Nonpharmacologic recommendations for ankylosing spondylitis aren’t often followed by rheumatologists in the Boston-based Partners Healthcare system, and probably elsewhere, according to a review presented at the virtual annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

The American College of Rheumatology, Spondylitis Association of America, and SPARTAN released joint guidelines for ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis in 2016. Nonpharmacologic recommendations for AS included regular disease activity monitoring using a validated measure and C-reactive protein or erythrocyte sedimentation rate; physical therapy (PT) or home back exercises; and screening for osteoporosis with dual x-ray absorptiometry (DXA) scanning.

However, “the extent to which these recommendations are followed in clinical practice is unknown,” said lead investigator Akash Patel, of the Brigham and Women’s Hospital Division of Rheumatology, Immunology, and Allergy, in Boston.

To find out, the team reviewed electronic records for 304 AS patients who had 564 rheumatology clinic visits with Brigham and Women’s and other Partners Healthcare physicians from July 1, 2016, to June 30, 2019.

Records documented DXA scans in less than 20% of visits. PT was documented in only 9% of visits, and home back exercise in just 7%. Inflammatory marker measurement was documented in about half of visits, and disease activity was measured in only 17%.

Comparing the first year of the study – right after the recommendations came out – to the third year, the team found just an 8% increase in disease activity documentation, and about a 3% increase in documentation of PT and back exercises.

In short, the recommendations “were performed at low frequencies in this study population,” Mr. Patel said at the meeting, which was held online this year because of the COVID-19 pandemic.

It’s unclear what’s going on. Perhaps some physicians disagree with the 2016 advice – the regular monitoring of disease activity, after all, was a conditional recommendation based on low-quality evidence. Other times, physicians might not have had enough time to talk about exercise or draw blood for AS biomarkers. Maybe they didn’t bring up PT when they knew their patients couldn’t afford the out-of-pocket cost.

Whatever the case, future iterations of the guidelines should include advice on how to implement them. “We believe that including some sort of strategy for rheumatologists may help increase compliance,” Mr. Patel said.

A member of the online viewing audience suggested that the problem may be widespread in rheumatology. "I think if we did this at my institution,” for example, “it would also look abysmal. I think we all just suck at this,” the attendee said.*

Mr. Patel and his team presented the results to Brigham and Women’s rheumatologists in February 2020, but it’s too early to tell if it made a difference.

It was a typical AS cohort. Almost three-quarters of the subjects were men; the average age was 50 years old; and the diagnosis was made by imaging. The majority of patients were HLA-B27 positive, and over one-third had a history of uveitis.

The study’s funding source and disclosures – if any – weren’t reported.

*Correction, 6/3/2020: A previous version of this story misattributed this quote.

aotto@mdedge.com

SOURCE: Patel A et al. SPARTAN 2020 abstract session May 15.

Nonpharmacologic recommendations for ankylosing spondylitis aren’t often followed by rheumatologists in the Boston-based Partners Healthcare system, and probably elsewhere, according to a review presented at the virtual annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

The American College of Rheumatology, Spondylitis Association of America, and SPARTAN released joint guidelines for ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis in 2016. Nonpharmacologic recommendations for AS included regular disease activity monitoring using a validated measure and C-reactive protein or erythrocyte sedimentation rate; physical therapy (PT) or home back exercises; and screening for osteoporosis with dual x-ray absorptiometry (DXA) scanning.

However, “the extent to which these recommendations are followed in clinical practice is unknown,” said lead investigator Akash Patel, of the Brigham and Women’s Hospital Division of Rheumatology, Immunology, and Allergy, in Boston.

To find out, the team reviewed electronic records for 304 AS patients who had 564 rheumatology clinic visits with Brigham and Women’s and other Partners Healthcare physicians from July 1, 2016, to June 30, 2019.

Records documented DXA scans in less than 20% of visits. PT was documented in only 9% of visits, and home back exercise in just 7%. Inflammatory marker measurement was documented in about half of visits, and disease activity was measured in only 17%.

Comparing the first year of the study – right after the recommendations came out – to the third year, the team found just an 8% increase in disease activity documentation, and about a 3% increase in documentation of PT and back exercises.

In short, the recommendations “were performed at low frequencies in this study population,” Mr. Patel said at the meeting, which was held online this year because of the COVID-19 pandemic.

It’s unclear what’s going on. Perhaps some physicians disagree with the 2016 advice – the regular monitoring of disease activity, after all, was a conditional recommendation based on low-quality evidence. Other times, physicians might not have had enough time to talk about exercise or draw blood for AS biomarkers. Maybe they didn’t bring up PT when they knew their patients couldn’t afford the out-of-pocket cost.

Whatever the case, future iterations of the guidelines should include advice on how to implement them. “We believe that including some sort of strategy for rheumatologists may help increase compliance,” Mr. Patel said.

A member of the online viewing audience suggested that the problem may be widespread in rheumatology. "I think if we did this at my institution,” for example, “it would also look abysmal. I think we all just suck at this,” the attendee said.*

Mr. Patel and his team presented the results to Brigham and Women’s rheumatologists in February 2020, but it’s too early to tell if it made a difference.

It was a typical AS cohort. Almost three-quarters of the subjects were men; the average age was 50 years old; and the diagnosis was made by imaging. The majority of patients were HLA-B27 positive, and over one-third had a history of uveitis.

The study’s funding source and disclosures – if any – weren’t reported.

*Correction, 6/3/2020: A previous version of this story misattributed this quote.

aotto@mdedge.com

SOURCE: Patel A et al. SPARTAN 2020 abstract session May 15.

Nonpharmacologic recommendations for ankylosing spondylitis aren’t often followed by rheumatologists in the Boston-based Partners Healthcare system, and probably elsewhere, according to a review presented at the virtual annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

The American College of Rheumatology, Spondylitis Association of America, and SPARTAN released joint guidelines for ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis in 2016. Nonpharmacologic recommendations for AS included regular disease activity monitoring using a validated measure and C-reactive protein or erythrocyte sedimentation rate; physical therapy (PT) or home back exercises; and screening for osteoporosis with dual x-ray absorptiometry (DXA) scanning.

However, “the extent to which these recommendations are followed in clinical practice is unknown,” said lead investigator Akash Patel, of the Brigham and Women’s Hospital Division of Rheumatology, Immunology, and Allergy, in Boston.

To find out, the team reviewed electronic records for 304 AS patients who had 564 rheumatology clinic visits with Brigham and Women’s and other Partners Healthcare physicians from July 1, 2016, to June 30, 2019.

Records documented DXA scans in less than 20% of visits. PT was documented in only 9% of visits, and home back exercise in just 7%. Inflammatory marker measurement was documented in about half of visits, and disease activity was measured in only 17%.

Comparing the first year of the study – right after the recommendations came out – to the third year, the team found just an 8% increase in disease activity documentation, and about a 3% increase in documentation of PT and back exercises.

In short, the recommendations “were performed at low frequencies in this study population,” Mr. Patel said at the meeting, which was held online this year because of the COVID-19 pandemic.

It’s unclear what’s going on. Perhaps some physicians disagree with the 2016 advice – the regular monitoring of disease activity, after all, was a conditional recommendation based on low-quality evidence. Other times, physicians might not have had enough time to talk about exercise or draw blood for AS biomarkers. Maybe they didn’t bring up PT when they knew their patients couldn’t afford the out-of-pocket cost.

Whatever the case, future iterations of the guidelines should include advice on how to implement them. “We believe that including some sort of strategy for rheumatologists may help increase compliance,” Mr. Patel said.

A member of the online viewing audience suggested that the problem may be widespread in rheumatology. "I think if we did this at my institution,” for example, “it would also look abysmal. I think we all just suck at this,” the attendee said.*

Mr. Patel and his team presented the results to Brigham and Women’s rheumatologists in February 2020, but it’s too early to tell if it made a difference.

It was a typical AS cohort. Almost three-quarters of the subjects were men; the average age was 50 years old; and the diagnosis was made by imaging. The majority of patients were HLA-B27 positive, and over one-third had a history of uveitis.

The study’s funding source and disclosures – if any – weren’t reported.

*Correction, 6/3/2020: A previous version of this story misattributed this quote.

aotto@mdedge.com

SOURCE: Patel A et al. SPARTAN 2020 abstract session May 15.

Substance use disorder and its daily consequences take no breaks even during a pandemic. The stressors created by COVID-19, including deaths of loved ones and the disruptions to normal life from policies aimed at flattening the curve, seem to have increased substance use.

Courtesy Dr. Keji Fagbemi

I practice as a hospitalist with an internal medicine background and specialty in addiction medicine at BronxCare Health System’s inpatient detoxification unit, a 24/7, 20-bed medically-supervised unit in South Bronx in New York City. It is one of the comprehensive services provided by the BronxCare’s life recovery center and addiction services, which also includes an outpatient clinic, opioid treatment program, inpatient rehab, and a half-way house. Inpatient detoxification units like ours are designed to treat serious addictions and chemical dependency and prevent and treat life-threatening withdrawal symptoms and signs or complications. Our patients come from all over the city and its adjoining suburbs, including from emergency room referrals, referral clinics, courts and the justice system, walk-ins, and self-referrals.

At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service. In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.

Individuals with substance use disorder have historically been a vulnerable and underserved population and possess high risk for multiple health problems as well as preexisting conditions. Many have limited life options financially, educationally, and with housing, and encounter barriers to accessing primary health care services, including preventive services. The introduction of the COVID-19 pandemic into these patients’ precarious health situations only made things worse as many of the limited resources for patients with substance use disorder were diverted to battling the pandemic. Numerous inpatient and outpatient addiction services, for example, were temporarily shut down. This has led to an increase in domestic violence, and psychiatric decompensation, including psychosis, suicidal attempts, and worsening of medical comorbidities in these patients.

Our wake-up call came when the first case of COVID-19 was confirmed in New York in early March. Within a short period of time the state became the epicenter for COVID-19. With the projection of millions of cases being positive and the number of new cases doubling every third day at the onset in New York City, we knew we had a battle brewing and needed to radically transform our mode of operation fast.

Our first task was to ensure the safety of our patients and the dedicated health workers attending to them. Instead of shutting down we decided to focus on education, screening, mask usage, social distancing, and intensifying hygiene. We streamlined the patient point of entry through one screening site, while also brushing up on our history-taking to intently screen for COVID-19. This included not just focusing on travels from China, but from Europe and other parts of the world.

Yes, we did ask patients about cough, fever, shortness of breath or difficulty breathing, feeling fatigued, severe body ache, and possible contact with someone who is sick or has traveled overseas. But we were also attuned to the increased rate of community spread and the presentation of other symptoms, such as loss of taste and smell, early in the process. Hence we were able to triage patients with suspected cases to the appropriate sections of the hospital for further screening, testing, and evaluation, instead of having those patients admitted to the detox unit.

Courtesy Dr. Keji Fagbemi

Dr. Fagbemi is a hospitalist at BronxCare Health System, a not-for-profit health and teaching hospital system serving South and Central Bronx in New York. He has no conflicts of interest to disclose.

Substance use disorder and its daily consequences take no breaks even during a pandemic. The stressors created by COVID-19, including deaths of loved ones and the disruptions to normal life from policies aimed at flattening the curve, seem to have increased substance use.

Courtesy Dr. Keji Fagbemi

I practice as a hospitalist with an internal medicine background and specialty in addiction medicine at BronxCare Health System’s inpatient detoxification unit, a 24/7, 20-bed medically-supervised unit in South Bronx in New York City. It is one of the comprehensive services provided by the BronxCare’s life recovery center and addiction services, which also includes an outpatient clinic, opioid treatment program, inpatient rehab, and a half-way house. Inpatient detoxification units like ours are designed to treat serious addictions and chemical dependency and prevent and treat life-threatening withdrawal symptoms and signs or complications. Our patients come from all over the city and its adjoining suburbs, including from emergency room referrals, referral clinics, courts and the justice system, walk-ins, and self-referrals.

At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service. In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.

Individuals with substance use disorder have historically been a vulnerable and underserved population and possess high risk for multiple health problems as well as preexisting conditions. Many have limited life options financially, educationally, and with housing, and encounter barriers to accessing primary health care services, including preventive services. The introduction of the COVID-19 pandemic into these patients’ precarious health situations only made things worse as many of the limited resources for patients with substance use disorder were diverted to battling the pandemic. Numerous inpatient and outpatient addiction services, for example, were temporarily shut down. This has led to an increase in domestic violence, and psychiatric decompensation, including psychosis, suicidal attempts, and worsening of medical comorbidities in these patients.

Our wake-up call came when the first case of COVID-19 was confirmed in New York in early March. Within a short period of time the state became the epicenter for COVID-19. With the projection of millions of cases being positive and the number of new cases doubling every third day at the onset in New York City, we knew we had a battle brewing and needed to radically transform our mode of operation fast.

Our first task was to ensure the safety of our patients and the dedicated health workers attending to them. Instead of shutting down we decided to focus on education, screening, mask usage, social distancing, and intensifying hygiene. We streamlined the patient point of entry through one screening site, while also brushing up on our history-taking to intently screen for COVID-19. This included not just focusing on travels from China, but from Europe and other parts of the world.

Yes, we did ask patients about cough, fever, shortness of breath or difficulty breathing, feeling fatigued, severe body ache, and possible contact with someone who is sick or has traveled overseas. But we were also attuned to the increased rate of community spread and the presentation of other symptoms, such as loss of taste and smell, early in the process. Hence we were able to triage patients with suspected cases to the appropriate sections of the hospital for further screening, testing, and evaluation, instead of having those patients admitted to the detox unit.

Courtesy Dr. Keji Fagbemi

Dr. Fagbemi is a hospitalist at BronxCare Health System, a not-for-profit health and teaching hospital system serving South and Central Bronx in New York. He has no conflicts of interest to disclose.

Substance use disorder and its daily consequences take no breaks even during a pandemic. The stressors created by COVID-19, including deaths of loved ones and the disruptions to normal life from policies aimed at flattening the curve, seem to have increased substance use.

Courtesy Dr. Keji Fagbemi

I practice as a hospitalist with an internal medicine background and specialty in addiction medicine at BronxCare Health System’s inpatient detoxification unit, a 24/7, 20-bed medically-supervised unit in South Bronx in New York City. It is one of the comprehensive services provided by the BronxCare’s life recovery center and addiction services, which also includes an outpatient clinic, opioid treatment program, inpatient rehab, and a half-way house. Inpatient detoxification units like ours are designed to treat serious addictions and chemical dependency and prevent and treat life-threatening withdrawal symptoms and signs or complications. Our patients come from all over the city and its adjoining suburbs, including from emergency room referrals, referral clinics, courts and the justice system, walk-ins, and self-referrals.

At a time when many inpatient detoxification units within the city were temporarily closed due to fear of inpatient spread of the virus or to provide extra COVID beds in anticipation for the peak surge, we have been able to provide a needed service. In fact, several other inpatient detoxification programs within the city have been able to refer their patients to our facility.

Individuals with substance use disorder have historically been a vulnerable and underserved population and possess high risk for multiple health problems as well as preexisting conditions. Many have limited life options financially, educationally, and with housing, and encounter barriers to accessing primary health care services, including preventive services. The introduction of the COVID-19 pandemic into these patients’ precarious health situations only made things worse as many of the limited resources for patients with substance use disorder were diverted to battling the pandemic. Numerous inpatient and outpatient addiction services, for example, were temporarily shut down. This has led to an increase in domestic violence, and psychiatric decompensation, including psychosis, suicidal attempts, and worsening of medical comorbidities in these patients.

Our wake-up call came when the first case of COVID-19 was confirmed in New York in early March. Within a short period of time the state became the epicenter for COVID-19. With the projection of millions of cases being positive and the number of new cases doubling every third day at the onset in New York City, we knew we had a battle brewing and needed to radically transform our mode of operation fast.

Our first task was to ensure the safety of our patients and the dedicated health workers attending to them. Instead of shutting down we decided to focus on education, screening, mask usage, social distancing, and intensifying hygiene. We streamlined the patient point of entry through one screening site, while also brushing up on our history-taking to intently screen for COVID-19. This included not just focusing on travels from China, but from Europe and other parts of the world.

Yes, we did ask patients about cough, fever, shortness of breath or difficulty breathing, feeling fatigued, severe body ache, and possible contact with someone who is sick or has traveled overseas. But we were also attuned to the increased rate of community spread and the presentation of other symptoms, such as loss of taste and smell, early in the process. Hence we were able to triage patients with suspected cases to the appropriate sections of the hospital for further screening, testing, and evaluation, instead of having those patients admitted to the detox unit.

Courtesy Dr. Keji Fagbemi

Dr. Fagbemi is a hospitalist at BronxCare Health System, a not-for-profit health and teaching hospital system serving South and Central Bronx in New York. He has no conflicts of interest to disclose.

Since the beginning of the pandemic, AGA has objected to the Centers for Medicare & Medicaid Services’ (CMS) low reimbursement rate for evaluation and management (E/M) services provided by telephone. Today, CMS fixed the problem. Retroactive to March 1, 2020, CMS will pay E/M services provided by telephone at the same rate as in-person, office/outpatient E/M services.

Thanks to everyone who helped us push CMS to address this issue. AGA worked together in coalition with other specialties and Congress on resolving this problem from the start of the pandemic.

Here are more details:

• Medicare’s updated guidance to physicians states, “Medicare payment for the telephone evaluation and management visits (CPT codes 99441-99443) is equivalent to the Medicare payment for office/outpatient visits with established patients effective March 1, 2020.
• The CMS press release outlined the new rates for telephone E/M:
• CMS is also increasing payments for these telephone visits to match payments for similar office and outpatient visits. This would increase payments for these services from a range of about $14-$41 to about $46-$110. The payments are retroactive to March 1, 2020.

We are pleased CMS listened to our message and has addressed this issue. Join the discussion on the AGA Community.

ginews@gastro.org

Since the beginning of the pandemic, AGA has objected to the Centers for Medicare & Medicaid Services’ (CMS) low reimbursement rate for evaluation and management (E/M) services provided by telephone. Today, CMS fixed the problem. Retroactive to March 1, 2020, CMS will pay E/M services provided by telephone at the same rate as in-person, office/outpatient E/M services.

Thanks to everyone who helped us push CMS to address this issue. AGA worked together in coalition with other specialties and Congress on resolving this problem from the start of the pandemic.

Here are more details:

• Medicare’s updated guidance to physicians states, “Medicare payment for the telephone evaluation and management visits (CPT codes 99441-99443) is equivalent to the Medicare payment for office/outpatient visits with established patients effective March 1, 2020.
• The CMS press release outlined the new rates for telephone E/M:
• CMS is also increasing payments for these telephone visits to match payments for similar office and outpatient visits. This would increase payments for these services from a range of about $14-$41 to about $46-$110. The payments are retroactive to March 1, 2020.

We are pleased CMS listened to our message and has addressed this issue. Join the discussion on the AGA Community.

ginews@gastro.org

Since the beginning of the pandemic, AGA has objected to the Centers for Medicare & Medicaid Services’ (CMS) low reimbursement rate for evaluation and management (E/M) services provided by telephone. Today, CMS fixed the problem. Retroactive to March 1, 2020, CMS will pay E/M services provided by telephone at the same rate as in-person, office/outpatient E/M services.

Thanks to everyone who helped us push CMS to address this issue. AGA worked together in coalition with other specialties and Congress on resolving this problem from the start of the pandemic.

Here are more details:

• Medicare’s updated guidance to physicians states, “Medicare payment for the telephone evaluation and management visits (CPT codes 99441-99443) is equivalent to the Medicare payment for office/outpatient visits with established patients effective March 1, 2020.
• The CMS press release outlined the new rates for telephone E/M:
• CMS is also increasing payments for these telephone visits to match payments for similar office and outpatient visits. This would increase payments for these services from a range of about $14-$41 to about $46-$110. The payments are retroactive to March 1, 2020.

We are pleased CMS listened to our message and has addressed this issue. Join the discussion on the AGA Community.

ginews@gastro.org

AGA has published new expert recommendations in Gastroenterology: AGA Institute Rapid Review of the GI and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19.

Key guidance for gastroenterologists:

• GI symptoms are not as common in COVID-19 as previously estimated: The overall prevalence was 7.7% (95% CI 7.4 to 8.6%) for diarrhea, 7.8% (95% CI: 7.1 to 8.5%) for nausea/vomiting, and 3.6% (95% CI 3.0 to 4.3%) for abdominal pain. Notably, in outpatients, the pooled prevalence of diarrhea is lower (4.0%).
• However, COVID-19 can present atypically, with GI symptoms: COVID-19 can present with diarrhea as an initial symptom, with a pooled prevalence of 7.9% across 35 studies, encompassing 9,717 patients. Most often, diarrhea is accompanied by other upper respiratory infection symptoms. However, in some cases, diarrhea can precede other symptoms by a few days, and COVID-19 may present as isolated GI symptoms prior to the development of upper respiratory infection symptoms.
• Monitor patients with new diarrhea, nausea, or vomiting for other COVID-19 symptoms: Patients should inform gastroenterologists if they begin to experience new fever, cough, shortness of breath, or other upper respiratory infection symptoms after the onset of GI symptoms. If this occurs, testing for COVID-19 should be considered.
• Abnormalities in liver function tests should prompt thorough evaluation: Liver test abnormalities can be seen in COVID-19 (in approximately 15% of patients); however, available data support that these abnormalities are more commonly attributable to secondary effects from severe disease, rather than primary virus-mediated liver injury. Therefore, it is important to consider alternative etiologies, such as viral hepatitis, when new elevations in aminotransferases are observed.

For all seven evidence-based recommendations and a detailed discussion, review the full publication in Gastroenterology.
 

Authors: Shahnaz Sultan, Osama Altayar, Shazia M. Siddique, Perica Davitkov, Joseph D. Feuerstein, Joseph K. Lim, Yngve Falck-Ytter, Hashem B. El-Serag on behalf of the AGA.

ginews@gastro.org

AGA has published new expert recommendations in Gastroenterology: AGA Institute Rapid Review of the GI and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19.

Key guidance for gastroenterologists:

• GI symptoms are not as common in COVID-19 as previously estimated: The overall prevalence was 7.7% (95% CI 7.4 to 8.6%) for diarrhea, 7.8% (95% CI: 7.1 to 8.5%) for nausea/vomiting, and 3.6% (95% CI 3.0 to 4.3%) for abdominal pain. Notably, in outpatients, the pooled prevalence of diarrhea is lower (4.0%).
• However, COVID-19 can present atypically, with GI symptoms: COVID-19 can present with diarrhea as an initial symptom, with a pooled prevalence of 7.9% across 35 studies, encompassing 9,717 patients. Most often, diarrhea is accompanied by other upper respiratory infection symptoms. However, in some cases, diarrhea can precede other symptoms by a few days, and COVID-19 may present as isolated GI symptoms prior to the development of upper respiratory infection symptoms.
• Monitor patients with new diarrhea, nausea, or vomiting for other COVID-19 symptoms: Patients should inform gastroenterologists if they begin to experience new fever, cough, shortness of breath, or other upper respiratory infection symptoms after the onset of GI symptoms. If this occurs, testing for COVID-19 should be considered.
• Abnormalities in liver function tests should prompt thorough evaluation: Liver test abnormalities can be seen in COVID-19 (in approximately 15% of patients); however, available data support that these abnormalities are more commonly attributable to secondary effects from severe disease, rather than primary virus-mediated liver injury. Therefore, it is important to consider alternative etiologies, such as viral hepatitis, when new elevations in aminotransferases are observed.

For all seven evidence-based recommendations and a detailed discussion, review the full publication in Gastroenterology.
 

Authors: Shahnaz Sultan, Osama Altayar, Shazia M. Siddique, Perica Davitkov, Joseph D. Feuerstein, Joseph K. Lim, Yngve Falck-Ytter, Hashem B. El-Serag on behalf of the AGA.

ginews@gastro.org

AGA has published new expert recommendations in Gastroenterology: AGA Institute Rapid Review of the GI and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19.

Key guidance for gastroenterologists:

• GI symptoms are not as common in COVID-19 as previously estimated: The overall prevalence was 7.7% (95% CI 7.4 to 8.6%) for diarrhea, 7.8% (95% CI: 7.1 to 8.5%) for nausea/vomiting, and 3.6% (95% CI 3.0 to 4.3%) for abdominal pain. Notably, in outpatients, the pooled prevalence of diarrhea is lower (4.0%).
• However, COVID-19 can present atypically, with GI symptoms: COVID-19 can present with diarrhea as an initial symptom, with a pooled prevalence of 7.9% across 35 studies, encompassing 9,717 patients. Most often, diarrhea is accompanied by other upper respiratory infection symptoms. However, in some cases, diarrhea can precede other symptoms by a few days, and COVID-19 may present as isolated GI symptoms prior to the development of upper respiratory infection symptoms.
• Monitor patients with new diarrhea, nausea, or vomiting for other COVID-19 symptoms: Patients should inform gastroenterologists if they begin to experience new fever, cough, shortness of breath, or other upper respiratory infection symptoms after the onset of GI symptoms. If this occurs, testing for COVID-19 should be considered.
• Abnormalities in liver function tests should prompt thorough evaluation: Liver test abnormalities can be seen in COVID-19 (in approximately 15% of patients); however, available data support that these abnormalities are more commonly attributable to secondary effects from severe disease, rather than primary virus-mediated liver injury. Therefore, it is important to consider alternative etiologies, such as viral hepatitis, when new elevations in aminotransferases are observed.

For all seven evidence-based recommendations and a detailed discussion, review the full publication in Gastroenterology.
 

Authors: Shahnaz Sultan, Osama Altayar, Shazia M. Siddique, Perica Davitkov, Joseph D. Feuerstein, Joseph K. Lim, Yngve Falck-Ytter, Hashem B. El-Serag on behalf of the AGA.

ginews@gastro.org

Author's note: This is the first of a two-part series. In December 2018, Atlanta Gastroenterology Associates partnered with Frazier Healthcare Partners to form the practice management company United Digestive (UD). Since that time, colleagues across the country have evaluated their own private equity prospects and partnerships, as well as monitored the progress of our transition.

Our guiding principle is to provide a best-in-class operational infrastructure, so independent gastroenterologists can focus on delivering the highest quality patient care. Thus, in the first year, significant efforts and capital have been invested into United Digestive’s scalable platform to promote organic growth, as well as facilitate a smooth transition for other groups and physicians joining the team. So how are things going? Enjoy this two-part article where we reached out to several team members from all levels within the organization and asked them to share their personal experiences – both highlights and challenges – during UD’s first year. Here’s what they had to say.
 

During the COVID-19 crisis, how has UD management responded? How has the UD management services organization model affected partner level physician (PLP) compensation?

Dr. Marc Rosenberg, UD Physician Executive Committee member:

• “Immediately, the entire leadership team recognized the threat of COVID to our community, patients, staff, and business. A multidisciplinary task force including clinical and business leaders utilized our PE partner’s vast resources, local hospital expertise, national societal recommendations and colleagues’ experiences from around the country to focus on protocols and procedures to protect our patients and staff. A few of the team’s timely decisions included: closing the majority of our patient fronting services, transitioning to telehealth, hiring an infection control consultant, allowing physical distancing of our staff with off sight work, instituting symptomatic pathways, donating personal protective gear to local hospitals, covering all benefits as well as provided resources to obtain government benefits to furloughed team members, developing a provider wellness program, and encouraging hospital coverage considerations for high risk providers. I also know the team is focusing on how we re-open at the appropriate time with necessary safety considerations, like investigating testing options and ensuring appropriate PPE is in place. The collaboration between clinical and business leadership has been tremendous through this evolving and challenging period. As for UD physician partner compensation, our model is uniquely organized such that the MSO covers all overhead expenses with partners contributing a fixed percentage of a partner’s collections, while others typically share overhead expenses. During uncertain times, like the COVID-19 crisis, it is reassuring to partners to know that they are not responsible for the cost of infrastructure (i.e. leases, capital equipment, EHR system, consultants, etc.) and staffing, including current and new associates.”

With formation of United Digestive as an MSO, has your day-to-day work life changed or your clinical decision-making been impacted?

Dr. Aja McCutchen, UD Physician Executive Committee Member:

• “With the formation of UD, my daily work life has changed very little; however, with their focus on improving “back-office” functions, my schedule is now fully optimized by reducing gaps from cancellations with same-day/next-day scheduling. In addition, the patient experience has been enhanced with decreased wait times, easier appointment scheduling, and quicker access to support staff. The procurement of business intelligence tools, and, more importantly, the implementation of dashboards, has provided much needed visibility across the organization allowing managerial decisions to be driven by accurate data.

From a clinical decision-making standpoint, Atlanta Gastroenterology was already armed with strong clinical teams and committees. We have been able to build upon our pre-existing committees and optimize their ability to steward best practices and develop clinical pathways. This, in turn, translates to consistency across the organization in the delivery of evidence-based, comprehensive GI care.”
 

Kimberly Orleck, PA-C, Advanced Practice Provider (APP) Supervisor:

• “The formation of UD has not affected my clinical decision-making abilities. In fact, this new platform is dedicated to empowering and establishing APPs as independent clinicians with appropriate physician oversight. As a result, I have welcomed more administrative responsibilities and have become more involved in business meetings and decision making. We have worked together to better utilize APPs using data to match supply with demand.”

Physician compensation improvement is typically a key concern for physicians who work with private equity MSOs. How has United Digestive performed for its partner-level physicians in year one?

Dr. Marc Rosenberg:

• “The MSO has helped to improve physician income – slowly at first and now on a steeper trajectory. We have been ahead of expected income improvement based on models we reviewed when evaluating the formations of an MSO in potential partnership with Frazier Healthcare Partners. United Digestive’s EBIDTA, of which each partner-level physician owns a significant percentage through shares from rollover proceeds, has grown impressively in one year. This has been achieved mostly through significant organic growth and to a lesser degree through mergers and acquisitions. UD has helped to enhance the bottom line through increased reimbursements from payor negotiated contracts, new revenue-generating service lines, and operational efficiencies.”

Dr. Patel and Dr. Sonnenshine are with Atlanta Gastroenterology Associates in Atlanta, which is part of United Digestive. They have no conflicts.

*This story was updated on 6/1/2020.

Author's note: This is the first of a two-part series. In December 2018, Atlanta Gastroenterology Associates partnered with Frazier Healthcare Partners to form the practice management company United Digestive (UD). Since that time, colleagues across the country have evaluated their own private equity prospects and partnerships, as well as monitored the progress of our transition.

Our guiding principle is to provide a best-in-class operational infrastructure, so independent gastroenterologists can focus on delivering the highest quality patient care. Thus, in the first year, significant efforts and capital have been invested into United Digestive’s scalable platform to promote organic growth, as well as facilitate a smooth transition for other groups and physicians joining the team. So how are things going? Enjoy this two-part article where we reached out to several team members from all levels within the organization and asked them to share their personal experiences – both highlights and challenges – during UD’s first year. Here’s what they had to say.
 

During the COVID-19 crisis, how has UD management responded? How has the UD management services organization model affected partner level physician (PLP) compensation?

Dr. Marc Rosenberg, UD Physician Executive Committee member:

• “Immediately, the entire leadership team recognized the threat of COVID to our community, patients, staff, and business. A multidisciplinary task force including clinical and business leaders utilized our PE partner’s vast resources, local hospital expertise, national societal recommendations and colleagues’ experiences from around the country to focus on protocols and procedures to protect our patients and staff. A few of the team’s timely decisions included: closing the majority of our patient fronting services, transitioning to telehealth, hiring an infection control consultant, allowing physical distancing of our staff with off sight work, instituting symptomatic pathways, donating personal protective gear to local hospitals, covering all benefits as well as provided resources to obtain government benefits to furloughed team members, developing a provider wellness program, and encouraging hospital coverage considerations for high risk providers. I also know the team is focusing on how we re-open at the appropriate time with necessary safety considerations, like investigating testing options and ensuring appropriate PPE is in place. The collaboration between clinical and business leadership has been tremendous through this evolving and challenging period. As for UD physician partner compensation, our model is uniquely organized such that the MSO covers all overhead expenses with partners contributing a fixed percentage of a partner’s collections, while others typically share overhead expenses. During uncertain times, like the COVID-19 crisis, it is reassuring to partners to know that they are not responsible for the cost of infrastructure (i.e. leases, capital equipment, EHR system, consultants, etc.) and staffing, including current and new associates.”

With formation of United Digestive as an MSO, has your day-to-day work life changed or your clinical decision-making been impacted?

Dr. Aja McCutchen, UD Physician Executive Committee Member:

• “With the formation of UD, my daily work life has changed very little; however, with their focus on improving “back-office” functions, my schedule is now fully optimized by reducing gaps from cancellations with same-day/next-day scheduling. In addition, the patient experience has been enhanced with decreased wait times, easier appointment scheduling, and quicker access to support staff. The procurement of business intelligence tools, and, more importantly, the implementation of dashboards, has provided much needed visibility across the organization allowing managerial decisions to be driven by accurate data.

From a clinical decision-making standpoint, Atlanta Gastroenterology was already armed with strong clinical teams and committees. We have been able to build upon our pre-existing committees and optimize their ability to steward best practices and develop clinical pathways. This, in turn, translates to consistency across the organization in the delivery of evidence-based, comprehensive GI care.”
 

Kimberly Orleck, PA-C, Advanced Practice Provider (APP) Supervisor:

• “The formation of UD has not affected my clinical decision-making abilities. In fact, this new platform is dedicated to empowering and establishing APPs as independent clinicians with appropriate physician oversight. As a result, I have welcomed more administrative responsibilities and have become more involved in business meetings and decision making. We have worked together to better utilize APPs using data to match supply with demand.”

Physician compensation improvement is typically a key concern for physicians who work with private equity MSOs. How has United Digestive performed for its partner-level physicians in year one?

Dr. Marc Rosenberg:

• “The MSO has helped to improve physician income – slowly at first and now on a steeper trajectory. We have been ahead of expected income improvement based on models we reviewed when evaluating the formations of an MSO in potential partnership with Frazier Healthcare Partners. United Digestive’s EBIDTA, of which each partner-level physician owns a significant percentage through shares from rollover proceeds, has grown impressively in one year. This has been achieved mostly through significant organic growth and to a lesser degree through mergers and acquisitions. UD has helped to enhance the bottom line through increased reimbursements from payor negotiated contracts, new revenue-generating service lines, and operational efficiencies.”

Dr. Patel and Dr. Sonnenshine are with Atlanta Gastroenterology Associates in Atlanta, which is part of United Digestive. They have no conflicts.

*This story was updated on 6/1/2020.

Author's note: This is the first of a two-part series. In December 2018, Atlanta Gastroenterology Associates partnered with Frazier Healthcare Partners to form the practice management company United Digestive (UD). Since that time, colleagues across the country have evaluated their own private equity prospects and partnerships, as well as monitored the progress of our transition.

Our guiding principle is to provide a best-in-class operational infrastructure, so independent gastroenterologists can focus on delivering the highest quality patient care. Thus, in the first year, significant efforts and capital have been invested into United Digestive’s scalable platform to promote organic growth, as well as facilitate a smooth transition for other groups and physicians joining the team. So how are things going? Enjoy this two-part article where we reached out to several team members from all levels within the organization and asked them to share their personal experiences – both highlights and challenges – during UD’s first year. Here’s what they had to say.
 

During the COVID-19 crisis, how has UD management responded? How has the UD management services organization model affected partner level physician (PLP) compensation?

Dr. Marc Rosenberg, UD Physician Executive Committee member:

• “Immediately, the entire leadership team recognized the threat of COVID to our community, patients, staff, and business. A multidisciplinary task force including clinical and business leaders utilized our PE partner’s vast resources, local hospital expertise, national societal recommendations and colleagues’ experiences from around the country to focus on protocols and procedures to protect our patients and staff. A few of the team’s timely decisions included: closing the majority of our patient fronting services, transitioning to telehealth, hiring an infection control consultant, allowing physical distancing of our staff with off sight work, instituting symptomatic pathways, donating personal protective gear to local hospitals, covering all benefits as well as provided resources to obtain government benefits to furloughed team members, developing a provider wellness program, and encouraging hospital coverage considerations for high risk providers. I also know the team is focusing on how we re-open at the appropriate time with necessary safety considerations, like investigating testing options and ensuring appropriate PPE is in place. The collaboration between clinical and business leadership has been tremendous through this evolving and challenging period. As for UD physician partner compensation, our model is uniquely organized such that the MSO covers all overhead expenses with partners contributing a fixed percentage of a partner’s collections, while others typically share overhead expenses. During uncertain times, like the COVID-19 crisis, it is reassuring to partners to know that they are not responsible for the cost of infrastructure (i.e. leases, capital equipment, EHR system, consultants, etc.) and staffing, including current and new associates.”

With formation of United Digestive as an MSO, has your day-to-day work life changed or your clinical decision-making been impacted?

Dr. Aja McCutchen, UD Physician Executive Committee Member:

• “With the formation of UD, my daily work life has changed very little; however, with their focus on improving “back-office” functions, my schedule is now fully optimized by reducing gaps from cancellations with same-day/next-day scheduling. In addition, the patient experience has been enhanced with decreased wait times, easier appointment scheduling, and quicker access to support staff. The procurement of business intelligence tools, and, more importantly, the implementation of dashboards, has provided much needed visibility across the organization allowing managerial decisions to be driven by accurate data.

From a clinical decision-making standpoint, Atlanta Gastroenterology was already armed with strong clinical teams and committees. We have been able to build upon our pre-existing committees and optimize their ability to steward best practices and develop clinical pathways. This, in turn, translates to consistency across the organization in the delivery of evidence-based, comprehensive GI care.”
 

Kimberly Orleck, PA-C, Advanced Practice Provider (APP) Supervisor:

• “The formation of UD has not affected my clinical decision-making abilities. In fact, this new platform is dedicated to empowering and establishing APPs as independent clinicians with appropriate physician oversight. As a result, I have welcomed more administrative responsibilities and have become more involved in business meetings and decision making. We have worked together to better utilize APPs using data to match supply with demand.”

Physician compensation improvement is typically a key concern for physicians who work with private equity MSOs. How has United Digestive performed for its partner-level physicians in year one?

Dr. Marc Rosenberg:

• “The MSO has helped to improve physician income – slowly at first and now on a steeper trajectory. We have been ahead of expected income improvement based on models we reviewed when evaluating the formations of an MSO in potential partnership with Frazier Healthcare Partners. United Digestive’s EBIDTA, of which each partner-level physician owns a significant percentage through shares from rollover proceeds, has grown impressively in one year. This has been achieved mostly through significant organic growth and to a lesser degree through mergers and acquisitions. UD has helped to enhance the bottom line through increased reimbursements from payor negotiated contracts, new revenue-generating service lines, and operational efficiencies.”

Dr. Patel and Dr. Sonnenshine are with Atlanta Gastroenterology Associates in Atlanta, which is part of United Digestive. They have no conflicts.

*This story was updated on 6/1/2020.

A simple tool to guide choice of antithrombotic therapy following total joint arthroplasty led to a reduction in pulmonary embolism (PE) after being introduced systemwide, according to a prospectively tracked evaluation of a large patient cohort. The results of the study were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.

“We developed a simplified scoring system for evaluating risk of thromboembolism and guiding prophylaxis that led to a significant reduction in events across a large integrated health care system,” reported James Wylie, MD, associate medical director for hip and knee preservation and orthopedic research at Intermountain Healthcare, Salt Lake City, Utah.

The goal of the methodology was to create a uniform and evidence-based approach to risk assessment in order to guide selection of appropriate venous thromboembolism (VTE) prophylaxis. The tool takes into account the need to individualize antithrombotic drugs for risk of both VTE and for bleeding.

“VTE is a major threat following total joint replacement, but not all patients require anticoagulants. Recent evidence supports a shift to aspirin for low-risk patients,” explained Dr. Wylie in an interview.

The risk tool assigns points for such factors as history of VTE, older age, history of coronary artery disease, history of cancer, and increased body mass index. There are two possible ratings to guide strategies. Those with standard risk are candidates for 81 mg of aspirin twice daily. Those with high risk are candidates for 2.5 mg of apixaban, also administered twice daily. Custom dosing of warfarin is an alternative for the latter group. Regardless of strategy, prophylaxis is administered for 30 days following arthroplasty

“The risk score is calculated automatically, because you have to click a box in the electronic medical record for all of those factors as part of admission orders,” Dr. Wylie said.

The protocol was introduced in July 2017 and adoption was tracked prospectively over 18 months. In an evaluable cohort of 20,284 patients, PE rates in the 71% of patients adherent to the protocol were compared with the 29% who were not.

Over the observation period, the rates of PE were 0.34% and 0.62% (P = .004) for those adherent and nonadherent, respectively. The rate of unplanned readmissions and death, which were secondary outcomes, were both numerically lower in the group treated by adherent surgeons, but the differences did not reach statistical significance.

Adoption of the protocol by surgeons did increase over the course of the observation period, and this correlated with a decrease in unplanned readmissions. Bleeding-related readmission was a rare event in this analysis and did not significantly increase over time, according to Dr. Wylie.

The risk assessment tool, developed by a multispecialty team at Intermountain Healthcare, was based on a review of hundreds of published papers and guidelines, according to Nathan Momberger, MD, who is the associate medical director of total joint replacement at Intermountain and was a coauthor on this study. A member of the team that developed the risk assessment tool, Dr. Momberger noted that new risk score was developed at a time when clinicians have been moving quickly away from warfarin to direct oral anticoagulants.

“None of our surgeons were using the same VTE prophylaxis when we started this project,” Dr. Momberger said. This was a motivation for developing a systemwide approach. In the 22 participating hospitals, there were 50 surgeons performing total knee arthroplasty and 40 surgeons were performing total hip surgery at the time the new protocol was introduced.

Further analyses will provide a more detailed analysis of the effect of the protocol on other thrombotic events, including deep vein thrombosis, and on cost. Since these data were analyzed, protocol adoption has increased and now exceeds 80%, according to Dr. Wylie.

Although a standardized approach to VTE prophylaxis following total joint arthroplasty is attractive, the ideal strategy remains controversial, according to Sunny Parikh, MD, an orthopedic surgeon affiliated with Colchester (England) General Hospital.

As a coauthor of a recent study that quantified symptomatic VTE rates at his and a neighboring hospital over a 3-year period (BMC Musculoskelet Disord. 2020;21:95), Dr. Parikh reported that VTE rates did not reach zero even with a prolonged course of the low-molecular-weight heparin enoxaparin.

At 90 days, the symptomatic VTE rate was only 0.3% for total knee arthroplasty but reached 1.2% for total hip arthroplasty.

“At the time of this study we were using enoxaparin for 28 days following total hip replacements and for 14 days following total knee replacements,” Dr. Parikh reported. Since this study, his institution has switched to a regimen recommended by the U.K.’s National Institute for Health and Clinical Excellence (NICE).

Under the NICE guidelines, VTE prophylaxis for total hip arthroplasty is 40 mg enoxaparin once daily for 14 days followed by 75 mg aspirin for another 14 days, according to Dr. Parikh. For total knee arthroplasty, the standard regimen is 75 mg aspirin for 14 days.

For those who might not be best managed with the standard approach, “there is no clear guideline.” Rather, in patients with renal or liver impairment, “we discuss the case with the hematology team to adjust the doses,” Dr. Parikh reported.

The advantage of a standardized approach applied to all or most patients is that is eliminates disparities, but Dr. Parikh agreed that risk-adjusted prophylaxis might be warranted for optimal outcomes.

Dr. Wylie reported a financial relationship with Arthrex.
 

A simple tool to guide choice of antithrombotic therapy following total joint arthroplasty led to a reduction in pulmonary embolism (PE) after being introduced systemwide, according to a prospectively tracked evaluation of a large patient cohort. The results of the study were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.

“We developed a simplified scoring system for evaluating risk of thromboembolism and guiding prophylaxis that led to a significant reduction in events across a large integrated health care system,” reported James Wylie, MD, associate medical director for hip and knee preservation and orthopedic research at Intermountain Healthcare, Salt Lake City, Utah.

The goal of the methodology was to create a uniform and evidence-based approach to risk assessment in order to guide selection of appropriate venous thromboembolism (VTE) prophylaxis. The tool takes into account the need to individualize antithrombotic drugs for risk of both VTE and for bleeding.

“VTE is a major threat following total joint replacement, but not all patients require anticoagulants. Recent evidence supports a shift to aspirin for low-risk patients,” explained Dr. Wylie in an interview.

The risk tool assigns points for such factors as history of VTE, older age, history of coronary artery disease, history of cancer, and increased body mass index. There are two possible ratings to guide strategies. Those with standard risk are candidates for 81 mg of aspirin twice daily. Those with high risk are candidates for 2.5 mg of apixaban, also administered twice daily. Custom dosing of warfarin is an alternative for the latter group. Regardless of strategy, prophylaxis is administered for 30 days following arthroplasty

“The risk score is calculated automatically, because you have to click a box in the electronic medical record for all of those factors as part of admission orders,” Dr. Wylie said.

The protocol was introduced in July 2017 and adoption was tracked prospectively over 18 months. In an evaluable cohort of 20,284 patients, PE rates in the 71% of patients adherent to the protocol were compared with the 29% who were not.

Over the observation period, the rates of PE were 0.34% and 0.62% (P = .004) for those adherent and nonadherent, respectively. The rate of unplanned readmissions and death, which were secondary outcomes, were both numerically lower in the group treated by adherent surgeons, but the differences did not reach statistical significance.

Adoption of the protocol by surgeons did increase over the course of the observation period, and this correlated with a decrease in unplanned readmissions. Bleeding-related readmission was a rare event in this analysis and did not significantly increase over time, according to Dr. Wylie.

The risk assessment tool, developed by a multispecialty team at Intermountain Healthcare, was based on a review of hundreds of published papers and guidelines, according to Nathan Momberger, MD, who is the associate medical director of total joint replacement at Intermountain and was a coauthor on this study. A member of the team that developed the risk assessment tool, Dr. Momberger noted that new risk score was developed at a time when clinicians have been moving quickly away from warfarin to direct oral anticoagulants.

“None of our surgeons were using the same VTE prophylaxis when we started this project,” Dr. Momberger said. This was a motivation for developing a systemwide approach. In the 22 participating hospitals, there were 50 surgeons performing total knee arthroplasty and 40 surgeons were performing total hip surgery at the time the new protocol was introduced.

Further analyses will provide a more detailed analysis of the effect of the protocol on other thrombotic events, including deep vein thrombosis, and on cost. Since these data were analyzed, protocol adoption has increased and now exceeds 80%, according to Dr. Wylie.

Although a standardized approach to VTE prophylaxis following total joint arthroplasty is attractive, the ideal strategy remains controversial, according to Sunny Parikh, MD, an orthopedic surgeon affiliated with Colchester (England) General Hospital.

As a coauthor of a recent study that quantified symptomatic VTE rates at his and a neighboring hospital over a 3-year period (BMC Musculoskelet Disord. 2020;21:95), Dr. Parikh reported that VTE rates did not reach zero even with a prolonged course of the low-molecular-weight heparin enoxaparin.

At 90 days, the symptomatic VTE rate was only 0.3% for total knee arthroplasty but reached 1.2% for total hip arthroplasty.

“At the time of this study we were using enoxaparin for 28 days following total hip replacements and for 14 days following total knee replacements,” Dr. Parikh reported. Since this study, his institution has switched to a regimen recommended by the U.K.’s National Institute for Health and Clinical Excellence (NICE).

Under the NICE guidelines, VTE prophylaxis for total hip arthroplasty is 40 mg enoxaparin once daily for 14 days followed by 75 mg aspirin for another 14 days, according to Dr. Parikh. For total knee arthroplasty, the standard regimen is 75 mg aspirin for 14 days.

For those who might not be best managed with the standard approach, “there is no clear guideline.” Rather, in patients with renal or liver impairment, “we discuss the case with the hematology team to adjust the doses,” Dr. Parikh reported.

The advantage of a standardized approach applied to all or most patients is that is eliminates disparities, but Dr. Parikh agreed that risk-adjusted prophylaxis might be warranted for optimal outcomes.

Dr. Wylie reported a financial relationship with Arthrex.
 

A simple tool to guide choice of antithrombotic therapy following total joint arthroplasty led to a reduction in pulmonary embolism (PE) after being introduced systemwide, according to a prospectively tracked evaluation of a large patient cohort. The results of the study were reported in an abstract scheduled for release at the annual meeting of the American Academy of Orthopaedic Surgeons. The meeting was canceled because of COVID-19.

“We developed a simplified scoring system for evaluating risk of thromboembolism and guiding prophylaxis that led to a significant reduction in events across a large integrated health care system,” reported James Wylie, MD, associate medical director for hip and knee preservation and orthopedic research at Intermountain Healthcare, Salt Lake City, Utah.

The goal of the methodology was to create a uniform and evidence-based approach to risk assessment in order to guide selection of appropriate venous thromboembolism (VTE) prophylaxis. The tool takes into account the need to individualize antithrombotic drugs for risk of both VTE and for bleeding.

“VTE is a major threat following total joint replacement, but not all patients require anticoagulants. Recent evidence supports a shift to aspirin for low-risk patients,” explained Dr. Wylie in an interview.

The risk tool assigns points for such factors as history of VTE, older age, history of coronary artery disease, history of cancer, and increased body mass index. There are two possible ratings to guide strategies. Those with standard risk are candidates for 81 mg of aspirin twice daily. Those with high risk are candidates for 2.5 mg of apixaban, also administered twice daily. Custom dosing of warfarin is an alternative for the latter group. Regardless of strategy, prophylaxis is administered for 30 days following arthroplasty

“The risk score is calculated automatically, because you have to click a box in the electronic medical record for all of those factors as part of admission orders,” Dr. Wylie said.

The protocol was introduced in July 2017 and adoption was tracked prospectively over 18 months. In an evaluable cohort of 20,284 patients, PE rates in the 71% of patients adherent to the protocol were compared with the 29% who were not.

Over the observation period, the rates of PE were 0.34% and 0.62% (P = .004) for those adherent and nonadherent, respectively. The rate of unplanned readmissions and death, which were secondary outcomes, were both numerically lower in the group treated by adherent surgeons, but the differences did not reach statistical significance.

Adoption of the protocol by surgeons did increase over the course of the observation period, and this correlated with a decrease in unplanned readmissions. Bleeding-related readmission was a rare event in this analysis and did not significantly increase over time, according to Dr. Wylie.

The risk assessment tool, developed by a multispecialty team at Intermountain Healthcare, was based on a review of hundreds of published papers and guidelines, according to Nathan Momberger, MD, who is the associate medical director of total joint replacement at Intermountain and was a coauthor on this study. A member of the team that developed the risk assessment tool, Dr. Momberger noted that new risk score was developed at a time when clinicians have been moving quickly away from warfarin to direct oral anticoagulants.

“None of our surgeons were using the same VTE prophylaxis when we started this project,” Dr. Momberger said. This was a motivation for developing a systemwide approach. In the 22 participating hospitals, there were 50 surgeons performing total knee arthroplasty and 40 surgeons were performing total hip surgery at the time the new protocol was introduced.

Further analyses will provide a more detailed analysis of the effect of the protocol on other thrombotic events, including deep vein thrombosis, and on cost. Since these data were analyzed, protocol adoption has increased and now exceeds 80%, according to Dr. Wylie.

Although a standardized approach to VTE prophylaxis following total joint arthroplasty is attractive, the ideal strategy remains controversial, according to Sunny Parikh, MD, an orthopedic surgeon affiliated with Colchester (England) General Hospital.

As a coauthor of a recent study that quantified symptomatic VTE rates at his and a neighboring hospital over a 3-year period (BMC Musculoskelet Disord. 2020;21:95), Dr. Parikh reported that VTE rates did not reach zero even with a prolonged course of the low-molecular-weight heparin enoxaparin.

At 90 days, the symptomatic VTE rate was only 0.3% for total knee arthroplasty but reached 1.2% for total hip arthroplasty.

“At the time of this study we were using enoxaparin for 28 days following total hip replacements and for 14 days following total knee replacements,” Dr. Parikh reported. Since this study, his institution has switched to a regimen recommended by the U.K.’s National Institute for Health and Clinical Excellence (NICE).

Under the NICE guidelines, VTE prophylaxis for total hip arthroplasty is 40 mg enoxaparin once daily for 14 days followed by 75 mg aspirin for another 14 days, according to Dr. Parikh. For total knee arthroplasty, the standard regimen is 75 mg aspirin for 14 days.

For those who might not be best managed with the standard approach, “there is no clear guideline.” Rather, in patients with renal or liver impairment, “we discuss the case with the hematology team to adjust the doses,” Dr. Parikh reported.

The advantage of a standardized approach applied to all or most patients is that is eliminates disparities, but Dr. Parikh agreed that risk-adjusted prophylaxis might be warranted for optimal outcomes.

Dr. Wylie reported a financial relationship with Arthrex.
 

Adding the AKT inhibitor ipatasertib to paclitaxel may provide an overall survival (OS) benefit for inoperable locally advanced/metastatic triple-negative breast cancer (TNBC), according to final results of the phase 2 LOTUS trial.

The median OS was 25.8 months in patients who received ipatasertib plus paclitaxel and 16.9 months in patients who received paclitaxel plus placebo. Although this difference was not statistically significant, it was “clinically meaningful,” according to Rebecca Dent, MD, of the National Cancer Center Singapore. Dr. Dent presented OS data from the LOTUS trial at the European Society of Medical Oncology: Breast Cancer virtual meeting.

Previously reported data showed a progression-free survival benefit in the ipatasertib arm, compared with the placebo arm – 6.2 months and 4.9 months, respectively (Lancet Oncol. 2017 Oct;18[10]:1360-72). An enhanced effect was noted in patients with PIK3CA/AKT1/PTEN–altered tumors, but the OS data were not mature at the time of that primary analysis.
 

Patients, treatment, and safety

LOTUS participants had measurable locally advanced/metastatic TNBC that was previously untreated with systemic therapy, and they were stratified by prior adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status.

Patients were randomized 1:1 to receive paclitaxel at a dose of 80 mg/m² on days 1, 8, and 15 of each 28-day cycle plus either placebo (n = 62) or ipatasertib at a dose of 400 mg on days 1-21 (n = 62).

The safety results didn’t differ between the primary and updated results, Dr. Dent noted.

“What we can say is that the combination is extremely well tolerated, especially when we compare it to other targeted agents targeting this pathway,” she said. “What we do see is noticeable diarrhea ... [and] an increase in sensory neuropathy, which is not entirely unexpected.”

Subsequent systemic anticancer therapy was required in 77% of patients in the ipatasertib arm and 90% of patients in the placebo arm.
 

OS results

The final OS data show a numerical advantage for patients in the ipatasertib arm compared with the placebo arm. The 1-year OS was 83% in the ipatasertib arm and 68% in the placebo arm. The median OS was 25.8 months and 16.9 months, respectively (stratified hazard ratio, 0.80).

“This is a clinically meaningful improvement of 9 months in overall survival, which is indeed not too dissimilar to what we have seen in patients with PD-L1-positive TNBC who are receiving immune checkpoint inhibition in combination with chemotherapy,” Dr. Dent said.

However, the 95% confidence interval for the stratified OS hazard ratio crossed 1 (0.50-1.28). Therefore, the findings require confirmatory phase 3 trial results, Dr. Dent said.

The OS improvements with ipatasertib were seen “in all biomarker-defined subgroups – PTEN normal or low, PIK3CA/AKT1/PTEN altered or non-altered,” she said. OS benefits were more pronounced in patients with altered PIK3C/AKT1/PTEN status, but the numbers are too small to make definitive conclusions, according to Dr. Dent.
 

‘Promising’ results, confirmation needed

Invited discussant Suzette Delaloge, MD, head of the breast cancer department at Gustave Roussy, Paris, said the OS findings from LOTUS are “quite promising,” and the safety data are “reassuring.”

The findings are comparable to those of the recently published PAKT trial (J Clin Oncol. 2020 Feb 10;38[5]:423-33), she said, noting that “AKT inhibition in combination with paclitaxel deserves phase 3 development, and this is ongoing in major phase 3 trials.”

Dr. Delaloge also noted that the efficacy may not be limited to PIK3CA/AKT–altered tumors, and given the heterogeneity of TNBC – which may explain the differences seen among various studies – “it is very important that such phase 3 trials ideally involve extensive genomical definitions of tumors so that we understand what it is we are talking about and what is the real effect of the drug.”

“The adequate positioning of AKT inhibition in competition/complementation with other ongoing strategies remains to be defined,” she said. “I think these drugs are ready for translation to early phases.”

Dr. Dent said the results of LOTUS warrant confirmation in the ongoing, randomized phase 3 IPATunity130 trial , in which researchers are evaluating first-line ipatasertib plus paclitaxel for metastatic TNBC. She noted that the small sample sizes and heterogeneity of TNBC among LOTUS participants limited the interpretation of the findings.

In another trial, IPATunity170, researchers are evaluating the first-line role of ipatasertib plus paclitaxel and atezolizumab in locally advanced or metastatic TNBC.

“This is an exciting triplet combination that’s been evaluated already in the phase 1 setting, and now we have a phase 3 study evaluating the triplet,” Dr. Dent said.

The LOTUS trial was funded by Roche/Genentech. Dr. Dent reported receiving honoraria from Roche, Novartis, Lilly, Pfizer, Eisai, Merck, and AstraZeneca. Dr. Delaloge reported personal financial interests in AstraZeneca until 2018 and travel and accommodation support from AstraZeneca, Pfizer, Roche, and Pierre Fabre.

sworcester@mdedge.com

SOURCE: Dent R et al. ESMO Breast Cancer 2020, Abstract 139O

Adding the AKT inhibitor ipatasertib to paclitaxel may provide an overall survival (OS) benefit for inoperable locally advanced/metastatic triple-negative breast cancer (TNBC), according to final results of the phase 2 LOTUS trial.

The median OS was 25.8 months in patients who received ipatasertib plus paclitaxel and 16.9 months in patients who received paclitaxel plus placebo. Although this difference was not statistically significant, it was “clinically meaningful,” according to Rebecca Dent, MD, of the National Cancer Center Singapore. Dr. Dent presented OS data from the LOTUS trial at the European Society of Medical Oncology: Breast Cancer virtual meeting.

Previously reported data showed a progression-free survival benefit in the ipatasertib arm, compared with the placebo arm – 6.2 months and 4.9 months, respectively (Lancet Oncol. 2017 Oct;18[10]:1360-72). An enhanced effect was noted in patients with PIK3CA/AKT1/PTEN–altered tumors, but the OS data were not mature at the time of that primary analysis.
 

Patients, treatment, and safety

LOTUS participants had measurable locally advanced/metastatic TNBC that was previously untreated with systemic therapy, and they were stratified by prior adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status.

Patients were randomized 1:1 to receive paclitaxel at a dose of 80 mg/m² on days 1, 8, and 15 of each 28-day cycle plus either placebo (n = 62) or ipatasertib at a dose of 400 mg on days 1-21 (n = 62).

The safety results didn’t differ between the primary and updated results, Dr. Dent noted.

“What we can say is that the combination is extremely well tolerated, especially when we compare it to other targeted agents targeting this pathway,” she said. “What we do see is noticeable diarrhea ... [and] an increase in sensory neuropathy, which is not entirely unexpected.”

Subsequent systemic anticancer therapy was required in 77% of patients in the ipatasertib arm and 90% of patients in the placebo arm.
 

OS results

The final OS data show a numerical advantage for patients in the ipatasertib arm compared with the placebo arm. The 1-year OS was 83% in the ipatasertib arm and 68% in the placebo arm. The median OS was 25.8 months and 16.9 months, respectively (stratified hazard ratio, 0.80).

“This is a clinically meaningful improvement of 9 months in overall survival, which is indeed not too dissimilar to what we have seen in patients with PD-L1-positive TNBC who are receiving immune checkpoint inhibition in combination with chemotherapy,” Dr. Dent said.

However, the 95% confidence interval for the stratified OS hazard ratio crossed 1 (0.50-1.28). Therefore, the findings require confirmatory phase 3 trial results, Dr. Dent said.

The OS improvements with ipatasertib were seen “in all biomarker-defined subgroups – PTEN normal or low, PIK3CA/AKT1/PTEN altered or non-altered,” she said. OS benefits were more pronounced in patients with altered PIK3C/AKT1/PTEN status, but the numbers are too small to make definitive conclusions, according to Dr. Dent.
 

‘Promising’ results, confirmation needed

Invited discussant Suzette Delaloge, MD, head of the breast cancer department at Gustave Roussy, Paris, said the OS findings from LOTUS are “quite promising,” and the safety data are “reassuring.”

The findings are comparable to those of the recently published PAKT trial (J Clin Oncol. 2020 Feb 10;38[5]:423-33), she said, noting that “AKT inhibition in combination with paclitaxel deserves phase 3 development, and this is ongoing in major phase 3 trials.”

Dr. Delaloge also noted that the efficacy may not be limited to PIK3CA/AKT–altered tumors, and given the heterogeneity of TNBC – which may explain the differences seen among various studies – “it is very important that such phase 3 trials ideally involve extensive genomical definitions of tumors so that we understand what it is we are talking about and what is the real effect of the drug.”

“The adequate positioning of AKT inhibition in competition/complementation with other ongoing strategies remains to be defined,” she said. “I think these drugs are ready for translation to early phases.”

Dr. Dent said the results of LOTUS warrant confirmation in the ongoing, randomized phase 3 IPATunity130 trial , in which researchers are evaluating first-line ipatasertib plus paclitaxel for metastatic TNBC. She noted that the small sample sizes and heterogeneity of TNBC among LOTUS participants limited the interpretation of the findings.

In another trial, IPATunity170, researchers are evaluating the first-line role of ipatasertib plus paclitaxel and atezolizumab in locally advanced or metastatic TNBC.

“This is an exciting triplet combination that’s been evaluated already in the phase 1 setting, and now we have a phase 3 study evaluating the triplet,” Dr. Dent said.

The LOTUS trial was funded by Roche/Genentech. Dr. Dent reported receiving honoraria from Roche, Novartis, Lilly, Pfizer, Eisai, Merck, and AstraZeneca. Dr. Delaloge reported personal financial interests in AstraZeneca until 2018 and travel and accommodation support from AstraZeneca, Pfizer, Roche, and Pierre Fabre.

sworcester@mdedge.com

SOURCE: Dent R et al. ESMO Breast Cancer 2020, Abstract 139O

Adding the AKT inhibitor ipatasertib to paclitaxel may provide an overall survival (OS) benefit for inoperable locally advanced/metastatic triple-negative breast cancer (TNBC), according to final results of the phase 2 LOTUS trial.

The median OS was 25.8 months in patients who received ipatasertib plus paclitaxel and 16.9 months in patients who received paclitaxel plus placebo. Although this difference was not statistically significant, it was “clinically meaningful,” according to Rebecca Dent, MD, of the National Cancer Center Singapore. Dr. Dent presented OS data from the LOTUS trial at the European Society of Medical Oncology: Breast Cancer virtual meeting.

Previously reported data showed a progression-free survival benefit in the ipatasertib arm, compared with the placebo arm – 6.2 months and 4.9 months, respectively (Lancet Oncol. 2017 Oct;18[10]:1360-72). An enhanced effect was noted in patients with PIK3CA/AKT1/PTEN–altered tumors, but the OS data were not mature at the time of that primary analysis.
 

Patients, treatment, and safety

LOTUS participants had measurable locally advanced/metastatic TNBC that was previously untreated with systemic therapy, and they were stratified by prior adjuvant therapy, chemotherapy-free interval, and tumor immunohistochemistry PTEN status.

Patients were randomized 1:1 to receive paclitaxel at a dose of 80 mg/m² on days 1, 8, and 15 of each 28-day cycle plus either placebo (n = 62) or ipatasertib at a dose of 400 mg on days 1-21 (n = 62).

The safety results didn’t differ between the primary and updated results, Dr. Dent noted.

“What we can say is that the combination is extremely well tolerated, especially when we compare it to other targeted agents targeting this pathway,” she said. “What we do see is noticeable diarrhea ... [and] an increase in sensory neuropathy, which is not entirely unexpected.”

Subsequent systemic anticancer therapy was required in 77% of patients in the ipatasertib arm and 90% of patients in the placebo arm.
 

OS results

The final OS data show a numerical advantage for patients in the ipatasertib arm compared with the placebo arm. The 1-year OS was 83% in the ipatasertib arm and 68% in the placebo arm. The median OS was 25.8 months and 16.9 months, respectively (stratified hazard ratio, 0.80).

“This is a clinically meaningful improvement of 9 months in overall survival, which is indeed not too dissimilar to what we have seen in patients with PD-L1-positive TNBC who are receiving immune checkpoint inhibition in combination with chemotherapy,” Dr. Dent said.

However, the 95% confidence interval for the stratified OS hazard ratio crossed 1 (0.50-1.28). Therefore, the findings require confirmatory phase 3 trial results, Dr. Dent said.

The OS improvements with ipatasertib were seen “in all biomarker-defined subgroups – PTEN normal or low, PIK3CA/AKT1/PTEN altered or non-altered,” she said. OS benefits were more pronounced in patients with altered PIK3C/AKT1/PTEN status, but the numbers are too small to make definitive conclusions, according to Dr. Dent.
 

‘Promising’ results, confirmation needed

Invited discussant Suzette Delaloge, MD, head of the breast cancer department at Gustave Roussy, Paris, said the OS findings from LOTUS are “quite promising,” and the safety data are “reassuring.”

The findings are comparable to those of the recently published PAKT trial (J Clin Oncol. 2020 Feb 10;38[5]:423-33), she said, noting that “AKT inhibition in combination with paclitaxel deserves phase 3 development, and this is ongoing in major phase 3 trials.”

Dr. Delaloge also noted that the efficacy may not be limited to PIK3CA/AKT–altered tumors, and given the heterogeneity of TNBC – which may explain the differences seen among various studies – “it is very important that such phase 3 trials ideally involve extensive genomical definitions of tumors so that we understand what it is we are talking about and what is the real effect of the drug.”

“The adequate positioning of AKT inhibition in competition/complementation with other ongoing strategies remains to be defined,” she said. “I think these drugs are ready for translation to early phases.”

Dr. Dent said the results of LOTUS warrant confirmation in the ongoing, randomized phase 3 IPATunity130 trial , in which researchers are evaluating first-line ipatasertib plus paclitaxel for metastatic TNBC. She noted that the small sample sizes and heterogeneity of TNBC among LOTUS participants limited the interpretation of the findings.

In another trial, IPATunity170, researchers are evaluating the first-line role of ipatasertib plus paclitaxel and atezolizumab in locally advanced or metastatic TNBC.

“This is an exciting triplet combination that’s been evaluated already in the phase 1 setting, and now we have a phase 3 study evaluating the triplet,” Dr. Dent said.

The LOTUS trial was funded by Roche/Genentech. Dr. Dent reported receiving honoraria from Roche, Novartis, Lilly, Pfizer, Eisai, Merck, and AstraZeneca. Dr. Delaloge reported personal financial interests in AstraZeneca until 2018 and travel and accommodation support from AstraZeneca, Pfizer, Roche, and Pierre Fabre.

sworcester@mdedge.com

SOURCE: Dent R et al. ESMO Breast Cancer 2020, Abstract 139O

The incidence of central nervous system (CNS) tumors appears lower in Chinese children from Hong Kong than in U.S. children of Asian/Pacific Islander (API) descent or of any ethnicity, results of a population-based study suggest.

Adjusted incidence rates of CNS tumors were significantly higher among children from the U.S. Surveillance, Epidemiology, and End Results (SEER) database than among children from a cancer registry in Hong Kong.

Anthony P. Y. Liu, MBBS, MMedSc, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues reported these findings in JCO Global Oncology.

The Hong Kong cohort originally included 526 patients, but only 508 of them were included in the comparison with the SEER patients. The SEER cohorts included 447 patients of API descent and 5,047 patients of all ethnicities.

In all cohorts, patients were younger than 18 years of age and had been diagnosed with a primary CNS tumor during 1999-2016.
 

Results

Age-, sex-, and study period–adjusted incidence rates of CNS tumors were significantly higher in the SEER cohorts than in the Hong Kong cohort (P < .001). The adjusted incidence rates were:

• 2.51 per 100,000 children in the Hong Kong cohort.
• 3.26 per 100,000 children among APIs in the SEER cohort.
• 4.10 per 100,000 children among all ethnicities in the SEER cohort.

Incidence rates of most tumor types were significantly lower in the Hong Kong cohort than in the entire SEER cohort. This includes choroid plexus tumors (0.08 vs. 0.16; P = .045), ependymomas (0.18 vs. 0.31; P = .005), and glial and neuronal tumors (0.94 vs. 2.61; P < .001). However, incidence rates of germ cell tumors were significantly higher in the Hong Kong cohort (0.57 vs. 0.24; P < .001).

For the most part, there were no significant differences in incidence by histology between the Hong Kong cohort and the API SEER cohort. The exception was glial and neuronal tumors, for which the incidence rate was lower in the Hong Kong cohort than in the API SEER cohort (0.94 vs. 1.74; P < .001).

The 5-year overall survival rate was significantly lower in the Hong Kong cohort than in the API and entire SEER cohorts – 66.8% , 75.3%, and 78.7%, respectively (P < .001). This appears to be driven by inferior survival among Hong Kong patients with glial and neuronal tumors. For other tumor types, there were no significant differences in survival across the cohorts.
 

Interpretation

“Dr. Liu and colleagues have conducted a very nice epidemiological study, and their results suggest that the incidence of pediatric brain tumors is much lower in Hong Kong compared to the incidence in the United States,” noted Eric Bouffet, MD, of the University of Toronto.

“These results are intriguing, and it is clear that large epidemiological studies are needed to better understand the impact of ethnic, genetic, and socio-environmental factors linked to the incidence of childhood cancer, and in particular childhood brain tumors,” Dr. Bouffet added.

“My suspicion is that the lower incidence of brain tumors in Hong Kong may relate to the omission of patients who did not have a biopsy from the dataset,” said David Ziegler, MD, PhD, of the University of New South Wales in Kensington, Australia.

Dr. Liu and colleagues acknowledged that this study had limitations. The Hong Kong data do not represent the entire Chinese population, the SEER registry represents only 34.6% of the U.S. population, and the SEER registry has substandard ancestry designation for APIs. In addition, neither dataset included information on disease progression/recurrence or treatment details.

The study was supported by the American Lebanese Syrian Associated Charities and the Children’s Cancer Foundation, Hong Kong. Study authors disclosed relationships with MSD Oncology, Genentech, and Kazia Pharmaceutical.

Dr. Ziegler reported having no conflicts of interest. Dr. Bouffet disclosed relationships with Bristol-Myers Squibb and Roche.

SOURCE: Liu APY et al. JCO Glob Oncol. 2020 May 11. doi: 10.1200/JGO.19.00378.

The incidence of central nervous system (CNS) tumors appears lower in Chinese children from Hong Kong than in U.S. children of Asian/Pacific Islander (API) descent or of any ethnicity, results of a population-based study suggest.

Adjusted incidence rates of CNS tumors were significantly higher among children from the U.S. Surveillance, Epidemiology, and End Results (SEER) database than among children from a cancer registry in Hong Kong.

Anthony P. Y. Liu, MBBS, MMedSc, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues reported these findings in JCO Global Oncology.

The Hong Kong cohort originally included 526 patients, but only 508 of them were included in the comparison with the SEER patients. The SEER cohorts included 447 patients of API descent and 5,047 patients of all ethnicities.

In all cohorts, patients were younger than 18 years of age and had been diagnosed with a primary CNS tumor during 1999-2016.
 

Results

Age-, sex-, and study period–adjusted incidence rates of CNS tumors were significantly higher in the SEER cohorts than in the Hong Kong cohort (P < .001). The adjusted incidence rates were:

• 2.51 per 100,000 children in the Hong Kong cohort.
• 3.26 per 100,000 children among APIs in the SEER cohort.
• 4.10 per 100,000 children among all ethnicities in the SEER cohort.

Incidence rates of most tumor types were significantly lower in the Hong Kong cohort than in the entire SEER cohort. This includes choroid plexus tumors (0.08 vs. 0.16; P = .045), ependymomas (0.18 vs. 0.31; P = .005), and glial and neuronal tumors (0.94 vs. 2.61; P < .001). However, incidence rates of germ cell tumors were significantly higher in the Hong Kong cohort (0.57 vs. 0.24; P < .001).

For the most part, there were no significant differences in incidence by histology between the Hong Kong cohort and the API SEER cohort. The exception was glial and neuronal tumors, for which the incidence rate was lower in the Hong Kong cohort than in the API SEER cohort (0.94 vs. 1.74; P < .001).

The 5-year overall survival rate was significantly lower in the Hong Kong cohort than in the API and entire SEER cohorts – 66.8% , 75.3%, and 78.7%, respectively (P < .001). This appears to be driven by inferior survival among Hong Kong patients with glial and neuronal tumors. For other tumor types, there were no significant differences in survival across the cohorts.
 

Interpretation

“Dr. Liu and colleagues have conducted a very nice epidemiological study, and their results suggest that the incidence of pediatric brain tumors is much lower in Hong Kong compared to the incidence in the United States,” noted Eric Bouffet, MD, of the University of Toronto.

“These results are intriguing, and it is clear that large epidemiological studies are needed to better understand the impact of ethnic, genetic, and socio-environmental factors linked to the incidence of childhood cancer, and in particular childhood brain tumors,” Dr. Bouffet added.

“My suspicion is that the lower incidence of brain tumors in Hong Kong may relate to the omission of patients who did not have a biopsy from the dataset,” said David Ziegler, MD, PhD, of the University of New South Wales in Kensington, Australia.

Dr. Liu and colleagues acknowledged that this study had limitations. The Hong Kong data do not represent the entire Chinese population, the SEER registry represents only 34.6% of the U.S. population, and the SEER registry has substandard ancestry designation for APIs. In addition, neither dataset included information on disease progression/recurrence or treatment details.

The study was supported by the American Lebanese Syrian Associated Charities and the Children’s Cancer Foundation, Hong Kong. Study authors disclosed relationships with MSD Oncology, Genentech, and Kazia Pharmaceutical.

Dr. Ziegler reported having no conflicts of interest. Dr. Bouffet disclosed relationships with Bristol-Myers Squibb and Roche.

SOURCE: Liu APY et al. JCO Glob Oncol. 2020 May 11. doi: 10.1200/JGO.19.00378.

The incidence of central nervous system (CNS) tumors appears lower in Chinese children from Hong Kong than in U.S. children of Asian/Pacific Islander (API) descent or of any ethnicity, results of a population-based study suggest.

Adjusted incidence rates of CNS tumors were significantly higher among children from the U.S. Surveillance, Epidemiology, and End Results (SEER) database than among children from a cancer registry in Hong Kong.

Anthony P. Y. Liu, MBBS, MMedSc, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues reported these findings in JCO Global Oncology.

The Hong Kong cohort originally included 526 patients, but only 508 of them were included in the comparison with the SEER patients. The SEER cohorts included 447 patients of API descent and 5,047 patients of all ethnicities.

In all cohorts, patients were younger than 18 years of age and had been diagnosed with a primary CNS tumor during 1999-2016.
 

Results

Age-, sex-, and study period–adjusted incidence rates of CNS tumors were significantly higher in the SEER cohorts than in the Hong Kong cohort (P < .001). The adjusted incidence rates were:

• 2.51 per 100,000 children in the Hong Kong cohort.
• 3.26 per 100,000 children among APIs in the SEER cohort.
• 4.10 per 100,000 children among all ethnicities in the SEER cohort.

Incidence rates of most tumor types were significantly lower in the Hong Kong cohort than in the entire SEER cohort. This includes choroid plexus tumors (0.08 vs. 0.16; P = .045), ependymomas (0.18 vs. 0.31; P = .005), and glial and neuronal tumors (0.94 vs. 2.61; P < .001). However, incidence rates of germ cell tumors were significantly higher in the Hong Kong cohort (0.57 vs. 0.24; P < .001).

For the most part, there were no significant differences in incidence by histology between the Hong Kong cohort and the API SEER cohort. The exception was glial and neuronal tumors, for which the incidence rate was lower in the Hong Kong cohort than in the API SEER cohort (0.94 vs. 1.74; P < .001).

The 5-year overall survival rate was significantly lower in the Hong Kong cohort than in the API and entire SEER cohorts – 66.8% , 75.3%, and 78.7%, respectively (P < .001). This appears to be driven by inferior survival among Hong Kong patients with glial and neuronal tumors. For other tumor types, there were no significant differences in survival across the cohorts.
 

Interpretation

“Dr. Liu and colleagues have conducted a very nice epidemiological study, and their results suggest that the incidence of pediatric brain tumors is much lower in Hong Kong compared to the incidence in the United States,” noted Eric Bouffet, MD, of the University of Toronto.

“These results are intriguing, and it is clear that large epidemiological studies are needed to better understand the impact of ethnic, genetic, and socio-environmental factors linked to the incidence of childhood cancer, and in particular childhood brain tumors,” Dr. Bouffet added.

“My suspicion is that the lower incidence of brain tumors in Hong Kong may relate to the omission of patients who did not have a biopsy from the dataset,” said David Ziegler, MD, PhD, of the University of New South Wales in Kensington, Australia.

Dr. Liu and colleagues acknowledged that this study had limitations. The Hong Kong data do not represent the entire Chinese population, the SEER registry represents only 34.6% of the U.S. population, and the SEER registry has substandard ancestry designation for APIs. In addition, neither dataset included information on disease progression/recurrence or treatment details.

The study was supported by the American Lebanese Syrian Associated Charities and the Children’s Cancer Foundation, Hong Kong. Study authors disclosed relationships with MSD Oncology, Genentech, and Kazia Pharmaceutical.

Dr. Ziegler reported having no conflicts of interest. Dr. Bouffet disclosed relationships with Bristol-Myers Squibb and Roche.

SOURCE: Liu APY et al. JCO Glob Oncol. 2020 May 11. doi: 10.1200/JGO.19.00378.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, AGAF, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, AGAF, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

For patients with inflammatory bowel disease (IBD) who develop coronavirus disease of 2019 (COVID-19), corticosteroid use may significantly increase risk of severe disease, according to data from more than 500 patients.

Use of sulfasalazine or 5-aminosalicylates (5-ASAs) also increased risk of severe COVID-19, albeit to a lesser degree, reported co-lead authors Erica J. Brenner, MD, of University of North Carolina Children’s Hospital, Chapel Hill, and Ryan C. Ungaro, MD, of Icahn School of Medicine at Mount Sinai, New York, and colleagues.

In contrast, tumor necrosis factor (TNF) blockers were not an independent risk factor for severe COVID-19.

“As TNF antagonists are the most commonly prescribed biologic therapy for patients with IBD, these initial findings should be reassuring to the large number of patients receiving TNF antagonist therapy and support their continued use during this current pandemic,” the investigators wrote in Gastroenterology.

These conclusions were drawn from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) database, a large registry actively collecting data from clinicians around the world.

In the present analysis, which involved 525 patients from 33 countries, the investigators searched for independent risk factors for severe COVID-19. Various factors were tested through multivariable regression, including age, comorbidities, usage of specific medications, and more.

The primary outcome was defined by a composite of hospitalization, ventilator use, or death, while secondary outcomes included a composite of hospitalization or death, as well as death alone.

The analysis revealed that patients receiving corticosteroids had an adjusted odds ratio of 6.87 (95% confidence interval, 2.30-20.51) for severe COVID-19, with increased risks also detected for both secondary outcomes. In contrast, TNF antagonist use was not significantly associated with the primary outcome; in fact, a possible protective effect was detected for hospitalization or death (aOR, 0.60; 95% CI, 0.38-0.96).

The investigators noted that the above findings aligned with extensive literature concerning infectious complications with corticosteroid use and “more recent commentary” surrounding TNF antagonists. Similarly, increased age and the presence of at least two comorbidities were each independently associated with increased risk of severe COVID-19, both of which are correlations that have been previously described.

But the threefold increased risk of severe COVID-19 associated with use of sulfasalazine or 5-ASAs (aOR, 3.14; 95% CI, 1.28-7.71) was a “surprising” finding, the investigators noted.

“In a direct comparison, we observed that 5-ASA/sulfasalazine–treated patients fared worse than those treated with TNF inhibitors,” the investigators wrote. “Although we cannot exclude unmeasured confounding, further exploration of biological mechanisms is warranted.”

David T. Rubin, MD, AGAF, of the University of Chicago agreed that the finding deserves further investigation, particularly since sulfasalazine and 5-ASAs represent the second most commonly prescribed medication class for IBD.

“The risk with 5-ASAs is of interest but not well explained by what we know about the safety or the mechanism of these therapies,” Dr. Rubin said. “Clearly, more work is needed.”

The risks associated with corticosteroids were particularly concerning, Dr. Rubin said, because 10%-20% of patients with IBD may be taking corticosteroids at any given time.

“Steroids are still the number one prescribed therapy for Crohn’s and colitis,” he said.

Still, Dr. Rubin advised against abrupt changes to drug regimens, especially if they are effectively controlling IBD.

“Patients should stay on their existing therapies and stay in remission,” Dr. Rubin said. “If you stop your therapies … you are more likely to relapse. When you relapse, you’re more likely to need steroids as a rescue therapy … or end up in the hospital, and those are not places we want you to be.”

Despite the risks associated with steroids and sulfasalazine/5-ASAs, Dr. Rubin had an optimistic take on the study, calling the findings “very reassuring” because they support continued usage of TNF inhibitors and other biologic agents during the pandemic. He also noted that the SECURE-IBD registry, which he has contributed to, represents “an extraordinary effort” from around the world.

“[This is] an unprecedented collaboration across a scale and timeframe that has really never been seen before in our field, and I would hazard a guess that it’s probably never been seen in most other fields right now,” he said.

Clinicians seeking more information about managing patients with IBD during the COVID-19 pandemic can find guidance in the recent AGA practice update, of which Dr. Rubin was the lead author. Clinicians who would like to contribute to the SECURE-IBD registry may do so at covidibd.org. The registry now includes more than 1,000 patients.

The study was funded by Clinical and Translational Science Award grants through Dr. Ungaro. The investigators disclosed relationships with Takeda, Janssen, Pfizer, and others. Dr. Rubin disclosed relationships with Gilead, Eli Lilly, Shire, and others.

Check out the AGA COVID-19 Resource Library for new clinical guidance, education, research and physician resources, including recent guidance on how to treat patients with IBD during the pandemic, at www.gastro.org/covid.

SOURCE: Brenner EJ et al. Gastroenterology. 2020 May 18. doi: 10.1053/j.gastro.2020.05.032.

Maternal vascular malperfusion and intervillous thrombi were more common in the placentas of women infected with SARS-CoV-2, compared with historic controls, report researchers who conducted the first-of-its-kind case series in the English literature. Nevertheless, the neonates in the report appear to be healthy so far and all tested negative for the virus.

Although the series examining placentas from 16 women is small, it carries a larger implication – that increased antenatal surveillance for pregnant women infected with SARS-CoV-2 may be indicated, the researchers noted.

Furthermore, the results could align with other reports of coagulation and vascular abnormalities among people with COVID-19. “I would say that our findings fit into that larger picture of vascular injury. This is developing, and there are some significant ways that these feeder vessels to the placenta are different, but if this is the emerging paradigm, our findings can fit into it,” Jeffrey A. Goldstein, MD, PhD, assistant professor of pathology at Northwestern University, Chicago, said in an interview.

The research was published in the American Journal of Clinical Pathology.

Prior case series reported in Wuhan, China, do not currently suggest that pregnant women are more likely to experience severe COVID-19, in contrast to observations during severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. “However,” the researchers noted, “adverse perinatal outcomes have been reported, including increased risks of miscarriage, preeclampsia, preterm birth, and stillbirth.”

To learn more, Dr. Goldstein, lead author Elisheva D. Shanes, MD, and colleagues examined the histology of placentas from women with COVID-19 giving birth between March 18 and May 5, 2020. They compared these placentas with over 17,000 historic controls and 215 women who had their placentas evaluated as part of a melanoma history study.

A total of 10 women were diagnosed with COVID-19 upon presentation to labor and delivery, 4 others were diagnosed approximately 1 month before delivery and the remaining 2 within 1 week of delivery. Ten of the patients were symptomatic and two required oxygen. None of the patients received intubation or died. A total of 14 patients delivered at term, 1 delivered at 34 weeks, and the remaining case experienced a 16-week intrauterine fetal demise (IUFD). The IUFD was excluded from subsequent statistical analysis.

The neonates each had a 5-minute Apgar score of 9. Most infants were discharged on the first or second day of life, and there were no neonatal deaths.
 

Key findings

Of the 15 placentas, 12 featured maternal vascular malperfusion. This rate was significantly higher than historic controls (P = .046) and melanoma study controls (P = .001).

Specific features varied between groups, with decidual arteriopathy, atherosis and fibrinoid necrosis of maternal vessels, and mural hypertrophy of membrane arterioles observed more often in COVID-19 cases than in all historical controls. In addition, peripheral infarctions, decidual arteriopathy, atherosis, and fibrinoid necrosis, and mural hypertrophy being more common in COVID-19 cases than in placentas of women with a history of melanoma.

In contrast, features of fetal vascular malperfusion were observed in 12 of 15 cases, but not at rates significantly different from the control groups. Chorangiosis, villous edema, and intervillous thrombi also were more common in the COVID-19 cohort.

Dr. Goldstein was surprised they did not observe much acute or chronic inflammation. “We see chronic inflammation in the placenta in response to many viruses, such as cytomegalovirus, so you might expect similar findings, but we didn’t see any increase above the controls.”

There are a couple of case reports of histiocytic intervillositis – a particularly severe form of chronic inflammation – associated with COVID-19, “but we didn’t see that in our study,” he added.
 

Clinical implications

The healthy neonatal outcomes reported in the study occurred despite the placental injury, which may be caused by the redundancy built into placentas for delivering oxygen and nutrients and for removing waste.

The negative COVID-19 test results in all infants also supports existing evidence that vertical transmission of the virus is uncommon. The finding also suggests that any damage to the placenta is likely related to maternal infection.

Only one mother in the COVID-19 cohort was hypertensive, which surprised the researchers because intervillous thrombi have been associated with maternal high blood pressure. “In the context of research suggesting an increase of thrombotic and thromboembolic disorders in COVID-19,” the researchers noted, “these may represent placental formation or deposition of thrombi in response to the virus.”

One of the priorities for the researchers going forward is to monitor the longer-term outcomes of the infants, Dr. Goldstein said. “We know the people in utero during the 1918-1919 flu pandemic had higher rates of heart disease and other long-term problems, so we want to be on the lookout for something similar.”
 

Valuable insight

“This is a comprehensive case series of this topic, with findings worth noting and sharing in a timely fashion,” Karen Mestan, MD, associate professor of pediatrics within the division of neonatology at Northwestern University, said when asked to comment on the study.

“The information is valuable to neonatologists as the short- and long-term effects of COVID-19 exposure on newborn infants are still largely unknown,” she added. “Details of placental pathology provide emerging insight and may help us understand mother-baby vertical transmission during the current pandemic.”

Dr. Goldstein and Dr. Mestan had no relevant financial disclosures.

SOURCE: Shanes ED et al. Am J Clin Pathol. 2020 May 22. doi: 10.1093/ajcp/aqaa089.

Maternal vascular malperfusion and intervillous thrombi were more common in the placentas of women infected with SARS-CoV-2, compared with historic controls, report researchers who conducted the first-of-its-kind case series in the English literature. Nevertheless, the neonates in the report appear to be healthy so far and all tested negative for the virus.

Although the series examining placentas from 16 women is small, it carries a larger implication – that increased antenatal surveillance for pregnant women infected with SARS-CoV-2 may be indicated, the researchers noted.

Furthermore, the results could align with other reports of coagulation and vascular abnormalities among people with COVID-19. “I would say that our findings fit into that larger picture of vascular injury. This is developing, and there are some significant ways that these feeder vessels to the placenta are different, but if this is the emerging paradigm, our findings can fit into it,” Jeffrey A. Goldstein, MD, PhD, assistant professor of pathology at Northwestern University, Chicago, said in an interview.

The research was published in the American Journal of Clinical Pathology.

Prior case series reported in Wuhan, China, do not currently suggest that pregnant women are more likely to experience severe COVID-19, in contrast to observations during severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. “However,” the researchers noted, “adverse perinatal outcomes have been reported, including increased risks of miscarriage, preeclampsia, preterm birth, and stillbirth.”

To learn more, Dr. Goldstein, lead author Elisheva D. Shanes, MD, and colleagues examined the histology of placentas from women with COVID-19 giving birth between March 18 and May 5, 2020. They compared these placentas with over 17,000 historic controls and 215 women who had their placentas evaluated as part of a melanoma history study.

A total of 10 women were diagnosed with COVID-19 upon presentation to labor and delivery, 4 others were diagnosed approximately 1 month before delivery and the remaining 2 within 1 week of delivery. Ten of the patients were symptomatic and two required oxygen. None of the patients received intubation or died. A total of 14 patients delivered at term, 1 delivered at 34 weeks, and the remaining case experienced a 16-week intrauterine fetal demise (IUFD). The IUFD was excluded from subsequent statistical analysis.

The neonates each had a 5-minute Apgar score of 9. Most infants were discharged on the first or second day of life, and there were no neonatal deaths.
 

Key findings

Of the 15 placentas, 12 featured maternal vascular malperfusion. This rate was significantly higher than historic controls (P = .046) and melanoma study controls (P = .001).

Specific features varied between groups, with decidual arteriopathy, atherosis and fibrinoid necrosis of maternal vessels, and mural hypertrophy of membrane arterioles observed more often in COVID-19 cases than in all historical controls. In addition, peripheral infarctions, decidual arteriopathy, atherosis, and fibrinoid necrosis, and mural hypertrophy being more common in COVID-19 cases than in placentas of women with a history of melanoma.

In contrast, features of fetal vascular malperfusion were observed in 12 of 15 cases, but not at rates significantly different from the control groups. Chorangiosis, villous edema, and intervillous thrombi also were more common in the COVID-19 cohort.

Dr. Goldstein was surprised they did not observe much acute or chronic inflammation. “We see chronic inflammation in the placenta in response to many viruses, such as cytomegalovirus, so you might expect similar findings, but we didn’t see any increase above the controls.”

There are a couple of case reports of histiocytic intervillositis – a particularly severe form of chronic inflammation – associated with COVID-19, “but we didn’t see that in our study,” he added.
 

Clinical implications

The healthy neonatal outcomes reported in the study occurred despite the placental injury, which may be caused by the redundancy built into placentas for delivering oxygen and nutrients and for removing waste.

The negative COVID-19 test results in all infants also supports existing evidence that vertical transmission of the virus is uncommon. The finding also suggests that any damage to the placenta is likely related to maternal infection.

Only one mother in the COVID-19 cohort was hypertensive, which surprised the researchers because intervillous thrombi have been associated with maternal high blood pressure. “In the context of research suggesting an increase of thrombotic and thromboembolic disorders in COVID-19,” the researchers noted, “these may represent placental formation or deposition of thrombi in response to the virus.”

One of the priorities for the researchers going forward is to monitor the longer-term outcomes of the infants, Dr. Goldstein said. “We know the people in utero during the 1918-1919 flu pandemic had higher rates of heart disease and other long-term problems, so we want to be on the lookout for something similar.”
 

Valuable insight

“This is a comprehensive case series of this topic, with findings worth noting and sharing in a timely fashion,” Karen Mestan, MD, associate professor of pediatrics within the division of neonatology at Northwestern University, said when asked to comment on the study.

“The information is valuable to neonatologists as the short- and long-term effects of COVID-19 exposure on newborn infants are still largely unknown,” she added. “Details of placental pathology provide emerging insight and may help us understand mother-baby vertical transmission during the current pandemic.”

Dr. Goldstein and Dr. Mestan had no relevant financial disclosures.

SOURCE: Shanes ED et al. Am J Clin Pathol. 2020 May 22. doi: 10.1093/ajcp/aqaa089.

Maternal vascular malperfusion and intervillous thrombi were more common in the placentas of women infected with SARS-CoV-2, compared with historic controls, report researchers who conducted the first-of-its-kind case series in the English literature. Nevertheless, the neonates in the report appear to be healthy so far and all tested negative for the virus.

Although the series examining placentas from 16 women is small, it carries a larger implication – that increased antenatal surveillance for pregnant women infected with SARS-CoV-2 may be indicated, the researchers noted.

Furthermore, the results could align with other reports of coagulation and vascular abnormalities among people with COVID-19. “I would say that our findings fit into that larger picture of vascular injury. This is developing, and there are some significant ways that these feeder vessels to the placenta are different, but if this is the emerging paradigm, our findings can fit into it,” Jeffrey A. Goldstein, MD, PhD, assistant professor of pathology at Northwestern University, Chicago, said in an interview.

The research was published in the American Journal of Clinical Pathology.

Prior case series reported in Wuhan, China, do not currently suggest that pregnant women are more likely to experience severe COVID-19, in contrast to observations during severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. “However,” the researchers noted, “adverse perinatal outcomes have been reported, including increased risks of miscarriage, preeclampsia, preterm birth, and stillbirth.”

To learn more, Dr. Goldstein, lead author Elisheva D. Shanes, MD, and colleagues examined the histology of placentas from women with COVID-19 giving birth between March 18 and May 5, 2020. They compared these placentas with over 17,000 historic controls and 215 women who had their placentas evaluated as part of a melanoma history study.

A total of 10 women were diagnosed with COVID-19 upon presentation to labor and delivery, 4 others were diagnosed approximately 1 month before delivery and the remaining 2 within 1 week of delivery. Ten of the patients were symptomatic and two required oxygen. None of the patients received intubation or died. A total of 14 patients delivered at term, 1 delivered at 34 weeks, and the remaining case experienced a 16-week intrauterine fetal demise (IUFD). The IUFD was excluded from subsequent statistical analysis.

The neonates each had a 5-minute Apgar score of 9. Most infants were discharged on the first or second day of life, and there were no neonatal deaths.
 

Key findings

Of the 15 placentas, 12 featured maternal vascular malperfusion. This rate was significantly higher than historic controls (P = .046) and melanoma study controls (P = .001).

Specific features varied between groups, with decidual arteriopathy, atherosis and fibrinoid necrosis of maternal vessels, and mural hypertrophy of membrane arterioles observed more often in COVID-19 cases than in all historical controls. In addition, peripheral infarctions, decidual arteriopathy, atherosis, and fibrinoid necrosis, and mural hypertrophy being more common in COVID-19 cases than in placentas of women with a history of melanoma.

In contrast, features of fetal vascular malperfusion were observed in 12 of 15 cases, but not at rates significantly different from the control groups. Chorangiosis, villous edema, and intervillous thrombi also were more common in the COVID-19 cohort.

Dr. Goldstein was surprised they did not observe much acute or chronic inflammation. “We see chronic inflammation in the placenta in response to many viruses, such as cytomegalovirus, so you might expect similar findings, but we didn’t see any increase above the controls.”

There are a couple of case reports of histiocytic intervillositis – a particularly severe form of chronic inflammation – associated with COVID-19, “but we didn’t see that in our study,” he added.
 

Clinical implications

The healthy neonatal outcomes reported in the study occurred despite the placental injury, which may be caused by the redundancy built into placentas for delivering oxygen and nutrients and for removing waste.

The negative COVID-19 test results in all infants also supports existing evidence that vertical transmission of the virus is uncommon. The finding also suggests that any damage to the placenta is likely related to maternal infection.

Only one mother in the COVID-19 cohort was hypertensive, which surprised the researchers because intervillous thrombi have been associated with maternal high blood pressure. “In the context of research suggesting an increase of thrombotic and thromboembolic disorders in COVID-19,” the researchers noted, “these may represent placental formation or deposition of thrombi in response to the virus.”

One of the priorities for the researchers going forward is to monitor the longer-term outcomes of the infants, Dr. Goldstein said. “We know the people in utero during the 1918-1919 flu pandemic had higher rates of heart disease and other long-term problems, so we want to be on the lookout for something similar.”
 

Valuable insight

“This is a comprehensive case series of this topic, with findings worth noting and sharing in a timely fashion,” Karen Mestan, MD, associate professor of pediatrics within the division of neonatology at Northwestern University, said when asked to comment on the study.

“The information is valuable to neonatologists as the short- and long-term effects of COVID-19 exposure on newborn infants are still largely unknown,” she added. “Details of placental pathology provide emerging insight and may help us understand mother-baby vertical transmission during the current pandemic.”

Dr. Goldstein and Dr. Mestan had no relevant financial disclosures.

SOURCE: Shanes ED et al. Am J Clin Pathol. 2020 May 22. doi: 10.1093/ajcp/aqaa089.