Correct answer: B. Selenium exposure. 
 
Rationale 
Helicobacter pylori infection is by far the most important risk factor for gastric cancer worldwide. Less common risk factors for gastric cancer include Lynch syndrome, Peutz-Jeghers syndrome, Menetrier's disease, and germline mutations in the CDH gene (encoding E-cadherin). However, there is some evidence that selenium, as well as high consumption of fruits and vegetables, may have protective effects against gastric cancer.  
 
References  
de Martel C et al. Gastroenterol Clin North Am. 2013 Jun;42(2):219-40.  
Giardiello FM et al. N Engl J Med. 1987 Jun 11;316(24):1511-4.  
Qiao YL et al. J Natl Cancer Inst. 2009 Apr 1;101(7):507-18. 

Correct answer: B. Selenium exposure. 
 
Rationale 
Helicobacter pylori infection is by far the most important risk factor for gastric cancer worldwide. Less common risk factors for gastric cancer include Lynch syndrome, Peutz-Jeghers syndrome, Menetrier's disease, and germline mutations in the CDH gene (encoding E-cadherin). However, there is some evidence that selenium, as well as high consumption of fruits and vegetables, may have protective effects against gastric cancer.  
 
References  
de Martel C et al. Gastroenterol Clin North Am. 2013 Jun;42(2):219-40.  
Giardiello FM et al. N Engl J Med. 1987 Jun 11;316(24):1511-4.  
Qiao YL et al. J Natl Cancer Inst. 2009 Apr 1;101(7):507-18. 

Correct answer: B. Selenium exposure. 
 
Rationale 
Helicobacter pylori infection is by far the most important risk factor for gastric cancer worldwide. Less common risk factors for gastric cancer include Lynch syndrome, Peutz-Jeghers syndrome, Menetrier's disease, and germline mutations in the CDH gene (encoding E-cadherin). However, there is some evidence that selenium, as well as high consumption of fruits and vegetables, may have protective effects against gastric cancer.  
 
References  
de Martel C et al. Gastroenterol Clin North Am. 2013 Jun;42(2):219-40.  
Giardiello FM et al. N Engl J Med. 1987 Jun 11;316(24):1511-4.  
Qiao YL et al. J Natl Cancer Inst. 2009 Apr 1;101(7):507-18. 

Correct answer: E. Cervical dysplasia. 
 
Rationale  
In a nationwide cohort study, women with Crohn's disease and ulcerative colitis were found to have an increased risk of cervical dysplasia. Patients with ulcerative colitis had increased risks of low- and high-grade squamous intraepithelial lesions, whereas patients with Crohn's disease also had increased risks of cervical cancer. Age-appropriate screening with pap smears is important for women diagnosed with inflammatory bowel disease regardless of treatment type.  
 
Reference  
Rungoe et al. Clin Gastroenterol Hepatol. 2015 Apr;13(4):693-700.e1.

Correct answer: E. Cervical dysplasia. 
 
Rationale  
In a nationwide cohort study, women with Crohn's disease and ulcerative colitis were found to have an increased risk of cervical dysplasia. Patients with ulcerative colitis had increased risks of low- and high-grade squamous intraepithelial lesions, whereas patients with Crohn's disease also had increased risks of cervical cancer. Age-appropriate screening with pap smears is important for women diagnosed with inflammatory bowel disease regardless of treatment type.  
 
Reference  
Rungoe et al. Clin Gastroenterol Hepatol. 2015 Apr;13(4):693-700.e1.

Correct answer: E. Cervical dysplasia. 
 
Rationale  
In a nationwide cohort study, women with Crohn's disease and ulcerative colitis were found to have an increased risk of cervical dysplasia. Patients with ulcerative colitis had increased risks of low- and high-grade squamous intraepithelial lesions, whereas patients with Crohn's disease also had increased risks of cervical cancer. Age-appropriate screening with pap smears is important for women diagnosed with inflammatory bowel disease regardless of treatment type.  
 
Reference  
Rungoe et al. Clin Gastroenterol Hepatol. 2015 Apr;13(4):693-700.e1.

Renal function should be considered when determining whether to pick ticagrelor-aspirin or clopidogrel-aspirin as the antiplatelet therapy for patients with minor stroke, according to new research.

The study, which was conducted in 202 centers in China and published in Annals of Internal Medicine, indicates that when patients had normal kidney function, ticagrelor-aspirin, compared with clopidogrel-aspirin, substantially reduced the risk for recurrent stroke within 90 days of follow-up.

However, this effect was not seen in patients with mildly, moderately or severely decreased kidney function.

Rates of severe or moderate bleeding did not differ substantially between the two treatments.
 

Results gleaned from CHANCE-2 data

The researchers, led by Anxin Wang, PhD, from Capital Medical University in Beijing, conducted a post hoc analysis of the CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial.

The trial included 6,378 patients who carried cytochrome P450 2C19 (CYP2C19) loss-of-function (LOF) alleles who had experienced a minor stroke or transient ischemic attack.

Patients received either ticagrelor-aspirin or clopidogrel-aspirin, and their renal function was measured by estimated glomerular filtration rate. The authors listed as a limitation that no data were available on the presence of albuminuria or proteinuria.

The researchers investigated what effect renal function had on the efficacy and safety of the therapies.
 

Differences in the therapies

Clopidogrel-aspirin is often recommended for preventing stroke. It can reduce thrombotic risk in patients with impaired kidney function, the authors noted. Ticagrelor can provide greater, faster, and more consistent P2Y12 inhibition than clopidogrel, and evidence shows it is effective in preventing stroke recurrence, particularly in people carrying CYP2C19 LOF alleles.

When people have reduced kidney function, clopidogrel may be harder to clear than ticagrelor and there may be increased plasma concentrations, so function is important to consider when choosing an antiplatelet therapy, the authors wrote.
 

Choice may come down to cost

Geoffrey Barnes, MD, MSc, associate professor of vascular and cardiovascular medicine at University of Michigan Medicine in Ann Arbor, said in an interview that there has been momentum toward ticagrelor as a more potent choice than clopidogrel not just in populations with minor stroke but for people with MI and coronary stents.

He said he found the results surprising and was intrigued that this paper suggests looking more skeptically at ticagrelor when kidney function is impaired.

Still, the choice may also come down to what the patient can afford at the pharmacy, he said.

“The reality is many patients still get clopidogrel either because that’s what their physicians have been prescribing for well over a decade or because of cost issues, and clopidogrel, for many patients, can be less expensive,” Dr. Barnes noted.

He said he would like to see more study in different populations as the prevalence of people carrying CYP2C19 allele differs by race and results might be different in a non-Asian population. That allele is thought to affect how clopidogrel is metabolized.
 

Study should spur more research

Nada El Husseini, MD, associate professor of neurology and Duke Telestroke Medical Director at Duke University Medical Center, Durham, N.C., said the study is hypothesis generating, but shouldn’t be thought of as the last word on the subject.

She pointed out some additional limitations of the study, including that it was a post hoc analysis. She explained that the question researchers asked in this study – about effect of kidney function on the safety and efficacy of the therapies – was not the focus of the original CHANCE-2 study, and, as such, the post hoc study may have been underpowered to answer the renal function question.

The authors acknowledged that limitation, noting that “the proportion of patients with severely decreased renal function was low.”

Among 6,378 patients, 4,050 (63.5%) had normal kidney function, 2,010 (31.5%) had mildly decreased function, and 318 (5.0%) had moderately to severely decreased function.

The study was funded by the Ministry of Science and Technology of the People’s Republic of China, the Beijing Municipal Science and Technology Commission, the Chinese Stroke Association, the National Science and Technology Major Project and the Beijing Municipal Administration of Hospitals Incubating Program). Salubris Pharmaceuticals contributed ticagrelor and, clopidogrel at no cost and with no restrictions. Dr. Wang reported no relevant financial relationships. Dr. Barnes and Dr. El Husseini reported no relevant financial relationships.

Renal function should be considered when determining whether to pick ticagrelor-aspirin or clopidogrel-aspirin as the antiplatelet therapy for patients with minor stroke, according to new research.

The study, which was conducted in 202 centers in China and published in Annals of Internal Medicine, indicates that when patients had normal kidney function, ticagrelor-aspirin, compared with clopidogrel-aspirin, substantially reduced the risk for recurrent stroke within 90 days of follow-up.

However, this effect was not seen in patients with mildly, moderately or severely decreased kidney function.

Rates of severe or moderate bleeding did not differ substantially between the two treatments.
 

Results gleaned from CHANCE-2 data

The researchers, led by Anxin Wang, PhD, from Capital Medical University in Beijing, conducted a post hoc analysis of the CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial.

The trial included 6,378 patients who carried cytochrome P450 2C19 (CYP2C19) loss-of-function (LOF) alleles who had experienced a minor stroke or transient ischemic attack.

Patients received either ticagrelor-aspirin or clopidogrel-aspirin, and their renal function was measured by estimated glomerular filtration rate. The authors listed as a limitation that no data were available on the presence of albuminuria or proteinuria.

The researchers investigated what effect renal function had on the efficacy and safety of the therapies.
 

Differences in the therapies

Clopidogrel-aspirin is often recommended for preventing stroke. It can reduce thrombotic risk in patients with impaired kidney function, the authors noted. Ticagrelor can provide greater, faster, and more consistent P2Y12 inhibition than clopidogrel, and evidence shows it is effective in preventing stroke recurrence, particularly in people carrying CYP2C19 LOF alleles.

When people have reduced kidney function, clopidogrel may be harder to clear than ticagrelor and there may be increased plasma concentrations, so function is important to consider when choosing an antiplatelet therapy, the authors wrote.
 

Choice may come down to cost

Geoffrey Barnes, MD, MSc, associate professor of vascular and cardiovascular medicine at University of Michigan Medicine in Ann Arbor, said in an interview that there has been momentum toward ticagrelor as a more potent choice than clopidogrel not just in populations with minor stroke but for people with MI and coronary stents.

He said he found the results surprising and was intrigued that this paper suggests looking more skeptically at ticagrelor when kidney function is impaired.

Still, the choice may also come down to what the patient can afford at the pharmacy, he said.

“The reality is many patients still get clopidogrel either because that’s what their physicians have been prescribing for well over a decade or because of cost issues, and clopidogrel, for many patients, can be less expensive,” Dr. Barnes noted.

He said he would like to see more study in different populations as the prevalence of people carrying CYP2C19 allele differs by race and results might be different in a non-Asian population. That allele is thought to affect how clopidogrel is metabolized.
 

Study should spur more research

Nada El Husseini, MD, associate professor of neurology and Duke Telestroke Medical Director at Duke University Medical Center, Durham, N.C., said the study is hypothesis generating, but shouldn’t be thought of as the last word on the subject.

She pointed out some additional limitations of the study, including that it was a post hoc analysis. She explained that the question researchers asked in this study – about effect of kidney function on the safety and efficacy of the therapies – was not the focus of the original CHANCE-2 study, and, as such, the post hoc study may have been underpowered to answer the renal function question.

The authors acknowledged that limitation, noting that “the proportion of patients with severely decreased renal function was low.”

Among 6,378 patients, 4,050 (63.5%) had normal kidney function, 2,010 (31.5%) had mildly decreased function, and 318 (5.0%) had moderately to severely decreased function.

The study was funded by the Ministry of Science and Technology of the People’s Republic of China, the Beijing Municipal Science and Technology Commission, the Chinese Stroke Association, the National Science and Technology Major Project and the Beijing Municipal Administration of Hospitals Incubating Program). Salubris Pharmaceuticals contributed ticagrelor and, clopidogrel at no cost and with no restrictions. Dr. Wang reported no relevant financial relationships. Dr. Barnes and Dr. El Husseini reported no relevant financial relationships.

Renal function should be considered when determining whether to pick ticagrelor-aspirin or clopidogrel-aspirin as the antiplatelet therapy for patients with minor stroke, according to new research.

The study, which was conducted in 202 centers in China and published in Annals of Internal Medicine, indicates that when patients had normal kidney function, ticagrelor-aspirin, compared with clopidogrel-aspirin, substantially reduced the risk for recurrent stroke within 90 days of follow-up.

However, this effect was not seen in patients with mildly, moderately or severely decreased kidney function.

Rates of severe or moderate bleeding did not differ substantially between the two treatments.
 

Results gleaned from CHANCE-2 data

The researchers, led by Anxin Wang, PhD, from Capital Medical University in Beijing, conducted a post hoc analysis of the CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) trial.

The trial included 6,378 patients who carried cytochrome P450 2C19 (CYP2C19) loss-of-function (LOF) alleles who had experienced a minor stroke or transient ischemic attack.

Patients received either ticagrelor-aspirin or clopidogrel-aspirin, and their renal function was measured by estimated glomerular filtration rate. The authors listed as a limitation that no data were available on the presence of albuminuria or proteinuria.

The researchers investigated what effect renal function had on the efficacy and safety of the therapies.
 

Differences in the therapies

Clopidogrel-aspirin is often recommended for preventing stroke. It can reduce thrombotic risk in patients with impaired kidney function, the authors noted. Ticagrelor can provide greater, faster, and more consistent P2Y12 inhibition than clopidogrel, and evidence shows it is effective in preventing stroke recurrence, particularly in people carrying CYP2C19 LOF alleles.

When people have reduced kidney function, clopidogrel may be harder to clear than ticagrelor and there may be increased plasma concentrations, so function is important to consider when choosing an antiplatelet therapy, the authors wrote.
 

Choice may come down to cost

Geoffrey Barnes, MD, MSc, associate professor of vascular and cardiovascular medicine at University of Michigan Medicine in Ann Arbor, said in an interview that there has been momentum toward ticagrelor as a more potent choice than clopidogrel not just in populations with minor stroke but for people with MI and coronary stents.

He said he found the results surprising and was intrigued that this paper suggests looking more skeptically at ticagrelor when kidney function is impaired.

Still, the choice may also come down to what the patient can afford at the pharmacy, he said.

“The reality is many patients still get clopidogrel either because that’s what their physicians have been prescribing for well over a decade or because of cost issues, and clopidogrel, for many patients, can be less expensive,” Dr. Barnes noted.

He said he would like to see more study in different populations as the prevalence of people carrying CYP2C19 allele differs by race and results might be different in a non-Asian population. That allele is thought to affect how clopidogrel is metabolized.
 

Study should spur more research

Nada El Husseini, MD, associate professor of neurology and Duke Telestroke Medical Director at Duke University Medical Center, Durham, N.C., said the study is hypothesis generating, but shouldn’t be thought of as the last word on the subject.

She pointed out some additional limitations of the study, including that it was a post hoc analysis. She explained that the question researchers asked in this study – about effect of kidney function on the safety and efficacy of the therapies – was not the focus of the original CHANCE-2 study, and, as such, the post hoc study may have been underpowered to answer the renal function question.

The authors acknowledged that limitation, noting that “the proportion of patients with severely decreased renal function was low.”

Among 6,378 patients, 4,050 (63.5%) had normal kidney function, 2,010 (31.5%) had mildly decreased function, and 318 (5.0%) had moderately to severely decreased function.

The study was funded by the Ministry of Science and Technology of the People’s Republic of China, the Beijing Municipal Science and Technology Commission, the Chinese Stroke Association, the National Science and Technology Major Project and the Beijing Municipal Administration of Hospitals Incubating Program). Salubris Pharmaceuticals contributed ticagrelor and, clopidogrel at no cost and with no restrictions. Dr. Wang reported no relevant financial relationships. Dr. Barnes and Dr. El Husseini reported no relevant financial relationships.

The effectiveness of up to three doses of COVID-19 vaccine was moderate overall and significantly lower among individuals with immunocompromising conditions, compared with the general population during the period of Omicron dominance, according to an analysis of data from more than 34,000 hospitalizations.

Previous studies have suggested lower COVID-19 vaccine effectiveness among immunocompromised individuals, compared with healthy individuals from the general population, but data from the period in which Omicron subvariants have been dominant are limited, wrote Amadea Britton, MD, of the Centers for Disease Control and Prevention’s COVID-19 Emergency Response Team, and colleagues.

The CDC currently recommends an expanded primary vaccine series of three doses of an mRNA vaccine, and the Advisory Committee on Immunization Practices has recommended a fourth dose with the new bivalent booster that contains elements of the Omicron variant, the researchers noted.

In a study published in the CDC’s Morbidity and Mortality Weekly Report, the researchers identified 34,220 adults with immunocompromising conditions who were hospitalized for COVID-19–like illness between Dec. 16, 2021, and Aug. 20, 2022. These conditions included solid malignancy (40.5%), hematologic malignancy (14.6%), rheumatologic or inflammatory disorder (24.4%), other intrinsic immune condition or immunodeficiency (38.5%), or organ or stem cell transplant (8.6%). They used data from the CDC’s VISION Network, a multistate database. The data include spring and summer 2022, when the BA.4 and BA.5 Omicron subvariants dominated other strains, and adults with immunocompromising conditions were eligible for a total of four vaccine doses (two primary doses and two boosters). The median age of the study population was 69 years, and 25.7%, 41.7%, and 7.0% had received two, three, and four doses, respectively, of COVID-19 vaccine.

Overall, vaccine effectiveness (VE) among immunocompromised patients was 34% after two vaccine doses, increasing to 71% during days 7-89 after a third dose, then declining to 41% 90 days or more after that dose.

During the full Omicron period, VE was 36% for 14 or more days after dose two, 69% for 7-89 days after dose three, and 44% for 90 or more days after dose three.

When VE was stratified by sublineage period, VE was higher 7 or more days after dose three during the predominance of BA.1 (67%), compared with VE during the dominant periods of BA.2/BA.2.12.1 (32%) and BA.4/BA.5 (35%).

In the later periods when Omicron BA.2/BA.2.12.1 and BA.4/BA.5 variants dominated, and individuals who had received three doses of vaccine were eligible for a fourth, VE against these variants was 32% 90 or more days after dose three and 43% 7 or more days after dose four.

VE was lowest among individuals with potentially more severe immunocompromising conditions, notably solid organ or stem cell transplants, the researchers wrote in their discussion.

The study findings were limited by several factors including the use of ICD-9 and -10 discharge diagnosis codes for immunocompromising conditions, potential confounding in VE models, lack of data on outpatient treatments such as nirmatelvir/ritonavir (Paxlovid), and lack of COVID-19 genomic sequencing data that may have affected which sublineage was identified, the researchers noted.

However, “this study confirms that even with boosters, immunocompromised adults, because of their weakened immune systems, are still at high risk of moderate to severe COVID,” said coauthor Brian Dixon, PhD, of the Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, in a press release about the study.

“Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP [Advisory Committee on Immunization Practices] recommendations,” the researchers concluded in the study.

The study was funded by the CDC. The researchers had no financial conflicts to disclose. The VISION Network is a collaboration between the CDC, the Regenstrief Institute, and seven health care systems across the United States: Columbia University Irving Medical Center (New York), HealthPartners (Wisconsin), Intermountain Healthcare (Utah), Kaiser Permanente Northern California, Kaiser Permanente Northwest (Washington State), the University of Colorado, and Paso Del Norte Health Information Exchange (Texas).

The effectiveness of up to three doses of COVID-19 vaccine was moderate overall and significantly lower among individuals with immunocompromising conditions, compared with the general population during the period of Omicron dominance, according to an analysis of data from more than 34,000 hospitalizations.

Previous studies have suggested lower COVID-19 vaccine effectiveness among immunocompromised individuals, compared with healthy individuals from the general population, but data from the period in which Omicron subvariants have been dominant are limited, wrote Amadea Britton, MD, of the Centers for Disease Control and Prevention’s COVID-19 Emergency Response Team, and colleagues.

The CDC currently recommends an expanded primary vaccine series of three doses of an mRNA vaccine, and the Advisory Committee on Immunization Practices has recommended a fourth dose with the new bivalent booster that contains elements of the Omicron variant, the researchers noted.

In a study published in the CDC’s Morbidity and Mortality Weekly Report, the researchers identified 34,220 adults with immunocompromising conditions who were hospitalized for COVID-19–like illness between Dec. 16, 2021, and Aug. 20, 2022. These conditions included solid malignancy (40.5%), hematologic malignancy (14.6%), rheumatologic or inflammatory disorder (24.4%), other intrinsic immune condition or immunodeficiency (38.5%), or organ or stem cell transplant (8.6%). They used data from the CDC’s VISION Network, a multistate database. The data include spring and summer 2022, when the BA.4 and BA.5 Omicron subvariants dominated other strains, and adults with immunocompromising conditions were eligible for a total of four vaccine doses (two primary doses and two boosters). The median age of the study population was 69 years, and 25.7%, 41.7%, and 7.0% had received two, three, and four doses, respectively, of COVID-19 vaccine.

Overall, vaccine effectiveness (VE) among immunocompromised patients was 34% after two vaccine doses, increasing to 71% during days 7-89 after a third dose, then declining to 41% 90 days or more after that dose.

During the full Omicron period, VE was 36% for 14 or more days after dose two, 69% for 7-89 days after dose three, and 44% for 90 or more days after dose three.

When VE was stratified by sublineage period, VE was higher 7 or more days after dose three during the predominance of BA.1 (67%), compared with VE during the dominant periods of BA.2/BA.2.12.1 (32%) and BA.4/BA.5 (35%).

In the later periods when Omicron BA.2/BA.2.12.1 and BA.4/BA.5 variants dominated, and individuals who had received three doses of vaccine were eligible for a fourth, VE against these variants was 32% 90 or more days after dose three and 43% 7 or more days after dose four.

VE was lowest among individuals with potentially more severe immunocompromising conditions, notably solid organ or stem cell transplants, the researchers wrote in their discussion.

The study findings were limited by several factors including the use of ICD-9 and -10 discharge diagnosis codes for immunocompromising conditions, potential confounding in VE models, lack of data on outpatient treatments such as nirmatelvir/ritonavir (Paxlovid), and lack of COVID-19 genomic sequencing data that may have affected which sublineage was identified, the researchers noted.

However, “this study confirms that even with boosters, immunocompromised adults, because of their weakened immune systems, are still at high risk of moderate to severe COVID,” said coauthor Brian Dixon, PhD, of the Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, in a press release about the study.

“Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP [Advisory Committee on Immunization Practices] recommendations,” the researchers concluded in the study.

The study was funded by the CDC. The researchers had no financial conflicts to disclose. The VISION Network is a collaboration between the CDC, the Regenstrief Institute, and seven health care systems across the United States: Columbia University Irving Medical Center (New York), HealthPartners (Wisconsin), Intermountain Healthcare (Utah), Kaiser Permanente Northern California, Kaiser Permanente Northwest (Washington State), the University of Colorado, and Paso Del Norte Health Information Exchange (Texas).

The effectiveness of up to three doses of COVID-19 vaccine was moderate overall and significantly lower among individuals with immunocompromising conditions, compared with the general population during the period of Omicron dominance, according to an analysis of data from more than 34,000 hospitalizations.

Previous studies have suggested lower COVID-19 vaccine effectiveness among immunocompromised individuals, compared with healthy individuals from the general population, but data from the period in which Omicron subvariants have been dominant are limited, wrote Amadea Britton, MD, of the Centers for Disease Control and Prevention’s COVID-19 Emergency Response Team, and colleagues.

The CDC currently recommends an expanded primary vaccine series of three doses of an mRNA vaccine, and the Advisory Committee on Immunization Practices has recommended a fourth dose with the new bivalent booster that contains elements of the Omicron variant, the researchers noted.

In a study published in the CDC’s Morbidity and Mortality Weekly Report, the researchers identified 34,220 adults with immunocompromising conditions who were hospitalized for COVID-19–like illness between Dec. 16, 2021, and Aug. 20, 2022. These conditions included solid malignancy (40.5%), hematologic malignancy (14.6%), rheumatologic or inflammatory disorder (24.4%), other intrinsic immune condition or immunodeficiency (38.5%), or organ or stem cell transplant (8.6%). They used data from the CDC’s VISION Network, a multistate database. The data include spring and summer 2022, when the BA.4 and BA.5 Omicron subvariants dominated other strains, and adults with immunocompromising conditions were eligible for a total of four vaccine doses (two primary doses and two boosters). The median age of the study population was 69 years, and 25.7%, 41.7%, and 7.0% had received two, three, and four doses, respectively, of COVID-19 vaccine.

Overall, vaccine effectiveness (VE) among immunocompromised patients was 34% after two vaccine doses, increasing to 71% during days 7-89 after a third dose, then declining to 41% 90 days or more after that dose.

During the full Omicron period, VE was 36% for 14 or more days after dose two, 69% for 7-89 days after dose three, and 44% for 90 or more days after dose three.

When VE was stratified by sublineage period, VE was higher 7 or more days after dose three during the predominance of BA.1 (67%), compared with VE during the dominant periods of BA.2/BA.2.12.1 (32%) and BA.4/BA.5 (35%).

In the later periods when Omicron BA.2/BA.2.12.1 and BA.4/BA.5 variants dominated, and individuals who had received three doses of vaccine were eligible for a fourth, VE against these variants was 32% 90 or more days after dose three and 43% 7 or more days after dose four.

VE was lowest among individuals with potentially more severe immunocompromising conditions, notably solid organ or stem cell transplants, the researchers wrote in their discussion.

The study findings were limited by several factors including the use of ICD-9 and -10 discharge diagnosis codes for immunocompromising conditions, potential confounding in VE models, lack of data on outpatient treatments such as nirmatelvir/ritonavir (Paxlovid), and lack of COVID-19 genomic sequencing data that may have affected which sublineage was identified, the researchers noted.

However, “this study confirms that even with boosters, immunocompromised adults, because of their weakened immune systems, are still at high risk of moderate to severe COVID,” said coauthor Brian Dixon, PhD, of the Regenstrief Institute and Indiana University Richard M. Fairbanks School of Public Health, Indianapolis, in a press release about the study.

“Given the incomplete protection against hospitalization afforded by monovalent COVID-19 vaccines, persons with immunocompromising conditions might benefit from updated bivalent vaccine booster doses that target recently circulating Omicron sublineages, in line with ACIP [Advisory Committee on Immunization Practices] recommendations,” the researchers concluded in the study.

The study was funded by the CDC. The researchers had no financial conflicts to disclose. The VISION Network is a collaboration between the CDC, the Regenstrief Institute, and seven health care systems across the United States: Columbia University Irving Medical Center (New York), HealthPartners (Wisconsin), Intermountain Healthcare (Utah), Kaiser Permanente Northern California, Kaiser Permanente Northwest (Washington State), the University of Colorado, and Paso Del Norte Health Information Exchange (Texas).

DENVER – The top three social media platforms used by patients who seek aesthetic medical treatments in the United States are Facebook, Instagram, and YouTube. However, in a recent survey, when asked if an aesthetic medical provider’s social media presence positively affects their desire to see that provider, 48% of patients were neutral or had no opinion, while 41% indicated yes.

Gerd Altmann/pixabay

Those are key findings from the survey, which aimed to evaluate the social media preferences and perceptions of patients who undergo aesthetic procedures.

“Aesthetic providers have firmly established a presence on social media,” Morgan Murphrey, MD, said at the annual meeting of the American Society for Dermatologic Surgery, where she presented the results. “According to the dermatology literature, somewhere between 25% and 50% of patients are looking up aesthetic providers on social media before they even see them in the clinic. This raises the question: How do patients perceive aesthetic providers that are on social media, and what do they want to see on their professional accounts?”

To find out, Dr. Murphrey, chief dermatology resident at the University of California, Davis, and Sabrina Fabi, MD, a San Diego–based cosmetic dermatologist, used Survey Monkey to randomly survey 2,063 individuals in the United States. They used descriptive statistics to analyze characteristics and responses of the study participants.

Of the 2,063 respondents, 651 (32%) indicated that they undergo medical aesthetic treatments including Botox injections, fillers, or laser procedures. More than half (56%) were women, 25% were 18-30 years old, 64% were 31-60 years old, and 11% were 61 years or older.

The three most common social media platforms they used were Facebook (70%), Instagram (65%), and YouTube (63%), followed by TikTok (45%) and Snapchat (29%). When the researchers stratified respondents by income level, individuals making $200,000 or more per year were statistically more likely to be on Instagram while those making less than $200,000 were more likely to be on Facebook and YouTube.

When asked if their aesthetic medical provider’s social media presence positively impacts their desire to see them as a patient, 48% of respondent were neutral or had no opinion, while 41% answered yes. “Only 2% felt strongly about this if the provider was on a specific social media platform, while 9% of respondents preferred that their provider not be on social media,” Dr. Murphrey added.

When asked if the number of social media followers influences their perception of an aesthetic provider as an expert, 43% of respondents answered no while 57% answered yes. “Once you get to about 20,000 followers, there seems to be somewhat of a law of diminishing returns in the number of followers,” she said. However, 55% indicated that they prefer to see a provider with a social media account that is verified with a blue check mark.

As for content published, 70% of respondents found it very important (36%) or important (34%) that a provider show before-and-after photos on their social media pages, while 67% said that they favor viewing personal content such as posts about the provider’s family and hobbies.

“This study summarizes to us that there is really low risk to creating a social media account; it’s something to think about,” Dr. Murphrey said. “Only 9% of respondents really didn’t want aesthetic providers to be on social media, but when we stratified our results, those individuals were less likely to be on social media themselves.”

Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the results, characterized the findings as important, “as the role of social media (especially visually based platforms like Instagram) will only continue to grow in our dermatologic and aesthetic practices.” Several studies have displayed a trend of plastic surgeons and other subspecialities outnumbering dermatologists within the aesthetic realm of social media, she noted. “As our patients increasingly seek out health care information and advice through these platforms, studies like Dr. Murphrey’s and Dr. Fabi’s are helpful in allowing us to better understand patient preferences and perspectives, in that we, as dermatologists, may be able to better aid their medical decisions in the future,” she added.

Neither the researchers nor Dr. Richey reported having relevant financial disclosures.

DENVER – The top three social media platforms used by patients who seek aesthetic medical treatments in the United States are Facebook, Instagram, and YouTube. However, in a recent survey, when asked if an aesthetic medical provider’s social media presence positively affects their desire to see that provider, 48% of patients were neutral or had no opinion, while 41% indicated yes.

Gerd Altmann/pixabay

Those are key findings from the survey, which aimed to evaluate the social media preferences and perceptions of patients who undergo aesthetic procedures.

“Aesthetic providers have firmly established a presence on social media,” Morgan Murphrey, MD, said at the annual meeting of the American Society for Dermatologic Surgery, where she presented the results. “According to the dermatology literature, somewhere between 25% and 50% of patients are looking up aesthetic providers on social media before they even see them in the clinic. This raises the question: How do patients perceive aesthetic providers that are on social media, and what do they want to see on their professional accounts?”

To find out, Dr. Murphrey, chief dermatology resident at the University of California, Davis, and Sabrina Fabi, MD, a San Diego–based cosmetic dermatologist, used Survey Monkey to randomly survey 2,063 individuals in the United States. They used descriptive statistics to analyze characteristics and responses of the study participants.

Of the 2,063 respondents, 651 (32%) indicated that they undergo medical aesthetic treatments including Botox injections, fillers, or laser procedures. More than half (56%) were women, 25% were 18-30 years old, 64% were 31-60 years old, and 11% were 61 years or older.

The three most common social media platforms they used were Facebook (70%), Instagram (65%), and YouTube (63%), followed by TikTok (45%) and Snapchat (29%). When the researchers stratified respondents by income level, individuals making $200,000 or more per year were statistically more likely to be on Instagram while those making less than $200,000 were more likely to be on Facebook and YouTube.

When asked if their aesthetic medical provider’s social media presence positively impacts their desire to see them as a patient, 48% of respondent were neutral or had no opinion, while 41% answered yes. “Only 2% felt strongly about this if the provider was on a specific social media platform, while 9% of respondents preferred that their provider not be on social media,” Dr. Murphrey added.

When asked if the number of social media followers influences their perception of an aesthetic provider as an expert, 43% of respondents answered no while 57% answered yes. “Once you get to about 20,000 followers, there seems to be somewhat of a law of diminishing returns in the number of followers,” she said. However, 55% indicated that they prefer to see a provider with a social media account that is verified with a blue check mark.

As for content published, 70% of respondents found it very important (36%) or important (34%) that a provider show before-and-after photos on their social media pages, while 67% said that they favor viewing personal content such as posts about the provider’s family and hobbies.

“This study summarizes to us that there is really low risk to creating a social media account; it’s something to think about,” Dr. Murphrey said. “Only 9% of respondents really didn’t want aesthetic providers to be on social media, but when we stratified our results, those individuals were less likely to be on social media themselves.”

Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the results, characterized the findings as important, “as the role of social media (especially visually based platforms like Instagram) will only continue to grow in our dermatologic and aesthetic practices.” Several studies have displayed a trend of plastic surgeons and other subspecialities outnumbering dermatologists within the aesthetic realm of social media, she noted. “As our patients increasingly seek out health care information and advice through these platforms, studies like Dr. Murphrey’s and Dr. Fabi’s are helpful in allowing us to better understand patient preferences and perspectives, in that we, as dermatologists, may be able to better aid their medical decisions in the future,” she added.

Neither the researchers nor Dr. Richey reported having relevant financial disclosures.

DENVER – The top three social media platforms used by patients who seek aesthetic medical treatments in the United States are Facebook, Instagram, and YouTube. However, in a recent survey, when asked if an aesthetic medical provider’s social media presence positively affects their desire to see that provider, 48% of patients were neutral or had no opinion, while 41% indicated yes.

Gerd Altmann/pixabay

Those are key findings from the survey, which aimed to evaluate the social media preferences and perceptions of patients who undergo aesthetic procedures.

“Aesthetic providers have firmly established a presence on social media,” Morgan Murphrey, MD, said at the annual meeting of the American Society for Dermatologic Surgery, where she presented the results. “According to the dermatology literature, somewhere between 25% and 50% of patients are looking up aesthetic providers on social media before they even see them in the clinic. This raises the question: How do patients perceive aesthetic providers that are on social media, and what do they want to see on their professional accounts?”

To find out, Dr. Murphrey, chief dermatology resident at the University of California, Davis, and Sabrina Fabi, MD, a San Diego–based cosmetic dermatologist, used Survey Monkey to randomly survey 2,063 individuals in the United States. They used descriptive statistics to analyze characteristics and responses of the study participants.

Of the 2,063 respondents, 651 (32%) indicated that they undergo medical aesthetic treatments including Botox injections, fillers, or laser procedures. More than half (56%) were women, 25% were 18-30 years old, 64% were 31-60 years old, and 11% were 61 years or older.

The three most common social media platforms they used were Facebook (70%), Instagram (65%), and YouTube (63%), followed by TikTok (45%) and Snapchat (29%). When the researchers stratified respondents by income level, individuals making $200,000 or more per year were statistically more likely to be on Instagram while those making less than $200,000 were more likely to be on Facebook and YouTube.

When asked if their aesthetic medical provider’s social media presence positively impacts their desire to see them as a patient, 48% of respondent were neutral or had no opinion, while 41% answered yes. “Only 2% felt strongly about this if the provider was on a specific social media platform, while 9% of respondents preferred that their provider not be on social media,” Dr. Murphrey added.

When asked if the number of social media followers influences their perception of an aesthetic provider as an expert, 43% of respondents answered no while 57% answered yes. “Once you get to about 20,000 followers, there seems to be somewhat of a law of diminishing returns in the number of followers,” she said. However, 55% indicated that they prefer to see a provider with a social media account that is verified with a blue check mark.

As for content published, 70% of respondents found it very important (36%) or important (34%) that a provider show before-and-after photos on their social media pages, while 67% said that they favor viewing personal content such as posts about the provider’s family and hobbies.

“This study summarizes to us that there is really low risk to creating a social media account; it’s something to think about,” Dr. Murphrey said. “Only 9% of respondents really didn’t want aesthetic providers to be on social media, but when we stratified our results, those individuals were less likely to be on social media themselves.”

Patricia Richey, MD, who practices Mohs surgery and cosmetic dermatology in Washington, D.C., and was asked to comment on the results, characterized the findings as important, “as the role of social media (especially visually based platforms like Instagram) will only continue to grow in our dermatologic and aesthetic practices.” Several studies have displayed a trend of plastic surgeons and other subspecialities outnumbering dermatologists within the aesthetic realm of social media, she noted. “As our patients increasingly seek out health care information and advice through these platforms, studies like Dr. Murphrey’s and Dr. Fabi’s are helpful in allowing us to better understand patient preferences and perspectives, in that we, as dermatologists, may be able to better aid their medical decisions in the future,” she added.

Neither the researchers nor Dr. Richey reported having relevant financial disclosures.

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants. 

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants. 

Acupuncture is a very popular treatment strategy in some areas of the world and is extensively applied in Chinese practice. Though this is a regularly applied treatment, a direct comparison with first-line antispasmodics has not been previously completed. The study by Shi and colleagues sought to compare the treatment of IBS using an adjusted indirect treatment comparison meta-analysis. This study proves that cimetropium was the most effective for relieving abdominal pain, whereas drotaverine, acupuncture, and pinaverium remained superior to the placebo. That being said, acupuncture was shown to be superior in relieving global IBS symptoms and caused fewer side effects than did antispasmodics. This shows that acupuncture may have a role in the treatment algorithm for IBS even outside of China, where it is used broadly.

The study by Formica and colleagues provides new insights on the etiology and pathogenesis of IBS. These insights include the positive correlation between disgust sensitivity and IBS quality of life (QOL) scores. The relationship between IBS and the emotional intensity of the experience of disgust is discussed throughout this study and more severe IBS-QOL scores were linked to those with high levels of disgust sensitivity. This study had gender limitations because of the low number of male participants, so these correlations were patterned mostly in female participants. 

When maternal-fetal medicine specialist Andra James, MD, MPH, trained as a midwife decades ago, women with sickle cell disease (SCD) were urged to never get pregnant. If they did, termination was considered the best option.

“If they did carry a pregnancy, the baby would not survive to the point of viability,” Dr. James, emeritus professor of obstetrics and gynecology at Duke University, Durham, N.C., recalled in an interview.

The fates of women with SCD have transformed dramatically since those grim days. In general, this blood disorder no longer robs patients of decades of life, and many women with SCD bear healthy children. But their pregnancies are still considered high risk with significant potential for health crises and death. Now, there’s a new complication: The overturning of Roe v. Wade.

Many states imposed tighter restrictions on abortions in the wake of the U.S. Supreme Court’s landmark Dobbs ruling, sparking worry among physicians that women with SCD won’t be able to get proper maternal care in some parts of the United States.

For example, women with SCD may be unable able to seek elective abortions in some states even if their pregnancies pose a danger to their lives. And abortion restrictions are imperiling access to a medication that’s used to treat miscarriages, which are more common in women with SCD.

“The situation with Dobbs is dire, and maternal health care is being compromised,” Johns Hopkins University pediatric hematologist Lydia Pecker, MD, who treats young people with SCD and studies its impact on pregnancy, said in an interview. “Women with sickle cell disease who are pregnant constitute an underserved and understudied population with special health care needs, and the Dobbs decision will only make providing their care even more difficult in many parts of the country.”

For her part, Dr. James described the risk to pregnant women with SCD this way: In the wake of the court ruling, “we increase the opportunity for them to lose their lives and for their babies to die.”
 

SCD’s impact on pregnancy

While physicians no longer advise women with SCD to avoid motherhood, pregnancy is still uniquely dangerous for them. “Most of them have babies and children who are thriving, but it’s not easy for them,” University of North Carolina at Chapel Hill hematologist and SCD specialist Jane Little, MD, said in an interview. And in some cases, she said, pregnancies “do not end well.”

For a 2022 report, Dr. Pecker and colleagues analyzed 2012-2018 data for 6,610 U.S. hospital admissions among women with SCD (87% of whom were Black). These women were more likely than were unaffected women to suffer severe maternal morbidity (odds ratio[OR], 4.63, 95% confidence interval [CI], 4.16-5.16, P < .001). Cerebrovascular event were especially more common in SCD (OR, 13.94, P < .001).

According to a 2019 report, pregnant women with SCD “are more likely to develop a host of complications, particularly hypertensive syndromes (such as preeclampsia), venous thromboembolism (VTE), preterm labor, and fetal loss. Newborns are more likely to have growth problems and prematurity.”

Although data are sparse, experts say it’s also clear that women with SCD face significantly higher risk of death in pregnancy compared to other women. In fact, the maternal mortality rate for females with SCD “is higher than for Black females without SCD, who already suffer from a higher mortality rate than White females during pregnancy and childbirth,” Andrea Roe, MD, MPH, assistant professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania, Philadelphia, said in an interview.

Women with SCD also are more likely to have premature and stillborn births.

Some of the health challenges in pregnant women with SCD stem from the body’s inability to boost blood production in order to supply the placenta, said Dr. James, the Duke University emeritus professor. “Her bone marrow is already turning out red blood cells as fast as it can.”

In addition, she said, these women are more susceptible to infection, blood clots, and damage to the kidneys and lungs.

Still, in most cases of SCD in pregnancy, “we counsel a woman that we can get you safely through it,” Dr. James said. “But there is a subset of patients that will have organ damage from their sickle cell disease and should not become pregnant or stay pregnant if they become pregnant.”
 

Court ruling limits options in some states

The Dobbs ruling affects pregnant women with SCD in two ways: It allows states to restrict or ban abortion to greater extents than were possible over the last 50 years, and it has spawned further limitations on access to mifepristone, which is commonly used to treat early miscarriages.

In some cases, Dr. James said, abortions in this population are elective. “People with sickle cell disease are frequently in pain, they are frequently hospitalized. They may have suffered strokes or subclinical strokes or have some cognitive impairment, and they don’t have the mental and physical fortitude [to tolerate pregnancy and birth].”

In other cases, abortions are medically necessary to preserve the mother’s life. The American Society of Hematology highlighted the risks posed by SCD to maternal health in a June 24 statement that criticized the Dobbs ruling. “In some cases, denying women their right to terminate a pregnancy puts them at risk of serious illness or death,” wrote Jane N. Winter, MD, president of ASH and professor of medicine at Northwestern University, Chicago.

There do not appear to be any statistics about abortion rates among women with SCD in the United States or whether the rates are higher than in other groups.

As for miscarriages in SCD, an analysis of first pregnancies in California women with SCD from 1991 to 2016 found that about 16% were “incomplete,” mainly (59.3%) from miscarriage.

The Dobbs ruling allows states to further restrict the drug combination of mifepristone and misoprostol, which is used to trigger abortions and to treat early pregnancy loss. Access to mifepristone was already limited prior to the ruling due to tight regulation, and advocates say it’s now even harder to get.
 

What now? Physicians urge focus on contraception

As the ramifications of the Dobbs ruling sink in, SCD specialists are emphasizing the importance of providing gynecological and contraceptive care to help women with the condition avoid unwanted pregnancies. At the University of North Carolina, “we’re pretty aggressive about trying to give women the option to see a gynecologist to get the best care they can,” Dr. Little said. “We have a shared gynecology and sickle cell clinic because we really want women to be making the choice [to become pregnant] when they are ready because it’s a strain on their health and their lives.”

Dr. Pecker, the Johns Hopkins University pediatric hematologist, urged colleagues to partner with maternal-fetal medicine specialists so they can quickly get help for pregnant patients when needed. “That way they can get high-quality pregnancy care and help to end pregnancies that need to be ended.”

She recommended “highly effective” progesterone-based birth control as the best first-line contraceptive for women with SCD. And, she said, every woman of child-bearing age with SCD should be assessed annually for their intentions regarding pregnancy. As she put it, “there’s so much that we can do to reduce harms.”

Dr. Pecker disclosed financial relationships with the National Institutes of Health, American Society of Hematology, Doris Duke Charitable Foundation, the Mellon Foundation, Global Blood Therapeutics, and Novo Nordisk. Dr. Little disclosed financial relationships with Global Blood Therapeutics, Bluebird Bio, and Forma Therapeutics. Dr. Roe has no disclosures.

When maternal-fetal medicine specialist Andra James, MD, MPH, trained as a midwife decades ago, women with sickle cell disease (SCD) were urged to never get pregnant. If they did, termination was considered the best option.

“If they did carry a pregnancy, the baby would not survive to the point of viability,” Dr. James, emeritus professor of obstetrics and gynecology at Duke University, Durham, N.C., recalled in an interview.

The fates of women with SCD have transformed dramatically since those grim days. In general, this blood disorder no longer robs patients of decades of life, and many women with SCD bear healthy children. But their pregnancies are still considered high risk with significant potential for health crises and death. Now, there’s a new complication: The overturning of Roe v. Wade.

Many states imposed tighter restrictions on abortions in the wake of the U.S. Supreme Court’s landmark Dobbs ruling, sparking worry among physicians that women with SCD won’t be able to get proper maternal care in some parts of the United States.

For example, women with SCD may be unable able to seek elective abortions in some states even if their pregnancies pose a danger to their lives. And abortion restrictions are imperiling access to a medication that’s used to treat miscarriages, which are more common in women with SCD.

“The situation with Dobbs is dire, and maternal health care is being compromised,” Johns Hopkins University pediatric hematologist Lydia Pecker, MD, who treats young people with SCD and studies its impact on pregnancy, said in an interview. “Women with sickle cell disease who are pregnant constitute an underserved and understudied population with special health care needs, and the Dobbs decision will only make providing their care even more difficult in many parts of the country.”

For her part, Dr. James described the risk to pregnant women with SCD this way: In the wake of the court ruling, “we increase the opportunity for them to lose their lives and for their babies to die.”
 

SCD’s impact on pregnancy

While physicians no longer advise women with SCD to avoid motherhood, pregnancy is still uniquely dangerous for them. “Most of them have babies and children who are thriving, but it’s not easy for them,” University of North Carolina at Chapel Hill hematologist and SCD specialist Jane Little, MD, said in an interview. And in some cases, she said, pregnancies “do not end well.”

For a 2022 report, Dr. Pecker and colleagues analyzed 2012-2018 data for 6,610 U.S. hospital admissions among women with SCD (87% of whom were Black). These women were more likely than were unaffected women to suffer severe maternal morbidity (odds ratio[OR], 4.63, 95% confidence interval [CI], 4.16-5.16, P < .001). Cerebrovascular event were especially more common in SCD (OR, 13.94, P < .001).

According to a 2019 report, pregnant women with SCD “are more likely to develop a host of complications, particularly hypertensive syndromes (such as preeclampsia), venous thromboembolism (VTE), preterm labor, and fetal loss. Newborns are more likely to have growth problems and prematurity.”

Although data are sparse, experts say it’s also clear that women with SCD face significantly higher risk of death in pregnancy compared to other women. In fact, the maternal mortality rate for females with SCD “is higher than for Black females without SCD, who already suffer from a higher mortality rate than White females during pregnancy and childbirth,” Andrea Roe, MD, MPH, assistant professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania, Philadelphia, said in an interview.

Women with SCD also are more likely to have premature and stillborn births.

Some of the health challenges in pregnant women with SCD stem from the body’s inability to boost blood production in order to supply the placenta, said Dr. James, the Duke University emeritus professor. “Her bone marrow is already turning out red blood cells as fast as it can.”

In addition, she said, these women are more susceptible to infection, blood clots, and damage to the kidneys and lungs.

Still, in most cases of SCD in pregnancy, “we counsel a woman that we can get you safely through it,” Dr. James said. “But there is a subset of patients that will have organ damage from their sickle cell disease and should not become pregnant or stay pregnant if they become pregnant.”
 

Court ruling limits options in some states

The Dobbs ruling affects pregnant women with SCD in two ways: It allows states to restrict or ban abortion to greater extents than were possible over the last 50 years, and it has spawned further limitations on access to mifepristone, which is commonly used to treat early miscarriages.

In some cases, Dr. James said, abortions in this population are elective. “People with sickle cell disease are frequently in pain, they are frequently hospitalized. They may have suffered strokes or subclinical strokes or have some cognitive impairment, and they don’t have the mental and physical fortitude [to tolerate pregnancy and birth].”

In other cases, abortions are medically necessary to preserve the mother’s life. The American Society of Hematology highlighted the risks posed by SCD to maternal health in a June 24 statement that criticized the Dobbs ruling. “In some cases, denying women their right to terminate a pregnancy puts them at risk of serious illness or death,” wrote Jane N. Winter, MD, president of ASH and professor of medicine at Northwestern University, Chicago.

There do not appear to be any statistics about abortion rates among women with SCD in the United States or whether the rates are higher than in other groups.

As for miscarriages in SCD, an analysis of first pregnancies in California women with SCD from 1991 to 2016 found that about 16% were “incomplete,” mainly (59.3%) from miscarriage.

The Dobbs ruling allows states to further restrict the drug combination of mifepristone and misoprostol, which is used to trigger abortions and to treat early pregnancy loss. Access to mifepristone was already limited prior to the ruling due to tight regulation, and advocates say it’s now even harder to get.
 

What now? Physicians urge focus on contraception

As the ramifications of the Dobbs ruling sink in, SCD specialists are emphasizing the importance of providing gynecological and contraceptive care to help women with the condition avoid unwanted pregnancies. At the University of North Carolina, “we’re pretty aggressive about trying to give women the option to see a gynecologist to get the best care they can,” Dr. Little said. “We have a shared gynecology and sickle cell clinic because we really want women to be making the choice [to become pregnant] when they are ready because it’s a strain on their health and their lives.”

Dr. Pecker, the Johns Hopkins University pediatric hematologist, urged colleagues to partner with maternal-fetal medicine specialists so they can quickly get help for pregnant patients when needed. “That way they can get high-quality pregnancy care and help to end pregnancies that need to be ended.”

She recommended “highly effective” progesterone-based birth control as the best first-line contraceptive for women with SCD. And, she said, every woman of child-bearing age with SCD should be assessed annually for their intentions regarding pregnancy. As she put it, “there’s so much that we can do to reduce harms.”

Dr. Pecker disclosed financial relationships with the National Institutes of Health, American Society of Hematology, Doris Duke Charitable Foundation, the Mellon Foundation, Global Blood Therapeutics, and Novo Nordisk. Dr. Little disclosed financial relationships with Global Blood Therapeutics, Bluebird Bio, and Forma Therapeutics. Dr. Roe has no disclosures.

When maternal-fetal medicine specialist Andra James, MD, MPH, trained as a midwife decades ago, women with sickle cell disease (SCD) were urged to never get pregnant. If they did, termination was considered the best option.

“If they did carry a pregnancy, the baby would not survive to the point of viability,” Dr. James, emeritus professor of obstetrics and gynecology at Duke University, Durham, N.C., recalled in an interview.

The fates of women with SCD have transformed dramatically since those grim days. In general, this blood disorder no longer robs patients of decades of life, and many women with SCD bear healthy children. But their pregnancies are still considered high risk with significant potential for health crises and death. Now, there’s a new complication: The overturning of Roe v. Wade.

Many states imposed tighter restrictions on abortions in the wake of the U.S. Supreme Court’s landmark Dobbs ruling, sparking worry among physicians that women with SCD won’t be able to get proper maternal care in some parts of the United States.

For example, women with SCD may be unable able to seek elective abortions in some states even if their pregnancies pose a danger to their lives. And abortion restrictions are imperiling access to a medication that’s used to treat miscarriages, which are more common in women with SCD.

“The situation with Dobbs is dire, and maternal health care is being compromised,” Johns Hopkins University pediatric hematologist Lydia Pecker, MD, who treats young people with SCD and studies its impact on pregnancy, said in an interview. “Women with sickle cell disease who are pregnant constitute an underserved and understudied population with special health care needs, and the Dobbs decision will only make providing their care even more difficult in many parts of the country.”

For her part, Dr. James described the risk to pregnant women with SCD this way: In the wake of the court ruling, “we increase the opportunity for them to lose their lives and for their babies to die.”
 

SCD’s impact on pregnancy

While physicians no longer advise women with SCD to avoid motherhood, pregnancy is still uniquely dangerous for them. “Most of them have babies and children who are thriving, but it’s not easy for them,” University of North Carolina at Chapel Hill hematologist and SCD specialist Jane Little, MD, said in an interview. And in some cases, she said, pregnancies “do not end well.”

For a 2022 report, Dr. Pecker and colleagues analyzed 2012-2018 data for 6,610 U.S. hospital admissions among women with SCD (87% of whom were Black). These women were more likely than were unaffected women to suffer severe maternal morbidity (odds ratio[OR], 4.63, 95% confidence interval [CI], 4.16-5.16, P < .001). Cerebrovascular event were especially more common in SCD (OR, 13.94, P < .001).

According to a 2019 report, pregnant women with SCD “are more likely to develop a host of complications, particularly hypertensive syndromes (such as preeclampsia), venous thromboembolism (VTE), preterm labor, and fetal loss. Newborns are more likely to have growth problems and prematurity.”

Although data are sparse, experts say it’s also clear that women with SCD face significantly higher risk of death in pregnancy compared to other women. In fact, the maternal mortality rate for females with SCD “is higher than for Black females without SCD, who already suffer from a higher mortality rate than White females during pregnancy and childbirth,” Andrea Roe, MD, MPH, assistant professor of obstetrics and gynecology at the Hospital of the University of Pennsylvania, Philadelphia, said in an interview.

Women with SCD also are more likely to have premature and stillborn births.

Some of the health challenges in pregnant women with SCD stem from the body’s inability to boost blood production in order to supply the placenta, said Dr. James, the Duke University emeritus professor. “Her bone marrow is already turning out red blood cells as fast as it can.”

In addition, she said, these women are more susceptible to infection, blood clots, and damage to the kidneys and lungs.

Still, in most cases of SCD in pregnancy, “we counsel a woman that we can get you safely through it,” Dr. James said. “But there is a subset of patients that will have organ damage from their sickle cell disease and should not become pregnant or stay pregnant if they become pregnant.”
 

Court ruling limits options in some states

The Dobbs ruling affects pregnant women with SCD in two ways: It allows states to restrict or ban abortion to greater extents than were possible over the last 50 years, and it has spawned further limitations on access to mifepristone, which is commonly used to treat early miscarriages.

In some cases, Dr. James said, abortions in this population are elective. “People with sickle cell disease are frequently in pain, they are frequently hospitalized. They may have suffered strokes or subclinical strokes or have some cognitive impairment, and they don’t have the mental and physical fortitude [to tolerate pregnancy and birth].”

In other cases, abortions are medically necessary to preserve the mother’s life. The American Society of Hematology highlighted the risks posed by SCD to maternal health in a June 24 statement that criticized the Dobbs ruling. “In some cases, denying women their right to terminate a pregnancy puts them at risk of serious illness or death,” wrote Jane N. Winter, MD, president of ASH and professor of medicine at Northwestern University, Chicago.

There do not appear to be any statistics about abortion rates among women with SCD in the United States or whether the rates are higher than in other groups.

As for miscarriages in SCD, an analysis of first pregnancies in California women with SCD from 1991 to 2016 found that about 16% were “incomplete,” mainly (59.3%) from miscarriage.

The Dobbs ruling allows states to further restrict the drug combination of mifepristone and misoprostol, which is used to trigger abortions and to treat early pregnancy loss. Access to mifepristone was already limited prior to the ruling due to tight regulation, and advocates say it’s now even harder to get.
 

What now? Physicians urge focus on contraception

As the ramifications of the Dobbs ruling sink in, SCD specialists are emphasizing the importance of providing gynecological and contraceptive care to help women with the condition avoid unwanted pregnancies. At the University of North Carolina, “we’re pretty aggressive about trying to give women the option to see a gynecologist to get the best care they can,” Dr. Little said. “We have a shared gynecology and sickle cell clinic because we really want women to be making the choice [to become pregnant] when they are ready because it’s a strain on their health and their lives.”

Dr. Pecker, the Johns Hopkins University pediatric hematologist, urged colleagues to partner with maternal-fetal medicine specialists so they can quickly get help for pregnant patients when needed. “That way they can get high-quality pregnancy care and help to end pregnancies that need to be ended.”

She recommended “highly effective” progesterone-based birth control as the best first-line contraceptive for women with SCD. And, she said, every woman of child-bearing age with SCD should be assessed annually for their intentions regarding pregnancy. As she put it, “there’s so much that we can do to reduce harms.”

Dr. Pecker disclosed financial relationships with the National Institutes of Health, American Society of Hematology, Doris Duke Charitable Foundation, the Mellon Foundation, Global Blood Therapeutics, and Novo Nordisk. Dr. Little disclosed financial relationships with Global Blood Therapeutics, Bluebird Bio, and Forma Therapeutics. Dr. Roe has no disclosures.

A large randomized trial that was investigating intensive lowering of blood pressure in acute ischemic stroke patients who had undergone mechanical thrombectomy has been stopped early because of safety concerns.

“Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischemic stroke due to intracranial large-vessel occlusion,” the investigators conclude.

Results from the ENCHANTED2/MT trial were presented by Craig Anderson, MD, professor of neurology and epidemiology, University of New South Wales, Sydney, during the 14th World Stroke Congress (WSC) in Singapore.

The study was simultaneously published online in The Lancet.

“What our results have pretty convincingly shown is that in acute stroke patients who have undergone mechanical thrombectomy, lowering blood pressure down to a systolic of 120 mm Hg for 3 days is too low for too long. We shouldn’t go that far down,” Dr. Anderson said in an interview.

Dr. Anderson said the trial has provided an important message for clinical practice.

“This result is not what we expected, but it is a definitive result and gives us a lower safety margin for blood pressure in acute ischemic stroke patients. This, in itself, is a big step forward.”

He noted that the optimum blood pressure for these patients is not known.

“We need to do further trials to determine optimum blood pressure in these acute patients, but perhaps we should be aiming more towards 140 mm Hg,” he suggested.

“But this trial shows us that in patients who have had successful clot retrieval with endovascular treatment for acute ischemic stroke, careful blood pressure management is important to avoid levels becoming too low. We have to make sure we don’t overshoot down to 120 mm Hg or below.”

The chair of the WSC session at which the trial was presented, Jeyaraj Pandian, MD, head of neurology at Christian Medical College, Ludhiana, India, who is the current vice-president of the World Stroke Organization, said: “This is a very important result. It has major practical implications.”

As background, Dr. Anderson explained that elevated blood pressure is very common in patients who have an acute ischemic stroke, and the higher the blood pressure, the higher the chances of having a worse outcome.

“Theoretically, if we can control the blood pressure, we may be able to improve outcomes,” he said.

In 2019, the first ENCHANTED trial reported that controlling blood pressure by a moderate amount – to around 140 mm Hg, which is lower than currently recommended in the guidelines – was linked to a reduction in bleeding complications of thrombolysis and appeared safe, but it did not improve recovery, Dr. Anderson noted.

“This trial was done before mechanical thrombectomy became routinely adopted, and this procedure has now become the standard of care for large-vessel occlusion strokes, but we don’t know what we should do about blood pressure in these patients,” he added.

A smaller French trial has suggested lowering blood pressure to 130 mm Hg, rather than a more liberal 130-180 mm Hg, was safe after successful mechanical thrombectomy, but there was no effect on functional outcome.

“In stroke patients with a large-vessel occlusion, blood pressure is often elevated to very high levels. There are wide ranges of opinions on what to do about this – whether it should be lowered, and by how much,” Dr. Anderson said. “We conducted the current ENCHANTED2/MT trial to look at this issue.”

The trial randomly assigned patients who had undergone successful mechanical clot retrieval and reperfusion but whose blood pressure was still elevated to two groups. In one group, blood pressure was aggressively lowered to less than 120 mm Hg within 1 hour of reperfusion, and blood pressure was kept at this level for 3 days. In the other group, a more liberal approach was used: Blood pressure was kept at 140-180 mm Hg.

The primary endpoint was disability, as measured by the Modified Rankin Scale (mRS) score at 90 days.

The study was started in China with the intention of expanding recruitment internationally. The planned enrollment was more than 2,000 patients.

However, in March of 2022, after 821 patients had been enrolled, the data safety monitoring board (DSMB) recommended that recruitment into the trial be suspended because of a safety signal. All of the patients who had been recruited were from China.

These patients were followed to obtain the 3-month outcome results, after which the DSMB recommended that the trial be stopped because safety was still a problem.

Mean systolic blood pressure was 125 mm Hg at 1 hour and 121 mm Hg at 24 hours in the more intensive-treatment group; it was 143 mm Hg at 1 hour and 139 mm Hg at 24 hours in the less intensive-treatment group, giving an adjusted mean difference over 24 hours of 18 mm Hg.
 

Worse disability scores

Results showed that the patients who underwent the more intensive blood pressure lowering had more disability at 3-month follow-up, with worse scores on a shift analysis of the mRS than those in the less intensive group (common odds ratio, 1.37; 95% confidence interval, 1.07-1.76).

The unfavorable shift in mRS scores in the more intensive group was consistent in adjusted sensitivity analysis, and there was no significant heterogeneity in the treatment effect on the primary outcome across all prespecified subgroups.

The incidence of death or neurologic deterioration at 7 days was higher in the more intensive-treatment group than the less intensive-treatment group (common OR, 1.53), and a between-group difference emerged at 24 hours.

The incidence of death or disability (mRS scores, 3-6) at 90 days was higher among patients in the more intensive-treatment group than the less intensive-treatment group (53% vs. 39%; OR, 1.85; P = .0001).

Among those who survived, more patients in the more intensive-treatment group had major disability (mRS scores, 3-5) at 90 days than did patients in the less intensive-treatment group (43% vs. 28%; OR, 2.07; P = .0001).
 

No difference in ICH or severe hypotension episodes

The incidence of symptomatic intracranial hemorrhage, mortality, and serious adverse events did not significantly differ between the two groups. There were no significant differences in recurrent ischemic stroke events at 90 days, and no episodes of severe hypotension were reported as a serious adverse event.

“Our results show that intensive lowering of blood pressure appears to be associated with worsening physical disability. While there was no difference in mortality rates between the two groups, the lower blood pressure appeared to compromise the ability to recover from the stroke,” Dr. Anderson said.

On the possible mechanism of harm, he suggested that the intensive blood pressure reduction might be interfering with blood flow through the injured part of the brain and impeding the ability to recover from the clot removal procedure.
 

What levels should be aimed for?

Dr. Anderson stressed that it was important to have conducted this trial.

“Current guidelines recommend very conservative level of blood pressure in acute ischemic stroke patients – to below 180 mm Hg. But no lower limit is recommended.

“Most clinicians aim for about the 140 mm Hg mark, but there is a large variation in opinion on what to do,” he said. “Some doctors treat aggressively, believing that lower pressures could be beneficial in preventing bleeding and swelling, and others prefer to keep levels higher. Our results have helped to give some guidance on this.”

Asked what he thought an optimum target would be, Dr. Anderson replied: “For now, I think a target of around 140 mm Hg systolic would be reasonable, and there is no evidence to move below that.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, a co-author of the ENCHANTED2/MT trial, also commented: “The real importance of these study results is that they show that lowering blood pressure too much is detrimental on outcome. My personal interpretation, looking at the results of this study but also on the previous studies, is that we should aim for a target of 140-150 mm Hg. This is true for patients with recanalization therapy. For patients without any therapy, I would even be more careful in lowering blood pressure and recommend just staying below 180 mm Hg.”

As to whether these results are generalizable to other populations, given that the patients were Chinese, Dr. Anderson noted that Asian people have higher rates of intracranial atherosclerosis and more blood pressure complications in the heart and kidney than White patients. Stroke management patterns also differ.

“These points raise questions about generalizability, and while I think this is an issue for consideration, I do not think it should detract from the clarity of these results,” he commented.

The study is supported by grants from the Shanghai Hospital Development Center, the National Health and Medical Research Council of Australia, the China Stroke Prevention Project, Shanghai Changhai Hospital, the Science and Technology Commission of Shanghai Municipality, Takeda China, Genesis Medtech, and Penumbra. Dr. Anderson has received grants from the National Health and Medical Research Council and Medical Research Futures Fund of Australia, the UK Medical Research Council, Penumbra, and Takeda China.

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

A large randomized trial that was investigating intensive lowering of blood pressure in acute ischemic stroke patients who had undergone mechanical thrombectomy has been stopped early because of safety concerns.

“Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischemic stroke due to intracranial large-vessel occlusion,” the investigators conclude.

Results from the ENCHANTED2/MT trial were presented by Craig Anderson, MD, professor of neurology and epidemiology, University of New South Wales, Sydney, during the 14th World Stroke Congress (WSC) in Singapore.

The study was simultaneously published online in The Lancet.

“What our results have pretty convincingly shown is that in acute stroke patients who have undergone mechanical thrombectomy, lowering blood pressure down to a systolic of 120 mm Hg for 3 days is too low for too long. We shouldn’t go that far down,” Dr. Anderson said in an interview.

Dr. Anderson said the trial has provided an important message for clinical practice.

“This result is not what we expected, but it is a definitive result and gives us a lower safety margin for blood pressure in acute ischemic stroke patients. This, in itself, is a big step forward.”

He noted that the optimum blood pressure for these patients is not known.

“We need to do further trials to determine optimum blood pressure in these acute patients, but perhaps we should be aiming more towards 140 mm Hg,” he suggested.

“But this trial shows us that in patients who have had successful clot retrieval with endovascular treatment for acute ischemic stroke, careful blood pressure management is important to avoid levels becoming too low. We have to make sure we don’t overshoot down to 120 mm Hg or below.”

The chair of the WSC session at which the trial was presented, Jeyaraj Pandian, MD, head of neurology at Christian Medical College, Ludhiana, India, who is the current vice-president of the World Stroke Organization, said: “This is a very important result. It has major practical implications.”

As background, Dr. Anderson explained that elevated blood pressure is very common in patients who have an acute ischemic stroke, and the higher the blood pressure, the higher the chances of having a worse outcome.

“Theoretically, if we can control the blood pressure, we may be able to improve outcomes,” he said.

In 2019, the first ENCHANTED trial reported that controlling blood pressure by a moderate amount – to around 140 mm Hg, which is lower than currently recommended in the guidelines – was linked to a reduction in bleeding complications of thrombolysis and appeared safe, but it did not improve recovery, Dr. Anderson noted.

“This trial was done before mechanical thrombectomy became routinely adopted, and this procedure has now become the standard of care for large-vessel occlusion strokes, but we don’t know what we should do about blood pressure in these patients,” he added.

A smaller French trial has suggested lowering blood pressure to 130 mm Hg, rather than a more liberal 130-180 mm Hg, was safe after successful mechanical thrombectomy, but there was no effect on functional outcome.

“In stroke patients with a large-vessel occlusion, blood pressure is often elevated to very high levels. There are wide ranges of opinions on what to do about this – whether it should be lowered, and by how much,” Dr. Anderson said. “We conducted the current ENCHANTED2/MT trial to look at this issue.”

The trial randomly assigned patients who had undergone successful mechanical clot retrieval and reperfusion but whose blood pressure was still elevated to two groups. In one group, blood pressure was aggressively lowered to less than 120 mm Hg within 1 hour of reperfusion, and blood pressure was kept at this level for 3 days. In the other group, a more liberal approach was used: Blood pressure was kept at 140-180 mm Hg.

The primary endpoint was disability, as measured by the Modified Rankin Scale (mRS) score at 90 days.

The study was started in China with the intention of expanding recruitment internationally. The planned enrollment was more than 2,000 patients.

However, in March of 2022, after 821 patients had been enrolled, the data safety monitoring board (DSMB) recommended that recruitment into the trial be suspended because of a safety signal. All of the patients who had been recruited were from China.

These patients were followed to obtain the 3-month outcome results, after which the DSMB recommended that the trial be stopped because safety was still a problem.

Mean systolic blood pressure was 125 mm Hg at 1 hour and 121 mm Hg at 24 hours in the more intensive-treatment group; it was 143 mm Hg at 1 hour and 139 mm Hg at 24 hours in the less intensive-treatment group, giving an adjusted mean difference over 24 hours of 18 mm Hg.
 

Worse disability scores

Results showed that the patients who underwent the more intensive blood pressure lowering had more disability at 3-month follow-up, with worse scores on a shift analysis of the mRS than those in the less intensive group (common odds ratio, 1.37; 95% confidence interval, 1.07-1.76).

The unfavorable shift in mRS scores in the more intensive group was consistent in adjusted sensitivity analysis, and there was no significant heterogeneity in the treatment effect on the primary outcome across all prespecified subgroups.

The incidence of death or neurologic deterioration at 7 days was higher in the more intensive-treatment group than the less intensive-treatment group (common OR, 1.53), and a between-group difference emerged at 24 hours.

The incidence of death or disability (mRS scores, 3-6) at 90 days was higher among patients in the more intensive-treatment group than the less intensive-treatment group (53% vs. 39%; OR, 1.85; P = .0001).

Among those who survived, more patients in the more intensive-treatment group had major disability (mRS scores, 3-5) at 90 days than did patients in the less intensive-treatment group (43% vs. 28%; OR, 2.07; P = .0001).
 

No difference in ICH or severe hypotension episodes

The incidence of symptomatic intracranial hemorrhage, mortality, and serious adverse events did not significantly differ between the two groups. There were no significant differences in recurrent ischemic stroke events at 90 days, and no episodes of severe hypotension were reported as a serious adverse event.

“Our results show that intensive lowering of blood pressure appears to be associated with worsening physical disability. While there was no difference in mortality rates between the two groups, the lower blood pressure appeared to compromise the ability to recover from the stroke,” Dr. Anderson said.

On the possible mechanism of harm, he suggested that the intensive blood pressure reduction might be interfering with blood flow through the injured part of the brain and impeding the ability to recover from the clot removal procedure.
 

What levels should be aimed for?

Dr. Anderson stressed that it was important to have conducted this trial.

“Current guidelines recommend very conservative level of blood pressure in acute ischemic stroke patients – to below 180 mm Hg. But no lower limit is recommended.

“Most clinicians aim for about the 140 mm Hg mark, but there is a large variation in opinion on what to do,” he said. “Some doctors treat aggressively, believing that lower pressures could be beneficial in preventing bleeding and swelling, and others prefer to keep levels higher. Our results have helped to give some guidance on this.”

Asked what he thought an optimum target would be, Dr. Anderson replied: “For now, I think a target of around 140 mm Hg systolic would be reasonable, and there is no evidence to move below that.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, a co-author of the ENCHANTED2/MT trial, also commented: “The real importance of these study results is that they show that lowering blood pressure too much is detrimental on outcome. My personal interpretation, looking at the results of this study but also on the previous studies, is that we should aim for a target of 140-150 mm Hg. This is true for patients with recanalization therapy. For patients without any therapy, I would even be more careful in lowering blood pressure and recommend just staying below 180 mm Hg.”

As to whether these results are generalizable to other populations, given that the patients were Chinese, Dr. Anderson noted that Asian people have higher rates of intracranial atherosclerosis and more blood pressure complications in the heart and kidney than White patients. Stroke management patterns also differ.

“These points raise questions about generalizability, and while I think this is an issue for consideration, I do not think it should detract from the clarity of these results,” he commented.

The study is supported by grants from the Shanghai Hospital Development Center, the National Health and Medical Research Council of Australia, the China Stroke Prevention Project, Shanghai Changhai Hospital, the Science and Technology Commission of Shanghai Municipality, Takeda China, Genesis Medtech, and Penumbra. Dr. Anderson has received grants from the National Health and Medical Research Council and Medical Research Futures Fund of Australia, the UK Medical Research Council, Penumbra, and Takeda China.

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

A large randomized trial that was investigating intensive lowering of blood pressure in acute ischemic stroke patients who had undergone mechanical thrombectomy has been stopped early because of safety concerns.

“Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischemic stroke due to intracranial large-vessel occlusion,” the investigators conclude.

Results from the ENCHANTED2/MT trial were presented by Craig Anderson, MD, professor of neurology and epidemiology, University of New South Wales, Sydney, during the 14th World Stroke Congress (WSC) in Singapore.

The study was simultaneously published online in The Lancet.

“What our results have pretty convincingly shown is that in acute stroke patients who have undergone mechanical thrombectomy, lowering blood pressure down to a systolic of 120 mm Hg for 3 days is too low for too long. We shouldn’t go that far down,” Dr. Anderson said in an interview.

Dr. Anderson said the trial has provided an important message for clinical practice.

“This result is not what we expected, but it is a definitive result and gives us a lower safety margin for blood pressure in acute ischemic stroke patients. This, in itself, is a big step forward.”

He noted that the optimum blood pressure for these patients is not known.

“We need to do further trials to determine optimum blood pressure in these acute patients, but perhaps we should be aiming more towards 140 mm Hg,” he suggested.

“But this trial shows us that in patients who have had successful clot retrieval with endovascular treatment for acute ischemic stroke, careful blood pressure management is important to avoid levels becoming too low. We have to make sure we don’t overshoot down to 120 mm Hg or below.”

The chair of the WSC session at which the trial was presented, Jeyaraj Pandian, MD, head of neurology at Christian Medical College, Ludhiana, India, who is the current vice-president of the World Stroke Organization, said: “This is a very important result. It has major practical implications.”

As background, Dr. Anderson explained that elevated blood pressure is very common in patients who have an acute ischemic stroke, and the higher the blood pressure, the higher the chances of having a worse outcome.

“Theoretically, if we can control the blood pressure, we may be able to improve outcomes,” he said.

In 2019, the first ENCHANTED trial reported that controlling blood pressure by a moderate amount – to around 140 mm Hg, which is lower than currently recommended in the guidelines – was linked to a reduction in bleeding complications of thrombolysis and appeared safe, but it did not improve recovery, Dr. Anderson noted.

“This trial was done before mechanical thrombectomy became routinely adopted, and this procedure has now become the standard of care for large-vessel occlusion strokes, but we don’t know what we should do about blood pressure in these patients,” he added.

A smaller French trial has suggested lowering blood pressure to 130 mm Hg, rather than a more liberal 130-180 mm Hg, was safe after successful mechanical thrombectomy, but there was no effect on functional outcome.

“In stroke patients with a large-vessel occlusion, blood pressure is often elevated to very high levels. There are wide ranges of opinions on what to do about this – whether it should be lowered, and by how much,” Dr. Anderson said. “We conducted the current ENCHANTED2/MT trial to look at this issue.”

The trial randomly assigned patients who had undergone successful mechanical clot retrieval and reperfusion but whose blood pressure was still elevated to two groups. In one group, blood pressure was aggressively lowered to less than 120 mm Hg within 1 hour of reperfusion, and blood pressure was kept at this level for 3 days. In the other group, a more liberal approach was used: Blood pressure was kept at 140-180 mm Hg.

The primary endpoint was disability, as measured by the Modified Rankin Scale (mRS) score at 90 days.

The study was started in China with the intention of expanding recruitment internationally. The planned enrollment was more than 2,000 patients.

However, in March of 2022, after 821 patients had been enrolled, the data safety monitoring board (DSMB) recommended that recruitment into the trial be suspended because of a safety signal. All of the patients who had been recruited were from China.

These patients were followed to obtain the 3-month outcome results, after which the DSMB recommended that the trial be stopped because safety was still a problem.

Mean systolic blood pressure was 125 mm Hg at 1 hour and 121 mm Hg at 24 hours in the more intensive-treatment group; it was 143 mm Hg at 1 hour and 139 mm Hg at 24 hours in the less intensive-treatment group, giving an adjusted mean difference over 24 hours of 18 mm Hg.
 

Worse disability scores

Results showed that the patients who underwent the more intensive blood pressure lowering had more disability at 3-month follow-up, with worse scores on a shift analysis of the mRS than those in the less intensive group (common odds ratio, 1.37; 95% confidence interval, 1.07-1.76).

The unfavorable shift in mRS scores in the more intensive group was consistent in adjusted sensitivity analysis, and there was no significant heterogeneity in the treatment effect on the primary outcome across all prespecified subgroups.

The incidence of death or neurologic deterioration at 7 days was higher in the more intensive-treatment group than the less intensive-treatment group (common OR, 1.53), and a between-group difference emerged at 24 hours.

The incidence of death or disability (mRS scores, 3-6) at 90 days was higher among patients in the more intensive-treatment group than the less intensive-treatment group (53% vs. 39%; OR, 1.85; P = .0001).

Among those who survived, more patients in the more intensive-treatment group had major disability (mRS scores, 3-5) at 90 days than did patients in the less intensive-treatment group (43% vs. 28%; OR, 2.07; P = .0001).
 

No difference in ICH or severe hypotension episodes

The incidence of symptomatic intracranial hemorrhage, mortality, and serious adverse events did not significantly differ between the two groups. There were no significant differences in recurrent ischemic stroke events at 90 days, and no episodes of severe hypotension were reported as a serious adverse event.

“Our results show that intensive lowering of blood pressure appears to be associated with worsening physical disability. While there was no difference in mortality rates between the two groups, the lower blood pressure appeared to compromise the ability to recover from the stroke,” Dr. Anderson said.

On the possible mechanism of harm, he suggested that the intensive blood pressure reduction might be interfering with blood flow through the injured part of the brain and impeding the ability to recover from the clot removal procedure.
 

What levels should be aimed for?

Dr. Anderson stressed that it was important to have conducted this trial.

“Current guidelines recommend very conservative level of blood pressure in acute ischemic stroke patients – to below 180 mm Hg. But no lower limit is recommended.

“Most clinicians aim for about the 140 mm Hg mark, but there is a large variation in opinion on what to do,” he said. “Some doctors treat aggressively, believing that lower pressures could be beneficial in preventing bleeding and swelling, and others prefer to keep levels higher. Our results have helped to give some guidance on this.”

Asked what he thought an optimum target would be, Dr. Anderson replied: “For now, I think a target of around 140 mm Hg systolic would be reasonable, and there is no evidence to move below that.”

Yvo Roos, MD, professor of acute neurology at University Medical Center, Amsterdam, a co-author of the ENCHANTED2/MT trial, also commented: “The real importance of these study results is that they show that lowering blood pressure too much is detrimental on outcome. My personal interpretation, looking at the results of this study but also on the previous studies, is that we should aim for a target of 140-150 mm Hg. This is true for patients with recanalization therapy. For patients without any therapy, I would even be more careful in lowering blood pressure and recommend just staying below 180 mm Hg.”

As to whether these results are generalizable to other populations, given that the patients were Chinese, Dr. Anderson noted that Asian people have higher rates of intracranial atherosclerosis and more blood pressure complications in the heart and kidney than White patients. Stroke management patterns also differ.

“These points raise questions about generalizability, and while I think this is an issue for consideration, I do not think it should detract from the clarity of these results,” he commented.

The study is supported by grants from the Shanghai Hospital Development Center, the National Health and Medical Research Council of Australia, the China Stroke Prevention Project, Shanghai Changhai Hospital, the Science and Technology Commission of Shanghai Municipality, Takeda China, Genesis Medtech, and Penumbra. Dr. Anderson has received grants from the National Health and Medical Research Council and Medical Research Futures Fund of Australia, the UK Medical Research Council, Penumbra, and Takeda China.

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

A new study based on U.S. veterans’ medical records adds to the evidence for a link between gout – especially poorly controlled cases – and cardiovascular disease (CVD) risk, Tate Johnson, MD, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network.

Gout was associated with a 68% increased risk of heart failure (HF) hospitalization, 25% increased risk of HF-related death, and a 22% increased risk of major adverse cardiovascular events (MACE), said Dr. Johnson, of the division of rheumatology at the University of Nebraska, Omaha.

Poorly controlled serum urate was associated with a higher risk of cardiovascular events, regardless of the use of urate-lowering therapy (ULT). He said more research is needed to see if there is a causal link between gout, hyperuricemia – or its treatment – and CVD risk.

Dr. Johnson and colleagues used records from the Veterans Health Administration for this study. They created a retrospective, matched cohort study that looked at records dating from January 1999 to September 2015. Patients with gout (≥ 2 ICD-9 codes) were matched 1:10 on age, sex, and year of VHA enrollment to patients without a gout ICD-9 code or a record of receiving ULT. They matched 559,243 people with gout to 5,407,379 people who did not have a diagnosis or a recorded treatment for this condition.

Over 43,331,604 person-years, Dr. Johnson and colleagues observed 137,162 CVD events in gout (incidence rate 33.96 per 1,000 person-years) vs. 879,903 in non-gout patients (IR 22.37 per 1,000 person-years). Gout was most strongly associated with HF hospitalization, with a nearly threefold higher risk (hazard ratio, 2.78; 95% confidence interval, 2.73-2.83), which attenuated but persisted after adjustment for additional CVD risk factors (adjusted hazard ratio, 1.68; 95% CI, 1.65-1.70) and excluding patients with prevalent HF (aHR, 1.60; 95% CI, 1.57-1.64).

People with gout were also at higher risk of HF-related death (aHR, 1.25; 95% CI, 1.21-1.29), MACE (aHR, 1.22; 95% CI, 1.21-1.23), and coronary artery disease–related death (aHR, 1.21; 95% CI, 1.20-1.22).

Among people with gout in the study, poor serum urate control was associated with a higher risk of all CVD events, with the highest CVD risk occurring in patients with inadequately controlled serum urate despite receipt of ULT, particularly related to HF hospitalization (aHR, 1.43; 95% CI, 1.34-1.52) and HF-related death (aHR, 1.47; 95% CI, 1.34-1.61).

Limits of the study include the generalizability of the study population. Reflecting the VHA’s patient population, 99% of the cohort were men, with 62% of the gout group and 59.4% of the control group identifying as White and non-Hispanic.

The study provides evidence that may be found only by studying medical records, Richard J. Johnson, MD, of the University of Colorado at Denver, Aurora, said in an interview.

Dr. Richard Johnson, who is not related to the author, said that only about one-third of people with gout are adequately treated, and about another one-third take urate-lowering therapy (ULT) but fail to get their serum urate level under control. But it would be unethical to design a clinical trial to study CVD risk and poorly controlled serum urate without ULT treatment.

“The only way you can figure out if uric acid lowering is going to help these guys is to actually do a study like this where you see the ones who don’t get adequate treatment versus adequate treatment and you show that there’s going to be a difference in outcome,” he said.

Dr. Richard Johnson contrasted this approach with the one used in the recently reported study that appeared to cast doubt on the link between serum uric acid levels and cardiovascular disease. The ALL-HEART trial found that allopurinol, a drug commonly used to treat gout, provided no benefit in terms of reducing cardiovascular events in patients with ischemic heart disease. But these patients did not have gout, and that was a critical difference, he said.

He noted that it was not surprising that the results of ALL-HEART were negative, given the study design.

“The ALL-HEART study treated people regardless of their uric acid level, and they also excluded subjects who had a history of gout,” he said. “Yet the risk associated with uric acid occurs primarily among those with elevated serum uric acid levels and those with gout.”

The study received funding from the Rheumatology Research Foundation and the VHA. Neither Dr. Tate Johnson nor Dr. Richard Johnson had any relevant disclosures.

A new study based on U.S. veterans’ medical records adds to the evidence for a link between gout – especially poorly controlled cases – and cardiovascular disease (CVD) risk, Tate Johnson, MD, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network.

Gout was associated with a 68% increased risk of heart failure (HF) hospitalization, 25% increased risk of HF-related death, and a 22% increased risk of major adverse cardiovascular events (MACE), said Dr. Johnson, of the division of rheumatology at the University of Nebraska, Omaha.

Poorly controlled serum urate was associated with a higher risk of cardiovascular events, regardless of the use of urate-lowering therapy (ULT). He said more research is needed to see if there is a causal link between gout, hyperuricemia – or its treatment – and CVD risk.

Dr. Johnson and colleagues used records from the Veterans Health Administration for this study. They created a retrospective, matched cohort study that looked at records dating from January 1999 to September 2015. Patients with gout (≥ 2 ICD-9 codes) were matched 1:10 on age, sex, and year of VHA enrollment to patients without a gout ICD-9 code or a record of receiving ULT. They matched 559,243 people with gout to 5,407,379 people who did not have a diagnosis or a recorded treatment for this condition.

Over 43,331,604 person-years, Dr. Johnson and colleagues observed 137,162 CVD events in gout (incidence rate 33.96 per 1,000 person-years) vs. 879,903 in non-gout patients (IR 22.37 per 1,000 person-years). Gout was most strongly associated with HF hospitalization, with a nearly threefold higher risk (hazard ratio, 2.78; 95% confidence interval, 2.73-2.83), which attenuated but persisted after adjustment for additional CVD risk factors (adjusted hazard ratio, 1.68; 95% CI, 1.65-1.70) and excluding patients with prevalent HF (aHR, 1.60; 95% CI, 1.57-1.64).

People with gout were also at higher risk of HF-related death (aHR, 1.25; 95% CI, 1.21-1.29), MACE (aHR, 1.22; 95% CI, 1.21-1.23), and coronary artery disease–related death (aHR, 1.21; 95% CI, 1.20-1.22).

Among people with gout in the study, poor serum urate control was associated with a higher risk of all CVD events, with the highest CVD risk occurring in patients with inadequately controlled serum urate despite receipt of ULT, particularly related to HF hospitalization (aHR, 1.43; 95% CI, 1.34-1.52) and HF-related death (aHR, 1.47; 95% CI, 1.34-1.61).

Limits of the study include the generalizability of the study population. Reflecting the VHA’s patient population, 99% of the cohort were men, with 62% of the gout group and 59.4% of the control group identifying as White and non-Hispanic.

The study provides evidence that may be found only by studying medical records, Richard J. Johnson, MD, of the University of Colorado at Denver, Aurora, said in an interview.

Dr. Richard Johnson, who is not related to the author, said that only about one-third of people with gout are adequately treated, and about another one-third take urate-lowering therapy (ULT) but fail to get their serum urate level under control. But it would be unethical to design a clinical trial to study CVD risk and poorly controlled serum urate without ULT treatment.

“The only way you can figure out if uric acid lowering is going to help these guys is to actually do a study like this where you see the ones who don’t get adequate treatment versus adequate treatment and you show that there’s going to be a difference in outcome,” he said.

Dr. Richard Johnson contrasted this approach with the one used in the recently reported study that appeared to cast doubt on the link between serum uric acid levels and cardiovascular disease. The ALL-HEART trial found that allopurinol, a drug commonly used to treat gout, provided no benefit in terms of reducing cardiovascular events in patients with ischemic heart disease. But these patients did not have gout, and that was a critical difference, he said.

He noted that it was not surprising that the results of ALL-HEART were negative, given the study design.

“The ALL-HEART study treated people regardless of their uric acid level, and they also excluded subjects who had a history of gout,” he said. “Yet the risk associated with uric acid occurs primarily among those with elevated serum uric acid levels and those with gout.”

The study received funding from the Rheumatology Research Foundation and the VHA. Neither Dr. Tate Johnson nor Dr. Richard Johnson had any relevant disclosures.

A new study based on U.S. veterans’ medical records adds to the evidence for a link between gout – especially poorly controlled cases – and cardiovascular disease (CVD) risk, Tate Johnson, MD, reported at the annual research symposium of the Gout, Hyperuricemia, and Crystal Associated Disease Network.

Gout was associated with a 68% increased risk of heart failure (HF) hospitalization, 25% increased risk of HF-related death, and a 22% increased risk of major adverse cardiovascular events (MACE), said Dr. Johnson, of the division of rheumatology at the University of Nebraska, Omaha.

Poorly controlled serum urate was associated with a higher risk of cardiovascular events, regardless of the use of urate-lowering therapy (ULT). He said more research is needed to see if there is a causal link between gout, hyperuricemia – or its treatment – and CVD risk.

Dr. Johnson and colleagues used records from the Veterans Health Administration for this study. They created a retrospective, matched cohort study that looked at records dating from January 1999 to September 2015. Patients with gout (≥ 2 ICD-9 codes) were matched 1:10 on age, sex, and year of VHA enrollment to patients without a gout ICD-9 code or a record of receiving ULT. They matched 559,243 people with gout to 5,407,379 people who did not have a diagnosis or a recorded treatment for this condition.

Over 43,331,604 person-years, Dr. Johnson and colleagues observed 137,162 CVD events in gout (incidence rate 33.96 per 1,000 person-years) vs. 879,903 in non-gout patients (IR 22.37 per 1,000 person-years). Gout was most strongly associated with HF hospitalization, with a nearly threefold higher risk (hazard ratio, 2.78; 95% confidence interval, 2.73-2.83), which attenuated but persisted after adjustment for additional CVD risk factors (adjusted hazard ratio, 1.68; 95% CI, 1.65-1.70) and excluding patients with prevalent HF (aHR, 1.60; 95% CI, 1.57-1.64).

People with gout were also at higher risk of HF-related death (aHR, 1.25; 95% CI, 1.21-1.29), MACE (aHR, 1.22; 95% CI, 1.21-1.23), and coronary artery disease–related death (aHR, 1.21; 95% CI, 1.20-1.22).

Among people with gout in the study, poor serum urate control was associated with a higher risk of all CVD events, with the highest CVD risk occurring in patients with inadequately controlled serum urate despite receipt of ULT, particularly related to HF hospitalization (aHR, 1.43; 95% CI, 1.34-1.52) and HF-related death (aHR, 1.47; 95% CI, 1.34-1.61).

Limits of the study include the generalizability of the study population. Reflecting the VHA’s patient population, 99% of the cohort were men, with 62% of the gout group and 59.4% of the control group identifying as White and non-Hispanic.

The study provides evidence that may be found only by studying medical records, Richard J. Johnson, MD, of the University of Colorado at Denver, Aurora, said in an interview.

Dr. Richard Johnson, who is not related to the author, said that only about one-third of people with gout are adequately treated, and about another one-third take urate-lowering therapy (ULT) but fail to get their serum urate level under control. But it would be unethical to design a clinical trial to study CVD risk and poorly controlled serum urate without ULT treatment.

“The only way you can figure out if uric acid lowering is going to help these guys is to actually do a study like this where you see the ones who don’t get adequate treatment versus adequate treatment and you show that there’s going to be a difference in outcome,” he said.

Dr. Richard Johnson contrasted this approach with the one used in the recently reported study that appeared to cast doubt on the link between serum uric acid levels and cardiovascular disease. The ALL-HEART trial found that allopurinol, a drug commonly used to treat gout, provided no benefit in terms of reducing cardiovascular events in patients with ischemic heart disease. But these patients did not have gout, and that was a critical difference, he said.

He noted that it was not surprising that the results of ALL-HEART were negative, given the study design.

“The ALL-HEART study treated people regardless of their uric acid level, and they also excluded subjects who had a history of gout,” he said. “Yet the risk associated with uric acid occurs primarily among those with elevated serum uric acid levels and those with gout.”

The study received funding from the Rheumatology Research Foundation and the VHA. Neither Dr. Tate Johnson nor Dr. Richard Johnson had any relevant disclosures.

An endoscopic severity score can achieve a higher specificity in predicting the need for selective immunosuppressive therapy among immune-mediated colitis patients than clinical symptom grading alone, according to new research presented at the annual meeting of the American College of Gastroenterology.

An endoscopy score cutoff of 4 or higher had a specificity of 82.8% across all colitis grades, and a cutoff of 5 or higher had a specificity of 87.6%, said Yinghong Wang, MD, PhD, a gastroenterologist at the University of Texas MD Anderson Cancer Center, Houston.

Immune-mediated colitis (IMC) is a common immune-related adverse event associated with immune checkpoint inhibitors. Dr. Wang and colleagues previously reported on endoscopic presentations of IMC, including severe inflammation with deep ulcerated mucosa; moderate to severe inflammation with diffuse erythema, superficial ulcers, exudate, and loss of vasculature; and mild inflammation with patchy erythema, aphtha, edema, or normal mucosa associated with histological inflammation.

An endoscopic severity score can achieve a higher specificity in predicting the need for selective immunosuppressive therapy among immune-mediated colitis patients than clinical symptom grading alone, according to new research presented at the annual meeting of the American College of Gastroenterology.

An endoscopy score cutoff of 4 or higher had a specificity of 82.8% across all colitis grades, and a cutoff of 5 or higher had a specificity of 87.6%, said Yinghong Wang, MD, PhD, a gastroenterologist at the University of Texas MD Anderson Cancer Center, Houston.

Immune-mediated colitis (IMC) is a common immune-related adverse event associated with immune checkpoint inhibitors. Dr. Wang and colleagues previously reported on endoscopic presentations of IMC, including severe inflammation with deep ulcerated mucosa; moderate to severe inflammation with diffuse erythema, superficial ulcers, exudate, and loss of vasculature; and mild inflammation with patchy erythema, aphtha, edema, or normal mucosa associated with histological inflammation.

An endoscopic severity score can achieve a higher specificity in predicting the need for selective immunosuppressive therapy among immune-mediated colitis patients than clinical symptom grading alone, according to new research presented at the annual meeting of the American College of Gastroenterology.

An endoscopy score cutoff of 4 or higher had a specificity of 82.8% across all colitis grades, and a cutoff of 5 or higher had a specificity of 87.6%, said Yinghong Wang, MD, PhD, a gastroenterologist at the University of Texas MD Anderson Cancer Center, Houston.

Immune-mediated colitis (IMC) is a common immune-related adverse event associated with immune checkpoint inhibitors. Dr. Wang and colleagues previously reported on endoscopic presentations of IMC, including severe inflammation with deep ulcerated mucosa; moderate to severe inflammation with diffuse erythema, superficial ulcers, exudate, and loss of vasculature; and mild inflammation with patchy erythema, aphtha, edema, or normal mucosa associated with histological inflammation.