Alpha-gal syndrome is an increasingly common cause of gastrointestinal issues that remains underrecognized by the medical community, according to an American Gastroenterological Association clinical practice update.

Although the allergic response is best known for a combination of anaphylaxis, skin changes, and gastrointestinal symptoms that occurs within hours of consuming mammalian-derived food products, health care providers should know that many patients experience gastrointestinal distress in the absence of other clinical signs, lead author Sarah K. McGill, MD, MSc, of the University of North Carolina at Chapel Hill, and colleagues reported.

“It is important for gastroenterologists to be aware of this condition and to be capable of diagnosing and treating it in a timely manner,” the investigators wrote in Clinical Gastroenterology and Hepatology.

To this end, Dr. McGill and colleagues drafted the present clinical practice update, covering pathogenesis, clinical manifestations, diagnosis, and management.

“The allergy in alpha-gal syndrome is to galactose alpha-1,3-galactose, an oligosaccharide on the cells of all nonprimate mammals,” the investigators wrote. “Surprisingly, sensitization to alpha-gal, that is, the process by which human beings develop IgE antibodies to the sugar, is understood to occur after the bite of a tick or parasitic infection. In the United States, the Lone Star tick, an ectoparasite whose principal host is deer, is strongly implicated.”

Gastrointestinal focused clinical research is scarce, the investigators noted, citing two observational studies involving 375 patients positive for alpha-gal IgE. Almost half of these patients (40.7%) had gastrointestinal symptoms alone. Across the entire population, the most common gastrointestinal symptoms were abdominal pain (71%) and vomiting (22%). About three out of four patients reported improvement on an alpha-gal avoidance diet.

“Clinicians should consider alpha-gal syndrome in the differential diagnosis of patients with unexplained gastrointestinal symptoms of abdominal pain, diarrhea, nausea, and vomiting, particularly those who live or have lived in an alpha-gal–prevalent area,” the investigators wrote.

In the United States, these areas span the domain of the Lone Star tick, including most of the East Coast, the central Midwest, the South, and all of Texas. Overseas, alpha-gal syndrome has been reported in Japan, Australia, Western Europe, and South Africa.

Clinical suspicion should be increased in patients with a history of tick bite, engagement in outdoor activities, and awakening in the night with gastrointestinal distress (because of the delay between allergen ingestion and symptom onset). Workup should include serum testing for alpha-gal IgE antibodies, according to the update. Serum positivity alone, however, is not sufficient for diagnosis. Alpha-gal syndrome must be confirmed by symptom resolution or improvement upon adherence to an alpha-gal avoidance diet for at least a month.

“During this time, patients may want to avoid eating at restaurants, which can easily cross-contaminate food, and processed food, which may contain alpha-gal in additives,” Dr. McGill and colleagues wrote.

Patients with alpha-gal syndrome who accidentally consume alpha-gal should take 25-50 mg of diphenhydramine and ensure access to a self-injectable epinephrine if symptoms progress, particularly if respiratory compromise occurs, they added.

The coauthors are Jana G. Hasash, MD, and Thomas A. Platts-Mills, MD, PhD.

The investigators disclosed relationships with Olympus America, Exact Sciences, Guardant Health, Finch Therapeutics, and others.

Alpha-gal syndrome is an increasingly common cause of gastrointestinal issues that remains underrecognized by the medical community, according to an American Gastroenterological Association clinical practice update.

Although the allergic response is best known for a combination of anaphylaxis, skin changes, and gastrointestinal symptoms that occurs within hours of consuming mammalian-derived food products, health care providers should know that many patients experience gastrointestinal distress in the absence of other clinical signs, lead author Sarah K. McGill, MD, MSc, of the University of North Carolina at Chapel Hill, and colleagues reported.

“It is important for gastroenterologists to be aware of this condition and to be capable of diagnosing and treating it in a timely manner,” the investigators wrote in Clinical Gastroenterology and Hepatology.

To this end, Dr. McGill and colleagues drafted the present clinical practice update, covering pathogenesis, clinical manifestations, diagnosis, and management.

“The allergy in alpha-gal syndrome is to galactose alpha-1,3-galactose, an oligosaccharide on the cells of all nonprimate mammals,” the investigators wrote. “Surprisingly, sensitization to alpha-gal, that is, the process by which human beings develop IgE antibodies to the sugar, is understood to occur after the bite of a tick or parasitic infection. In the United States, the Lone Star tick, an ectoparasite whose principal host is deer, is strongly implicated.”

Gastrointestinal focused clinical research is scarce, the investigators noted, citing two observational studies involving 375 patients positive for alpha-gal IgE. Almost half of these patients (40.7%) had gastrointestinal symptoms alone. Across the entire population, the most common gastrointestinal symptoms were abdominal pain (71%) and vomiting (22%). About three out of four patients reported improvement on an alpha-gal avoidance diet.

“Clinicians should consider alpha-gal syndrome in the differential diagnosis of patients with unexplained gastrointestinal symptoms of abdominal pain, diarrhea, nausea, and vomiting, particularly those who live or have lived in an alpha-gal–prevalent area,” the investigators wrote.

In the United States, these areas span the domain of the Lone Star tick, including most of the East Coast, the central Midwest, the South, and all of Texas. Overseas, alpha-gal syndrome has been reported in Japan, Australia, Western Europe, and South Africa.

Clinical suspicion should be increased in patients with a history of tick bite, engagement in outdoor activities, and awakening in the night with gastrointestinal distress (because of the delay between allergen ingestion and symptom onset). Workup should include serum testing for alpha-gal IgE antibodies, according to the update. Serum positivity alone, however, is not sufficient for diagnosis. Alpha-gal syndrome must be confirmed by symptom resolution or improvement upon adherence to an alpha-gal avoidance diet for at least a month.

“During this time, patients may want to avoid eating at restaurants, which can easily cross-contaminate food, and processed food, which may contain alpha-gal in additives,” Dr. McGill and colleagues wrote.

Patients with alpha-gal syndrome who accidentally consume alpha-gal should take 25-50 mg of diphenhydramine and ensure access to a self-injectable epinephrine if symptoms progress, particularly if respiratory compromise occurs, they added.

The coauthors are Jana G. Hasash, MD, and Thomas A. Platts-Mills, MD, PhD.

The investigators disclosed relationships with Olympus America, Exact Sciences, Guardant Health, Finch Therapeutics, and others.

Alpha-gal syndrome is an increasingly common cause of gastrointestinal issues that remains underrecognized by the medical community, according to an American Gastroenterological Association clinical practice update.

Although the allergic response is best known for a combination of anaphylaxis, skin changes, and gastrointestinal symptoms that occurs within hours of consuming mammalian-derived food products, health care providers should know that many patients experience gastrointestinal distress in the absence of other clinical signs, lead author Sarah K. McGill, MD, MSc, of the University of North Carolina at Chapel Hill, and colleagues reported.

“It is important for gastroenterologists to be aware of this condition and to be capable of diagnosing and treating it in a timely manner,” the investigators wrote in Clinical Gastroenterology and Hepatology.

To this end, Dr. McGill and colleagues drafted the present clinical practice update, covering pathogenesis, clinical manifestations, diagnosis, and management.

“The allergy in alpha-gal syndrome is to galactose alpha-1,3-galactose, an oligosaccharide on the cells of all nonprimate mammals,” the investigators wrote. “Surprisingly, sensitization to alpha-gal, that is, the process by which human beings develop IgE antibodies to the sugar, is understood to occur after the bite of a tick or parasitic infection. In the United States, the Lone Star tick, an ectoparasite whose principal host is deer, is strongly implicated.”

Gastrointestinal focused clinical research is scarce, the investigators noted, citing two observational studies involving 375 patients positive for alpha-gal IgE. Almost half of these patients (40.7%) had gastrointestinal symptoms alone. Across the entire population, the most common gastrointestinal symptoms were abdominal pain (71%) and vomiting (22%). About three out of four patients reported improvement on an alpha-gal avoidance diet.

“Clinicians should consider alpha-gal syndrome in the differential diagnosis of patients with unexplained gastrointestinal symptoms of abdominal pain, diarrhea, nausea, and vomiting, particularly those who live or have lived in an alpha-gal–prevalent area,” the investigators wrote.

In the United States, these areas span the domain of the Lone Star tick, including most of the East Coast, the central Midwest, the South, and all of Texas. Overseas, alpha-gal syndrome has been reported in Japan, Australia, Western Europe, and South Africa.

Clinical suspicion should be increased in patients with a history of tick bite, engagement in outdoor activities, and awakening in the night with gastrointestinal distress (because of the delay between allergen ingestion and symptom onset). Workup should include serum testing for alpha-gal IgE antibodies, according to the update. Serum positivity alone, however, is not sufficient for diagnosis. Alpha-gal syndrome must be confirmed by symptom resolution or improvement upon adherence to an alpha-gal avoidance diet for at least a month.

“During this time, patients may want to avoid eating at restaurants, which can easily cross-contaminate food, and processed food, which may contain alpha-gal in additives,” Dr. McGill and colleagues wrote.

Patients with alpha-gal syndrome who accidentally consume alpha-gal should take 25-50 mg of diphenhydramine and ensure access to a self-injectable epinephrine if symptoms progress, particularly if respiratory compromise occurs, they added.

The coauthors are Jana G. Hasash, MD, and Thomas A. Platts-Mills, MD, PhD.

The investigators disclosed relationships with Olympus America, Exact Sciences, Guardant Health, Finch Therapeutics, and others.

Investigators have identified four blood biomarkers that could potentially be used to predict, diagnose, and monitor treatment response for posttraumatic stress disorder.

“More accurate means of predicting or screening for PTSD could help to overcome the disorder by identifying individuals at high risk of developing PTSD and providing them with early intervention or prevention strategies,” said study investigator Stacy-Ann Miller, MS.

She also noted that the biomarkers could be used to monitor treatment for PTSD, identify subtypes of PTSD, and lead to a new understanding of the mechanisms underlying PTSD.

The findings were presented at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology.
 

Toward better clinical assessment

The findings originated from research conducted by the Department of Defense–initiated PTSD Systems Biology Consortium. The consortium’s goals include developing a reproducible panel of blood-based biomarkers with high sensitivity and specificity for PTSD diagnosis and is made up of about 45 researchers, led by Marti Jett, PhD, Charles Marmar, MD, and Francis J. Doyle III, PhD.

The researchers analyzed blood samples from 1,000 active-duty Army personnel from the 101st Airborne at Fort Campbell, Ky. Participants were assessed before and after deployment to Afghanistan in February 2014 and are referred to as the Fort Campbell Cohort (FCC). Participants’ age ranged from 25 to 30 and approximately 6% were female.

Investigators collected blood samples from the service members and looked for four biomarkers: glycolytic ratio, arginine, serotonin, and glutamate. The team then divided the participants into four groups – those with PTSD (PTSD Checklist score above 30), those who were subthreshold for PTSD (PTSD Checklist score 15-30), those who had high resilience, and those who had low levels of resilience.

The resilience groups were determined based on answers to the Generalized Anxiety Disorder Questionnaire, Patient Health Questionnaire, Pittsburgh Sleep Quality Index, Intensive Combat Exposure (DRRI-D), the number of deployments, whether they had moderate or severe traumatic brain injury, and scores on the Alcohol Use Disorders Identification Test.

Those who scored in the high range at current or prior time points or who were PTSD/subthreshold at prior time points were placed in the low resilience group.

Ms. Miller noted that those in the PTSD group had more severe symptoms than those in the PTSD subthreshold group based on the longitudinal clinical assessment at 3-6 months, 5 years, and longer post deployment. The low resilience group had a much higher rate of PTSD post deployment than the high resilience group.

Investigators found participants with PTSD or subthreshold PTSD had significantly higher glycolic ratios and lower arginine than those with high resilience. They also found that those with PTSD had significantly lower serotonin and higher glutamate levels versus those with high resilience. These associations were independent of factors such as sex, age, body mass index, smoking, and caffeine consumption.

Ms. Miller said that the study results require further validation by the consortium’s labs and third-party labs.

“We are also interested in determining the most appropriate time to screen soldiers for PTSD, as it has been noted that the time period where we see the most psychological issues is around 2-3 months post return from deployment and when the soldier is preparing for their next assignment, perhaps a next deployment,” she said.

She added that previous studies have identified several promising biomarkers of PTSD. “However, like much of the research data, the study sample was comprised mainly of combat-exposed males. With more women serving on the front lines, the military faces new challenges in how combat affects females in the military,” including sex-specific biomarkers that will improve clinical assessment for female soldiers.

Eventually, the team would also like to be able to apply their research to the civilian population experiencing PTSD.

“Our research is anticipated to be useful in helping the medical provider select appropriate therapeutic interventions,” Ms. Miller said.

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

Investigators have identified four blood biomarkers that could potentially be used to predict, diagnose, and monitor treatment response for posttraumatic stress disorder.

“More accurate means of predicting or screening for PTSD could help to overcome the disorder by identifying individuals at high risk of developing PTSD and providing them with early intervention or prevention strategies,” said study investigator Stacy-Ann Miller, MS.

She also noted that the biomarkers could be used to monitor treatment for PTSD, identify subtypes of PTSD, and lead to a new understanding of the mechanisms underlying PTSD.

The findings were presented at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology.
 

Toward better clinical assessment

The findings originated from research conducted by the Department of Defense–initiated PTSD Systems Biology Consortium. The consortium’s goals include developing a reproducible panel of blood-based biomarkers with high sensitivity and specificity for PTSD diagnosis and is made up of about 45 researchers, led by Marti Jett, PhD, Charles Marmar, MD, and Francis J. Doyle III, PhD.

The researchers analyzed blood samples from 1,000 active-duty Army personnel from the 101st Airborne at Fort Campbell, Ky. Participants were assessed before and after deployment to Afghanistan in February 2014 and are referred to as the Fort Campbell Cohort (FCC). Participants’ age ranged from 25 to 30 and approximately 6% were female.

Investigators collected blood samples from the service members and looked for four biomarkers: glycolytic ratio, arginine, serotonin, and glutamate. The team then divided the participants into four groups – those with PTSD (PTSD Checklist score above 30), those who were subthreshold for PTSD (PTSD Checklist score 15-30), those who had high resilience, and those who had low levels of resilience.

The resilience groups were determined based on answers to the Generalized Anxiety Disorder Questionnaire, Patient Health Questionnaire, Pittsburgh Sleep Quality Index, Intensive Combat Exposure (DRRI-D), the number of deployments, whether they had moderate or severe traumatic brain injury, and scores on the Alcohol Use Disorders Identification Test.

Those who scored in the high range at current or prior time points or who were PTSD/subthreshold at prior time points were placed in the low resilience group.

Ms. Miller noted that those in the PTSD group had more severe symptoms than those in the PTSD subthreshold group based on the longitudinal clinical assessment at 3-6 months, 5 years, and longer post deployment. The low resilience group had a much higher rate of PTSD post deployment than the high resilience group.

Investigators found participants with PTSD or subthreshold PTSD had significantly higher glycolic ratios and lower arginine than those with high resilience. They also found that those with PTSD had significantly lower serotonin and higher glutamate levels versus those with high resilience. These associations were independent of factors such as sex, age, body mass index, smoking, and caffeine consumption.

Ms. Miller said that the study results require further validation by the consortium’s labs and third-party labs.

“We are also interested in determining the most appropriate time to screen soldiers for PTSD, as it has been noted that the time period where we see the most psychological issues is around 2-3 months post return from deployment and when the soldier is preparing for their next assignment, perhaps a next deployment,” she said.

She added that previous studies have identified several promising biomarkers of PTSD. “However, like much of the research data, the study sample was comprised mainly of combat-exposed males. With more women serving on the front lines, the military faces new challenges in how combat affects females in the military,” including sex-specific biomarkers that will improve clinical assessment for female soldiers.

Eventually, the team would also like to be able to apply their research to the civilian population experiencing PTSD.

“Our research is anticipated to be useful in helping the medical provider select appropriate therapeutic interventions,” Ms. Miller said.

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

Investigators have identified four blood biomarkers that could potentially be used to predict, diagnose, and monitor treatment response for posttraumatic stress disorder.

“More accurate means of predicting or screening for PTSD could help to overcome the disorder by identifying individuals at high risk of developing PTSD and providing them with early intervention or prevention strategies,” said study investigator Stacy-Ann Miller, MS.

She also noted that the biomarkers could be used to monitor treatment for PTSD, identify subtypes of PTSD, and lead to a new understanding of the mechanisms underlying PTSD.

The findings were presented at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology.
 

Toward better clinical assessment

The findings originated from research conducted by the Department of Defense–initiated PTSD Systems Biology Consortium. The consortium’s goals include developing a reproducible panel of blood-based biomarkers with high sensitivity and specificity for PTSD diagnosis and is made up of about 45 researchers, led by Marti Jett, PhD, Charles Marmar, MD, and Francis J. Doyle III, PhD.

The researchers analyzed blood samples from 1,000 active-duty Army personnel from the 101st Airborne at Fort Campbell, Ky. Participants were assessed before and after deployment to Afghanistan in February 2014 and are referred to as the Fort Campbell Cohort (FCC). Participants’ age ranged from 25 to 30 and approximately 6% were female.

Investigators collected blood samples from the service members and looked for four biomarkers: glycolytic ratio, arginine, serotonin, and glutamate. The team then divided the participants into four groups – those with PTSD (PTSD Checklist score above 30), those who were subthreshold for PTSD (PTSD Checklist score 15-30), those who had high resilience, and those who had low levels of resilience.

The resilience groups were determined based on answers to the Generalized Anxiety Disorder Questionnaire, Patient Health Questionnaire, Pittsburgh Sleep Quality Index, Intensive Combat Exposure (DRRI-D), the number of deployments, whether they had moderate or severe traumatic brain injury, and scores on the Alcohol Use Disorders Identification Test.

Those who scored in the high range at current or prior time points or who were PTSD/subthreshold at prior time points were placed in the low resilience group.

Ms. Miller noted that those in the PTSD group had more severe symptoms than those in the PTSD subthreshold group based on the longitudinal clinical assessment at 3-6 months, 5 years, and longer post deployment. The low resilience group had a much higher rate of PTSD post deployment than the high resilience group.

Investigators found participants with PTSD or subthreshold PTSD had significantly higher glycolic ratios and lower arginine than those with high resilience. They also found that those with PTSD had significantly lower serotonin and higher glutamate levels versus those with high resilience. These associations were independent of factors such as sex, age, body mass index, smoking, and caffeine consumption.

Ms. Miller said that the study results require further validation by the consortium’s labs and third-party labs.

“We are also interested in determining the most appropriate time to screen soldiers for PTSD, as it has been noted that the time period where we see the most psychological issues is around 2-3 months post return from deployment and when the soldier is preparing for their next assignment, perhaps a next deployment,” she said.

She added that previous studies have identified several promising biomarkers of PTSD. “However, like much of the research data, the study sample was comprised mainly of combat-exposed males. With more women serving on the front lines, the military faces new challenges in how combat affects females in the military,” including sex-specific biomarkers that will improve clinical assessment for female soldiers.

Eventually, the team would also like to be able to apply their research to the civilian population experiencing PTSD.

“Our research is anticipated to be useful in helping the medical provider select appropriate therapeutic interventions,” Ms. Miller said.

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

Some patients with HER2-positive breast cancer can reduce the intensity of adjuvant chemotherapy while maintaining the full benefits in terms of prognosis, new data suggest. Lowering the intensity of chemotherapy also reduces the adverse events that are associated with it.

An open-label study of about 400 participants indicated that 12 weeks of treatment with paclitaxel (Abraxane) and trastuzumab (Herceptin), followed by 9 months of trastuzumab monotherapy, was associated with very good long-term outcomes for patients with certain HER2-positive breast cancers. Few distant recurrences were observed, and tolerability was good.

The study was conducted by a team that included researchers from the European Institute of Oncology in Milan, one of the main oncology institutes in Italy.

“HER2-positive breast cancers harbor a particularly poor prognosis, compared with HER2-negative tumors, if left untreated. However, the blockade of HER2 with trastuzumab, when added to adjuvant multiagent chemotherapy, has been shown to improve outcomes for this population,” wrote the researchers, led by Sara M. Tolaney, MD, chief of breast oncology at Dana-Farber Cancer Institute in Boston. “To our knowledge, this is the first study to report the long-term outcomes of patients with small, node-negative, HER2-positive breast cancers prospectively treated with a de-escalated adjuvant regimen.”

The study was published in the March issue of The Lancet Oncology.
 

Avoiding side effects

HER2-positive breast cancers, which are characterized by amplification of the HER2 gene and overexpression of the HER2 protein, account for 15% of new cases of localized breast cancer. They are more aggressive and resistant to some anticancer treatments but show sensitivity to stronger chemotherapy.

“We presented the 10-year analysis, which shows that survival for breast cancer among the 406 patients recruited in the study was 98.8% after 10 years, with only 6 recurrences,” study author Paolo Tarantino, MD, researcher at the European Institute of Oncology and clinical research fellow at Dana-Farber Cancer Institute, Boston, said in a statement. “Our data support the use of the de-escalated adjuvant paclitaxel trastuzumab regimen as an adequate standard for small HER2-positive breast cancers, which avoids the side effects of polychemotherapy.”

The researchers also focused on patient selection and identified a significant relationship between the value of HER2DX, a new diagnostic tool capable of describing multiple characteristics of HER2-positive breast cancer, and the prognosis. If future research validates these preliminary results, the biomarker may help to further customize cancer treatments in the future, according to Dr. Tarantino.
 

‘A valuable alternative’

“This is the 10-year update of the APT study, which is not randomized and has no control arm,” Alessandra Gennari, MD, PhD, associate professor of oncology at the University of Eastern Piedmont and head of oncology at Maggiore University Hospital in Novara, Italy, said in an interview. Dr. Gennari, who was not involved in the study, was lead author of the European Society for Medical Oncology’s 2021 guidelines on metastatic breast cancer. “This study shows, nevertheless, that in a subpopulation of HER2-positive patients with low to moderate risk of recurrence, the de-escalation of chemotherapy together with trastuzumab is a valuable alternative to more complex regimens with chemotherapy agents and is very well tolerated.”

Dr. Gennari’s comment echoes those of an editorial that accompanied the Lancet Oncology study. “This work represents a milestone in the history of breast cancer: We have definitively shown that for early HER2-positive tumors, you can do less by getting more,” coauthor Giuseppe Curigliano, MD, PhD, full professor of medical oncology at University of Milan and head of early drug development at the European Institute of Oncology, told this news organization. “It completes a pathway started by my group at the European Institute of Oncology in 2009, when we showed that HER2-positive tumors have a very good prognosis if diagnosed at a very early stage, and therefore can be treated with less aggressive and less toxic chemotherapies.” Candiolo Cancer Institute oncologists Elena Geuna, MD, and Filippo Montemurro, MD, coauthored the editorial with Dr. Curigliano.

Research on de-escalation increased after that study, and data showed that a lighter chemotherapy regimen is safe and effective and allows patients to live longer and with fewer side effects. “This finding immediately changed clinical practice, and the newly published work now adds an important piece: De-escalation maintains its benefit over the long term, beyond 10 years,” said Dr. Curigliano. “It also shows that in the future, we could identify the patients that will benefit from doing more, but also those that will benefit from doing even less, thanks to the new marker HER2DX.”

The study was funded by Genentech. Dr. Tolaney has received consulting or advisory board fees from Genentech, AstraZeneca, Eli Lilly, Merck, Novartis, Pfizer, Gilead, BMS, Eisai, Sanofi, and other pharmaceutical companies. Dr. Tarantino has received consulting or advisory board fees from AstraZeneca, Daiichi Sankyo, and Lilly, and has received payment or honoraria for educational events from AstraZeneca and Daiichi Sankyo. Dr. Curigliano and Dr. Gennari reported no relevant financial relationships.
 

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

Some patients with HER2-positive breast cancer can reduce the intensity of adjuvant chemotherapy while maintaining the full benefits in terms of prognosis, new data suggest. Lowering the intensity of chemotherapy also reduces the adverse events that are associated with it.

An open-label study of about 400 participants indicated that 12 weeks of treatment with paclitaxel (Abraxane) and trastuzumab (Herceptin), followed by 9 months of trastuzumab monotherapy, was associated with very good long-term outcomes for patients with certain HER2-positive breast cancers. Few distant recurrences were observed, and tolerability was good.

The study was conducted by a team that included researchers from the European Institute of Oncology in Milan, one of the main oncology institutes in Italy.

“HER2-positive breast cancers harbor a particularly poor prognosis, compared with HER2-negative tumors, if left untreated. However, the blockade of HER2 with trastuzumab, when added to adjuvant multiagent chemotherapy, has been shown to improve outcomes for this population,” wrote the researchers, led by Sara M. Tolaney, MD, chief of breast oncology at Dana-Farber Cancer Institute in Boston. “To our knowledge, this is the first study to report the long-term outcomes of patients with small, node-negative, HER2-positive breast cancers prospectively treated with a de-escalated adjuvant regimen.”

The study was published in the March issue of The Lancet Oncology.
 

Avoiding side effects

HER2-positive breast cancers, which are characterized by amplification of the HER2 gene and overexpression of the HER2 protein, account for 15% of new cases of localized breast cancer. They are more aggressive and resistant to some anticancer treatments but show sensitivity to stronger chemotherapy.

“We presented the 10-year analysis, which shows that survival for breast cancer among the 406 patients recruited in the study was 98.8% after 10 years, with only 6 recurrences,” study author Paolo Tarantino, MD, researcher at the European Institute of Oncology and clinical research fellow at Dana-Farber Cancer Institute, Boston, said in a statement. “Our data support the use of the de-escalated adjuvant paclitaxel trastuzumab regimen as an adequate standard for small HER2-positive breast cancers, which avoids the side effects of polychemotherapy.”

The researchers also focused on patient selection and identified a significant relationship between the value of HER2DX, a new diagnostic tool capable of describing multiple characteristics of HER2-positive breast cancer, and the prognosis. If future research validates these preliminary results, the biomarker may help to further customize cancer treatments in the future, according to Dr. Tarantino.
 

‘A valuable alternative’

“This is the 10-year update of the APT study, which is not randomized and has no control arm,” Alessandra Gennari, MD, PhD, associate professor of oncology at the University of Eastern Piedmont and head of oncology at Maggiore University Hospital in Novara, Italy, said in an interview. Dr. Gennari, who was not involved in the study, was lead author of the European Society for Medical Oncology’s 2021 guidelines on metastatic breast cancer. “This study shows, nevertheless, that in a subpopulation of HER2-positive patients with low to moderate risk of recurrence, the de-escalation of chemotherapy together with trastuzumab is a valuable alternative to more complex regimens with chemotherapy agents and is very well tolerated.”

Dr. Gennari’s comment echoes those of an editorial that accompanied the Lancet Oncology study. “This work represents a milestone in the history of breast cancer: We have definitively shown that for early HER2-positive tumors, you can do less by getting more,” coauthor Giuseppe Curigliano, MD, PhD, full professor of medical oncology at University of Milan and head of early drug development at the European Institute of Oncology, told this news organization. “It completes a pathway started by my group at the European Institute of Oncology in 2009, when we showed that HER2-positive tumors have a very good prognosis if diagnosed at a very early stage, and therefore can be treated with less aggressive and less toxic chemotherapies.” Candiolo Cancer Institute oncologists Elena Geuna, MD, and Filippo Montemurro, MD, coauthored the editorial with Dr. Curigliano.

Research on de-escalation increased after that study, and data showed that a lighter chemotherapy regimen is safe and effective and allows patients to live longer and with fewer side effects. “This finding immediately changed clinical practice, and the newly published work now adds an important piece: De-escalation maintains its benefit over the long term, beyond 10 years,” said Dr. Curigliano. “It also shows that in the future, we could identify the patients that will benefit from doing more, but also those that will benefit from doing even less, thanks to the new marker HER2DX.”

The study was funded by Genentech. Dr. Tolaney has received consulting or advisory board fees from Genentech, AstraZeneca, Eli Lilly, Merck, Novartis, Pfizer, Gilead, BMS, Eisai, Sanofi, and other pharmaceutical companies. Dr. Tarantino has received consulting or advisory board fees from AstraZeneca, Daiichi Sankyo, and Lilly, and has received payment or honoraria for educational events from AstraZeneca and Daiichi Sankyo. Dr. Curigliano and Dr. Gennari reported no relevant financial relationships.
 

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

Some patients with HER2-positive breast cancer can reduce the intensity of adjuvant chemotherapy while maintaining the full benefits in terms of prognosis, new data suggest. Lowering the intensity of chemotherapy also reduces the adverse events that are associated with it.

An open-label study of about 400 participants indicated that 12 weeks of treatment with paclitaxel (Abraxane) and trastuzumab (Herceptin), followed by 9 months of trastuzumab monotherapy, was associated with very good long-term outcomes for patients with certain HER2-positive breast cancers. Few distant recurrences were observed, and tolerability was good.

The study was conducted by a team that included researchers from the European Institute of Oncology in Milan, one of the main oncology institutes in Italy.

“HER2-positive breast cancers harbor a particularly poor prognosis, compared with HER2-negative tumors, if left untreated. However, the blockade of HER2 with trastuzumab, when added to adjuvant multiagent chemotherapy, has been shown to improve outcomes for this population,” wrote the researchers, led by Sara M. Tolaney, MD, chief of breast oncology at Dana-Farber Cancer Institute in Boston. “To our knowledge, this is the first study to report the long-term outcomes of patients with small, node-negative, HER2-positive breast cancers prospectively treated with a de-escalated adjuvant regimen.”

The study was published in the March issue of The Lancet Oncology.
 

Avoiding side effects

HER2-positive breast cancers, which are characterized by amplification of the HER2 gene and overexpression of the HER2 protein, account for 15% of new cases of localized breast cancer. They are more aggressive and resistant to some anticancer treatments but show sensitivity to stronger chemotherapy.

“We presented the 10-year analysis, which shows that survival for breast cancer among the 406 patients recruited in the study was 98.8% after 10 years, with only 6 recurrences,” study author Paolo Tarantino, MD, researcher at the European Institute of Oncology and clinical research fellow at Dana-Farber Cancer Institute, Boston, said in a statement. “Our data support the use of the de-escalated adjuvant paclitaxel trastuzumab regimen as an adequate standard for small HER2-positive breast cancers, which avoids the side effects of polychemotherapy.”

The researchers also focused on patient selection and identified a significant relationship between the value of HER2DX, a new diagnostic tool capable of describing multiple characteristics of HER2-positive breast cancer, and the prognosis. If future research validates these preliminary results, the biomarker may help to further customize cancer treatments in the future, according to Dr. Tarantino.
 

‘A valuable alternative’

“This is the 10-year update of the APT study, which is not randomized and has no control arm,” Alessandra Gennari, MD, PhD, associate professor of oncology at the University of Eastern Piedmont and head of oncology at Maggiore University Hospital in Novara, Italy, said in an interview. Dr. Gennari, who was not involved in the study, was lead author of the European Society for Medical Oncology’s 2021 guidelines on metastatic breast cancer. “This study shows, nevertheless, that in a subpopulation of HER2-positive patients with low to moderate risk of recurrence, the de-escalation of chemotherapy together with trastuzumab is a valuable alternative to more complex regimens with chemotherapy agents and is very well tolerated.”

Dr. Gennari’s comment echoes those of an editorial that accompanied the Lancet Oncology study. “This work represents a milestone in the history of breast cancer: We have definitively shown that for early HER2-positive tumors, you can do less by getting more,” coauthor Giuseppe Curigliano, MD, PhD, full professor of medical oncology at University of Milan and head of early drug development at the European Institute of Oncology, told this news organization. “It completes a pathway started by my group at the European Institute of Oncology in 2009, when we showed that HER2-positive tumors have a very good prognosis if diagnosed at a very early stage, and therefore can be treated with less aggressive and less toxic chemotherapies.” Candiolo Cancer Institute oncologists Elena Geuna, MD, and Filippo Montemurro, MD, coauthored the editorial with Dr. Curigliano.

Research on de-escalation increased after that study, and data showed that a lighter chemotherapy regimen is safe and effective and allows patients to live longer and with fewer side effects. “This finding immediately changed clinical practice, and the newly published work now adds an important piece: De-escalation maintains its benefit over the long term, beyond 10 years,” said Dr. Curigliano. “It also shows that in the future, we could identify the patients that will benefit from doing more, but also those that will benefit from doing even less, thanks to the new marker HER2DX.”

The study was funded by Genentech. Dr. Tolaney has received consulting or advisory board fees from Genentech, AstraZeneca, Eli Lilly, Merck, Novartis, Pfizer, Gilead, BMS, Eisai, Sanofi, and other pharmaceutical companies. Dr. Tarantino has received consulting or advisory board fees from AstraZeneca, Daiichi Sankyo, and Lilly, and has received payment or honoraria for educational events from AstraZeneca and Daiichi Sankyo. Dr. Curigliano and Dr. Gennari reported no relevant financial relationships.
 

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

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

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

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

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

Processed and ultraprocessed food consumption has been shown to increase the risk for various cancers. A new analysis suggests that replacing even a small amount of such foods with an equal amount of minimally processed options may reduce that risk.

Using data from more than 450,000 participants, the dietary substitution analysis found that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall by 4% as well as the risk for several cancer types, including esophageal squamous cell carcinoma by 43% and hepatocellular carcinoma by 23%.

Making this substitution with ultraprocessed foods also appeared to lower cancer risk but often to a lesser degree. For instance, swapping 10% of ultraprocessed foods for minimally processed foods lowered the overall cancer risk by just 1%, the risk of hepatocellular carcinoma by 27%, and the risk of esophageal squamous cell carcinoma by 20%.

Overall, “this study suggests that the replacement of processed and ultraprocessed foods and drinks with an equal amount of minimally processed foods might reduce the risk of various cancer types,” Nathalie Kliemann, PhD, from the World Health Organization’s International Agency for Research on Cancer, Lyon, France, and colleagues concluded.

The findings were published in The Lancet Planetary Health.

Processed and ultraprocessed foods tend to have high-energy density and low nutritional value, and some epidemiological evidence indicates a possible link between consuming ultraprocessed food and cancer outcomes.

Dr. Kliemann and colleagues, for instance, recently published a study showing a link between ultraprocessed food consumption and increased risk for cancer, particularly ovarian cancer, as well as increased risk of dying from cancer. That study of nearly 200,000 middle-aged adults in the UK Biobank database showed that, for each 10 percentage point increase in the consumption of ultraprocessed foods, there was a 2% increase in the overall incidence of cancer and a 19% increase in ovarian cancer incidence.

However, conflicting reports exist, and research exploring associations between processed foods and cancer remains limited.

The researchers wanted to better understand the potential association between the degree of food processing and risk for cancer in a larger cohort of individuals.

The investigators performed a dietary substitution analysis using data from more than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and looking at 25 anatomical sites. EPIC study participants, who had no cancer diagnoses prior to enrollment, were identified between March 1991 and July 2001. Of the 450,111 included in the analysis, 47,573 were diagnosed with cancer during a mean follow-up of 14.1 years. Mean age at recruitment was 51 years, and mean BMI was 25.3 kg/m².

Food items were classified according to their level of processing using the NOVA classification system: minimally or nonprocessed foods (NOVA 1), processed culinary ingredients (NOVA 2), processed foods (NOVA 3), and ultraprocessed foods (NOVA 4). The investigators highlighted comparisons between NOVA 1 and NOVA 3 and between NOVA 1 and NOVA 4.

The analysis revealed that swapping out just 10% of processed foods with minimally processed foods significantly lowered the risk for cancer overall (hazard ratio, 0.96) as well as for esophageal squamous cell carcinoma (HR, 0.57), hepatocellular carcinoma (HR, 0.77), head and neck cancers (HR, 0.80), colon cancer (HR, 0,88), rectal cancer (HR, 0.90), and postmenopausal breast cancer (HR, 0.93)

Swapping 10% of ultraprocessed foods for minimally processed foods lowered the risk of cancer overall only slightly (HR, 0.99) as well as the risk for various cancer types, including hepatocellular carcinoma (HR, 0.73), head and neck cancers (HR, 0.80), esophageal adenocarcinoma (HR, 0.80), and colon cancer (HR, 0.93).

The authors noted several limitations to the analysis, perhaps most notably that intake of ultraprocessed foods contributed to about 32% of total daily energy intake among study participants, but today that percentage could be nearly double across European countries.

“This discrepancy might explain the fewer significant associations observed between ultraprocessed foods and cancer risk than in processed foods and cancer risk,” the authors suggested.

The findings are “broadly in line with current evidence,” but the authors also noted some inconsistencies. For example, the current study showed a positive association between processed food consumption and risk for colorectal cancer and postmenopausal breast cancer, whereas other studies have not.

Overall, though, the authors concluded that increased consumption of minimally processed and fresh foods was associated with reduced overall risk for cancer and risk for specific cancers, and increased consumption of processed and ultraprocessed foods was associated with increased cancer risks.

This study “is the largest study investigating these associations between food processing and cancer risk and therefore has greater power to detect differences in populations, potentially explaining why we found overall more significant results for different cancer sites than other cohorts,” Dr. Kliemann and colleagues wrote.

This study was funded by Cancer Research UK, the French National Cancer Institute, and World Cancer Research Fund International. The authors declared no competing interests.

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

A whole new, tiny level of hangry

Ever been so hungry that everything just got on your nerves? Maybe you feel a little snappy right now? Like you’ll just lash out unless you get something to eat? Been there. And so have bacteria.

New research shows that some bacteria go into a full-on Hulk smash if they’re not getting the nutrients they need by releasing toxins into the body. Sounds like a bacterial temper tantrum.

Rosenthal et al.

Even though two cells may be genetically identical, they don’t always behave the same in a bacterial community. Some do their job and stay in line, but some evil twins rage out and make people sick by releasing toxins into the environment, Adam Rosenthal, PhD, of the University of North Carolina and his colleagues discovered.

To figure out why some cells were all business as usual while others were not, the investigators looked at Clostridium perfringens, a bacterium found in the intestines of humans and other vertebrates. When the C. perfringens cells were fed a little acetate to munch on, the hangry cells calmed down faster than a kid with a bag of fruit snacks, reducing toxin levels. Some cells even disappeared, falling in line with their model-citizen counterparts.

So what does this really mean? More research, duh. Now that we know nutrients play a role in toxicity, it may open the door to finding a way to fight against antibiotic resistance in humans and reduce antibiotic use in the food industry.

So think to yourself. Are you bothered for no reason? Getting a little testy with your friends and coworkers? Maybe you just haven’t eaten in a while. You’re literally not alone. Even a single-cell organism can behave based on its hunger levels.

Now go have a snack. Your bacteria are getting restless.
 

The very hangry iguana?

Imagine yourself on a warm, sunny tropical beach. You are enjoying a piece of cake as you take in the slow beat of the waves lapping against the shore. Life is as good as it could be.

Then you feel a presence nearby. Hostility. Hunger. A set of feral, covetous eyes in the nearby jungle. A reptilian beast stalks you, and its all-encompassing sweet tooth desires your cake.

Wait, hold on, what?

As an unfortunate 3-year-old on vacation in Costa Rica found out, there’s at least one iguana in the world out there with a taste for sugar (better than a taste for blood, we suppose).

Ulrike Mai/Pixabay

While out on the beach, the lizard darted out of nowhere, bit the girl on the back of the hand, and stole her cake. Still not the worst party guest ever. The child was taken to a local clinic, where the wound was cleaned and a 5-day antibiotic treatment (lizards carry salmonella) was provided. Things seemed fine, and the girl returned home without incident.

But of course, that’s not the end of the story. Five months later, the girl’s parents noticed a red bump at the wound site. Over the next 3 months, the surrounding skin grew red and painful. A trip to the hospital in California revealed that she had a ganglion cyst and a discharge of pus. Turns out our cake-obsessed lizard friend did give the little girl a gift: the first known human case of Mycobacterium marinum infection following an iguana bite on record.

M. marinum, which causes a disease similar to tuberculosis, typically infects fish but can infect humans if skin wounds are exposed to contaminated water. It’s also resistant to most antibiotics, which is why the first round didn’t clear up the infection. A second round of more-potent antibiotics seems to be working well.

So, to sum up, this poor child got bitten by a lizard, had her cake stolen, and contracted a rare illness in exchange. For a 3-year-old, that’s gotta be in the top-10 worst days ever. Unless, of course, we’re actually living in the Marvel universe (sorry, multiverse at this point). Then we’re totally going to see the emergence of the new superhero Iguana Girl in 15 years or so. Keep your eyes open.
 

No allergies? Let them give up cake

Allergy season is already here – starting earlier every year, it seems – and many people are not happy about it. So unhappy, actually, that there’s a list of things they would be willing to give up for a year to get rid of their of allergies, according to a survey conducted by OnePoll on behalf of Flonase.

nicoletaionescu/Getty Images

Nearly 40% of 2,000 respondents with allergies would go a year without eating cake or chocolate or playing video games in exchange for allergy-free status, the survey results show. Almost as many would forgo coffee (38%) or pizza (37%) for a year, while 36% would stay off social media and 31% would take a pay cut or give up their smartphones, the Independent reported.

More than half of the allergic Americans – 54%, to be exact – who were polled this past winter – Feb. 24 to March 1, to be exact – consider allergy symptoms to be the most frustrating part of the spring. Annoying things that were less frustrating to the group included mosquitoes (41%), filing tax returns (38%), and daylight savings time (37%).

The Trump arraignment circus, of course, occurred too late to make the list, as did the big “We’re going back to the office! No wait, we’re closing the office forever!” email extravaganza and emotional roller coaster. That second one, however, did not get nearly as much media coverage.

A whole new, tiny level of hangry

Ever been so hungry that everything just got on your nerves? Maybe you feel a little snappy right now? Like you’ll just lash out unless you get something to eat? Been there. And so have bacteria.

New research shows that some bacteria go into a full-on Hulk smash if they’re not getting the nutrients they need by releasing toxins into the body. Sounds like a bacterial temper tantrum.

Rosenthal et al.

Even though two cells may be genetically identical, they don’t always behave the same in a bacterial community. Some do their job and stay in line, but some evil twins rage out and make people sick by releasing toxins into the environment, Adam Rosenthal, PhD, of the University of North Carolina and his colleagues discovered.

To figure out why some cells were all business as usual while others were not, the investigators looked at Clostridium perfringens, a bacterium found in the intestines of humans and other vertebrates. When the C. perfringens cells were fed a little acetate to munch on, the hangry cells calmed down faster than a kid with a bag of fruit snacks, reducing toxin levels. Some cells even disappeared, falling in line with their model-citizen counterparts.

So what does this really mean? More research, duh. Now that we know nutrients play a role in toxicity, it may open the door to finding a way to fight against antibiotic resistance in humans and reduce antibiotic use in the food industry.

So think to yourself. Are you bothered for no reason? Getting a little testy with your friends and coworkers? Maybe you just haven’t eaten in a while. You’re literally not alone. Even a single-cell organism can behave based on its hunger levels.

Now go have a snack. Your bacteria are getting restless.
 

The very hangry iguana?

Imagine yourself on a warm, sunny tropical beach. You are enjoying a piece of cake as you take in the slow beat of the waves lapping against the shore. Life is as good as it could be.

Then you feel a presence nearby. Hostility. Hunger. A set of feral, covetous eyes in the nearby jungle. A reptilian beast stalks you, and its all-encompassing sweet tooth desires your cake.

Wait, hold on, what?

As an unfortunate 3-year-old on vacation in Costa Rica found out, there’s at least one iguana in the world out there with a taste for sugar (better than a taste for blood, we suppose).

Ulrike Mai/Pixabay

While out on the beach, the lizard darted out of nowhere, bit the girl on the back of the hand, and stole her cake. Still not the worst party guest ever. The child was taken to a local clinic, where the wound was cleaned and a 5-day antibiotic treatment (lizards carry salmonella) was provided. Things seemed fine, and the girl returned home without incident.

But of course, that’s not the end of the story. Five months later, the girl’s parents noticed a red bump at the wound site. Over the next 3 months, the surrounding skin grew red and painful. A trip to the hospital in California revealed that she had a ganglion cyst and a discharge of pus. Turns out our cake-obsessed lizard friend did give the little girl a gift: the first known human case of Mycobacterium marinum infection following an iguana bite on record.

M. marinum, which causes a disease similar to tuberculosis, typically infects fish but can infect humans if skin wounds are exposed to contaminated water. It’s also resistant to most antibiotics, which is why the first round didn’t clear up the infection. A second round of more-potent antibiotics seems to be working well.

So, to sum up, this poor child got bitten by a lizard, had her cake stolen, and contracted a rare illness in exchange. For a 3-year-old, that’s gotta be in the top-10 worst days ever. Unless, of course, we’re actually living in the Marvel universe (sorry, multiverse at this point). Then we’re totally going to see the emergence of the new superhero Iguana Girl in 15 years or so. Keep your eyes open.
 

No allergies? Let them give up cake

Allergy season is already here – starting earlier every year, it seems – and many people are not happy about it. So unhappy, actually, that there’s a list of things they would be willing to give up for a year to get rid of their of allergies, according to a survey conducted by OnePoll on behalf of Flonase.

nicoletaionescu/Getty Images

Nearly 40% of 2,000 respondents with allergies would go a year without eating cake or chocolate or playing video games in exchange for allergy-free status, the survey results show. Almost as many would forgo coffee (38%) or pizza (37%) for a year, while 36% would stay off social media and 31% would take a pay cut or give up their smartphones, the Independent reported.

More than half of the allergic Americans – 54%, to be exact – who were polled this past winter – Feb. 24 to March 1, to be exact – consider allergy symptoms to be the most frustrating part of the spring. Annoying things that were less frustrating to the group included mosquitoes (41%), filing tax returns (38%), and daylight savings time (37%).

The Trump arraignment circus, of course, occurred too late to make the list, as did the big “We’re going back to the office! No wait, we’re closing the office forever!” email extravaganza and emotional roller coaster. That second one, however, did not get nearly as much media coverage.

A whole new, tiny level of hangry

Ever been so hungry that everything just got on your nerves? Maybe you feel a little snappy right now? Like you’ll just lash out unless you get something to eat? Been there. And so have bacteria.

New research shows that some bacteria go into a full-on Hulk smash if they’re not getting the nutrients they need by releasing toxins into the body. Sounds like a bacterial temper tantrum.

Rosenthal et al.

Even though two cells may be genetically identical, they don’t always behave the same in a bacterial community. Some do their job and stay in line, but some evil twins rage out and make people sick by releasing toxins into the environment, Adam Rosenthal, PhD, of the University of North Carolina and his colleagues discovered.

To figure out why some cells were all business as usual while others were not, the investigators looked at Clostridium perfringens, a bacterium found in the intestines of humans and other vertebrates. When the C. perfringens cells were fed a little acetate to munch on, the hangry cells calmed down faster than a kid with a bag of fruit snacks, reducing toxin levels. Some cells even disappeared, falling in line with their model-citizen counterparts.

So what does this really mean? More research, duh. Now that we know nutrients play a role in toxicity, it may open the door to finding a way to fight against antibiotic resistance in humans and reduce antibiotic use in the food industry.

So think to yourself. Are you bothered for no reason? Getting a little testy with your friends and coworkers? Maybe you just haven’t eaten in a while. You’re literally not alone. Even a single-cell organism can behave based on its hunger levels.

Now go have a snack. Your bacteria are getting restless.
 

The very hangry iguana?

Imagine yourself on a warm, sunny tropical beach. You are enjoying a piece of cake as you take in the slow beat of the waves lapping against the shore. Life is as good as it could be.

Then you feel a presence nearby. Hostility. Hunger. A set of feral, covetous eyes in the nearby jungle. A reptilian beast stalks you, and its all-encompassing sweet tooth desires your cake.

Wait, hold on, what?

As an unfortunate 3-year-old on vacation in Costa Rica found out, there’s at least one iguana in the world out there with a taste for sugar (better than a taste for blood, we suppose).

Ulrike Mai/Pixabay

While out on the beach, the lizard darted out of nowhere, bit the girl on the back of the hand, and stole her cake. Still not the worst party guest ever. The child was taken to a local clinic, where the wound was cleaned and a 5-day antibiotic treatment (lizards carry salmonella) was provided. Things seemed fine, and the girl returned home without incident.

But of course, that’s not the end of the story. Five months later, the girl’s parents noticed a red bump at the wound site. Over the next 3 months, the surrounding skin grew red and painful. A trip to the hospital in California revealed that she had a ganglion cyst and a discharge of pus. Turns out our cake-obsessed lizard friend did give the little girl a gift: the first known human case of Mycobacterium marinum infection following an iguana bite on record.

M. marinum, which causes a disease similar to tuberculosis, typically infects fish but can infect humans if skin wounds are exposed to contaminated water. It’s also resistant to most antibiotics, which is why the first round didn’t clear up the infection. A second round of more-potent antibiotics seems to be working well.

So, to sum up, this poor child got bitten by a lizard, had her cake stolen, and contracted a rare illness in exchange. For a 3-year-old, that’s gotta be in the top-10 worst days ever. Unless, of course, we’re actually living in the Marvel universe (sorry, multiverse at this point). Then we’re totally going to see the emergence of the new superhero Iguana Girl in 15 years or so. Keep your eyes open.
 

No allergies? Let them give up cake

Allergy season is already here – starting earlier every year, it seems – and many people are not happy about it. So unhappy, actually, that there’s a list of things they would be willing to give up for a year to get rid of their of allergies, according to a survey conducted by OnePoll on behalf of Flonase.

nicoletaionescu/Getty Images

Nearly 40% of 2,000 respondents with allergies would go a year without eating cake or chocolate or playing video games in exchange for allergy-free status, the survey results show. Almost as many would forgo coffee (38%) or pizza (37%) for a year, while 36% would stay off social media and 31% would take a pay cut or give up their smartphones, the Independent reported.

More than half of the allergic Americans – 54%, to be exact – who were polled this past winter – Feb. 24 to March 1, to be exact – consider allergy symptoms to be the most frustrating part of the spring. Annoying things that were less frustrating to the group included mosquitoes (41%), filing tax returns (38%), and daylight savings time (37%).

The Trump arraignment circus, of course, occurred too late to make the list, as did the big “We’re going back to the office! No wait, we’re closing the office forever!” email extravaganza and emotional roller coaster. That second one, however, did not get nearly as much media coverage.

Endoscopic ultrasound–guided gallbladder drainage (EUS-GBD) should be considered for patients with acute cholecystitis who are unable to undergo surgery, according to a recent clinical practice update by the American Gastroenterological Association.

The update, written by Shayan S. Irani, MD, of Virginia Mason Medical Center, Seattle, and colleagues, also covers techniques and outcomes of EUS-GBD and provides suggestions for training and patient selection.

“In this clinical practice update, we comment on the role of EUS-GBD (compared with ET-GBD [endoscopic treatment via transpapillary gallbladder drainage] and PT [percutaneous transhepatic]-GBD) in the management of acute cholecystitis, and describe its indications, contraindications, procedural considerations, and associated adverse events,” the authors wrote in Clinical Gastroenterology and Hepatology.

Dr. Irani and colleagues noted that EUS-GBD is a valuable alternative to PT-GBD, which can have a significant morbidity, and ET-GBD has been associated with relatively lower technical and clinical success rates in the presence of obstructing pathology of the cystic duct. Advances in lumen-apposing metal stents have further improved outcomes in EUS-GBD, as demonstrated by multiple case series and comparative trials.

According to the update, EUS-GBD is suggested in three scenarios: for draining the gallbladder in patients with acute cholecystitis who are at high risk for surgery, for removing percutaneous cholecystostomy drains in patients who cannot undergo cholecystectomy, and for draining malignant biliary obstruction in patients who have not responded to other treatments. EUS-GBD is contraindicated in patients with significant coagulopathy, large-volume uncontrolled ascites, or gallbladder perforation.

Dr. Irani and colleagues also noted that, between the three main techniques mentioned above, EUS-GBD has the lowest risk of recurrent cholecystitis, whereas ET-GBD and PT-GBD present slightly lower mortality rates.

While the update provides technical guidance on performing EUS-GBD, Dr. Irani and colleagues make clear that EUS-GBD is a highly specialized procedure that requires sufficient training to optimal results.

“Performing the procedure has an associated learning curve and requires advanced EUS training,” they wrote. “Two recent publications have suggested that the minimum number of procedures to gain competency should be approximately 19-25 procedures.”

Addressing unmet needs, Dr. Irani and colleagues suggested that more research is needed to standardize patient selection, procedure technique, and stent follow-up evaluation.

Ongoing studies aim to address whether endoscopic management of cholecystitis and symptomatic gallstones could become a mainstream treatment in the future, they wrote, but “we are still a long way from abandoning standard of care with cholecystectomy.”

This clinical practice update was commissioned by the AGA. Dr. Irani is a consultant for Boston Scientific, ConMed, and GORE; one coauthor received research support from Boston Scientific and Olympus and is a consultant and speaker for Boston Scientific, Cook, Medtronic, Olympus and ConMed. The remaining coauthor disclosed no conflicts.

Endoscopic ultrasound–guided gallbladder drainage (EUS-GBD) should be considered for patients with acute cholecystitis who are unable to undergo surgery, according to a recent clinical practice update by the American Gastroenterological Association.

The update, written by Shayan S. Irani, MD, of Virginia Mason Medical Center, Seattle, and colleagues, also covers techniques and outcomes of EUS-GBD and provides suggestions for training and patient selection.

“In this clinical practice update, we comment on the role of EUS-GBD (compared with ET-GBD [endoscopic treatment via transpapillary gallbladder drainage] and PT [percutaneous transhepatic]-GBD) in the management of acute cholecystitis, and describe its indications, contraindications, procedural considerations, and associated adverse events,” the authors wrote in Clinical Gastroenterology and Hepatology.

Dr. Irani and colleagues noted that EUS-GBD is a valuable alternative to PT-GBD, which can have a significant morbidity, and ET-GBD has been associated with relatively lower technical and clinical success rates in the presence of obstructing pathology of the cystic duct. Advances in lumen-apposing metal stents have further improved outcomes in EUS-GBD, as demonstrated by multiple case series and comparative trials.

According to the update, EUS-GBD is suggested in three scenarios: for draining the gallbladder in patients with acute cholecystitis who are at high risk for surgery, for removing percutaneous cholecystostomy drains in patients who cannot undergo cholecystectomy, and for draining malignant biliary obstruction in patients who have not responded to other treatments. EUS-GBD is contraindicated in patients with significant coagulopathy, large-volume uncontrolled ascites, or gallbladder perforation.

Dr. Irani and colleagues also noted that, between the three main techniques mentioned above, EUS-GBD has the lowest risk of recurrent cholecystitis, whereas ET-GBD and PT-GBD present slightly lower mortality rates.

While the update provides technical guidance on performing EUS-GBD, Dr. Irani and colleagues make clear that EUS-GBD is a highly specialized procedure that requires sufficient training to optimal results.

“Performing the procedure has an associated learning curve and requires advanced EUS training,” they wrote. “Two recent publications have suggested that the minimum number of procedures to gain competency should be approximately 19-25 procedures.”

Addressing unmet needs, Dr. Irani and colleagues suggested that more research is needed to standardize patient selection, procedure technique, and stent follow-up evaluation.

Ongoing studies aim to address whether endoscopic management of cholecystitis and symptomatic gallstones could become a mainstream treatment in the future, they wrote, but “we are still a long way from abandoning standard of care with cholecystectomy.”

This clinical practice update was commissioned by the AGA. Dr. Irani is a consultant for Boston Scientific, ConMed, and GORE; one coauthor received research support from Boston Scientific and Olympus and is a consultant and speaker for Boston Scientific, Cook, Medtronic, Olympus and ConMed. The remaining coauthor disclosed no conflicts.

Endoscopic ultrasound–guided gallbladder drainage (EUS-GBD) should be considered for patients with acute cholecystitis who are unable to undergo surgery, according to a recent clinical practice update by the American Gastroenterological Association.

The update, written by Shayan S. Irani, MD, of Virginia Mason Medical Center, Seattle, and colleagues, also covers techniques and outcomes of EUS-GBD and provides suggestions for training and patient selection.

“In this clinical practice update, we comment on the role of EUS-GBD (compared with ET-GBD [endoscopic treatment via transpapillary gallbladder drainage] and PT [percutaneous transhepatic]-GBD) in the management of acute cholecystitis, and describe its indications, contraindications, procedural considerations, and associated adverse events,” the authors wrote in Clinical Gastroenterology and Hepatology.

Dr. Irani and colleagues noted that EUS-GBD is a valuable alternative to PT-GBD, which can have a significant morbidity, and ET-GBD has been associated with relatively lower technical and clinical success rates in the presence of obstructing pathology of the cystic duct. Advances in lumen-apposing metal stents have further improved outcomes in EUS-GBD, as demonstrated by multiple case series and comparative trials.

According to the update, EUS-GBD is suggested in three scenarios: for draining the gallbladder in patients with acute cholecystitis who are at high risk for surgery, for removing percutaneous cholecystostomy drains in patients who cannot undergo cholecystectomy, and for draining malignant biliary obstruction in patients who have not responded to other treatments. EUS-GBD is contraindicated in patients with significant coagulopathy, large-volume uncontrolled ascites, or gallbladder perforation.

Dr. Irani and colleagues also noted that, between the three main techniques mentioned above, EUS-GBD has the lowest risk of recurrent cholecystitis, whereas ET-GBD and PT-GBD present slightly lower mortality rates.

While the update provides technical guidance on performing EUS-GBD, Dr. Irani and colleagues make clear that EUS-GBD is a highly specialized procedure that requires sufficient training to optimal results.

“Performing the procedure has an associated learning curve and requires advanced EUS training,” they wrote. “Two recent publications have suggested that the minimum number of procedures to gain competency should be approximately 19-25 procedures.”

Addressing unmet needs, Dr. Irani and colleagues suggested that more research is needed to standardize patient selection, procedure technique, and stent follow-up evaluation.

Ongoing studies aim to address whether endoscopic management of cholecystitis and symptomatic gallstones could become a mainstream treatment in the future, they wrote, but “we are still a long way from abandoning standard of care with cholecystectomy.”

This clinical practice update was commissioned by the AGA. Dr. Irani is a consultant for Boston Scientific, ConMed, and GORE; one coauthor received research support from Boston Scientific and Olympus and is a consultant and speaker for Boston Scientific, Cook, Medtronic, Olympus and ConMed. The remaining coauthor disclosed no conflicts.

Researchers have found for the first time that COVID infection has crossed the placenta and caused brain damage in two newborns, according to a study published online today in Pediatrics .

One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.

Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.

Zelda Calvert

“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
 

Both infants negative for the virus at birth

The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.

Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.

Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.

Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.

“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.

Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.

Seizures started on day 1 of life

The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.

“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.

Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.

Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.

The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.

Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.

Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
 

Mothers had very different presentations

Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.

One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.

In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.

He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
 

Instances are rare

The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.

Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”

Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.

Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.

Researchers have found for the first time that COVID infection has crossed the placenta and caused brain damage in two newborns, according to a study published online today in Pediatrics .

One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.

Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.

Zelda Calvert

“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
 

Both infants negative for the virus at birth

The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.

Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.

Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.

Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.

“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.

Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.

Seizures started on day 1 of life

The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.

“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.

Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.

Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.

The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.

Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.

Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
 

Mothers had very different presentations

Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.

One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.

In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.

He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
 

Instances are rare

The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.

Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”

Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.

Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.

Researchers have found for the first time that COVID infection has crossed the placenta and caused brain damage in two newborns, according to a study published online today in Pediatrics .

One of the infants died at 13 months and the other remained in hospice care at time of manuscript submission.

Lead author Merline Benny, MD, with the division of neonatology, department of pediatrics at University of Miami, and colleagues briefed reporters today ahead of the release.

Zelda Calvert

“This is a first,” said senior author Shahnaz Duara, MD, medical director of the Neonatal Intensive Care Unit at Holtz Children’s Hospital, Miami, explaining it is the first study to confirm cross-placental SARS-CoV-2 transmission leading to brain injury in a newborn.
 

Both infants negative for the virus at birth

The two infants were admitted in the early days of the pandemic in the Delta wave to the neonatal ICU at Holtz Children’s Hospital at University of Miami/Jackson Memorial Medical Center.

Both infants tested negative for the virus at birth, but had significantly elevated SARS-CoV-2 antibodies in their blood, indicating that either antibodies crossed the placenta, or the virus crossed and the immune response was the baby’s.

Dr. Benny explained that the researchers have seen, to this point, more than 700 mother/infant pairs in whom the mother tested positive for COVID in Jackson hospital.

Most who tested positive for COVID were asymptomatic and most of the mothers and infants left the hospital without complications.

“However, (these) two babies had a very unusual clinical picture,” Dr. Benny said.

Those infants were born to mothers who became COVID positive in the second trimester and delivered a few weeks later.

Seizures started on day 1 of life

The babies began to seize from the first day of life. They had profound low tone (hypotonia) in their clinical exam, Dr. Benny explained.

“We had absolutely no good explanation for the early seizures and the degree of brain injury we saw,” Dr. Duara said.

Dr. Benny said that as their bodies grew, they had very small head circumference. Unlike some babies born with the Zika virus, these babies were not microcephalic at birth. Brain imaging on the two babies indicated significant brain atrophy, and neurodevelopment exams showed significant delay.

Discussions began with the center’s multidisciplinary team including neurologists, pathologists, neuroradiologists, and obstetricians who cared for both the mothers and the babies.

The experts examined the placentas and found some characteristic COVID changes and presence of the COVID virus. This was accompanied by increased markers for inflammation and a severe reduction in a hormone critical for placental health and brain development.

Examining the infant’s autopsy findings further raised suspicions of maternal transmission, something that had not been documented before.

Coauthor Ali G. Saad, MD, pediatric and perinatal pathology director at Miami, said, “I have seen literally thousands of brains in autopsies over the last 14 years, and this was the most dramatic case of leukoencephalopathy or loss of white matter in a patient with no significant reason. That’s what triggered the investigation.”
 

Mothers had very different presentations

Coauthor Michael J. Paidas, MD, with the department of obstetrics, gynecology, and reproductive sciences at Miami, pointed out that the circumstances of the two mothers, who were in their 20s, were very different.

One mother delivered at 32 weeks and had a very severe COVID presentation and spent a month in the intensive care unit. The team decided to deliver the child to save the mother, Dr. Paidas said.

In contrast, the other mother had asymptomatic COVID infection in the second trimester and delivered at full term.

He said one of the early suspicions in the babies’ presentations was hypoxic ischemic encephalopathy. “But it wasn’t lack of blood flow to the placenta that caused this,” he said. “As best we can tell, it was the viral infection.”
 

Instances are rare

The researchers emphasized that these instances are rare and have not been seen before or since the period of this study to their knowledge.

Dr. Duara said, “This is something we want to alert the medical community to more than the general public. We do not want the lay public to be panicked. We’re trying to understand what made these two pregnancies different, so we can direct research towards protecting vulnerable babies.”

Previous data have indicated a relatively benign status in infants who test negative for the COVID virus after birth. Dr. Benny added that COVID vaccination has been found safe in pregnancy and both vaccination and breastfeeding can help passage of antibodies to the infant and help protect the baby. Because these cases happened in the early days of the pandemic, no vaccines were available.

Dr. Paidas received funding from BioIncept to study hypoxic-ischemic encephalopathy with Preimplantation Factor, is a scientific advisory board member, and has stock options. Dr. Paidas and coauthor Dr. Jayakumar are coinventors of SPIKENET, University of Miami, patent pending 2023. The other authors have no conflicts of interest to disclose.

Rapid weight gain (RWG) in infants and the mother’s prepregnancy overweight have a synergistic effect in increasing the odds that a child will develop overweight or obesity, new research suggests.

Findings were published online in Pediatrics.

Each factor has independently been associated with higher risk of childhood obesity but whether the two factors together exacerbate the risk has not been well studied, according to the authors led by Stephanie Gilley, MD, PhD, department of pediatrics, section of nutrition, University of Colorado at Denver, Aurora.

“Pediatric providers should monitor infants for RWG, especially in the context of maternal obesity, to reduce future risk of obesity,” the authors conclude.

Dr. Gilley’s team studied mother-infant dyads (n = 414) from the Healthy Start Study, an observational prebirth cohort. RWG was defined as a weight-for-age z score increase of at least 0.67 from birth to 3-7 months.

They found that RWG boosted the link between prepregnancy body mass index (ppBMI) and BMI z score, especially in female infants. Females exposed to both maternal obesity with RWG had an average BMI at the 94th percentile (1.50 increase in childhood BMI z score) “nearly at the cutoff for classification of obesity,” compared with those exposed to normal ppBMI with no RWG, who had an average childhood BMI at the 51st percentile.

“Currently, our nutrition recommendations as pediatricians are that all children are fed the same, essentially, after they’re born. We don’t have different growth parameters or different trajectories or targets for children who may have had different in utero exposures,” Dr. Gilley said.

Do some children need more monitoring for RWG?

Though we can’t necessarily draw conclusions from this one study, she says, the findings raise the question of whether children who were exposed in utero to obesity should be monitored for RWG more closely.

Lydia Shook, MD, Mass General Brigham maternal-fetal specialist and codirector of the Diabetes in Pregnancy Program at Massachusetts General Hospital in Boston, said she was struck by the finding in this study that with female infants, but not males, RWG significantly modified the association between ppBMI and early childhood BMI z scores.

“It’s an interesting finding and should be followed up with larger cohorts,” she said, noting that some previous studies have shown males are more vulnerable to maternal obesity and RWG.

“[Often] when we stratify by sex, you really need larger groups to be able to see the differences well,” Dr. Shook said.

She said she also found it interesting that when the researchers adjusted for breastfeeding status or caloric intake in childhood, the findings did not substantially change.

“That’s something that would warrant further investigation in an observational study or controlled trial,” Dr. Shook said.

Preventing rapid weight gain

The authors note that they did not consider possible interventions for preventing RGW in the study, although there are many, Dr. Gilley said.

Dr. Gilley also noted that a limitation of this study is that the population studied was primarily White.

Recent studies have shown the benefits of responsive parenting (RP) interventions, including a large study in 2022 geared toward Black families to teach better infant sleep practices as a way to prevent rapid weight gain.

That study, which tested the SAAF intervention, (Strong African American Families) found that “RP infants were nearly half as likely to experience upward crossing of two major weight-for-age percentile lines (14.1%), compared with control infants (24.2%); P = .09; odds ratio, 0.52; 95% confidence interval, 0.24-1.12.”

Along with sleep interventions, Dr. Gilley said, some researchers are studying the effects on RWG of better paternal engagement, or more involvement with the Women, Infants, and Children program, particularly with lower-income families.

Other studies have looked at breastfeeding vs. formula feeding – “but there have been mixed results there” – and responsive feeding practices, such as teaching families to recognize when a baby is full.

Dr. Gilley said she hopes this work will help broaden the thinking when it comes to infant weight gain.

“We spend a lot of time thinking about babies who are not growing fast enough and very little time thinking about babies who are growing too fast,” she said, “especially in those first 4-6 months of life.”

Dr. Gilley points to a study that illustrates that point. Pesch et al. concluded in a 2021 study based on interviews that pediatricians “are uncertain about the concept, definition, management, and long-term risks of rapid infant weight gain.”

Authors and Dr. Gilley declare no relevant financial relationships.

Rapid weight gain (RWG) in infants and the mother’s prepregnancy overweight have a synergistic effect in increasing the odds that a child will develop overweight or obesity, new research suggests.

Findings were published online in Pediatrics.

Each factor has independently been associated with higher risk of childhood obesity but whether the two factors together exacerbate the risk has not been well studied, according to the authors led by Stephanie Gilley, MD, PhD, department of pediatrics, section of nutrition, University of Colorado at Denver, Aurora.

“Pediatric providers should monitor infants for RWG, especially in the context of maternal obesity, to reduce future risk of obesity,” the authors conclude.

Dr. Gilley’s team studied mother-infant dyads (n = 414) from the Healthy Start Study, an observational prebirth cohort. RWG was defined as a weight-for-age z score increase of at least 0.67 from birth to 3-7 months.

They found that RWG boosted the link between prepregnancy body mass index (ppBMI) and BMI z score, especially in female infants. Females exposed to both maternal obesity with RWG had an average BMI at the 94th percentile (1.50 increase in childhood BMI z score) “nearly at the cutoff for classification of obesity,” compared with those exposed to normal ppBMI with no RWG, who had an average childhood BMI at the 51st percentile.

“Currently, our nutrition recommendations as pediatricians are that all children are fed the same, essentially, after they’re born. We don’t have different growth parameters or different trajectories or targets for children who may have had different in utero exposures,” Dr. Gilley said.

Do some children need more monitoring for RWG?

Though we can’t necessarily draw conclusions from this one study, she says, the findings raise the question of whether children who were exposed in utero to obesity should be monitored for RWG more closely.

Lydia Shook, MD, Mass General Brigham maternal-fetal specialist and codirector of the Diabetes in Pregnancy Program at Massachusetts General Hospital in Boston, said she was struck by the finding in this study that with female infants, but not males, RWG significantly modified the association between ppBMI and early childhood BMI z scores.

“It’s an interesting finding and should be followed up with larger cohorts,” she said, noting that some previous studies have shown males are more vulnerable to maternal obesity and RWG.

“[Often] when we stratify by sex, you really need larger groups to be able to see the differences well,” Dr. Shook said.

She said she also found it interesting that when the researchers adjusted for breastfeeding status or caloric intake in childhood, the findings did not substantially change.

“That’s something that would warrant further investigation in an observational study or controlled trial,” Dr. Shook said.

Preventing rapid weight gain

The authors note that they did not consider possible interventions for preventing RGW in the study, although there are many, Dr. Gilley said.

Dr. Gilley also noted that a limitation of this study is that the population studied was primarily White.

Recent studies have shown the benefits of responsive parenting (RP) interventions, including a large study in 2022 geared toward Black families to teach better infant sleep practices as a way to prevent rapid weight gain.

That study, which tested the SAAF intervention, (Strong African American Families) found that “RP infants were nearly half as likely to experience upward crossing of two major weight-for-age percentile lines (14.1%), compared with control infants (24.2%); P = .09; odds ratio, 0.52; 95% confidence interval, 0.24-1.12.”

Along with sleep interventions, Dr. Gilley said, some researchers are studying the effects on RWG of better paternal engagement, or more involvement with the Women, Infants, and Children program, particularly with lower-income families.

Other studies have looked at breastfeeding vs. formula feeding – “but there have been mixed results there” – and responsive feeding practices, such as teaching families to recognize when a baby is full.

Dr. Gilley said she hopes this work will help broaden the thinking when it comes to infant weight gain.

“We spend a lot of time thinking about babies who are not growing fast enough and very little time thinking about babies who are growing too fast,” she said, “especially in those first 4-6 months of life.”

Dr. Gilley points to a study that illustrates that point. Pesch et al. concluded in a 2021 study based on interviews that pediatricians “are uncertain about the concept, definition, management, and long-term risks of rapid infant weight gain.”

Authors and Dr. Gilley declare no relevant financial relationships.

Rapid weight gain (RWG) in infants and the mother’s prepregnancy overweight have a synergistic effect in increasing the odds that a child will develop overweight or obesity, new research suggests.

Findings were published online in Pediatrics.

Each factor has independently been associated with higher risk of childhood obesity but whether the two factors together exacerbate the risk has not been well studied, according to the authors led by Stephanie Gilley, MD, PhD, department of pediatrics, section of nutrition, University of Colorado at Denver, Aurora.

“Pediatric providers should monitor infants for RWG, especially in the context of maternal obesity, to reduce future risk of obesity,” the authors conclude.

Dr. Gilley’s team studied mother-infant dyads (n = 414) from the Healthy Start Study, an observational prebirth cohort. RWG was defined as a weight-for-age z score increase of at least 0.67 from birth to 3-7 months.

They found that RWG boosted the link between prepregnancy body mass index (ppBMI) and BMI z score, especially in female infants. Females exposed to both maternal obesity with RWG had an average BMI at the 94th percentile (1.50 increase in childhood BMI z score) “nearly at the cutoff for classification of obesity,” compared with those exposed to normal ppBMI with no RWG, who had an average childhood BMI at the 51st percentile.

“Currently, our nutrition recommendations as pediatricians are that all children are fed the same, essentially, after they’re born. We don’t have different growth parameters or different trajectories or targets for children who may have had different in utero exposures,” Dr. Gilley said.

Do some children need more monitoring for RWG?

Though we can’t necessarily draw conclusions from this one study, she says, the findings raise the question of whether children who were exposed in utero to obesity should be monitored for RWG more closely.

Lydia Shook, MD, Mass General Brigham maternal-fetal specialist and codirector of the Diabetes in Pregnancy Program at Massachusetts General Hospital in Boston, said she was struck by the finding in this study that with female infants, but not males, RWG significantly modified the association between ppBMI and early childhood BMI z scores.

“It’s an interesting finding and should be followed up with larger cohorts,” she said, noting that some previous studies have shown males are more vulnerable to maternal obesity and RWG.

“[Often] when we stratify by sex, you really need larger groups to be able to see the differences well,” Dr. Shook said.

She said she also found it interesting that when the researchers adjusted for breastfeeding status or caloric intake in childhood, the findings did not substantially change.

“That’s something that would warrant further investigation in an observational study or controlled trial,” Dr. Shook said.

Preventing rapid weight gain

The authors note that they did not consider possible interventions for preventing RGW in the study, although there are many, Dr. Gilley said.

Dr. Gilley also noted that a limitation of this study is that the population studied was primarily White.

Recent studies have shown the benefits of responsive parenting (RP) interventions, including a large study in 2022 geared toward Black families to teach better infant sleep practices as a way to prevent rapid weight gain.

That study, which tested the SAAF intervention, (Strong African American Families) found that “RP infants were nearly half as likely to experience upward crossing of two major weight-for-age percentile lines (14.1%), compared with control infants (24.2%); P = .09; odds ratio, 0.52; 95% confidence interval, 0.24-1.12.”

Along with sleep interventions, Dr. Gilley said, some researchers are studying the effects on RWG of better paternal engagement, or more involvement with the Women, Infants, and Children program, particularly with lower-income families.

Other studies have looked at breastfeeding vs. formula feeding – “but there have been mixed results there” – and responsive feeding practices, such as teaching families to recognize when a baby is full.

Dr. Gilley said she hopes this work will help broaden the thinking when it comes to infant weight gain.

“We spend a lot of time thinking about babies who are not growing fast enough and very little time thinking about babies who are growing too fast,” she said, “especially in those first 4-6 months of life.”

Dr. Gilley points to a study that illustrates that point. Pesch et al. concluded in a 2021 study based on interviews that pediatricians “are uncertain about the concept, definition, management, and long-term risks of rapid infant weight gain.”

Authors and Dr. Gilley declare no relevant financial relationships.

An updated consensus statement on transcatheter left atrial appendage closure (LAAC) has put a newfound focus on patient selection for the procedure, specifically recommending that the procedure is appropriate for patients with nonvalvular atrial fibrillation who have risk for thromboembolism, aren’t well suited for direct oral anticoagulants (DOACs) and have a good chance of living for at least another year.

The statement, published online in the Journal of the Society for Cardiovascular Angiography & Interventions, also makes recommendations for how much experience operators should have, how many procedures they should perform to keep their skills up, and when and how to use imaging and prescribe DOACs, among other suggestions.

The statement represents the first updated guidance for LAAC since 2015. “Since then this field has really expanded and evolved,” writing group chair Jacqueline Saw, MD, said in an interview. “For instance, the indications are more matured and specific, and the procedural technical steps have matured. Imaging has also advanced, there’s more understanding about postprocedural care and there are also new devices that have been approved.”

Dr. Saw, an interventional cardiologist at Vancouver General Hospital and St. Paul’s Hospital, and a professor at the University of British Columbia in Vancouver, called the statement “a piece that puts everything together.”

“This document really summarizes the whole practice for doing transcatheter procedures,” she added, “so it’s all-in-one document in terms of recommendation of who we do the procedure for, how we should do it, how we should image and guide the procedure, and what complications to look out for and how to manage patients post procedure, be it with antithrombotic therapy and/or device surveillance.”

 13 recommendations

In all, the statement carries 13 recommendations for LAAC. The Society for Cardiovascular Angiography & Interventions and the Heart Rhythm Society commissioned the writing group. The American College of Cardiology and Society of Cardiovascular Computed Tomography have endorsed the statement. The following are among the recommendations:

• Transcatheter LAAC is appropriate for patients with nonvalvular atrial fibrillation with high thromboembolic risk but for whom long-term oral anticoagulation may be contraindicated and who have at least 1 year’s life expectancy.
• Operators should have performed at least 50 prior left-sided ablations or structural procedures and at least 25 transseptal punctures (TSPs). Interventional-imaging physicians should have experience in guiding 25 or more TSPs before supporting LAAC procedures independently.
• To maintain skills, operators should do 25 or more TSPs and at least 12 LAACs over each 2-year period.
• On-site cardiovascular surgery backup should be available for new programs and for operators early in their learning curve.
• Baseline imaging with transesophageal echocardiography (TEE) or cardiac computed tomography should be performed before LAAC.
• Intraprocedural imaging guidance with TEE or intracardiac echocardiography.
• Follow labeling of each specific LAAC device for technical aspects of the procedure.
• Familiarity with avoiding, recognizing, and managing LAAC complications.
• Predischarge 2-dimensional TEE to rule out pericardial effusion and device embolization.
• Anticoagulation for device-related thrombus.
• Make all efforts to minimize peridevice leaks during implantation because their clinical impact and management isn’t well understood.
• Antithrombotic therapy with warfarin, DOAC, or dual-antiplatelet therapy after LAAC based on the studied regimen and instructions for each specific device, tailored to the bleeding risks for each patient.
• TEE or cardiac computed tomography at 45-90 days after LAAC for device surveillance to assess for peridevice leak and device-related thrombus.

The statement also includes precautionary recommendations. It advises against using routine closure of LAAC-associated iatrogenic atrial septal defects and states that combined procedures with LAAC, such as structural interventions and pulmonary vein isolation, should be avoided because randomized controlled trial data are pending.

“These recommendations are based upon data from updated publications and randomized trial data as well as large registries, including the National Cardiovascular Data Registry, so I think this is a very practical statement that puts all these pieces together for any budding interventionalist doing this procedure and even experienced operations,” Dr. Saw said.

Authors of an accompanying editorial agreed that the “rigorous standards” set out in the statement will help maintain “a high level of procedural safety in the setting of rapid expansion.”

The editorialists, Faisal M. Merchant, MD, of Emory University, Atlanta, and Mohamad Alkhouli, MD, professor of medicine at Mayo Clinic School of Medicine, Rochester, Minn., point out that the incidence of pericardial effusion has decreased from more than 5% in the pivotal Watchman trials to less than 1.5% in the most recent report from the National Cardiovascular Data Registry, which shows that more than 100,000 procedures have been performed in the United States.

But most important as the field moves forward, they stress, is patient selection. The recommendation of limiting patients to those with a life expectancy of 1 year “is a tacit recognition of the fact that the benefits of LAAC take time to accrue, and many older and frail patients are unlikely to derive meaningful benefit.”

Dr. Merchant and Dr. Alkhouli also note that there remains a conundrum in patient selection that remains from the original LAAC trials, which enrolled patients who were eligible for anticoagulation. “Somewhat paradoxically, after its approval, LAAC is mostly prescribed to patients who are not felt to be good anticoagulation candidates.” This leaves physicians “in the precarious position of extrapolating data to patients who were excluded from the original clinical trials.”

Therefore, the consensus statement “is right to put patient selection front and center in its recommendations, but as the field of LAAC comes of age, better evidence to support patient selection will be the real sign of maturity.”

Dr. Saw said she envisions another update over the next 2 years or so as ongoing clinical trials comparing DOAC and LAAC, namely the CHAMPION-AF and OPTION trials, report results.

Dr. Saw and Dr. Merchant, reported no conflicts of interest. Dr. Alkhouli has financial ties to Boston Scientific, Abbott, and Philips.

An updated consensus statement on transcatheter left atrial appendage closure (LAAC) has put a newfound focus on patient selection for the procedure, specifically recommending that the procedure is appropriate for patients with nonvalvular atrial fibrillation who have risk for thromboembolism, aren’t well suited for direct oral anticoagulants (DOACs) and have a good chance of living for at least another year.

The statement, published online in the Journal of the Society for Cardiovascular Angiography & Interventions, also makes recommendations for how much experience operators should have, how many procedures they should perform to keep their skills up, and when and how to use imaging and prescribe DOACs, among other suggestions.

The statement represents the first updated guidance for LAAC since 2015. “Since then this field has really expanded and evolved,” writing group chair Jacqueline Saw, MD, said in an interview. “For instance, the indications are more matured and specific, and the procedural technical steps have matured. Imaging has also advanced, there’s more understanding about postprocedural care and there are also new devices that have been approved.”

Dr. Saw, an interventional cardiologist at Vancouver General Hospital and St. Paul’s Hospital, and a professor at the University of British Columbia in Vancouver, called the statement “a piece that puts everything together.”

“This document really summarizes the whole practice for doing transcatheter procedures,” she added, “so it’s all-in-one document in terms of recommendation of who we do the procedure for, how we should do it, how we should image and guide the procedure, and what complications to look out for and how to manage patients post procedure, be it with antithrombotic therapy and/or device surveillance.”

 13 recommendations

In all, the statement carries 13 recommendations for LAAC. The Society for Cardiovascular Angiography & Interventions and the Heart Rhythm Society commissioned the writing group. The American College of Cardiology and Society of Cardiovascular Computed Tomography have endorsed the statement. The following are among the recommendations:

• Transcatheter LAAC is appropriate for patients with nonvalvular atrial fibrillation with high thromboembolic risk but for whom long-term oral anticoagulation may be contraindicated and who have at least 1 year’s life expectancy.
• Operators should have performed at least 50 prior left-sided ablations or structural procedures and at least 25 transseptal punctures (TSPs). Interventional-imaging physicians should have experience in guiding 25 or more TSPs before supporting LAAC procedures independently.
• To maintain skills, operators should do 25 or more TSPs and at least 12 LAACs over each 2-year period.
• On-site cardiovascular surgery backup should be available for new programs and for operators early in their learning curve.
• Baseline imaging with transesophageal echocardiography (TEE) or cardiac computed tomography should be performed before LAAC.
• Intraprocedural imaging guidance with TEE or intracardiac echocardiography.
• Follow labeling of each specific LAAC device for technical aspects of the procedure.
• Familiarity with avoiding, recognizing, and managing LAAC complications.
• Predischarge 2-dimensional TEE to rule out pericardial effusion and device embolization.
• Anticoagulation for device-related thrombus.
• Make all efforts to minimize peridevice leaks during implantation because their clinical impact and management isn’t well understood.
• Antithrombotic therapy with warfarin, DOAC, or dual-antiplatelet therapy after LAAC based on the studied regimen and instructions for each specific device, tailored to the bleeding risks for each patient.
• TEE or cardiac computed tomography at 45-90 days after LAAC for device surveillance to assess for peridevice leak and device-related thrombus.

The statement also includes precautionary recommendations. It advises against using routine closure of LAAC-associated iatrogenic atrial septal defects and states that combined procedures with LAAC, such as structural interventions and pulmonary vein isolation, should be avoided because randomized controlled trial data are pending.

“These recommendations are based upon data from updated publications and randomized trial data as well as large registries, including the National Cardiovascular Data Registry, so I think this is a very practical statement that puts all these pieces together for any budding interventionalist doing this procedure and even experienced operations,” Dr. Saw said.

Authors of an accompanying editorial agreed that the “rigorous standards” set out in the statement will help maintain “a high level of procedural safety in the setting of rapid expansion.”

The editorialists, Faisal M. Merchant, MD, of Emory University, Atlanta, and Mohamad Alkhouli, MD, professor of medicine at Mayo Clinic School of Medicine, Rochester, Minn., point out that the incidence of pericardial effusion has decreased from more than 5% in the pivotal Watchman trials to less than 1.5% in the most recent report from the National Cardiovascular Data Registry, which shows that more than 100,000 procedures have been performed in the United States.

But most important as the field moves forward, they stress, is patient selection. The recommendation of limiting patients to those with a life expectancy of 1 year “is a tacit recognition of the fact that the benefits of LAAC take time to accrue, and many older and frail patients are unlikely to derive meaningful benefit.”

Dr. Merchant and Dr. Alkhouli also note that there remains a conundrum in patient selection that remains from the original LAAC trials, which enrolled patients who were eligible for anticoagulation. “Somewhat paradoxically, after its approval, LAAC is mostly prescribed to patients who are not felt to be good anticoagulation candidates.” This leaves physicians “in the precarious position of extrapolating data to patients who were excluded from the original clinical trials.”

Therefore, the consensus statement “is right to put patient selection front and center in its recommendations, but as the field of LAAC comes of age, better evidence to support patient selection will be the real sign of maturity.”

Dr. Saw said she envisions another update over the next 2 years or so as ongoing clinical trials comparing DOAC and LAAC, namely the CHAMPION-AF and OPTION trials, report results.

Dr. Saw and Dr. Merchant, reported no conflicts of interest. Dr. Alkhouli has financial ties to Boston Scientific, Abbott, and Philips.

An updated consensus statement on transcatheter left atrial appendage closure (LAAC) has put a newfound focus on patient selection for the procedure, specifically recommending that the procedure is appropriate for patients with nonvalvular atrial fibrillation who have risk for thromboembolism, aren’t well suited for direct oral anticoagulants (DOACs) and have a good chance of living for at least another year.

The statement, published online in the Journal of the Society for Cardiovascular Angiography & Interventions, also makes recommendations for how much experience operators should have, how many procedures they should perform to keep their skills up, and when and how to use imaging and prescribe DOACs, among other suggestions.

The statement represents the first updated guidance for LAAC since 2015. “Since then this field has really expanded and evolved,” writing group chair Jacqueline Saw, MD, said in an interview. “For instance, the indications are more matured and specific, and the procedural technical steps have matured. Imaging has also advanced, there’s more understanding about postprocedural care and there are also new devices that have been approved.”

Dr. Saw, an interventional cardiologist at Vancouver General Hospital and St. Paul’s Hospital, and a professor at the University of British Columbia in Vancouver, called the statement “a piece that puts everything together.”

“This document really summarizes the whole practice for doing transcatheter procedures,” she added, “so it’s all-in-one document in terms of recommendation of who we do the procedure for, how we should do it, how we should image and guide the procedure, and what complications to look out for and how to manage patients post procedure, be it with antithrombotic therapy and/or device surveillance.”

 13 recommendations

In all, the statement carries 13 recommendations for LAAC. The Society for Cardiovascular Angiography & Interventions and the Heart Rhythm Society commissioned the writing group. The American College of Cardiology and Society of Cardiovascular Computed Tomography have endorsed the statement. The following are among the recommendations:

• Transcatheter LAAC is appropriate for patients with nonvalvular atrial fibrillation with high thromboembolic risk but for whom long-term oral anticoagulation may be contraindicated and who have at least 1 year’s life expectancy.
• Operators should have performed at least 50 prior left-sided ablations or structural procedures and at least 25 transseptal punctures (TSPs). Interventional-imaging physicians should have experience in guiding 25 or more TSPs before supporting LAAC procedures independently.
• To maintain skills, operators should do 25 or more TSPs and at least 12 LAACs over each 2-year period.
• On-site cardiovascular surgery backup should be available for new programs and for operators early in their learning curve.
• Baseline imaging with transesophageal echocardiography (TEE) or cardiac computed tomography should be performed before LAAC.
• Intraprocedural imaging guidance with TEE or intracardiac echocardiography.
• Follow labeling of each specific LAAC device for technical aspects of the procedure.
• Familiarity with avoiding, recognizing, and managing LAAC complications.
• Predischarge 2-dimensional TEE to rule out pericardial effusion and device embolization.
• Anticoagulation for device-related thrombus.
• Make all efforts to minimize peridevice leaks during implantation because their clinical impact and management isn’t well understood.
• Antithrombotic therapy with warfarin, DOAC, or dual-antiplatelet therapy after LAAC based on the studied regimen and instructions for each specific device, tailored to the bleeding risks for each patient.
• TEE or cardiac computed tomography at 45-90 days after LAAC for device surveillance to assess for peridevice leak and device-related thrombus.

The statement also includes precautionary recommendations. It advises against using routine closure of LAAC-associated iatrogenic atrial septal defects and states that combined procedures with LAAC, such as structural interventions and pulmonary vein isolation, should be avoided because randomized controlled trial data are pending.

“These recommendations are based upon data from updated publications and randomized trial data as well as large registries, including the National Cardiovascular Data Registry, so I think this is a very practical statement that puts all these pieces together for any budding interventionalist doing this procedure and even experienced operations,” Dr. Saw said.

Authors of an accompanying editorial agreed that the “rigorous standards” set out in the statement will help maintain “a high level of procedural safety in the setting of rapid expansion.”

The editorialists, Faisal M. Merchant, MD, of Emory University, Atlanta, and Mohamad Alkhouli, MD, professor of medicine at Mayo Clinic School of Medicine, Rochester, Minn., point out that the incidence of pericardial effusion has decreased from more than 5% in the pivotal Watchman trials to less than 1.5% in the most recent report from the National Cardiovascular Data Registry, which shows that more than 100,000 procedures have been performed in the United States.

But most important as the field moves forward, they stress, is patient selection. The recommendation of limiting patients to those with a life expectancy of 1 year “is a tacit recognition of the fact that the benefits of LAAC take time to accrue, and many older and frail patients are unlikely to derive meaningful benefit.”

Dr. Merchant and Dr. Alkhouli also note that there remains a conundrum in patient selection that remains from the original LAAC trials, which enrolled patients who were eligible for anticoagulation. “Somewhat paradoxically, after its approval, LAAC is mostly prescribed to patients who are not felt to be good anticoagulation candidates.” This leaves physicians “in the precarious position of extrapolating data to patients who were excluded from the original clinical trials.”

Therefore, the consensus statement “is right to put patient selection front and center in its recommendations, but as the field of LAAC comes of age, better evidence to support patient selection will be the real sign of maturity.”

Dr. Saw said she envisions another update over the next 2 years or so as ongoing clinical trials comparing DOAC and LAAC, namely the CHAMPION-AF and OPTION trials, report results.

Dr. Saw and Dr. Merchant, reported no conflicts of interest. Dr. Alkhouli has financial ties to Boston Scientific, Abbott, and Philips.

NEW ORLEANS – Demonstrated adherence to professional and ethical principles is one of the six core competencies for the dermatology residency curriculum set by the Accreditation Council for Graduate Medical Education, but results from a national survey of dermatology residency program directors suggest that ethics training is not a priority.

Of the 139 dermatology residency program or associate program directors surveyed in 2022, only 43% responded. Of these, 55% said that their program had no ethics curriculum. Among programs with an ethics curriculum, 75% were implemented in the past 10 years, and the most common settings for teaching ethics were formal didactics (32%) and ad hoc during clinical encounters (28%). Reported barriers to implementing and/or maintaining an ethics curriculum included a lack of time (30%), lack of faculty with expertise (24%), and lack of useful resources (20%).

“Clearly, medical ethics is needed more to be part of our dermatology residency curriculum,” one of the study authors, Jane M. Grant-Kels, MD, professor of dermatology, pathology, and pediatrics, and founding chair of dermatology at the University of Connecticut, Farmington, said during a plenary lecture at the annual meeting of the American Academy of Dermatology. “Why? Because even though we’re physicians, and some of us have big egos, we are just human beings. We have all the faults and frailties of other humans. What we do as doctors often has unintended consequences that impact patients and society at large.”

American Academy of Dermatology

Dr. Grant-Kels, one of the editors of the textbook “Dermatoethics”, said that, while she does not believe that physicians are intentionally unethical, “we stumble into bad behavior because we fool ourselves. We think that we are ethical. We think our colleagues are ethical, and we don’t view them with a clear, transparent eye. This is referred to as ethical fading or bounded ethicality.”

Similar to religion and good behavior, one can’t really teach someone to be ethical, she continued. “But you can teach people to think about ethics and to recognize an ethical dilemma when they’re in one,” she said. “Most articles that are available [pertain to] whether ethics can be taught or not, but there are very few resources available on how to actually teach ethics.”

That, she added, has been her goal for the last 2 decades: “How do I teach ethics without sounding like I’m more ethical than anybody else, and how do I make it relevant and fun? It’s a difficult challenge.”

Pillars of medical ethics

Dr. Grant-Kels defined ethics as a way of determining how individuals ought to act based on concepts of right and wrong. An ethical dilemma is when an individual faces two competing possibilities: either both justifiable or both unjustifiable, and you have to make a decision. The four pillars of medical ethics, she noted, are beneficence (the notion that the patient’s best interests come first); nonmaleficence (do no intentional harm); autonomy (the patient’s right to refuse or choose a treatment); and justice (fairness in how health care is distributed).

“Medical ethics are the moral principles by which physicians should conduct themselves,” she said. “There is normative ethics, which involves decisions about which moral norms or ethical arguments should we accept and why; and applied ethics, or applications of these norms to specific problems or cases. No ethics is better than bad ethics, and we can see that even in today’s world. The lack of ethics, or poor ethics, or the wrong ethics has terrible consequences.”

Ethics instruction

Dr. Grant-Kels provided a “top 10 list” of tips for incorporating ethics instruction into dermatology residency programs and clinical practices:

• Make room for ethics in your curriculum. “It’s not science, and it needs to be discussed and developed with faculty and residents,” she said.
• Focus on real situations that residents will experience. Discuss what you should do, what you might have done, and why.
• Share stories and be truthful. Include other faculty members, “because you need different perspectives,” she said.
• Go beyond what is right and wrong, and the rationale. “You have to talk about the impact, because decisions you make have unintended consequences for individual patients and for patient care in general,” Dr. Grant-Kels said.
• Practice, practice, practice. Make time for discussions involving ethics, “because it takes a lot of education to be able to identify ethical issues and process them,” she said. “The truth is, we can rationalize almost anything and convince ourselves that we made the right choice. That’s why we need to continue to practice good ethics.”
• Challenge the residents. “Decisions are not always straightforward,” she said. “Pressures push us and we start to justify small decisions and then bigger decisions. This is a very gray zone. What’s ethical for one person may not be ethical to another.”
• Encourage residents and colleagues to ask the right questions and give them confidence to make the right decisions. “We have to work in an environment of ethics,” Dr. Grant-Kels said. “Many of us are role models, and we are not always behaving the way we should be. As role models, we need to be aware of that.”
• Expose residents to a variety of issues. Ethics vary depending on the situation, the people involved, and the information presented.
• Ethics cannot just come up in an ethics class. “We need to foster a culture of ethics,” she said. “If things go wrong and unethical behavior is noted, it needs to be brought to the floor and discussed.”
• Discuss the misguided pursuit of happiness and ethical decision-making. In the opinion of Dr. Grant-Kels, people can behave badly when they’re pursuing something like a career advancement, a new house, or an expensive object like a car or a boat. “They think that if they get that job or get that promotion or if they buy that big house or they buy that sports car, they’re going to be really happy,” she said.

“That’s called impact bias, which causes focalism, where you focus on that one thing, like ‘I’m going to make a lot of money’ or ‘I’m going to buy that big house on the mountain.’ The truth is, buying that car doesn’t make you happy. Buying that big house doesn’t make you happy. We need to combat focalism with professionalism, which means conducting oneself with responsibility, integrity, accountability, and excellence. Practicing ethical medicine is not a luxury; it’s a requirement. We should all try for aspirational ethics.”

Dr. Grant-Kels reported having no relevant financial disclosures.

NEW ORLEANS – Demonstrated adherence to professional and ethical principles is one of the six core competencies for the dermatology residency curriculum set by the Accreditation Council for Graduate Medical Education, but results from a national survey of dermatology residency program directors suggest that ethics training is not a priority.

Of the 139 dermatology residency program or associate program directors surveyed in 2022, only 43% responded. Of these, 55% said that their program had no ethics curriculum. Among programs with an ethics curriculum, 75% were implemented in the past 10 years, and the most common settings for teaching ethics were formal didactics (32%) and ad hoc during clinical encounters (28%). Reported barriers to implementing and/or maintaining an ethics curriculum included a lack of time (30%), lack of faculty with expertise (24%), and lack of useful resources (20%).

“Clearly, medical ethics is needed more to be part of our dermatology residency curriculum,” one of the study authors, Jane M. Grant-Kels, MD, professor of dermatology, pathology, and pediatrics, and founding chair of dermatology at the University of Connecticut, Farmington, said during a plenary lecture at the annual meeting of the American Academy of Dermatology. “Why? Because even though we’re physicians, and some of us have big egos, we are just human beings. We have all the faults and frailties of other humans. What we do as doctors often has unintended consequences that impact patients and society at large.”

American Academy of Dermatology

Dr. Grant-Kels, one of the editors of the textbook “Dermatoethics”, said that, while she does not believe that physicians are intentionally unethical, “we stumble into bad behavior because we fool ourselves. We think that we are ethical. We think our colleagues are ethical, and we don’t view them with a clear, transparent eye. This is referred to as ethical fading or bounded ethicality.”

Similar to religion and good behavior, one can’t really teach someone to be ethical, she continued. “But you can teach people to think about ethics and to recognize an ethical dilemma when they’re in one,” she said. “Most articles that are available [pertain to] whether ethics can be taught or not, but there are very few resources available on how to actually teach ethics.”

That, she added, has been her goal for the last 2 decades: “How do I teach ethics without sounding like I’m more ethical than anybody else, and how do I make it relevant and fun? It’s a difficult challenge.”

Pillars of medical ethics

Dr. Grant-Kels defined ethics as a way of determining how individuals ought to act based on concepts of right and wrong. An ethical dilemma is when an individual faces two competing possibilities: either both justifiable or both unjustifiable, and you have to make a decision. The four pillars of medical ethics, she noted, are beneficence (the notion that the patient’s best interests come first); nonmaleficence (do no intentional harm); autonomy (the patient’s right to refuse or choose a treatment); and justice (fairness in how health care is distributed).

“Medical ethics are the moral principles by which physicians should conduct themselves,” she said. “There is normative ethics, which involves decisions about which moral norms or ethical arguments should we accept and why; and applied ethics, or applications of these norms to specific problems or cases. No ethics is better than bad ethics, and we can see that even in today’s world. The lack of ethics, or poor ethics, or the wrong ethics has terrible consequences.”

Ethics instruction

Dr. Grant-Kels provided a “top 10 list” of tips for incorporating ethics instruction into dermatology residency programs and clinical practices:

• Make room for ethics in your curriculum. “It’s not science, and it needs to be discussed and developed with faculty and residents,” she said.
• Focus on real situations that residents will experience. Discuss what you should do, what you might have done, and why.
• Share stories and be truthful. Include other faculty members, “because you need different perspectives,” she said.
• Go beyond what is right and wrong, and the rationale. “You have to talk about the impact, because decisions you make have unintended consequences for individual patients and for patient care in general,” Dr. Grant-Kels said.
• Practice, practice, practice. Make time for discussions involving ethics, “because it takes a lot of education to be able to identify ethical issues and process them,” she said. “The truth is, we can rationalize almost anything and convince ourselves that we made the right choice. That’s why we need to continue to practice good ethics.”
• Challenge the residents. “Decisions are not always straightforward,” she said. “Pressures push us and we start to justify small decisions and then bigger decisions. This is a very gray zone. What’s ethical for one person may not be ethical to another.”
• Encourage residents and colleagues to ask the right questions and give them confidence to make the right decisions. “We have to work in an environment of ethics,” Dr. Grant-Kels said. “Many of us are role models, and we are not always behaving the way we should be. As role models, we need to be aware of that.”
• Expose residents to a variety of issues. Ethics vary depending on the situation, the people involved, and the information presented.
• Ethics cannot just come up in an ethics class. “We need to foster a culture of ethics,” she said. “If things go wrong and unethical behavior is noted, it needs to be brought to the floor and discussed.”
• Discuss the misguided pursuit of happiness and ethical decision-making. In the opinion of Dr. Grant-Kels, people can behave badly when they’re pursuing something like a career advancement, a new house, or an expensive object like a car or a boat. “They think that if they get that job or get that promotion or if they buy that big house or they buy that sports car, they’re going to be really happy,” she said.

“That’s called impact bias, which causes focalism, where you focus on that one thing, like ‘I’m going to make a lot of money’ or ‘I’m going to buy that big house on the mountain.’ The truth is, buying that car doesn’t make you happy. Buying that big house doesn’t make you happy. We need to combat focalism with professionalism, which means conducting oneself with responsibility, integrity, accountability, and excellence. Practicing ethical medicine is not a luxury; it’s a requirement. We should all try for aspirational ethics.”

Dr. Grant-Kels reported having no relevant financial disclosures.

NEW ORLEANS – Demonstrated adherence to professional and ethical principles is one of the six core competencies for the dermatology residency curriculum set by the Accreditation Council for Graduate Medical Education, but results from a national survey of dermatology residency program directors suggest that ethics training is not a priority.

Of the 139 dermatology residency program or associate program directors surveyed in 2022, only 43% responded. Of these, 55% said that their program had no ethics curriculum. Among programs with an ethics curriculum, 75% were implemented in the past 10 years, and the most common settings for teaching ethics were formal didactics (32%) and ad hoc during clinical encounters (28%). Reported barriers to implementing and/or maintaining an ethics curriculum included a lack of time (30%), lack of faculty with expertise (24%), and lack of useful resources (20%).

“Clearly, medical ethics is needed more to be part of our dermatology residency curriculum,” one of the study authors, Jane M. Grant-Kels, MD, professor of dermatology, pathology, and pediatrics, and founding chair of dermatology at the University of Connecticut, Farmington, said during a plenary lecture at the annual meeting of the American Academy of Dermatology. “Why? Because even though we’re physicians, and some of us have big egos, we are just human beings. We have all the faults and frailties of other humans. What we do as doctors often has unintended consequences that impact patients and society at large.”

American Academy of Dermatology

Dr. Grant-Kels, one of the editors of the textbook “Dermatoethics”, said that, while she does not believe that physicians are intentionally unethical, “we stumble into bad behavior because we fool ourselves. We think that we are ethical. We think our colleagues are ethical, and we don’t view them with a clear, transparent eye. This is referred to as ethical fading or bounded ethicality.”

Similar to religion and good behavior, one can’t really teach someone to be ethical, she continued. “But you can teach people to think about ethics and to recognize an ethical dilemma when they’re in one,” she said. “Most articles that are available [pertain to] whether ethics can be taught or not, but there are very few resources available on how to actually teach ethics.”

That, she added, has been her goal for the last 2 decades: “How do I teach ethics without sounding like I’m more ethical than anybody else, and how do I make it relevant and fun? It’s a difficult challenge.”

Pillars of medical ethics

Dr. Grant-Kels defined ethics as a way of determining how individuals ought to act based on concepts of right and wrong. An ethical dilemma is when an individual faces two competing possibilities: either both justifiable or both unjustifiable, and you have to make a decision. The four pillars of medical ethics, she noted, are beneficence (the notion that the patient’s best interests come first); nonmaleficence (do no intentional harm); autonomy (the patient’s right to refuse or choose a treatment); and justice (fairness in how health care is distributed).

“Medical ethics are the moral principles by which physicians should conduct themselves,” she said. “There is normative ethics, which involves decisions about which moral norms or ethical arguments should we accept and why; and applied ethics, or applications of these norms to specific problems or cases. No ethics is better than bad ethics, and we can see that even in today’s world. The lack of ethics, or poor ethics, or the wrong ethics has terrible consequences.”

Ethics instruction

Dr. Grant-Kels provided a “top 10 list” of tips for incorporating ethics instruction into dermatology residency programs and clinical practices:

• Make room for ethics in your curriculum. “It’s not science, and it needs to be discussed and developed with faculty and residents,” she said.
• Focus on real situations that residents will experience. Discuss what you should do, what you might have done, and why.
• Share stories and be truthful. Include other faculty members, “because you need different perspectives,” she said.
• Go beyond what is right and wrong, and the rationale. “You have to talk about the impact, because decisions you make have unintended consequences for individual patients and for patient care in general,” Dr. Grant-Kels said.
• Practice, practice, practice. Make time for discussions involving ethics, “because it takes a lot of education to be able to identify ethical issues and process them,” she said. “The truth is, we can rationalize almost anything and convince ourselves that we made the right choice. That’s why we need to continue to practice good ethics.”
• Challenge the residents. “Decisions are not always straightforward,” she said. “Pressures push us and we start to justify small decisions and then bigger decisions. This is a very gray zone. What’s ethical for one person may not be ethical to another.”
• Encourage residents and colleagues to ask the right questions and give them confidence to make the right decisions. “We have to work in an environment of ethics,” Dr. Grant-Kels said. “Many of us are role models, and we are not always behaving the way we should be. As role models, we need to be aware of that.”
• Expose residents to a variety of issues. Ethics vary depending on the situation, the people involved, and the information presented.
• Ethics cannot just come up in an ethics class. “We need to foster a culture of ethics,” she said. “If things go wrong and unethical behavior is noted, it needs to be brought to the floor and discussed.”
• Discuss the misguided pursuit of happiness and ethical decision-making. In the opinion of Dr. Grant-Kels, people can behave badly when they’re pursuing something like a career advancement, a new house, or an expensive object like a car or a boat. “They think that if they get that job or get that promotion or if they buy that big house or they buy that sports car, they’re going to be really happy,” she said.

“That’s called impact bias, which causes focalism, where you focus on that one thing, like ‘I’m going to make a lot of money’ or ‘I’m going to buy that big house on the mountain.’ The truth is, buying that car doesn’t make you happy. Buying that big house doesn’t make you happy. We need to combat focalism with professionalism, which means conducting oneself with responsibility, integrity, accountability, and excellence. Practicing ethical medicine is not a luxury; it’s a requirement. We should all try for aspirational ethics.”

Dr. Grant-Kels reported having no relevant financial disclosures.