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Naltrexone cuts hospitalization, deaths in alcohol use disorder
Naltrexone reduces the risk for hospitalization for alcohol use disorder (AUD), regardless of whether it is used alone or in conjunction with disulfiram or acamprosate, research suggests.
Investigators analyzed 10-year data on more than 125,000 Swedish residents with AUD and found that naltrexone, used as monotherapy or combined with acamprosate or disulfiram, was associated with significantly lower risk for AUD hospitalization or all-cause hospitalization in comparison with patients who did not use AUD medication. The patients ranged in age from 16 to 64 years.
By contrast, benzodiazepines and acamprosate monotherapy were associated with increased risk for AUD hospitalization.
“The take-home message for practicing clinicians would be that especially naltrexone use is associated with favorable treatment outcomes and should be utilized as part of the treatment protocol for AUD,” study investigator Milja Heikkinen, MD, specialist in forensic psychiatry and addiction medicine, University of Eastern Finland, Kuopio, told this news organization.
On the other hand, “benzodiazepines should be avoided and should not be administered other than for alcohol withdrawal symptoms,” she said.
The study was published online Jan. 4 in Addiction.
Real-world data
Previous research has shown that disulfiram, acamprosate, naltrexone, and nalmefene are efficacious in treating AUD, but most studies have been randomized controlled trials or meta-analyses, the authors write.
“Very little is known about overall health outcomes (such as risks of hospitalization and mortality) associated with specific treatments in real-world circumstances,” they write.
“The study was motivated by the fact that, although AUD is a significant public health concern, very little is known, especially about the comparative effectiveness of medications indicated in AUD,” said Dr. Heikkinen.
who had been diagnosed with AUD (62.5% men; mean [standard deviation] age, 38.1 [15.9] years). They followed the cohort over a median of 4.6 years (interquartile range, 2.1-.2 years).
During the follow-up period, roughly one-fourth of patients (25.6) underwent treatment with one or more drugs.
The main outcome measure was AUD-related hospitalization. Secondary outcomes were hospitalization for any cause and for alcohol-related somatic causes; all-cause mortality; and work disability.
Two types of analyses were conducted. The within-individual analyses, designed to eliminate selection bias, compared the use of a medication to periods during which the same individual was not using the medication.
Between-individual analyses (adjusted for sex, age, educational level, number of previous AUD-related hospitalizations, time since first AUD diagnosis, comorbidities, and use of other medications) utilized a “traditional” multivariate-adjusted Cox hazards regression model.
AUD pharmacotherapy ‘underutilized’
Close to one-fourth of patients (23.9%) experienced the main outcome event (AUD-related hospitalization) during the follow-up period.
The within-individual analysis showed that naltrexone – whether used as monotherapy or adjunctively with disulfiram or acamprosate – “was associated with a significantly lower risk of AUD-related hospitalization, compared to those time periods in which the same individual did not use any AUD medication,” the authors report.
By contrast, they state, acamprosate monotherapy and benzodiazepines were associated with a significantly higher risk for AUD-related hospitalization.
Similar results were obtained in the between-individual analysis. Longer duration of naltrexone use was associated with lower risk for AUD-related hospitalization.
The pattern was also found when the outcome was hospitalization for any cause. However, unlike the findings of the within-individual model, the second model found that acamprosate monotherapy was not associated with a higher risk for any-cause hospitalization.
Polytherapy, including combinations of the four AUD medications, as well as disulfiram monotherapy were similarly associated with lower risk for hospitalization for alcohol-related somatic causes.
Of the overall cohort, 6.2% died during the follow-up period. No association was found between disulfiram, acamprosate, nalmefene, and naltrexone use and all-cause mortality. By contrast, benzodiazepine use was associated with a significantly higher mortality rate (hazard ratio, 1.11; 95% confidence interval, 1.04-1.19).
“AUD drugs are underutilized, despite AUD being a significant public health concern,” Dr. Heikkinen noted. On the other hand, benzodiazepine use is “very common.”
‘Ravages’ of benzodiazepines
Commenting on the study in an interview, John Krystal, MD, professor and chair of psychiatry and director of the Center for the Translational Neuroscience of Alcoholism, Yale University, New Haven, Conn., said, “The main message from the study for practicing clinicians is that treatment works.”
Dr. Krystal, who was not involved with the study, noted that “many practicing clinicians are discouraged by the course of their patients with AUD, and this study highlights that naltrexone, perhaps in combination with other medications, may be effective in preventing hospitalization and, presumably, other hospitalization-related complications of AUD.”
Also commenting on the study, Raymond Anton, MD, professor, department of psychiatry and behavioral sciences, Medical University of South Carolina, Charleston, suggested that the “clinical knowledge of the harm of benzodiazepines in those with AUD is reinforced by these findings.”
In fact, the harm of benzodiazepines might be the study’s “most important message ... [a message that was] recently highlighted by the Netflix series “The Queen’s Gambit”, which shows the ravages of using both together, or how one leads to potential addiction with the other,” said Dr. Anton, who was not involved with the study.
The other “big take-home message is that naltrexone should be used more frequently,” said Dr. Anton, distinguished professor of psychiatry at the university and scientific director of the Charleston Alcohol Research Center. He noted that there are “recent data suggesting some clinical and genetic indicators that predict responsiveness to these medications, improving efficacy.”
The study was funded by the Finnish Ministry of Social Affairs and Health. Dr. Heikkinen reports no relevant financial relationships. The other authors’ disclosures are listed on the original article. Dr. Krystal consults for companies currently developing other treatments for AUDs and receives medications to test from AstraZeneca and Novartis for NIAAA-funded research programs. Dr. Anton has consulted for Alkermes, Lipha, and Lundbeck in the past. He is also chair of the Alcohol Clinical Trials Initiative, which is a public-private partnership partially sponsored by several companies and has received grant funding from the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism to study pharmacotherapies, including naltrexone, nalmefene, and acamprosate.
A version of this article first appeared on Medscape.com.
Naltrexone reduces the risk for hospitalization for alcohol use disorder (AUD), regardless of whether it is used alone or in conjunction with disulfiram or acamprosate, research suggests.
Investigators analyzed 10-year data on more than 125,000 Swedish residents with AUD and found that naltrexone, used as monotherapy or combined with acamprosate or disulfiram, was associated with significantly lower risk for AUD hospitalization or all-cause hospitalization in comparison with patients who did not use AUD medication. The patients ranged in age from 16 to 64 years.
By contrast, benzodiazepines and acamprosate monotherapy were associated with increased risk for AUD hospitalization.
“The take-home message for practicing clinicians would be that especially naltrexone use is associated with favorable treatment outcomes and should be utilized as part of the treatment protocol for AUD,” study investigator Milja Heikkinen, MD, specialist in forensic psychiatry and addiction medicine, University of Eastern Finland, Kuopio, told this news organization.
On the other hand, “benzodiazepines should be avoided and should not be administered other than for alcohol withdrawal symptoms,” she said.
The study was published online Jan. 4 in Addiction.
Real-world data
Previous research has shown that disulfiram, acamprosate, naltrexone, and nalmefene are efficacious in treating AUD, but most studies have been randomized controlled trials or meta-analyses, the authors write.
“Very little is known about overall health outcomes (such as risks of hospitalization and mortality) associated with specific treatments in real-world circumstances,” they write.
“The study was motivated by the fact that, although AUD is a significant public health concern, very little is known, especially about the comparative effectiveness of medications indicated in AUD,” said Dr. Heikkinen.
who had been diagnosed with AUD (62.5% men; mean [standard deviation] age, 38.1 [15.9] years). They followed the cohort over a median of 4.6 years (interquartile range, 2.1-.2 years).
During the follow-up period, roughly one-fourth of patients (25.6) underwent treatment with one or more drugs.
The main outcome measure was AUD-related hospitalization. Secondary outcomes were hospitalization for any cause and for alcohol-related somatic causes; all-cause mortality; and work disability.
Two types of analyses were conducted. The within-individual analyses, designed to eliminate selection bias, compared the use of a medication to periods during which the same individual was not using the medication.
Between-individual analyses (adjusted for sex, age, educational level, number of previous AUD-related hospitalizations, time since first AUD diagnosis, comorbidities, and use of other medications) utilized a “traditional” multivariate-adjusted Cox hazards regression model.
AUD pharmacotherapy ‘underutilized’
Close to one-fourth of patients (23.9%) experienced the main outcome event (AUD-related hospitalization) during the follow-up period.
The within-individual analysis showed that naltrexone – whether used as monotherapy or adjunctively with disulfiram or acamprosate – “was associated with a significantly lower risk of AUD-related hospitalization, compared to those time periods in which the same individual did not use any AUD medication,” the authors report.
By contrast, they state, acamprosate monotherapy and benzodiazepines were associated with a significantly higher risk for AUD-related hospitalization.
Similar results were obtained in the between-individual analysis. Longer duration of naltrexone use was associated with lower risk for AUD-related hospitalization.
The pattern was also found when the outcome was hospitalization for any cause. However, unlike the findings of the within-individual model, the second model found that acamprosate monotherapy was not associated with a higher risk for any-cause hospitalization.
Polytherapy, including combinations of the four AUD medications, as well as disulfiram monotherapy were similarly associated with lower risk for hospitalization for alcohol-related somatic causes.
Of the overall cohort, 6.2% died during the follow-up period. No association was found between disulfiram, acamprosate, nalmefene, and naltrexone use and all-cause mortality. By contrast, benzodiazepine use was associated with a significantly higher mortality rate (hazard ratio, 1.11; 95% confidence interval, 1.04-1.19).
“AUD drugs are underutilized, despite AUD being a significant public health concern,” Dr. Heikkinen noted. On the other hand, benzodiazepine use is “very common.”
‘Ravages’ of benzodiazepines
Commenting on the study in an interview, John Krystal, MD, professor and chair of psychiatry and director of the Center for the Translational Neuroscience of Alcoholism, Yale University, New Haven, Conn., said, “The main message from the study for practicing clinicians is that treatment works.”
Dr. Krystal, who was not involved with the study, noted that “many practicing clinicians are discouraged by the course of their patients with AUD, and this study highlights that naltrexone, perhaps in combination with other medications, may be effective in preventing hospitalization and, presumably, other hospitalization-related complications of AUD.”
Also commenting on the study, Raymond Anton, MD, professor, department of psychiatry and behavioral sciences, Medical University of South Carolina, Charleston, suggested that the “clinical knowledge of the harm of benzodiazepines in those with AUD is reinforced by these findings.”
In fact, the harm of benzodiazepines might be the study’s “most important message ... [a message that was] recently highlighted by the Netflix series “The Queen’s Gambit”, which shows the ravages of using both together, or how one leads to potential addiction with the other,” said Dr. Anton, who was not involved with the study.
The other “big take-home message is that naltrexone should be used more frequently,” said Dr. Anton, distinguished professor of psychiatry at the university and scientific director of the Charleston Alcohol Research Center. He noted that there are “recent data suggesting some clinical and genetic indicators that predict responsiveness to these medications, improving efficacy.”
The study was funded by the Finnish Ministry of Social Affairs and Health. Dr. Heikkinen reports no relevant financial relationships. The other authors’ disclosures are listed on the original article. Dr. Krystal consults for companies currently developing other treatments for AUDs and receives medications to test from AstraZeneca and Novartis for NIAAA-funded research programs. Dr. Anton has consulted for Alkermes, Lipha, and Lundbeck in the past. He is also chair of the Alcohol Clinical Trials Initiative, which is a public-private partnership partially sponsored by several companies and has received grant funding from the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism to study pharmacotherapies, including naltrexone, nalmefene, and acamprosate.
A version of this article first appeared on Medscape.com.
Naltrexone reduces the risk for hospitalization for alcohol use disorder (AUD), regardless of whether it is used alone or in conjunction with disulfiram or acamprosate, research suggests.
Investigators analyzed 10-year data on more than 125,000 Swedish residents with AUD and found that naltrexone, used as monotherapy or combined with acamprosate or disulfiram, was associated with significantly lower risk for AUD hospitalization or all-cause hospitalization in comparison with patients who did not use AUD medication. The patients ranged in age from 16 to 64 years.
By contrast, benzodiazepines and acamprosate monotherapy were associated with increased risk for AUD hospitalization.
“The take-home message for practicing clinicians would be that especially naltrexone use is associated with favorable treatment outcomes and should be utilized as part of the treatment protocol for AUD,” study investigator Milja Heikkinen, MD, specialist in forensic psychiatry and addiction medicine, University of Eastern Finland, Kuopio, told this news organization.
On the other hand, “benzodiazepines should be avoided and should not be administered other than for alcohol withdrawal symptoms,” she said.
The study was published online Jan. 4 in Addiction.
Real-world data
Previous research has shown that disulfiram, acamprosate, naltrexone, and nalmefene are efficacious in treating AUD, but most studies have been randomized controlled trials or meta-analyses, the authors write.
“Very little is known about overall health outcomes (such as risks of hospitalization and mortality) associated with specific treatments in real-world circumstances,” they write.
“The study was motivated by the fact that, although AUD is a significant public health concern, very little is known, especially about the comparative effectiveness of medications indicated in AUD,” said Dr. Heikkinen.
who had been diagnosed with AUD (62.5% men; mean [standard deviation] age, 38.1 [15.9] years). They followed the cohort over a median of 4.6 years (interquartile range, 2.1-.2 years).
During the follow-up period, roughly one-fourth of patients (25.6) underwent treatment with one or more drugs.
The main outcome measure was AUD-related hospitalization. Secondary outcomes were hospitalization for any cause and for alcohol-related somatic causes; all-cause mortality; and work disability.
Two types of analyses were conducted. The within-individual analyses, designed to eliminate selection bias, compared the use of a medication to periods during which the same individual was not using the medication.
Between-individual analyses (adjusted for sex, age, educational level, number of previous AUD-related hospitalizations, time since first AUD diagnosis, comorbidities, and use of other medications) utilized a “traditional” multivariate-adjusted Cox hazards regression model.
AUD pharmacotherapy ‘underutilized’
Close to one-fourth of patients (23.9%) experienced the main outcome event (AUD-related hospitalization) during the follow-up period.
The within-individual analysis showed that naltrexone – whether used as monotherapy or adjunctively with disulfiram or acamprosate – “was associated with a significantly lower risk of AUD-related hospitalization, compared to those time periods in which the same individual did not use any AUD medication,” the authors report.
By contrast, they state, acamprosate monotherapy and benzodiazepines were associated with a significantly higher risk for AUD-related hospitalization.
Similar results were obtained in the between-individual analysis. Longer duration of naltrexone use was associated with lower risk for AUD-related hospitalization.
The pattern was also found when the outcome was hospitalization for any cause. However, unlike the findings of the within-individual model, the second model found that acamprosate monotherapy was not associated with a higher risk for any-cause hospitalization.
Polytherapy, including combinations of the four AUD medications, as well as disulfiram monotherapy were similarly associated with lower risk for hospitalization for alcohol-related somatic causes.
Of the overall cohort, 6.2% died during the follow-up period. No association was found between disulfiram, acamprosate, nalmefene, and naltrexone use and all-cause mortality. By contrast, benzodiazepine use was associated with a significantly higher mortality rate (hazard ratio, 1.11; 95% confidence interval, 1.04-1.19).
“AUD drugs are underutilized, despite AUD being a significant public health concern,” Dr. Heikkinen noted. On the other hand, benzodiazepine use is “very common.”
‘Ravages’ of benzodiazepines
Commenting on the study in an interview, John Krystal, MD, professor and chair of psychiatry and director of the Center for the Translational Neuroscience of Alcoholism, Yale University, New Haven, Conn., said, “The main message from the study for practicing clinicians is that treatment works.”
Dr. Krystal, who was not involved with the study, noted that “many practicing clinicians are discouraged by the course of their patients with AUD, and this study highlights that naltrexone, perhaps in combination with other medications, may be effective in preventing hospitalization and, presumably, other hospitalization-related complications of AUD.”
Also commenting on the study, Raymond Anton, MD, professor, department of psychiatry and behavioral sciences, Medical University of South Carolina, Charleston, suggested that the “clinical knowledge of the harm of benzodiazepines in those with AUD is reinforced by these findings.”
In fact, the harm of benzodiazepines might be the study’s “most important message ... [a message that was] recently highlighted by the Netflix series “The Queen’s Gambit”, which shows the ravages of using both together, or how one leads to potential addiction with the other,” said Dr. Anton, who was not involved with the study.
The other “big take-home message is that naltrexone should be used more frequently,” said Dr. Anton, distinguished professor of psychiatry at the university and scientific director of the Charleston Alcohol Research Center. He noted that there are “recent data suggesting some clinical and genetic indicators that predict responsiveness to these medications, improving efficacy.”
The study was funded by the Finnish Ministry of Social Affairs and Health. Dr. Heikkinen reports no relevant financial relationships. The other authors’ disclosures are listed on the original article. Dr. Krystal consults for companies currently developing other treatments for AUDs and receives medications to test from AstraZeneca and Novartis for NIAAA-funded research programs. Dr. Anton has consulted for Alkermes, Lipha, and Lundbeck in the past. He is also chair of the Alcohol Clinical Trials Initiative, which is a public-private partnership partially sponsored by several companies and has received grant funding from the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism to study pharmacotherapies, including naltrexone, nalmefene, and acamprosate.
A version of this article first appeared on Medscape.com.
A hard-to-reach bleeding lesion
The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.
As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.
The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.
Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)
Yang YW, DiCaudo DJ. Effects of curettage after shave biopsy of unexpected melanoma: a retrospective review. J Am Acad Dermatol. 2018;78:1000-1002.
The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.
As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.
The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.
Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)
The history and exam were all suspicious for basal cell carcinoma (BCC), the most common of all cancers in the United States. (In African Americans, the most common skin cancer is squamous cell carcinoma). The suspicious lesion in this case was in a crevice, making it difficult to obtain a shave or punch biopsy.
As a result, a 4-mm disposable sterile curette was used (Figure). After informed consent was obtained, the lesion was cleansed with alcohol and marked with a surgical marker. Then, buffered lidocaine 1% with epinephrine was injected with a small syringe. Using a firm scraping motion with gentle rotation, a 4-mm sample of the lesion was quickly obtained and placed in standard formalin. Hemostasis was immediately obtained with firm application of 70% aluminum chloride in water using a cotton-tipped applicator. Heavy petrolatum was applied as a dressing.
The patient was confirmed to have a BCC and underwent Mohs surgery with clear margins after 1 stage. This case demonstrates the utility of a curette as a biopsy instrument for patients presenting with suspicious lesions in hard-to-reach places.
Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)
Yang YW, DiCaudo DJ. Effects of curettage after shave biopsy of unexpected melanoma: a retrospective review. J Am Acad Dermatol. 2018;78:1000-1002.
Yang YW, DiCaudo DJ. Effects of curettage after shave biopsy of unexpected melanoma: a retrospective review. J Am Acad Dermatol. 2018;78:1000-1002.
NAFLD linked to worse outcomes in IBD
Nonalcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD) is associated with worse outcomes, and that relationship may be influenced by nonmetabolic factors. That is the conclusion of a new nationwide database analysis. NAFLD is common in IBD, with an estimated prevalence of 27%-32%.
Previous, smaller studies showed possible links between NAFLD and a history of IBD surgery, IBD disease activity, and metabolic factors, “but none of the studies looked at it on the scale that we did, and our study was more focused on outcomes than simply examining factors associated with both NAFLD and IBD,” Shaya Noorian, MD, of UCLA Medical Center in Los Angeles, said in an interview. Dr. Noorian presented the research at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Noorian and colleagues found higher rates of hospital readmission, longer hospitalization, and higher costs, but not higher rates of death among patients with both Crohn’s disease or ulcerative colitis and NAFLD. The researchers analyzed data from patients in the Nationwide Readmissions Database (2016-2017), using ICD-10 codes to identify patients with IBD and NAFLD, along with propensity-matched controls. The study included 3,655 with Crohn’s disease and NAFLD and 7,482 without, and there were 2,026 with ulcerative colitis and NAFLD 4,094 without.
IBD hospital readmission rates were higher with comorbid NAFLD in Crohn’s disease (hazard ratio, 1.98; 95% confidence interval, 1.8-2.17; P < .001) and ulcerative colitis (HR, 1.97; 95% CI, 1.67-2.32; P < .001). Comorbid NAFLD was associated with additional length of stay Crohn’s disease (0.74 days; 95% CI, 0.29-1.18; P < .01) and ulcerative colitis (0.84 days; 0.32-1.35, respectively; P < .01), and there was additional cost of care with both Crohn’s disease ($7,766; 95% CI, $2,693-$12,839; P < .01) and ulcerative colitis ($11,496; 95% CI, $4,361-$18,631; P < .01).
Kaplan Meier curves for IBD readmission-free survival versus days since discharge showed clear separation in both Crohn’s disease and ulcerative colitis among patients with versus those without NAFLD.
Although evidence points to nonmetabolic factors being involved, metabolic factors such as obesity and diabetes are likely important as well. “We still do recognize that it’s very likely that these metabolic factors play a role in developing NAFLD in IBD. I think the fact that there are worse outcomes in patients with NAFLD supports the fact that we should do our best to control the metabolic factors like diabetes, obesity, et cetera. We don’t want to minimize that aspect of it. But I think the fact that there were still worse outcomes after adjusting for metabolic factors emphasizes the importance of researching these factors further to see which ones are the main contributors. If we can find the main contributor, whether that’s medication, IBD disease burden, or history of surgery, perhaps we can use that information to prevent development or progression of NAFLD,” said Dr. Noorian.
“Historical reports have examined the relationship between Crohn’s disease and NAFLD. The currently study included both Crohn’s and ulcerative colitis, thus impressively demonstrating the importance of this interaction across IBD,” said Matthew Ciorba, MD, director of the IBD Center at Washington University in St. Louis, who attended the session.
“This is the largest study to date, and the signal is very clear. It really does underscore the need [to study not just how] medications and other factors influence the clinical syndrome, but how it happens mechanistically. There are a multitude of metabolic interactions going on between the gut and liver. We need to understand this better – not just at the systemic level, but at the enterohepatic circulation level,” said Dr. Ciorba.
Possible mechanisms include liver toxicity due to medication, IBD-associated inflammation, or changes to gut bacteria, according to Dr. Noorian.
The study also brings to light something that could become an emerging problem. “In the past, Crohn’s patients were oftentimes thin because their Crohn’s disease wasn’t well treated. They were taking steroids all the time, so they had fat redistribution, including to the liver. Now we see IBD patients who are obese, and most are not underweight. It has become a compounding problem at this point with both conditions contributing to morbidity,” said Dr. Ciorba.
The study had no source of funding. Dr. Noorian and Dr. Ciorba have no relevant financial disclosures.
Nonalcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD) is associated with worse outcomes, and that relationship may be influenced by nonmetabolic factors. That is the conclusion of a new nationwide database analysis. NAFLD is common in IBD, with an estimated prevalence of 27%-32%.
Previous, smaller studies showed possible links between NAFLD and a history of IBD surgery, IBD disease activity, and metabolic factors, “but none of the studies looked at it on the scale that we did, and our study was more focused on outcomes than simply examining factors associated with both NAFLD and IBD,” Shaya Noorian, MD, of UCLA Medical Center in Los Angeles, said in an interview. Dr. Noorian presented the research at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Noorian and colleagues found higher rates of hospital readmission, longer hospitalization, and higher costs, but not higher rates of death among patients with both Crohn’s disease or ulcerative colitis and NAFLD. The researchers analyzed data from patients in the Nationwide Readmissions Database (2016-2017), using ICD-10 codes to identify patients with IBD and NAFLD, along with propensity-matched controls. The study included 3,655 with Crohn’s disease and NAFLD and 7,482 without, and there were 2,026 with ulcerative colitis and NAFLD 4,094 without.
IBD hospital readmission rates were higher with comorbid NAFLD in Crohn’s disease (hazard ratio, 1.98; 95% confidence interval, 1.8-2.17; P < .001) and ulcerative colitis (HR, 1.97; 95% CI, 1.67-2.32; P < .001). Comorbid NAFLD was associated with additional length of stay Crohn’s disease (0.74 days; 95% CI, 0.29-1.18; P < .01) and ulcerative colitis (0.84 days; 0.32-1.35, respectively; P < .01), and there was additional cost of care with both Crohn’s disease ($7,766; 95% CI, $2,693-$12,839; P < .01) and ulcerative colitis ($11,496; 95% CI, $4,361-$18,631; P < .01).
Kaplan Meier curves for IBD readmission-free survival versus days since discharge showed clear separation in both Crohn’s disease and ulcerative colitis among patients with versus those without NAFLD.
Although evidence points to nonmetabolic factors being involved, metabolic factors such as obesity and diabetes are likely important as well. “We still do recognize that it’s very likely that these metabolic factors play a role in developing NAFLD in IBD. I think the fact that there are worse outcomes in patients with NAFLD supports the fact that we should do our best to control the metabolic factors like diabetes, obesity, et cetera. We don’t want to minimize that aspect of it. But I think the fact that there were still worse outcomes after adjusting for metabolic factors emphasizes the importance of researching these factors further to see which ones are the main contributors. If we can find the main contributor, whether that’s medication, IBD disease burden, or history of surgery, perhaps we can use that information to prevent development or progression of NAFLD,” said Dr. Noorian.
“Historical reports have examined the relationship between Crohn’s disease and NAFLD. The currently study included both Crohn’s and ulcerative colitis, thus impressively demonstrating the importance of this interaction across IBD,” said Matthew Ciorba, MD, director of the IBD Center at Washington University in St. Louis, who attended the session.
“This is the largest study to date, and the signal is very clear. It really does underscore the need [to study not just how] medications and other factors influence the clinical syndrome, but how it happens mechanistically. There are a multitude of metabolic interactions going on between the gut and liver. We need to understand this better – not just at the systemic level, but at the enterohepatic circulation level,” said Dr. Ciorba.
Possible mechanisms include liver toxicity due to medication, IBD-associated inflammation, or changes to gut bacteria, according to Dr. Noorian.
The study also brings to light something that could become an emerging problem. “In the past, Crohn’s patients were oftentimes thin because their Crohn’s disease wasn’t well treated. They were taking steroids all the time, so they had fat redistribution, including to the liver. Now we see IBD patients who are obese, and most are not underweight. It has become a compounding problem at this point with both conditions contributing to morbidity,” said Dr. Ciorba.
The study had no source of funding. Dr. Noorian and Dr. Ciorba have no relevant financial disclosures.
Nonalcoholic fatty liver disease (NAFLD) in patients with inflammatory bowel disease (IBD) is associated with worse outcomes, and that relationship may be influenced by nonmetabolic factors. That is the conclusion of a new nationwide database analysis. NAFLD is common in IBD, with an estimated prevalence of 27%-32%.
Previous, smaller studies showed possible links between NAFLD and a history of IBD surgery, IBD disease activity, and metabolic factors, “but none of the studies looked at it on the scale that we did, and our study was more focused on outcomes than simply examining factors associated with both NAFLD and IBD,” Shaya Noorian, MD, of UCLA Medical Center in Los Angeles, said in an interview. Dr. Noorian presented the research at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
Dr. Noorian and colleagues found higher rates of hospital readmission, longer hospitalization, and higher costs, but not higher rates of death among patients with both Crohn’s disease or ulcerative colitis and NAFLD. The researchers analyzed data from patients in the Nationwide Readmissions Database (2016-2017), using ICD-10 codes to identify patients with IBD and NAFLD, along with propensity-matched controls. The study included 3,655 with Crohn’s disease and NAFLD and 7,482 without, and there were 2,026 with ulcerative colitis and NAFLD 4,094 without.
IBD hospital readmission rates were higher with comorbid NAFLD in Crohn’s disease (hazard ratio, 1.98; 95% confidence interval, 1.8-2.17; P < .001) and ulcerative colitis (HR, 1.97; 95% CI, 1.67-2.32; P < .001). Comorbid NAFLD was associated with additional length of stay Crohn’s disease (0.74 days; 95% CI, 0.29-1.18; P < .01) and ulcerative colitis (0.84 days; 0.32-1.35, respectively; P < .01), and there was additional cost of care with both Crohn’s disease ($7,766; 95% CI, $2,693-$12,839; P < .01) and ulcerative colitis ($11,496; 95% CI, $4,361-$18,631; P < .01).
Kaplan Meier curves for IBD readmission-free survival versus days since discharge showed clear separation in both Crohn’s disease and ulcerative colitis among patients with versus those without NAFLD.
Although evidence points to nonmetabolic factors being involved, metabolic factors such as obesity and diabetes are likely important as well. “We still do recognize that it’s very likely that these metabolic factors play a role in developing NAFLD in IBD. I think the fact that there are worse outcomes in patients with NAFLD supports the fact that we should do our best to control the metabolic factors like diabetes, obesity, et cetera. We don’t want to minimize that aspect of it. But I think the fact that there were still worse outcomes after adjusting for metabolic factors emphasizes the importance of researching these factors further to see which ones are the main contributors. If we can find the main contributor, whether that’s medication, IBD disease burden, or history of surgery, perhaps we can use that information to prevent development or progression of NAFLD,” said Dr. Noorian.
“Historical reports have examined the relationship between Crohn’s disease and NAFLD. The currently study included both Crohn’s and ulcerative colitis, thus impressively demonstrating the importance of this interaction across IBD,” said Matthew Ciorba, MD, director of the IBD Center at Washington University in St. Louis, who attended the session.
“This is the largest study to date, and the signal is very clear. It really does underscore the need [to study not just how] medications and other factors influence the clinical syndrome, but how it happens mechanistically. There are a multitude of metabolic interactions going on between the gut and liver. We need to understand this better – not just at the systemic level, but at the enterohepatic circulation level,” said Dr. Ciorba.
Possible mechanisms include liver toxicity due to medication, IBD-associated inflammation, or changes to gut bacteria, according to Dr. Noorian.
The study also brings to light something that could become an emerging problem. “In the past, Crohn’s patients were oftentimes thin because their Crohn’s disease wasn’t well treated. They were taking steroids all the time, so they had fat redistribution, including to the liver. Now we see IBD patients who are obese, and most are not underweight. It has become a compounding problem at this point with both conditions contributing to morbidity,” said Dr. Ciorba.
The study had no source of funding. Dr. Noorian and Dr. Ciorba have no relevant financial disclosures.
FROM THE CROHN’S & COLITIS CONGRESS
Can ‘big’ be healthy? Yes – and no
While many people were committing to their New Year’s resolutions to lose weight, in January 2020 Cosmopolitan UK magazine released covers portraying 11 women of different shapes and sizes, with the headline, “This is healthy!” Each version of the cover features one or more of the 11 women wearing athletic gear and makeup, some of whom are caught mid-action – boxing, doing yoga, or simply rejoicing in being who they are. Seeing these, I was reminded of a patient I cared for as an intern.
Janet Spears (not her real name) was thin. Standing barely 5 feet 3 inches, she weighed 110 pounds. For those out there who think of size in terms of body mass index (BMI), it was about 20 kg/m2, solidly in the “normal” category. At the age of 62, despite this healthy BMI, she had so much plaque in her arteries that she needed surgery to improve blood flow to her foot.
Admittedly, whenever I had read about people with high cholesterol, type 2 diabetes, or atherosclerosis, I pictured bigger people. But when I met Ms. Spears, I realized that one’s health cannot necessarily be inferred from physical appearance.
As a bariatric surgeon board certified in obesity medicine, I’ve probably spent more time thinking and learning about obesity than most people – and yet I still didn’t know what to make of the Cosmopolitan covers.
I saw the reaction on Twitter before I saw the magazines themselves, and I quickly observed a number of people decrying the covers, suggesting that they promote obesity:
Multiple people suggested that this was inappropriate, especially in the context of the COVID-19 pandemic and the fact that people with obesity are at risk for worse outcomes, compared with those without obesity. (As an aside, these comments suggest that people did not read the associated article, which is about fitness and body image more than it is about obesity.)
Does size reflect health?
Putting the pandemic aside for a moment, the question the magazine covers raise is whether physical appearance reflects health. That’s what got me thinking about Ms. Spears, who, though appearing healthy, was sick enough that she needed to have major surgery. This whole conversation hinges, of course, on one’s definition of health.
A common knee-jerk response, especially from physicians, would be to say that obesity is by definition unhealthy. Some researchers have suggested though that a segment of people with obesity fall into a category called metabolically healthy obesity, which is typically characterized by a limited set of data such as cholesterol, blood sugar, and blood pressure. Indeed, some people with obesity have normal values in those categories.
Being metabolically healthy, however, does not preclude other medical problems associated with obesity, including joint pain, cancer, and mood disorders, among other issues. So even those who have metabolically healthy obesity are not necessarily immune to the many other obesity-related conditions.
What about body positivity?
As I delved further into the conversation about these covers, I saw people embracing the idea of promoting different-sized bodies. With almost two thirds of the U.S. population having overweight or obesity, one might argue that it’s high time magazine covers and the media reflect the reality in our hometowns. Unrealistic images in the media are associated with negative self-image and disordered eating, so perhaps embracing the shapes of real people may help us all have healthier attitudes toward our bodies.
That said, this idea can be taken too far. The Health at Every Size movement, which some might consider to be the ultimate body-positivity movement, espouses the idea that size and health are completely unrelated. That crosses a line between what we know to be true – that, at a population level, higher weight is associated with more medical problems – and fake news.
Another idea to consider is fitness, as opposed to health. Fitness can be defined multiple ways, but if we consider it to be measured exercise capacity, those who are more fit have a longer life expectancy than those with lower fitness levels at a given BMI. While some feel that the Cosmopolitan covers promote obesity and are therefore irresponsible, it’s at least as likely that highlighting people with obesity being active may inspire others with obesity to do the same.
Now let’s bring the pandemic back into the picture. As much as we all wish that it was over, with uncontrolled spread in every state and record numbers of people dying, COVID-19 is still very much a part of our reality. Having obesity increases the risk of having a severe case of COVID-19 if infected. Patients with obesity are also more likely than those without obesity to be hospitalized, require intensive care, and die with COVID-19.
Guiding the conversation
Pandemic or not, the truth is that obesity is related to multiple medical problems. That does not mean that every person with obesity has medical problems. The musician Lizzo, for example, is someone with obesity who considers herself to be healthy. She posts images and videos of working out and shares her personal fitness routine with her millions of fans. As a physician, I worry about the medical conditions – metabolic or otherwise – that someone like her may develop. But I love how she embraces who she is while striving to be healthier.
Most of the critical comments I have seen about the Cosmopolitan covers have, at best, bordered on fat shaming; others are solidly in that category. And the vitriol aimed at the larger models is despicable. It seems that conversations about obesity often vacillate from one extreme (fat shaming) to the other (extreme body positivity).
Although it may not sell magazines, I would love to see more nuanced, fact-based discussions, both in the media and in our clinics. We can start by acknowledging the fact that people of different sizes can be healthy. The truth is that we can’t tell very much about a person’s health from their outward appearance, and we should probably stop trying to make such inferences.
Assessment of health is most accurately judged by each person with their medical team, not by observers who use media images as part of their own propaganda machine, pushing one extreme view or another. As physicians, we have the opportunity and the responsibility to support our patients in the pursuit of health, without shame or judgment. Maybe that’s a New Year’s resolution worth committing to.
Arghavan Salles, MD, PhD, is a bariatric surgeon.
A version of this article first appeared on Medscape.com.
While many people were committing to their New Year’s resolutions to lose weight, in January 2020 Cosmopolitan UK magazine released covers portraying 11 women of different shapes and sizes, with the headline, “This is healthy!” Each version of the cover features one or more of the 11 women wearing athletic gear and makeup, some of whom are caught mid-action – boxing, doing yoga, or simply rejoicing in being who they are. Seeing these, I was reminded of a patient I cared for as an intern.
Janet Spears (not her real name) was thin. Standing barely 5 feet 3 inches, she weighed 110 pounds. For those out there who think of size in terms of body mass index (BMI), it was about 20 kg/m2, solidly in the “normal” category. At the age of 62, despite this healthy BMI, she had so much plaque in her arteries that she needed surgery to improve blood flow to her foot.
Admittedly, whenever I had read about people with high cholesterol, type 2 diabetes, or atherosclerosis, I pictured bigger people. But when I met Ms. Spears, I realized that one’s health cannot necessarily be inferred from physical appearance.
As a bariatric surgeon board certified in obesity medicine, I’ve probably spent more time thinking and learning about obesity than most people – and yet I still didn’t know what to make of the Cosmopolitan covers.
I saw the reaction on Twitter before I saw the magazines themselves, and I quickly observed a number of people decrying the covers, suggesting that they promote obesity:
Multiple people suggested that this was inappropriate, especially in the context of the COVID-19 pandemic and the fact that people with obesity are at risk for worse outcomes, compared with those without obesity. (As an aside, these comments suggest that people did not read the associated article, which is about fitness and body image more than it is about obesity.)
Does size reflect health?
Putting the pandemic aside for a moment, the question the magazine covers raise is whether physical appearance reflects health. That’s what got me thinking about Ms. Spears, who, though appearing healthy, was sick enough that she needed to have major surgery. This whole conversation hinges, of course, on one’s definition of health.
A common knee-jerk response, especially from physicians, would be to say that obesity is by definition unhealthy. Some researchers have suggested though that a segment of people with obesity fall into a category called metabolically healthy obesity, which is typically characterized by a limited set of data such as cholesterol, blood sugar, and blood pressure. Indeed, some people with obesity have normal values in those categories.
Being metabolically healthy, however, does not preclude other medical problems associated with obesity, including joint pain, cancer, and mood disorders, among other issues. So even those who have metabolically healthy obesity are not necessarily immune to the many other obesity-related conditions.
What about body positivity?
As I delved further into the conversation about these covers, I saw people embracing the idea of promoting different-sized bodies. With almost two thirds of the U.S. population having overweight or obesity, one might argue that it’s high time magazine covers and the media reflect the reality in our hometowns. Unrealistic images in the media are associated with negative self-image and disordered eating, so perhaps embracing the shapes of real people may help us all have healthier attitudes toward our bodies.
That said, this idea can be taken too far. The Health at Every Size movement, which some might consider to be the ultimate body-positivity movement, espouses the idea that size and health are completely unrelated. That crosses a line between what we know to be true – that, at a population level, higher weight is associated with more medical problems – and fake news.
Another idea to consider is fitness, as opposed to health. Fitness can be defined multiple ways, but if we consider it to be measured exercise capacity, those who are more fit have a longer life expectancy than those with lower fitness levels at a given BMI. While some feel that the Cosmopolitan covers promote obesity and are therefore irresponsible, it’s at least as likely that highlighting people with obesity being active may inspire others with obesity to do the same.
Now let’s bring the pandemic back into the picture. As much as we all wish that it was over, with uncontrolled spread in every state and record numbers of people dying, COVID-19 is still very much a part of our reality. Having obesity increases the risk of having a severe case of COVID-19 if infected. Patients with obesity are also more likely than those without obesity to be hospitalized, require intensive care, and die with COVID-19.
Guiding the conversation
Pandemic or not, the truth is that obesity is related to multiple medical problems. That does not mean that every person with obesity has medical problems. The musician Lizzo, for example, is someone with obesity who considers herself to be healthy. She posts images and videos of working out and shares her personal fitness routine with her millions of fans. As a physician, I worry about the medical conditions – metabolic or otherwise – that someone like her may develop. But I love how she embraces who she is while striving to be healthier.
Most of the critical comments I have seen about the Cosmopolitan covers have, at best, bordered on fat shaming; others are solidly in that category. And the vitriol aimed at the larger models is despicable. It seems that conversations about obesity often vacillate from one extreme (fat shaming) to the other (extreme body positivity).
Although it may not sell magazines, I would love to see more nuanced, fact-based discussions, both in the media and in our clinics. We can start by acknowledging the fact that people of different sizes can be healthy. The truth is that we can’t tell very much about a person’s health from their outward appearance, and we should probably stop trying to make such inferences.
Assessment of health is most accurately judged by each person with their medical team, not by observers who use media images as part of their own propaganda machine, pushing one extreme view or another. As physicians, we have the opportunity and the responsibility to support our patients in the pursuit of health, without shame or judgment. Maybe that’s a New Year’s resolution worth committing to.
Arghavan Salles, MD, PhD, is a bariatric surgeon.
A version of this article first appeared on Medscape.com.
While many people were committing to their New Year’s resolutions to lose weight, in January 2020 Cosmopolitan UK magazine released covers portraying 11 women of different shapes and sizes, with the headline, “This is healthy!” Each version of the cover features one or more of the 11 women wearing athletic gear and makeup, some of whom are caught mid-action – boxing, doing yoga, or simply rejoicing in being who they are. Seeing these, I was reminded of a patient I cared for as an intern.
Janet Spears (not her real name) was thin. Standing barely 5 feet 3 inches, she weighed 110 pounds. For those out there who think of size in terms of body mass index (BMI), it was about 20 kg/m2, solidly in the “normal” category. At the age of 62, despite this healthy BMI, she had so much plaque in her arteries that she needed surgery to improve blood flow to her foot.
Admittedly, whenever I had read about people with high cholesterol, type 2 diabetes, or atherosclerosis, I pictured bigger people. But when I met Ms. Spears, I realized that one’s health cannot necessarily be inferred from physical appearance.
As a bariatric surgeon board certified in obesity medicine, I’ve probably spent more time thinking and learning about obesity than most people – and yet I still didn’t know what to make of the Cosmopolitan covers.
I saw the reaction on Twitter before I saw the magazines themselves, and I quickly observed a number of people decrying the covers, suggesting that they promote obesity:
Multiple people suggested that this was inappropriate, especially in the context of the COVID-19 pandemic and the fact that people with obesity are at risk for worse outcomes, compared with those without obesity. (As an aside, these comments suggest that people did not read the associated article, which is about fitness and body image more than it is about obesity.)
Does size reflect health?
Putting the pandemic aside for a moment, the question the magazine covers raise is whether physical appearance reflects health. That’s what got me thinking about Ms. Spears, who, though appearing healthy, was sick enough that she needed to have major surgery. This whole conversation hinges, of course, on one’s definition of health.
A common knee-jerk response, especially from physicians, would be to say that obesity is by definition unhealthy. Some researchers have suggested though that a segment of people with obesity fall into a category called metabolically healthy obesity, which is typically characterized by a limited set of data such as cholesterol, blood sugar, and blood pressure. Indeed, some people with obesity have normal values in those categories.
Being metabolically healthy, however, does not preclude other medical problems associated with obesity, including joint pain, cancer, and mood disorders, among other issues. So even those who have metabolically healthy obesity are not necessarily immune to the many other obesity-related conditions.
What about body positivity?
As I delved further into the conversation about these covers, I saw people embracing the idea of promoting different-sized bodies. With almost two thirds of the U.S. population having overweight or obesity, one might argue that it’s high time magazine covers and the media reflect the reality in our hometowns. Unrealistic images in the media are associated with negative self-image and disordered eating, so perhaps embracing the shapes of real people may help us all have healthier attitudes toward our bodies.
That said, this idea can be taken too far. The Health at Every Size movement, which some might consider to be the ultimate body-positivity movement, espouses the idea that size and health are completely unrelated. That crosses a line between what we know to be true – that, at a population level, higher weight is associated with more medical problems – and fake news.
Another idea to consider is fitness, as opposed to health. Fitness can be defined multiple ways, but if we consider it to be measured exercise capacity, those who are more fit have a longer life expectancy than those with lower fitness levels at a given BMI. While some feel that the Cosmopolitan covers promote obesity and are therefore irresponsible, it’s at least as likely that highlighting people with obesity being active may inspire others with obesity to do the same.
Now let’s bring the pandemic back into the picture. As much as we all wish that it was over, with uncontrolled spread in every state and record numbers of people dying, COVID-19 is still very much a part of our reality. Having obesity increases the risk of having a severe case of COVID-19 if infected. Patients with obesity are also more likely than those without obesity to be hospitalized, require intensive care, and die with COVID-19.
Guiding the conversation
Pandemic or not, the truth is that obesity is related to multiple medical problems. That does not mean that every person with obesity has medical problems. The musician Lizzo, for example, is someone with obesity who considers herself to be healthy. She posts images and videos of working out and shares her personal fitness routine with her millions of fans. As a physician, I worry about the medical conditions – metabolic or otherwise – that someone like her may develop. But I love how she embraces who she is while striving to be healthier.
Most of the critical comments I have seen about the Cosmopolitan covers have, at best, bordered on fat shaming; others are solidly in that category. And the vitriol aimed at the larger models is despicable. It seems that conversations about obesity often vacillate from one extreme (fat shaming) to the other (extreme body positivity).
Although it may not sell magazines, I would love to see more nuanced, fact-based discussions, both in the media and in our clinics. We can start by acknowledging the fact that people of different sizes can be healthy. The truth is that we can’t tell very much about a person’s health from their outward appearance, and we should probably stop trying to make such inferences.
Assessment of health is most accurately judged by each person with their medical team, not by observers who use media images as part of their own propaganda machine, pushing one extreme view or another. As physicians, we have the opportunity and the responsibility to support our patients in the pursuit of health, without shame or judgment. Maybe that’s a New Year’s resolution worth committing to.
Arghavan Salles, MD, PhD, is a bariatric surgeon.
A version of this article first appeared on Medscape.com.
Menopause, not aging, may influence brain volume
Postmenopausal women not only have larger brain volume than women who are premenopausal, but they also experience larger reductions in brain volume over time, reported Ananthan Ambikairajah of the Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, and associates. Their report was published in Menopause.
In this large population-based cohort of 5,072 women aged 37-73 years, the goal of the study was to look at links between brain volume and measures of menstruation history, such as menopausal status, age at menopause, age at menarche, and the duration of a woman’s reproductive stage, but to do so within the context of how it relates to dementia prevalence. Citing a study in The Lancet Neurology, the authors noted that the age-standardized prevalence for dementia is 17% higher in women than in men, and they speculated that it may be important to look beyond age for answers.
What about menstrual history and Alzheimer’s disease?
According to the Framingham Study in Neurology, the remaining lifetime risk of Alzheimer’s disease (AD) is nearly double for a 65-year-old woman (12%) compared with a 65-year-old man (6.3%), leading Mr. Ambikairajah and associates to conclude that “menstruation history may also be particularly relevant, given that it is unique to female aging.” They further speculated, citing several related studies, that because AD pathology is initiated decades prior to the onset of clinical signs, menstruation history and its effects on brain health may, in fact, be reflected in brain volume.
Postmenopausal women had 0.82% and 1.33% larger total brain and hippocampal volume, respectively, compared with premenopausal women. Postmenopausal women had a 23% greater decrease in total brain volume but not in hippocampal volume over time, compared with premenopausal women.
As Braak and Braak illustrated in Acta Neuropathologica, chronic inflammation has been linked to brain shrinkage “consistent with the pattern of results in the present study,” Mr. Ambikairajah and colleagues noted, adding that longitudinal neuroimaging/biomarker studies are needed to explore this further.
What made this study unique was its ability to match pre- and postmenopausal women for age, a critically important attribute “given that aging and menopause both progress concurrently, which can make it difficult to determine the individual contribution of each for measures of brain health,” the authors explained.
In an interview, Constance Bohon, MD, an ob.gyn. in private practice and assistant clinical professor, George Washington University, Washington, observed: “The conclusion [in this study] is that an early age of menarche, delayed age of menopause and increased duration of the reproductive stage is negatively associated with brain volume.”
What of the neuroprotective effects of endogenous estrogen?
“Their findings are not consistent with a neuroprotective effect of endogenous estrogen exposure on brain volume,” she noted, adding that the study “did not assess the effect of exogenous estrogen on brain volume. Neither was the effect of exogenous or endogenous estrogen on cerebral blood flow assessed. In a study published in Obstetrics & Gynecology, the conclusion was that oophorectomy before the age of natural menopause is associated with a decrease in cognitive impairment and dementia. There was no assessment of brain volume or cerebral blood flow. Likewise in a report published in Neurobiology of Aging, Maki P and Resnick S M. concluded that estrogen helps maintain hippocampal and prefrontal function as women age,” observed Dr. Bohon, noting that the study did not assess brain volume.
“It is unclear whether the most predictive assessment for worsening cognition and dementia is the finding of decreased total brain volume, decreased hippocampal volume, or decreased cerebral blood flow. The effect of both endogenous and exogenous estrogen on the risk for dementia needs further evaluation,” she cautioned.
Mr. Ambikairajah cited one financial disclosure; the remaining contributors had no relevant disclosures.
Postmenopausal women not only have larger brain volume than women who are premenopausal, but they also experience larger reductions in brain volume over time, reported Ananthan Ambikairajah of the Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, and associates. Their report was published in Menopause.
In this large population-based cohort of 5,072 women aged 37-73 years, the goal of the study was to look at links between brain volume and measures of menstruation history, such as menopausal status, age at menopause, age at menarche, and the duration of a woman’s reproductive stage, but to do so within the context of how it relates to dementia prevalence. Citing a study in The Lancet Neurology, the authors noted that the age-standardized prevalence for dementia is 17% higher in women than in men, and they speculated that it may be important to look beyond age for answers.
What about menstrual history and Alzheimer’s disease?
According to the Framingham Study in Neurology, the remaining lifetime risk of Alzheimer’s disease (AD) is nearly double for a 65-year-old woman (12%) compared with a 65-year-old man (6.3%), leading Mr. Ambikairajah and associates to conclude that “menstruation history may also be particularly relevant, given that it is unique to female aging.” They further speculated, citing several related studies, that because AD pathology is initiated decades prior to the onset of clinical signs, menstruation history and its effects on brain health may, in fact, be reflected in brain volume.
Postmenopausal women had 0.82% and 1.33% larger total brain and hippocampal volume, respectively, compared with premenopausal women. Postmenopausal women had a 23% greater decrease in total brain volume but not in hippocampal volume over time, compared with premenopausal women.
As Braak and Braak illustrated in Acta Neuropathologica, chronic inflammation has been linked to brain shrinkage “consistent with the pattern of results in the present study,” Mr. Ambikairajah and colleagues noted, adding that longitudinal neuroimaging/biomarker studies are needed to explore this further.
What made this study unique was its ability to match pre- and postmenopausal women for age, a critically important attribute “given that aging and menopause both progress concurrently, which can make it difficult to determine the individual contribution of each for measures of brain health,” the authors explained.
In an interview, Constance Bohon, MD, an ob.gyn. in private practice and assistant clinical professor, George Washington University, Washington, observed: “The conclusion [in this study] is that an early age of menarche, delayed age of menopause and increased duration of the reproductive stage is negatively associated with brain volume.”
What of the neuroprotective effects of endogenous estrogen?
“Their findings are not consistent with a neuroprotective effect of endogenous estrogen exposure on brain volume,” she noted, adding that the study “did not assess the effect of exogenous estrogen on brain volume. Neither was the effect of exogenous or endogenous estrogen on cerebral blood flow assessed. In a study published in Obstetrics & Gynecology, the conclusion was that oophorectomy before the age of natural menopause is associated with a decrease in cognitive impairment and dementia. There was no assessment of brain volume or cerebral blood flow. Likewise in a report published in Neurobiology of Aging, Maki P and Resnick S M. concluded that estrogen helps maintain hippocampal and prefrontal function as women age,” observed Dr. Bohon, noting that the study did not assess brain volume.
“It is unclear whether the most predictive assessment for worsening cognition and dementia is the finding of decreased total brain volume, decreased hippocampal volume, or decreased cerebral blood flow. The effect of both endogenous and exogenous estrogen on the risk for dementia needs further evaluation,” she cautioned.
Mr. Ambikairajah cited one financial disclosure; the remaining contributors had no relevant disclosures.
Postmenopausal women not only have larger brain volume than women who are premenopausal, but they also experience larger reductions in brain volume over time, reported Ananthan Ambikairajah of the Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, and associates. Their report was published in Menopause.
In this large population-based cohort of 5,072 women aged 37-73 years, the goal of the study was to look at links between brain volume and measures of menstruation history, such as menopausal status, age at menopause, age at menarche, and the duration of a woman’s reproductive stage, but to do so within the context of how it relates to dementia prevalence. Citing a study in The Lancet Neurology, the authors noted that the age-standardized prevalence for dementia is 17% higher in women than in men, and they speculated that it may be important to look beyond age for answers.
What about menstrual history and Alzheimer’s disease?
According to the Framingham Study in Neurology, the remaining lifetime risk of Alzheimer’s disease (AD) is nearly double for a 65-year-old woman (12%) compared with a 65-year-old man (6.3%), leading Mr. Ambikairajah and associates to conclude that “menstruation history may also be particularly relevant, given that it is unique to female aging.” They further speculated, citing several related studies, that because AD pathology is initiated decades prior to the onset of clinical signs, menstruation history and its effects on brain health may, in fact, be reflected in brain volume.
Postmenopausal women had 0.82% and 1.33% larger total brain and hippocampal volume, respectively, compared with premenopausal women. Postmenopausal women had a 23% greater decrease in total brain volume but not in hippocampal volume over time, compared with premenopausal women.
As Braak and Braak illustrated in Acta Neuropathologica, chronic inflammation has been linked to brain shrinkage “consistent with the pattern of results in the present study,” Mr. Ambikairajah and colleagues noted, adding that longitudinal neuroimaging/biomarker studies are needed to explore this further.
What made this study unique was its ability to match pre- and postmenopausal women for age, a critically important attribute “given that aging and menopause both progress concurrently, which can make it difficult to determine the individual contribution of each for measures of brain health,” the authors explained.
In an interview, Constance Bohon, MD, an ob.gyn. in private practice and assistant clinical professor, George Washington University, Washington, observed: “The conclusion [in this study] is that an early age of menarche, delayed age of menopause and increased duration of the reproductive stage is negatively associated with brain volume.”
What of the neuroprotective effects of endogenous estrogen?
“Their findings are not consistent with a neuroprotective effect of endogenous estrogen exposure on brain volume,” she noted, adding that the study “did not assess the effect of exogenous estrogen on brain volume. Neither was the effect of exogenous or endogenous estrogen on cerebral blood flow assessed. In a study published in Obstetrics & Gynecology, the conclusion was that oophorectomy before the age of natural menopause is associated with a decrease in cognitive impairment and dementia. There was no assessment of brain volume or cerebral blood flow. Likewise in a report published in Neurobiology of Aging, Maki P and Resnick S M. concluded that estrogen helps maintain hippocampal and prefrontal function as women age,” observed Dr. Bohon, noting that the study did not assess brain volume.
“It is unclear whether the most predictive assessment for worsening cognition and dementia is the finding of decreased total brain volume, decreased hippocampal volume, or decreased cerebral blood flow. The effect of both endogenous and exogenous estrogen on the risk for dementia needs further evaluation,” she cautioned.
Mr. Ambikairajah cited one financial disclosure; the remaining contributors had no relevant disclosures.
FROM MENOPAUSE
New COPD mortality risk model includes imaging-derived variables
All-cause mortality in patients with COPD over 10 years of follow-up was accurately predicted by a newly developed model based on a point system incorporating imaging-derived variables.
Identifying risk factors is important to develop treatments and preventive strategies, but the role of imaging variables in COPD mortality among smokers has not been well studied, wrote investigator Matthew Strand, PhD, of National Jewish Health in Denver, and colleagues.
An established risk model is the body mass index–airflow Obstruction-Dyspnea-Exercise capacity (BODE) index, developed to predict mortality in COPD patients over a 4-year period. The investigators noted that while models such as BODE provide useful information about predictors of mortality in COPD, they were developed using participants in the Global initiative for obstructive Lung Disease (GOLD) spirometry grades 1-4, and have been largely constructed without quantitative computed tomography (CT) imaging variables until recently.
“The BODE index was created as a simple point scoring system to predict risk of all-cause mortality within 4 years, and is based on FEV1 [forced expiratory volume at 1 second], [6-minute walk test], dyspnea and BMI, a subset of predictors we considered in our model,” the investigators noted. The new model includes data from pulmonary function tests and volumetric CT scans.
In a study published in Chronic Obstructive Pulmonary Diseases, the researchers identified 9,074 current and past smokers in the COPD Genetic Epidemiology study (COPDGene) for whom complete data were available. They developed a point system to determine mortality risk in current and former smokers after controlling for multiple risk factors. The average age of the study population was 60 years. All participants were current or former smokers with a smoking history of at least 10 pack-years.
Assessments of the study participants included a medical history, pre- and post-bronchodilator spirometry, a 6-minute walk distance test, and inspiratory and expiratory CT scans. The researchers analyzed mortality risk in the context of Global Initiative for Obstructive Lung Disease (GOLD) classifications of patients in the sample.
Overall, the average 10-year mortality risk was 18% for women and 25% for men. Performance on the 6-minute walk test (distances less than 500 feet), FEV1 (less than 20), and older age (80 years and older) were the strongest predictors of mortality.
The model showed strong predictive accuracy, with an area under the receiver operating characteristic curve averaging 0.797 that was validated in an external cohort, the researchers said.
The study findings were limited by the observational design that does not allow for estimating the causal effects of such modifiable factors as smoking cessation, that might impact the walking test and FEV1 values, the researchers noted. In addition, the model did not allow for testing the effects of smoking vs. not smoking.
However, the model developed in the study “will allow physicians and patients to better understand factors affecting risk of an adverse event, some of which may be modifiable,” the researchers said. “The risk estimates can be used to target groups of individuals for future clinical trials, including those not currently classified as having COPD based on GOLD criteria,” they said.
The study was supported by the National Heart, Lung, and Blood Institute and by the COPD Foundation through contributions to an industry advisory committee including AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.
All-cause mortality in patients with COPD over 10 years of follow-up was accurately predicted by a newly developed model based on a point system incorporating imaging-derived variables.
Identifying risk factors is important to develop treatments and preventive strategies, but the role of imaging variables in COPD mortality among smokers has not been well studied, wrote investigator Matthew Strand, PhD, of National Jewish Health in Denver, and colleagues.
An established risk model is the body mass index–airflow Obstruction-Dyspnea-Exercise capacity (BODE) index, developed to predict mortality in COPD patients over a 4-year period. The investigators noted that while models such as BODE provide useful information about predictors of mortality in COPD, they were developed using participants in the Global initiative for obstructive Lung Disease (GOLD) spirometry grades 1-4, and have been largely constructed without quantitative computed tomography (CT) imaging variables until recently.
“The BODE index was created as a simple point scoring system to predict risk of all-cause mortality within 4 years, and is based on FEV1 [forced expiratory volume at 1 second], [6-minute walk test], dyspnea and BMI, a subset of predictors we considered in our model,” the investigators noted. The new model includes data from pulmonary function tests and volumetric CT scans.
In a study published in Chronic Obstructive Pulmonary Diseases, the researchers identified 9,074 current and past smokers in the COPD Genetic Epidemiology study (COPDGene) for whom complete data were available. They developed a point system to determine mortality risk in current and former smokers after controlling for multiple risk factors. The average age of the study population was 60 years. All participants were current or former smokers with a smoking history of at least 10 pack-years.
Assessments of the study participants included a medical history, pre- and post-bronchodilator spirometry, a 6-minute walk distance test, and inspiratory and expiratory CT scans. The researchers analyzed mortality risk in the context of Global Initiative for Obstructive Lung Disease (GOLD) classifications of patients in the sample.
Overall, the average 10-year mortality risk was 18% for women and 25% for men. Performance on the 6-minute walk test (distances less than 500 feet), FEV1 (less than 20), and older age (80 years and older) were the strongest predictors of mortality.
The model showed strong predictive accuracy, with an area under the receiver operating characteristic curve averaging 0.797 that was validated in an external cohort, the researchers said.
The study findings were limited by the observational design that does not allow for estimating the causal effects of such modifiable factors as smoking cessation, that might impact the walking test and FEV1 values, the researchers noted. In addition, the model did not allow for testing the effects of smoking vs. not smoking.
However, the model developed in the study “will allow physicians and patients to better understand factors affecting risk of an adverse event, some of which may be modifiable,” the researchers said. “The risk estimates can be used to target groups of individuals for future clinical trials, including those not currently classified as having COPD based on GOLD criteria,” they said.
The study was supported by the National Heart, Lung, and Blood Institute and by the COPD Foundation through contributions to an industry advisory committee including AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.
All-cause mortality in patients with COPD over 10 years of follow-up was accurately predicted by a newly developed model based on a point system incorporating imaging-derived variables.
Identifying risk factors is important to develop treatments and preventive strategies, but the role of imaging variables in COPD mortality among smokers has not been well studied, wrote investigator Matthew Strand, PhD, of National Jewish Health in Denver, and colleagues.
An established risk model is the body mass index–airflow Obstruction-Dyspnea-Exercise capacity (BODE) index, developed to predict mortality in COPD patients over a 4-year period. The investigators noted that while models such as BODE provide useful information about predictors of mortality in COPD, they were developed using participants in the Global initiative for obstructive Lung Disease (GOLD) spirometry grades 1-4, and have been largely constructed without quantitative computed tomography (CT) imaging variables until recently.
“The BODE index was created as a simple point scoring system to predict risk of all-cause mortality within 4 years, and is based on FEV1 [forced expiratory volume at 1 second], [6-minute walk test], dyspnea and BMI, a subset of predictors we considered in our model,” the investigators noted. The new model includes data from pulmonary function tests and volumetric CT scans.
In a study published in Chronic Obstructive Pulmonary Diseases, the researchers identified 9,074 current and past smokers in the COPD Genetic Epidemiology study (COPDGene) for whom complete data were available. They developed a point system to determine mortality risk in current and former smokers after controlling for multiple risk factors. The average age of the study population was 60 years. All participants were current or former smokers with a smoking history of at least 10 pack-years.
Assessments of the study participants included a medical history, pre- and post-bronchodilator spirometry, a 6-minute walk distance test, and inspiratory and expiratory CT scans. The researchers analyzed mortality risk in the context of Global Initiative for Obstructive Lung Disease (GOLD) classifications of patients in the sample.
Overall, the average 10-year mortality risk was 18% for women and 25% for men. Performance on the 6-minute walk test (distances less than 500 feet), FEV1 (less than 20), and older age (80 years and older) were the strongest predictors of mortality.
The model showed strong predictive accuracy, with an area under the receiver operating characteristic curve averaging 0.797 that was validated in an external cohort, the researchers said.
The study findings were limited by the observational design that does not allow for estimating the causal effects of such modifiable factors as smoking cessation, that might impact the walking test and FEV1 values, the researchers noted. In addition, the model did not allow for testing the effects of smoking vs. not smoking.
However, the model developed in the study “will allow physicians and patients to better understand factors affecting risk of an adverse event, some of which may be modifiable,” the researchers said. “The risk estimates can be used to target groups of individuals for future clinical trials, including those not currently classified as having COPD based on GOLD criteria,” they said.
The study was supported by the National Heart, Lung, and Blood Institute and by the COPD Foundation through contributions to an industry advisory committee including AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.
FROM CHRONIC OBSTRUCTIVE PULMONARY DISEASES
CDC: 20% of people in the U.S. are infected with an STD
Among the more than 320 million people in the United States, there was a prevalence estimate of 67.6 million sexually transmitted infections at the time of assessment in 2018, according to the results of an epidemiologic study using multiple data sources, including the National Health and Nutrition Examination Survey (NHANES).
In addition, almost half of the incident STIs occurred in the 15- to 24-year age bracket, according to a report published online in Sexually Transmitted Diseases. Researchers estimated the combined number of prevalent and incident infections of eight STIs in the United States in 2018: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes (caused by herpes simplex virus type 2 [HSV-2]), human papillomavirus (HPV), sexually transmitted hepatitis B virus (HBV), and sexually transmitted HIV.
The estimated incidences of these STIs in this update, the first since 2008, were made using more recent data and improved estimation methods to provide updated STI prevalence and incidence estimates for 2018, both overall and by disease. “Having a combined estimate is crucial for policy purposes to illustrate the importance of STIs in the United States,” according to Kristen M. Kreisel, PhD, an epidemiologist at the Centers for Disease Control and Prevention, division of STD prevention, and colleagues.
The number of prevalent and incident infections were obtained by multiplying each STI’s updated per capita estimates by the 2018 full resident population estimates from the American Community Survey.
Detailed results
Chlamydia. The prevalence of chlamydia was estimated using 2015-2018 NHANES data, which was then used to create a modeled prevalence in 2018, according to the authors. There were an estimated 2.4 million prevalent urogenital chlamydial infections among persons aged 15-39 years in 2018; 1.1 and 1.3 million infections among men and women, respectively. Individuals aged 15-24 years comprised 56.7% and 75.8% of all infections in men and women respectively.
Gonorrhea. The prevalence of gonorrhea was estimated using ordinary differential equation based modeling. The number of prevalent urogenital gonococcal infections in 2018 among 15- to 39-year-olds was 209,000 overall; 50,000 in men and 155,000 in women. Of these, 113,000 (54.1%) occurred in 15- to 24-year-olds.
Trichomoniasis. The prevalence of trichomoniasis was estimated using 2015-2018 NHANES data, which was then used to create a modeled prevalence in 2018, according to the authors. The number of prevalent Trichomonas infections among 15- to 59-year-olds was 2.6 million, with 470,000 in men and 2.1 million in women. Persons aged 15-24 years comprised 15.6% of all prevalent infections, according to the authors.
Syphilis. The number of estimated prevalent syphilitic infections (all stages) among 14- to 49-year-old persons in 2018 was 156,000, with infections in men comprising 71.8% of all infections. Infections in both men and women aged 14-24 years accounted for about 25% of all infections, with 36,000 total prevalent syphilitic infections among 14- to 24-year-olds in 2018.
Genital herpes. The prevalence of genital herpes (caused by HSV-2) was estimated using 2015-2018 NHANES data, according to the authors. In persons aged 15-49 years in 2018, there were 18.6 million prevalent HSV-2 infections; 6.4 million among men and 12.2 million among women. Infections in 15- to 24-year-olds comprised 7.1% of all prevalent HSV-2 infections.
HPV. The prevalence of HPV was estimated using 2013-2016 NHANES data, which was assumed to reflect stable prevalence in 2018, according to the authors. Among 15- to 59-year-olds, the estimated number of persons, men, and women infected with one or more disease-associated HPV types in 2018 was 42.5, 23.4, and 19.2 million, respectively, with an estimated 9.0 million (21%) 15- to 24-year-olds infected,
HBV. NHANES 2013-2018 data were used to estimate the prevalence of sexually transmitted chronic HBV infections in 2018, according to the authors. The estimated number of infections among persons aged 15 years and older in 2018 was 103,000 (51,000 men and 52,000 women). There small sample size of individuals aged 15-24 years in the NHANES database made it impossible to obtain an accurate estimate for this group, according to the authors.
HIV. Data from the National HIV Surveillance System were used to estimate the prevalence and incidence of sexually transmitted HIV infections for persons aged 13 years and older in 2018. A total of 984,000 individuals aged 13 years and older were estimated to be living with sexually transmitted HIV at the end of 2018, according to the authors. Nearly 80% were men. In the 13- to 24-year-old age bracket, there were an estimated 45,400 living with sexually transmitted HIV.
Billions in costs
Commenting on the study by the CDC researchers, Raul Romaguera, acting director for CDC’s division of STD prevention, stated in a press release: “There are significant human and financial costs associated with these infections, and we know from other studies that cuts in STI prevention efforts result in higher costs down the road. Preventing STIs could save billions in medical costs, but more importantly, prevention would improve the health and lives of millions of people.”
“About 20% of the total U.S. population had an STI at a given point in 2018, while nearly half of all incident infections occurred in people aged 15-24 years. Focusing STI prevention efforts on the 15- to 24-year-old population may be key to lowering the STI burden in the U.S.,” the researchers concluded.
The authors reported that they had no disclosures.
Among the more than 320 million people in the United States, there was a prevalence estimate of 67.6 million sexually transmitted infections at the time of assessment in 2018, according to the results of an epidemiologic study using multiple data sources, including the National Health and Nutrition Examination Survey (NHANES).
In addition, almost half of the incident STIs occurred in the 15- to 24-year age bracket, according to a report published online in Sexually Transmitted Diseases. Researchers estimated the combined number of prevalent and incident infections of eight STIs in the United States in 2018: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes (caused by herpes simplex virus type 2 [HSV-2]), human papillomavirus (HPV), sexually transmitted hepatitis B virus (HBV), and sexually transmitted HIV.
The estimated incidences of these STIs in this update, the first since 2008, were made using more recent data and improved estimation methods to provide updated STI prevalence and incidence estimates for 2018, both overall and by disease. “Having a combined estimate is crucial for policy purposes to illustrate the importance of STIs in the United States,” according to Kristen M. Kreisel, PhD, an epidemiologist at the Centers for Disease Control and Prevention, division of STD prevention, and colleagues.
The number of prevalent and incident infections were obtained by multiplying each STI’s updated per capita estimates by the 2018 full resident population estimates from the American Community Survey.
Detailed results
Chlamydia. The prevalence of chlamydia was estimated using 2015-2018 NHANES data, which was then used to create a modeled prevalence in 2018, according to the authors. There were an estimated 2.4 million prevalent urogenital chlamydial infections among persons aged 15-39 years in 2018; 1.1 and 1.3 million infections among men and women, respectively. Individuals aged 15-24 years comprised 56.7% and 75.8% of all infections in men and women respectively.
Gonorrhea. The prevalence of gonorrhea was estimated using ordinary differential equation based modeling. The number of prevalent urogenital gonococcal infections in 2018 among 15- to 39-year-olds was 209,000 overall; 50,000 in men and 155,000 in women. Of these, 113,000 (54.1%) occurred in 15- to 24-year-olds.
Trichomoniasis. The prevalence of trichomoniasis was estimated using 2015-2018 NHANES data, which was then used to create a modeled prevalence in 2018, according to the authors. The number of prevalent Trichomonas infections among 15- to 59-year-olds was 2.6 million, with 470,000 in men and 2.1 million in women. Persons aged 15-24 years comprised 15.6% of all prevalent infections, according to the authors.
Syphilis. The number of estimated prevalent syphilitic infections (all stages) among 14- to 49-year-old persons in 2018 was 156,000, with infections in men comprising 71.8% of all infections. Infections in both men and women aged 14-24 years accounted for about 25% of all infections, with 36,000 total prevalent syphilitic infections among 14- to 24-year-olds in 2018.
Genital herpes. The prevalence of genital herpes (caused by HSV-2) was estimated using 2015-2018 NHANES data, according to the authors. In persons aged 15-49 years in 2018, there were 18.6 million prevalent HSV-2 infections; 6.4 million among men and 12.2 million among women. Infections in 15- to 24-year-olds comprised 7.1% of all prevalent HSV-2 infections.
HPV. The prevalence of HPV was estimated using 2013-2016 NHANES data, which was assumed to reflect stable prevalence in 2018, according to the authors. Among 15- to 59-year-olds, the estimated number of persons, men, and women infected with one or more disease-associated HPV types in 2018 was 42.5, 23.4, and 19.2 million, respectively, with an estimated 9.0 million (21%) 15- to 24-year-olds infected,
HBV. NHANES 2013-2018 data were used to estimate the prevalence of sexually transmitted chronic HBV infections in 2018, according to the authors. The estimated number of infections among persons aged 15 years and older in 2018 was 103,000 (51,000 men and 52,000 women). There small sample size of individuals aged 15-24 years in the NHANES database made it impossible to obtain an accurate estimate for this group, according to the authors.
HIV. Data from the National HIV Surveillance System were used to estimate the prevalence and incidence of sexually transmitted HIV infections for persons aged 13 years and older in 2018. A total of 984,000 individuals aged 13 years and older were estimated to be living with sexually transmitted HIV at the end of 2018, according to the authors. Nearly 80% were men. In the 13- to 24-year-old age bracket, there were an estimated 45,400 living with sexually transmitted HIV.
Billions in costs
Commenting on the study by the CDC researchers, Raul Romaguera, acting director for CDC’s division of STD prevention, stated in a press release: “There are significant human and financial costs associated with these infections, and we know from other studies that cuts in STI prevention efforts result in higher costs down the road. Preventing STIs could save billions in medical costs, but more importantly, prevention would improve the health and lives of millions of people.”
“About 20% of the total U.S. population had an STI at a given point in 2018, while nearly half of all incident infections occurred in people aged 15-24 years. Focusing STI prevention efforts on the 15- to 24-year-old population may be key to lowering the STI burden in the U.S.,” the researchers concluded.
The authors reported that they had no disclosures.
Among the more than 320 million people in the United States, there was a prevalence estimate of 67.6 million sexually transmitted infections at the time of assessment in 2018, according to the results of an epidemiologic study using multiple data sources, including the National Health and Nutrition Examination Survey (NHANES).
In addition, almost half of the incident STIs occurred in the 15- to 24-year age bracket, according to a report published online in Sexually Transmitted Diseases. Researchers estimated the combined number of prevalent and incident infections of eight STIs in the United States in 2018: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes (caused by herpes simplex virus type 2 [HSV-2]), human papillomavirus (HPV), sexually transmitted hepatitis B virus (HBV), and sexually transmitted HIV.
The estimated incidences of these STIs in this update, the first since 2008, were made using more recent data and improved estimation methods to provide updated STI prevalence and incidence estimates for 2018, both overall and by disease. “Having a combined estimate is crucial for policy purposes to illustrate the importance of STIs in the United States,” according to Kristen M. Kreisel, PhD, an epidemiologist at the Centers for Disease Control and Prevention, division of STD prevention, and colleagues.
The number of prevalent and incident infections were obtained by multiplying each STI’s updated per capita estimates by the 2018 full resident population estimates from the American Community Survey.
Detailed results
Chlamydia. The prevalence of chlamydia was estimated using 2015-2018 NHANES data, which was then used to create a modeled prevalence in 2018, according to the authors. There were an estimated 2.4 million prevalent urogenital chlamydial infections among persons aged 15-39 years in 2018; 1.1 and 1.3 million infections among men and women, respectively. Individuals aged 15-24 years comprised 56.7% and 75.8% of all infections in men and women respectively.
Gonorrhea. The prevalence of gonorrhea was estimated using ordinary differential equation based modeling. The number of prevalent urogenital gonococcal infections in 2018 among 15- to 39-year-olds was 209,000 overall; 50,000 in men and 155,000 in women. Of these, 113,000 (54.1%) occurred in 15- to 24-year-olds.
Trichomoniasis. The prevalence of trichomoniasis was estimated using 2015-2018 NHANES data, which was then used to create a modeled prevalence in 2018, according to the authors. The number of prevalent Trichomonas infections among 15- to 59-year-olds was 2.6 million, with 470,000 in men and 2.1 million in women. Persons aged 15-24 years comprised 15.6% of all prevalent infections, according to the authors.
Syphilis. The number of estimated prevalent syphilitic infections (all stages) among 14- to 49-year-old persons in 2018 was 156,000, with infections in men comprising 71.8% of all infections. Infections in both men and women aged 14-24 years accounted for about 25% of all infections, with 36,000 total prevalent syphilitic infections among 14- to 24-year-olds in 2018.
Genital herpes. The prevalence of genital herpes (caused by HSV-2) was estimated using 2015-2018 NHANES data, according to the authors. In persons aged 15-49 years in 2018, there were 18.6 million prevalent HSV-2 infections; 6.4 million among men and 12.2 million among women. Infections in 15- to 24-year-olds comprised 7.1% of all prevalent HSV-2 infections.
HPV. The prevalence of HPV was estimated using 2013-2016 NHANES data, which was assumed to reflect stable prevalence in 2018, according to the authors. Among 15- to 59-year-olds, the estimated number of persons, men, and women infected with one or more disease-associated HPV types in 2018 was 42.5, 23.4, and 19.2 million, respectively, with an estimated 9.0 million (21%) 15- to 24-year-olds infected,
HBV. NHANES 2013-2018 data were used to estimate the prevalence of sexually transmitted chronic HBV infections in 2018, according to the authors. The estimated number of infections among persons aged 15 years and older in 2018 was 103,000 (51,000 men and 52,000 women). There small sample size of individuals aged 15-24 years in the NHANES database made it impossible to obtain an accurate estimate for this group, according to the authors.
HIV. Data from the National HIV Surveillance System were used to estimate the prevalence and incidence of sexually transmitted HIV infections for persons aged 13 years and older in 2018. A total of 984,000 individuals aged 13 years and older were estimated to be living with sexually transmitted HIV at the end of 2018, according to the authors. Nearly 80% were men. In the 13- to 24-year-old age bracket, there were an estimated 45,400 living with sexually transmitted HIV.
Billions in costs
Commenting on the study by the CDC researchers, Raul Romaguera, acting director for CDC’s division of STD prevention, stated in a press release: “There are significant human and financial costs associated with these infections, and we know from other studies that cuts in STI prevention efforts result in higher costs down the road. Preventing STIs could save billions in medical costs, but more importantly, prevention would improve the health and lives of millions of people.”
“About 20% of the total U.S. population had an STI at a given point in 2018, while nearly half of all incident infections occurred in people aged 15-24 years. Focusing STI prevention efforts on the 15- to 24-year-old population may be key to lowering the STI burden in the U.S.,” the researchers concluded.
The authors reported that they had no disclosures.
FROM SEXUALLY TRANSMITTED DISEASES
AI can identify biomarkers and potentially guide therapy in NSCLC
Researchers developed deep learning models that could accurately predict a patient’s PD-L1 and EGFR mutation status without the need for a biopsy. If these models are validated in prospective trials, they could guide treatment decisions in patients with NSCLC, according to the researchers.
Wei Mu, PhD, of Moffitt Cancer Center and Research Institute in Tampa, Fla., described this research at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-03).
Rationale
Guidelines from the National Comprehensive Cancer Network (NCCN) endorse tailored treatment for patients with NSCLC; namely, immune checkpoint inhibitors for those with PD-L1-positive tumors and EGFR tyrosine kinase inhibitors for patients with tumors harboring a mutation in EGFR.
However, the conventional approach to ascertaining tumor status for these biomarkers has disadvantages, Dr. Mu noted.
“Both require biopsy, which may fail due to insufficient quality of the tissue and, particularly for NSCLC, may increase the chance of morbidity,” Dr. Mu said.
In addition, there is room for improvement in the rigor of the biomarker assays, and there can be substantial wait times for results.
To address these issues, Dr. Mu and colleagues explored an AI radiomics approach using PET/CT scans.
“We know that EGFR mutation and positive PD-L1 expression may change the metabolism of the peritumor and intratumor microenvironment,” Dr. Mu explained. “Therefore, we had the hypothesis that they can be captured by the FDG-PET/CT images.”
Results
The investigators used FDG-PET/CT images from 837 patients with advanced NSCLC treated at four institutions. The team developed AI deep learning models that generated one score for PD-L1 positivity and another score for presence of an EGFR mutation, as well as an associated algorithm that would direct patients to the appropriate treatments depending on the scores.
Results for the PD-L1 deep learning score showed good accuracy in predicting positivity for this ligand, with an area under the curve of 0.89 in the training cohort, 0.84 in the validation cohort, and 0.82 in an external test cohort, Dr. Mu reported. All exceeded the corresponding areas under the curve for maximal standardized uptake values.
Moreover, the score was prognostic and statistically indistinguishable from PD-L1 status determined by immunohistochemistry in predicting progression-free survival.
Similarly, the EGFR deep learning score showed good accuracy in predicting mutational status, with an area under the curve of 0.86 in the training cohort, 0.83 in the validation cohort, and 0.81 in an external test cohort. It outperformed a clinical score based on sex, smoking status, tumor histology, and maximal standardized uptake value in each cohort.
The EGFR deep learning score was prognostic and statistically indistinguishable from EGFR mutational status determined by polymerase chain reaction in predicting progression-free survival.
The models showed good stability when size of the input region of interest was varied, and when different radiologists delineated the region of interest, with an intraclass correlation coefficient of 0.91.
“We developed deep learning models to predict PD-L1 status and EGFR mutation with high accuracy. Using the generated deep learning scores, we obtained a noninvasive treatment decision support tool, which may be useful as a clinical decision support tool pending validation of its clinical utility in a large prospective trial,” Dr. Mu summarized. “Using our tool, NSCLC patients could be directly offered a treatment decision without the need of biopsy.”
“In the future, we will perform a prospective observational trial to compare the results of our noninvasive treatment decision tool with molecular biomarker–based NCCN guidelines,” she said.
The investigators plan to add ALK rearrangement status and prediction of serious adverse events and cachexia to the decision support tool.
Dr. Mu disclosed no conflicts of interest. The study did not have specific funding.
Researchers developed deep learning models that could accurately predict a patient’s PD-L1 and EGFR mutation status without the need for a biopsy. If these models are validated in prospective trials, they could guide treatment decisions in patients with NSCLC, according to the researchers.
Wei Mu, PhD, of Moffitt Cancer Center and Research Institute in Tampa, Fla., described this research at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-03).
Rationale
Guidelines from the National Comprehensive Cancer Network (NCCN) endorse tailored treatment for patients with NSCLC; namely, immune checkpoint inhibitors for those with PD-L1-positive tumors and EGFR tyrosine kinase inhibitors for patients with tumors harboring a mutation in EGFR.
However, the conventional approach to ascertaining tumor status for these biomarkers has disadvantages, Dr. Mu noted.
“Both require biopsy, which may fail due to insufficient quality of the tissue and, particularly for NSCLC, may increase the chance of morbidity,” Dr. Mu said.
In addition, there is room for improvement in the rigor of the biomarker assays, and there can be substantial wait times for results.
To address these issues, Dr. Mu and colleagues explored an AI radiomics approach using PET/CT scans.
“We know that EGFR mutation and positive PD-L1 expression may change the metabolism of the peritumor and intratumor microenvironment,” Dr. Mu explained. “Therefore, we had the hypothesis that they can be captured by the FDG-PET/CT images.”
Results
The investigators used FDG-PET/CT images from 837 patients with advanced NSCLC treated at four institutions. The team developed AI deep learning models that generated one score for PD-L1 positivity and another score for presence of an EGFR mutation, as well as an associated algorithm that would direct patients to the appropriate treatments depending on the scores.
Results for the PD-L1 deep learning score showed good accuracy in predicting positivity for this ligand, with an area under the curve of 0.89 in the training cohort, 0.84 in the validation cohort, and 0.82 in an external test cohort, Dr. Mu reported. All exceeded the corresponding areas under the curve for maximal standardized uptake values.
Moreover, the score was prognostic and statistically indistinguishable from PD-L1 status determined by immunohistochemistry in predicting progression-free survival.
Similarly, the EGFR deep learning score showed good accuracy in predicting mutational status, with an area under the curve of 0.86 in the training cohort, 0.83 in the validation cohort, and 0.81 in an external test cohort. It outperformed a clinical score based on sex, smoking status, tumor histology, and maximal standardized uptake value in each cohort.
The EGFR deep learning score was prognostic and statistically indistinguishable from EGFR mutational status determined by polymerase chain reaction in predicting progression-free survival.
The models showed good stability when size of the input region of interest was varied, and when different radiologists delineated the region of interest, with an intraclass correlation coefficient of 0.91.
“We developed deep learning models to predict PD-L1 status and EGFR mutation with high accuracy. Using the generated deep learning scores, we obtained a noninvasive treatment decision support tool, which may be useful as a clinical decision support tool pending validation of its clinical utility in a large prospective trial,” Dr. Mu summarized. “Using our tool, NSCLC patients could be directly offered a treatment decision without the need of biopsy.”
“In the future, we will perform a prospective observational trial to compare the results of our noninvasive treatment decision tool with molecular biomarker–based NCCN guidelines,” she said.
The investigators plan to add ALK rearrangement status and prediction of serious adverse events and cachexia to the decision support tool.
Dr. Mu disclosed no conflicts of interest. The study did not have specific funding.
Researchers developed deep learning models that could accurately predict a patient’s PD-L1 and EGFR mutation status without the need for a biopsy. If these models are validated in prospective trials, they could guide treatment decisions in patients with NSCLC, according to the researchers.
Wei Mu, PhD, of Moffitt Cancer Center and Research Institute in Tampa, Fla., described this research at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (abstract PR-03).
Rationale
Guidelines from the National Comprehensive Cancer Network (NCCN) endorse tailored treatment for patients with NSCLC; namely, immune checkpoint inhibitors for those with PD-L1-positive tumors and EGFR tyrosine kinase inhibitors for patients with tumors harboring a mutation in EGFR.
However, the conventional approach to ascertaining tumor status for these biomarkers has disadvantages, Dr. Mu noted.
“Both require biopsy, which may fail due to insufficient quality of the tissue and, particularly for NSCLC, may increase the chance of morbidity,” Dr. Mu said.
In addition, there is room for improvement in the rigor of the biomarker assays, and there can be substantial wait times for results.
To address these issues, Dr. Mu and colleagues explored an AI radiomics approach using PET/CT scans.
“We know that EGFR mutation and positive PD-L1 expression may change the metabolism of the peritumor and intratumor microenvironment,” Dr. Mu explained. “Therefore, we had the hypothesis that they can be captured by the FDG-PET/CT images.”
Results
The investigators used FDG-PET/CT images from 837 patients with advanced NSCLC treated at four institutions. The team developed AI deep learning models that generated one score for PD-L1 positivity and another score for presence of an EGFR mutation, as well as an associated algorithm that would direct patients to the appropriate treatments depending on the scores.
Results for the PD-L1 deep learning score showed good accuracy in predicting positivity for this ligand, with an area under the curve of 0.89 in the training cohort, 0.84 in the validation cohort, and 0.82 in an external test cohort, Dr. Mu reported. All exceeded the corresponding areas under the curve for maximal standardized uptake values.
Moreover, the score was prognostic and statistically indistinguishable from PD-L1 status determined by immunohistochemistry in predicting progression-free survival.
Similarly, the EGFR deep learning score showed good accuracy in predicting mutational status, with an area under the curve of 0.86 in the training cohort, 0.83 in the validation cohort, and 0.81 in an external test cohort. It outperformed a clinical score based on sex, smoking status, tumor histology, and maximal standardized uptake value in each cohort.
The EGFR deep learning score was prognostic and statistically indistinguishable from EGFR mutational status determined by polymerase chain reaction in predicting progression-free survival.
The models showed good stability when size of the input region of interest was varied, and when different radiologists delineated the region of interest, with an intraclass correlation coefficient of 0.91.
“We developed deep learning models to predict PD-L1 status and EGFR mutation with high accuracy. Using the generated deep learning scores, we obtained a noninvasive treatment decision support tool, which may be useful as a clinical decision support tool pending validation of its clinical utility in a large prospective trial,” Dr. Mu summarized. “Using our tool, NSCLC patients could be directly offered a treatment decision without the need of biopsy.”
“In the future, we will perform a prospective observational trial to compare the results of our noninvasive treatment decision tool with molecular biomarker–based NCCN guidelines,” she said.
The investigators plan to add ALK rearrangement status and prediction of serious adverse events and cachexia to the decision support tool.
Dr. Mu disclosed no conflicts of interest. The study did not have specific funding.
FROM AACR: AI, DIAGNOSIS, AND IMAGING 2021
Myocarditis by CMR may be rare after COVID-19 in elite athletes
Two recent observational studies suggest that myocarditis, at least on cardiac magnetic resonance (CMR) imaging, might be far less common in elite-level athletes recovering from COVID-19 than suggested in influential earlier reports.
Both new studies documented a rate less than one-quarter as high as those previously reported from smaller cohorts, raising questions about the diagnostic yield of CMR in highly conditioned athletes with recent COVID-19 absent other evidence, such as from biomarker assays or electrocardiography (ECG).
That could have implications for some top-tier university athletics programs that mandate CMR imaging, biomarker assays, and other evaluations for myocarditis on all their players who test positive for SARS-CoV-2 before they can return to play.
The findings collectively point to CMR imaging features that might be a hallmark of an athlete’s heart, characterized by normal myocardial remodeling brought on by elite-level exercise training, which in athletes with recent COVID-19 could be misinterpreted as evidence of myocarditis. That may have thrown off prevalence estimates in the literature, the studies’ investigators speculated.
The two studies were retrospective takes on university athletes who underwent CMR imaging while recovering from COVID-19, who were either asymptomatic or with only mild to moderate symptoms and were generally without ECG or troponin evidence of myocarditis.
One of them showed a less than 2% incidence of myocarditis by CMR among 145 such cases, a low yield for imaging that is “raising doubt regarding its utility to evaluate athletes without a clinical presentation or abnormal ancillary tests to support the diagnosis of myocarditis,” argues a report published Jan. 14 in JAMA Cardiology, with lead author Jitka Starekova, MD, University of Wisconsin – Madison.
“Part of the problem is that occult myocarditis is, at least with other viruses, a risk factor for sudden death in competitive athletes. So you don’t want to let one slip through the cracks,” senior author Scott B. Reeder, MD, PhD, from the same institution, said in an interview.
Whether a policy of routine CMR imaging in elite athletes who test positive for the new coronavirus is better than more selective use driven by symptoms or other screening tests is unknown. But the more pressing issue, Dr. Reeder said, “is if they have a normal electrocardiogram and troponins, do they still need cardiac magnetic resonance imaging?”
The current study, he said, “certainly provides helpful evidence that maybe we don’t need as many.”
The other study, which featured two control groups, saw a similarly low incidence of myocarditis by CMR in athletes with recent COVID-19. One of the control groups included university athletes imaged prior to the advent of SARS-CoV-2 in the university’s region of the country. The other consisted of apparently healthy adult nonathletes.
Armed with two non-COVID-19 cohorts and two athlete cohorts, the researchers found comparable rates of myocarditis by CMR in both the COVID-19 athletes and the healthy athletes. And only 3% of the COVID-19 athletes had the tell-tale CMR signs, notes the report, published Dec. 17 in Circulation, with lead author Daniel E. Clark, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn.
Reassurance and concern
“The incidence is much lower than we feared, and so that’s reassuring,” Clark said in an interview. Still, the athletes with myocarditis by CMR “would have been completely missed by a protocol that did not include cardiac MR, and that’s concerning,” he said. “Both had active myocarditis.”
The study’s two non-COVID-19 control groups – elite athletes in one and nonathletes in the other – allowed them to tease out the potential contribution of athletic myocardial remodeling to CMR features that could be interpreted as scar tissue, which are characterized by late gadolinium enhancement (LGE).
As it turned out, focal regions of LGE located in the right ventricular (RV) septum on the scans were often seen in both athlete cohorts. “This kind of trivial nonischemic fibrosis in the mid RV septal insertion site was common among athletic control subjects. It was seen in 24% of them, which is almost identical to the percentage that we saw in the COVID-19 athletes, 22%,” Dr. Clark said.
The LGE finding, wrote Dr. Clark and coauthors, “may represent remodeling from athletic training, and should not be conflated with myocarditis.”
Of note, the other study saw a comparable incidence of the same or a very similar CMR feature in its athletes; 26% of the Wisconsin COVID-19 athlete cohort showed limited focal LGE in the inferior RV insertion site.
“And you get a little bit in the mid-septum, as well,” Dr. Reeder said. But the sign, in the absence of any corresponding T2 abnormalities, was not judged to represent myocarditis. “We interpreted all of these studies with this potential confounder in mind.”
Conceivably, Dr. Reeder proposed, the earlier studies may have “over-called” the prevalence of myocarditis in their cohorts. “I haven’t seen their images, but it’s possible there could be false-positives.”
It’s noteworthy that the Vanderbilt and Wisconsin reports saw closely similar incidences of the tell-tale CMR sign in all the athlete cohorts whether or not COVID-19 was involved, Aaron L. Baggish, MD, Massachusetts General Hospital, Boston, said in an interview.
“It looks very much like just an unrecognized part of athletic remodeling and isn’t in any way, shape, or form implicated as being a COVID-related issue,” said Dr. Baggish, who directs the cardiovascular performance program at his center and is unaffiliated with either study.
Still, that connection remains unproven given how little is yet known about the prevalence of clinically important myocarditis in milder cases of COVID-19, according to an accompanying editorial from Jonathan H. Kim, MD, MSc.
Although isolated LGE at the interventricular RV insertion site is “more commonly described among masters-level endurance athletes, the clinical significance and prevalence of this finding in youthful athletes is uncertain and should not be assumed to be a normal consequence of intense athletic training in young competitive athletes,” argued Dr. Kim, of Emory University, Atlanta.
There’s probably little about being a young competitive athlete that would render a person any more or less prone to COVID-19 cardiac involvement, Dr. Baggish said. Rather, “I think what we’re seeing, as the studies continue to come out, is that prevalence estimates are getting into the low single digits.”
The estimates are similar to those associated with influenza before the COVID-19 age; about 2% of patients showed cardiac involvement, Dr. Baggish said. “So the degree to which COVID is a special virus from this perspective, I think, is still a topic of some debate.”
The two current studies have limitations and neither is positioned to change practice, he said. “I would say that they are both kind of important, reassuring pieces of an unfinished jigsaw puzzle. But we still don’t know what the picture on the puzzle is.”
Routine CMR for positive cases
The University of Wisconsin group looked at all of the institution’s competitive athletes who underwent gadolinium-enhanced CMR imaging and other tests during recovery from COVID-19 from the beginning of the pandemic to the end of November 2020.
The imaging was performed on average about 2 weeks after a first positive SARS-CoV-2 assay result. About one-half and one-fourth of the cohort had experienced mild and moderate symptoms, respectively, and about 17% were asymptomatic; none had been hospitalized.
All CMR scans were reviewed by two experienced radiologists for, among other things, evidence of myocarditis according to modified Lake Louise criteria, the group wrote. Those criteria are based on CMR markers of fibrosis and other characteristics of scarring from myocarditis.
Such evidence was seen in only two members of the cohort, or 1.4%, one with elevated troponins but normal with respect to other biomarkers, and the other negative for all assays. Both were asymptomatic at the time of imaging, the report noted.
The Vanderbilt analysis from Dr. Clark and associates centered on 59 university athletes recently with COVID-19 who underwent CMR imaging along with other tests about 3 weeks after confirmation of SARS-CoV-2 infection. Symptoms had been mild in 78% of the group, and the remainder were asymptomatic.
They were compared with 60 retrospectively identified college athletes and elite-conditioned military personnel who had undergone CMR imaging prior to the advent of COVID-19, and to 27 apparently healthy nonathlete adults in whom CMR had been previously performed to define normal CMR imaging criteria at that center.
The only two post-COVID-19 athletes who met modified Lake Louise criteria for myocarditis showed no abnormalities on ECG or myocardial strain echocardiography, and had normal troponins, the group reported.
The COVID-19 athletes showed increased cardiac chamber volumes and myocardial mass “consistent with athletic remodeling,” compared with the healthy control subjects, the group wrote. But “most standard CMR parameters were similar” between the COVID-19 athletes and the control athletes, consistent with the 22% and 24% rates, respectively, for the finding of focal late LGE isolated to the inferoseptal RV insertion site.
At the end of the day, all published experiences on athletes with recent COVID-19 “are descriptive studies, without any hint of follow-up,” Dr. Baggish noted, so their clinical implications are unknown.
“We need time to sit and watch to see what happens to these individuals,” he said. “And if the answer is nothing, then that’s a very reassuring story. If the answer is that we start to see events, then that’s really important for us to take stock of.”
Dr. Starekova had no disclosures. Dr. Reeder reports that the University of Wisconsin receives research support from GE Healthcare and Bracco Diagnostics; and that he has ownership interests in Calimetrix, Reveal Pharmaceuticals, Cellectar Biosciences, Elucent Medical, and HeartVista; and has received grant support from Bayer Healthcare. Disclosures for the other coauthors are in the report. Dr. Clark and coauthors had no disclosures. Dr. Baggish reported no conflicts. Kim discloses receiving funding from the National Heart, Lung, and Blood Institute; compensation as team cardiologist for the Atlanta Falcons; and research stipends from the Atlanta Track Club.
A version of this article first appeared on Medscape.com.
Two recent observational studies suggest that myocarditis, at least on cardiac magnetic resonance (CMR) imaging, might be far less common in elite-level athletes recovering from COVID-19 than suggested in influential earlier reports.
Both new studies documented a rate less than one-quarter as high as those previously reported from smaller cohorts, raising questions about the diagnostic yield of CMR in highly conditioned athletes with recent COVID-19 absent other evidence, such as from biomarker assays or electrocardiography (ECG).
That could have implications for some top-tier university athletics programs that mandate CMR imaging, biomarker assays, and other evaluations for myocarditis on all their players who test positive for SARS-CoV-2 before they can return to play.
The findings collectively point to CMR imaging features that might be a hallmark of an athlete’s heart, characterized by normal myocardial remodeling brought on by elite-level exercise training, which in athletes with recent COVID-19 could be misinterpreted as evidence of myocarditis. That may have thrown off prevalence estimates in the literature, the studies’ investigators speculated.
The two studies were retrospective takes on university athletes who underwent CMR imaging while recovering from COVID-19, who were either asymptomatic or with only mild to moderate symptoms and were generally without ECG or troponin evidence of myocarditis.
One of them showed a less than 2% incidence of myocarditis by CMR among 145 such cases, a low yield for imaging that is “raising doubt regarding its utility to evaluate athletes without a clinical presentation or abnormal ancillary tests to support the diagnosis of myocarditis,” argues a report published Jan. 14 in JAMA Cardiology, with lead author Jitka Starekova, MD, University of Wisconsin – Madison.
“Part of the problem is that occult myocarditis is, at least with other viruses, a risk factor for sudden death in competitive athletes. So you don’t want to let one slip through the cracks,” senior author Scott B. Reeder, MD, PhD, from the same institution, said in an interview.
Whether a policy of routine CMR imaging in elite athletes who test positive for the new coronavirus is better than more selective use driven by symptoms or other screening tests is unknown. But the more pressing issue, Dr. Reeder said, “is if they have a normal electrocardiogram and troponins, do they still need cardiac magnetic resonance imaging?”
The current study, he said, “certainly provides helpful evidence that maybe we don’t need as many.”
The other study, which featured two control groups, saw a similarly low incidence of myocarditis by CMR in athletes with recent COVID-19. One of the control groups included university athletes imaged prior to the advent of SARS-CoV-2 in the university’s region of the country. The other consisted of apparently healthy adult nonathletes.
Armed with two non-COVID-19 cohorts and two athlete cohorts, the researchers found comparable rates of myocarditis by CMR in both the COVID-19 athletes and the healthy athletes. And only 3% of the COVID-19 athletes had the tell-tale CMR signs, notes the report, published Dec. 17 in Circulation, with lead author Daniel E. Clark, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn.
Reassurance and concern
“The incidence is much lower than we feared, and so that’s reassuring,” Clark said in an interview. Still, the athletes with myocarditis by CMR “would have been completely missed by a protocol that did not include cardiac MR, and that’s concerning,” he said. “Both had active myocarditis.”
The study’s two non-COVID-19 control groups – elite athletes in one and nonathletes in the other – allowed them to tease out the potential contribution of athletic myocardial remodeling to CMR features that could be interpreted as scar tissue, which are characterized by late gadolinium enhancement (LGE).
As it turned out, focal regions of LGE located in the right ventricular (RV) septum on the scans were often seen in both athlete cohorts. “This kind of trivial nonischemic fibrosis in the mid RV septal insertion site was common among athletic control subjects. It was seen in 24% of them, which is almost identical to the percentage that we saw in the COVID-19 athletes, 22%,” Dr. Clark said.
The LGE finding, wrote Dr. Clark and coauthors, “may represent remodeling from athletic training, and should not be conflated with myocarditis.”
Of note, the other study saw a comparable incidence of the same or a very similar CMR feature in its athletes; 26% of the Wisconsin COVID-19 athlete cohort showed limited focal LGE in the inferior RV insertion site.
“And you get a little bit in the mid-septum, as well,” Dr. Reeder said. But the sign, in the absence of any corresponding T2 abnormalities, was not judged to represent myocarditis. “We interpreted all of these studies with this potential confounder in mind.”
Conceivably, Dr. Reeder proposed, the earlier studies may have “over-called” the prevalence of myocarditis in their cohorts. “I haven’t seen their images, but it’s possible there could be false-positives.”
It’s noteworthy that the Vanderbilt and Wisconsin reports saw closely similar incidences of the tell-tale CMR sign in all the athlete cohorts whether or not COVID-19 was involved, Aaron L. Baggish, MD, Massachusetts General Hospital, Boston, said in an interview.
“It looks very much like just an unrecognized part of athletic remodeling and isn’t in any way, shape, or form implicated as being a COVID-related issue,” said Dr. Baggish, who directs the cardiovascular performance program at his center and is unaffiliated with either study.
Still, that connection remains unproven given how little is yet known about the prevalence of clinically important myocarditis in milder cases of COVID-19, according to an accompanying editorial from Jonathan H. Kim, MD, MSc.
Although isolated LGE at the interventricular RV insertion site is “more commonly described among masters-level endurance athletes, the clinical significance and prevalence of this finding in youthful athletes is uncertain and should not be assumed to be a normal consequence of intense athletic training in young competitive athletes,” argued Dr. Kim, of Emory University, Atlanta.
There’s probably little about being a young competitive athlete that would render a person any more or less prone to COVID-19 cardiac involvement, Dr. Baggish said. Rather, “I think what we’re seeing, as the studies continue to come out, is that prevalence estimates are getting into the low single digits.”
The estimates are similar to those associated with influenza before the COVID-19 age; about 2% of patients showed cardiac involvement, Dr. Baggish said. “So the degree to which COVID is a special virus from this perspective, I think, is still a topic of some debate.”
The two current studies have limitations and neither is positioned to change practice, he said. “I would say that they are both kind of important, reassuring pieces of an unfinished jigsaw puzzle. But we still don’t know what the picture on the puzzle is.”
Routine CMR for positive cases
The University of Wisconsin group looked at all of the institution’s competitive athletes who underwent gadolinium-enhanced CMR imaging and other tests during recovery from COVID-19 from the beginning of the pandemic to the end of November 2020.
The imaging was performed on average about 2 weeks after a first positive SARS-CoV-2 assay result. About one-half and one-fourth of the cohort had experienced mild and moderate symptoms, respectively, and about 17% were asymptomatic; none had been hospitalized.
All CMR scans were reviewed by two experienced radiologists for, among other things, evidence of myocarditis according to modified Lake Louise criteria, the group wrote. Those criteria are based on CMR markers of fibrosis and other characteristics of scarring from myocarditis.
Such evidence was seen in only two members of the cohort, or 1.4%, one with elevated troponins but normal with respect to other biomarkers, and the other negative for all assays. Both were asymptomatic at the time of imaging, the report noted.
The Vanderbilt analysis from Dr. Clark and associates centered on 59 university athletes recently with COVID-19 who underwent CMR imaging along with other tests about 3 weeks after confirmation of SARS-CoV-2 infection. Symptoms had been mild in 78% of the group, and the remainder were asymptomatic.
They were compared with 60 retrospectively identified college athletes and elite-conditioned military personnel who had undergone CMR imaging prior to the advent of COVID-19, and to 27 apparently healthy nonathlete adults in whom CMR had been previously performed to define normal CMR imaging criteria at that center.
The only two post-COVID-19 athletes who met modified Lake Louise criteria for myocarditis showed no abnormalities on ECG or myocardial strain echocardiography, and had normal troponins, the group reported.
The COVID-19 athletes showed increased cardiac chamber volumes and myocardial mass “consistent with athletic remodeling,” compared with the healthy control subjects, the group wrote. But “most standard CMR parameters were similar” between the COVID-19 athletes and the control athletes, consistent with the 22% and 24% rates, respectively, for the finding of focal late LGE isolated to the inferoseptal RV insertion site.
At the end of the day, all published experiences on athletes with recent COVID-19 “are descriptive studies, without any hint of follow-up,” Dr. Baggish noted, so their clinical implications are unknown.
“We need time to sit and watch to see what happens to these individuals,” he said. “And if the answer is nothing, then that’s a very reassuring story. If the answer is that we start to see events, then that’s really important for us to take stock of.”
Dr. Starekova had no disclosures. Dr. Reeder reports that the University of Wisconsin receives research support from GE Healthcare and Bracco Diagnostics; and that he has ownership interests in Calimetrix, Reveal Pharmaceuticals, Cellectar Biosciences, Elucent Medical, and HeartVista; and has received grant support from Bayer Healthcare. Disclosures for the other coauthors are in the report. Dr. Clark and coauthors had no disclosures. Dr. Baggish reported no conflicts. Kim discloses receiving funding from the National Heart, Lung, and Blood Institute; compensation as team cardiologist for the Atlanta Falcons; and research stipends from the Atlanta Track Club.
A version of this article first appeared on Medscape.com.
Two recent observational studies suggest that myocarditis, at least on cardiac magnetic resonance (CMR) imaging, might be far less common in elite-level athletes recovering from COVID-19 than suggested in influential earlier reports.
Both new studies documented a rate less than one-quarter as high as those previously reported from smaller cohorts, raising questions about the diagnostic yield of CMR in highly conditioned athletes with recent COVID-19 absent other evidence, such as from biomarker assays or electrocardiography (ECG).
That could have implications for some top-tier university athletics programs that mandate CMR imaging, biomarker assays, and other evaluations for myocarditis on all their players who test positive for SARS-CoV-2 before they can return to play.
The findings collectively point to CMR imaging features that might be a hallmark of an athlete’s heart, characterized by normal myocardial remodeling brought on by elite-level exercise training, which in athletes with recent COVID-19 could be misinterpreted as evidence of myocarditis. That may have thrown off prevalence estimates in the literature, the studies’ investigators speculated.
The two studies were retrospective takes on university athletes who underwent CMR imaging while recovering from COVID-19, who were either asymptomatic or with only mild to moderate symptoms and were generally without ECG or troponin evidence of myocarditis.
One of them showed a less than 2% incidence of myocarditis by CMR among 145 such cases, a low yield for imaging that is “raising doubt regarding its utility to evaluate athletes without a clinical presentation or abnormal ancillary tests to support the diagnosis of myocarditis,” argues a report published Jan. 14 in JAMA Cardiology, with lead author Jitka Starekova, MD, University of Wisconsin – Madison.
“Part of the problem is that occult myocarditis is, at least with other viruses, a risk factor for sudden death in competitive athletes. So you don’t want to let one slip through the cracks,” senior author Scott B. Reeder, MD, PhD, from the same institution, said in an interview.
Whether a policy of routine CMR imaging in elite athletes who test positive for the new coronavirus is better than more selective use driven by symptoms or other screening tests is unknown. But the more pressing issue, Dr. Reeder said, “is if they have a normal electrocardiogram and troponins, do they still need cardiac magnetic resonance imaging?”
The current study, he said, “certainly provides helpful evidence that maybe we don’t need as many.”
The other study, which featured two control groups, saw a similarly low incidence of myocarditis by CMR in athletes with recent COVID-19. One of the control groups included university athletes imaged prior to the advent of SARS-CoV-2 in the university’s region of the country. The other consisted of apparently healthy adult nonathletes.
Armed with two non-COVID-19 cohorts and two athlete cohorts, the researchers found comparable rates of myocarditis by CMR in both the COVID-19 athletes and the healthy athletes. And only 3% of the COVID-19 athletes had the tell-tale CMR signs, notes the report, published Dec. 17 in Circulation, with lead author Daniel E. Clark, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn.
Reassurance and concern
“The incidence is much lower than we feared, and so that’s reassuring,” Clark said in an interview. Still, the athletes with myocarditis by CMR “would have been completely missed by a protocol that did not include cardiac MR, and that’s concerning,” he said. “Both had active myocarditis.”
The study’s two non-COVID-19 control groups – elite athletes in one and nonathletes in the other – allowed them to tease out the potential contribution of athletic myocardial remodeling to CMR features that could be interpreted as scar tissue, which are characterized by late gadolinium enhancement (LGE).
As it turned out, focal regions of LGE located in the right ventricular (RV) septum on the scans were often seen in both athlete cohorts. “This kind of trivial nonischemic fibrosis in the mid RV septal insertion site was common among athletic control subjects. It was seen in 24% of them, which is almost identical to the percentage that we saw in the COVID-19 athletes, 22%,” Dr. Clark said.
The LGE finding, wrote Dr. Clark and coauthors, “may represent remodeling from athletic training, and should not be conflated with myocarditis.”
Of note, the other study saw a comparable incidence of the same or a very similar CMR feature in its athletes; 26% of the Wisconsin COVID-19 athlete cohort showed limited focal LGE in the inferior RV insertion site.
“And you get a little bit in the mid-septum, as well,” Dr. Reeder said. But the sign, in the absence of any corresponding T2 abnormalities, was not judged to represent myocarditis. “We interpreted all of these studies with this potential confounder in mind.”
Conceivably, Dr. Reeder proposed, the earlier studies may have “over-called” the prevalence of myocarditis in their cohorts. “I haven’t seen their images, but it’s possible there could be false-positives.”
It’s noteworthy that the Vanderbilt and Wisconsin reports saw closely similar incidences of the tell-tale CMR sign in all the athlete cohorts whether or not COVID-19 was involved, Aaron L. Baggish, MD, Massachusetts General Hospital, Boston, said in an interview.
“It looks very much like just an unrecognized part of athletic remodeling and isn’t in any way, shape, or form implicated as being a COVID-related issue,” said Dr. Baggish, who directs the cardiovascular performance program at his center and is unaffiliated with either study.
Still, that connection remains unproven given how little is yet known about the prevalence of clinically important myocarditis in milder cases of COVID-19, according to an accompanying editorial from Jonathan H. Kim, MD, MSc.
Although isolated LGE at the interventricular RV insertion site is “more commonly described among masters-level endurance athletes, the clinical significance and prevalence of this finding in youthful athletes is uncertain and should not be assumed to be a normal consequence of intense athletic training in young competitive athletes,” argued Dr. Kim, of Emory University, Atlanta.
There’s probably little about being a young competitive athlete that would render a person any more or less prone to COVID-19 cardiac involvement, Dr. Baggish said. Rather, “I think what we’re seeing, as the studies continue to come out, is that prevalence estimates are getting into the low single digits.”
The estimates are similar to those associated with influenza before the COVID-19 age; about 2% of patients showed cardiac involvement, Dr. Baggish said. “So the degree to which COVID is a special virus from this perspective, I think, is still a topic of some debate.”
The two current studies have limitations and neither is positioned to change practice, he said. “I would say that they are both kind of important, reassuring pieces of an unfinished jigsaw puzzle. But we still don’t know what the picture on the puzzle is.”
Routine CMR for positive cases
The University of Wisconsin group looked at all of the institution’s competitive athletes who underwent gadolinium-enhanced CMR imaging and other tests during recovery from COVID-19 from the beginning of the pandemic to the end of November 2020.
The imaging was performed on average about 2 weeks after a first positive SARS-CoV-2 assay result. About one-half and one-fourth of the cohort had experienced mild and moderate symptoms, respectively, and about 17% were asymptomatic; none had been hospitalized.
All CMR scans were reviewed by two experienced radiologists for, among other things, evidence of myocarditis according to modified Lake Louise criteria, the group wrote. Those criteria are based on CMR markers of fibrosis and other characteristics of scarring from myocarditis.
Such evidence was seen in only two members of the cohort, or 1.4%, one with elevated troponins but normal with respect to other biomarkers, and the other negative for all assays. Both were asymptomatic at the time of imaging, the report noted.
The Vanderbilt analysis from Dr. Clark and associates centered on 59 university athletes recently with COVID-19 who underwent CMR imaging along with other tests about 3 weeks after confirmation of SARS-CoV-2 infection. Symptoms had been mild in 78% of the group, and the remainder were asymptomatic.
They were compared with 60 retrospectively identified college athletes and elite-conditioned military personnel who had undergone CMR imaging prior to the advent of COVID-19, and to 27 apparently healthy nonathlete adults in whom CMR had been previously performed to define normal CMR imaging criteria at that center.
The only two post-COVID-19 athletes who met modified Lake Louise criteria for myocarditis showed no abnormalities on ECG or myocardial strain echocardiography, and had normal troponins, the group reported.
The COVID-19 athletes showed increased cardiac chamber volumes and myocardial mass “consistent with athletic remodeling,” compared with the healthy control subjects, the group wrote. But “most standard CMR parameters were similar” between the COVID-19 athletes and the control athletes, consistent with the 22% and 24% rates, respectively, for the finding of focal late LGE isolated to the inferoseptal RV insertion site.
At the end of the day, all published experiences on athletes with recent COVID-19 “are descriptive studies, without any hint of follow-up,” Dr. Baggish noted, so their clinical implications are unknown.
“We need time to sit and watch to see what happens to these individuals,” he said. “And if the answer is nothing, then that’s a very reassuring story. If the answer is that we start to see events, then that’s really important for us to take stock of.”
Dr. Starekova had no disclosures. Dr. Reeder reports that the University of Wisconsin receives research support from GE Healthcare and Bracco Diagnostics; and that he has ownership interests in Calimetrix, Reveal Pharmaceuticals, Cellectar Biosciences, Elucent Medical, and HeartVista; and has received grant support from Bayer Healthcare. Disclosures for the other coauthors are in the report. Dr. Clark and coauthors had no disclosures. Dr. Baggish reported no conflicts. Kim discloses receiving funding from the National Heart, Lung, and Blood Institute; compensation as team cardiologist for the Atlanta Falcons; and research stipends from the Atlanta Track Club.
A version of this article first appeared on Medscape.com.
Intraoperative rupture of ovarian cancer: Does it worsen outcomes?
Intact removal of an ovarian cyst is a well-established gynecologic surgical principle because ovarian cancer is definitively diagnosed only in retrospect (after ovarian extraction) and intraoperative cyst rupture upstages an otherwise nonmetastatic cancer to stage IC. This lumps cancers that are ruptured during surgical extraction together with those that have spontaneously ruptured or have surface excrescences. The theoretical rationale for this “lumping” is that contact between malignant cells from the ruptured cyst may take hold on peritoneal surfaces resulting in development of metastases. To offset this theoretical risk, it has been recommended that all stage IC ovarian cancer is treated with chemotherapy, whereas low-grade stage IA and IB cancers generally are not. No conscientious surgeon wants their surgical intervention to be the cause of a patient needing toxic chemotherapy. But is the contact between malignant cyst fluid and the peritoneum truly as bad as a spontaneous breach of the surface of the tumor? Or is cyst rupture a confounder for other adverse prognostic features, such as histologic cell type and dense pelvic attachments? If ovarian cyst rupture is an independent risk factor for patients with stage I ovarian cancer, strategies should be employed to avoid this occurrence, and we should understand how to counsel and treat patients in whom this has occurred.
In 2017 the International Federation of Gynecology and Obstetrics (FIGO) staging of epithelial ovarian cancer subcategorized stage IC. This group encompasses women with contact between malignant cells and the peritoneum in the absence of other extraovarian disease. The table includes these distinct groupings. Stage IC1 includes patients in whom intraoperative spill occurred. Stage IC2 includes women with preoperative cyst rupture, and or microscopic or macroscopic surface involvement because the data support that these cases carry a poorer prognosis, compared with those with intraoperative rupture (IC1).1 The final subcategory, IC3, includes women who have washings (obtained at the onset of surgery, prior to manipulation of the tumor) that were positive for malignant cells, denoting preexisting contact between the tumor and peritoneum and a phenotypically more aggressive tumor.
The clinical significance of ovarian cancer capsule rupture has been evaluated in multiple studies with some mixed results.1 Consistently, it is reported that preoperative rupture, surface or capsular involvement, and preexisting peritoneal circulation of metastatic cells all portend a poorer prognosis; however, it is less clear that iatrogenic surgical rupture has the same deleterious association. In a large retrospective series from Japan, the authors evaluated 15,163 cases of stage I ovarian cancer and identified 7,227 cases of iatrogenic (intraoperative) cyst rupture.2 These cases were significantly more likely to occur among clear cell cancers, and were more likely to occur in younger patients. Worse prognosis was associated with cell type (clear cell cancers), but non–clear cell cancers (such as serous, mucinous, and endometrioid) did not have a higher hazard ratio for death when intraoperative rupture occurred. But why would intraoperative cyst rupture result in worse prognosis for only one histologic cell type? The authors hypothesized that perhaps rupture was more likely to occur during extraction of these clear cell tumors because they were associated with dense adhesions from associated endometriosis, and perhaps an adverse biologic phenomenon associated with infiltrative endometriosis is driving the behavior of this cancer.
The Japanese study also looked at the effect of chemotherapy on these same patients’ outcomes. Interestingly, the addition of chemotherapy did not improve survival for the patients with stage IC1 cancers, which was in contrast to the improved survival seen when chemotherapy was given to those with spontaneous rupture or ovarian surface involvement (IC2, IC3). These data support differentiating the subgroups of stage IC cancer in treatment decision-making, and suggest that adjuvant chemotherapy might be avoided for patients with nonclear cell stage IC1 ovarian cancer. While the outcomes are worse for patients with ruptured clear cell cancers, current therapeutic options for clear cell cancers are limited because of their known resistance to traditional agents, and outcomes for women with clear cell cancer can be worse across all stages.
While cyst rupture may not always negatively affect prognosis, the goal of surgery remains an intact removal, which influences decisions regarding surgical approach. Most adnexal masses are removed via minimally invasive surgery (MIS). MIS is associated with benefits of morbidity and cost, and therefore should be considered wherever feasible. However, MIS is associated with an increased risk of ovarian cyst rupture, likely because of the rigid instrumentation used when approaching a curved structure, in addition to the disparity in size of the pathology, compared with the extraction site incision.3 When weighing the benefits and risks of different surgical approaches, it is important to gauge the probability of malignancy. Not all complex ovarian masses associated with elevations in tumor markers are malignant, and certainly most that are associated with normal tumor markers are not. If the preoperative clinical data suggest that the mass is more likely to be malignant (e.g., mostly solid, vascular tumors with very elevated tumor markers), consideration might be made to abandoning a purely minimally invasive approach to a hand-assisted MIS or laparotomy approach. However, it would seem that abandoning an MIS approach to remove every ovarian cyst is unwise given that there is clear patient benefit with MIS and, as discussed above, most cases of iatrogenic malignant cyst rupture are unavoidable even with laparotomy, and do not necessarily independently portend poorer survival or mandate chemotherapy.
Surgeons should be both nuanced and flexible and apply some basic rules of thumb when approaching the diagnostically uncertain adnexal mass. Peritoneal washings should be obtained at the commencement of the case to discriminate those cases of true stage IC3. The peritoneum parallel to the ovarian vessel should be extensively opened to a level above the pelvic brim. In order to do this, the physiological attachments between the sigmoid colon or cecum and the suspensory ligament of the ovary may need to be carefully mobilized. This allows for retroperitoneal identification of the ureter and skeletonization of the ovarian vessels at least 2 cm proximal to their insertion into the ovary and avoidance of contact with the ovary itself (which may have a fragile capsule) or incomplete ovarian resection. If the ovary remains invested close to the sidewall or colonic structures and the appropriate peritoneal and retroperitoneal mobilization has not occurred, the surgeon may unavoidably rupture the ovarian cyst as they try to “hug” the ovary with their bites of tissue in an attempt to avoid visceral injury. There is little role for an ovarian cystectomy in a postmenopausal woman undergoing surgery for a complex adnexal mass, particularly if she has elevated tumor markers, because the process of performing ovarian cystectomy commonly invokes cyst rupture or fragmentation. Ovarian cystectomy should be reserved for premenopausal women with adnexal masses at low suspicion for malignancy. If the adnexa appears densely adherent to adjacent structures – for example, associated with infiltrative endometriosis – consideration for laparotomy or a hand-assisted approach may be necessary; in such cases, even open surgery can result in cyst rupture, and the morbidity of conversion to laparotomy should be weighed for individual cases.
Finally, retrieval of the ovarian specimen should occur intact without morcellation. There should be no uncontained morcellation of adnexal structures during retrieval of even normal-appearing ovaries. The preferred retrieval method is to place the adnexa in an appropriately sized retrieval bag, after which contained morcellation or drainage can occur to facilitate removal through a laparoscopic incision. Contained morcellation is very difficult for large solid masses through a laparoscopic port site; in these cases, extension of the incision may be necessary.
While operative spill of an ovarian cancer does upstage nonmetastatic ovarian cancer, it is unclear that, in most cases, this is independently associated with worse prognosis, and chemotherapy may not always be of added value. However, best surgical practice should always include strategies to minimize the chance of rupture when approaching adnexal masses, particularly those at highest likelihood of malignancy.
References
1. Kim HS et al. Eur J Surg Oncol. 2013 Mar 39(3):279-89.
2. Matsuo K et al. Obstet Gynecol. 2019 Nov;134(5):1017-26.
3. Matsuo K et al. JAMA Oncol. 2020 Jul 1;6(7):1110-3.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.
Intact removal of an ovarian cyst is a well-established gynecologic surgical principle because ovarian cancer is definitively diagnosed only in retrospect (after ovarian extraction) and intraoperative cyst rupture upstages an otherwise nonmetastatic cancer to stage IC. This lumps cancers that are ruptured during surgical extraction together with those that have spontaneously ruptured or have surface excrescences. The theoretical rationale for this “lumping” is that contact between malignant cells from the ruptured cyst may take hold on peritoneal surfaces resulting in development of metastases. To offset this theoretical risk, it has been recommended that all stage IC ovarian cancer is treated with chemotherapy, whereas low-grade stage IA and IB cancers generally are not. No conscientious surgeon wants their surgical intervention to be the cause of a patient needing toxic chemotherapy. But is the contact between malignant cyst fluid and the peritoneum truly as bad as a spontaneous breach of the surface of the tumor? Or is cyst rupture a confounder for other adverse prognostic features, such as histologic cell type and dense pelvic attachments? If ovarian cyst rupture is an independent risk factor for patients with stage I ovarian cancer, strategies should be employed to avoid this occurrence, and we should understand how to counsel and treat patients in whom this has occurred.
In 2017 the International Federation of Gynecology and Obstetrics (FIGO) staging of epithelial ovarian cancer subcategorized stage IC. This group encompasses women with contact between malignant cells and the peritoneum in the absence of other extraovarian disease. The table includes these distinct groupings. Stage IC1 includes patients in whom intraoperative spill occurred. Stage IC2 includes women with preoperative cyst rupture, and or microscopic or macroscopic surface involvement because the data support that these cases carry a poorer prognosis, compared with those with intraoperative rupture (IC1).1 The final subcategory, IC3, includes women who have washings (obtained at the onset of surgery, prior to manipulation of the tumor) that were positive for malignant cells, denoting preexisting contact between the tumor and peritoneum and a phenotypically more aggressive tumor.
The clinical significance of ovarian cancer capsule rupture has been evaluated in multiple studies with some mixed results.1 Consistently, it is reported that preoperative rupture, surface or capsular involvement, and preexisting peritoneal circulation of metastatic cells all portend a poorer prognosis; however, it is less clear that iatrogenic surgical rupture has the same deleterious association. In a large retrospective series from Japan, the authors evaluated 15,163 cases of stage I ovarian cancer and identified 7,227 cases of iatrogenic (intraoperative) cyst rupture.2 These cases were significantly more likely to occur among clear cell cancers, and were more likely to occur in younger patients. Worse prognosis was associated with cell type (clear cell cancers), but non–clear cell cancers (such as serous, mucinous, and endometrioid) did not have a higher hazard ratio for death when intraoperative rupture occurred. But why would intraoperative cyst rupture result in worse prognosis for only one histologic cell type? The authors hypothesized that perhaps rupture was more likely to occur during extraction of these clear cell tumors because they were associated with dense adhesions from associated endometriosis, and perhaps an adverse biologic phenomenon associated with infiltrative endometriosis is driving the behavior of this cancer.
The Japanese study also looked at the effect of chemotherapy on these same patients’ outcomes. Interestingly, the addition of chemotherapy did not improve survival for the patients with stage IC1 cancers, which was in contrast to the improved survival seen when chemotherapy was given to those with spontaneous rupture or ovarian surface involvement (IC2, IC3). These data support differentiating the subgroups of stage IC cancer in treatment decision-making, and suggest that adjuvant chemotherapy might be avoided for patients with nonclear cell stage IC1 ovarian cancer. While the outcomes are worse for patients with ruptured clear cell cancers, current therapeutic options for clear cell cancers are limited because of their known resistance to traditional agents, and outcomes for women with clear cell cancer can be worse across all stages.
While cyst rupture may not always negatively affect prognosis, the goal of surgery remains an intact removal, which influences decisions regarding surgical approach. Most adnexal masses are removed via minimally invasive surgery (MIS). MIS is associated with benefits of morbidity and cost, and therefore should be considered wherever feasible. However, MIS is associated with an increased risk of ovarian cyst rupture, likely because of the rigid instrumentation used when approaching a curved structure, in addition to the disparity in size of the pathology, compared with the extraction site incision.3 When weighing the benefits and risks of different surgical approaches, it is important to gauge the probability of malignancy. Not all complex ovarian masses associated with elevations in tumor markers are malignant, and certainly most that are associated with normal tumor markers are not. If the preoperative clinical data suggest that the mass is more likely to be malignant (e.g., mostly solid, vascular tumors with very elevated tumor markers), consideration might be made to abandoning a purely minimally invasive approach to a hand-assisted MIS or laparotomy approach. However, it would seem that abandoning an MIS approach to remove every ovarian cyst is unwise given that there is clear patient benefit with MIS and, as discussed above, most cases of iatrogenic malignant cyst rupture are unavoidable even with laparotomy, and do not necessarily independently portend poorer survival or mandate chemotherapy.
Surgeons should be both nuanced and flexible and apply some basic rules of thumb when approaching the diagnostically uncertain adnexal mass. Peritoneal washings should be obtained at the commencement of the case to discriminate those cases of true stage IC3. The peritoneum parallel to the ovarian vessel should be extensively opened to a level above the pelvic brim. In order to do this, the physiological attachments between the sigmoid colon or cecum and the suspensory ligament of the ovary may need to be carefully mobilized. This allows for retroperitoneal identification of the ureter and skeletonization of the ovarian vessels at least 2 cm proximal to their insertion into the ovary and avoidance of contact with the ovary itself (which may have a fragile capsule) or incomplete ovarian resection. If the ovary remains invested close to the sidewall or colonic structures and the appropriate peritoneal and retroperitoneal mobilization has not occurred, the surgeon may unavoidably rupture the ovarian cyst as they try to “hug” the ovary with their bites of tissue in an attempt to avoid visceral injury. There is little role for an ovarian cystectomy in a postmenopausal woman undergoing surgery for a complex adnexal mass, particularly if she has elevated tumor markers, because the process of performing ovarian cystectomy commonly invokes cyst rupture or fragmentation. Ovarian cystectomy should be reserved for premenopausal women with adnexal masses at low suspicion for malignancy. If the adnexa appears densely adherent to adjacent structures – for example, associated with infiltrative endometriosis – consideration for laparotomy or a hand-assisted approach may be necessary; in such cases, even open surgery can result in cyst rupture, and the morbidity of conversion to laparotomy should be weighed for individual cases.
Finally, retrieval of the ovarian specimen should occur intact without morcellation. There should be no uncontained morcellation of adnexal structures during retrieval of even normal-appearing ovaries. The preferred retrieval method is to place the adnexa in an appropriately sized retrieval bag, after which contained morcellation or drainage can occur to facilitate removal through a laparoscopic incision. Contained morcellation is very difficult for large solid masses through a laparoscopic port site; in these cases, extension of the incision may be necessary.
While operative spill of an ovarian cancer does upstage nonmetastatic ovarian cancer, it is unclear that, in most cases, this is independently associated with worse prognosis, and chemotherapy may not always be of added value. However, best surgical practice should always include strategies to minimize the chance of rupture when approaching adnexal masses, particularly those at highest likelihood of malignancy.
References
1. Kim HS et al. Eur J Surg Oncol. 2013 Mar 39(3):279-89.
2. Matsuo K et al. Obstet Gynecol. 2019 Nov;134(5):1017-26.
3. Matsuo K et al. JAMA Oncol. 2020 Jul 1;6(7):1110-3.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.
Intact removal of an ovarian cyst is a well-established gynecologic surgical principle because ovarian cancer is definitively diagnosed only in retrospect (after ovarian extraction) and intraoperative cyst rupture upstages an otherwise nonmetastatic cancer to stage IC. This lumps cancers that are ruptured during surgical extraction together with those that have spontaneously ruptured or have surface excrescences. The theoretical rationale for this “lumping” is that contact between malignant cells from the ruptured cyst may take hold on peritoneal surfaces resulting in development of metastases. To offset this theoretical risk, it has been recommended that all stage IC ovarian cancer is treated with chemotherapy, whereas low-grade stage IA and IB cancers generally are not. No conscientious surgeon wants their surgical intervention to be the cause of a patient needing toxic chemotherapy. But is the contact between malignant cyst fluid and the peritoneum truly as bad as a spontaneous breach of the surface of the tumor? Or is cyst rupture a confounder for other adverse prognostic features, such as histologic cell type and dense pelvic attachments? If ovarian cyst rupture is an independent risk factor for patients with stage I ovarian cancer, strategies should be employed to avoid this occurrence, and we should understand how to counsel and treat patients in whom this has occurred.
In 2017 the International Federation of Gynecology and Obstetrics (FIGO) staging of epithelial ovarian cancer subcategorized stage IC. This group encompasses women with contact between malignant cells and the peritoneum in the absence of other extraovarian disease. The table includes these distinct groupings. Stage IC1 includes patients in whom intraoperative spill occurred. Stage IC2 includes women with preoperative cyst rupture, and or microscopic or macroscopic surface involvement because the data support that these cases carry a poorer prognosis, compared with those with intraoperative rupture (IC1).1 The final subcategory, IC3, includes women who have washings (obtained at the onset of surgery, prior to manipulation of the tumor) that were positive for malignant cells, denoting preexisting contact between the tumor and peritoneum and a phenotypically more aggressive tumor.
The clinical significance of ovarian cancer capsule rupture has been evaluated in multiple studies with some mixed results.1 Consistently, it is reported that preoperative rupture, surface or capsular involvement, and preexisting peritoneal circulation of metastatic cells all portend a poorer prognosis; however, it is less clear that iatrogenic surgical rupture has the same deleterious association. In a large retrospective series from Japan, the authors evaluated 15,163 cases of stage I ovarian cancer and identified 7,227 cases of iatrogenic (intraoperative) cyst rupture.2 These cases were significantly more likely to occur among clear cell cancers, and were more likely to occur in younger patients. Worse prognosis was associated with cell type (clear cell cancers), but non–clear cell cancers (such as serous, mucinous, and endometrioid) did not have a higher hazard ratio for death when intraoperative rupture occurred. But why would intraoperative cyst rupture result in worse prognosis for only one histologic cell type? The authors hypothesized that perhaps rupture was more likely to occur during extraction of these clear cell tumors because they were associated with dense adhesions from associated endometriosis, and perhaps an adverse biologic phenomenon associated with infiltrative endometriosis is driving the behavior of this cancer.
The Japanese study also looked at the effect of chemotherapy on these same patients’ outcomes. Interestingly, the addition of chemotherapy did not improve survival for the patients with stage IC1 cancers, which was in contrast to the improved survival seen when chemotherapy was given to those with spontaneous rupture or ovarian surface involvement (IC2, IC3). These data support differentiating the subgroups of stage IC cancer in treatment decision-making, and suggest that adjuvant chemotherapy might be avoided for patients with nonclear cell stage IC1 ovarian cancer. While the outcomes are worse for patients with ruptured clear cell cancers, current therapeutic options for clear cell cancers are limited because of their known resistance to traditional agents, and outcomes for women with clear cell cancer can be worse across all stages.
While cyst rupture may not always negatively affect prognosis, the goal of surgery remains an intact removal, which influences decisions regarding surgical approach. Most adnexal masses are removed via minimally invasive surgery (MIS). MIS is associated with benefits of morbidity and cost, and therefore should be considered wherever feasible. However, MIS is associated with an increased risk of ovarian cyst rupture, likely because of the rigid instrumentation used when approaching a curved structure, in addition to the disparity in size of the pathology, compared with the extraction site incision.3 When weighing the benefits and risks of different surgical approaches, it is important to gauge the probability of malignancy. Not all complex ovarian masses associated with elevations in tumor markers are malignant, and certainly most that are associated with normal tumor markers are not. If the preoperative clinical data suggest that the mass is more likely to be malignant (e.g., mostly solid, vascular tumors with very elevated tumor markers), consideration might be made to abandoning a purely minimally invasive approach to a hand-assisted MIS or laparotomy approach. However, it would seem that abandoning an MIS approach to remove every ovarian cyst is unwise given that there is clear patient benefit with MIS and, as discussed above, most cases of iatrogenic malignant cyst rupture are unavoidable even with laparotomy, and do not necessarily independently portend poorer survival or mandate chemotherapy.
Surgeons should be both nuanced and flexible and apply some basic rules of thumb when approaching the diagnostically uncertain adnexal mass. Peritoneal washings should be obtained at the commencement of the case to discriminate those cases of true stage IC3. The peritoneum parallel to the ovarian vessel should be extensively opened to a level above the pelvic brim. In order to do this, the physiological attachments between the sigmoid colon or cecum and the suspensory ligament of the ovary may need to be carefully mobilized. This allows for retroperitoneal identification of the ureter and skeletonization of the ovarian vessels at least 2 cm proximal to their insertion into the ovary and avoidance of contact with the ovary itself (which may have a fragile capsule) or incomplete ovarian resection. If the ovary remains invested close to the sidewall or colonic structures and the appropriate peritoneal and retroperitoneal mobilization has not occurred, the surgeon may unavoidably rupture the ovarian cyst as they try to “hug” the ovary with their bites of tissue in an attempt to avoid visceral injury. There is little role for an ovarian cystectomy in a postmenopausal woman undergoing surgery for a complex adnexal mass, particularly if she has elevated tumor markers, because the process of performing ovarian cystectomy commonly invokes cyst rupture or fragmentation. Ovarian cystectomy should be reserved for premenopausal women with adnexal masses at low suspicion for malignancy. If the adnexa appears densely adherent to adjacent structures – for example, associated with infiltrative endometriosis – consideration for laparotomy or a hand-assisted approach may be necessary; in such cases, even open surgery can result in cyst rupture, and the morbidity of conversion to laparotomy should be weighed for individual cases.
Finally, retrieval of the ovarian specimen should occur intact without morcellation. There should be no uncontained morcellation of adnexal structures during retrieval of even normal-appearing ovaries. The preferred retrieval method is to place the adnexa in an appropriately sized retrieval bag, after which contained morcellation or drainage can occur to facilitate removal through a laparoscopic incision. Contained morcellation is very difficult for large solid masses through a laparoscopic port site; in these cases, extension of the incision may be necessary.
While operative spill of an ovarian cancer does upstage nonmetastatic ovarian cancer, it is unclear that, in most cases, this is independently associated with worse prognosis, and chemotherapy may not always be of added value. However, best surgical practice should always include strategies to minimize the chance of rupture when approaching adnexal masses, particularly those at highest likelihood of malignancy.
References
1. Kim HS et al. Eur J Surg Oncol. 2013 Mar 39(3):279-89.
2. Matsuo K et al. Obstet Gynecol. 2019 Nov;134(5):1017-26.
3. Matsuo K et al. JAMA Oncol. 2020 Jul 1;6(7):1110-3.
Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.