percentage of 8-year-old White children (2.4%).

This is the opposite of racial and ethnic differences seen in previous ADDM reports for 8-year-olds. These shifts may reflect improved screening, awareness, and access to services among historically underserved groups, the CDC said.

Disparities for co-occurring intellectual disability have also persisted, with a higher percentage of Black children with autism identified with intellectual disability compared with White, Hispanic, or Asian/Pacific Islander children with autism. These differences could relate in part to access to services that diagnose and support children with autism, the CDC noted.

Overall, autism prevalence within the 11 ADDM communities was nearly four times higher for boys than girls. However, it’s the first time that the prevalence of autism among 8-year-old girls has topped 1%.
 

Community differences

Autism prevalence in the 11 ADDM communities ranged from 1 in 43 (2.3%) children in Maryland to 1 in 22 (4.5%) in California – variations that could be due to how communities identify children with autism.

This variability affords an opportunity to compare local policies and models for delivering diagnostic and interventional services that could enhance autism identification and provide more comprehensive support to people with autism, the CDC said.
 

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

Childhood autism rates have ticked up once again, according to the latest data from Centers for Disease Control and Prevention.

According to the CDC, 1 in 36 (2.8%) 8-year-old children have been identified with autism spectrum disorder (ASD) – up from the previous 2018 estimate of 1 in 44 (2.3%).

The updated data come from 11 communities in the Autism and Developmental Disabilities Monitoring (ADDM) network and were published online in Morbidity and Mortality Weekly Report.

A separate report in the MMWR on 4-year-old children in the same 11 communities highlights the impact of COVID-19, showing disruptions in progress in early autism detection.

In the early months of the pandemic, 4-year-old children were less likely to have an evaluation or be identified with ASD than 8-year-old children when they were the same age. This coincides with interruptions in childcare and health care services during the COVID-19 pandemic.

“Disruptions due to the pandemic in the timely evaluation of children and delays in connecting children to the services and support they need could have long-lasting effects,” Karen Remley, MD, director of CDC’s National Center on Birth Defects and Developmental Disabilities, said in a statement.

“The data in this report can help communities better understand how the pandemic impacted early identification of autism in young children and anticipate future needs as these children get older,” Dr. Remley noted.
 

Shifting demographics

The latest data also show that ASD prevalence among Asian, Black, and Hispanic children was at least 30% higher in 2020 than in 2018, and ASD prevalence among White children was 14.6% higher than in 2018.

For the first time, according to the CDC, the percentage of 8-year-old Asian/Pacific Islander (3.3%), Hispanic (3.2%) and Black (2.9%) children identified with autism was higher than the percentage of 8-year-old White children (2.4%).

This is the opposite of racial and ethnic differences seen in previous ADDM reports for 8-year-olds. These shifts may reflect improved screening, awareness, and access to services among historically underserved groups, the CDC said.

Disparities for co-occurring intellectual disability have also persisted, with a higher percentage of Black children with autism identified with intellectual disability compared with White, Hispanic, or Asian/Pacific Islander children with autism. These differences could relate in part to access to services that diagnose and support children with autism, the CDC noted.

Overall, autism prevalence within the 11 ADDM communities was nearly four times higher for boys than girls. However, it’s the first time that the prevalence of autism among 8-year-old girls has topped 1%.
 

Community differences

Autism prevalence in the 11 ADDM communities ranged from 1 in 43 (2.3%) children in Maryland to 1 in 22 (4.5%) in California – variations that could be due to how communities identify children with autism.

This variability affords an opportunity to compare local policies and models for delivering diagnostic and interventional services that could enhance autism identification and provide more comprehensive support to people with autism, the CDC said.
 

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

Childhood autism rates have ticked up once again, according to the latest data from Centers for Disease Control and Prevention.

According to the CDC, 1 in 36 (2.8%) 8-year-old children have been identified with autism spectrum disorder (ASD) – up from the previous 2018 estimate of 1 in 44 (2.3%).

The updated data come from 11 communities in the Autism and Developmental Disabilities Monitoring (ADDM) network and were published online in Morbidity and Mortality Weekly Report.

A separate report in the MMWR on 4-year-old children in the same 11 communities highlights the impact of COVID-19, showing disruptions in progress in early autism detection.

In the early months of the pandemic, 4-year-old children were less likely to have an evaluation or be identified with ASD than 8-year-old children when they were the same age. This coincides with interruptions in childcare and health care services during the COVID-19 pandemic.

“Disruptions due to the pandemic in the timely evaluation of children and delays in connecting children to the services and support they need could have long-lasting effects,” Karen Remley, MD, director of CDC’s National Center on Birth Defects and Developmental Disabilities, said in a statement.

“The data in this report can help communities better understand how the pandemic impacted early identification of autism in young children and anticipate future needs as these children get older,” Dr. Remley noted.
 

Shifting demographics

The latest data also show that ASD prevalence among Asian, Black, and Hispanic children was at least 30% higher in 2020 than in 2018, and ASD prevalence among White children was 14.6% higher than in 2018.

For the first time, according to the CDC, the percentage of 8-year-old Asian/Pacific Islander (3.3%), Hispanic (3.2%) and Black (2.9%) children identified with autism was higher than the percentage of 8-year-old White children (2.4%).

This is the opposite of racial and ethnic differences seen in previous ADDM reports for 8-year-olds. These shifts may reflect improved screening, awareness, and access to services among historically underserved groups, the CDC said.

Disparities for co-occurring intellectual disability have also persisted, with a higher percentage of Black children with autism identified with intellectual disability compared with White, Hispanic, or Asian/Pacific Islander children with autism. These differences could relate in part to access to services that diagnose and support children with autism, the CDC noted.

Overall, autism prevalence within the 11 ADDM communities was nearly four times higher for boys than girls. However, it’s the first time that the prevalence of autism among 8-year-old girls has topped 1%.
 

Community differences

Autism prevalence in the 11 ADDM communities ranged from 1 in 43 (2.3%) children in Maryland to 1 in 22 (4.5%) in California – variations that could be due to how communities identify children with autism.

This variability affords an opportunity to compare local policies and models for delivering diagnostic and interventional services that could enhance autism identification and provide more comprehensive support to people with autism, the CDC said.
 

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

Cases of acquired hypogammaglobulinemia are expected to rise, as patients live longer with such B-cell malignancies as chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma, and multiple myeloma. But there’s a striking shortage of research into the best prophylactic approaches to prevent infections, a new systematic review and meta-analysis showed.

Researchers found just 22 randomized controlled studies into prophylactic strategies, with several of them conducted prior to 2000. According to the report, published in Blood Advances, the studies together only evaluated a few thousand participants.

Reliable findings are so sparse that study coauthor Zoe McQuilten, MBBS, PhD, MD, a hematologist at Monash University, Melbourne, said “we simply don’t know” which preventive strategy is most effective. This is especially worrisome because more patients will survive their cancers and “be at risk of infection or have significant cytopenias and will experience impaired quality of life as a result,” she said in an interview.

The study authors launched the analysis to better understand the evidence regarding infection prevention and to guide the development of clinical trials, study coauthor Robert Weinkove, MBBS, PhD, a hematologist at Malaghan Institute of Medical Research, Wellington, New Zealand, said in an interview.

As he explained, targeted therapies have revolutionized the treatment of some B-cell cancers. They also have boosted the number of patients who survive the diseases yet still have profound hypogammaglobulinemia.

“Indeed, we may soon reach the point at which infection, and not tumor progression, is the leading cause of death for patients with certain B-cell cancers,” he said. “The evidence base for managing hypogammaglobulinemia is largely based on randomized trials of immunoglobulin replacement conducted in the 1980s and early 1990s, before the advent of B cell–targeted therapies. Immunoglobulin replacement is a costly intervention, and many countries are facing a shortage of immunoglobulin.”

The report authors identified 22 total randomized controlled trials, including one led by Dr. McQuilten: 8 studies into prophylactic immunoglobulin (n = 370; all but 1 study published prior to 2000), 5 into prophylactic antibiotics (n = 1,587), 7 into vaccination (n = 3,996), and 1 comparing immunoglobulin versus antibiotics (n = 60).

No evidence was found to support a lowering of risk by prophylactic antibiotics, although they caused adverse events.

Prophylactic immunoglobulin also caused adverse events, but a meta-analysis found that it reduced the risk of clinically documented infection by 28% (n = 2 trials; relative risk, 0.72; 95% confidence interval, 0.54-0.96). Three trials reported adverse events and found a higher risk overall (RR, 2.23; 95% CI, 1.67-2.99).

Varicella zoster virus vaccination reduced the risk of one or more infections by 63% (n = 5 trials, RR, 0.37; 95% CI, 0.30-0.45, n = 3,515). Prophylactic antibiotics did not reduce the risk.

No intervention reduced all-cause mortality.

“Our findings should be interpreted with caution, Dr. McQuilten said, “because of the low number of patients, high risk of bias in the included studies, and lack of contemporary data applicable to the current standard of care for such patients.”

The lack of useful data is surprising, she said, especially considering “how commonly these interventions are used in current clinical practice and the cost and supply constraints for immunoglobulin. Given the variation in international guidelines, rising global demand and cost of immunoglobulin, and concerns regarding antimicrobial resistance, more evidence is needed to inform infection prevention strategies for this patient population.”

More data is expected soon. One ongoing study is examining intravenous immunoglobulin versus placebo in patients with CLL. It’s expected to be completed in September 2023.

What should clinicians do for now? “Given the lack of a proven survival benefit in favor of prophylactic immunoglobulin replacement, one strategy is to maximize use of vaccination and to educate both patients and clinicians regarding the need for early treatment of infections,” Dr. Weinkove said. “For people who have recurrent or severe infections despite these measures, both immunoglobulin replacement and prophylactic antibiotics are clinical options. It would be reasonable to take account of patient preference, logistical considerations, and reimbursement and availability in deciding between these options.”

He added that, “for people with severe hypogammaglobulinemia who experience recurrent or severe infections despite prophylactic antibiotics, switching to immunoglobulin replacement would be appropriate. We advocate enrollment in clinical trials, if possible.”

In an interview, Juthaporn Cowan, MD, PhD, an infectious disease physician with the University of Ottawa, said many patients with B-cell lymphomas develop acquired hypogammaglobulinemia. “Patients tend to get prolonged colds, frequent sinusitis, bronchitis, or pneumonia. Some can end up with severe infection. Many patients told me that, even though their cancer is cured or in remission, quality of life is still quite poor due to these infections and fatigue.”

Dr. Cowan said the new report is somewhat useful, although “concluding that vaccination reduces infection is misleading. Vaccination reduces the infection that patients were vaccinated against. Patients who received Shingrix will have less shingles but will continue to have bronchitis and other infections.”

As for advice for clinicians, she said preventing acquired hypogammaglobulinemia is difficult since it can be caused by the malignancies, by treatment, or both. “The other item to consider is that we do not know how long we should continue [immunoglobulin] treatment in these patients. I have a patient post CAR [chimeric antigen receptor] T therapy who still does not have B-cell 5-6 years after CAR T, while I have lymphoma patients who could safely discontinue [immunoglobulin] treatment in a few years.”

Dr. Cowan added that patients on immunoglobulin treatment can still get opportunistic infections from cytomegalovirus or herpes simplex virus “because the mechanism of host defense against these infections is different. Antimicrobial prophylaxis should still be considered as vaccination is not available for every single potential opportunistic infection.”

Australia funded the research through the National Blood Authority. Dr. McQuilten and Dr. Weinkove reported no disclosures. Other report authors disclosed ties with Aegros, CSL Behring, Janssen, AbbVie, and BeiGene. Monash University has received funding for unrelated projects from CSL Behring. Dr. Cowan reports honoraria from Takeda, CSL Behring, Octapharma, GlaxoSmithKline, Merck, and AstraZeneca.

Cases of acquired hypogammaglobulinemia are expected to rise, as patients live longer with such B-cell malignancies as chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma, and multiple myeloma. But there’s a striking shortage of research into the best prophylactic approaches to prevent infections, a new systematic review and meta-analysis showed.

Researchers found just 22 randomized controlled studies into prophylactic strategies, with several of them conducted prior to 2000. According to the report, published in Blood Advances, the studies together only evaluated a few thousand participants.

Reliable findings are so sparse that study coauthor Zoe McQuilten, MBBS, PhD, MD, a hematologist at Monash University, Melbourne, said “we simply don’t know” which preventive strategy is most effective. This is especially worrisome because more patients will survive their cancers and “be at risk of infection or have significant cytopenias and will experience impaired quality of life as a result,” she said in an interview.

The study authors launched the analysis to better understand the evidence regarding infection prevention and to guide the development of clinical trials, study coauthor Robert Weinkove, MBBS, PhD, a hematologist at Malaghan Institute of Medical Research, Wellington, New Zealand, said in an interview.

As he explained, targeted therapies have revolutionized the treatment of some B-cell cancers. They also have boosted the number of patients who survive the diseases yet still have profound hypogammaglobulinemia.

“Indeed, we may soon reach the point at which infection, and not tumor progression, is the leading cause of death for patients with certain B-cell cancers,” he said. “The evidence base for managing hypogammaglobulinemia is largely based on randomized trials of immunoglobulin replacement conducted in the 1980s and early 1990s, before the advent of B cell–targeted therapies. Immunoglobulin replacement is a costly intervention, and many countries are facing a shortage of immunoglobulin.”

The report authors identified 22 total randomized controlled trials, including one led by Dr. McQuilten: 8 studies into prophylactic immunoglobulin (n = 370; all but 1 study published prior to 2000), 5 into prophylactic antibiotics (n = 1,587), 7 into vaccination (n = 3,996), and 1 comparing immunoglobulin versus antibiotics (n = 60).

No evidence was found to support a lowering of risk by prophylactic antibiotics, although they caused adverse events.

Prophylactic immunoglobulin also caused adverse events, but a meta-analysis found that it reduced the risk of clinically documented infection by 28% (n = 2 trials; relative risk, 0.72; 95% confidence interval, 0.54-0.96). Three trials reported adverse events and found a higher risk overall (RR, 2.23; 95% CI, 1.67-2.99).

Varicella zoster virus vaccination reduced the risk of one or more infections by 63% (n = 5 trials, RR, 0.37; 95% CI, 0.30-0.45, n = 3,515). Prophylactic antibiotics did not reduce the risk.

No intervention reduced all-cause mortality.

“Our findings should be interpreted with caution, Dr. McQuilten said, “because of the low number of patients, high risk of bias in the included studies, and lack of contemporary data applicable to the current standard of care for such patients.”

The lack of useful data is surprising, she said, especially considering “how commonly these interventions are used in current clinical practice and the cost and supply constraints for immunoglobulin. Given the variation in international guidelines, rising global demand and cost of immunoglobulin, and concerns regarding antimicrobial resistance, more evidence is needed to inform infection prevention strategies for this patient population.”

More data is expected soon. One ongoing study is examining intravenous immunoglobulin versus placebo in patients with CLL. It’s expected to be completed in September 2023.

What should clinicians do for now? “Given the lack of a proven survival benefit in favor of prophylactic immunoglobulin replacement, one strategy is to maximize use of vaccination and to educate both patients and clinicians regarding the need for early treatment of infections,” Dr. Weinkove said. “For people who have recurrent or severe infections despite these measures, both immunoglobulin replacement and prophylactic antibiotics are clinical options. It would be reasonable to take account of patient preference, logistical considerations, and reimbursement and availability in deciding between these options.”

He added that, “for people with severe hypogammaglobulinemia who experience recurrent or severe infections despite prophylactic antibiotics, switching to immunoglobulin replacement would be appropriate. We advocate enrollment in clinical trials, if possible.”

In an interview, Juthaporn Cowan, MD, PhD, an infectious disease physician with the University of Ottawa, said many patients with B-cell lymphomas develop acquired hypogammaglobulinemia. “Patients tend to get prolonged colds, frequent sinusitis, bronchitis, or pneumonia. Some can end up with severe infection. Many patients told me that, even though their cancer is cured or in remission, quality of life is still quite poor due to these infections and fatigue.”

Dr. Cowan said the new report is somewhat useful, although “concluding that vaccination reduces infection is misleading. Vaccination reduces the infection that patients were vaccinated against. Patients who received Shingrix will have less shingles but will continue to have bronchitis and other infections.”

As for advice for clinicians, she said preventing acquired hypogammaglobulinemia is difficult since it can be caused by the malignancies, by treatment, or both. “The other item to consider is that we do not know how long we should continue [immunoglobulin] treatment in these patients. I have a patient post CAR [chimeric antigen receptor] T therapy who still does not have B-cell 5-6 years after CAR T, while I have lymphoma patients who could safely discontinue [immunoglobulin] treatment in a few years.”

Dr. Cowan added that patients on immunoglobulin treatment can still get opportunistic infections from cytomegalovirus or herpes simplex virus “because the mechanism of host defense against these infections is different. Antimicrobial prophylaxis should still be considered as vaccination is not available for every single potential opportunistic infection.”

Australia funded the research through the National Blood Authority. Dr. McQuilten and Dr. Weinkove reported no disclosures. Other report authors disclosed ties with Aegros, CSL Behring, Janssen, AbbVie, and BeiGene. Monash University has received funding for unrelated projects from CSL Behring. Dr. Cowan reports honoraria from Takeda, CSL Behring, Octapharma, GlaxoSmithKline, Merck, and AstraZeneca.

Cases of acquired hypogammaglobulinemia are expected to rise, as patients live longer with such B-cell malignancies as chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma, and multiple myeloma. But there’s a striking shortage of research into the best prophylactic approaches to prevent infections, a new systematic review and meta-analysis showed.

Researchers found just 22 randomized controlled studies into prophylactic strategies, with several of them conducted prior to 2000. According to the report, published in Blood Advances, the studies together only evaluated a few thousand participants.

Reliable findings are so sparse that study coauthor Zoe McQuilten, MBBS, PhD, MD, a hematologist at Monash University, Melbourne, said “we simply don’t know” which preventive strategy is most effective. This is especially worrisome because more patients will survive their cancers and “be at risk of infection or have significant cytopenias and will experience impaired quality of life as a result,” she said in an interview.

The study authors launched the analysis to better understand the evidence regarding infection prevention and to guide the development of clinical trials, study coauthor Robert Weinkove, MBBS, PhD, a hematologist at Malaghan Institute of Medical Research, Wellington, New Zealand, said in an interview.

As he explained, targeted therapies have revolutionized the treatment of some B-cell cancers. They also have boosted the number of patients who survive the diseases yet still have profound hypogammaglobulinemia.

“Indeed, we may soon reach the point at which infection, and not tumor progression, is the leading cause of death for patients with certain B-cell cancers,” he said. “The evidence base for managing hypogammaglobulinemia is largely based on randomized trials of immunoglobulin replacement conducted in the 1980s and early 1990s, before the advent of B cell–targeted therapies. Immunoglobulin replacement is a costly intervention, and many countries are facing a shortage of immunoglobulin.”

The report authors identified 22 total randomized controlled trials, including one led by Dr. McQuilten: 8 studies into prophylactic immunoglobulin (n = 370; all but 1 study published prior to 2000), 5 into prophylactic antibiotics (n = 1,587), 7 into vaccination (n = 3,996), and 1 comparing immunoglobulin versus antibiotics (n = 60).

No evidence was found to support a lowering of risk by prophylactic antibiotics, although they caused adverse events.

Prophylactic immunoglobulin also caused adverse events, but a meta-analysis found that it reduced the risk of clinically documented infection by 28% (n = 2 trials; relative risk, 0.72; 95% confidence interval, 0.54-0.96). Three trials reported adverse events and found a higher risk overall (RR, 2.23; 95% CI, 1.67-2.99).

Varicella zoster virus vaccination reduced the risk of one or more infections by 63% (n = 5 trials, RR, 0.37; 95% CI, 0.30-0.45, n = 3,515). Prophylactic antibiotics did not reduce the risk.

No intervention reduced all-cause mortality.

“Our findings should be interpreted with caution, Dr. McQuilten said, “because of the low number of patients, high risk of bias in the included studies, and lack of contemporary data applicable to the current standard of care for such patients.”

The lack of useful data is surprising, she said, especially considering “how commonly these interventions are used in current clinical practice and the cost and supply constraints for immunoglobulin. Given the variation in international guidelines, rising global demand and cost of immunoglobulin, and concerns regarding antimicrobial resistance, more evidence is needed to inform infection prevention strategies for this patient population.”

More data is expected soon. One ongoing study is examining intravenous immunoglobulin versus placebo in patients with CLL. It’s expected to be completed in September 2023.

What should clinicians do for now? “Given the lack of a proven survival benefit in favor of prophylactic immunoglobulin replacement, one strategy is to maximize use of vaccination and to educate both patients and clinicians regarding the need for early treatment of infections,” Dr. Weinkove said. “For people who have recurrent or severe infections despite these measures, both immunoglobulin replacement and prophylactic antibiotics are clinical options. It would be reasonable to take account of patient preference, logistical considerations, and reimbursement and availability in deciding between these options.”

He added that, “for people with severe hypogammaglobulinemia who experience recurrent or severe infections despite prophylactic antibiotics, switching to immunoglobulin replacement would be appropriate. We advocate enrollment in clinical trials, if possible.”

In an interview, Juthaporn Cowan, MD, PhD, an infectious disease physician with the University of Ottawa, said many patients with B-cell lymphomas develop acquired hypogammaglobulinemia. “Patients tend to get prolonged colds, frequent sinusitis, bronchitis, or pneumonia. Some can end up with severe infection. Many patients told me that, even though their cancer is cured or in remission, quality of life is still quite poor due to these infections and fatigue.”

Dr. Cowan said the new report is somewhat useful, although “concluding that vaccination reduces infection is misleading. Vaccination reduces the infection that patients were vaccinated against. Patients who received Shingrix will have less shingles but will continue to have bronchitis and other infections.”

As for advice for clinicians, she said preventing acquired hypogammaglobulinemia is difficult since it can be caused by the malignancies, by treatment, or both. “The other item to consider is that we do not know how long we should continue [immunoglobulin] treatment in these patients. I have a patient post CAR [chimeric antigen receptor] T therapy who still does not have B-cell 5-6 years after CAR T, while I have lymphoma patients who could safely discontinue [immunoglobulin] treatment in a few years.”

Dr. Cowan added that patients on immunoglobulin treatment can still get opportunistic infections from cytomegalovirus or herpes simplex virus “because the mechanism of host defense against these infections is different. Antimicrobial prophylaxis should still be considered as vaccination is not available for every single potential opportunistic infection.”

Australia funded the research through the National Blood Authority. Dr. McQuilten and Dr. Weinkove reported no disclosures. Other report authors disclosed ties with Aegros, CSL Behring, Janssen, AbbVie, and BeiGene. Monash University has received funding for unrelated projects from CSL Behring. Dr. Cowan reports honoraria from Takeda, CSL Behring, Octapharma, GlaxoSmithKline, Merck, and AstraZeneca.

Among patients who undergo forceps-assisted vaginal delivery, obesity does not appear to be associated with increased risk for complications such as injuries to the anal sphincter or the need for their babies to be admitted to the neonatal intensive care unit, researchers have found.

But obesity does appear to increase the chances that when physicians attempt operative vaginal delivery with either forceps or a vacuum, patients will wind up undergoing cesarean delivery, another study found.

Taken together, the new data may help inform physicians’ decisions about when to consider operative vaginal delivery as an alternative to emergency cesarean births.

A prospective study showed that failed operative vaginal delivery – that is, a cesarean delivery after an attempted operative vaginal delivery – occurred for 10.1% of patients with obesity and 4.2% of those without obesity.

Researchers presented the findings at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“We want to really try to reduce the rate of C-sections and primary cesarean deliveries. One of the ways to do that is to attempt operative vaginal delivery,” said Marissa Platner, MD, assistant professor of maternal-fetal medicine at Emory University School of Medicine, Atlanta, who was not involved in the new research.

Data on how obesity influences risks with operative vaginal delivery have been limited and mixed, the researchers said.

To examine how often attempted operative vaginal delivery fails in patients with obesity, Jennifer Grasch, MD, a maternal-fetal medicine fellow at the Ohio State University Wexner Medical Center, Columbus, and her colleagues conducted a secondary analysis of data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, which included more than 10,000 participants.

“We know that cesarean sections among people with obesity are associated with increased complications, such as higher rates of infection and wound complications, than for people with lower BMI,” Dr. Grasch said. “Operative vaginal delivery can be an alternative to cesarean delivery in some situations, so we were interested in whether attempted operative vaginal delivery was also associated with higher rates of complications in individuals with obesity than those without obesity.”

The researchers focused on 791 patients with an attempted operative vaginal delivery. About 40% had a BMI of 30 or greater. Clinicians used a vacuum in approximately 60% of the attempts.

After an attempted vacuum-assisted delivery, neonatal morbidity was more common for infants whose mothers had obesity than for those whose mothers did not (32.7% vs. 22.3%; adjusted odds ratio, 1.61 [1.07-2.43]). Neonatal morbidity did not differ by obesity status following forceps-attempted delivery. Other adverse outcomes, including measures of maternal morbidity, did not significantly differ by obesity status, according to the researchers.
 

Choice may come down to experience

Several factors influence whether a clinician chooses forceps- or vacuum-assisted delivery or cesarean delivery, “but one of the most important is experience,” Dr. Grasch said. “Complication rates with both forms of operative vaginal delivery are low, yet there has been a trend toward lower rates of both in the last few decades.”

Elizabeth Cochrane, MD, a maternal-fetal medicine fellow at Mount Sinai Hospital, New York, and her colleagues investigated the relationship between obesity and adverse outcomes among patients with forceps-assisted vaginal deliveries.

The researchers analyzed data from 897 patients who underwent a forceps-assisted vaginal delivery between 2017 and 2021; 29% had a BMI of 30 or greater.

Injuries to the anal sphincter – which can lead to fecal incontinence – occurred in 18.7% of patients without obesity and in 17.7% of those with obesity. Admission to the neonatal intensive care unit occurred in 11.5% of patients without obesity and in 12.3% of patients with obesity. The differences were not statistically significant.

The bottom line: For forceps-assisted vaginal delivery, “obesity does not appear to be associated with increased rates” of adverse outcomes for mothers or newborns, the researchers concluded.
 

Reassuring data

The study by Dr. Cochrane’s group “provides helpful information for providers to be reassured when they are performing forceps deliveries” for patients with obesity, Dr. Platner said.

Rates of obesity have risen in the United States, and physicians often wonder whether a patient with obesity could be a candidate for forceps-assisted delivery, Dr. Cochrane said. In 2019, 29% of women had obesity before becoming pregnant.

“It all really comes down to how comfortable the provider is in that skill set and also the overall clinical scenario,” she said. “Sometimes an operative delivery with forceps or a vacuum can be the fastest way to deliver a baby when there is acute concern for maternal decompensation or fetal decompensation.”

The alternative is an emergency cesarean delivery. Given that those operations can be riskier and more difficult for patients with higher BMIs, a forceps-assisted delivery may be “an interesting alternative to emergency caesarean sections, as long as it is in an appropriate clinical setting with providers who feel very confident and comfortable using those devices,” Dr. Cochrane said.

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

Among patients who undergo forceps-assisted vaginal delivery, obesity does not appear to be associated with increased risk for complications such as injuries to the anal sphincter or the need for their babies to be admitted to the neonatal intensive care unit, researchers have found.

But obesity does appear to increase the chances that when physicians attempt operative vaginal delivery with either forceps or a vacuum, patients will wind up undergoing cesarean delivery, another study found.

Taken together, the new data may help inform physicians’ decisions about when to consider operative vaginal delivery as an alternative to emergency cesarean births.

A prospective study showed that failed operative vaginal delivery – that is, a cesarean delivery after an attempted operative vaginal delivery – occurred for 10.1% of patients with obesity and 4.2% of those without obesity.

Researchers presented the findings at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“We want to really try to reduce the rate of C-sections and primary cesarean deliveries. One of the ways to do that is to attempt operative vaginal delivery,” said Marissa Platner, MD, assistant professor of maternal-fetal medicine at Emory University School of Medicine, Atlanta, who was not involved in the new research.

Data on how obesity influences risks with operative vaginal delivery have been limited and mixed, the researchers said.

To examine how often attempted operative vaginal delivery fails in patients with obesity, Jennifer Grasch, MD, a maternal-fetal medicine fellow at the Ohio State University Wexner Medical Center, Columbus, and her colleagues conducted a secondary analysis of data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, which included more than 10,000 participants.

“We know that cesarean sections among people with obesity are associated with increased complications, such as higher rates of infection and wound complications, than for people with lower BMI,” Dr. Grasch said. “Operative vaginal delivery can be an alternative to cesarean delivery in some situations, so we were interested in whether attempted operative vaginal delivery was also associated with higher rates of complications in individuals with obesity than those without obesity.”

The researchers focused on 791 patients with an attempted operative vaginal delivery. About 40% had a BMI of 30 or greater. Clinicians used a vacuum in approximately 60% of the attempts.

After an attempted vacuum-assisted delivery, neonatal morbidity was more common for infants whose mothers had obesity than for those whose mothers did not (32.7% vs. 22.3%; adjusted odds ratio, 1.61 [1.07-2.43]). Neonatal morbidity did not differ by obesity status following forceps-attempted delivery. Other adverse outcomes, including measures of maternal morbidity, did not significantly differ by obesity status, according to the researchers.
 

Choice may come down to experience

Several factors influence whether a clinician chooses forceps- or vacuum-assisted delivery or cesarean delivery, “but one of the most important is experience,” Dr. Grasch said. “Complication rates with both forms of operative vaginal delivery are low, yet there has been a trend toward lower rates of both in the last few decades.”

Elizabeth Cochrane, MD, a maternal-fetal medicine fellow at Mount Sinai Hospital, New York, and her colleagues investigated the relationship between obesity and adverse outcomes among patients with forceps-assisted vaginal deliveries.

The researchers analyzed data from 897 patients who underwent a forceps-assisted vaginal delivery between 2017 and 2021; 29% had a BMI of 30 or greater.

Injuries to the anal sphincter – which can lead to fecal incontinence – occurred in 18.7% of patients without obesity and in 17.7% of those with obesity. Admission to the neonatal intensive care unit occurred in 11.5% of patients without obesity and in 12.3% of patients with obesity. The differences were not statistically significant.

The bottom line: For forceps-assisted vaginal delivery, “obesity does not appear to be associated with increased rates” of adverse outcomes for mothers or newborns, the researchers concluded.
 

Reassuring data

The study by Dr. Cochrane’s group “provides helpful information for providers to be reassured when they are performing forceps deliveries” for patients with obesity, Dr. Platner said.

Rates of obesity have risen in the United States, and physicians often wonder whether a patient with obesity could be a candidate for forceps-assisted delivery, Dr. Cochrane said. In 2019, 29% of women had obesity before becoming pregnant.

“It all really comes down to how comfortable the provider is in that skill set and also the overall clinical scenario,” she said. “Sometimes an operative delivery with forceps or a vacuum can be the fastest way to deliver a baby when there is acute concern for maternal decompensation or fetal decompensation.”

The alternative is an emergency cesarean delivery. Given that those operations can be riskier and more difficult for patients with higher BMIs, a forceps-assisted delivery may be “an interesting alternative to emergency caesarean sections, as long as it is in an appropriate clinical setting with providers who feel very confident and comfortable using those devices,” Dr. Cochrane said.

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

Among patients who undergo forceps-assisted vaginal delivery, obesity does not appear to be associated with increased risk for complications such as injuries to the anal sphincter or the need for their babies to be admitted to the neonatal intensive care unit, researchers have found.

But obesity does appear to increase the chances that when physicians attempt operative vaginal delivery with either forceps or a vacuum, patients will wind up undergoing cesarean delivery, another study found.

Taken together, the new data may help inform physicians’ decisions about when to consider operative vaginal delivery as an alternative to emergency cesarean births.

A prospective study showed that failed operative vaginal delivery – that is, a cesarean delivery after an attempted operative vaginal delivery – occurred for 10.1% of patients with obesity and 4.2% of those without obesity.

Researchers presented the findings at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“We want to really try to reduce the rate of C-sections and primary cesarean deliveries. One of the ways to do that is to attempt operative vaginal delivery,” said Marissa Platner, MD, assistant professor of maternal-fetal medicine at Emory University School of Medicine, Atlanta, who was not involved in the new research.

Data on how obesity influences risks with operative vaginal delivery have been limited and mixed, the researchers said.

To examine how often attempted operative vaginal delivery fails in patients with obesity, Jennifer Grasch, MD, a maternal-fetal medicine fellow at the Ohio State University Wexner Medical Center, Columbus, and her colleagues conducted a secondary analysis of data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, which included more than 10,000 participants.

“We know that cesarean sections among people with obesity are associated with increased complications, such as higher rates of infection and wound complications, than for people with lower BMI,” Dr. Grasch said. “Operative vaginal delivery can be an alternative to cesarean delivery in some situations, so we were interested in whether attempted operative vaginal delivery was also associated with higher rates of complications in individuals with obesity than those without obesity.”

The researchers focused on 791 patients with an attempted operative vaginal delivery. About 40% had a BMI of 30 or greater. Clinicians used a vacuum in approximately 60% of the attempts.

After an attempted vacuum-assisted delivery, neonatal morbidity was more common for infants whose mothers had obesity than for those whose mothers did not (32.7% vs. 22.3%; adjusted odds ratio, 1.61 [1.07-2.43]). Neonatal morbidity did not differ by obesity status following forceps-attempted delivery. Other adverse outcomes, including measures of maternal morbidity, did not significantly differ by obesity status, according to the researchers.
 

Choice may come down to experience

Several factors influence whether a clinician chooses forceps- or vacuum-assisted delivery or cesarean delivery, “but one of the most important is experience,” Dr. Grasch said. “Complication rates with both forms of operative vaginal delivery are low, yet there has been a trend toward lower rates of both in the last few decades.”

Elizabeth Cochrane, MD, a maternal-fetal medicine fellow at Mount Sinai Hospital, New York, and her colleagues investigated the relationship between obesity and adverse outcomes among patients with forceps-assisted vaginal deliveries.

The researchers analyzed data from 897 patients who underwent a forceps-assisted vaginal delivery between 2017 and 2021; 29% had a BMI of 30 or greater.

Injuries to the anal sphincter – which can lead to fecal incontinence – occurred in 18.7% of patients without obesity and in 17.7% of those with obesity. Admission to the neonatal intensive care unit occurred in 11.5% of patients without obesity and in 12.3% of patients with obesity. The differences were not statistically significant.

The bottom line: For forceps-assisted vaginal delivery, “obesity does not appear to be associated with increased rates” of adverse outcomes for mothers or newborns, the researchers concluded.
 

Reassuring data

The study by Dr. Cochrane’s group “provides helpful information for providers to be reassured when they are performing forceps deliveries” for patients with obesity, Dr. Platner said.

Rates of obesity have risen in the United States, and physicians often wonder whether a patient with obesity could be a candidate for forceps-assisted delivery, Dr. Cochrane said. In 2019, 29% of women had obesity before becoming pregnant.

“It all really comes down to how comfortable the provider is in that skill set and also the overall clinical scenario,” she said. “Sometimes an operative delivery with forceps or a vacuum can be the fastest way to deliver a baby when there is acute concern for maternal decompensation or fetal decompensation.”

The alternative is an emergency cesarean delivery. Given that those operations can be riskier and more difficult for patients with higher BMIs, a forceps-assisted delivery may be “an interesting alternative to emergency caesarean sections, as long as it is in an appropriate clinical setting with providers who feel very confident and comfortable using those devices,” Dr. Cochrane said.

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

NEW ORLEANS – Adults with moderate to severe chronic hand eczema who were randomized to treatment with delgocitinib cream had significantly greater improvement in efficacy outcomes at 16 weeks, compared with those who received vehicle cream, results from a pivotal phase 3 trial showed.

“Chronic hand eczema is the most frequent chronic inflammatory disorder affecting the hands,” Robert Bissonnette, MD, a dermatologist who is founder and CEO of Innovaderm Research, said at the annual meeting of the American Academy of Dermatology, where the study was presented during a late-breaking research session. “It’s associated with pain, pruritus, and has a huge impact on quality of life,” and results with current topical treatments are often unsatisfactory, he noted.

Delgocitinib is an investigational topical pan-JAK inhibitor that inhibits activation of the JAK-STAT pathway and targets key mediators of chronic hand eczema. In a phase 2b dose-ranging trial, twice-daily treatment with delgocitinib cream demonstrated significantly greater efficacy, compared with the cream vehicle, and was well tolerated in adults with mild to severe chronic hand eczema.

Injenerker/Getty Images

For the phase 3 study, known as DELTA 1, researchers randomized 487 adults with moderate to severe chronic hand eczema to receive twice-daily applications of delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. After week 16, patients had the option to enter a long-term extension trial, which is currently ongoing. DELTA 1 was limited to adults with a diagnosis of chronic hand eczema defined as hand eczema that had persisted for more than 3 months or had returned more than twice within the past 12 months; an Investigator’s Global Assessment for chronic hand eczema (IGA-CHE) score of 3 (moderate) or 4 (severe); a weekly average Hand Eczema Symptom Diary (HESD) itch score of 4 or more points, and a medical history of inadequate response to topical corticosteroids within the past 12 months or for whom treatment with topical corticosteroids was not medically advisable.

The IGA-CHE scale used in the trial was new, “where, in order to be almost clear, the only sign that could be present on the skin was barely perceptible erythema,” Dr. Bissonnette said. He noted that he has used many IGA scales over the more than 25 years he has been involved with clinical trials, and “this was the first that used a scale with a bar so high.” Key secondary endpoints include a 75% and 90% improvement in Hand Eczema Severity Index (HECSI) from baseline at week 16 and a 4-point or greater improvement in the Dermatology Life Quality Index (DLQI) from baseline at week 16.

The median age of patients was 44 years, 88% were White, 4% were Asian, 1% were Black, and the remainder were from other racial groups. One-third of patients (33%) had severe hand eczema based on their IGA-CHE score, the median HECSI was 65 (in line with severe disease), and the median DLQI was 12. As for previous chronic hand eczema treatments, 19% had undergone phototherapy, 14% had tried oral retinoids, and 12% had tried oral corticosteroids.

In the study, a greater proportion of delgocitinib-treated patients achieved the primary endpoint of IGA-CHE 0/1, compared with the cream vehicle group at week 4 (15.4% vs. 4.9%; P < .001); week 8 (22.8% vs. 10.5%; P = .001), and week 16 (19.7% vs. 9.9%; P = .006). “As early as week 2, there is a separation between cream and vehicle,” Dr. Bissonnette said. When reviewing the results and the patients in the trial, he said that, in his personal opinion, “I don’t think this is uniquely representative of the efficacy of the drug,” because of the IGA scale that was used, which set such a high bar for efficacy.

As for secondary endpoints, a greater proportion of delgocitinib-treated patients than those in the vehicle group achieved a HESCI-75 (49.2% vs. 23.5%), a HECSI-90 (29.5% vs. 12.3%), and a 4-point or greater improvement on the DLQI (74.4% vs 50%; P < .001 for all endpoints).

Delgocitinib had a similar safety profile as the vehicle over 16 weeks, with no difference between the delgocitinib and vehicle arms in the proportion of patients who had adverse events (45.2% vs. 50.6%, respectively) and serious adverse events (1.8% vs. 1.9%). The most common adverse events (defined as 5% or greater in any treatment group) during the study were COVID-19 infections and nasopharyngitis; rates were comparable in the two arms.

Raj Chovatiya, MD, PhD, a dermatologist who directs the Center for Eczema and Itch at Northwestern University, Chicago, who was asked to comment on the study, said that chronic hand eczema can be functionally limiting for many patients. “Given its focal symptoms but multifaceted immunopathogenesis, topical JAK inhibition represents a rational strategy for targeted treatment,” Dr. Chovatiya told this news organization. He was not an investigator in the trial.

“In the phase 3 DELTA 1 study, topical delgocitinib cream was superior to vehicle control with nearly one out of five patients achieving clear or almost clear skin, with no difference in total adverse events between groups. While both comparative and long-term data would be helpful to better assess how delgocitinib cream stacks up against common topical anti-inflammatories and how it may be used for a chronic condition that typically requires ongoing treatment, these findings move us closer to a potential first-in-class approved therapy for chronic hand eczema.”

Dr. Bissonnette disclosed that he served as a consultant and investigator for the developer of delgocitinib, LEO Pharma, on this study. He has also received grants and research funding from many other pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for several pharmaceutical companies, including LEO Pharma.

NEW ORLEANS – Adults with moderate to severe chronic hand eczema who were randomized to treatment with delgocitinib cream had significantly greater improvement in efficacy outcomes at 16 weeks, compared with those who received vehicle cream, results from a pivotal phase 3 trial showed.

“Chronic hand eczema is the most frequent chronic inflammatory disorder affecting the hands,” Robert Bissonnette, MD, a dermatologist who is founder and CEO of Innovaderm Research, said at the annual meeting of the American Academy of Dermatology, where the study was presented during a late-breaking research session. “It’s associated with pain, pruritus, and has a huge impact on quality of life,” and results with current topical treatments are often unsatisfactory, he noted.

Delgocitinib is an investigational topical pan-JAK inhibitor that inhibits activation of the JAK-STAT pathway and targets key mediators of chronic hand eczema. In a phase 2b dose-ranging trial, twice-daily treatment with delgocitinib cream demonstrated significantly greater efficacy, compared with the cream vehicle, and was well tolerated in adults with mild to severe chronic hand eczema.

Injenerker/Getty Images

For the phase 3 study, known as DELTA 1, researchers randomized 487 adults with moderate to severe chronic hand eczema to receive twice-daily applications of delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. After week 16, patients had the option to enter a long-term extension trial, which is currently ongoing. DELTA 1 was limited to adults with a diagnosis of chronic hand eczema defined as hand eczema that had persisted for more than 3 months or had returned more than twice within the past 12 months; an Investigator’s Global Assessment for chronic hand eczema (IGA-CHE) score of 3 (moderate) or 4 (severe); a weekly average Hand Eczema Symptom Diary (HESD) itch score of 4 or more points, and a medical history of inadequate response to topical corticosteroids within the past 12 months or for whom treatment with topical corticosteroids was not medically advisable.

The IGA-CHE scale used in the trial was new, “where, in order to be almost clear, the only sign that could be present on the skin was barely perceptible erythema,” Dr. Bissonnette said. He noted that he has used many IGA scales over the more than 25 years he has been involved with clinical trials, and “this was the first that used a scale with a bar so high.” Key secondary endpoints include a 75% and 90% improvement in Hand Eczema Severity Index (HECSI) from baseline at week 16 and a 4-point or greater improvement in the Dermatology Life Quality Index (DLQI) from baseline at week 16.

The median age of patients was 44 years, 88% were White, 4% were Asian, 1% were Black, and the remainder were from other racial groups. One-third of patients (33%) had severe hand eczema based on their IGA-CHE score, the median HECSI was 65 (in line with severe disease), and the median DLQI was 12. As for previous chronic hand eczema treatments, 19% had undergone phototherapy, 14% had tried oral retinoids, and 12% had tried oral corticosteroids.

In the study, a greater proportion of delgocitinib-treated patients achieved the primary endpoint of IGA-CHE 0/1, compared with the cream vehicle group at week 4 (15.4% vs. 4.9%; P < .001); week 8 (22.8% vs. 10.5%; P = .001), and week 16 (19.7% vs. 9.9%; P = .006). “As early as week 2, there is a separation between cream and vehicle,” Dr. Bissonnette said. When reviewing the results and the patients in the trial, he said that, in his personal opinion, “I don’t think this is uniquely representative of the efficacy of the drug,” because of the IGA scale that was used, which set such a high bar for efficacy.

As for secondary endpoints, a greater proportion of delgocitinib-treated patients than those in the vehicle group achieved a HESCI-75 (49.2% vs. 23.5%), a HECSI-90 (29.5% vs. 12.3%), and a 4-point or greater improvement on the DLQI (74.4% vs 50%; P < .001 for all endpoints).

Delgocitinib had a similar safety profile as the vehicle over 16 weeks, with no difference between the delgocitinib and vehicle arms in the proportion of patients who had adverse events (45.2% vs. 50.6%, respectively) and serious adverse events (1.8% vs. 1.9%). The most common adverse events (defined as 5% or greater in any treatment group) during the study were COVID-19 infections and nasopharyngitis; rates were comparable in the two arms.

Raj Chovatiya, MD, PhD, a dermatologist who directs the Center for Eczema and Itch at Northwestern University, Chicago, who was asked to comment on the study, said that chronic hand eczema can be functionally limiting for many patients. “Given its focal symptoms but multifaceted immunopathogenesis, topical JAK inhibition represents a rational strategy for targeted treatment,” Dr. Chovatiya told this news organization. He was not an investigator in the trial.

“In the phase 3 DELTA 1 study, topical delgocitinib cream was superior to vehicle control with nearly one out of five patients achieving clear or almost clear skin, with no difference in total adverse events between groups. While both comparative and long-term data would be helpful to better assess how delgocitinib cream stacks up against common topical anti-inflammatories and how it may be used for a chronic condition that typically requires ongoing treatment, these findings move us closer to a potential first-in-class approved therapy for chronic hand eczema.”

Dr. Bissonnette disclosed that he served as a consultant and investigator for the developer of delgocitinib, LEO Pharma, on this study. He has also received grants and research funding from many other pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for several pharmaceutical companies, including LEO Pharma.

NEW ORLEANS – Adults with moderate to severe chronic hand eczema who were randomized to treatment with delgocitinib cream had significantly greater improvement in efficacy outcomes at 16 weeks, compared with those who received vehicle cream, results from a pivotal phase 3 trial showed.

“Chronic hand eczema is the most frequent chronic inflammatory disorder affecting the hands,” Robert Bissonnette, MD, a dermatologist who is founder and CEO of Innovaderm Research, said at the annual meeting of the American Academy of Dermatology, where the study was presented during a late-breaking research session. “It’s associated with pain, pruritus, and has a huge impact on quality of life,” and results with current topical treatments are often unsatisfactory, he noted.

Delgocitinib is an investigational topical pan-JAK inhibitor that inhibits activation of the JAK-STAT pathway and targets key mediators of chronic hand eczema. In a phase 2b dose-ranging trial, twice-daily treatment with delgocitinib cream demonstrated significantly greater efficacy, compared with the cream vehicle, and was well tolerated in adults with mild to severe chronic hand eczema.

Injenerker/Getty Images

For the phase 3 study, known as DELTA 1, researchers randomized 487 adults with moderate to severe chronic hand eczema to receive twice-daily applications of delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. After week 16, patients had the option to enter a long-term extension trial, which is currently ongoing. DELTA 1 was limited to adults with a diagnosis of chronic hand eczema defined as hand eczema that had persisted for more than 3 months or had returned more than twice within the past 12 months; an Investigator’s Global Assessment for chronic hand eczema (IGA-CHE) score of 3 (moderate) or 4 (severe); a weekly average Hand Eczema Symptom Diary (HESD) itch score of 4 or more points, and a medical history of inadequate response to topical corticosteroids within the past 12 months or for whom treatment with topical corticosteroids was not medically advisable.

The IGA-CHE scale used in the trial was new, “where, in order to be almost clear, the only sign that could be present on the skin was barely perceptible erythema,” Dr. Bissonnette said. He noted that he has used many IGA scales over the more than 25 years he has been involved with clinical trials, and “this was the first that used a scale with a bar so high.” Key secondary endpoints include a 75% and 90% improvement in Hand Eczema Severity Index (HECSI) from baseline at week 16 and a 4-point or greater improvement in the Dermatology Life Quality Index (DLQI) from baseline at week 16.

The median age of patients was 44 years, 88% were White, 4% were Asian, 1% were Black, and the remainder were from other racial groups. One-third of patients (33%) had severe hand eczema based on their IGA-CHE score, the median HECSI was 65 (in line with severe disease), and the median DLQI was 12. As for previous chronic hand eczema treatments, 19% had undergone phototherapy, 14% had tried oral retinoids, and 12% had tried oral corticosteroids.

In the study, a greater proportion of delgocitinib-treated patients achieved the primary endpoint of IGA-CHE 0/1, compared with the cream vehicle group at week 4 (15.4% vs. 4.9%; P < .001); week 8 (22.8% vs. 10.5%; P = .001), and week 16 (19.7% vs. 9.9%; P = .006). “As early as week 2, there is a separation between cream and vehicle,” Dr. Bissonnette said. When reviewing the results and the patients in the trial, he said that, in his personal opinion, “I don’t think this is uniquely representative of the efficacy of the drug,” because of the IGA scale that was used, which set such a high bar for efficacy.

As for secondary endpoints, a greater proportion of delgocitinib-treated patients than those in the vehicle group achieved a HESCI-75 (49.2% vs. 23.5%), a HECSI-90 (29.5% vs. 12.3%), and a 4-point or greater improvement on the DLQI (74.4% vs 50%; P < .001 for all endpoints).

Delgocitinib had a similar safety profile as the vehicle over 16 weeks, with no difference between the delgocitinib and vehicle arms in the proportion of patients who had adverse events (45.2% vs. 50.6%, respectively) and serious adverse events (1.8% vs. 1.9%). The most common adverse events (defined as 5% or greater in any treatment group) during the study were COVID-19 infections and nasopharyngitis; rates were comparable in the two arms.

Raj Chovatiya, MD, PhD, a dermatologist who directs the Center for Eczema and Itch at Northwestern University, Chicago, who was asked to comment on the study, said that chronic hand eczema can be functionally limiting for many patients. “Given its focal symptoms but multifaceted immunopathogenesis, topical JAK inhibition represents a rational strategy for targeted treatment,” Dr. Chovatiya told this news organization. He was not an investigator in the trial.

“In the phase 3 DELTA 1 study, topical delgocitinib cream was superior to vehicle control with nearly one out of five patients achieving clear or almost clear skin, with no difference in total adverse events between groups. While both comparative and long-term data would be helpful to better assess how delgocitinib cream stacks up against common topical anti-inflammatories and how it may be used for a chronic condition that typically requires ongoing treatment, these findings move us closer to a potential first-in-class approved therapy for chronic hand eczema.”

Dr. Bissonnette disclosed that he served as a consultant and investigator for the developer of delgocitinib, LEO Pharma, on this study. He has also received grants and research funding from many other pharmaceutical companies. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for several pharmaceutical companies, including LEO Pharma.

Surgeons who accept vacations and other freebies from medical device companies could face penalties like fines, stricter oversight, and even jail time, according to experts familiar with the federal Anti-Kickback Statute.

Historically, enforcement actions have primarily focused on the person or organization offering the perks – and not necessarily the physicians accepting it, Steven W. Ortquist, founder and principal of Arete Compliance Solutions, LLC, in Phoenix, told this news organization.

But that’s changing.

“In recent years, we are seeing a trend toward holding physicians and others on the receiving end of the inducement accountable as well,” said Mr. Ortquist, who is a past board member and president of the Health Care Compliance Association. He noted that authorities usually pursue the inducing company first before moving on to individual clinicians or practices.

The Department of Justice followed a similar pattern in a recently announced kickback settlement that ensnared an intraocular lens distributor, an ophthalmology equipment supplier, two CEOs, and a surgeon. Precision Lens must pay more than $43 million for offering high-end vacations and other expensive perks to surgeons who used its cataract products.

The verdict marks the end of a 6-week civil jury trial, where evidence emerged that Paul Ehlen, owner of Precision Lens and its parent company, Cameron-Ehlen Group, maintained a secret “slush fund” for paying kickbacks to ophthalmic surgeons. The inducement scheme netted the Minnesota-based company millions in sales and led to the submission of 64,575 false Medicare claims from 2006 to 2015, a violation of the Anti-Kickback Statute and the False Claims Act.

According to court documents, physicians received luxury travel and entertainment packages, including skiing, fishing, and golfing excursions at exclusive destinations, often traveling via private jet to attend Broadway musicals and major sporting events. Mr. Ehlen and company representatives also sold frequent flyer miles to physicians at a steep discount, allowing them to take personal and business trips below fair market value.

Federal authorities initially announced an investigation into the business practices of Precision Lens in 2017 after receiving a whistleblower complaint from Kipp Fesenmaier, a former executive at Sightpath Medical, an ophthalmology supplier and “corporate partner” of Precision Lens. Mr. Fesenmaier alleged that both companies were involved in an inducement scheme.

Sightpath Medical and its CEO, James Tiffany, agreed to a $12 million settlement to resolve the kickback allegations.

The Department of Justice subsequently investigated Jitendra Swarup, MD, an ophthalmologist and cataract surgeon who allegedly received “unlawful remuneration from Sightpath, Precision, and Ehlen” and filed false insurance claims. In addition to accepting expensive hunting and fishing trips from the medical device companies, Dr. Swarup was paid more than $100,000 per year for consulting services he did not fully render.

Dr. Swarup agreed to a nearly $3 million settlement and participation in a 3-year corporate integrity agreement with the Office of Inspector General. In exchange for compliance with such contracts, the OIG permits physicians to continue participating in Medicare, Medicaid, and other federal health care programs.

In a statement from attorneys, Precision Lens and Mr. Ehlen pledged to appeal the verdict and “defend ... our wholly appropriate actions” while remaining focused on their commitment to health care clinicians and manufacturers.
 

‘Endless’ opportunities for inducement

Unfortunately, opportunities for inducement are “endless,” experts say. Extravagant trips, dinners, and gifts can trigger a violation, but so can nearly anything of value.

Just last year, Biotronik reached a $12.95 million settlement amid allegations that company representatives wined and dined physicians to induce their use of its pacemakers and defibrillators. To date, no physicians have been charged.

But after a record-breaking number of whistleblower judgments last fiscal year totaling more than $2 billion, physicians should take note, Radha Bhatnagar, Esq, director of compliance at The CM Group, told the news organization.

“When manufacturers offer physicians kickbacks with the added element of fraudulent Medicare or Medicaid reimbursements, that is typically when manufacturers and individuals face civil and criminal liability,” said Ms. Bhatnagar, something the Department of Justice alluded to when announcing a settlement involving 15 Texas physicians last year.

In another case, Kingsley R. Chin, an orthopedic surgeon and designer of a spinal implant, was indicted in 2021 for paying millions of dollars in sham consulting fees to physicians who used his products. At least six surgeons who accepted money from Dr. Chin were later named in a civil case and ordered to pay $3.3 million in penalties.

Jason Montone, DO, an orthopedic surgeon who accepted the illicit payments, agreed to a plea deal with a reduced prison sentence, 1 year of supervised release, and a fine of $379,000.

Although Dr. Chin’s sentencing hasn’t been announced, violating kickback laws can result in a sentence of up to 10 years.
 

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

Surgeons who accept vacations and other freebies from medical device companies could face penalties like fines, stricter oversight, and even jail time, according to experts familiar with the federal Anti-Kickback Statute.

Historically, enforcement actions have primarily focused on the person or organization offering the perks – and not necessarily the physicians accepting it, Steven W. Ortquist, founder and principal of Arete Compliance Solutions, LLC, in Phoenix, told this news organization.

But that’s changing.

“In recent years, we are seeing a trend toward holding physicians and others on the receiving end of the inducement accountable as well,” said Mr. Ortquist, who is a past board member and president of the Health Care Compliance Association. He noted that authorities usually pursue the inducing company first before moving on to individual clinicians or practices.

The Department of Justice followed a similar pattern in a recently announced kickback settlement that ensnared an intraocular lens distributor, an ophthalmology equipment supplier, two CEOs, and a surgeon. Precision Lens must pay more than $43 million for offering high-end vacations and other expensive perks to surgeons who used its cataract products.

The verdict marks the end of a 6-week civil jury trial, where evidence emerged that Paul Ehlen, owner of Precision Lens and its parent company, Cameron-Ehlen Group, maintained a secret “slush fund” for paying kickbacks to ophthalmic surgeons. The inducement scheme netted the Minnesota-based company millions in sales and led to the submission of 64,575 false Medicare claims from 2006 to 2015, a violation of the Anti-Kickback Statute and the False Claims Act.

According to court documents, physicians received luxury travel and entertainment packages, including skiing, fishing, and golfing excursions at exclusive destinations, often traveling via private jet to attend Broadway musicals and major sporting events. Mr. Ehlen and company representatives also sold frequent flyer miles to physicians at a steep discount, allowing them to take personal and business trips below fair market value.

Federal authorities initially announced an investigation into the business practices of Precision Lens in 2017 after receiving a whistleblower complaint from Kipp Fesenmaier, a former executive at Sightpath Medical, an ophthalmology supplier and “corporate partner” of Precision Lens. Mr. Fesenmaier alleged that both companies were involved in an inducement scheme.

Sightpath Medical and its CEO, James Tiffany, agreed to a $12 million settlement to resolve the kickback allegations.

The Department of Justice subsequently investigated Jitendra Swarup, MD, an ophthalmologist and cataract surgeon who allegedly received “unlawful remuneration from Sightpath, Precision, and Ehlen” and filed false insurance claims. In addition to accepting expensive hunting and fishing trips from the medical device companies, Dr. Swarup was paid more than $100,000 per year for consulting services he did not fully render.

Dr. Swarup agreed to a nearly $3 million settlement and participation in a 3-year corporate integrity agreement with the Office of Inspector General. In exchange for compliance with such contracts, the OIG permits physicians to continue participating in Medicare, Medicaid, and other federal health care programs.

In a statement from attorneys, Precision Lens and Mr. Ehlen pledged to appeal the verdict and “defend ... our wholly appropriate actions” while remaining focused on their commitment to health care clinicians and manufacturers.
 

‘Endless’ opportunities for inducement

Unfortunately, opportunities for inducement are “endless,” experts say. Extravagant trips, dinners, and gifts can trigger a violation, but so can nearly anything of value.

Just last year, Biotronik reached a $12.95 million settlement amid allegations that company representatives wined and dined physicians to induce their use of its pacemakers and defibrillators. To date, no physicians have been charged.

But after a record-breaking number of whistleblower judgments last fiscal year totaling more than $2 billion, physicians should take note, Radha Bhatnagar, Esq, director of compliance at The CM Group, told the news organization.

“When manufacturers offer physicians kickbacks with the added element of fraudulent Medicare or Medicaid reimbursements, that is typically when manufacturers and individuals face civil and criminal liability,” said Ms. Bhatnagar, something the Department of Justice alluded to when announcing a settlement involving 15 Texas physicians last year.

In another case, Kingsley R. Chin, an orthopedic surgeon and designer of a spinal implant, was indicted in 2021 for paying millions of dollars in sham consulting fees to physicians who used his products. At least six surgeons who accepted money from Dr. Chin were later named in a civil case and ordered to pay $3.3 million in penalties.

Jason Montone, DO, an orthopedic surgeon who accepted the illicit payments, agreed to a plea deal with a reduced prison sentence, 1 year of supervised release, and a fine of $379,000.

Although Dr. Chin’s sentencing hasn’t been announced, violating kickback laws can result in a sentence of up to 10 years.
 

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

Surgeons who accept vacations and other freebies from medical device companies could face penalties like fines, stricter oversight, and even jail time, according to experts familiar with the federal Anti-Kickback Statute.

Historically, enforcement actions have primarily focused on the person or organization offering the perks – and not necessarily the physicians accepting it, Steven W. Ortquist, founder and principal of Arete Compliance Solutions, LLC, in Phoenix, told this news organization.

But that’s changing.

“In recent years, we are seeing a trend toward holding physicians and others on the receiving end of the inducement accountable as well,” said Mr. Ortquist, who is a past board member and president of the Health Care Compliance Association. He noted that authorities usually pursue the inducing company first before moving on to individual clinicians or practices.

The Department of Justice followed a similar pattern in a recently announced kickback settlement that ensnared an intraocular lens distributor, an ophthalmology equipment supplier, two CEOs, and a surgeon. Precision Lens must pay more than $43 million for offering high-end vacations and other expensive perks to surgeons who used its cataract products.

The verdict marks the end of a 6-week civil jury trial, where evidence emerged that Paul Ehlen, owner of Precision Lens and its parent company, Cameron-Ehlen Group, maintained a secret “slush fund” for paying kickbacks to ophthalmic surgeons. The inducement scheme netted the Minnesota-based company millions in sales and led to the submission of 64,575 false Medicare claims from 2006 to 2015, a violation of the Anti-Kickback Statute and the False Claims Act.

According to court documents, physicians received luxury travel and entertainment packages, including skiing, fishing, and golfing excursions at exclusive destinations, often traveling via private jet to attend Broadway musicals and major sporting events. Mr. Ehlen and company representatives also sold frequent flyer miles to physicians at a steep discount, allowing them to take personal and business trips below fair market value.

Federal authorities initially announced an investigation into the business practices of Precision Lens in 2017 after receiving a whistleblower complaint from Kipp Fesenmaier, a former executive at Sightpath Medical, an ophthalmology supplier and “corporate partner” of Precision Lens. Mr. Fesenmaier alleged that both companies were involved in an inducement scheme.

Sightpath Medical and its CEO, James Tiffany, agreed to a $12 million settlement to resolve the kickback allegations.

The Department of Justice subsequently investigated Jitendra Swarup, MD, an ophthalmologist and cataract surgeon who allegedly received “unlawful remuneration from Sightpath, Precision, and Ehlen” and filed false insurance claims. In addition to accepting expensive hunting and fishing trips from the medical device companies, Dr. Swarup was paid more than $100,000 per year for consulting services he did not fully render.

Dr. Swarup agreed to a nearly $3 million settlement and participation in a 3-year corporate integrity agreement with the Office of Inspector General. In exchange for compliance with such contracts, the OIG permits physicians to continue participating in Medicare, Medicaid, and other federal health care programs.

In a statement from attorneys, Precision Lens and Mr. Ehlen pledged to appeal the verdict and “defend ... our wholly appropriate actions” while remaining focused on their commitment to health care clinicians and manufacturers.
 

‘Endless’ opportunities for inducement

Unfortunately, opportunities for inducement are “endless,” experts say. Extravagant trips, dinners, and gifts can trigger a violation, but so can nearly anything of value.

Just last year, Biotronik reached a $12.95 million settlement amid allegations that company representatives wined and dined physicians to induce their use of its pacemakers and defibrillators. To date, no physicians have been charged.

But after a record-breaking number of whistleblower judgments last fiscal year totaling more than $2 billion, physicians should take note, Radha Bhatnagar, Esq, director of compliance at The CM Group, told the news organization.

“When manufacturers offer physicians kickbacks with the added element of fraudulent Medicare or Medicaid reimbursements, that is typically when manufacturers and individuals face civil and criminal liability,” said Ms. Bhatnagar, something the Department of Justice alluded to when announcing a settlement involving 15 Texas physicians last year.

In another case, Kingsley R. Chin, an orthopedic surgeon and designer of a spinal implant, was indicted in 2021 for paying millions of dollars in sham consulting fees to physicians who used his products. At least six surgeons who accepted money from Dr. Chin were later named in a civil case and ordered to pay $3.3 million in penalties.

Jason Montone, DO, an orthopedic surgeon who accepted the illicit payments, agreed to a plea deal with a reduced prison sentence, 1 year of supervised release, and a fine of $379,000.

Although Dr. Chin’s sentencing hasn’t been announced, violating kickback laws can result in a sentence of up to 10 years.
 

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

A doctor and one of Idaho’s premier emergency medicine groups must pay millions of dollars to a stroke patient and his wife in what is being called the second-largest medical malpractice award in the state’s history, according to a report in the Idaho Capital Sun.

The suit, which took nearly 5 years after filing to wend its way through the courts, stems from an incident that took place in the early morning of March 29, 2016. An Ada County resident peered into the family bathroom and discovered that her husband, Carl B. Stiefel, lay on the floor confused and vomiting and complaining of a severe headache. Recently, the man had experienced several of these same symptoms, plus sinus congestion, dizziness, and tinnitus.

As Mr. Stiefel’s confusion worsened, his wife called for an ambulance, which arrived at the local hospital emergency department (ED) at 4:12 AM. Within approximately 11 minutes, the patient was examined by a doctor and later underwent a cranial CT scan, which a second doctor said showed “no intracranial process.”

Mr. Stiefel’s condition improved somewhat, although his dizziness persisted, leaving him still unable to walk. At this point, his primary ED doctor admitted him to the hospital for “benign positional vertigo.” The doctor also joined colleagues in suggesting that the patient might well be a candidate for an MRI, just in case his condition failed to improve over the next few hours.

But the transfer from the ED to the main hospital reportedly took at least 3 hours, during which time Mr. Stiefel’s condition deteriorated. Once admitted, he was observed by a healthcare provider — the news report doesn’t indicate precisely who — to be “delirious without meaningful interaction.” At least 4 hours would pass before the patient was seen by still another doctor, as the plaintiffs later claimed.

The patient remained disoriented and restless as the day unfolded. The MRI contemplated earlier was finally ordered, but the scan wasn’t available for several hours, according to nursing notes cited by the plaintiffs in their lawsuit.

Finally, the scan was administered at about 5:50 PM, almost 12 hours since Mr. Stiefel had first arrived at the ED. It showed that he had a torn artery in his neck and was experiencing a stroke. This was, clearly, a very different diagnosis from the one that his admitting doctor had entered into his notes.

A surgeon operated to repair the arterial tear, but the patient’s condition continued to worsen. Over the next 3 weeks, Mr. Stiefel went from the hospital to a local rehab facility, and back to the hospital with bacterial meningitis. Ultimately, he was diagnosed with “an irreparable brain injury,” which ultimately left him disabled and unable to work.

At this point, he and his wife sued a broad range of defendants — a radiology group, individual healthcare providers employed by the hospital, the primary ED physician, and that doctor’s emergency medicine group. In the nearly 5 intervening years, each of the named defendants settled, except the ED doctor and the emergency medicine group.

The two remaining defendants vigorously contested the claims against them, denying “any and all allegations of responsibility and liability” and contending that the patient’s injuries resulted from unforeseen complications rather than the care that had been administered.

The Ada County jury disagreed, however. It found that the primary ED doctor — and by extension the group to which the doctor belonged — did in fact negligently and recklessly fail to meet the proper standard of care, leading directly to the patient’s life-altering injuries.

For this failure, the jury awarded the plaintiffs $13.5 million, well over the state’s current inflation-adjusted cap of $400,000. (To date, Idaho’s largest med-mal award is nearly $30 million, handed down more than 20 years ago.)

At press time, there was no word of an appeal. 
 

Man sues dentist, ends up changing state medical malpractice law

In a surprise move, the Connecticut Supreme Court in mid-February reversed its own precedent regarding a 2005 law requiring certain pre-litigation steps be taken before state residents are permitted to file a medical malpractice claim, as a story in the Claims Journal reports.

In its 2011 review of that earlier law — passed to ensure that complainants had a reasonable basis for their claims — the high court went the legislature one better. It held that state courts had no “personal jurisdiction” in adjudicating malpractice claims in the absence of required supporting documents — specifically, a proper certificate and opinion letter from “a similar healthcare provider.”

For the past 12 years, this meant that any suit lacking the proper documents could not only be halted but dismissed with prejudice, meaning that such a case couldn’t be refiled.

That interpretation of the law was eventually challenged, however, by a Connecticut man who sued his dentist. Filed in 2018, the suit alleged that, during a root canal, the dentist had failed to properly diagnose and treat his patient’s dental abscess, which ultimately required surgery.

Complying with what he regarded as state law, the man attached a letter of opinion to his complaint, which testified to the merits of his claim. But, in a twist with significant consequences, the letter was written by an endodontist, not a general dentist. In response, the dentist’s attorneys submitted a motion to dismiss to the trial court, arguing that the plaintiff had breached the “similar provider” provision and that therefore the opinion letter was defective and the entire suit should be dismissed.

The trial court agreed — and the Connecticut Appellate Court went on to affirm the lower-court ruling. The case might have ended there, but the plaintiff appealed to the Connecticut Supreme Court, which agreed to review the appellate court finding. 

In a 6-0 decision, the high court looked back on its 2011 interpretation of the med-mal statute, which in the intervening years had given rise to “a body of case law.” The problem with that body of law, the justices argued, was that it had “imposed substantially greater burdens on plaintiffs than the legislature intended” — and it did so “by allowing potentially curable, technical, pre-litigation defects to defeat otherwise meritorious malpractice actions, sometimes after several years of litigation.”

In short, said the justices, there was nothing in the original statute that required a court to dismiss a suit once it found a letter of opinion to be deficient. This was a “curable” defect, one that shouldn’t be allowed to derail an otherwise meritorious claim.

As for the case that prompted the high court’s latest review — that is, the Connecticut man’s suit against his dentist — the justices found that the appellate court had also erred when it tossed out the endodontist’s opinion letter. Technically, the dentist might not have been an endodontist, said the justices, but he had in fact practiced in the field during the course of a long career, so close enough.

The justices kicked the case back to the trial court, with instructions that it deny the defendant’s motion to dismiss.
 

Stakeholders divided over new awards cap

Last month, Iowa Gov. Kim Reynolds signed a bill into law that limits the amount of noneconomic damages a successful med-mal plaintiff can collect, explains a story posted on Radio Iowa, among other news sites.

Under the new law, the limit for suits involving hospitals is capped at $2 million — while those involving all other healthcare providers are capped at $1 million. Beginning in 2028, those caps will be adjusted annually for inflation by 2.1%.

“When mistakes happen, Iowans deserve compensation, but arbitrary multimillion-dollar awards do more than that,” said Gov. Reynolds. “They act as a tax on all Iowans by raising the cost of care. They drive medical clinics out of business and medical students out of state.”

The CEO of Knoxville Hospital and Clinics — a well-known regional provider — agreed, saying that the new law helped to make Iowa “a more attractive place to practice medicine.”

But most Democrats in the GOP-controlled legislature — and 16 Republicans — voted against the legislation. For her part, House Minority Leader Jennifer Konfrst said there was absolutely no evidence that states with caps fared any better with medical workforce shortages than states without caps.
 

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

A doctor and one of Idaho’s premier emergency medicine groups must pay millions of dollars to a stroke patient and his wife in what is being called the second-largest medical malpractice award in the state’s history, according to a report in the Idaho Capital Sun.

The suit, which took nearly 5 years after filing to wend its way through the courts, stems from an incident that took place in the early morning of March 29, 2016. An Ada County resident peered into the family bathroom and discovered that her husband, Carl B. Stiefel, lay on the floor confused and vomiting and complaining of a severe headache. Recently, the man had experienced several of these same symptoms, plus sinus congestion, dizziness, and tinnitus.

As Mr. Stiefel’s confusion worsened, his wife called for an ambulance, which arrived at the local hospital emergency department (ED) at 4:12 AM. Within approximately 11 minutes, the patient was examined by a doctor and later underwent a cranial CT scan, which a second doctor said showed “no intracranial process.”

Mr. Stiefel’s condition improved somewhat, although his dizziness persisted, leaving him still unable to walk. At this point, his primary ED doctor admitted him to the hospital for “benign positional vertigo.” The doctor also joined colleagues in suggesting that the patient might well be a candidate for an MRI, just in case his condition failed to improve over the next few hours.

But the transfer from the ED to the main hospital reportedly took at least 3 hours, during which time Mr. Stiefel’s condition deteriorated. Once admitted, he was observed by a healthcare provider — the news report doesn’t indicate precisely who — to be “delirious without meaningful interaction.” At least 4 hours would pass before the patient was seen by still another doctor, as the plaintiffs later claimed.

The patient remained disoriented and restless as the day unfolded. The MRI contemplated earlier was finally ordered, but the scan wasn’t available for several hours, according to nursing notes cited by the plaintiffs in their lawsuit.

Finally, the scan was administered at about 5:50 PM, almost 12 hours since Mr. Stiefel had first arrived at the ED. It showed that he had a torn artery in his neck and was experiencing a stroke. This was, clearly, a very different diagnosis from the one that his admitting doctor had entered into his notes.

A surgeon operated to repair the arterial tear, but the patient’s condition continued to worsen. Over the next 3 weeks, Mr. Stiefel went from the hospital to a local rehab facility, and back to the hospital with bacterial meningitis. Ultimately, he was diagnosed with “an irreparable brain injury,” which ultimately left him disabled and unable to work.

At this point, he and his wife sued a broad range of defendants — a radiology group, individual healthcare providers employed by the hospital, the primary ED physician, and that doctor’s emergency medicine group. In the nearly 5 intervening years, each of the named defendants settled, except the ED doctor and the emergency medicine group.

The two remaining defendants vigorously contested the claims against them, denying “any and all allegations of responsibility and liability” and contending that the patient’s injuries resulted from unforeseen complications rather than the care that had been administered.

The Ada County jury disagreed, however. It found that the primary ED doctor — and by extension the group to which the doctor belonged — did in fact negligently and recklessly fail to meet the proper standard of care, leading directly to the patient’s life-altering injuries.

For this failure, the jury awarded the plaintiffs $13.5 million, well over the state’s current inflation-adjusted cap of $400,000. (To date, Idaho’s largest med-mal award is nearly $30 million, handed down more than 20 years ago.)

At press time, there was no word of an appeal. 
 

Man sues dentist, ends up changing state medical malpractice law

In a surprise move, the Connecticut Supreme Court in mid-February reversed its own precedent regarding a 2005 law requiring certain pre-litigation steps be taken before state residents are permitted to file a medical malpractice claim, as a story in the Claims Journal reports.

In its 2011 review of that earlier law — passed to ensure that complainants had a reasonable basis for their claims — the high court went the legislature one better. It held that state courts had no “personal jurisdiction” in adjudicating malpractice claims in the absence of required supporting documents — specifically, a proper certificate and opinion letter from “a similar healthcare provider.”

For the past 12 years, this meant that any suit lacking the proper documents could not only be halted but dismissed with prejudice, meaning that such a case couldn’t be refiled.

That interpretation of the law was eventually challenged, however, by a Connecticut man who sued his dentist. Filed in 2018, the suit alleged that, during a root canal, the dentist had failed to properly diagnose and treat his patient’s dental abscess, which ultimately required surgery.

Complying with what he regarded as state law, the man attached a letter of opinion to his complaint, which testified to the merits of his claim. But, in a twist with significant consequences, the letter was written by an endodontist, not a general dentist. In response, the dentist’s attorneys submitted a motion to dismiss to the trial court, arguing that the plaintiff had breached the “similar provider” provision and that therefore the opinion letter was defective and the entire suit should be dismissed.

The trial court agreed — and the Connecticut Appellate Court went on to affirm the lower-court ruling. The case might have ended there, but the plaintiff appealed to the Connecticut Supreme Court, which agreed to review the appellate court finding. 

In a 6-0 decision, the high court looked back on its 2011 interpretation of the med-mal statute, which in the intervening years had given rise to “a body of case law.” The problem with that body of law, the justices argued, was that it had “imposed substantially greater burdens on plaintiffs than the legislature intended” — and it did so “by allowing potentially curable, technical, pre-litigation defects to defeat otherwise meritorious malpractice actions, sometimes after several years of litigation.”

In short, said the justices, there was nothing in the original statute that required a court to dismiss a suit once it found a letter of opinion to be deficient. This was a “curable” defect, one that shouldn’t be allowed to derail an otherwise meritorious claim.

As for the case that prompted the high court’s latest review — that is, the Connecticut man’s suit against his dentist — the justices found that the appellate court had also erred when it tossed out the endodontist’s opinion letter. Technically, the dentist might not have been an endodontist, said the justices, but he had in fact practiced in the field during the course of a long career, so close enough.

The justices kicked the case back to the trial court, with instructions that it deny the defendant’s motion to dismiss.
 

Stakeholders divided over new awards cap

Last month, Iowa Gov. Kim Reynolds signed a bill into law that limits the amount of noneconomic damages a successful med-mal plaintiff can collect, explains a story posted on Radio Iowa, among other news sites.

Under the new law, the limit for suits involving hospitals is capped at $2 million — while those involving all other healthcare providers are capped at $1 million. Beginning in 2028, those caps will be adjusted annually for inflation by 2.1%.

“When mistakes happen, Iowans deserve compensation, but arbitrary multimillion-dollar awards do more than that,” said Gov. Reynolds. “They act as a tax on all Iowans by raising the cost of care. They drive medical clinics out of business and medical students out of state.”

The CEO of Knoxville Hospital and Clinics — a well-known regional provider — agreed, saying that the new law helped to make Iowa “a more attractive place to practice medicine.”

But most Democrats in the GOP-controlled legislature — and 16 Republicans — voted against the legislation. For her part, House Minority Leader Jennifer Konfrst said there was absolutely no evidence that states with caps fared any better with medical workforce shortages than states without caps.
 

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

A doctor and one of Idaho’s premier emergency medicine groups must pay millions of dollars to a stroke patient and his wife in what is being called the second-largest medical malpractice award in the state’s history, according to a report in the Idaho Capital Sun.

The suit, which took nearly 5 years after filing to wend its way through the courts, stems from an incident that took place in the early morning of March 29, 2016. An Ada County resident peered into the family bathroom and discovered that her husband, Carl B. Stiefel, lay on the floor confused and vomiting and complaining of a severe headache. Recently, the man had experienced several of these same symptoms, plus sinus congestion, dizziness, and tinnitus.

As Mr. Stiefel’s confusion worsened, his wife called for an ambulance, which arrived at the local hospital emergency department (ED) at 4:12 AM. Within approximately 11 minutes, the patient was examined by a doctor and later underwent a cranial CT scan, which a second doctor said showed “no intracranial process.”

Mr. Stiefel’s condition improved somewhat, although his dizziness persisted, leaving him still unable to walk. At this point, his primary ED doctor admitted him to the hospital for “benign positional vertigo.” The doctor also joined colleagues in suggesting that the patient might well be a candidate for an MRI, just in case his condition failed to improve over the next few hours.

But the transfer from the ED to the main hospital reportedly took at least 3 hours, during which time Mr. Stiefel’s condition deteriorated. Once admitted, he was observed by a healthcare provider — the news report doesn’t indicate precisely who — to be “delirious without meaningful interaction.” At least 4 hours would pass before the patient was seen by still another doctor, as the plaintiffs later claimed.

The patient remained disoriented and restless as the day unfolded. The MRI contemplated earlier was finally ordered, but the scan wasn’t available for several hours, according to nursing notes cited by the plaintiffs in their lawsuit.

Finally, the scan was administered at about 5:50 PM, almost 12 hours since Mr. Stiefel had first arrived at the ED. It showed that he had a torn artery in his neck and was experiencing a stroke. This was, clearly, a very different diagnosis from the one that his admitting doctor had entered into his notes.

A surgeon operated to repair the arterial tear, but the patient’s condition continued to worsen. Over the next 3 weeks, Mr. Stiefel went from the hospital to a local rehab facility, and back to the hospital with bacterial meningitis. Ultimately, he was diagnosed with “an irreparable brain injury,” which ultimately left him disabled and unable to work.

At this point, he and his wife sued a broad range of defendants — a radiology group, individual healthcare providers employed by the hospital, the primary ED physician, and that doctor’s emergency medicine group. In the nearly 5 intervening years, each of the named defendants settled, except the ED doctor and the emergency medicine group.

The two remaining defendants vigorously contested the claims against them, denying “any and all allegations of responsibility and liability” and contending that the patient’s injuries resulted from unforeseen complications rather than the care that had been administered.

The Ada County jury disagreed, however. It found that the primary ED doctor — and by extension the group to which the doctor belonged — did in fact negligently and recklessly fail to meet the proper standard of care, leading directly to the patient’s life-altering injuries.

For this failure, the jury awarded the plaintiffs $13.5 million, well over the state’s current inflation-adjusted cap of $400,000. (To date, Idaho’s largest med-mal award is nearly $30 million, handed down more than 20 years ago.)

At press time, there was no word of an appeal. 
 

Man sues dentist, ends up changing state medical malpractice law

In a surprise move, the Connecticut Supreme Court in mid-February reversed its own precedent regarding a 2005 law requiring certain pre-litigation steps be taken before state residents are permitted to file a medical malpractice claim, as a story in the Claims Journal reports.

In its 2011 review of that earlier law — passed to ensure that complainants had a reasonable basis for their claims — the high court went the legislature one better. It held that state courts had no “personal jurisdiction” in adjudicating malpractice claims in the absence of required supporting documents — specifically, a proper certificate and opinion letter from “a similar healthcare provider.”

For the past 12 years, this meant that any suit lacking the proper documents could not only be halted but dismissed with prejudice, meaning that such a case couldn’t be refiled.

That interpretation of the law was eventually challenged, however, by a Connecticut man who sued his dentist. Filed in 2018, the suit alleged that, during a root canal, the dentist had failed to properly diagnose and treat his patient’s dental abscess, which ultimately required surgery.

Complying with what he regarded as state law, the man attached a letter of opinion to his complaint, which testified to the merits of his claim. But, in a twist with significant consequences, the letter was written by an endodontist, not a general dentist. In response, the dentist’s attorneys submitted a motion to dismiss to the trial court, arguing that the plaintiff had breached the “similar provider” provision and that therefore the opinion letter was defective and the entire suit should be dismissed.

The trial court agreed — and the Connecticut Appellate Court went on to affirm the lower-court ruling. The case might have ended there, but the plaintiff appealed to the Connecticut Supreme Court, which agreed to review the appellate court finding. 

In a 6-0 decision, the high court looked back on its 2011 interpretation of the med-mal statute, which in the intervening years had given rise to “a body of case law.” The problem with that body of law, the justices argued, was that it had “imposed substantially greater burdens on plaintiffs than the legislature intended” — and it did so “by allowing potentially curable, technical, pre-litigation defects to defeat otherwise meritorious malpractice actions, sometimes after several years of litigation.”

In short, said the justices, there was nothing in the original statute that required a court to dismiss a suit once it found a letter of opinion to be deficient. This was a “curable” defect, one that shouldn’t be allowed to derail an otherwise meritorious claim.

As for the case that prompted the high court’s latest review — that is, the Connecticut man’s suit against his dentist — the justices found that the appellate court had also erred when it tossed out the endodontist’s opinion letter. Technically, the dentist might not have been an endodontist, said the justices, but he had in fact practiced in the field during the course of a long career, so close enough.

The justices kicked the case back to the trial court, with instructions that it deny the defendant’s motion to dismiss.
 

Stakeholders divided over new awards cap

Last month, Iowa Gov. Kim Reynolds signed a bill into law that limits the amount of noneconomic damages a successful med-mal plaintiff can collect, explains a story posted on Radio Iowa, among other news sites.

Under the new law, the limit for suits involving hospitals is capped at $2 million — while those involving all other healthcare providers are capped at $1 million. Beginning in 2028, those caps will be adjusted annually for inflation by 2.1%.

“When mistakes happen, Iowans deserve compensation, but arbitrary multimillion-dollar awards do more than that,” said Gov. Reynolds. “They act as a tax on all Iowans by raising the cost of care. They drive medical clinics out of business and medical students out of state.”

The CEO of Knoxville Hospital and Clinics — a well-known regional provider — agreed, saying that the new law helped to make Iowa “a more attractive place to practice medicine.”

But most Democrats in the GOP-controlled legislature — and 16 Republicans — voted against the legislation. For her part, House Minority Leader Jennifer Konfrst said there was absolutely no evidence that states with caps fared any better with medical workforce shortages than states without caps.
 

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

New research shows that chemicals from car exhaust, wildfires, and cigarette smoke impair the skin’s ability to make healthy oil, making it more likely to get eczema.

The finding points scientists toward how to better treat the skin ailment. There are now more than three times as many eczema cases as there were in the 1970s, and it now affects as many as 20% of children and 10% of adults.

“I think these authors are spot-on in recognizing that the incidence of allergic conditions is increasing concurrently with how different pollutants are increasing in our environment,” said Denver-based pediatric allergist and immunologist Jessica Hui, MD, according to NBC News. “We’re finally understanding more about why people are getting eczema.”

Some people get eczema because of genetics, but the new research built on the previous understanding of how chemicals called diisocyanates can trigger the eczema symptoms of severe itching, skin redness, and oozing or painful rashes. An experiment on mice showed that exposure to a specific part of diisocyanates, called isocyanates, disrupted oil production that the skin needs to stay healthy.

Researchers at the National Institutes of Health “found that when bacteria that live on healthy skin are exposed to isocyanate, they must adapt to survive,” the agency summarized in a news release. “When they adapt, these bacteria shift their metabolism away from making the lipids, or oils, that skin needs to stay healthy. This finding suggests that eczema may be treatable by replacing the modified skin bacteria with healthy bacteria.”

The study was published in the journal Science Advances.

The chemicals also trigger a message to the brain that causes skin inflammation and itching, lead researcher Ian Myles, MD, told NBC News. Dr. Myles is also chief of the Epithelial Research Unit in the National Institute of Allergy and Infectious Diseases Laboratory of Clinical Immunology and Microbiology.

“So much of this is out of our control. I mean, you can’t shut the highways down,” he said of the environmental sources.

Previous research that explored attempting to restore healthy skin bacteria called Roseomonas mucosa to treat eczema symptoms had mixed results. The NIH says it has made the bacteria available “for commercial, nontherapeutic development ... as a potentially beneficial probiotic.”

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

New research shows that chemicals from car exhaust, wildfires, and cigarette smoke impair the skin’s ability to make healthy oil, making it more likely to get eczema.

The finding points scientists toward how to better treat the skin ailment. There are now more than three times as many eczema cases as there were in the 1970s, and it now affects as many as 20% of children and 10% of adults.

“I think these authors are spot-on in recognizing that the incidence of allergic conditions is increasing concurrently with how different pollutants are increasing in our environment,” said Denver-based pediatric allergist and immunologist Jessica Hui, MD, according to NBC News. “We’re finally understanding more about why people are getting eczema.”

Some people get eczema because of genetics, but the new research built on the previous understanding of how chemicals called diisocyanates can trigger the eczema symptoms of severe itching, skin redness, and oozing or painful rashes. An experiment on mice showed that exposure to a specific part of diisocyanates, called isocyanates, disrupted oil production that the skin needs to stay healthy.

Researchers at the National Institutes of Health “found that when bacteria that live on healthy skin are exposed to isocyanate, they must adapt to survive,” the agency summarized in a news release. “When they adapt, these bacteria shift their metabolism away from making the lipids, or oils, that skin needs to stay healthy. This finding suggests that eczema may be treatable by replacing the modified skin bacteria with healthy bacteria.”

The study was published in the journal Science Advances.

The chemicals also trigger a message to the brain that causes skin inflammation and itching, lead researcher Ian Myles, MD, told NBC News. Dr. Myles is also chief of the Epithelial Research Unit in the National Institute of Allergy and Infectious Diseases Laboratory of Clinical Immunology and Microbiology.

“So much of this is out of our control. I mean, you can’t shut the highways down,” he said of the environmental sources.

Previous research that explored attempting to restore healthy skin bacteria called Roseomonas mucosa to treat eczema symptoms had mixed results. The NIH says it has made the bacteria available “for commercial, nontherapeutic development ... as a potentially beneficial probiotic.”

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

New research shows that chemicals from car exhaust, wildfires, and cigarette smoke impair the skin’s ability to make healthy oil, making it more likely to get eczema.

The finding points scientists toward how to better treat the skin ailment. There are now more than three times as many eczema cases as there were in the 1970s, and it now affects as many as 20% of children and 10% of adults.

“I think these authors are spot-on in recognizing that the incidence of allergic conditions is increasing concurrently with how different pollutants are increasing in our environment,” said Denver-based pediatric allergist and immunologist Jessica Hui, MD, according to NBC News. “We’re finally understanding more about why people are getting eczema.”

Some people get eczema because of genetics, but the new research built on the previous understanding of how chemicals called diisocyanates can trigger the eczema symptoms of severe itching, skin redness, and oozing or painful rashes. An experiment on mice showed that exposure to a specific part of diisocyanates, called isocyanates, disrupted oil production that the skin needs to stay healthy.

Researchers at the National Institutes of Health “found that when bacteria that live on healthy skin are exposed to isocyanate, they must adapt to survive,” the agency summarized in a news release. “When they adapt, these bacteria shift their metabolism away from making the lipids, or oils, that skin needs to stay healthy. This finding suggests that eczema may be treatable by replacing the modified skin bacteria with healthy bacteria.”

The study was published in the journal Science Advances.

The chemicals also trigger a message to the brain that causes skin inflammation and itching, lead researcher Ian Myles, MD, told NBC News. Dr. Myles is also chief of the Epithelial Research Unit in the National Institute of Allergy and Infectious Diseases Laboratory of Clinical Immunology and Microbiology.

“So much of this is out of our control. I mean, you can’t shut the highways down,” he said of the environmental sources.

Previous research that explored attempting to restore healthy skin bacteria called Roseomonas mucosa to treat eczema symptoms had mixed results. The NIH says it has made the bacteria available “for commercial, nontherapeutic development ... as a potentially beneficial probiotic.”

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

The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.

Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.

The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.

Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.

The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.

“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.

The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).

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

The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.

Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.

The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.

Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.

The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.

“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.

The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).

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

The Food and Drug Administration has approved a citrate-free, 100 mg/mL formulation of the biosimilar adalimumab-adaz (Hyrimoz), according to a statement from manufacturer Sandoz.

Hyrimoz, a tumor necrosis factor (TNF) blocker that is biosimilar to its reference product Humira, was approved by the FDA in 2018 at a concentration of 50 mg/mL for rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The high-concentration formula is indicated for these same conditions.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Sandoz said that it intends to launch the citrate-free formulation in the United States on July 1. It will be one of up to nine other adalimumab biosimilars that are expected to launch in July. On January 31, Amjevita (adalimumab-atto) became the first adalimumab biosimilar to launch in the United States.

The current label for Hyrimoz contains a black box warning emphasizing certain risks, notably the increased risk for serious infections, such as tuberculosis or sepsis, and an increased risk of malignancy, particularly lymphomas.

Adverse effects associated with Hyrimoz with an incidence greater than 10% include upper respiratory infections and sinusitis, injection-site reactions, headache, and rash.

The approval for the high-concentration formulation was based on data from a phase 1 pharmacokinetics bridging study that compared Hyrimoz 50 mg/mL and citrate-free Hyrimoz 100 mg/mL.

“This study met all of the primary objectives, demonstrating comparable pharmacokinetics and showing similar safety and immunogenicity of the Hyrimoz 50 mg/mL and Hyrimoz [100 mg/mL],” according to Sandoz, a division of Novartis.

The approval for Hyrimoz 50 mg/mL in 2018 was based on preclinical and clinical research comparing Hyrimoz and Humira. In a phase 3 trial published in the British Journal of Dermatology, which included adults with clinically stable but active moderate to severe chronic plaque psoriasis, Hyrimoz and Humira showed a similar percentage of patients met the primary endpoint of a 75% reduction or more in Psoriasis Area and Severity Index (PASI 75) score at 16 weeks, compared with baseline (66.8% and 65%, respectively).

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

The relatively recent innovation of heart transplantation after circulatory death of the donor is increasing the number of donor hearts available and leading to many more lives on the heart transplant waiting list being saved. Experts agree it’s a major and very welcome advance in medicine.

However, some of the processes involved in one approach to donation after circulatory death has raised ethical concerns and questions about whether they violate the “dead donor rule” – a principle that requires patients be declared dead before removal of life-sustaining organs for transplant.  

Rasi Bhadramani/iStock/Getty Images

Experts in the fields of transplantation and medical ethics have yet to reach consensus, causing problems for the transplant community, who worry that this could cause a loss of confidence in the entire transplant process.
 

A new pathway for heart transplantation

The traditional approach to transplantation is to retrieve organs from a donor who has been declared brain dead, known as “donation after brain death (DBD).” These patients have usually suffered a catastrophic brain injury but survived to get to intensive care.

As the brain swells because of injury, it becomes evident that all brain function is lost, and the patient is declared brain dead. However, breathing is maintained by the ventilator and the heart is still beating. Because the organs are being oxygenated, there is no immediate rush to retrieve the organs and the heart can be evaluated for its suitability for transplant in a calm and methodical way before it is removed.  

However, there is a massive shortage of organs, especially hearts, partially because of the limited number of donors who are declared brain dead in that setting.

In recent years, another pathway for organ transplantation has become available: “donation after circulatory death (DCD).” These patients also have suffered a catastrophic brain injury considered to be nonsurvivable, but unlike the DBD situation, the brain still has some function, so the patient does not meet the criteria for brain death. 

Still, because the patient is considered to have no chance of a meaningful recovery, the family often recognizes the futility of treatment and agrees to the withdrawal of life support. When this happens, the heart normally stops beating after a period of time. There is then a “stand-off time” – normally 5 minutes – after which death is declared and the organs can be removed. 

The difficulty with this approach, however, is that because the heart has been stopped, it has been deprived of oxygen, potentially causing injury. While DCD has been practiced for several years to retrieve organs such as the kidney, liver, lungs, and pancreas, the heart is more difficult as it is more susceptible to oxygen deprivation. And for the heart to be assessed for transplant suitability, it should ideally be beating, so it has to be reperfused and restarted quickly after death has been declared.

For many years it was thought the oxygen deprivation that occurs after circulatory death would be too much to provide a functional organ. But researchers in the United Kingdom and Australia developed techniques to overcome this problem, and early DCD heart transplants took place in 2014 in Australia, and in 2015 in the United Kingdom.

Heart transplantation after circulatory death has now become a routine part of the transplant program in many countries, including the United States, Spain, Belgium, the Netherlands, and Austria.

In the United States, 348 DCD heart transplants were performed in 2022, with numbers expected to reach 700 to 800 this year as more centers come online.

It is expected that most countries with heart transplant programs will follow suit and the number of donor hearts will increase by up to 30% worldwide because of DCD.  

Currently, there are about 8,000 heart transplants worldwide each year and with DCD this could rise to about 10,000, potentially an extra 2,000 lives saved each year, experts estimate.  

Two different approaches to DCD heart transplantation have been developed.
 

The direct procurement approach

The Australian group, based at St. Vincent’s Hospital in Sydney, developed a technique referred to as “direct procurement”: after the standoff period and declaration of circulatory death, the chest is opened, and the heart is removed. New technology, the Organ Care System (OCS) heart box (Transmedics), is then used to reperfuse and restart the heart outside the body so its suitability for transplant can be assessed.

The heart is kept perfused and beating in the OCS box while it is being transported to the recipient. This has enabled longer transit times than the traditional way of transporting the nonbeating heart on ice.

Peter MacDonald, MD, PhD, from the St Vincent’s group that developed this approach, said, “Most people thought a heart from a DCD donor would not survive transport – that the injury to the heart from the combination of life support withdrawal, stand-off time, and cold storage would be too much. But we modeled the process in the lab and were able to show that we were able to get the heart beating again after withdrawal of life support.”

Dr. McDonald noted that “the recipient of their first human DCD heart transplant using this machine in 2014 is still alive and well.” The Australian group has now done 85 of these DCD heart transplants, and they have increased the number of heart transplant procedures at St. Vincent’s Hospital by 25%.
 

Normothermic regional perfusion (NRP)  

The U.K. group, based at the Royal Papworth Hospital in Cambridge, England, developed a different approach to DCD: After the standoff period and the declaration of circulatory death, the donor is connected to a heart/lung machine using extracorporeal membrane oxygenation (ECMO) so that the heart is perfused and starts beating again inside the body. This approach is known as normothermic regional perfusion (NRP).

Marius Berman, MD, surgical lead for Transplantation and Mechanical Circulatory Support at Papworth, explained that the NRP approach allows the heart to be perfused and restarted faster than direct procurement, resulting in a shorter ischemic time. The heart can be evaluated thoroughly for suitability for transplantation in situ before committing to transplantation, and because the heart is less damaged, it can be transported on ice without use of the OCS box.

“DCD is more complicated than DBD, because the heart has stopped and has to be restarted. Retrieval teams have to be very experienced,” Dr. Berman noted. “This is more of an issue for the direct procurement approach, where the chest has to be opened and the heart retrieved as fast as possible. It is a rush. The longer time without the heart being perfused correlates to an increased incidence of primary graft dysfunction. With NRP, we can get the heart started again more quickly, which is crucial.”

Stephen Large, MBBS, another cardiothoracic surgeon with the Papworth team, added that they have reduced ischemic time to about 15 minutes. “That’s considerably shorter than reperfusing the heart outside the body,” he said. “This results in a healthier organ for the recipient.” 

The NRP approach is also less expensive than direct procurement as one OCS box costs about $75,000.

He pointed out that the NRP approach can also be used for heart transplants in children and even small babies, while currently the direct procurement technique is not typically suitable for children because the OCS box was not designed for small hearts. 

DCD, using either technique, has increased the heart transplant rate by 40% at Papworth, and is being used at all seven transplant centers in the United Kingdom, “a world first,” noted Dr. Large.

The Papworth team recently published its 5-year experience with 25 NRP transplants and 85 direct procurement transplants. Survival in recipients was no different, although there was some suggestion that the NRP hearts may have been in slightly better condition, possibly being more resistant to immunological rejection.
 

Ethical concerns about NRP

Restarting the circulation during the NRP process has raised ethical concerns.

When the NRP technique was first used in the United States, these ethical questions were raised by several groups, including the American College of Physicians (ACP).

Harry Peled, MD, Providence St. Jude Medical Center, Fullerton, Calif., coauthor of a recent Viewpoint on the issue, is board-certified in both cardiology and critical care, and said he is a supporter of DCD using direct procurement, but he does not believe that NRP is ethical at present. He is not part of the ACP, but said his views align with those of the organization.

There are two ethical problems with NRP, he said. The first is whether by restarting the circulation, the NRP process violates the U.S. definition of death, and retrieval of organs would therefore violate the dead donor rule. 

“American law states that death is the irreversible cessation of brain function or of circulatory function. But with NRP, the circulation is artificially restored, so the cessation of circulatory function is not irreversible,” Dr. Peled pointed out.

“I have no problem with DCD using direct procurement as we are not restarting the circulation. But NRP is restarting the circulation and that is a problem for me,” Dr. Peled said. “I would argue that by performing NRP, we are resuscitating the patient.”

The second ethical problem with NRP is concern about whether, during the process, there would be any circulation to the brain, and if so, would this be enough to restore some brain function? Before NRP is started, the main arch vessel arteries to the head are clamped to prevent flow to the brain, but there are worries that some blood flow may still be possible through small collateral vessels.

“We have established that these patients do not have enough brain function for a meaningful life, which is why a decision has been made to remove life support, but they have not been declared brain dead,” Dr. Peled said.

With direct procurement, the circulation is not restarted so there is no chance that any brain function will be restored, he said. “But with NRP, because the arch vessels have to be clamped to prevent brain circulation, that is admitting there is concern that brain function may be restored if circulation to the brain is reestablished, and brain function is compatible with life. As we do not know whether there is any meaningful circulation to the brain via the small collaterals, there is, in effect, a risk of bringing the patient back to life.”

The other major concern for some is whether even a very small amount of circulation to the brain would be enough to support consciousness, and “we don’t know that for certain,” Dr. Peled said.
 

The argument for NRP

Nader Moazami, MD, professor of cardiovascular surgery, NYU Langone Health, New York, is one of the more vocal proponents of NRP for DCD heart transplantation in the United States, and has coauthored responses to these ethical concerns.

“People are confusing many issues to produce an argument against NRP,” he said.

“Our position is that death has already been declared based on the lack of circulatory function for over 5 minutes and this has been with the full agreement of the family, knowing that the patient has no chance of a meaningful life. No one is thinking of trying to resuscitate the patient. It has already been established that any future efforts to resuscitate are futile. In this case, we are not resuscitating the patient by restarting the circulation. It is just regional perfusion of the organs.”

Dr. Moazami pointed out this concept was accepted for the practice of abdominal DCD when it first started in the United States in the 1990s where cold perfusion was used to preserve the abdominal organs before they were retrieved from the body.

“The new approach of using NRP is similar except that it involves circulating warm blood, which will preserve organs better and result in higher quality organs for the recipient.”

On the issue of concern about possible circulation to the brain, Dr. Moazami said: “The ethical critics of NRP are questioning whether the brain may not be dead. We are arguing that the patient has already been declared dead as they have had a circulatory death. You cannot die twice.”

He maintained that the clamping of the arch vessels to the head will ensure that when the circulation is restarted “the natural process of circulatory death leading to brain death will continue to progress.” 

On the concerns about possible collateral flow to the brain, Dr. Moazami said there is no evidence that this occurs. “Prominent neurologists have said it is impossible for collaterals to provide any meaningful blood flow to the brain in this situation. And even if there is small amount of blood flow to the brain, this would be insufficient to maintain any meaningful brain function.”

But Dr. Peled argues that this has not been proved. “Even though we don’t think there is enough circulation to the brain for any function with NRP, we don’t know that with 100% certainty,” he said. “In my view, if there is a possibility of even the smallest amount of brain flow, we are going against the dead donor rule. We are rewriting the rules of death.”

Dr. Moazami countered: “Nothing in life is 100%, particularly in medicine. With that argument can you also prove with 100% certainty to me that there is absolutely no brain function with regular direct procurement DCD?  We know that brain death has started, but the question is: Has it been completed? We don’t know the answer to this question with 100% certainty, but that is the case for regular direct procurement DCD as well, and that has been accepted by almost everyone.

“The whole issue revolves around when are we comfortable that death has occurred,” he said. “Those against NRP are concerned that organs are being taken before the patient is dead. But the key point is that the patient has already been declared dead.”

Since there is some concern over the ethics of NRP, why not just stick to DCD with direct procurement?

Dr. Moazami argued that NRP results in healthier organs. “NRP allows more successful heart transplants, liver transplants, lung transplants. It preserves all the organs better,” he said. “This will have a big impact on recipients – they would obviously much prefer a healthier organ. In addition, the process is easier and cheaper, so more centers will be able to do it, therefore more transplants will get done and more lives will be saved if NRP is used.”

He added: “I am a physician taking care of sick patients. I believe I have to respect the wishes of the donor and the donor family; make sure I’m not doing any harm to the donor; and ensure the best quality possible of the organ I am retrieving to best serve the recipient. I am happy I am doing this by using NRP for DCD heart transplantation.”

But Dr. Peled argued that while NRP may have some possible advantages over direct procurement, that does not justify allowing a process to go ahead that is unethical.

“The fact that NRP may result in some benefits doesn’t justify violating the dead donor rule or the possibility, however small, of causing pain to the donor. If it’s unethical, it’s unethical. Full stop,” he said.

“I feel that NRP is not respecting the rights of our patients and that the process does not have adequate transparency. We took it to our local ethics committee, and they decided not to approve NRP in our health care system. I agree with this decision,” Dr. Peled said.  

“The trouble is different experts and different countries are not in agreement about this,” he added. “Reasonable, well-informed people are in disagreement. I do not believe we can have a standard of care where there is not consensus.”
 

Cautious nod

In a 2022 consensus statement, the International Society for Heart and Lung Transplantation (ISHLT) gave a cautious nod toward DCD and NRP, dependent on local recommendations.

The ISHLT conclusion reads: “With appropriate consideration of the ethical principles involved in organ donation, DCD can be undertaken in a morally permissible manner. In all cases, the introduction of DCD programs should be in accordance with local legal regulations. Countries lacking a DCD pathway should be encouraged to develop national ethical, professional, and legal frameworks to address both public and professional concerns.”

The author of a recent editorial on the subject, Ulrich P. Jorde, MD, head of the heart transplant program at Montefiore Medical Center, New York, said, “DCD is a great step forward. People regularly die on the heart transplant waiting list. DCD will increase the supply of donor hearts by 20% to 30%.”

However, he noted that while most societies have agreed on a protocol for organ donation based on brain death, the situation is more complicated with circulatory death.

“Different countries have different definitions of circulatory death. How long do we have to wait after the heart has stopped beating before the patient is declared dead? Most countries have agreed on 5 minutes, but other countries have imposed different periods and as such, different definitions of death.

“The ISHLT statement says that restarting the circulation is acceptable if death has been certified according to prevailing law and surgical interventions are undertaken to preclude any restoration of cerebral circulation. But our problem is that different regional societies have different definitions of circulatory, death which makes the situation confusing.”

Dr. Jorde added: “We also have to weigh the wishes of the donor and their family. If family, advocating what are presumed to be the donor’s wishes, have decided that DCD would be acceptable and they understand the concept and wish to donate the organs after circulatory death, this should be strongly considered under the concept of self-determination, a basic human right.”
 

Variations in practice around the world 

This ethical debate has led to large variations in practice around the world, with some countries, such as Spain, allowing both methods of DCD, while Australia allows direct procurement but not NRP, and Germany currently does not allow DCD at all.

In the United States, things are even more complicated, with some states allowing NRP while others don’t. Even within states, some hospitals and transplant organizations allow NRP, and others don’t. 

David A. D’Alessandro, MD, cardiac surgeon at Massachusetts General Hospital, Boston, uses only the direct procurement approach as his region does not allow NRP.

“The direct procurement approach is not controversial and to me that’s a big advantage. I believe we need to agree on the ethics first, and then get into a debate about which technique is better,” he told this news organization.

Dr. D’Alessandro and his group recently published the results of their study, with direct procurement DCD heart transplantation showing similar short-term clinical outcomes to DBD.

“We are only doing direct procurement and we are seeing good results that appear to be comparable to DBD. That is good enough for me,” he said.

Dr. D’Alessandro estimates that in the United States both types of DCD procedures are currently being done about equally.

“Anything we can do to increase the amount of hearts available for transplantation is a big deal,” he said. “At the moment, only the very sickest patients get a heart transplant, and many patients die on the transplant waiting list. Very sadly, many young people die every year from a circulatory death after having life support withdrawn. Before DCD, these beautiful functional organs were not able to be used. Now we have a way of saving lives with these organs.”

Dr. D’Alessandro noted that more and more centers in the United States are starting to perform DCD heart transplants. 

“Not every transplant center may join in as the DCD procedures are very resource-intensive and time-consuming. For low-volume transplant centers, it may not be worth the expense and anguish to do DCD heart transplants. But bigger centers will need to engage in DCD to remain competitive. My guess is that 50%-70% of U.S. transplant centers will do DCD in future.”

He said he thinks it is a “medical shortcoming” that agreement cannot be reached on the ethics of NRP. “In an ideal world everyone would be on the same page. It makes me a bit uncomfortable that some people think it’s okay and some people don’t.”

Adam DeVore, MD, a cardiologist at Duke University Medical Center, Durham, N.C., the first U.S. center to perform an adult DCD heart transplant, reported that his institution uses both methods, with the choice sometimes depending on how far the heart must travel.

“If the recipient is near, NRP may be chosen as the heart is transported on ice, but if it needs to go further away we are more likely to choose direct procurement and use of the OCS box,” he said. 

“I am really proud of what we’ve been able to do, helping to introduce DCD in the U.S.,” Dr. DeVore said. “This is having a massive benefit in increasing the number of hearts for donation with great outcomes.”  

But he acknowledged that the whole concept of DCD is somewhat controversial.  

“The idea of brain death really came about for the purpose of heart donation. The two things are very intricately tied. Trying to do heart donation without brain death having been declared is foreign to people. Also, in DCD there is the issue of [this]: When life support is removed, how long do we wait before death can be declared? That could be in conflict with how long the organ needs to remain viable. We are going through the process now of looking at these questions. There is a lot of variation in the U.S. about the withdrawal of care and the declaration of death, which is not completely standardized.

“But the concept of circulatory death itself is accepted after the withdrawal of life support. I think it’s the rush to take the organs out that makes it more difficult.”

Dr. DeVore said the field is moving forward now. “As the process has become more common, people have become more comfortable, probably because of the big difference it will make to saving lives. But we do need to try and standardize best practices.”

A recent Canadian review of the ethics of DCD concluded that the direct procurement approach would be in alignment with current medical guidelines, but that further work is required to evaluate the consistency of NRP with current Canadian death determination policy and to ensure the absence of brain perfusion during this process.

In the United Kingdom, the definition of death is brain-based, and brain death is defined on a neurological basis.

Dr. Stephen Large from Papworth explained that this recognizes the presence of brain-stem death through brain stem reflex testing after the withdrawal of life support, cardiorespiratory arrest and 5 further minutes of ischemia. As long as NRP does not restore intracranial (brainstem) perfusion after death has been confirmed, then it is consistent with laws for death determination and therefore both direct procurement and NRP are permissible.

However, the question over possible collateral flow to the brain has led the United Kingdom to pause the NRP technique as routine practice while this is investigated further. So, at the present time, the vast majority of DCD heart transplants are being conducted using the direct procurement approach.

But the United Kingdom is facing the bigger challenge: national funding that will soon end. “The DCD program in the U.K. has been extremely successful, increasing heart transplant rates by up to 28%,” Dr. Berman said. “Everybody wants it to continue. But at present the DCD program only has national funding in the U.K. until March 2023. We don’t know what will happen after that.”

The current model in the United Kingdom consists of three specialized DCD heart retrieval teams, a national protocol of direct organ procurement and delivery of DCD hearts to all seven transplant programs, both adult and pediatric.

If the national funding is not extended, “we will go back to individual hospitals trying to fund their own programs. That will be a serious threat to the program and could result in a large reduction in heart transplants,” said Dr. Berman.
 

Definition of death  

The crux of the issue with regard to NRP seems to be variations in how death is defined and the interpretation of those definitions.  

DCD donors will have had many tests indicating severe brain damage, a neurologist will have declared the prognosis is futile, and relatives will have agreed to withdraw life support, Dr. Jorde said. “The heart stops beating, and the stand-off time means that blood flow to the brain ceases completely for at least 5 minutes before circulatory death is declared. This is enough on its own to stop brain function.”

Dr. Large made the point that by the time the circulation is reestablished with NRP, more time has elapsed, and the brain will have been without perfusion for much longer than 5 minutes, so it would be “physiologically almost impossible” for there to be any blood flow to the brain.

“Because these brains are already very damaged before life support was removed, the intracranial pressure is high, which will further discourage blood flow to the brain,” he said. Then the donor goes through a period of anoxic heart arrest, up to 16 minutes at a minimum of no blood supply, enough on its own to stop meaningful brain function. 

“It’s asking an awful lot to believe that there might be any brain function left,” he said. “And if, on reestablishing the circulation with NRP, there is any blood in the collaterals, the pressure of such flow is so low it won’t enter the brain.”

Dr. Large also pointed out that the fact that the United Kingdom requires a neurologic definition for brain-stem death makes the process easier. 

In Australia, St. Vincent’s cardiologist Dr. MacDonald noted that death is defined as the irreversible cessation of circulation, so the NRP procedure is not allowed.

“With NRP, there is an ethical dilemma over whether the patient has legally died or not. Different countries have different ways of defining death. Perhaps society will have to review of the definition of death,” he suggested. Death is a process, “but for organ donation, we have to choose a moment in time of that process that satisfies everyone – when there is no prospect of recovery of the donor but the organs can still be utilized without harming the donor.” 

Dr. MacDonald said the field is in transition. “I don’t want to argue that one technique is better than the other; I think it’s good to have access to both techniques. Anything that will increase the number of transplants we can do is a good thing.”
 

Collaborative decision

Everyone seems to agree that there should be an effort to try to define death in a uniform way worldwide, and that international, national and local regulations are aligned with each other.

Dr. Jorde said: “It is of critical importance that local guidelines are streamlined, firstly in any one given country and then globally, and these things must be discussed transparently within society with all stakeholders – doctors, patients, citizens.”

Dr. Peled, from Providence St. Jude in California, concurred: “There is the possibility that we could change the definition of death, but that cannot be a decision based solely on transplant organizations. It has to be a collaborative decision with a large input from groups who do not have an interest in the procurement of organs.”

He added: “The dialogue so far has been civil, and everybody is trying to do the right thing. My hope is that as a civilized society we will figure out a way forward. At present, there is significant controversy about NRP, and families need to know that. My main concern is that if there is any lack of transparency in getting informed consent, then this risks people losing trust in the donation system.” 

Dr. Moazami, from NYU Langone, said the controversy has cast a cloud over the practice of NRP throughout the world. “We need to get it sorted out.”

He said he believes the way forward is to settle the question of whether there is any meaningful blood flow to the brain with the NRP technique.

“This is where the research has to focus. I believe this concern is hypothetical, but I am happy to do the studies to confirm that. Then, the issue should come to a rest. I think that is the right way forward – to do the studies rather than enforcing a moratorium on the practice because of a hypothetical concern.”

These studies on blood flow to the brain are now getting started in both the United Kingdom and the United States.

The U.K. study is being run by Antonio Rubino, MD, consultant in cardiothoracic anesthesia and intensive care at Papworth Hospital NHS Foundation and clinical lead, organ donation. Dr. Rubino explained that the study will assess cerebral blood flow using CT angiography of the brain. “We hypothesize that this will provide evidence to indicate that brain blood flow is not present during NRP and promote trust in the use of NRP in routine practice,” he said.

Dr. Large said: “Rather than having these tortured arguments, we will do the measurements. For the sake of society in this situation, I think it’s good to stop and take a breath. We must measure this, and we are doing just that.”

If there is any blood flow at all, Dr. Large said they will then have to seek expert guidance. “Say we find there is 50 mL of blood flow and normal blood flow is 1,500 mL/min. We will need expert guidance on whether it is remotely possible to be sentient on that. I would say it would be extraordinarily unlikely.”  

Dr. Berman summarized the situation: “DCD is increasing the availability of hearts for transplant. This is saving lives, reducing the number of patients on the waiting list, and reducing hospital stays for patients unable to leave the hospital without a transplant. It is definitely here to stay. It is crucial that it gets funded properly, and it is also crucial that we resolve the NRP ethical issues as soon as possible.”

He is hopeful that some of these issues will be resolved this year.

Dr. MacDonald reported he has received “in-kind” support from Transmedics through provision of research modules for preclinical research studies. Dr. D’Alessandro reported he is on the speakers bureau for Abiomed, not relevant to this article. No other relevant disclosures were reported.
 

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

The relatively recent innovation of heart transplantation after circulatory death of the donor is increasing the number of donor hearts available and leading to many more lives on the heart transplant waiting list being saved. Experts agree it’s a major and very welcome advance in medicine.

However, some of the processes involved in one approach to donation after circulatory death has raised ethical concerns and questions about whether they violate the “dead donor rule” – a principle that requires patients be declared dead before removal of life-sustaining organs for transplant.  

Rasi Bhadramani/iStock/Getty Images

Experts in the fields of transplantation and medical ethics have yet to reach consensus, causing problems for the transplant community, who worry that this could cause a loss of confidence in the entire transplant process.
 

A new pathway for heart transplantation

The traditional approach to transplantation is to retrieve organs from a donor who has been declared brain dead, known as “donation after brain death (DBD).” These patients have usually suffered a catastrophic brain injury but survived to get to intensive care.

As the brain swells because of injury, it becomes evident that all brain function is lost, and the patient is declared brain dead. However, breathing is maintained by the ventilator and the heart is still beating. Because the organs are being oxygenated, there is no immediate rush to retrieve the organs and the heart can be evaluated for its suitability for transplant in a calm and methodical way before it is removed.  

However, there is a massive shortage of organs, especially hearts, partially because of the limited number of donors who are declared brain dead in that setting.

In recent years, another pathway for organ transplantation has become available: “donation after circulatory death (DCD).” These patients also have suffered a catastrophic brain injury considered to be nonsurvivable, but unlike the DBD situation, the brain still has some function, so the patient does not meet the criteria for brain death. 

Still, because the patient is considered to have no chance of a meaningful recovery, the family often recognizes the futility of treatment and agrees to the withdrawal of life support. When this happens, the heart normally stops beating after a period of time. There is then a “stand-off time” – normally 5 minutes – after which death is declared and the organs can be removed. 

The difficulty with this approach, however, is that because the heart has been stopped, it has been deprived of oxygen, potentially causing injury. While DCD has been practiced for several years to retrieve organs such as the kidney, liver, lungs, and pancreas, the heart is more difficult as it is more susceptible to oxygen deprivation. And for the heart to be assessed for transplant suitability, it should ideally be beating, so it has to be reperfused and restarted quickly after death has been declared.

For many years it was thought the oxygen deprivation that occurs after circulatory death would be too much to provide a functional organ. But researchers in the United Kingdom and Australia developed techniques to overcome this problem, and early DCD heart transplants took place in 2014 in Australia, and in 2015 in the United Kingdom.

Heart transplantation after circulatory death has now become a routine part of the transplant program in many countries, including the United States, Spain, Belgium, the Netherlands, and Austria.

In the United States, 348 DCD heart transplants were performed in 2022, with numbers expected to reach 700 to 800 this year as more centers come online.

It is expected that most countries with heart transplant programs will follow suit and the number of donor hearts will increase by up to 30% worldwide because of DCD.  

Currently, there are about 8,000 heart transplants worldwide each year and with DCD this could rise to about 10,000, potentially an extra 2,000 lives saved each year, experts estimate.  

Two different approaches to DCD heart transplantation have been developed.
 

The direct procurement approach

The Australian group, based at St. Vincent’s Hospital in Sydney, developed a technique referred to as “direct procurement”: after the standoff period and declaration of circulatory death, the chest is opened, and the heart is removed. New technology, the Organ Care System (OCS) heart box (Transmedics), is then used to reperfuse and restart the heart outside the body so its suitability for transplant can be assessed.

The heart is kept perfused and beating in the OCS box while it is being transported to the recipient. This has enabled longer transit times than the traditional way of transporting the nonbeating heart on ice.

Peter MacDonald, MD, PhD, from the St Vincent’s group that developed this approach, said, “Most people thought a heart from a DCD donor would not survive transport – that the injury to the heart from the combination of life support withdrawal, stand-off time, and cold storage would be too much. But we modeled the process in the lab and were able to show that we were able to get the heart beating again after withdrawal of life support.”

Dr. McDonald noted that “the recipient of their first human DCD heart transplant using this machine in 2014 is still alive and well.” The Australian group has now done 85 of these DCD heart transplants, and they have increased the number of heart transplant procedures at St. Vincent’s Hospital by 25%.
 

Normothermic regional perfusion (NRP)  

The U.K. group, based at the Royal Papworth Hospital in Cambridge, England, developed a different approach to DCD: After the standoff period and the declaration of circulatory death, the donor is connected to a heart/lung machine using extracorporeal membrane oxygenation (ECMO) so that the heart is perfused and starts beating again inside the body. This approach is known as normothermic regional perfusion (NRP).

Marius Berman, MD, surgical lead for Transplantation and Mechanical Circulatory Support at Papworth, explained that the NRP approach allows the heart to be perfused and restarted faster than direct procurement, resulting in a shorter ischemic time. The heart can be evaluated thoroughly for suitability for transplantation in situ before committing to transplantation, and because the heart is less damaged, it can be transported on ice without use of the OCS box.

“DCD is more complicated than DBD, because the heart has stopped and has to be restarted. Retrieval teams have to be very experienced,” Dr. Berman noted. “This is more of an issue for the direct procurement approach, where the chest has to be opened and the heart retrieved as fast as possible. It is a rush. The longer time without the heart being perfused correlates to an increased incidence of primary graft dysfunction. With NRP, we can get the heart started again more quickly, which is crucial.”

Stephen Large, MBBS, another cardiothoracic surgeon with the Papworth team, added that they have reduced ischemic time to about 15 minutes. “That’s considerably shorter than reperfusing the heart outside the body,” he said. “This results in a healthier organ for the recipient.” 

The NRP approach is also less expensive than direct procurement as one OCS box costs about $75,000.

He pointed out that the NRP approach can also be used for heart transplants in children and even small babies, while currently the direct procurement technique is not typically suitable for children because the OCS box was not designed for small hearts. 

DCD, using either technique, has increased the heart transplant rate by 40% at Papworth, and is being used at all seven transplant centers in the United Kingdom, “a world first,” noted Dr. Large.

The Papworth team recently published its 5-year experience with 25 NRP transplants and 85 direct procurement transplants. Survival in recipients was no different, although there was some suggestion that the NRP hearts may have been in slightly better condition, possibly being more resistant to immunological rejection.
 

Ethical concerns about NRP

Restarting the circulation during the NRP process has raised ethical concerns.

When the NRP technique was first used in the United States, these ethical questions were raised by several groups, including the American College of Physicians (ACP).

Harry Peled, MD, Providence St. Jude Medical Center, Fullerton, Calif., coauthor of a recent Viewpoint on the issue, is board-certified in both cardiology and critical care, and said he is a supporter of DCD using direct procurement, but he does not believe that NRP is ethical at present. He is not part of the ACP, but said his views align with those of the organization.

There are two ethical problems with NRP, he said. The first is whether by restarting the circulation, the NRP process violates the U.S. definition of death, and retrieval of organs would therefore violate the dead donor rule. 

“American law states that death is the irreversible cessation of brain function or of circulatory function. But with NRP, the circulation is artificially restored, so the cessation of circulatory function is not irreversible,” Dr. Peled pointed out.

“I have no problem with DCD using direct procurement as we are not restarting the circulation. But NRP is restarting the circulation and that is a problem for me,” Dr. Peled said. “I would argue that by performing NRP, we are resuscitating the patient.”

The second ethical problem with NRP is concern about whether, during the process, there would be any circulation to the brain, and if so, would this be enough to restore some brain function? Before NRP is started, the main arch vessel arteries to the head are clamped to prevent flow to the brain, but there are worries that some blood flow may still be possible through small collateral vessels.

“We have established that these patients do not have enough brain function for a meaningful life, which is why a decision has been made to remove life support, but they have not been declared brain dead,” Dr. Peled said.

With direct procurement, the circulation is not restarted so there is no chance that any brain function will be restored, he said. “But with NRP, because the arch vessels have to be clamped to prevent brain circulation, that is admitting there is concern that brain function may be restored if circulation to the brain is reestablished, and brain function is compatible with life. As we do not know whether there is any meaningful circulation to the brain via the small collaterals, there is, in effect, a risk of bringing the patient back to life.”

The other major concern for some is whether even a very small amount of circulation to the brain would be enough to support consciousness, and “we don’t know that for certain,” Dr. Peled said.
 

The argument for NRP

Nader Moazami, MD, professor of cardiovascular surgery, NYU Langone Health, New York, is one of the more vocal proponents of NRP for DCD heart transplantation in the United States, and has coauthored responses to these ethical concerns.

“People are confusing many issues to produce an argument against NRP,” he said.

“Our position is that death has already been declared based on the lack of circulatory function for over 5 minutes and this has been with the full agreement of the family, knowing that the patient has no chance of a meaningful life. No one is thinking of trying to resuscitate the patient. It has already been established that any future efforts to resuscitate are futile. In this case, we are not resuscitating the patient by restarting the circulation. It is just regional perfusion of the organs.”

Dr. Moazami pointed out this concept was accepted for the practice of abdominal DCD when it first started in the United States in the 1990s where cold perfusion was used to preserve the abdominal organs before they were retrieved from the body.

“The new approach of using NRP is similar except that it involves circulating warm blood, which will preserve organs better and result in higher quality organs for the recipient.”

On the issue of concern about possible circulation to the brain, Dr. Moazami said: “The ethical critics of NRP are questioning whether the brain may not be dead. We are arguing that the patient has already been declared dead as they have had a circulatory death. You cannot die twice.”

He maintained that the clamping of the arch vessels to the head will ensure that when the circulation is restarted “the natural process of circulatory death leading to brain death will continue to progress.” 

On the concerns about possible collateral flow to the brain, Dr. Moazami said there is no evidence that this occurs. “Prominent neurologists have said it is impossible for collaterals to provide any meaningful blood flow to the brain in this situation. And even if there is small amount of blood flow to the brain, this would be insufficient to maintain any meaningful brain function.”

But Dr. Peled argues that this has not been proved. “Even though we don’t think there is enough circulation to the brain for any function with NRP, we don’t know that with 100% certainty,” he said. “In my view, if there is a possibility of even the smallest amount of brain flow, we are going against the dead donor rule. We are rewriting the rules of death.”

Dr. Moazami countered: “Nothing in life is 100%, particularly in medicine. With that argument can you also prove with 100% certainty to me that there is absolutely no brain function with regular direct procurement DCD?  We know that brain death has started, but the question is: Has it been completed? We don’t know the answer to this question with 100% certainty, but that is the case for regular direct procurement DCD as well, and that has been accepted by almost everyone.

“The whole issue revolves around when are we comfortable that death has occurred,” he said. “Those against NRP are concerned that organs are being taken before the patient is dead. But the key point is that the patient has already been declared dead.”

Since there is some concern over the ethics of NRP, why not just stick to DCD with direct procurement?

Dr. Moazami argued that NRP results in healthier organs. “NRP allows more successful heart transplants, liver transplants, lung transplants. It preserves all the organs better,” he said. “This will have a big impact on recipients – they would obviously much prefer a healthier organ. In addition, the process is easier and cheaper, so more centers will be able to do it, therefore more transplants will get done and more lives will be saved if NRP is used.”

He added: “I am a physician taking care of sick patients. I believe I have to respect the wishes of the donor and the donor family; make sure I’m not doing any harm to the donor; and ensure the best quality possible of the organ I am retrieving to best serve the recipient. I am happy I am doing this by using NRP for DCD heart transplantation.”

But Dr. Peled argued that while NRP may have some possible advantages over direct procurement, that does not justify allowing a process to go ahead that is unethical.

“The fact that NRP may result in some benefits doesn’t justify violating the dead donor rule or the possibility, however small, of causing pain to the donor. If it’s unethical, it’s unethical. Full stop,” he said.

“I feel that NRP is not respecting the rights of our patients and that the process does not have adequate transparency. We took it to our local ethics committee, and they decided not to approve NRP in our health care system. I agree with this decision,” Dr. Peled said.  

“The trouble is different experts and different countries are not in agreement about this,” he added. “Reasonable, well-informed people are in disagreement. I do not believe we can have a standard of care where there is not consensus.”
 

Cautious nod

In a 2022 consensus statement, the International Society for Heart and Lung Transplantation (ISHLT) gave a cautious nod toward DCD and NRP, dependent on local recommendations.

The ISHLT conclusion reads: “With appropriate consideration of the ethical principles involved in organ donation, DCD can be undertaken in a morally permissible manner. In all cases, the introduction of DCD programs should be in accordance with local legal regulations. Countries lacking a DCD pathway should be encouraged to develop national ethical, professional, and legal frameworks to address both public and professional concerns.”

The author of a recent editorial on the subject, Ulrich P. Jorde, MD, head of the heart transplant program at Montefiore Medical Center, New York, said, “DCD is a great step forward. People regularly die on the heart transplant waiting list. DCD will increase the supply of donor hearts by 20% to 30%.”

However, he noted that while most societies have agreed on a protocol for organ donation based on brain death, the situation is more complicated with circulatory death.

“Different countries have different definitions of circulatory death. How long do we have to wait after the heart has stopped beating before the patient is declared dead? Most countries have agreed on 5 minutes, but other countries have imposed different periods and as such, different definitions of death.

“The ISHLT statement says that restarting the circulation is acceptable if death has been certified according to prevailing law and surgical interventions are undertaken to preclude any restoration of cerebral circulation. But our problem is that different regional societies have different definitions of circulatory, death which makes the situation confusing.”

Dr. Jorde added: “We also have to weigh the wishes of the donor and their family. If family, advocating what are presumed to be the donor’s wishes, have decided that DCD would be acceptable and they understand the concept and wish to donate the organs after circulatory death, this should be strongly considered under the concept of self-determination, a basic human right.”
 

Variations in practice around the world 

This ethical debate has led to large variations in practice around the world, with some countries, such as Spain, allowing both methods of DCD, while Australia allows direct procurement but not NRP, and Germany currently does not allow DCD at all.

In the United States, things are even more complicated, with some states allowing NRP while others don’t. Even within states, some hospitals and transplant organizations allow NRP, and others don’t. 

David A. D’Alessandro, MD, cardiac surgeon at Massachusetts General Hospital, Boston, uses only the direct procurement approach as his region does not allow NRP.

“The direct procurement approach is not controversial and to me that’s a big advantage. I believe we need to agree on the ethics first, and then get into a debate about which technique is better,” he told this news organization.

Dr. D’Alessandro and his group recently published the results of their study, with direct procurement DCD heart transplantation showing similar short-term clinical outcomes to DBD.

“We are only doing direct procurement and we are seeing good results that appear to be comparable to DBD. That is good enough for me,” he said.

Dr. D’Alessandro estimates that in the United States both types of DCD procedures are currently being done about equally.

“Anything we can do to increase the amount of hearts available for transplantation is a big deal,” he said. “At the moment, only the very sickest patients get a heart transplant, and many patients die on the transplant waiting list. Very sadly, many young people die every year from a circulatory death after having life support withdrawn. Before DCD, these beautiful functional organs were not able to be used. Now we have a way of saving lives with these organs.”

Dr. D’Alessandro noted that more and more centers in the United States are starting to perform DCD heart transplants. 

“Not every transplant center may join in as the DCD procedures are very resource-intensive and time-consuming. For low-volume transplant centers, it may not be worth the expense and anguish to do DCD heart transplants. But bigger centers will need to engage in DCD to remain competitive. My guess is that 50%-70% of U.S. transplant centers will do DCD in future.”

He said he thinks it is a “medical shortcoming” that agreement cannot be reached on the ethics of NRP. “In an ideal world everyone would be on the same page. It makes me a bit uncomfortable that some people think it’s okay and some people don’t.”

Adam DeVore, MD, a cardiologist at Duke University Medical Center, Durham, N.C., the first U.S. center to perform an adult DCD heart transplant, reported that his institution uses both methods, with the choice sometimes depending on how far the heart must travel.

“If the recipient is near, NRP may be chosen as the heart is transported on ice, but if it needs to go further away we are more likely to choose direct procurement and use of the OCS box,” he said. 

“I am really proud of what we’ve been able to do, helping to introduce DCD in the U.S.,” Dr. DeVore said. “This is having a massive benefit in increasing the number of hearts for donation with great outcomes.”  

But he acknowledged that the whole concept of DCD is somewhat controversial.  

“The idea of brain death really came about for the purpose of heart donation. The two things are very intricately tied. Trying to do heart donation without brain death having been declared is foreign to people. Also, in DCD there is the issue of [this]: When life support is removed, how long do we wait before death can be declared? That could be in conflict with how long the organ needs to remain viable. We are going through the process now of looking at these questions. There is a lot of variation in the U.S. about the withdrawal of care and the declaration of death, which is not completely standardized.

“But the concept of circulatory death itself is accepted after the withdrawal of life support. I think it’s the rush to take the organs out that makes it more difficult.”

Dr. DeVore said the field is moving forward now. “As the process has become more common, people have become more comfortable, probably because of the big difference it will make to saving lives. But we do need to try and standardize best practices.”

A recent Canadian review of the ethics of DCD concluded that the direct procurement approach would be in alignment with current medical guidelines, but that further work is required to evaluate the consistency of NRP with current Canadian death determination policy and to ensure the absence of brain perfusion during this process.

In the United Kingdom, the definition of death is brain-based, and brain death is defined on a neurological basis.

Dr. Stephen Large from Papworth explained that this recognizes the presence of brain-stem death through brain stem reflex testing after the withdrawal of life support, cardiorespiratory arrest and 5 further minutes of ischemia. As long as NRP does not restore intracranial (brainstem) perfusion after death has been confirmed, then it is consistent with laws for death determination and therefore both direct procurement and NRP are permissible.

However, the question over possible collateral flow to the brain has led the United Kingdom to pause the NRP technique as routine practice while this is investigated further. So, at the present time, the vast majority of DCD heart transplants are being conducted using the direct procurement approach.

But the United Kingdom is facing the bigger challenge: national funding that will soon end. “The DCD program in the U.K. has been extremely successful, increasing heart transplant rates by up to 28%,” Dr. Berman said. “Everybody wants it to continue. But at present the DCD program only has national funding in the U.K. until March 2023. We don’t know what will happen after that.”

The current model in the United Kingdom consists of three specialized DCD heart retrieval teams, a national protocol of direct organ procurement and delivery of DCD hearts to all seven transplant programs, both adult and pediatric.

If the national funding is not extended, “we will go back to individual hospitals trying to fund their own programs. That will be a serious threat to the program and could result in a large reduction in heart transplants,” said Dr. Berman.
 

Definition of death  

The crux of the issue with regard to NRP seems to be variations in how death is defined and the interpretation of those definitions.  

DCD donors will have had many tests indicating severe brain damage, a neurologist will have declared the prognosis is futile, and relatives will have agreed to withdraw life support, Dr. Jorde said. “The heart stops beating, and the stand-off time means that blood flow to the brain ceases completely for at least 5 minutes before circulatory death is declared. This is enough on its own to stop brain function.”

Dr. Large made the point that by the time the circulation is reestablished with NRP, more time has elapsed, and the brain will have been without perfusion for much longer than 5 minutes, so it would be “physiologically almost impossible” for there to be any blood flow to the brain.

“Because these brains are already very damaged before life support was removed, the intracranial pressure is high, which will further discourage blood flow to the brain,” he said. Then the donor goes through a period of anoxic heart arrest, up to 16 minutes at a minimum of no blood supply, enough on its own to stop meaningful brain function. 

“It’s asking an awful lot to believe that there might be any brain function left,” he said. “And if, on reestablishing the circulation with NRP, there is any blood in the collaterals, the pressure of such flow is so low it won’t enter the brain.”

Dr. Large also pointed out that the fact that the United Kingdom requires a neurologic definition for brain-stem death makes the process easier. 

In Australia, St. Vincent’s cardiologist Dr. MacDonald noted that death is defined as the irreversible cessation of circulation, so the NRP procedure is not allowed.

“With NRP, there is an ethical dilemma over whether the patient has legally died or not. Different countries have different ways of defining death. Perhaps society will have to review of the definition of death,” he suggested. Death is a process, “but for organ donation, we have to choose a moment in time of that process that satisfies everyone – when there is no prospect of recovery of the donor but the organs can still be utilized without harming the donor.” 

Dr. MacDonald said the field is in transition. “I don’t want to argue that one technique is better than the other; I think it’s good to have access to both techniques. Anything that will increase the number of transplants we can do is a good thing.”
 

Collaborative decision

Everyone seems to agree that there should be an effort to try to define death in a uniform way worldwide, and that international, national and local regulations are aligned with each other.

Dr. Jorde said: “It is of critical importance that local guidelines are streamlined, firstly in any one given country and then globally, and these things must be discussed transparently within society with all stakeholders – doctors, patients, citizens.”

Dr. Peled, from Providence St. Jude in California, concurred: “There is the possibility that we could change the definition of death, but that cannot be a decision based solely on transplant organizations. It has to be a collaborative decision with a large input from groups who do not have an interest in the procurement of organs.”

He added: “The dialogue so far has been civil, and everybody is trying to do the right thing. My hope is that as a civilized society we will figure out a way forward. At present, there is significant controversy about NRP, and families need to know that. My main concern is that if there is any lack of transparency in getting informed consent, then this risks people losing trust in the donation system.” 

Dr. Moazami, from NYU Langone, said the controversy has cast a cloud over the practice of NRP throughout the world. “We need to get it sorted out.”

He said he believes the way forward is to settle the question of whether there is any meaningful blood flow to the brain with the NRP technique.

“This is where the research has to focus. I believe this concern is hypothetical, but I am happy to do the studies to confirm that. Then, the issue should come to a rest. I think that is the right way forward – to do the studies rather than enforcing a moratorium on the practice because of a hypothetical concern.”

These studies on blood flow to the brain are now getting started in both the United Kingdom and the United States.

The U.K. study is being run by Antonio Rubino, MD, consultant in cardiothoracic anesthesia and intensive care at Papworth Hospital NHS Foundation and clinical lead, organ donation. Dr. Rubino explained that the study will assess cerebral blood flow using CT angiography of the brain. “We hypothesize that this will provide evidence to indicate that brain blood flow is not present during NRP and promote trust in the use of NRP in routine practice,” he said.

Dr. Large said: “Rather than having these tortured arguments, we will do the measurements. For the sake of society in this situation, I think it’s good to stop and take a breath. We must measure this, and we are doing just that.”

If there is any blood flow at all, Dr. Large said they will then have to seek expert guidance. “Say we find there is 50 mL of blood flow and normal blood flow is 1,500 mL/min. We will need expert guidance on whether it is remotely possible to be sentient on that. I would say it would be extraordinarily unlikely.”  

Dr. Berman summarized the situation: “DCD is increasing the availability of hearts for transplant. This is saving lives, reducing the number of patients on the waiting list, and reducing hospital stays for patients unable to leave the hospital without a transplant. It is definitely here to stay. It is crucial that it gets funded properly, and it is also crucial that we resolve the NRP ethical issues as soon as possible.”

He is hopeful that some of these issues will be resolved this year.

Dr. MacDonald reported he has received “in-kind” support from Transmedics through provision of research modules for preclinical research studies. Dr. D’Alessandro reported he is on the speakers bureau for Abiomed, not relevant to this article. No other relevant disclosures were reported.
 

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

The relatively recent innovation of heart transplantation after circulatory death of the donor is increasing the number of donor hearts available and leading to many more lives on the heart transplant waiting list being saved. Experts agree it’s a major and very welcome advance in medicine.

However, some of the processes involved in one approach to donation after circulatory death has raised ethical concerns and questions about whether they violate the “dead donor rule” – a principle that requires patients be declared dead before removal of life-sustaining organs for transplant.  

Rasi Bhadramani/iStock/Getty Images

Experts in the fields of transplantation and medical ethics have yet to reach consensus, causing problems for the transplant community, who worry that this could cause a loss of confidence in the entire transplant process.
 

A new pathway for heart transplantation

The traditional approach to transplantation is to retrieve organs from a donor who has been declared brain dead, known as “donation after brain death (DBD).” These patients have usually suffered a catastrophic brain injury but survived to get to intensive care.

As the brain swells because of injury, it becomes evident that all brain function is lost, and the patient is declared brain dead. However, breathing is maintained by the ventilator and the heart is still beating. Because the organs are being oxygenated, there is no immediate rush to retrieve the organs and the heart can be evaluated for its suitability for transplant in a calm and methodical way before it is removed.  

However, there is a massive shortage of organs, especially hearts, partially because of the limited number of donors who are declared brain dead in that setting.

In recent years, another pathway for organ transplantation has become available: “donation after circulatory death (DCD).” These patients also have suffered a catastrophic brain injury considered to be nonsurvivable, but unlike the DBD situation, the brain still has some function, so the patient does not meet the criteria for brain death. 

Still, because the patient is considered to have no chance of a meaningful recovery, the family often recognizes the futility of treatment and agrees to the withdrawal of life support. When this happens, the heart normally stops beating after a period of time. There is then a “stand-off time” – normally 5 minutes – after which death is declared and the organs can be removed. 

The difficulty with this approach, however, is that because the heart has been stopped, it has been deprived of oxygen, potentially causing injury. While DCD has been practiced for several years to retrieve organs such as the kidney, liver, lungs, and pancreas, the heart is more difficult as it is more susceptible to oxygen deprivation. And for the heart to be assessed for transplant suitability, it should ideally be beating, so it has to be reperfused and restarted quickly after death has been declared.

For many years it was thought the oxygen deprivation that occurs after circulatory death would be too much to provide a functional organ. But researchers in the United Kingdom and Australia developed techniques to overcome this problem, and early DCD heart transplants took place in 2014 in Australia, and in 2015 in the United Kingdom.

Heart transplantation after circulatory death has now become a routine part of the transplant program in many countries, including the United States, Spain, Belgium, the Netherlands, and Austria.

In the United States, 348 DCD heart transplants were performed in 2022, with numbers expected to reach 700 to 800 this year as more centers come online.

It is expected that most countries with heart transplant programs will follow suit and the number of donor hearts will increase by up to 30% worldwide because of DCD.  

Currently, there are about 8,000 heart transplants worldwide each year and with DCD this could rise to about 10,000, potentially an extra 2,000 lives saved each year, experts estimate.  

Two different approaches to DCD heart transplantation have been developed.
 

The direct procurement approach

The Australian group, based at St. Vincent’s Hospital in Sydney, developed a technique referred to as “direct procurement”: after the standoff period and declaration of circulatory death, the chest is opened, and the heart is removed. New technology, the Organ Care System (OCS) heart box (Transmedics), is then used to reperfuse and restart the heart outside the body so its suitability for transplant can be assessed.

The heart is kept perfused and beating in the OCS box while it is being transported to the recipient. This has enabled longer transit times than the traditional way of transporting the nonbeating heart on ice.

Peter MacDonald, MD, PhD, from the St Vincent’s group that developed this approach, said, “Most people thought a heart from a DCD donor would not survive transport – that the injury to the heart from the combination of life support withdrawal, stand-off time, and cold storage would be too much. But we modeled the process in the lab and were able to show that we were able to get the heart beating again after withdrawal of life support.”

Dr. McDonald noted that “the recipient of their first human DCD heart transplant using this machine in 2014 is still alive and well.” The Australian group has now done 85 of these DCD heart transplants, and they have increased the number of heart transplant procedures at St. Vincent’s Hospital by 25%.
 

Normothermic regional perfusion (NRP)  

The U.K. group, based at the Royal Papworth Hospital in Cambridge, England, developed a different approach to DCD: After the standoff period and the declaration of circulatory death, the donor is connected to a heart/lung machine using extracorporeal membrane oxygenation (ECMO) so that the heart is perfused and starts beating again inside the body. This approach is known as normothermic regional perfusion (NRP).

Marius Berman, MD, surgical lead for Transplantation and Mechanical Circulatory Support at Papworth, explained that the NRP approach allows the heart to be perfused and restarted faster than direct procurement, resulting in a shorter ischemic time. The heart can be evaluated thoroughly for suitability for transplantation in situ before committing to transplantation, and because the heart is less damaged, it can be transported on ice without use of the OCS box.

“DCD is more complicated than DBD, because the heart has stopped and has to be restarted. Retrieval teams have to be very experienced,” Dr. Berman noted. “This is more of an issue for the direct procurement approach, where the chest has to be opened and the heart retrieved as fast as possible. It is a rush. The longer time without the heart being perfused correlates to an increased incidence of primary graft dysfunction. With NRP, we can get the heart started again more quickly, which is crucial.”

Stephen Large, MBBS, another cardiothoracic surgeon with the Papworth team, added that they have reduced ischemic time to about 15 minutes. “That’s considerably shorter than reperfusing the heart outside the body,” he said. “This results in a healthier organ for the recipient.” 

The NRP approach is also less expensive than direct procurement as one OCS box costs about $75,000.

He pointed out that the NRP approach can also be used for heart transplants in children and even small babies, while currently the direct procurement technique is not typically suitable for children because the OCS box was not designed for small hearts. 

DCD, using either technique, has increased the heart transplant rate by 40% at Papworth, and is being used at all seven transplant centers in the United Kingdom, “a world first,” noted Dr. Large.

The Papworth team recently published its 5-year experience with 25 NRP transplants and 85 direct procurement transplants. Survival in recipients was no different, although there was some suggestion that the NRP hearts may have been in slightly better condition, possibly being more resistant to immunological rejection.
 

Ethical concerns about NRP

Restarting the circulation during the NRP process has raised ethical concerns.

When the NRP technique was first used in the United States, these ethical questions were raised by several groups, including the American College of Physicians (ACP).

Harry Peled, MD, Providence St. Jude Medical Center, Fullerton, Calif., coauthor of a recent Viewpoint on the issue, is board-certified in both cardiology and critical care, and said he is a supporter of DCD using direct procurement, but he does not believe that NRP is ethical at present. He is not part of the ACP, but said his views align with those of the organization.

There are two ethical problems with NRP, he said. The first is whether by restarting the circulation, the NRP process violates the U.S. definition of death, and retrieval of organs would therefore violate the dead donor rule. 

“American law states that death is the irreversible cessation of brain function or of circulatory function. But with NRP, the circulation is artificially restored, so the cessation of circulatory function is not irreversible,” Dr. Peled pointed out.

“I have no problem with DCD using direct procurement as we are not restarting the circulation. But NRP is restarting the circulation and that is a problem for me,” Dr. Peled said. “I would argue that by performing NRP, we are resuscitating the patient.”

The second ethical problem with NRP is concern about whether, during the process, there would be any circulation to the brain, and if so, would this be enough to restore some brain function? Before NRP is started, the main arch vessel arteries to the head are clamped to prevent flow to the brain, but there are worries that some blood flow may still be possible through small collateral vessels.

“We have established that these patients do not have enough brain function for a meaningful life, which is why a decision has been made to remove life support, but they have not been declared brain dead,” Dr. Peled said.

With direct procurement, the circulation is not restarted so there is no chance that any brain function will be restored, he said. “But with NRP, because the arch vessels have to be clamped to prevent brain circulation, that is admitting there is concern that brain function may be restored if circulation to the brain is reestablished, and brain function is compatible with life. As we do not know whether there is any meaningful circulation to the brain via the small collaterals, there is, in effect, a risk of bringing the patient back to life.”

The other major concern for some is whether even a very small amount of circulation to the brain would be enough to support consciousness, and “we don’t know that for certain,” Dr. Peled said.
 

The argument for NRP

Nader Moazami, MD, professor of cardiovascular surgery, NYU Langone Health, New York, is one of the more vocal proponents of NRP for DCD heart transplantation in the United States, and has coauthored responses to these ethical concerns.

“People are confusing many issues to produce an argument against NRP,” he said.

“Our position is that death has already been declared based on the lack of circulatory function for over 5 minutes and this has been with the full agreement of the family, knowing that the patient has no chance of a meaningful life. No one is thinking of trying to resuscitate the patient. It has already been established that any future efforts to resuscitate are futile. In this case, we are not resuscitating the patient by restarting the circulation. It is just regional perfusion of the organs.”

Dr. Moazami pointed out this concept was accepted for the practice of abdominal DCD when it first started in the United States in the 1990s where cold perfusion was used to preserve the abdominal organs before they were retrieved from the body.

“The new approach of using NRP is similar except that it involves circulating warm blood, which will preserve organs better and result in higher quality organs for the recipient.”

On the issue of concern about possible circulation to the brain, Dr. Moazami said: “The ethical critics of NRP are questioning whether the brain may not be dead. We are arguing that the patient has already been declared dead as they have had a circulatory death. You cannot die twice.”

He maintained that the clamping of the arch vessels to the head will ensure that when the circulation is restarted “the natural process of circulatory death leading to brain death will continue to progress.” 

On the concerns about possible collateral flow to the brain, Dr. Moazami said there is no evidence that this occurs. “Prominent neurologists have said it is impossible for collaterals to provide any meaningful blood flow to the brain in this situation. And even if there is small amount of blood flow to the brain, this would be insufficient to maintain any meaningful brain function.”

But Dr. Peled argues that this has not been proved. “Even though we don’t think there is enough circulation to the brain for any function with NRP, we don’t know that with 100% certainty,” he said. “In my view, if there is a possibility of even the smallest amount of brain flow, we are going against the dead donor rule. We are rewriting the rules of death.”

Dr. Moazami countered: “Nothing in life is 100%, particularly in medicine. With that argument can you also prove with 100% certainty to me that there is absolutely no brain function with regular direct procurement DCD?  We know that brain death has started, but the question is: Has it been completed? We don’t know the answer to this question with 100% certainty, but that is the case for regular direct procurement DCD as well, and that has been accepted by almost everyone.

“The whole issue revolves around when are we comfortable that death has occurred,” he said. “Those against NRP are concerned that organs are being taken before the patient is dead. But the key point is that the patient has already been declared dead.”

Since there is some concern over the ethics of NRP, why not just stick to DCD with direct procurement?

Dr. Moazami argued that NRP results in healthier organs. “NRP allows more successful heart transplants, liver transplants, lung transplants. It preserves all the organs better,” he said. “This will have a big impact on recipients – they would obviously much prefer a healthier organ. In addition, the process is easier and cheaper, so more centers will be able to do it, therefore more transplants will get done and more lives will be saved if NRP is used.”

He added: “I am a physician taking care of sick patients. I believe I have to respect the wishes of the donor and the donor family; make sure I’m not doing any harm to the donor; and ensure the best quality possible of the organ I am retrieving to best serve the recipient. I am happy I am doing this by using NRP for DCD heart transplantation.”

But Dr. Peled argued that while NRP may have some possible advantages over direct procurement, that does not justify allowing a process to go ahead that is unethical.

“The fact that NRP may result in some benefits doesn’t justify violating the dead donor rule or the possibility, however small, of causing pain to the donor. If it’s unethical, it’s unethical. Full stop,” he said.

“I feel that NRP is not respecting the rights of our patients and that the process does not have adequate transparency. We took it to our local ethics committee, and they decided not to approve NRP in our health care system. I agree with this decision,” Dr. Peled said.  

“The trouble is different experts and different countries are not in agreement about this,” he added. “Reasonable, well-informed people are in disagreement. I do not believe we can have a standard of care where there is not consensus.”
 

Cautious nod

In a 2022 consensus statement, the International Society for Heart and Lung Transplantation (ISHLT) gave a cautious nod toward DCD and NRP, dependent on local recommendations.

The ISHLT conclusion reads: “With appropriate consideration of the ethical principles involved in organ donation, DCD can be undertaken in a morally permissible manner. In all cases, the introduction of DCD programs should be in accordance with local legal regulations. Countries lacking a DCD pathway should be encouraged to develop national ethical, professional, and legal frameworks to address both public and professional concerns.”

The author of a recent editorial on the subject, Ulrich P. Jorde, MD, head of the heart transplant program at Montefiore Medical Center, New York, said, “DCD is a great step forward. People regularly die on the heart transplant waiting list. DCD will increase the supply of donor hearts by 20% to 30%.”

However, he noted that while most societies have agreed on a protocol for organ donation based on brain death, the situation is more complicated with circulatory death.

“Different countries have different definitions of circulatory death. How long do we have to wait after the heart has stopped beating before the patient is declared dead? Most countries have agreed on 5 minutes, but other countries have imposed different periods and as such, different definitions of death.

“The ISHLT statement says that restarting the circulation is acceptable if death has been certified according to prevailing law and surgical interventions are undertaken to preclude any restoration of cerebral circulation. But our problem is that different regional societies have different definitions of circulatory, death which makes the situation confusing.”

Dr. Jorde added: “We also have to weigh the wishes of the donor and their family. If family, advocating what are presumed to be the donor’s wishes, have decided that DCD would be acceptable and they understand the concept and wish to donate the organs after circulatory death, this should be strongly considered under the concept of self-determination, a basic human right.”
 

Variations in practice around the world 

This ethical debate has led to large variations in practice around the world, with some countries, such as Spain, allowing both methods of DCD, while Australia allows direct procurement but not NRP, and Germany currently does not allow DCD at all.

In the United States, things are even more complicated, with some states allowing NRP while others don’t. Even within states, some hospitals and transplant organizations allow NRP, and others don’t. 

David A. D’Alessandro, MD, cardiac surgeon at Massachusetts General Hospital, Boston, uses only the direct procurement approach as his region does not allow NRP.

“The direct procurement approach is not controversial and to me that’s a big advantage. I believe we need to agree on the ethics first, and then get into a debate about which technique is better,” he told this news organization.

Dr. D’Alessandro and his group recently published the results of their study, with direct procurement DCD heart transplantation showing similar short-term clinical outcomes to DBD.

“We are only doing direct procurement and we are seeing good results that appear to be comparable to DBD. That is good enough for me,” he said.

Dr. D’Alessandro estimates that in the United States both types of DCD procedures are currently being done about equally.

“Anything we can do to increase the amount of hearts available for transplantation is a big deal,” he said. “At the moment, only the very sickest patients get a heart transplant, and many patients die on the transplant waiting list. Very sadly, many young people die every year from a circulatory death after having life support withdrawn. Before DCD, these beautiful functional organs were not able to be used. Now we have a way of saving lives with these organs.”

Dr. D’Alessandro noted that more and more centers in the United States are starting to perform DCD heart transplants. 

“Not every transplant center may join in as the DCD procedures are very resource-intensive and time-consuming. For low-volume transplant centers, it may not be worth the expense and anguish to do DCD heart transplants. But bigger centers will need to engage in DCD to remain competitive. My guess is that 50%-70% of U.S. transplant centers will do DCD in future.”

He said he thinks it is a “medical shortcoming” that agreement cannot be reached on the ethics of NRP. “In an ideal world everyone would be on the same page. It makes me a bit uncomfortable that some people think it’s okay and some people don’t.”

Adam DeVore, MD, a cardiologist at Duke University Medical Center, Durham, N.C., the first U.S. center to perform an adult DCD heart transplant, reported that his institution uses both methods, with the choice sometimes depending on how far the heart must travel.

“If the recipient is near, NRP may be chosen as the heart is transported on ice, but if it needs to go further away we are more likely to choose direct procurement and use of the OCS box,” he said. 

“I am really proud of what we’ve been able to do, helping to introduce DCD in the U.S.,” Dr. DeVore said. “This is having a massive benefit in increasing the number of hearts for donation with great outcomes.”  

But he acknowledged that the whole concept of DCD is somewhat controversial.  

“The idea of brain death really came about for the purpose of heart donation. The two things are very intricately tied. Trying to do heart donation without brain death having been declared is foreign to people. Also, in DCD there is the issue of [this]: When life support is removed, how long do we wait before death can be declared? That could be in conflict with how long the organ needs to remain viable. We are going through the process now of looking at these questions. There is a lot of variation in the U.S. about the withdrawal of care and the declaration of death, which is not completely standardized.

“But the concept of circulatory death itself is accepted after the withdrawal of life support. I think it’s the rush to take the organs out that makes it more difficult.”

Dr. DeVore said the field is moving forward now. “As the process has become more common, people have become more comfortable, probably because of the big difference it will make to saving lives. But we do need to try and standardize best practices.”

A recent Canadian review of the ethics of DCD concluded that the direct procurement approach would be in alignment with current medical guidelines, but that further work is required to evaluate the consistency of NRP with current Canadian death determination policy and to ensure the absence of brain perfusion during this process.

In the United Kingdom, the definition of death is brain-based, and brain death is defined on a neurological basis.

Dr. Stephen Large from Papworth explained that this recognizes the presence of brain-stem death through brain stem reflex testing after the withdrawal of life support, cardiorespiratory arrest and 5 further minutes of ischemia. As long as NRP does not restore intracranial (brainstem) perfusion after death has been confirmed, then it is consistent with laws for death determination and therefore both direct procurement and NRP are permissible.

However, the question over possible collateral flow to the brain has led the United Kingdom to pause the NRP technique as routine practice while this is investigated further. So, at the present time, the vast majority of DCD heart transplants are being conducted using the direct procurement approach.

But the United Kingdom is facing the bigger challenge: national funding that will soon end. “The DCD program in the U.K. has been extremely successful, increasing heart transplant rates by up to 28%,” Dr. Berman said. “Everybody wants it to continue. But at present the DCD program only has national funding in the U.K. until March 2023. We don’t know what will happen after that.”

The current model in the United Kingdom consists of three specialized DCD heart retrieval teams, a national protocol of direct organ procurement and delivery of DCD hearts to all seven transplant programs, both adult and pediatric.

If the national funding is not extended, “we will go back to individual hospitals trying to fund their own programs. That will be a serious threat to the program and could result in a large reduction in heart transplants,” said Dr. Berman.
 

Definition of death  

The crux of the issue with regard to NRP seems to be variations in how death is defined and the interpretation of those definitions.  

DCD donors will have had many tests indicating severe brain damage, a neurologist will have declared the prognosis is futile, and relatives will have agreed to withdraw life support, Dr. Jorde said. “The heart stops beating, and the stand-off time means that blood flow to the brain ceases completely for at least 5 minutes before circulatory death is declared. This is enough on its own to stop brain function.”

Dr. Large made the point that by the time the circulation is reestablished with NRP, more time has elapsed, and the brain will have been without perfusion for much longer than 5 minutes, so it would be “physiologically almost impossible” for there to be any blood flow to the brain.

“Because these brains are already very damaged before life support was removed, the intracranial pressure is high, which will further discourage blood flow to the brain,” he said. Then the donor goes through a period of anoxic heart arrest, up to 16 minutes at a minimum of no blood supply, enough on its own to stop meaningful brain function. 

“It’s asking an awful lot to believe that there might be any brain function left,” he said. “And if, on reestablishing the circulation with NRP, there is any blood in the collaterals, the pressure of such flow is so low it won’t enter the brain.”

Dr. Large also pointed out that the fact that the United Kingdom requires a neurologic definition for brain-stem death makes the process easier. 

In Australia, St. Vincent’s cardiologist Dr. MacDonald noted that death is defined as the irreversible cessation of circulation, so the NRP procedure is not allowed.

“With NRP, there is an ethical dilemma over whether the patient has legally died or not. Different countries have different ways of defining death. Perhaps society will have to review of the definition of death,” he suggested. Death is a process, “but for organ donation, we have to choose a moment in time of that process that satisfies everyone – when there is no prospect of recovery of the donor but the organs can still be utilized without harming the donor.” 

Dr. MacDonald said the field is in transition. “I don’t want to argue that one technique is better than the other; I think it’s good to have access to both techniques. Anything that will increase the number of transplants we can do is a good thing.”
 

Collaborative decision

Everyone seems to agree that there should be an effort to try to define death in a uniform way worldwide, and that international, national and local regulations are aligned with each other.

Dr. Jorde said: “It is of critical importance that local guidelines are streamlined, firstly in any one given country and then globally, and these things must be discussed transparently within society with all stakeholders – doctors, patients, citizens.”

Dr. Peled, from Providence St. Jude in California, concurred: “There is the possibility that we could change the definition of death, but that cannot be a decision based solely on transplant organizations. It has to be a collaborative decision with a large input from groups who do not have an interest in the procurement of organs.”

He added: “The dialogue so far has been civil, and everybody is trying to do the right thing. My hope is that as a civilized society we will figure out a way forward. At present, there is significant controversy about NRP, and families need to know that. My main concern is that if there is any lack of transparency in getting informed consent, then this risks people losing trust in the donation system.” 

Dr. Moazami, from NYU Langone, said the controversy has cast a cloud over the practice of NRP throughout the world. “We need to get it sorted out.”

He said he believes the way forward is to settle the question of whether there is any meaningful blood flow to the brain with the NRP technique.

“This is where the research has to focus. I believe this concern is hypothetical, but I am happy to do the studies to confirm that. Then, the issue should come to a rest. I think that is the right way forward – to do the studies rather than enforcing a moratorium on the practice because of a hypothetical concern.”

These studies on blood flow to the brain are now getting started in both the United Kingdom and the United States.

The U.K. study is being run by Antonio Rubino, MD, consultant in cardiothoracic anesthesia and intensive care at Papworth Hospital NHS Foundation and clinical lead, organ donation. Dr. Rubino explained that the study will assess cerebral blood flow using CT angiography of the brain. “We hypothesize that this will provide evidence to indicate that brain blood flow is not present during NRP and promote trust in the use of NRP in routine practice,” he said.

Dr. Large said: “Rather than having these tortured arguments, we will do the measurements. For the sake of society in this situation, I think it’s good to stop and take a breath. We must measure this, and we are doing just that.”

If there is any blood flow at all, Dr. Large said they will then have to seek expert guidance. “Say we find there is 50 mL of blood flow and normal blood flow is 1,500 mL/min. We will need expert guidance on whether it is remotely possible to be sentient on that. I would say it would be extraordinarily unlikely.”  

Dr. Berman summarized the situation: “DCD is increasing the availability of hearts for transplant. This is saving lives, reducing the number of patients on the waiting list, and reducing hospital stays for patients unable to leave the hospital without a transplant. It is definitely here to stay. It is crucial that it gets funded properly, and it is also crucial that we resolve the NRP ethical issues as soon as possible.”

He is hopeful that some of these issues will be resolved this year.

Dr. MacDonald reported he has received “in-kind” support from Transmedics through provision of research modules for preclinical research studies. Dr. D’Alessandro reported he is on the speakers bureau for Abiomed, not relevant to this article. No other relevant disclosures were reported.
 

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

Anifrolumab appears to improve outcomes in patients with refractory discoid lupus erythematosus (DLE), especially in those with severe or recalcitrant disease, a small retrospective study reports.

DLE, the most common form of chronic cutaneous lupus erythematosus, can permanently scar and disfigure patients, and traditional treatments such as antimalarials, steroid-sparing immunosuppressive agents, thalidomide, retinoids, and lenalidomide don’t consistently improve refractory DLE, the authors noted.

“All patients demonstrated significant improvement in symptomatology and disease activity within 2 months of initiating anifrolumab,” lead study author Katharina Shaw, MD, of the department of dermatology of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues wrote in a research letter published in JAMA Dermatology. “These early results highlight the potential for anifrolumab to be a viable therapeutic option for patients with DLE, particularly those with severe or recalcitrant disease.”

The Food and Drug Administration approved anifrolumab (Saphnelo), a human monoclonal antibody targeting type 1 interferon receptor subunit 1, in 2021 for adults with moderate to severe systemic lupus erythematosus, but it has not been approved for the treatment of DLE.

Dr. Shaw and colleagues queried the medical records from Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, to find all cases of DLE based on biopsy, expert opinion, or both from January 2000 to October 2022.

The researchers identified eight female patients who had received anifrolumab for at least 8 weeks. The women were aged between 19 and 75 years (median, 42.5 years), and all had DLE recalcitrant to standard therapies and had been treated with hydroxychloroquine and between 1 and 10 other drugs, most commonly methotrexate and mycophenolate mofetil (MMF).

The authors looked for improvements in patient-reported symptoms and Cutaneous Lupus Erythematosus Disease Area and Severity Index scores, including CLASI A (activity) score 0-70, and CLASI-D (damage) score 0-56.

All patients showed significantly improved symptoms and disease activity within 2 months of their first infusion of the treatment. The mean decrease and mean percentage decrease in CLASI-A scores were 17.1 and 65.1%, respectively. The mean decrease and mean percentage decrease in CLASI-D scores were 0.5 and 2.9%, respectively.

The rapid clinical improvements with anifrolumab, compared with improvements with traditional medications, were striking, the authors wrote. “Given the risk for permanent scarring, dyspigmentation, and alopecia with poorly controlled DLE, the importance of rapidly mitigating disease activity cannot be overemphasized.”

They acknowledged that the results are limited by the study’s small sample size and retrospective design, and they recommend larger related prospective studies.

Dr. Kaveh Ardalan

Asked to comment on the results, Kaveh Ardalan, MD, MS, assistant professor of pediatrics in the division of pediatric rheumatology at Duke University, Durham, N.C., said that finding new DLE therapeutics is important because of the huge impact of uncontrolled DLE on patients’ quality of life, body image, and social roles.

Dr. Ardalan noted that he sees DLE in his pediatric patients, “either as an isolated finding or in the context of systemic lupus erythematosus. Anifrolumab is not approved by the FDA to treat DLE or children.

“Randomized controlled trials, including the TULIP-1 and TULIP-2 studies of anifrolumab in systemic lupus, have indicated that lupus skin manifestations can improve in patients who receive anifrolumab,” said Dr. Ardalan, who was not involved in the study. “And we know that type I interferons are major drivers of cutaneous disease activity in patients with lupus, so targeting that mechanism with anifrolumab makes biological sense.”

The authors’ use of the validated CLASI classification system to quantify disease activity and damage over time, and their determination of the length of time for the drug to take effect are strengths of the study, he added.

Funding information was not provided. Two authors reported financial relationships with Pfizer, which does not manufacture anifrolumab. Dr. Ardalan reported no conflicts of interest with the study.

Anifrolumab appears to improve outcomes in patients with refractory discoid lupus erythematosus (DLE), especially in those with severe or recalcitrant disease, a small retrospective study reports.

DLE, the most common form of chronic cutaneous lupus erythematosus, can permanently scar and disfigure patients, and traditional treatments such as antimalarials, steroid-sparing immunosuppressive agents, thalidomide, retinoids, and lenalidomide don’t consistently improve refractory DLE, the authors noted.

“All patients demonstrated significant improvement in symptomatology and disease activity within 2 months of initiating anifrolumab,” lead study author Katharina Shaw, MD, of the department of dermatology of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues wrote in a research letter published in JAMA Dermatology. “These early results highlight the potential for anifrolumab to be a viable therapeutic option for patients with DLE, particularly those with severe or recalcitrant disease.”

The Food and Drug Administration approved anifrolumab (Saphnelo), a human monoclonal antibody targeting type 1 interferon receptor subunit 1, in 2021 for adults with moderate to severe systemic lupus erythematosus, but it has not been approved for the treatment of DLE.

Dr. Shaw and colleagues queried the medical records from Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, to find all cases of DLE based on biopsy, expert opinion, or both from January 2000 to October 2022.

The researchers identified eight female patients who had received anifrolumab for at least 8 weeks. The women were aged between 19 and 75 years (median, 42.5 years), and all had DLE recalcitrant to standard therapies and had been treated with hydroxychloroquine and between 1 and 10 other drugs, most commonly methotrexate and mycophenolate mofetil (MMF).

The authors looked for improvements in patient-reported symptoms and Cutaneous Lupus Erythematosus Disease Area and Severity Index scores, including CLASI A (activity) score 0-70, and CLASI-D (damage) score 0-56.

All patients showed significantly improved symptoms and disease activity within 2 months of their first infusion of the treatment. The mean decrease and mean percentage decrease in CLASI-A scores were 17.1 and 65.1%, respectively. The mean decrease and mean percentage decrease in CLASI-D scores were 0.5 and 2.9%, respectively.

The rapid clinical improvements with anifrolumab, compared with improvements with traditional medications, were striking, the authors wrote. “Given the risk for permanent scarring, dyspigmentation, and alopecia with poorly controlled DLE, the importance of rapidly mitigating disease activity cannot be overemphasized.”

They acknowledged that the results are limited by the study’s small sample size and retrospective design, and they recommend larger related prospective studies.

Dr. Kaveh Ardalan

Asked to comment on the results, Kaveh Ardalan, MD, MS, assistant professor of pediatrics in the division of pediatric rheumatology at Duke University, Durham, N.C., said that finding new DLE therapeutics is important because of the huge impact of uncontrolled DLE on patients’ quality of life, body image, and social roles.

Dr. Ardalan noted that he sees DLE in his pediatric patients, “either as an isolated finding or in the context of systemic lupus erythematosus. Anifrolumab is not approved by the FDA to treat DLE or children.

“Randomized controlled trials, including the TULIP-1 and TULIP-2 studies of anifrolumab in systemic lupus, have indicated that lupus skin manifestations can improve in patients who receive anifrolumab,” said Dr. Ardalan, who was not involved in the study. “And we know that type I interferons are major drivers of cutaneous disease activity in patients with lupus, so targeting that mechanism with anifrolumab makes biological sense.”

The authors’ use of the validated CLASI classification system to quantify disease activity and damage over time, and their determination of the length of time for the drug to take effect are strengths of the study, he added.

Funding information was not provided. Two authors reported financial relationships with Pfizer, which does not manufacture anifrolumab. Dr. Ardalan reported no conflicts of interest with the study.

Anifrolumab appears to improve outcomes in patients with refractory discoid lupus erythematosus (DLE), especially in those with severe or recalcitrant disease, a small retrospective study reports.

DLE, the most common form of chronic cutaneous lupus erythematosus, can permanently scar and disfigure patients, and traditional treatments such as antimalarials, steroid-sparing immunosuppressive agents, thalidomide, retinoids, and lenalidomide don’t consistently improve refractory DLE, the authors noted.

“All patients demonstrated significant improvement in symptomatology and disease activity within 2 months of initiating anifrolumab,” lead study author Katharina Shaw, MD, of the department of dermatology of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues wrote in a research letter published in JAMA Dermatology. “These early results highlight the potential for anifrolumab to be a viable therapeutic option for patients with DLE, particularly those with severe or recalcitrant disease.”

The Food and Drug Administration approved anifrolumab (Saphnelo), a human monoclonal antibody targeting type 1 interferon receptor subunit 1, in 2021 for adults with moderate to severe systemic lupus erythematosus, but it has not been approved for the treatment of DLE.

Dr. Shaw and colleagues queried the medical records from Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, to find all cases of DLE based on biopsy, expert opinion, or both from January 2000 to October 2022.

The researchers identified eight female patients who had received anifrolumab for at least 8 weeks. The women were aged between 19 and 75 years (median, 42.5 years), and all had DLE recalcitrant to standard therapies and had been treated with hydroxychloroquine and between 1 and 10 other drugs, most commonly methotrexate and mycophenolate mofetil (MMF).

The authors looked for improvements in patient-reported symptoms and Cutaneous Lupus Erythematosus Disease Area and Severity Index scores, including CLASI A (activity) score 0-70, and CLASI-D (damage) score 0-56.

All patients showed significantly improved symptoms and disease activity within 2 months of their first infusion of the treatment. The mean decrease and mean percentage decrease in CLASI-A scores were 17.1 and 65.1%, respectively. The mean decrease and mean percentage decrease in CLASI-D scores were 0.5 and 2.9%, respectively.

The rapid clinical improvements with anifrolumab, compared with improvements with traditional medications, were striking, the authors wrote. “Given the risk for permanent scarring, dyspigmentation, and alopecia with poorly controlled DLE, the importance of rapidly mitigating disease activity cannot be overemphasized.”

They acknowledged that the results are limited by the study’s small sample size and retrospective design, and they recommend larger related prospective studies.

Dr. Kaveh Ardalan

Asked to comment on the results, Kaveh Ardalan, MD, MS, assistant professor of pediatrics in the division of pediatric rheumatology at Duke University, Durham, N.C., said that finding new DLE therapeutics is important because of the huge impact of uncontrolled DLE on patients’ quality of life, body image, and social roles.

Dr. Ardalan noted that he sees DLE in his pediatric patients, “either as an isolated finding or in the context of systemic lupus erythematosus. Anifrolumab is not approved by the FDA to treat DLE or children.

“Randomized controlled trials, including the TULIP-1 and TULIP-2 studies of anifrolumab in systemic lupus, have indicated that lupus skin manifestations can improve in patients who receive anifrolumab,” said Dr. Ardalan, who was not involved in the study. “And we know that type I interferons are major drivers of cutaneous disease activity in patients with lupus, so targeting that mechanism with anifrolumab makes biological sense.”

The authors’ use of the validated CLASI classification system to quantify disease activity and damage over time, and their determination of the length of time for the drug to take effect are strengths of the study, he added.

Funding information was not provided. Two authors reported financial relationships with Pfizer, which does not manufacture anifrolumab. Dr. Ardalan reported no conflicts of interest with the study.