Arguably, no topic during an infertility consultation generates more of an emotional reaction than discussing body mass index (BMI), particularly when it is high. Patients have become increasingly sensitive to weight discussions with their physicians because of concerns about body shaming. Among patients with an elevated BMI, criticism on social media of health care professionals’ counseling and a preemptive presentation of “Don’t Weigh Me” cards have become popular responses. Despite the medical evidence on impaired reproduction with an abnormal BMI, patients are choosing to forgo the topic. Research has demonstrated “extensive evidence [of] strong weight bias” in a wide range of health staff.¹ A “viral” TikTok study revealed that medical “gaslighting” founded in weight stigma and bias is harmful, as reported on KevinMD.com.² This month, we review the effect of abnormal BMI, both high and low, on reproduction and pregnancy.

A method to assess relative weight was first described in 1832 as its ratio in kilograms divided by the square of the height in meters, or the Quetelet Index. The search for a functional assessment of relative body weight began after World War II when reports by actuaries noted the increased mortality of overweight policyholders. The relationship between weight and cardiovascular disease was further revealed in epidemiologic studies. The Quetelet Index became the BMI in 1972.³

Weight measurement is a mainstay in the assessment of a patient’s vital signs along with blood pressure, pulse rate, respiration rate, and temperature. Weight is vital to the calculation of medication dosage – for instance, administration of conscious sedative drugs, methotrexate, and gonadotropins. Some state boards of medicine, such as Florida, have a limitation on patient BMI at office-based surgery centers (40 kg/m²).
 

Obesity is a disease

As reported by the World Health Organization in 2022, the disease of obesity is an epidemic afflicting more than 1 billion people worldwide, or 1 in 8 individuals globally.⁴ The health implications of an elevated BMI include increased mortality, diabetes, heart disease, and stroke, physical limitations to activities of daily living, and complications affecting reproduction.

Female obesity is related to poorer outcomes in natural and assisted conception, including an increased risk of miscarriage. Compared with normal-weight women, those with obesity are three times more likely to have ovulatory dysfunction,⁵ infertility,⁶ a lower chance for conception,⁷ higher rate of miscarriage, and low birth weight.^8,9During pregnancy, women with obesity have three to four times higher rates of gestational diabetes and preeclampsia,¹⁰ as well as likelihood of delivering preterm,¹¹ having a fetus with macrosomia and birth defects, and a 1.3- to 2.1-times higher risk of stillbirth.¹²

Obesity is present in 40%-80% of women with polycystic ovary syndrome,¹³ the most common cause of ovulatory dysfunction from dysregulation of the hypothalamic-pituitary-ovarian axis. While PCOS is associated with reproductive and metabolic consequences, even in regularly ovulating women, increasing obesity appears to be associated with decreasing spontaneous pregnancy rates and increased time to pregnancy.¹⁴

Obesity and IVF

Women with obesity have reduced success with assisted reproductive technology, an increased number of canceled cycles, and poorer quality oocytes retrieved. A prospective cohort study of nearly 2,000 women reported that every 5 kg of body weight increase (from the patient’s baseline weight at age 18) was associated with a 5% increase in the mean duration of time required for conception (95% confidence interval, 3%-7%).¹⁵ Given that approximately 90% of these women had regular menstrual cycles, ovulatory dysfunction was not the suspected pathophysiology.

A meta-analysis of 21 cohort studies reported a lower likelihood of live birth following in vitro fertilization for women with obesity, compared with normal-weight women (risk ratio, 0.85; 95% CI, 0.82-0.87).¹⁶ A further subgroup analysis that evaluated only women with PCOS showed a reduction in the live birth rate following IVF for individuals with obesity, compared with normal-weight individuals (RR, 0.78; 95% CI, 0.74-0.82).

In a retrospective study of almost 500,000 fresh autologous IVF cycles, women with obesity had a 6% reduction in pregnancy rates and a 13% reduction in live birth rates, compared with normal-weight women. Both high and low BMI were associated with an increased risk of low birth weight and preterm delivery.¹⁷ The live birth rates per transfer for normal-weight and higher-weight women were 38% and 33%, respectively.

Contrarily, a randomized controlled trial showed that an intensive weight-reduction program resulted in a large weight loss but did not substantially affect live birth rates in women with obesity scheduled for IVF.¹⁸

Low BMI

A noteworthy cause of low BMI is functional hypothalamic amenorrhea (FHA), a disorder with low energy availability either from decreased caloric intake and/or excessive energy expenditure associated with eating disorders, excessive exercise, and stress. Consequently, a reduced GnRH drive results in a decreased pulse frequency and amplitude leading to low levels of follicle-stimulating hormone and luteinizing hormone, resulting in anovulation. Correction of lifestyle behaviors related to FHA can restore menstrual cycles. After normal weight is achieved, it appears unlikely that fertility is affected.¹⁹ In 47% of adolescent patients with anorexia, menses spontaneously returned within the first 12 months after admission, with an improved prognosis in secondary over primary amenorrhea.^20,21 Interestingly, mildly and significantly underweight infertile women have pregnancy and live birth rates similar to normal-weight patients after IVF treatment.²²

Pregnancy is complicated in underweight women, resulting in an increased risk of anemia, fetal growth retardation, and low birth weight, as well as preterm birth.²¹

Take-home message

The extremes of BMI both impair natural reproduction. Elevated BMI reduces success with IVF but rapid weight loss prior to IVF does not improve outcomes. A normal BMI is the goal for optimal reproductive and pregnancy health.

Dr. Trolice is director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
 

References

1. Talumaa B et al. Obesity Rev. 2022;23:e13494.

2. https://bit.ly/3rHCivE.

3. Eknoyan G. Nephrol Dial Transplant. 2008;23:47-51.

4. Wells JCK. Dis Models Mech. 2012;5:595-607.

5. Brewer CJ and Balen AH. Reproduction. 2010;140:347-64.

6. Silvestris E et al. Reprod Biol Endocrinol. 2018;16:22.

7. Wise LA et al. Hum Reprod. 2010;25:253-64.

8. Bellver J. Curr Opin Obstet Gynecol. 2022;34:114-21.

9. Dickey RP et al. Am J Obstet Gynecol. 2013;209:349.e1.

10. Alwash SM et al. Obes Res Clin Pract. 2021;15:425-30.

11. Cnattingius S et al. JAMA. 2013;309:2362-70.

12. Aune D et al. JAMA. 2014;311:1536-46.

13. Sam S. Obes Manag. 2007;3:69-73.

14. van der Steeg JW et al. Hum Reprod. 2008;23:324-8.

15. Gaskins AJ et al. Obstet Gynecol. 2015;126:850-8.

16. Sermondade N et al. Hum Reprod Update. 2019;25:439-519.

17. Kawwass JF et al. Fertil Steril. 2016;106[7]:1742-50.

18. Einarsson S et al. Hum Reprod. 2017;32:1621-30.

19. Chaer R et al. Diseases. 2020;8:46.

20. Dempfle A et al. Psychiatry. 2013;13:308.

21. Verma A and Shrimali L. J Clin Diagn Res. 2012;6:1531-3.

22. Romanski PA et al. Reprod Biomed Online. 2020;42:366-74.

Arguably, no topic during an infertility consultation generates more of an emotional reaction than discussing body mass index (BMI), particularly when it is high. Patients have become increasingly sensitive to weight discussions with their physicians because of concerns about body shaming. Among patients with an elevated BMI, criticism on social media of health care professionals’ counseling and a preemptive presentation of “Don’t Weigh Me” cards have become popular responses. Despite the medical evidence on impaired reproduction with an abnormal BMI, patients are choosing to forgo the topic. Research has demonstrated “extensive evidence [of] strong weight bias” in a wide range of health staff.¹ A “viral” TikTok study revealed that medical “gaslighting” founded in weight stigma and bias is harmful, as reported on KevinMD.com.² This month, we review the effect of abnormal BMI, both high and low, on reproduction and pregnancy.

A method to assess relative weight was first described in 1832 as its ratio in kilograms divided by the square of the height in meters, or the Quetelet Index. The search for a functional assessment of relative body weight began after World War II when reports by actuaries noted the increased mortality of overweight policyholders. The relationship between weight and cardiovascular disease was further revealed in epidemiologic studies. The Quetelet Index became the BMI in 1972.³

Weight measurement is a mainstay in the assessment of a patient’s vital signs along with blood pressure, pulse rate, respiration rate, and temperature. Weight is vital to the calculation of medication dosage – for instance, administration of conscious sedative drugs, methotrexate, and gonadotropins. Some state boards of medicine, such as Florida, have a limitation on patient BMI at office-based surgery centers (40 kg/m²).
 

Obesity is a disease

As reported by the World Health Organization in 2022, the disease of obesity is an epidemic afflicting more than 1 billion people worldwide, or 1 in 8 individuals globally.⁴ The health implications of an elevated BMI include increased mortality, diabetes, heart disease, and stroke, physical limitations to activities of daily living, and complications affecting reproduction.

Female obesity is related to poorer outcomes in natural and assisted conception, including an increased risk of miscarriage. Compared with normal-weight women, those with obesity are three times more likely to have ovulatory dysfunction,⁵ infertility,⁶ a lower chance for conception,⁷ higher rate of miscarriage, and low birth weight.^8,9During pregnancy, women with obesity have three to four times higher rates of gestational diabetes and preeclampsia,¹⁰ as well as likelihood of delivering preterm,¹¹ having a fetus with macrosomia and birth defects, and a 1.3- to 2.1-times higher risk of stillbirth.¹²

Obesity is present in 40%-80% of women with polycystic ovary syndrome,¹³ the most common cause of ovulatory dysfunction from dysregulation of the hypothalamic-pituitary-ovarian axis. While PCOS is associated with reproductive and metabolic consequences, even in regularly ovulating women, increasing obesity appears to be associated with decreasing spontaneous pregnancy rates and increased time to pregnancy.¹⁴

Obesity and IVF

Women with obesity have reduced success with assisted reproductive technology, an increased number of canceled cycles, and poorer quality oocytes retrieved. A prospective cohort study of nearly 2,000 women reported that every 5 kg of body weight increase (from the patient’s baseline weight at age 18) was associated with a 5% increase in the mean duration of time required for conception (95% confidence interval, 3%-7%).¹⁵ Given that approximately 90% of these women had regular menstrual cycles, ovulatory dysfunction was not the suspected pathophysiology.

A meta-analysis of 21 cohort studies reported a lower likelihood of live birth following in vitro fertilization for women with obesity, compared with normal-weight women (risk ratio, 0.85; 95% CI, 0.82-0.87).¹⁶ A further subgroup analysis that evaluated only women with PCOS showed a reduction in the live birth rate following IVF for individuals with obesity, compared with normal-weight individuals (RR, 0.78; 95% CI, 0.74-0.82).

In a retrospective study of almost 500,000 fresh autologous IVF cycles, women with obesity had a 6% reduction in pregnancy rates and a 13% reduction in live birth rates, compared with normal-weight women. Both high and low BMI were associated with an increased risk of low birth weight and preterm delivery.¹⁷ The live birth rates per transfer for normal-weight and higher-weight women were 38% and 33%, respectively.

Contrarily, a randomized controlled trial showed that an intensive weight-reduction program resulted in a large weight loss but did not substantially affect live birth rates in women with obesity scheduled for IVF.¹⁸

Low BMI

A noteworthy cause of low BMI is functional hypothalamic amenorrhea (FHA), a disorder with low energy availability either from decreased caloric intake and/or excessive energy expenditure associated with eating disorders, excessive exercise, and stress. Consequently, a reduced GnRH drive results in a decreased pulse frequency and amplitude leading to low levels of follicle-stimulating hormone and luteinizing hormone, resulting in anovulation. Correction of lifestyle behaviors related to FHA can restore menstrual cycles. After normal weight is achieved, it appears unlikely that fertility is affected.¹⁹ In 47% of adolescent patients with anorexia, menses spontaneously returned within the first 12 months after admission, with an improved prognosis in secondary over primary amenorrhea.^20,21 Interestingly, mildly and significantly underweight infertile women have pregnancy and live birth rates similar to normal-weight patients after IVF treatment.²²

Pregnancy is complicated in underweight women, resulting in an increased risk of anemia, fetal growth retardation, and low birth weight, as well as preterm birth.²¹

Take-home message

The extremes of BMI both impair natural reproduction. Elevated BMI reduces success with IVF but rapid weight loss prior to IVF does not improve outcomes. A normal BMI is the goal for optimal reproductive and pregnancy health.

Dr. Trolice is director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
 

References

1. Talumaa B et al. Obesity Rev. 2022;23:e13494.

2. https://bit.ly/3rHCivE.

3. Eknoyan G. Nephrol Dial Transplant. 2008;23:47-51.

4. Wells JCK. Dis Models Mech. 2012;5:595-607.

5. Brewer CJ and Balen AH. Reproduction. 2010;140:347-64.

6. Silvestris E et al. Reprod Biol Endocrinol. 2018;16:22.

7. Wise LA et al. Hum Reprod. 2010;25:253-64.

8. Bellver J. Curr Opin Obstet Gynecol. 2022;34:114-21.

9. Dickey RP et al. Am J Obstet Gynecol. 2013;209:349.e1.

10. Alwash SM et al. Obes Res Clin Pract. 2021;15:425-30.

11. Cnattingius S et al. JAMA. 2013;309:2362-70.

12. Aune D et al. JAMA. 2014;311:1536-46.

13. Sam S. Obes Manag. 2007;3:69-73.

14. van der Steeg JW et al. Hum Reprod. 2008;23:324-8.

15. Gaskins AJ et al. Obstet Gynecol. 2015;126:850-8.

16. Sermondade N et al. Hum Reprod Update. 2019;25:439-519.

17. Kawwass JF et al. Fertil Steril. 2016;106[7]:1742-50.

18. Einarsson S et al. Hum Reprod. 2017;32:1621-30.

19. Chaer R et al. Diseases. 2020;8:46.

20. Dempfle A et al. Psychiatry. 2013;13:308.

21. Verma A and Shrimali L. J Clin Diagn Res. 2012;6:1531-3.

22. Romanski PA et al. Reprod Biomed Online. 2020;42:366-74.

Arguably, no topic during an infertility consultation generates more of an emotional reaction than discussing body mass index (BMI), particularly when it is high. Patients have become increasingly sensitive to weight discussions with their physicians because of concerns about body shaming. Among patients with an elevated BMI, criticism on social media of health care professionals’ counseling and a preemptive presentation of “Don’t Weigh Me” cards have become popular responses. Despite the medical evidence on impaired reproduction with an abnormal BMI, patients are choosing to forgo the topic. Research has demonstrated “extensive evidence [of] strong weight bias” in a wide range of health staff.¹ A “viral” TikTok study revealed that medical “gaslighting” founded in weight stigma and bias is harmful, as reported on KevinMD.com.² This month, we review the effect of abnormal BMI, both high and low, on reproduction and pregnancy.

A method to assess relative weight was first described in 1832 as its ratio in kilograms divided by the square of the height in meters, or the Quetelet Index. The search for a functional assessment of relative body weight began after World War II when reports by actuaries noted the increased mortality of overweight policyholders. The relationship between weight and cardiovascular disease was further revealed in epidemiologic studies. The Quetelet Index became the BMI in 1972.³

Weight measurement is a mainstay in the assessment of a patient’s vital signs along with blood pressure, pulse rate, respiration rate, and temperature. Weight is vital to the calculation of medication dosage – for instance, administration of conscious sedative drugs, methotrexate, and gonadotropins. Some state boards of medicine, such as Florida, have a limitation on patient BMI at office-based surgery centers (40 kg/m²).
 

Obesity is a disease

As reported by the World Health Organization in 2022, the disease of obesity is an epidemic afflicting more than 1 billion people worldwide, or 1 in 8 individuals globally.⁴ The health implications of an elevated BMI include increased mortality, diabetes, heart disease, and stroke, physical limitations to activities of daily living, and complications affecting reproduction.

Female obesity is related to poorer outcomes in natural and assisted conception, including an increased risk of miscarriage. Compared with normal-weight women, those with obesity are three times more likely to have ovulatory dysfunction,⁵ infertility,⁶ a lower chance for conception,⁷ higher rate of miscarriage, and low birth weight.^8,9During pregnancy, women with obesity have three to four times higher rates of gestational diabetes and preeclampsia,¹⁰ as well as likelihood of delivering preterm,¹¹ having a fetus with macrosomia and birth defects, and a 1.3- to 2.1-times higher risk of stillbirth.¹²

Obesity is present in 40%-80% of women with polycystic ovary syndrome,¹³ the most common cause of ovulatory dysfunction from dysregulation of the hypothalamic-pituitary-ovarian axis. While PCOS is associated with reproductive and metabolic consequences, even in regularly ovulating women, increasing obesity appears to be associated with decreasing spontaneous pregnancy rates and increased time to pregnancy.¹⁴

Obesity and IVF

Women with obesity have reduced success with assisted reproductive technology, an increased number of canceled cycles, and poorer quality oocytes retrieved. A prospective cohort study of nearly 2,000 women reported that every 5 kg of body weight increase (from the patient’s baseline weight at age 18) was associated with a 5% increase in the mean duration of time required for conception (95% confidence interval, 3%-7%).¹⁵ Given that approximately 90% of these women had regular menstrual cycles, ovulatory dysfunction was not the suspected pathophysiology.

A meta-analysis of 21 cohort studies reported a lower likelihood of live birth following in vitro fertilization for women with obesity, compared with normal-weight women (risk ratio, 0.85; 95% CI, 0.82-0.87).¹⁶ A further subgroup analysis that evaluated only women with PCOS showed a reduction in the live birth rate following IVF for individuals with obesity, compared with normal-weight individuals (RR, 0.78; 95% CI, 0.74-0.82).

In a retrospective study of almost 500,000 fresh autologous IVF cycles, women with obesity had a 6% reduction in pregnancy rates and a 13% reduction in live birth rates, compared with normal-weight women. Both high and low BMI were associated with an increased risk of low birth weight and preterm delivery.¹⁷ The live birth rates per transfer for normal-weight and higher-weight women were 38% and 33%, respectively.

Contrarily, a randomized controlled trial showed that an intensive weight-reduction program resulted in a large weight loss but did not substantially affect live birth rates in women with obesity scheduled for IVF.¹⁸

Low BMI

A noteworthy cause of low BMI is functional hypothalamic amenorrhea (FHA), a disorder with low energy availability either from decreased caloric intake and/or excessive energy expenditure associated with eating disorders, excessive exercise, and stress. Consequently, a reduced GnRH drive results in a decreased pulse frequency and amplitude leading to low levels of follicle-stimulating hormone and luteinizing hormone, resulting in anovulation. Correction of lifestyle behaviors related to FHA can restore menstrual cycles. After normal weight is achieved, it appears unlikely that fertility is affected.¹⁹ In 47% of adolescent patients with anorexia, menses spontaneously returned within the first 12 months after admission, with an improved prognosis in secondary over primary amenorrhea.^20,21 Interestingly, mildly and significantly underweight infertile women have pregnancy and live birth rates similar to normal-weight patients after IVF treatment.²²

Pregnancy is complicated in underweight women, resulting in an increased risk of anemia, fetal growth retardation, and low birth weight, as well as preterm birth.²¹

Take-home message

The extremes of BMI both impair natural reproduction. Elevated BMI reduces success with IVF but rapid weight loss prior to IVF does not improve outcomes. A normal BMI is the goal for optimal reproductive and pregnancy health.

Dr. Trolice is director of the IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando.
 

References

1. Talumaa B et al. Obesity Rev. 2022;23:e13494.

2. https://bit.ly/3rHCivE.

3. Eknoyan G. Nephrol Dial Transplant. 2008;23:47-51.

4. Wells JCK. Dis Models Mech. 2012;5:595-607.

5. Brewer CJ and Balen AH. Reproduction. 2010;140:347-64.

6. Silvestris E et al. Reprod Biol Endocrinol. 2018;16:22.

7. Wise LA et al. Hum Reprod. 2010;25:253-64.

8. Bellver J. Curr Opin Obstet Gynecol. 2022;34:114-21.

9. Dickey RP et al. Am J Obstet Gynecol. 2013;209:349.e1.

10. Alwash SM et al. Obes Res Clin Pract. 2021;15:425-30.

11. Cnattingius S et al. JAMA. 2013;309:2362-70.

12. Aune D et al. JAMA. 2014;311:1536-46.

13. Sam S. Obes Manag. 2007;3:69-73.

14. van der Steeg JW et al. Hum Reprod. 2008;23:324-8.

15. Gaskins AJ et al. Obstet Gynecol. 2015;126:850-8.

16. Sermondade N et al. Hum Reprod Update. 2019;25:439-519.

17. Kawwass JF et al. Fertil Steril. 2016;106[7]:1742-50.

18. Einarsson S et al. Hum Reprod. 2017;32:1621-30.

19. Chaer R et al. Diseases. 2020;8:46.

20. Dempfle A et al. Psychiatry. 2013;13:308.

21. Verma A and Shrimali L. J Clin Diagn Res. 2012;6:1531-3.

22. Romanski PA et al. Reprod Biomed Online. 2020;42:366-74.

When a consumer uses a health plan provider directory to look up a physician, there’s a high probability that the entry for that doctor is incomplete or inaccurate. The Centers for Medicare & Medicaid Services would like to change that by creating a National Directory of Healthcare Providers and Services, which the agency believes would be more valuable to consumers.

In asking for public comments on whether and how it should establish the directory, CMS argues that this data repository would help patients locate physicians and could help with care coordination, health information exchange, and public health data reporting.

However, it’s not clear that such a directory would be any better than current insurance company listings or that people would use it. But a national directory could benefit physician practices by reducing their administrative work, according to observers.

In requesting public comment on the proposed national directory, CMS explains that provider organizations face “redundant and burdensome reporting requirements to multiple databases.” The directory could greatly reduce this challenge by requiring health care organizations to report provider information to a single database. Currently, physician practices have to submit these data to an average of 20 payers each, according to CMS.

“Right now, [physicians are] inundated with requests, and it takes a lot of time to update this stuff,” said David Zetter, a practice management consultant in Mechanicsburg, Pa.. “If there were one national repository of this information, that would be a good move.”

CMS envisions the National Directory as a central hub from which payers could obtain the latest provider data, which would be updated through a standardized application programming interface (API). Consequently, the insurers would no longer need to have providers submit this information to them separately.

CMS is soliciting input on what should be included in the directory. It notes that in addition to contact information, insurer directories also include a physicians’ specialties, health plan affiliations, and whether they accept new patients.

CMS’ 60-day public comment period ends Dec. 6. After that, the agency will decide what steps to take if it is decided that CMS has the legal authority to create the directory.
 

Terrible track record

In its annual reviews of health plan directories, CMS found that, from 2017 to 2022, only 47% of provider entries were complete. Only 73% of the providers could be matched to published directories. And only 28% of the provider names, addresses, and specialties in the directories matched those in the National Provider Identifier (NPI) registry.

Many of the mistakes in provider directories stem from errors made by practice staff, who have many other duties besides updating directory data. Yet an astonishing amount of time and effort is devoted to this task. A 2019 survey found that physician practices spend $2.76 billion annually on directory maintenance, or nearly $1000 per month per practice, on average.

The Council for Affordable Quality Healthcare, which conducted the survey, estimated that placing all directory data collection on a single platform could save the average practice $4,746 per year. For all practices in the United States, that works out to about $1.1 billion annually, CAQH said.
 

Pros and cons of national directory

For all the money spent on maintaining provider directories, consumers don’t use them very much. According to a 2021 Press Ganey survey, fewer than 5% of consumers seeking a primary care doctor get their information from an insurer or a benefits manager. About half search the internet first, and 24% seek a referral from a physician.

A national provider directory would be useful only if it were done right, Mr. Zetter said. Citing the inaccuracy and incompleteness of health plan directories, he said it was likely that a national directory would have similar problems. Data entered by practice staff would have to be automatically validated, perhaps through use of some kind of AI algorithm.
 

Effect on coordination of care

Mr. Zetter doubts the directory could improve care coordination, because primary care doctors usually refer patients to specialists they already know.

But Julia Adler-Milstein, PhD, professor of medicine and director of the Center for Clinical Informatics at the University of California, San Francisco, said that a national directory could improve communications among providers when patients select specialists outside of their primary care physician’s referral network.

“Especially if it’s not an established referral relationship, that’s where a national directory would be helpful, not only to locate the physicians but also to understand their preferences in how they’d like to receive information,” she said in an interview.

Dr. Adler-Milstein worries less than Mr. Zetter does about the challenge of ensuring the accuracy of data in the directory. She pointed out that the National Plan and Provider Enumeration System, which includes the NPI registry, has done a good job of validating provider name, address, and specialty information.

Dr. Adler-Milstein is more concerned about whether the proposed directory would address physician preferences as to how they wish to receive information. For example, while some physicians may prefer to be contacted directly, others may prefer or are required to communicate through their practices or health systems.
 

Efficiency in data exchange

The API used by the proposed directory would be based on the Fast Health Interoperability Resources standard that all electronic health record vendors must now include in their products. That raises the question of whether communications using contact information from the directory would be sent through a secure email system or through integrated EHR systems, Dr. Adler-Milstein said.

“I’m not sure whether the directory could support that [integration],” she said. “If it focuses on the concept of secure email exchange, that’s a relatively inefficient way of doing it,” because providers want clinical messages to pop up in their EHR workflow rather than their inboxes.

Nevertheless, Dr. Milstein-Adler added, the directory “would clearly take a lot of today’s manual work out of the system. I think organizations like UCSF would be very motivated to support the directory, knowing that people were going to a single source to find the updated information, including preferences in how we’d like people to communicate with us. There would be a lot of efficiency reasons for organizations to use this national directory.”

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

When a consumer uses a health plan provider directory to look up a physician, there’s a high probability that the entry for that doctor is incomplete or inaccurate. The Centers for Medicare & Medicaid Services would like to change that by creating a National Directory of Healthcare Providers and Services, which the agency believes would be more valuable to consumers.

In asking for public comments on whether and how it should establish the directory, CMS argues that this data repository would help patients locate physicians and could help with care coordination, health information exchange, and public health data reporting.

However, it’s not clear that such a directory would be any better than current insurance company listings or that people would use it. But a national directory could benefit physician practices by reducing their administrative work, according to observers.

In requesting public comment on the proposed national directory, CMS explains that provider organizations face “redundant and burdensome reporting requirements to multiple databases.” The directory could greatly reduce this challenge by requiring health care organizations to report provider information to a single database. Currently, physician practices have to submit these data to an average of 20 payers each, according to CMS.

“Right now, [physicians are] inundated with requests, and it takes a lot of time to update this stuff,” said David Zetter, a practice management consultant in Mechanicsburg, Pa.. “If there were one national repository of this information, that would be a good move.”

CMS envisions the National Directory as a central hub from which payers could obtain the latest provider data, which would be updated through a standardized application programming interface (API). Consequently, the insurers would no longer need to have providers submit this information to them separately.

CMS is soliciting input on what should be included in the directory. It notes that in addition to contact information, insurer directories also include a physicians’ specialties, health plan affiliations, and whether they accept new patients.

CMS’ 60-day public comment period ends Dec. 6. After that, the agency will decide what steps to take if it is decided that CMS has the legal authority to create the directory.
 

Terrible track record

In its annual reviews of health plan directories, CMS found that, from 2017 to 2022, only 47% of provider entries were complete. Only 73% of the providers could be matched to published directories. And only 28% of the provider names, addresses, and specialties in the directories matched those in the National Provider Identifier (NPI) registry.

Many of the mistakes in provider directories stem from errors made by practice staff, who have many other duties besides updating directory data. Yet an astonishing amount of time and effort is devoted to this task. A 2019 survey found that physician practices spend $2.76 billion annually on directory maintenance, or nearly $1000 per month per practice, on average.

The Council for Affordable Quality Healthcare, which conducted the survey, estimated that placing all directory data collection on a single platform could save the average practice $4,746 per year. For all practices in the United States, that works out to about $1.1 billion annually, CAQH said.
 

Pros and cons of national directory

For all the money spent on maintaining provider directories, consumers don’t use them very much. According to a 2021 Press Ganey survey, fewer than 5% of consumers seeking a primary care doctor get their information from an insurer or a benefits manager. About half search the internet first, and 24% seek a referral from a physician.

A national provider directory would be useful only if it were done right, Mr. Zetter said. Citing the inaccuracy and incompleteness of health plan directories, he said it was likely that a national directory would have similar problems. Data entered by practice staff would have to be automatically validated, perhaps through use of some kind of AI algorithm.
 

Effect on coordination of care

Mr. Zetter doubts the directory could improve care coordination, because primary care doctors usually refer patients to specialists they already know.

But Julia Adler-Milstein, PhD, professor of medicine and director of the Center for Clinical Informatics at the University of California, San Francisco, said that a national directory could improve communications among providers when patients select specialists outside of their primary care physician’s referral network.

“Especially if it’s not an established referral relationship, that’s where a national directory would be helpful, not only to locate the physicians but also to understand their preferences in how they’d like to receive information,” she said in an interview.

Dr. Adler-Milstein worries less than Mr. Zetter does about the challenge of ensuring the accuracy of data in the directory. She pointed out that the National Plan and Provider Enumeration System, which includes the NPI registry, has done a good job of validating provider name, address, and specialty information.

Dr. Adler-Milstein is more concerned about whether the proposed directory would address physician preferences as to how they wish to receive information. For example, while some physicians may prefer to be contacted directly, others may prefer or are required to communicate through their practices or health systems.
 

Efficiency in data exchange

The API used by the proposed directory would be based on the Fast Health Interoperability Resources standard that all electronic health record vendors must now include in their products. That raises the question of whether communications using contact information from the directory would be sent through a secure email system or through integrated EHR systems, Dr. Adler-Milstein said.

“I’m not sure whether the directory could support that [integration],” she said. “If it focuses on the concept of secure email exchange, that’s a relatively inefficient way of doing it,” because providers want clinical messages to pop up in their EHR workflow rather than their inboxes.

Nevertheless, Dr. Milstein-Adler added, the directory “would clearly take a lot of today’s manual work out of the system. I think organizations like UCSF would be very motivated to support the directory, knowing that people were going to a single source to find the updated information, including preferences in how we’d like people to communicate with us. There would be a lot of efficiency reasons for organizations to use this national directory.”

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

When a consumer uses a health plan provider directory to look up a physician, there’s a high probability that the entry for that doctor is incomplete or inaccurate. The Centers for Medicare & Medicaid Services would like to change that by creating a National Directory of Healthcare Providers and Services, which the agency believes would be more valuable to consumers.

In asking for public comments on whether and how it should establish the directory, CMS argues that this data repository would help patients locate physicians and could help with care coordination, health information exchange, and public health data reporting.

However, it’s not clear that such a directory would be any better than current insurance company listings or that people would use it. But a national directory could benefit physician practices by reducing their administrative work, according to observers.

In requesting public comment on the proposed national directory, CMS explains that provider organizations face “redundant and burdensome reporting requirements to multiple databases.” The directory could greatly reduce this challenge by requiring health care organizations to report provider information to a single database. Currently, physician practices have to submit these data to an average of 20 payers each, according to CMS.

“Right now, [physicians are] inundated with requests, and it takes a lot of time to update this stuff,” said David Zetter, a practice management consultant in Mechanicsburg, Pa.. “If there were one national repository of this information, that would be a good move.”

CMS envisions the National Directory as a central hub from which payers could obtain the latest provider data, which would be updated through a standardized application programming interface (API). Consequently, the insurers would no longer need to have providers submit this information to them separately.

CMS is soliciting input on what should be included in the directory. It notes that in addition to contact information, insurer directories also include a physicians’ specialties, health plan affiliations, and whether they accept new patients.

CMS’ 60-day public comment period ends Dec. 6. After that, the agency will decide what steps to take if it is decided that CMS has the legal authority to create the directory.
 

Terrible track record

In its annual reviews of health plan directories, CMS found that, from 2017 to 2022, only 47% of provider entries were complete. Only 73% of the providers could be matched to published directories. And only 28% of the provider names, addresses, and specialties in the directories matched those in the National Provider Identifier (NPI) registry.

Many of the mistakes in provider directories stem from errors made by practice staff, who have many other duties besides updating directory data. Yet an astonishing amount of time and effort is devoted to this task. A 2019 survey found that physician practices spend $2.76 billion annually on directory maintenance, or nearly $1000 per month per practice, on average.

The Council for Affordable Quality Healthcare, which conducted the survey, estimated that placing all directory data collection on a single platform could save the average practice $4,746 per year. For all practices in the United States, that works out to about $1.1 billion annually, CAQH said.
 

Pros and cons of national directory

For all the money spent on maintaining provider directories, consumers don’t use them very much. According to a 2021 Press Ganey survey, fewer than 5% of consumers seeking a primary care doctor get their information from an insurer or a benefits manager. About half search the internet first, and 24% seek a referral from a physician.

A national provider directory would be useful only if it were done right, Mr. Zetter said. Citing the inaccuracy and incompleteness of health plan directories, he said it was likely that a national directory would have similar problems. Data entered by practice staff would have to be automatically validated, perhaps through use of some kind of AI algorithm.
 

Effect on coordination of care

Mr. Zetter doubts the directory could improve care coordination, because primary care doctors usually refer patients to specialists they already know.

But Julia Adler-Milstein, PhD, professor of medicine and director of the Center for Clinical Informatics at the University of California, San Francisco, said that a national directory could improve communications among providers when patients select specialists outside of their primary care physician’s referral network.

“Especially if it’s not an established referral relationship, that’s where a national directory would be helpful, not only to locate the physicians but also to understand their preferences in how they’d like to receive information,” she said in an interview.

Dr. Adler-Milstein worries less than Mr. Zetter does about the challenge of ensuring the accuracy of data in the directory. She pointed out that the National Plan and Provider Enumeration System, which includes the NPI registry, has done a good job of validating provider name, address, and specialty information.

Dr. Adler-Milstein is more concerned about whether the proposed directory would address physician preferences as to how they wish to receive information. For example, while some physicians may prefer to be contacted directly, others may prefer or are required to communicate through their practices or health systems.
 

Efficiency in data exchange

The API used by the proposed directory would be based on the Fast Health Interoperability Resources standard that all electronic health record vendors must now include in their products. That raises the question of whether communications using contact information from the directory would be sent through a secure email system or through integrated EHR systems, Dr. Adler-Milstein said.

“I’m not sure whether the directory could support that [integration],” she said. “If it focuses on the concept of secure email exchange, that’s a relatively inefficient way of doing it,” because providers want clinical messages to pop up in their EHR workflow rather than their inboxes.

Nevertheless, Dr. Milstein-Adler added, the directory “would clearly take a lot of today’s manual work out of the system. I think organizations like UCSF would be very motivated to support the directory, knowing that people were going to a single source to find the updated information, including preferences in how we’d like people to communicate with us. There would be a lot of efficiency reasons for organizations to use this national directory.”

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

Expanding eligibility for active surveillance in low-risk papillary thyroid cancer appears to be safe, a new prospective trial indicates.

Researchers found that doubling the limits for tumor size to 2 cm and nearly doubling the limits for tumor growth in low-risk papillary thyroid cancer showed no increased risk of adverse outcomes or mortality for patients undergoing active surveillance versus surgery.

“The results of this nonrandomized controlled trial suggest the basis of a more permissive strategy for thyroid cancer management, strengthening the evidence for active surveillance and broadening potential candidacy to most diagnosed thyroid cancers,” the authors conclude. “By extending [tumor] size/growth limits, these study results potentially broaden the potential candidacy for active surveillance and reduce the likelihood of surgery by lengthening the window of observation.”

However, “the expanded parameters are quite controversial,” first author Allen S. Ho, MD, of Cedars-Sinai Medical Center, Los Angeles, told this news organization. Prior studies have only examined tumor size limits up to 1 cm and “clinicians rarely recommend active surveillance up to 2 cm,” Dr. Ho noted. “As far as we know, Cedars-Sinai is the only place that will consider it.”

In addition, the ultimate decision surrounding active surveillance versus surgery may depend on the patient’s level of anxiety, researchers found.

The research was published in JAMA Oncology.

The potential to expand criteria for thyroid cancer active surveillance comes amid ongoing concerns surrounding overtreatment. Advances in technology have led to increased detection of small, often indolent thyroid cancers that can likely be monitored safely through active surveillance but may present decision-making challenges for clinicians about whether to treat or watch and wait.

Similar challenges in prostate cancer have been addressed with tiered risk stratification, but such guidelines have not been as firmly established in thyroid cancer.

Guidelines from the American Thyroid Association in 2015 suggest active surveillance as an alternative for very low-risk tumors; however, studies in general have recommended the approach for initial tumor sizes of only up to 1 cm and with growth of less than 3 mm. And overall, active surveillance has not been broadly adopted as an option in thyroid cancer, the authors explained.

To determine if criteria for active surveillance can be safely expanded to tumors up to 2 cm and for those with growth up to 5 mm, Dr. Ho and colleagues compared outcomes among 222 patients with Bethesda 5 or 6 nodules of 2 cm or smaller who received either active surveillance or immediate surgery.

The patients were recruited from Cedars-Sinai Medical Center between 2014 and 2021. Patients were a median 46.8 years old; 76% were female.

The median size of tumors was 11 mm, with about 60% representing larger tumors (10.1 to 20 mm) and 20.6% measuring 15.1 to 20 mm.

About half of patients (n = 112) chose active surveillance. The median size of tumors in this group was smaller than those in the surgery group (10.1 mm vs. 12 mm). Tumor growth exceeded 5 mm in 3.6% of cases, and tumor volume increases of more than 100% occurred in 7% of cases.

With a mean follow-up of 37 months, 90% (101) of those on active surveillance continued with that approach. Notably, 41% of these patients demonstrated a decrease in tumor size, and no cases of metastatic lymph nodes or distant metastases emerged.

Of the 110 patients who elected to undergo immediate surgery, 19% (21) had equivocal-risk or undetermined features on final pathology, but the disease severity for these patients remained classified as stage I thyroid cancer.

The disease-specific survival and overall survival rates were the same in both groups, at 100%.

Although a general concern is that larger tumors may be more likely to grow, it’s important to note that “papillary thyroid cancer exists in a spectrum,” Dr. Ho explained. What that means is “some smaller cancers grow quickly, while some larger cancers are stable for decades.”

“We believe that a 1 cm cutoff is arbitrary,” Dr. Ho said, adding that 2 cm cancers that grow will still be within the therapeutic window for safe surgery.

However, a key factor in treatment decisions is patient fear. The authors also looked at the anxiety levels in both groups, using the 18-item Thyroid Cancer Modified Anxiety Scale.

Among the 59 patients who participated, those who chose immediate surgery had significantly higher baseline anxiety levels, compared with those who opted for active surveillance. Notably, these higher rates of anxiety endured over time, including after the intervention.

“It is unsurprising that patients choosing surgery possess a higher baseline level of worry,” Dr. Ho said. “However, we were astonished to find that such patients retained high levels of worry, even after surgery and presumed cure of their cancer.”

The role of the anxiety, however, underscores the need for clinicians to be mindful of the often profound psychological impacts of cancer, even low-risk disease.

“We always encourage clinicians to educate patients on active surveillance, especially as it gets highlighted more in official guidelines,” Dr. Ho noted. “However, we certainly acknowledge that cancer is a life-changing diagnosis, and the term can carry enormous psychological weight.”

The authors also acknowledged several study limitations, including the single-center, nonrandomized design and small sample size, and urge follow-up analyses to “independently verify our findings.”

In an accompanying editorial, Andrea L. Merrill, MD, from Boston Medical Center, and Priya H. Dedhia, MD, PhD, with Ohio State University Wexner Medical Center, said the findings have important clinical implications.

“This provocative study not only lays the groundwork for expanding active surveillance criteria for low-risk papillary thyroid cancer but may also improve use of current American Thyroid Association guidelines for active surveillance by demonstrating that use of active surveillance for Bethesda 5 or 6 nodules 20 mm or smaller was not associated with an increase in staging or disease-specific mortality,” they write.

The study is also notable for being among the first to assess the role of patient anxiety in the selection of immediate surgery versus active surveillance, Dr. Merrill and Dr. Dedhia added.

“These findings imply that patient anxiety should be an essential component of shared decision-making and selection of strategies for low-risk papillary thyroid cancer,” they say.

The study authors and editorial authors report no relevant financial relationships.

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

Expanding eligibility for active surveillance in low-risk papillary thyroid cancer appears to be safe, a new prospective trial indicates.

Researchers found that doubling the limits for tumor size to 2 cm and nearly doubling the limits for tumor growth in low-risk papillary thyroid cancer showed no increased risk of adverse outcomes or mortality for patients undergoing active surveillance versus surgery.

“The results of this nonrandomized controlled trial suggest the basis of a more permissive strategy for thyroid cancer management, strengthening the evidence for active surveillance and broadening potential candidacy to most diagnosed thyroid cancers,” the authors conclude. “By extending [tumor] size/growth limits, these study results potentially broaden the potential candidacy for active surveillance and reduce the likelihood of surgery by lengthening the window of observation.”

However, “the expanded parameters are quite controversial,” first author Allen S. Ho, MD, of Cedars-Sinai Medical Center, Los Angeles, told this news organization. Prior studies have only examined tumor size limits up to 1 cm and “clinicians rarely recommend active surveillance up to 2 cm,” Dr. Ho noted. “As far as we know, Cedars-Sinai is the only place that will consider it.”

In addition, the ultimate decision surrounding active surveillance versus surgery may depend on the patient’s level of anxiety, researchers found.

The research was published in JAMA Oncology.

The potential to expand criteria for thyroid cancer active surveillance comes amid ongoing concerns surrounding overtreatment. Advances in technology have led to increased detection of small, often indolent thyroid cancers that can likely be monitored safely through active surveillance but may present decision-making challenges for clinicians about whether to treat or watch and wait.

Similar challenges in prostate cancer have been addressed with tiered risk stratification, but such guidelines have not been as firmly established in thyroid cancer.

Guidelines from the American Thyroid Association in 2015 suggest active surveillance as an alternative for very low-risk tumors; however, studies in general have recommended the approach for initial tumor sizes of only up to 1 cm and with growth of less than 3 mm. And overall, active surveillance has not been broadly adopted as an option in thyroid cancer, the authors explained.

To determine if criteria for active surveillance can be safely expanded to tumors up to 2 cm and for those with growth up to 5 mm, Dr. Ho and colleagues compared outcomes among 222 patients with Bethesda 5 or 6 nodules of 2 cm or smaller who received either active surveillance or immediate surgery.

The patients were recruited from Cedars-Sinai Medical Center between 2014 and 2021. Patients were a median 46.8 years old; 76% were female.

The median size of tumors was 11 mm, with about 60% representing larger tumors (10.1 to 20 mm) and 20.6% measuring 15.1 to 20 mm.

About half of patients (n = 112) chose active surveillance. The median size of tumors in this group was smaller than those in the surgery group (10.1 mm vs. 12 mm). Tumor growth exceeded 5 mm in 3.6% of cases, and tumor volume increases of more than 100% occurred in 7% of cases.

With a mean follow-up of 37 months, 90% (101) of those on active surveillance continued with that approach. Notably, 41% of these patients demonstrated a decrease in tumor size, and no cases of metastatic lymph nodes or distant metastases emerged.

Of the 110 patients who elected to undergo immediate surgery, 19% (21) had equivocal-risk or undetermined features on final pathology, but the disease severity for these patients remained classified as stage I thyroid cancer.

The disease-specific survival and overall survival rates were the same in both groups, at 100%.

Although a general concern is that larger tumors may be more likely to grow, it’s important to note that “papillary thyroid cancer exists in a spectrum,” Dr. Ho explained. What that means is “some smaller cancers grow quickly, while some larger cancers are stable for decades.”

“We believe that a 1 cm cutoff is arbitrary,” Dr. Ho said, adding that 2 cm cancers that grow will still be within the therapeutic window for safe surgery.

However, a key factor in treatment decisions is patient fear. The authors also looked at the anxiety levels in both groups, using the 18-item Thyroid Cancer Modified Anxiety Scale.

Among the 59 patients who participated, those who chose immediate surgery had significantly higher baseline anxiety levels, compared with those who opted for active surveillance. Notably, these higher rates of anxiety endured over time, including after the intervention.

“It is unsurprising that patients choosing surgery possess a higher baseline level of worry,” Dr. Ho said. “However, we were astonished to find that such patients retained high levels of worry, even after surgery and presumed cure of their cancer.”

The role of the anxiety, however, underscores the need for clinicians to be mindful of the often profound psychological impacts of cancer, even low-risk disease.

“We always encourage clinicians to educate patients on active surveillance, especially as it gets highlighted more in official guidelines,” Dr. Ho noted. “However, we certainly acknowledge that cancer is a life-changing diagnosis, and the term can carry enormous psychological weight.”

The authors also acknowledged several study limitations, including the single-center, nonrandomized design and small sample size, and urge follow-up analyses to “independently verify our findings.”

In an accompanying editorial, Andrea L. Merrill, MD, from Boston Medical Center, and Priya H. Dedhia, MD, PhD, with Ohio State University Wexner Medical Center, said the findings have important clinical implications.

“This provocative study not only lays the groundwork for expanding active surveillance criteria for low-risk papillary thyroid cancer but may also improve use of current American Thyroid Association guidelines for active surveillance by demonstrating that use of active surveillance for Bethesda 5 or 6 nodules 20 mm or smaller was not associated with an increase in staging or disease-specific mortality,” they write.

The study is also notable for being among the first to assess the role of patient anxiety in the selection of immediate surgery versus active surveillance, Dr. Merrill and Dr. Dedhia added.

“These findings imply that patient anxiety should be an essential component of shared decision-making and selection of strategies for low-risk papillary thyroid cancer,” they say.

The study authors and editorial authors report no relevant financial relationships.

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

Expanding eligibility for active surveillance in low-risk papillary thyroid cancer appears to be safe, a new prospective trial indicates.

Researchers found that doubling the limits for tumor size to 2 cm and nearly doubling the limits for tumor growth in low-risk papillary thyroid cancer showed no increased risk of adverse outcomes or mortality for patients undergoing active surveillance versus surgery.

“The results of this nonrandomized controlled trial suggest the basis of a more permissive strategy for thyroid cancer management, strengthening the evidence for active surveillance and broadening potential candidacy to most diagnosed thyroid cancers,” the authors conclude. “By extending [tumor] size/growth limits, these study results potentially broaden the potential candidacy for active surveillance and reduce the likelihood of surgery by lengthening the window of observation.”

However, “the expanded parameters are quite controversial,” first author Allen S. Ho, MD, of Cedars-Sinai Medical Center, Los Angeles, told this news organization. Prior studies have only examined tumor size limits up to 1 cm and “clinicians rarely recommend active surveillance up to 2 cm,” Dr. Ho noted. “As far as we know, Cedars-Sinai is the only place that will consider it.”

In addition, the ultimate decision surrounding active surveillance versus surgery may depend on the patient’s level of anxiety, researchers found.

The research was published in JAMA Oncology.

The potential to expand criteria for thyroid cancer active surveillance comes amid ongoing concerns surrounding overtreatment. Advances in technology have led to increased detection of small, often indolent thyroid cancers that can likely be monitored safely through active surveillance but may present decision-making challenges for clinicians about whether to treat or watch and wait.

Similar challenges in prostate cancer have been addressed with tiered risk stratification, but such guidelines have not been as firmly established in thyroid cancer.

Guidelines from the American Thyroid Association in 2015 suggest active surveillance as an alternative for very low-risk tumors; however, studies in general have recommended the approach for initial tumor sizes of only up to 1 cm and with growth of less than 3 mm. And overall, active surveillance has not been broadly adopted as an option in thyroid cancer, the authors explained.

To determine if criteria for active surveillance can be safely expanded to tumors up to 2 cm and for those with growth up to 5 mm, Dr. Ho and colleagues compared outcomes among 222 patients with Bethesda 5 or 6 nodules of 2 cm or smaller who received either active surveillance or immediate surgery.

The patients were recruited from Cedars-Sinai Medical Center between 2014 and 2021. Patients were a median 46.8 years old; 76% were female.

The median size of tumors was 11 mm, with about 60% representing larger tumors (10.1 to 20 mm) and 20.6% measuring 15.1 to 20 mm.

About half of patients (n = 112) chose active surveillance. The median size of tumors in this group was smaller than those in the surgery group (10.1 mm vs. 12 mm). Tumor growth exceeded 5 mm in 3.6% of cases, and tumor volume increases of more than 100% occurred in 7% of cases.

With a mean follow-up of 37 months, 90% (101) of those on active surveillance continued with that approach. Notably, 41% of these patients demonstrated a decrease in tumor size, and no cases of metastatic lymph nodes or distant metastases emerged.

Of the 110 patients who elected to undergo immediate surgery, 19% (21) had equivocal-risk or undetermined features on final pathology, but the disease severity for these patients remained classified as stage I thyroid cancer.

The disease-specific survival and overall survival rates were the same in both groups, at 100%.

Although a general concern is that larger tumors may be more likely to grow, it’s important to note that “papillary thyroid cancer exists in a spectrum,” Dr. Ho explained. What that means is “some smaller cancers grow quickly, while some larger cancers are stable for decades.”

“We believe that a 1 cm cutoff is arbitrary,” Dr. Ho said, adding that 2 cm cancers that grow will still be within the therapeutic window for safe surgery.

However, a key factor in treatment decisions is patient fear. The authors also looked at the anxiety levels in both groups, using the 18-item Thyroid Cancer Modified Anxiety Scale.

Among the 59 patients who participated, those who chose immediate surgery had significantly higher baseline anxiety levels, compared with those who opted for active surveillance. Notably, these higher rates of anxiety endured over time, including after the intervention.

“It is unsurprising that patients choosing surgery possess a higher baseline level of worry,” Dr. Ho said. “However, we were astonished to find that such patients retained high levels of worry, even after surgery and presumed cure of their cancer.”

The role of the anxiety, however, underscores the need for clinicians to be mindful of the often profound psychological impacts of cancer, even low-risk disease.

“We always encourage clinicians to educate patients on active surveillance, especially as it gets highlighted more in official guidelines,” Dr. Ho noted. “However, we certainly acknowledge that cancer is a life-changing diagnosis, and the term can carry enormous psychological weight.”

The authors also acknowledged several study limitations, including the single-center, nonrandomized design and small sample size, and urge follow-up analyses to “independently verify our findings.”

In an accompanying editorial, Andrea L. Merrill, MD, from Boston Medical Center, and Priya H. Dedhia, MD, PhD, with Ohio State University Wexner Medical Center, said the findings have important clinical implications.

“This provocative study not only lays the groundwork for expanding active surveillance criteria for low-risk papillary thyroid cancer but may also improve use of current American Thyroid Association guidelines for active surveillance by demonstrating that use of active surveillance for Bethesda 5 or 6 nodules 20 mm or smaller was not associated with an increase in staging or disease-specific mortality,” they write.

The study is also notable for being among the first to assess the role of patient anxiety in the selection of immediate surgery versus active surveillance, Dr. Merrill and Dr. Dedhia added.

“These findings imply that patient anxiety should be an essential component of shared decision-making and selection of strategies for low-risk papillary thyroid cancer,” they say.

The study authors and editorial authors report no relevant financial relationships.

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

MONTREAL – Pediatric patients with low-risk differentiated thyroid cancer (DTC) who are spared radioactive iodine (RAI) therapy show no increases in the risk of remission, compared with those who do receive it, supporting guidelines that recommend against use of RAI in such patients.

“In 2015, when the American Thyroid Association [ATA] created their pediatric guidelines [on RAI therapy in DTC], they were taking a leap of faith that these [pediatric DTC] patients would be able to achieve remission without RAI,” said first author Mya Bojarsky, Children’s Hospital of Philadelphia (CHOP), when presenting the findings at the American Thyroid Association annual meeting.

“This is the first study to validate those guidelines and support the sentiment that for ATA low-risk pediatric thyroid cancer patients, withholding RAI therapy is clinically beneficial as it reduces exposure to radiation while having no negative impact on remission,” she said.

Prior to 2015, thyroidectomy in combination with RAI was the standard treatment for DTC in pediatric patients. However, data showing that radiation exposure in children increases the risk of secondary hematologic malignancies by 51% and solid malignancies by 23% over a lifetime raised concerns and led to a push to change the treatment approach.

In response, the 2015 ATA pediatric guidelines recommended that patients not receive RAI for the treatment of DTC that was mostly confined to the thyroid (N0 or minimal N1a disease).

Senior author Andrew J. Bauer, MD, noted that, in addition to being the first study to confirm that withholding RAI in low-risk patients is associated with the same rate of achieving remission as patients treated with RAI, the study also endorses that assessments at 1 year can be reliable predictors of remission.

“For these patients, the 1-year mark post-initial treatment (thyroidectomy) is an early and accurate time point for initial assessment of remission, with increasing rates of remission with continued surveillance (at last clinical follow-up) of approximately 90% 2 years post initial treatment,” said Dr. Bauer, medical director, CHOP, and professor of pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

“This approach has recently been validated through a prospective study in adult patients,” he added. A large recent study of 730 patients, published in the New England Journal of Medicine, supported the omission of RAI in low-risk DTC in adults, showing that, compared with those who received RAI, the no-RAI group was noninferior in the occurrence of functional, structural, and biologic events at 3 years.
 

Safe to eliminate RAI therapy in low-risk DTC in children

With limited data on how or if the change in treatment had an impact on rates of remission in pediatric patients, Ms. Bojarsky and colleagues conducted a retrospective cohort study of patients under the age of 19 years with ATA low-risk DTC who had undergone a total thyroidectomy at CHOP between 2010 and 2020.

Overall, they identified 95 patients, including 50 who had been treated with RAI in addition to thyroidectomy and 45 who did not receive RAI. Among those who did receive RAI, 31 were treated prior to 2015, and 19 were treated after 2019.

For the study, remission was defined as having undetectable thyroglobulin levels as well as no evidence of disease by ultrasound, Ms. Bojarsky said.

“This is important to show, because we want to ensure that as we are reducing our RAI use in the pediatric population, we were not negatively impacting their ability to achieve remission,” she explained.

The percentage of low-risk pediatric patients with DTC treated with RAI had already dropped from 100% in 2010 down to 38% by 2015 when the guidelines were issued, and after a slight rise to 50% by 2018, the practice plummeted to 0% by 2020, the study shows.

In terms of remission, at 1 year post-treatment, 80% of patients who received RAI were in remission, and the rate was even slightly higher, at 84%, among those who did not receive RAI, for a difference that was not significant.

Further looking at disease status as of the last clinical evaluation, 90% in the group treated with RAI had no evidence of disease at a median of 4.9 years of follow-up, and the rate was 87% in the group not receiving RAI, which had a median of 2.7 years of follow-up.

“In ATA low-risk patients, there is no detriment in achieving remission if RAI therapy is withheld,” say investigators.   

The median tumor size in the RAI group was larger (19.5 mm vs. 12.0 mm; P < .001), and the primary tumor was T1 in 44% of the RAI group but 82% in the no-RAI group (P < .001).

The lymph node status was N0 in 72% of those receiving RAI and 76% in the no RAI group, which was not significantly different.

The leading risk factors associated with treatment with RAI included larger primary tumor size (OR, 1.07; P = .003), lymph node metastasis (OR, 3.72; P = .036), and surgery pre-2015 (OR, 9.83; P < .001).

RAI administration, N1a disease, and surgery prior to 2015 were not independent risk factors for evidence of persistent disease or indeterminate status.

Ms. Bojarsky has reported no relevant financial relationships.

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

MONTREAL – Pediatric patients with low-risk differentiated thyroid cancer (DTC) who are spared radioactive iodine (RAI) therapy show no increases in the risk of remission, compared with those who do receive it, supporting guidelines that recommend against use of RAI in such patients.

“In 2015, when the American Thyroid Association [ATA] created their pediatric guidelines [on RAI therapy in DTC], they were taking a leap of faith that these [pediatric DTC] patients would be able to achieve remission without RAI,” said first author Mya Bojarsky, Children’s Hospital of Philadelphia (CHOP), when presenting the findings at the American Thyroid Association annual meeting.

“This is the first study to validate those guidelines and support the sentiment that for ATA low-risk pediatric thyroid cancer patients, withholding RAI therapy is clinically beneficial as it reduces exposure to radiation while having no negative impact on remission,” she said.

Prior to 2015, thyroidectomy in combination with RAI was the standard treatment for DTC in pediatric patients. However, data showing that radiation exposure in children increases the risk of secondary hematologic malignancies by 51% and solid malignancies by 23% over a lifetime raised concerns and led to a push to change the treatment approach.

In response, the 2015 ATA pediatric guidelines recommended that patients not receive RAI for the treatment of DTC that was mostly confined to the thyroid (N0 or minimal N1a disease).

Senior author Andrew J. Bauer, MD, noted that, in addition to being the first study to confirm that withholding RAI in low-risk patients is associated with the same rate of achieving remission as patients treated with RAI, the study also endorses that assessments at 1 year can be reliable predictors of remission.

“For these patients, the 1-year mark post-initial treatment (thyroidectomy) is an early and accurate time point for initial assessment of remission, with increasing rates of remission with continued surveillance (at last clinical follow-up) of approximately 90% 2 years post initial treatment,” said Dr. Bauer, medical director, CHOP, and professor of pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

“This approach has recently been validated through a prospective study in adult patients,” he added. A large recent study of 730 patients, published in the New England Journal of Medicine, supported the omission of RAI in low-risk DTC in adults, showing that, compared with those who received RAI, the no-RAI group was noninferior in the occurrence of functional, structural, and biologic events at 3 years.
 

Safe to eliminate RAI therapy in low-risk DTC in children

With limited data on how or if the change in treatment had an impact on rates of remission in pediatric patients, Ms. Bojarsky and colleagues conducted a retrospective cohort study of patients under the age of 19 years with ATA low-risk DTC who had undergone a total thyroidectomy at CHOP between 2010 and 2020.

Overall, they identified 95 patients, including 50 who had been treated with RAI in addition to thyroidectomy and 45 who did not receive RAI. Among those who did receive RAI, 31 were treated prior to 2015, and 19 were treated after 2019.

For the study, remission was defined as having undetectable thyroglobulin levels as well as no evidence of disease by ultrasound, Ms. Bojarsky said.

“This is important to show, because we want to ensure that as we are reducing our RAI use in the pediatric population, we were not negatively impacting their ability to achieve remission,” she explained.

The percentage of low-risk pediatric patients with DTC treated with RAI had already dropped from 100% in 2010 down to 38% by 2015 when the guidelines were issued, and after a slight rise to 50% by 2018, the practice plummeted to 0% by 2020, the study shows.

In terms of remission, at 1 year post-treatment, 80% of patients who received RAI were in remission, and the rate was even slightly higher, at 84%, among those who did not receive RAI, for a difference that was not significant.

Further looking at disease status as of the last clinical evaluation, 90% in the group treated with RAI had no evidence of disease at a median of 4.9 years of follow-up, and the rate was 87% in the group not receiving RAI, which had a median of 2.7 years of follow-up.

“In ATA low-risk patients, there is no detriment in achieving remission if RAI therapy is withheld,” say investigators.   

The median tumor size in the RAI group was larger (19.5 mm vs. 12.0 mm; P < .001), and the primary tumor was T1 in 44% of the RAI group but 82% in the no-RAI group (P < .001).

The lymph node status was N0 in 72% of those receiving RAI and 76% in the no RAI group, which was not significantly different.

The leading risk factors associated with treatment with RAI included larger primary tumor size (OR, 1.07; P = .003), lymph node metastasis (OR, 3.72; P = .036), and surgery pre-2015 (OR, 9.83; P < .001).

RAI administration, N1a disease, and surgery prior to 2015 were not independent risk factors for evidence of persistent disease or indeterminate status.

Ms. Bojarsky has reported no relevant financial relationships.

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

MONTREAL – Pediatric patients with low-risk differentiated thyroid cancer (DTC) who are spared radioactive iodine (RAI) therapy show no increases in the risk of remission, compared with those who do receive it, supporting guidelines that recommend against use of RAI in such patients.

“In 2015, when the American Thyroid Association [ATA] created their pediatric guidelines [on RAI therapy in DTC], they were taking a leap of faith that these [pediatric DTC] patients would be able to achieve remission without RAI,” said first author Mya Bojarsky, Children’s Hospital of Philadelphia (CHOP), when presenting the findings at the American Thyroid Association annual meeting.

“This is the first study to validate those guidelines and support the sentiment that for ATA low-risk pediatric thyroid cancer patients, withholding RAI therapy is clinically beneficial as it reduces exposure to radiation while having no negative impact on remission,” she said.

Prior to 2015, thyroidectomy in combination with RAI was the standard treatment for DTC in pediatric patients. However, data showing that radiation exposure in children increases the risk of secondary hematologic malignancies by 51% and solid malignancies by 23% over a lifetime raised concerns and led to a push to change the treatment approach.

In response, the 2015 ATA pediatric guidelines recommended that patients not receive RAI for the treatment of DTC that was mostly confined to the thyroid (N0 or minimal N1a disease).

Senior author Andrew J. Bauer, MD, noted that, in addition to being the first study to confirm that withholding RAI in low-risk patients is associated with the same rate of achieving remission as patients treated with RAI, the study also endorses that assessments at 1 year can be reliable predictors of remission.

“For these patients, the 1-year mark post-initial treatment (thyroidectomy) is an early and accurate time point for initial assessment of remission, with increasing rates of remission with continued surveillance (at last clinical follow-up) of approximately 90% 2 years post initial treatment,” said Dr. Bauer, medical director, CHOP, and professor of pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

“This approach has recently been validated through a prospective study in adult patients,” he added. A large recent study of 730 patients, published in the New England Journal of Medicine, supported the omission of RAI in low-risk DTC in adults, showing that, compared with those who received RAI, the no-RAI group was noninferior in the occurrence of functional, structural, and biologic events at 3 years.
 

Safe to eliminate RAI therapy in low-risk DTC in children

With limited data on how or if the change in treatment had an impact on rates of remission in pediatric patients, Ms. Bojarsky and colleagues conducted a retrospective cohort study of patients under the age of 19 years with ATA low-risk DTC who had undergone a total thyroidectomy at CHOP between 2010 and 2020.

Overall, they identified 95 patients, including 50 who had been treated with RAI in addition to thyroidectomy and 45 who did not receive RAI. Among those who did receive RAI, 31 were treated prior to 2015, and 19 were treated after 2019.

For the study, remission was defined as having undetectable thyroglobulin levels as well as no evidence of disease by ultrasound, Ms. Bojarsky said.

“This is important to show, because we want to ensure that as we are reducing our RAI use in the pediatric population, we were not negatively impacting their ability to achieve remission,” she explained.

The percentage of low-risk pediatric patients with DTC treated with RAI had already dropped from 100% in 2010 down to 38% by 2015 when the guidelines were issued, and after a slight rise to 50% by 2018, the practice plummeted to 0% by 2020, the study shows.

In terms of remission, at 1 year post-treatment, 80% of patients who received RAI were in remission, and the rate was even slightly higher, at 84%, among those who did not receive RAI, for a difference that was not significant.

Further looking at disease status as of the last clinical evaluation, 90% in the group treated with RAI had no evidence of disease at a median of 4.9 years of follow-up, and the rate was 87% in the group not receiving RAI, which had a median of 2.7 years of follow-up.

“In ATA low-risk patients, there is no detriment in achieving remission if RAI therapy is withheld,” say investigators.   

The median tumor size in the RAI group was larger (19.5 mm vs. 12.0 mm; P < .001), and the primary tumor was T1 in 44% of the RAI group but 82% in the no-RAI group (P < .001).

The lymph node status was N0 in 72% of those receiving RAI and 76% in the no RAI group, which was not significantly different.

The leading risk factors associated with treatment with RAI included larger primary tumor size (OR, 1.07; P = .003), lymph node metastasis (OR, 3.72; P = .036), and surgery pre-2015 (OR, 9.83; P < .001).

RAI administration, N1a disease, and surgery prior to 2015 were not independent risk factors for evidence of persistent disease or indeterminate status.

Ms. Bojarsky has reported no relevant financial relationships.

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

Women eating a reduced-fat vegan diet combined with a daily serving of soybeans experienced a 78% reduction in frequency of menopausal hot flashes over 12 weeks, in a small, nonblinded, randomized-controlled trial.

“We do not fully understand yet why this combination works, but it seems that these three elements are key: avoiding animal products, reducing fat, and adding a serving of soybeans,” lead researcher Neal Barnard, MD, explained in a press release. “These new results suggest that a diet change should be considered as a first-line treatment for troublesome vasomotor symptoms, including night sweats and hot flashes,” added Dr. Barnard, who is president of the Physicians Committee for Responsible Medicine, and adjunct professor at George Washington University, Washington. 

Elliott O’Donovan Photography

But, while “the findings from this very small study complement everything we know about the benefits of an excellent diet and the health benefits of soy,” they should be interpreted with some caution, commented Susan Reed, MD, president of the North American Menopause Society, and associate program director of the women’s reproductive research program at the University of Washington, Seattle.

For the trial, called WAVS (Women’s Study for the Alleviation of Vasomotor Symptoms), the researchers randomized 84 postmenopausal women with at least two moderate to severe hot flashes daily to either the intervention or usual diet, with a total of 71 subjects completing the 12-week study, published in Menopause. Criteria for exclusion included any cause of vasomotor symptoms other than natural menopause, current use of a low-fat, vegan diet that includes daily soy products, soy allergy, and body mass index < 18.5 kg/m².

Participants in the intervention group were asked to avoid animal-derived foods, minimize their use of oils and fatty foods such as nuts and avocados, and include half a cup (86 g) of cooked soybeans daily in their diets. They were also offered 1-hour virtual group meetings each week, in which a registered dietitian or research staff provided information on food preparation and managing common dietary challenges.

Control group participants were asked to continue their usual diets and attend four 1-hour group sessions.

At baseline and then after the 12-week study period, dietary intake was self-recorded for 2 weekdays and 1 weekend day, hot flash frequency and severity was recorded for 1 week using a mobile app, and the effect of menopausal symptoms on quality of life was measured using the vasomotor, psychosocial, physical, and sexual domains of the Menopause-Specific Quality of Life (MENQOL) questionnaire.

Equol production was also assessed in a subset of 15 intervention and 12 control participants who had urinary isoflavone concentrations measured after eating half a cup (86 g) of soybeans twice daily for 3 days. This was based on the theory that diets such as the intervention in this study “seem to foster the growth of gut bacteria capable of converting daidzein to equol,” noted the authors. The ability to produce equol is detected more frequently in individuals following vegetarian diets than in omnivores and … has been proposed as a factor in soy’s apparent health benefits.”

The study found that total hot flash frequency decreased by 78% in the intervention group (P < .001) and 39% (P < .001) in the control group (between-group P = .003), and moderate to severe hot flashes decreased by 88% versus 34%, respectively (from 5.0 to 0.6 per day, P < .001 vs. from 4.4 to 2.9 per day, P < .001; between-group P < .001). Among participants with at least seven moderate to severe hot flashes per day at baseline, moderate to severe hot flashes decreased by 93% (from 10.6 to 0.7 per day) in the intervention group (P < .001) and 36% (from 9.0 to 5.8 per day) in the control group (P = .01, between-group P < .001). The changes in hot flashes were paralleled by changes in the MENQOL findings, with significant between-group differences in the vasomotor (P = 0.004), physical (P = 0.01), and sexual (P = 0.03) domains.

Changes in frequency of severe hot flashes correlated directly with changes in fat intake, and inversely with changes in carbohydrate and fiber intake, such that “the greater the reduction in fat intake and the greater the increases in carbohydrate and fiber consumption, the greater the reduction in severe hot flashes,” noted the researchers. Mean body weight also decreased by 3.6 kg in the intervention group and 0.2 kg in the control group (P < .001). “Equol-production status had no apparent effect on hot flashes,” they added.

The study is the second phase of WAVS, which comprises two parts, the first of which showed similar results, but was conducted in the fall, raising questions about whether cooler temperatures were partly responsible for the results. Phase 2 of WAVS enrolled participants in the spring “ruling out the effect of outside temperature,” noted the authors.

“Eating a healthy diet at midlife is so important for long-term health and a sense of well-being for peri- and postmenopausal women,” said Dr Reed, but she urged caution in interpreting the findings. “This was an unblinded study,” she told this news organization. “Women were recruited to this study anticipating that they would be in a study on a soy diet. Individuals who sign up for a study are hoping for benefit from the intervention. The controls who don’t get the soy diet are often disappointed, so there is no benefit from a nonblinded control arm for their hot flashes. And that is exactly what we saw here. Blinded studies can hide what you are getting, so everyone in the study (intervention and controls) has the same anticipated benefit.  But you cannot blind a soy diet.”

Dr. Reed also noted that, while the biologic mechanism of benefit should be equol production, this was not shown – given that both equol producers and nonproducers in the soy intervention reported marked symptom reduction.

“Only prior studies with estrogen interventions have observed reductions of hot flashes of the amount reported here,” she concluded. “Hopefully future large studies will clarify the role of soy diet for decreasing hot flashes.”

Dr. Barnard writes books and articles and gives lectures related to nutrition and health and has received royalties and honoraria from these sources. Dr. Reed has no relevant disclosures.

Women eating a reduced-fat vegan diet combined with a daily serving of soybeans experienced a 78% reduction in frequency of menopausal hot flashes over 12 weeks, in a small, nonblinded, randomized-controlled trial.

“We do not fully understand yet why this combination works, but it seems that these three elements are key: avoiding animal products, reducing fat, and adding a serving of soybeans,” lead researcher Neal Barnard, MD, explained in a press release. “These new results suggest that a diet change should be considered as a first-line treatment for troublesome vasomotor symptoms, including night sweats and hot flashes,” added Dr. Barnard, who is president of the Physicians Committee for Responsible Medicine, and adjunct professor at George Washington University, Washington. 

Elliott O’Donovan Photography

But, while “the findings from this very small study complement everything we know about the benefits of an excellent diet and the health benefits of soy,” they should be interpreted with some caution, commented Susan Reed, MD, president of the North American Menopause Society, and associate program director of the women’s reproductive research program at the University of Washington, Seattle.

For the trial, called WAVS (Women’s Study for the Alleviation of Vasomotor Symptoms), the researchers randomized 84 postmenopausal women with at least two moderate to severe hot flashes daily to either the intervention or usual diet, with a total of 71 subjects completing the 12-week study, published in Menopause. Criteria for exclusion included any cause of vasomotor symptoms other than natural menopause, current use of a low-fat, vegan diet that includes daily soy products, soy allergy, and body mass index < 18.5 kg/m².

Participants in the intervention group were asked to avoid animal-derived foods, minimize their use of oils and fatty foods such as nuts and avocados, and include half a cup (86 g) of cooked soybeans daily in their diets. They were also offered 1-hour virtual group meetings each week, in which a registered dietitian or research staff provided information on food preparation and managing common dietary challenges.

Control group participants were asked to continue their usual diets and attend four 1-hour group sessions.

At baseline and then after the 12-week study period, dietary intake was self-recorded for 2 weekdays and 1 weekend day, hot flash frequency and severity was recorded for 1 week using a mobile app, and the effect of menopausal symptoms on quality of life was measured using the vasomotor, psychosocial, physical, and sexual domains of the Menopause-Specific Quality of Life (MENQOL) questionnaire.

Equol production was also assessed in a subset of 15 intervention and 12 control participants who had urinary isoflavone concentrations measured after eating half a cup (86 g) of soybeans twice daily for 3 days. This was based on the theory that diets such as the intervention in this study “seem to foster the growth of gut bacteria capable of converting daidzein to equol,” noted the authors. The ability to produce equol is detected more frequently in individuals following vegetarian diets than in omnivores and … has been proposed as a factor in soy’s apparent health benefits.”

The study found that total hot flash frequency decreased by 78% in the intervention group (P < .001) and 39% (P < .001) in the control group (between-group P = .003), and moderate to severe hot flashes decreased by 88% versus 34%, respectively (from 5.0 to 0.6 per day, P < .001 vs. from 4.4 to 2.9 per day, P < .001; between-group P < .001). Among participants with at least seven moderate to severe hot flashes per day at baseline, moderate to severe hot flashes decreased by 93% (from 10.6 to 0.7 per day) in the intervention group (P < .001) and 36% (from 9.0 to 5.8 per day) in the control group (P = .01, between-group P < .001). The changes in hot flashes were paralleled by changes in the MENQOL findings, with significant between-group differences in the vasomotor (P = 0.004), physical (P = 0.01), and sexual (P = 0.03) domains.

Changes in frequency of severe hot flashes correlated directly with changes in fat intake, and inversely with changes in carbohydrate and fiber intake, such that “the greater the reduction in fat intake and the greater the increases in carbohydrate and fiber consumption, the greater the reduction in severe hot flashes,” noted the researchers. Mean body weight also decreased by 3.6 kg in the intervention group and 0.2 kg in the control group (P < .001). “Equol-production status had no apparent effect on hot flashes,” they added.

The study is the second phase of WAVS, which comprises two parts, the first of which showed similar results, but was conducted in the fall, raising questions about whether cooler temperatures were partly responsible for the results. Phase 2 of WAVS enrolled participants in the spring “ruling out the effect of outside temperature,” noted the authors.

“Eating a healthy diet at midlife is so important for long-term health and a sense of well-being for peri- and postmenopausal women,” said Dr Reed, but she urged caution in interpreting the findings. “This was an unblinded study,” she told this news organization. “Women were recruited to this study anticipating that they would be in a study on a soy diet. Individuals who sign up for a study are hoping for benefit from the intervention. The controls who don’t get the soy diet are often disappointed, so there is no benefit from a nonblinded control arm for their hot flashes. And that is exactly what we saw here. Blinded studies can hide what you are getting, so everyone in the study (intervention and controls) has the same anticipated benefit.  But you cannot blind a soy diet.”

Dr. Reed also noted that, while the biologic mechanism of benefit should be equol production, this was not shown – given that both equol producers and nonproducers in the soy intervention reported marked symptom reduction.

“Only prior studies with estrogen interventions have observed reductions of hot flashes of the amount reported here,” she concluded. “Hopefully future large studies will clarify the role of soy diet for decreasing hot flashes.”

Dr. Barnard writes books and articles and gives lectures related to nutrition and health and has received royalties and honoraria from these sources. Dr. Reed has no relevant disclosures.

Women eating a reduced-fat vegan diet combined with a daily serving of soybeans experienced a 78% reduction in frequency of menopausal hot flashes over 12 weeks, in a small, nonblinded, randomized-controlled trial.

“We do not fully understand yet why this combination works, but it seems that these three elements are key: avoiding animal products, reducing fat, and adding a serving of soybeans,” lead researcher Neal Barnard, MD, explained in a press release. “These new results suggest that a diet change should be considered as a first-line treatment for troublesome vasomotor symptoms, including night sweats and hot flashes,” added Dr. Barnard, who is president of the Physicians Committee for Responsible Medicine, and adjunct professor at George Washington University, Washington. 

Elliott O’Donovan Photography

But, while “the findings from this very small study complement everything we know about the benefits of an excellent diet and the health benefits of soy,” they should be interpreted with some caution, commented Susan Reed, MD, president of the North American Menopause Society, and associate program director of the women’s reproductive research program at the University of Washington, Seattle.

For the trial, called WAVS (Women’s Study for the Alleviation of Vasomotor Symptoms), the researchers randomized 84 postmenopausal women with at least two moderate to severe hot flashes daily to either the intervention or usual diet, with a total of 71 subjects completing the 12-week study, published in Menopause. Criteria for exclusion included any cause of vasomotor symptoms other than natural menopause, current use of a low-fat, vegan diet that includes daily soy products, soy allergy, and body mass index < 18.5 kg/m².

Participants in the intervention group were asked to avoid animal-derived foods, minimize their use of oils and fatty foods such as nuts and avocados, and include half a cup (86 g) of cooked soybeans daily in their diets. They were also offered 1-hour virtual group meetings each week, in which a registered dietitian or research staff provided information on food preparation and managing common dietary challenges.

Control group participants were asked to continue their usual diets and attend four 1-hour group sessions.

At baseline and then after the 12-week study period, dietary intake was self-recorded for 2 weekdays and 1 weekend day, hot flash frequency and severity was recorded for 1 week using a mobile app, and the effect of menopausal symptoms on quality of life was measured using the vasomotor, psychosocial, physical, and sexual domains of the Menopause-Specific Quality of Life (MENQOL) questionnaire.

Equol production was also assessed in a subset of 15 intervention and 12 control participants who had urinary isoflavone concentrations measured after eating half a cup (86 g) of soybeans twice daily for 3 days. This was based on the theory that diets such as the intervention in this study “seem to foster the growth of gut bacteria capable of converting daidzein to equol,” noted the authors. The ability to produce equol is detected more frequently in individuals following vegetarian diets than in omnivores and … has been proposed as a factor in soy’s apparent health benefits.”

The study found that total hot flash frequency decreased by 78% in the intervention group (P < .001) and 39% (P < .001) in the control group (between-group P = .003), and moderate to severe hot flashes decreased by 88% versus 34%, respectively (from 5.0 to 0.6 per day, P < .001 vs. from 4.4 to 2.9 per day, P < .001; between-group P < .001). Among participants with at least seven moderate to severe hot flashes per day at baseline, moderate to severe hot flashes decreased by 93% (from 10.6 to 0.7 per day) in the intervention group (P < .001) and 36% (from 9.0 to 5.8 per day) in the control group (P = .01, between-group P < .001). The changes in hot flashes were paralleled by changes in the MENQOL findings, with significant between-group differences in the vasomotor (P = 0.004), physical (P = 0.01), and sexual (P = 0.03) domains.

Changes in frequency of severe hot flashes correlated directly with changes in fat intake, and inversely with changes in carbohydrate and fiber intake, such that “the greater the reduction in fat intake and the greater the increases in carbohydrate and fiber consumption, the greater the reduction in severe hot flashes,” noted the researchers. Mean body weight also decreased by 3.6 kg in the intervention group and 0.2 kg in the control group (P < .001). “Equol-production status had no apparent effect on hot flashes,” they added.

The study is the second phase of WAVS, which comprises two parts, the first of which showed similar results, but was conducted in the fall, raising questions about whether cooler temperatures were partly responsible for the results. Phase 2 of WAVS enrolled participants in the spring “ruling out the effect of outside temperature,” noted the authors.

“Eating a healthy diet at midlife is so important for long-term health and a sense of well-being for peri- and postmenopausal women,” said Dr Reed, but she urged caution in interpreting the findings. “This was an unblinded study,” she told this news organization. “Women were recruited to this study anticipating that they would be in a study on a soy diet. Individuals who sign up for a study are hoping for benefit from the intervention. The controls who don’t get the soy diet are often disappointed, so there is no benefit from a nonblinded control arm for their hot flashes. And that is exactly what we saw here. Blinded studies can hide what you are getting, so everyone in the study (intervention and controls) has the same anticipated benefit.  But you cannot blind a soy diet.”

Dr. Reed also noted that, while the biologic mechanism of benefit should be equol production, this was not shown – given that both equol producers and nonproducers in the soy intervention reported marked symptom reduction.

“Only prior studies with estrogen interventions have observed reductions of hot flashes of the amount reported here,” she concluded. “Hopefully future large studies will clarify the role of soy diet for decreasing hot flashes.”

Dr. Barnard writes books and articles and gives lectures related to nutrition and health and has received royalties and honoraria from these sources. Dr. Reed has no relevant disclosures.

The nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) unexpectedly showed that it might protect against incident infective pneumonia and COVID-19. The finding was based on secondary analyses run on more than 13,000 people enrolled in the two pivotal trials for finerenone.

Finerenone was approved by the Food and Drug Administration in 2021 for slowing progressive renal dysfunction and preventing cardiovascular events in adults with type 2 diabetes and chronic kidney disease (CKD).
 

‘Striking reduction in the risk of pneumonia’

The “striking reduction in risk of pneumonia” in a new analysis suggests that “the propagation of pulmonary infection into lobar or bronchial consolidation may be reduced by finerenone,” write Bertram Pitt, MD, and coauthors in a report published on October 26 in JAMA Network Open.

They also suggest that if further studies confirm that finerenone treatment reduces complications from pneumonia and COVID-19, it would have “significant medical implications,” especially because of the limited treatment options now available for complications from COVID-19.

The new analyses used the FIDELITY dataset, a prespecified merging of results from the FIDELIO-DKD and FIGARO-DKD trials, which together enrolled 13,026 people with type 2 diabetes and CKD, as determined on the basis of the patients’ having a urine albumin-to-creatinine ratio of at least 30 mg/g.

The primary outcomes of these trials showed that treatment with finerenone led to significant slowing of the progression of CKD and a significant reduction in the incidence of cardiovascular events, compared with placebo during median follow-up of 3 years.

The new, secondary analyses focused on the 6.0% of participants in whom there was evidence of pneumonia and the 1.6% in whom there was evidence of having COVID-19. Pneumonia was the most common serious adverse event in the two trials, a finding consistent with the documented risk for pneumonia faced by people with CKD.
 

Finerenone linked with a 29% relative reduction in pneumonia

When analyzed by treatment, the incidence of pneumonia was 4.7% among those who received finerenone and 6.7% among those who received placebo. This translated into a significant relative risk reduction of 29% associated with finerenone treatment.

Analysis of COVID-19 adverse events showed a 1.3% incidence among those who received finerenone and a 1.8% incidence among those in the placebo group, which translated into a significant 27% relative risk reduction linked with finerenone treatment.

In contrast, the data showed no reduced incidence of several other respiratory infections among the finerenone recipients, including nasopharyngitis, bronchitis, and influenza. The data also showed no signal that pneumonia or COVID-19 was more severe among the people who did not receive finerenone, nor did finerenone treatment appear to affect pneumonia recovery.
 

Analysis based on adverse events reports

These secondary analyses are far from definitive. The authors relied on pneumonia and COVID-19 being reported as adverse events. Each investigator diagnosed pneumonia at their discretion, and the trials did not specify diagnostic criteria. The authors also acknowledge that testing for COVID-19 was “not widespread” and that one of the two pivotal trials largely ran prior to the onset of the COVID-19 pandemic so that only 6 participants developed COVID-19 symptoms out of more than 5,700 enrolled.

The authors hypothesize that several actions of finerenone might potentially help mediate an effect on pneumonia and COVID-19: improvements in pulmonary inflammation and fibrosis, upregulation of expression of angiotensin converting enzyme 2, and amelioration of right heart pressure and pulmonary congestion. Also, antagonizing the mineralocorticoid receptor on monocytes and macrophages may block macrophage infiltration and accumulation of active macrophages, which can mediate the pulmonary tissue damage caused by COVID-19.

The FIDELIO-DKD and FIGARO-DKD trials and the FIDELITY combined database were sponsored by Bayer, the company that markets finerenone (Kerendia). Dr. Pitt has received personal fees from Bayer and personal fees and stock options from numerous other companies. Several coauthors reported having a financial relationship with Bayer, as well as with other companies.

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

The nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) unexpectedly showed that it might protect against incident infective pneumonia and COVID-19. The finding was based on secondary analyses run on more than 13,000 people enrolled in the two pivotal trials for finerenone.

Finerenone was approved by the Food and Drug Administration in 2021 for slowing progressive renal dysfunction and preventing cardiovascular events in adults with type 2 diabetes and chronic kidney disease (CKD).
 

‘Striking reduction in the risk of pneumonia’

The “striking reduction in risk of pneumonia” in a new analysis suggests that “the propagation of pulmonary infection into lobar or bronchial consolidation may be reduced by finerenone,” write Bertram Pitt, MD, and coauthors in a report published on October 26 in JAMA Network Open.

They also suggest that if further studies confirm that finerenone treatment reduces complications from pneumonia and COVID-19, it would have “significant medical implications,” especially because of the limited treatment options now available for complications from COVID-19.

The new analyses used the FIDELITY dataset, a prespecified merging of results from the FIDELIO-DKD and FIGARO-DKD trials, which together enrolled 13,026 people with type 2 diabetes and CKD, as determined on the basis of the patients’ having a urine albumin-to-creatinine ratio of at least 30 mg/g.

The primary outcomes of these trials showed that treatment with finerenone led to significant slowing of the progression of CKD and a significant reduction in the incidence of cardiovascular events, compared with placebo during median follow-up of 3 years.

The new, secondary analyses focused on the 6.0% of participants in whom there was evidence of pneumonia and the 1.6% in whom there was evidence of having COVID-19. Pneumonia was the most common serious adverse event in the two trials, a finding consistent with the documented risk for pneumonia faced by people with CKD.
 

Finerenone linked with a 29% relative reduction in pneumonia

When analyzed by treatment, the incidence of pneumonia was 4.7% among those who received finerenone and 6.7% among those who received placebo. This translated into a significant relative risk reduction of 29% associated with finerenone treatment.

Analysis of COVID-19 adverse events showed a 1.3% incidence among those who received finerenone and a 1.8% incidence among those in the placebo group, which translated into a significant 27% relative risk reduction linked with finerenone treatment.

In contrast, the data showed no reduced incidence of several other respiratory infections among the finerenone recipients, including nasopharyngitis, bronchitis, and influenza. The data also showed no signal that pneumonia or COVID-19 was more severe among the people who did not receive finerenone, nor did finerenone treatment appear to affect pneumonia recovery.
 

Analysis based on adverse events reports

These secondary analyses are far from definitive. The authors relied on pneumonia and COVID-19 being reported as adverse events. Each investigator diagnosed pneumonia at their discretion, and the trials did not specify diagnostic criteria. The authors also acknowledge that testing for COVID-19 was “not widespread” and that one of the two pivotal trials largely ran prior to the onset of the COVID-19 pandemic so that only 6 participants developed COVID-19 symptoms out of more than 5,700 enrolled.

The authors hypothesize that several actions of finerenone might potentially help mediate an effect on pneumonia and COVID-19: improvements in pulmonary inflammation and fibrosis, upregulation of expression of angiotensin converting enzyme 2, and amelioration of right heart pressure and pulmonary congestion. Also, antagonizing the mineralocorticoid receptor on monocytes and macrophages may block macrophage infiltration and accumulation of active macrophages, which can mediate the pulmonary tissue damage caused by COVID-19.

The FIDELIO-DKD and FIGARO-DKD trials and the FIDELITY combined database were sponsored by Bayer, the company that markets finerenone (Kerendia). Dr. Pitt has received personal fees from Bayer and personal fees and stock options from numerous other companies. Several coauthors reported having a financial relationship with Bayer, as well as with other companies.

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

The nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) unexpectedly showed that it might protect against incident infective pneumonia and COVID-19. The finding was based on secondary analyses run on more than 13,000 people enrolled in the two pivotal trials for finerenone.

Finerenone was approved by the Food and Drug Administration in 2021 for slowing progressive renal dysfunction and preventing cardiovascular events in adults with type 2 diabetes and chronic kidney disease (CKD).
 

‘Striking reduction in the risk of pneumonia’

The “striking reduction in risk of pneumonia” in a new analysis suggests that “the propagation of pulmonary infection into lobar or bronchial consolidation may be reduced by finerenone,” write Bertram Pitt, MD, and coauthors in a report published on October 26 in JAMA Network Open.

They also suggest that if further studies confirm that finerenone treatment reduces complications from pneumonia and COVID-19, it would have “significant medical implications,” especially because of the limited treatment options now available for complications from COVID-19.

The new analyses used the FIDELITY dataset, a prespecified merging of results from the FIDELIO-DKD and FIGARO-DKD trials, which together enrolled 13,026 people with type 2 diabetes and CKD, as determined on the basis of the patients’ having a urine albumin-to-creatinine ratio of at least 30 mg/g.

The primary outcomes of these trials showed that treatment with finerenone led to significant slowing of the progression of CKD and a significant reduction in the incidence of cardiovascular events, compared with placebo during median follow-up of 3 years.

The new, secondary analyses focused on the 6.0% of participants in whom there was evidence of pneumonia and the 1.6% in whom there was evidence of having COVID-19. Pneumonia was the most common serious adverse event in the two trials, a finding consistent with the documented risk for pneumonia faced by people with CKD.
 

Finerenone linked with a 29% relative reduction in pneumonia

When analyzed by treatment, the incidence of pneumonia was 4.7% among those who received finerenone and 6.7% among those who received placebo. This translated into a significant relative risk reduction of 29% associated with finerenone treatment.

Analysis of COVID-19 adverse events showed a 1.3% incidence among those who received finerenone and a 1.8% incidence among those in the placebo group, which translated into a significant 27% relative risk reduction linked with finerenone treatment.

In contrast, the data showed no reduced incidence of several other respiratory infections among the finerenone recipients, including nasopharyngitis, bronchitis, and influenza. The data also showed no signal that pneumonia or COVID-19 was more severe among the people who did not receive finerenone, nor did finerenone treatment appear to affect pneumonia recovery.
 

Analysis based on adverse events reports

These secondary analyses are far from definitive. The authors relied on pneumonia and COVID-19 being reported as adverse events. Each investigator diagnosed pneumonia at their discretion, and the trials did not specify diagnostic criteria. The authors also acknowledge that testing for COVID-19 was “not widespread” and that one of the two pivotal trials largely ran prior to the onset of the COVID-19 pandemic so that only 6 participants developed COVID-19 symptoms out of more than 5,700 enrolled.

The authors hypothesize that several actions of finerenone might potentially help mediate an effect on pneumonia and COVID-19: improvements in pulmonary inflammation and fibrosis, upregulation of expression of angiotensin converting enzyme 2, and amelioration of right heart pressure and pulmonary congestion. Also, antagonizing the mineralocorticoid receptor on monocytes and macrophages may block macrophage infiltration and accumulation of active macrophages, which can mediate the pulmonary tissue damage caused by COVID-19.

The FIDELIO-DKD and FIGARO-DKD trials and the FIDELITY combined database were sponsored by Bayer, the company that markets finerenone (Kerendia). Dr. Pitt has received personal fees from Bayer and personal fees and stock options from numerous other companies. Several coauthors reported having a financial relationship with Bayer, as well as with other companies.

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

Smokers who quit before age 35 showed a "substantial" reduction in risk, compared with people who never smoked, according to a new national study.

Researchers also quantified the benefit of quitting for those older than 35. The added risk of death associated with smoking was reduced by 90% for those who quit before age 45 and 66% for those who quit at ages 45 to 64.

“The distal nature of the health consequences for young smokers is a challenge for professionals trying to motivate quitting in younger age groups. Without a proximal goal, it is tempting for smokers to abandon a quit attempt with cognitions such as ‘I don’t really need to do it just now,’ ” John P. Pierce, PhD, director for Population Sciences at UC-San Diego’s Moores Cancer Center, wrote in a commentary. 

Current smokers were twice as likely to die from any cause during the study, compared with the group researchers called “never smokers,” who were defined as smoking fewer than 100 lifetime cigarettes. 

Published in JAMA Network Open, the study involved 551,388 U.S. participants using information collected by the CDC from 1997 to 2018. Researchers collected data for specific causes of death of participants through the end of 2019.

The results echo past findings but also established whether demographic factors such as a smoker’s race and gender impact the benefits of quitting. (In many areas of health research, a person’s race or gender is associated with varying risks.)

The researchers found that the benefits of quitting smoking in reducing risk of death are comparable across demographic groups.

“Among former smokers in each racial and ethnic group, whether male or female, quitting was associated with reductions of approximately 80% of the excess mortality associated with continued smoking,” the authors stated. “These associations were generally consistent for deaths from cancer, cardiovascular disease, and lower respiratory disease.”

The findings are also important for guiding stop-smoking efforts because while smoking nationwide has decreased, the reduction has varied across demographic groups.

“Monitoring the association of smoking with mortality by race, ethnicity, and sex is critical to understanding how the U.S. tobacco epidemic continues to evolve over time and who is most affected by the changes,” the authors stated. “Despite continued decreases in U.S. smoking prevalence in recent decades, progress has not been equal across demographic groups. Recent progress in raising the quit ratio among U.S. ever-smokers overall has been modest, and the quit ratio has been consistently lower among Black and Hispanic ever-smokers than among non-Hispanic White ever-smokers.”

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

This article was updated 10/27/22.

Smokers who quit before age 35 showed a "substantial" reduction in risk, compared with people who never smoked, according to a new national study.

Researchers also quantified the benefit of quitting for those older than 35. The added risk of death associated with smoking was reduced by 90% for those who quit before age 45 and 66% for those who quit at ages 45 to 64.

“The distal nature of the health consequences for young smokers is a challenge for professionals trying to motivate quitting in younger age groups. Without a proximal goal, it is tempting for smokers to abandon a quit attempt with cognitions such as ‘I don’t really need to do it just now,’ ” John P. Pierce, PhD, director for Population Sciences at UC-San Diego’s Moores Cancer Center, wrote in a commentary. 

Current smokers were twice as likely to die from any cause during the study, compared with the group researchers called “never smokers,” who were defined as smoking fewer than 100 lifetime cigarettes. 

Published in JAMA Network Open, the study involved 551,388 U.S. participants using information collected by the CDC from 1997 to 2018. Researchers collected data for specific causes of death of participants through the end of 2019.

The results echo past findings but also established whether demographic factors such as a smoker’s race and gender impact the benefits of quitting. (In many areas of health research, a person’s race or gender is associated with varying risks.)

The researchers found that the benefits of quitting smoking in reducing risk of death are comparable across demographic groups.

“Among former smokers in each racial and ethnic group, whether male or female, quitting was associated with reductions of approximately 80% of the excess mortality associated with continued smoking,” the authors stated. “These associations were generally consistent for deaths from cancer, cardiovascular disease, and lower respiratory disease.”

The findings are also important for guiding stop-smoking efforts because while smoking nationwide has decreased, the reduction has varied across demographic groups.

“Monitoring the association of smoking with mortality by race, ethnicity, and sex is critical to understanding how the U.S. tobacco epidemic continues to evolve over time and who is most affected by the changes,” the authors stated. “Despite continued decreases in U.S. smoking prevalence in recent decades, progress has not been equal across demographic groups. Recent progress in raising the quit ratio among U.S. ever-smokers overall has been modest, and the quit ratio has been consistently lower among Black and Hispanic ever-smokers than among non-Hispanic White ever-smokers.”

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

This article was updated 10/27/22.

Smokers who quit before age 35 showed a "substantial" reduction in risk, compared with people who never smoked, according to a new national study.

Researchers also quantified the benefit of quitting for those older than 35. The added risk of death associated with smoking was reduced by 90% for those who quit before age 45 and 66% for those who quit at ages 45 to 64.

“The distal nature of the health consequences for young smokers is a challenge for professionals trying to motivate quitting in younger age groups. Without a proximal goal, it is tempting for smokers to abandon a quit attempt with cognitions such as ‘I don’t really need to do it just now,’ ” John P. Pierce, PhD, director for Population Sciences at UC-San Diego’s Moores Cancer Center, wrote in a commentary. 

Current smokers were twice as likely to die from any cause during the study, compared with the group researchers called “never smokers,” who were defined as smoking fewer than 100 lifetime cigarettes. 

Published in JAMA Network Open, the study involved 551,388 U.S. participants using information collected by the CDC from 1997 to 2018. Researchers collected data for specific causes of death of participants through the end of 2019.

The results echo past findings but also established whether demographic factors such as a smoker’s race and gender impact the benefits of quitting. (In many areas of health research, a person’s race or gender is associated with varying risks.)

The researchers found that the benefits of quitting smoking in reducing risk of death are comparable across demographic groups.

“Among former smokers in each racial and ethnic group, whether male or female, quitting was associated with reductions of approximately 80% of the excess mortality associated with continued smoking,” the authors stated. “These associations were generally consistent for deaths from cancer, cardiovascular disease, and lower respiratory disease.”

The findings are also important for guiding stop-smoking efforts because while smoking nationwide has decreased, the reduction has varied across demographic groups.

“Monitoring the association of smoking with mortality by race, ethnicity, and sex is critical to understanding how the U.S. tobacco epidemic continues to evolve over time and who is most affected by the changes,” the authors stated. “Despite continued decreases in U.S. smoking prevalence in recent decades, progress has not been equal across demographic groups. Recent progress in raising the quit ratio among U.S. ever-smokers overall has been modest, and the quit ratio has been consistently lower among Black and Hispanic ever-smokers than among non-Hispanic White ever-smokers.”

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

This article was updated 10/27/22.

“We eat first with our eyes.” 

The Roman foodie Apicius is thought to have uttered those words in the 1st century A.D. Now, some 2,000 years later, scientists may be proving him right. 

Massachusetts Institute of Technology researchers have discovered a previously unknown part of the brain that lights up when we see food. Dubbed the “ventral food component,” this part resides in the brain’s visual cortex, in a region known to play a role in identifying faces, scenes, and words. 

The study, published in the journal Current Biology, involved using artificial intelligence (AI) technology to build a computer model of this part of the brain. Similar models are emerging across fields of research to simulate and study complex systems of the body. A computer model of the digestive system was recently used to determine the best body position for taking a pill. 

“The research is still cutting-edge,” says study author Meenakshi Khosla, PhD. “There’s a lot more to be done to understand whether this region is the same or different in different individuals, and how it is modulated by experience or familiarity with different kinds of foods.”

Pinpointing those differences could provide insights into how people choose what they eat, or even help us learn what drives eating disorders, Dr. Khosla says. 

Part of what makes this study unique was the researchers’ approach, dubbed “hypothesis neutral.” Instead of setting out to prove or disprove a firm hypothesis, they simply started exploring the data to see what they could find. The goal: To go beyond “the idiosyncratic hypotheses scientists have already thought to test,” the paper says. So, they began sifting through a public database called the Natural Scenes Dataset, an inventory of brain scans from eight volunteers viewing 56,720 images. 

As expected, the software analyzing the dataset spotted brain regions already known to be triggered by images of faces, bodies, words, and scenes. But to the researchers’ surprise, the analysis also revealed a previously unknown part of the brain that seemed to be responding to images of food. 

“Our first reaction was, ‘That’s cute and all, but it can’t possibly be true,’ ” Dr. Khosla says. 

To confirm their discovery, the researchers used the data to train a computer model of this part of the brain, a process that takes less than an hour. Then they fed the model more than 1.2 million new images. 

Sure enough, the model lit up in response to food. Color didn’t matter – even black-and-white food images triggered it, though not as strongly as color ones. And the model could tell the difference between food and objects that looked like food: a banana versus a crescent moon, or a blueberry muffin versus a puppy with a muffin-like face. 

From the human data, the researchers found that some people responded slightly more to processed foods like pizza than unprocessed foods like apples. They hope to explore how other things, such as liking or disliking a food, may affect a person’s response to that food. 

This technology could open up other areas of research as well. Dr. Khosla hopes to use it to explore how the brain responds to social cues like body language and facial expressions. 

For now, Dr. Khosla has already begun to verify the computer model in real people by scanning the brains of a new set of volunteers. “We collected pilot data in a few subjects recently and were able to localize this component,” she says. 

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

“We eat first with our eyes.” 

The Roman foodie Apicius is thought to have uttered those words in the 1st century A.D. Now, some 2,000 years later, scientists may be proving him right. 

Massachusetts Institute of Technology researchers have discovered a previously unknown part of the brain that lights up when we see food. Dubbed the “ventral food component,” this part resides in the brain’s visual cortex, in a region known to play a role in identifying faces, scenes, and words. 

The study, published in the journal Current Biology, involved using artificial intelligence (AI) technology to build a computer model of this part of the brain. Similar models are emerging across fields of research to simulate and study complex systems of the body. A computer model of the digestive system was recently used to determine the best body position for taking a pill. 

“The research is still cutting-edge,” says study author Meenakshi Khosla, PhD. “There’s a lot more to be done to understand whether this region is the same or different in different individuals, and how it is modulated by experience or familiarity with different kinds of foods.”

Pinpointing those differences could provide insights into how people choose what they eat, or even help us learn what drives eating disorders, Dr. Khosla says. 

Part of what makes this study unique was the researchers’ approach, dubbed “hypothesis neutral.” Instead of setting out to prove or disprove a firm hypothesis, they simply started exploring the data to see what they could find. The goal: To go beyond “the idiosyncratic hypotheses scientists have already thought to test,” the paper says. So, they began sifting through a public database called the Natural Scenes Dataset, an inventory of brain scans from eight volunteers viewing 56,720 images. 

As expected, the software analyzing the dataset spotted brain regions already known to be triggered by images of faces, bodies, words, and scenes. But to the researchers’ surprise, the analysis also revealed a previously unknown part of the brain that seemed to be responding to images of food. 

“Our first reaction was, ‘That’s cute and all, but it can’t possibly be true,’ ” Dr. Khosla says. 

To confirm their discovery, the researchers used the data to train a computer model of this part of the brain, a process that takes less than an hour. Then they fed the model more than 1.2 million new images. 

Sure enough, the model lit up in response to food. Color didn’t matter – even black-and-white food images triggered it, though not as strongly as color ones. And the model could tell the difference between food and objects that looked like food: a banana versus a crescent moon, or a blueberry muffin versus a puppy with a muffin-like face. 

From the human data, the researchers found that some people responded slightly more to processed foods like pizza than unprocessed foods like apples. They hope to explore how other things, such as liking or disliking a food, may affect a person’s response to that food. 

This technology could open up other areas of research as well. Dr. Khosla hopes to use it to explore how the brain responds to social cues like body language and facial expressions. 

For now, Dr. Khosla has already begun to verify the computer model in real people by scanning the brains of a new set of volunteers. “We collected pilot data in a few subjects recently and were able to localize this component,” she says. 

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

“We eat first with our eyes.” 

The Roman foodie Apicius is thought to have uttered those words in the 1st century A.D. Now, some 2,000 years later, scientists may be proving him right. 

Massachusetts Institute of Technology researchers have discovered a previously unknown part of the brain that lights up when we see food. Dubbed the “ventral food component,” this part resides in the brain’s visual cortex, in a region known to play a role in identifying faces, scenes, and words. 

The study, published in the journal Current Biology, involved using artificial intelligence (AI) technology to build a computer model of this part of the brain. Similar models are emerging across fields of research to simulate and study complex systems of the body. A computer model of the digestive system was recently used to determine the best body position for taking a pill. 

“The research is still cutting-edge,” says study author Meenakshi Khosla, PhD. “There’s a lot more to be done to understand whether this region is the same or different in different individuals, and how it is modulated by experience or familiarity with different kinds of foods.”

Pinpointing those differences could provide insights into how people choose what they eat, or even help us learn what drives eating disorders, Dr. Khosla says. 

Part of what makes this study unique was the researchers’ approach, dubbed “hypothesis neutral.” Instead of setting out to prove or disprove a firm hypothesis, they simply started exploring the data to see what they could find. The goal: To go beyond “the idiosyncratic hypotheses scientists have already thought to test,” the paper says. So, they began sifting through a public database called the Natural Scenes Dataset, an inventory of brain scans from eight volunteers viewing 56,720 images. 

As expected, the software analyzing the dataset spotted brain regions already known to be triggered by images of faces, bodies, words, and scenes. But to the researchers’ surprise, the analysis also revealed a previously unknown part of the brain that seemed to be responding to images of food. 

“Our first reaction was, ‘That’s cute and all, but it can’t possibly be true,’ ” Dr. Khosla says. 

To confirm their discovery, the researchers used the data to train a computer model of this part of the brain, a process that takes less than an hour. Then they fed the model more than 1.2 million new images. 

Sure enough, the model lit up in response to food. Color didn’t matter – even black-and-white food images triggered it, though not as strongly as color ones. And the model could tell the difference between food and objects that looked like food: a banana versus a crescent moon, or a blueberry muffin versus a puppy with a muffin-like face. 

From the human data, the researchers found that some people responded slightly more to processed foods like pizza than unprocessed foods like apples. They hope to explore how other things, such as liking or disliking a food, may affect a person’s response to that food. 

This technology could open up other areas of research as well. Dr. Khosla hopes to use it to explore how the brain responds to social cues like body language and facial expressions. 

For now, Dr. Khosla has already begun to verify the computer model in real people by scanning the brains of a new set of volunteers. “We collected pilot data in a few subjects recently and were able to localize this component,” she says. 

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

Masks can be scary on Halloween, but more so when they come with scrubs, scalpels, and God complexes. In March, Medscape readers chose their favorite characters and performers in the Hollywood health care system. As a Halloween treat, we follow up with a dozen of our favorite Evil Doctors from a deep bench (and no, Dr Evil didn’t go to medical school; neither did Dr No, for that matter). Before you see these folks who’d rather haunt than heal, we urge you to seek a second opinion.

George Harris (Richard Widmark, “Coma,” 1978)

“Medicine is now a great social force,” says Dr. George Harris (Richard Widmark), chief of surgery at Boston Memorial. Because the public trusts doctors, “we’ll make the hard decisions” – like choosing which young, healthy patients to put into an irreversible coma to harvest their organs. Harris’ audience of one here is Dr. Susan Wheeler (Genevieve Bujold), the upstart who has uncovered his plot, and whom Harris has just drugged to prepare her as his next unintentional donor. “Coma” was based on a bestseller by Robin Cook and directed by Michael Crichton, who left Harvard Medical School for a career in popular books and films, including “The Andromeda Strain” and “Jurassic Park.” Although Dr. Harris starts out as a reassuring friend and mentor to Dr. Wheeler, older moviegoers won’t forget that he launched to stardom by tossing a woman in a wheelchair down the stairs in 1947’s “Kiss of Death.”
 

Christian Szell (Laurence Olivier, “Marathon Man,” 1976)

He may look harmless, but Christian Szell (Laurence Olivier) is a sadist with a secret, a stash, and throat-slitting skills. Szell, a dentist known as the White Angel of Auschwitz for his war crimes, stops at nothing to protect the diamonds he stole from his victims in the camps. In one of Hollywood’s most infamous torture scenes, Szell tries to extract information from Babe Levy (Dustin Hoffman), an innocent grad student, plying the tools of his trade. When Szell asks, “Is it safe?” he’s not curious about whether Babe’s insurance covers anesthesia.

Orin Scrivello (Steve Martin, “Little Shop of Horrors,” 1986)

Sticking with deranged dentists, Orin Scrivello, DDS, (Steve Martin) sings and dances his way into your nightmares buoyed by copious helpings of nitrous oxide. Orin’s too-encouraging momma told him to parlay his sadistic tendencies into a career “where people will pay you to be inhumane.” Sonny listened. Moviegoers were treated to screeching sound effects of a tooth getting yanked during an Elvis-like musical number shot in part from inside a patient’s mouth. Martin makes a creepy scene more fun than a long, slow root canal.

Henry Frankenstein (Colin Clive, “Frankenstein,” 1931)

His alarming need for fresh corpses forced Henry Frankenstein (Colin Clive) to leave medical school and experiment solo in a castle. He insists to his betrothed that he hasn’t gone mad when she arrives as  he is bringing a dead body back to life during a raging lightning storm. When she and Henry’s mentor, Dr Waldman, witness him succeed, Waldman warns Henry that the former owner of the purloined brain was a notorious criminal. When Henry exclaims: “It’s alive, it’s alive !” little did he know that he created the face (Boris Karloff) that would launch a thousand sequels, a spectacular satire, and untold Halloween masks.

Dr. Gogol (Peter Lorre, “Mad Love,” 1935)

A few years after playing doctor Frankenstein, Colin Clive became the patient of a mad medic himself. A concert pianist whose hands have been mangled in a train wreck, Clive’s wife turns to Dr. Gogol (Peter Lorre, in his Hollywood debut), who promises to surgically reattach the musician’s hands. Unfortunately, Gogol is so obsessed with the wife, a star of gory stage shows, that he has created a wax figure of her. He schemes to win her in the flesh by attaching a murderer’s hands to Clive, then frame him for committing murder with those hands. Gogol utters the madman’s lament: “I have conquered science. Why can’t I conquer love?” A modern remake would surely have him asking, “Why do they swipe left?

Hannibal Lecter (Anthony Hopkins, “Silence of the Lambs,” 1991)

The FBI, hunting for a serial killer, sends trainee Clarice Starling (Jodie Foster) to seek insight into the murderer from the imprisoned Dr. Hannibal Lecter (Anthony Hopkins), a brilliant psychiatrist with a penchant for murder — and a taste for the flesh of his victims. Lecter proves to be a menace from their first meeting; the bars and glass surrounding his cell offer Clarice no protection from his gaze and ability to read her mind. In his own way, the urbane, pathologically charming Lecter takes a shine to Clarice, helping with the case while embarking on another murderous spree against men who recently wronged her. When he escapes, his plans do not include dinner with – or of – Clarice, but others, well, they’re not so lucky.

Henry Jekyll (Fredric March, “Dr. Jekyll and Mr. Hyde,” 1931)

Henry Jekyll (Fredric March) is a jumble of personalities. By day, he’s a kindly doctor in Victorian London with an American accent. But he is so determined to split good and evil personalities that he devises a potion to outsource his id. As he watches himself morph into Mr. Hyde – a hairy, cone-headed dude in serious need of an orthodontist – he exclaims, “Free! Free at last!” Free, that is, for his simian side to engage in debauchery, abuse, self-hatred, intimations of rape, and ultimately murder – all of which are explored in this pre-Code film, the first talkie version of Robert Louis Stevenson’s story.

Dr. Moreau (Charles Laughton, “Island of Lost Souls,” 1932)

“Strange-looking natives you have here,” shipwreck victim Edward Parker (Richard Arlen) tells his host, the white-suited, whip-wielding Dr Moreau. Before long, we learn that Moreau’s evil veterinary talents  have created an island population of human/beast hybrids who are forced to follow his laws – especially one forbidding them from eating meat or walking on all fours. Lawbreakers get taken to the House of Pain, a medical setting which, as its name suggests, lacks adequate analgesia. Burt Lancaster and Marlon Brando took on the Moreau role in later versions, but Laughton is the creepiest when he asks, “Do you know what it means to feel like God?” The film was banned for years in Britain, and H.G. Wells despised this take on his antivivisection tale.

Charles Nichols (Jeroen Krabbé, “The Fugitive,” 1993)

Richard Kimble, a Chicago vascular surgeon, arrives home to find that a man just brutally murdered his loving wife. The killer escapes, and Kimble falls into the frame-up. Convicted for the murder and headed to prison, Kimble breaks free in an epic escape scene. He spends the rest of the movie all but giving his right arm to find the murderer, while being pursued by a dogged U.S. Marshal played with gusto by Tommy Lee Jones. Kimble eventually discovers that his colleague, Dr. Charles Nichols (Jeroen Krabbé), is not quite the best friend a man could have – or the most ethical of clinical investigators.

Elliot and Beverly Mantle (Jeremy Irons, “Dead Ringers,” 1988)

“You’ve got to try the movie star,” fertility specialist Elliot Mantle (Jeremy Irons) implores to his identical but meek twin brother, Beverly (also Jeremy Irons), talking about an actress-patient (Genevieve Bujold) as if she were a menu item. Beverly shares a practice with Elliot, along with a soul and an easily satisfied drug addiction. Beverly is unaware that Elliot seduces patients before passing them off to his brother, including the actress. Beverly is in love with the actress, which upsets the equilibrium of their shared soul. He aims to fix this, but not without some trauma involving freakish and unsanitary operating implements.

Dean Armitage (Bradley Whitford, “Get Out,” 2017)

Neurosurgeon Dean Armitage (Bradley Whitford) was such a fan of President Obama that he would have voted for him a third time if he could. At least, that’s how he portrays himself to Chris (Daniel Kaluuya), an African American photographer and the new boyfriend of Armitage’s White daughter. The Armitage estate has plenty of people of color – on staff, anyway – but Chris finds them odd and distant. It turns out that a gathering of rich White people is in fact an auction for his eyesight. Horror ensues. The main message from this film is not unlike that of Russian operatives who fall out of favor with the Kremlin: Don’t drink the tea.

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

Masks can be scary on Halloween, but more so when they come with scrubs, scalpels, and God complexes. In March, Medscape readers chose their favorite characters and performers in the Hollywood health care system. As a Halloween treat, we follow up with a dozen of our favorite Evil Doctors from a deep bench (and no, Dr Evil didn’t go to medical school; neither did Dr No, for that matter). Before you see these folks who’d rather haunt than heal, we urge you to seek a second opinion.

George Harris (Richard Widmark, “Coma,” 1978)

“Medicine is now a great social force,” says Dr. George Harris (Richard Widmark), chief of surgery at Boston Memorial. Because the public trusts doctors, “we’ll make the hard decisions” – like choosing which young, healthy patients to put into an irreversible coma to harvest their organs. Harris’ audience of one here is Dr. Susan Wheeler (Genevieve Bujold), the upstart who has uncovered his plot, and whom Harris has just drugged to prepare her as his next unintentional donor. “Coma” was based on a bestseller by Robin Cook and directed by Michael Crichton, who left Harvard Medical School for a career in popular books and films, including “The Andromeda Strain” and “Jurassic Park.” Although Dr. Harris starts out as a reassuring friend and mentor to Dr. Wheeler, older moviegoers won’t forget that he launched to stardom by tossing a woman in a wheelchair down the stairs in 1947’s “Kiss of Death.”
 

Christian Szell (Laurence Olivier, “Marathon Man,” 1976)

He may look harmless, but Christian Szell (Laurence Olivier) is a sadist with a secret, a stash, and throat-slitting skills. Szell, a dentist known as the White Angel of Auschwitz for his war crimes, stops at nothing to protect the diamonds he stole from his victims in the camps. In one of Hollywood’s most infamous torture scenes, Szell tries to extract information from Babe Levy (Dustin Hoffman), an innocent grad student, plying the tools of his trade. When Szell asks, “Is it safe?” he’s not curious about whether Babe’s insurance covers anesthesia.

Orin Scrivello (Steve Martin, “Little Shop of Horrors,” 1986)

Sticking with deranged dentists, Orin Scrivello, DDS, (Steve Martin) sings and dances his way into your nightmares buoyed by copious helpings of nitrous oxide. Orin’s too-encouraging momma told him to parlay his sadistic tendencies into a career “where people will pay you to be inhumane.” Sonny listened. Moviegoers were treated to screeching sound effects of a tooth getting yanked during an Elvis-like musical number shot in part from inside a patient’s mouth. Martin makes a creepy scene more fun than a long, slow root canal.

Henry Frankenstein (Colin Clive, “Frankenstein,” 1931)

His alarming need for fresh corpses forced Henry Frankenstein (Colin Clive) to leave medical school and experiment solo in a castle. He insists to his betrothed that he hasn’t gone mad when she arrives as  he is bringing a dead body back to life during a raging lightning storm. When she and Henry’s mentor, Dr Waldman, witness him succeed, Waldman warns Henry that the former owner of the purloined brain was a notorious criminal. When Henry exclaims: “It’s alive, it’s alive !” little did he know that he created the face (Boris Karloff) that would launch a thousand sequels, a spectacular satire, and untold Halloween masks.

Dr. Gogol (Peter Lorre, “Mad Love,” 1935)

A few years after playing doctor Frankenstein, Colin Clive became the patient of a mad medic himself. A concert pianist whose hands have been mangled in a train wreck, Clive’s wife turns to Dr. Gogol (Peter Lorre, in his Hollywood debut), who promises to surgically reattach the musician’s hands. Unfortunately, Gogol is so obsessed with the wife, a star of gory stage shows, that he has created a wax figure of her. He schemes to win her in the flesh by attaching a murderer’s hands to Clive, then frame him for committing murder with those hands. Gogol utters the madman’s lament: “I have conquered science. Why can’t I conquer love?” A modern remake would surely have him asking, “Why do they swipe left?

Hannibal Lecter (Anthony Hopkins, “Silence of the Lambs,” 1991)

The FBI, hunting for a serial killer, sends trainee Clarice Starling (Jodie Foster) to seek insight into the murderer from the imprisoned Dr. Hannibal Lecter (Anthony Hopkins), a brilliant psychiatrist with a penchant for murder — and a taste for the flesh of his victims. Lecter proves to be a menace from their first meeting; the bars and glass surrounding his cell offer Clarice no protection from his gaze and ability to read her mind. In his own way, the urbane, pathologically charming Lecter takes a shine to Clarice, helping with the case while embarking on another murderous spree against men who recently wronged her. When he escapes, his plans do not include dinner with – or of – Clarice, but others, well, they’re not so lucky.

Henry Jekyll (Fredric March, “Dr. Jekyll and Mr. Hyde,” 1931)

Henry Jekyll (Fredric March) is a jumble of personalities. By day, he’s a kindly doctor in Victorian London with an American accent. But he is so determined to split good and evil personalities that he devises a potion to outsource his id. As he watches himself morph into Mr. Hyde – a hairy, cone-headed dude in serious need of an orthodontist – he exclaims, “Free! Free at last!” Free, that is, for his simian side to engage in debauchery, abuse, self-hatred, intimations of rape, and ultimately murder – all of which are explored in this pre-Code film, the first talkie version of Robert Louis Stevenson’s story.

Dr. Moreau (Charles Laughton, “Island of Lost Souls,” 1932)

“Strange-looking natives you have here,” shipwreck victim Edward Parker (Richard Arlen) tells his host, the white-suited, whip-wielding Dr Moreau. Before long, we learn that Moreau’s evil veterinary talents  have created an island population of human/beast hybrids who are forced to follow his laws – especially one forbidding them from eating meat or walking on all fours. Lawbreakers get taken to the House of Pain, a medical setting which, as its name suggests, lacks adequate analgesia. Burt Lancaster and Marlon Brando took on the Moreau role in later versions, but Laughton is the creepiest when he asks, “Do you know what it means to feel like God?” The film was banned for years in Britain, and H.G. Wells despised this take on his antivivisection tale.

Charles Nichols (Jeroen Krabbé, “The Fugitive,” 1993)

Richard Kimble, a Chicago vascular surgeon, arrives home to find that a man just brutally murdered his loving wife. The killer escapes, and Kimble falls into the frame-up. Convicted for the murder and headed to prison, Kimble breaks free in an epic escape scene. He spends the rest of the movie all but giving his right arm to find the murderer, while being pursued by a dogged U.S. Marshal played with gusto by Tommy Lee Jones. Kimble eventually discovers that his colleague, Dr. Charles Nichols (Jeroen Krabbé), is not quite the best friend a man could have – or the most ethical of clinical investigators.

Elliot and Beverly Mantle (Jeremy Irons, “Dead Ringers,” 1988)

“You’ve got to try the movie star,” fertility specialist Elliot Mantle (Jeremy Irons) implores to his identical but meek twin brother, Beverly (also Jeremy Irons), talking about an actress-patient (Genevieve Bujold) as if she were a menu item. Beverly shares a practice with Elliot, along with a soul and an easily satisfied drug addiction. Beverly is unaware that Elliot seduces patients before passing them off to his brother, including the actress. Beverly is in love with the actress, which upsets the equilibrium of their shared soul. He aims to fix this, but not without some trauma involving freakish and unsanitary operating implements.

Dean Armitage (Bradley Whitford, “Get Out,” 2017)

Neurosurgeon Dean Armitage (Bradley Whitford) was such a fan of President Obama that he would have voted for him a third time if he could. At least, that’s how he portrays himself to Chris (Daniel Kaluuya), an African American photographer and the new boyfriend of Armitage’s White daughter. The Armitage estate has plenty of people of color – on staff, anyway – but Chris finds them odd and distant. It turns out that a gathering of rich White people is in fact an auction for his eyesight. Horror ensues. The main message from this film is not unlike that of Russian operatives who fall out of favor with the Kremlin: Don’t drink the tea.

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

Masks can be scary on Halloween, but more so when they come with scrubs, scalpels, and God complexes. In March, Medscape readers chose their favorite characters and performers in the Hollywood health care system. As a Halloween treat, we follow up with a dozen of our favorite Evil Doctors from a deep bench (and no, Dr Evil didn’t go to medical school; neither did Dr No, for that matter). Before you see these folks who’d rather haunt than heal, we urge you to seek a second opinion.

George Harris (Richard Widmark, “Coma,” 1978)

“Medicine is now a great social force,” says Dr. George Harris (Richard Widmark), chief of surgery at Boston Memorial. Because the public trusts doctors, “we’ll make the hard decisions” – like choosing which young, healthy patients to put into an irreversible coma to harvest their organs. Harris’ audience of one here is Dr. Susan Wheeler (Genevieve Bujold), the upstart who has uncovered his plot, and whom Harris has just drugged to prepare her as his next unintentional donor. “Coma” was based on a bestseller by Robin Cook and directed by Michael Crichton, who left Harvard Medical School for a career in popular books and films, including “The Andromeda Strain” and “Jurassic Park.” Although Dr. Harris starts out as a reassuring friend and mentor to Dr. Wheeler, older moviegoers won’t forget that he launched to stardom by tossing a woman in a wheelchair down the stairs in 1947’s “Kiss of Death.”
 

Christian Szell (Laurence Olivier, “Marathon Man,” 1976)

He may look harmless, but Christian Szell (Laurence Olivier) is a sadist with a secret, a stash, and throat-slitting skills. Szell, a dentist known as the White Angel of Auschwitz for his war crimes, stops at nothing to protect the diamonds he stole from his victims in the camps. In one of Hollywood’s most infamous torture scenes, Szell tries to extract information from Babe Levy (Dustin Hoffman), an innocent grad student, plying the tools of his trade. When Szell asks, “Is it safe?” he’s not curious about whether Babe’s insurance covers anesthesia.

Orin Scrivello (Steve Martin, “Little Shop of Horrors,” 1986)

Sticking with deranged dentists, Orin Scrivello, DDS, (Steve Martin) sings and dances his way into your nightmares buoyed by copious helpings of nitrous oxide. Orin’s too-encouraging momma told him to parlay his sadistic tendencies into a career “where people will pay you to be inhumane.” Sonny listened. Moviegoers were treated to screeching sound effects of a tooth getting yanked during an Elvis-like musical number shot in part from inside a patient’s mouth. Martin makes a creepy scene more fun than a long, slow root canal.

Henry Frankenstein (Colin Clive, “Frankenstein,” 1931)

His alarming need for fresh corpses forced Henry Frankenstein (Colin Clive) to leave medical school and experiment solo in a castle. He insists to his betrothed that he hasn’t gone mad when she arrives as  he is bringing a dead body back to life during a raging lightning storm. When she and Henry’s mentor, Dr Waldman, witness him succeed, Waldman warns Henry that the former owner of the purloined brain was a notorious criminal. When Henry exclaims: “It’s alive, it’s alive !” little did he know that he created the face (Boris Karloff) that would launch a thousand sequels, a spectacular satire, and untold Halloween masks.

Dr. Gogol (Peter Lorre, “Mad Love,” 1935)

A few years after playing doctor Frankenstein, Colin Clive became the patient of a mad medic himself. A concert pianist whose hands have been mangled in a train wreck, Clive’s wife turns to Dr. Gogol (Peter Lorre, in his Hollywood debut), who promises to surgically reattach the musician’s hands. Unfortunately, Gogol is so obsessed with the wife, a star of gory stage shows, that he has created a wax figure of her. He schemes to win her in the flesh by attaching a murderer’s hands to Clive, then frame him for committing murder with those hands. Gogol utters the madman’s lament: “I have conquered science. Why can’t I conquer love?” A modern remake would surely have him asking, “Why do they swipe left?

Hannibal Lecter (Anthony Hopkins, “Silence of the Lambs,” 1991)

The FBI, hunting for a serial killer, sends trainee Clarice Starling (Jodie Foster) to seek insight into the murderer from the imprisoned Dr. Hannibal Lecter (Anthony Hopkins), a brilliant psychiatrist with a penchant for murder — and a taste for the flesh of his victims. Lecter proves to be a menace from their first meeting; the bars and glass surrounding his cell offer Clarice no protection from his gaze and ability to read her mind. In his own way, the urbane, pathologically charming Lecter takes a shine to Clarice, helping with the case while embarking on another murderous spree against men who recently wronged her. When he escapes, his plans do not include dinner with – or of – Clarice, but others, well, they’re not so lucky.

Henry Jekyll (Fredric March, “Dr. Jekyll and Mr. Hyde,” 1931)

Henry Jekyll (Fredric March) is a jumble of personalities. By day, he’s a kindly doctor in Victorian London with an American accent. But he is so determined to split good and evil personalities that he devises a potion to outsource his id. As he watches himself morph into Mr. Hyde – a hairy, cone-headed dude in serious need of an orthodontist – he exclaims, “Free! Free at last!” Free, that is, for his simian side to engage in debauchery, abuse, self-hatred, intimations of rape, and ultimately murder – all of which are explored in this pre-Code film, the first talkie version of Robert Louis Stevenson’s story.

Dr. Moreau (Charles Laughton, “Island of Lost Souls,” 1932)

“Strange-looking natives you have here,” shipwreck victim Edward Parker (Richard Arlen) tells his host, the white-suited, whip-wielding Dr Moreau. Before long, we learn that Moreau’s evil veterinary talents  have created an island population of human/beast hybrids who are forced to follow his laws – especially one forbidding them from eating meat or walking on all fours. Lawbreakers get taken to the House of Pain, a medical setting which, as its name suggests, lacks adequate analgesia. Burt Lancaster and Marlon Brando took on the Moreau role in later versions, but Laughton is the creepiest when he asks, “Do you know what it means to feel like God?” The film was banned for years in Britain, and H.G. Wells despised this take on his antivivisection tale.

Charles Nichols (Jeroen Krabbé, “The Fugitive,” 1993)

Richard Kimble, a Chicago vascular surgeon, arrives home to find that a man just brutally murdered his loving wife. The killer escapes, and Kimble falls into the frame-up. Convicted for the murder and headed to prison, Kimble breaks free in an epic escape scene. He spends the rest of the movie all but giving his right arm to find the murderer, while being pursued by a dogged U.S. Marshal played with gusto by Tommy Lee Jones. Kimble eventually discovers that his colleague, Dr. Charles Nichols (Jeroen Krabbé), is not quite the best friend a man could have – or the most ethical of clinical investigators.

Elliot and Beverly Mantle (Jeremy Irons, “Dead Ringers,” 1988)

“You’ve got to try the movie star,” fertility specialist Elliot Mantle (Jeremy Irons) implores to his identical but meek twin brother, Beverly (also Jeremy Irons), talking about an actress-patient (Genevieve Bujold) as if she were a menu item. Beverly shares a practice with Elliot, along with a soul and an easily satisfied drug addiction. Beverly is unaware that Elliot seduces patients before passing them off to his brother, including the actress. Beverly is in love with the actress, which upsets the equilibrium of their shared soul. He aims to fix this, but not without some trauma involving freakish and unsanitary operating implements.

Dean Armitage (Bradley Whitford, “Get Out,” 2017)

Neurosurgeon Dean Armitage (Bradley Whitford) was such a fan of President Obama that he would have voted for him a third time if he could. At least, that’s how he portrays himself to Chris (Daniel Kaluuya), an African American photographer and the new boyfriend of Armitage’s White daughter. The Armitage estate has plenty of people of color – on staff, anyway – but Chris finds them odd and distant. It turns out that a gathering of rich White people is in fact an auction for his eyesight. Horror ensues. The main message from this film is not unlike that of Russian operatives who fall out of favor with the Kremlin: Don’t drink the tea.

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

An “exciting” new gene-editing strategy means those born with a rare inherited disease of the immune system could be treated by repairing a fault in their cells.

Scientists have hailed new research that found faulty cells responsible for the immune system disease CTLA-4 insufficiency can be repaired with a pioneering gene editing technique.

CTLA-4 is a protein produced by T cells that helps to control the activity of the immune system. Most people carry two working copies of the gene responsible for producing CTLA-4, but those who have only one functional copy produce too little of the protein to sufficiently regulate the immune system.

For patients with the condition, CTLA-4 insufficiency causes regulatory T cells to function abnormally, leading to severe autoimmunity. The authors explained that the condition also affects effector T cells and thereby “hampers their immune system’s ‘memory,’ ” meaning patients can “struggle to fight off recurring infections by the same viruses and bacteria.” In some cases, it can also lead to lymphomas.
 

Gene editing to ‘cut’ out faulty genes and ‘paste’ in ‘corrected’ ones

The research, published in Science Translational Medicine, and led by scientists from University College London, demonstrated in human cells and in mice that the cell fault can be repaired.

The scientists used “cut-and-paste” gene-editing techniques. First, they used the CRISPR/Cas9 system to target the faulty gene in human T cells taken from patients with CTLA-4 insufficiency, and then snip the faulty CTLA-4 gene in two. Then, to repair the errors a corrected sequence of DNA – delivered to the cell using a modified virus – was pasted over the faulty part of the gene using a cellular DNA repair mechanism known as homology-directed repair.

The authors explained that this allowed them to “preserve” important sequences within the CTLA-4 gene – known as the intron – that allow it to be switched on and off by the cell only when needed. 

The outcome was “restored levels of CTLA-4 in the cells to those seen in healthy T cells,” the authors said.

Claire Booth, PhD, Mahboubian professor of gene therapy and pediatric immunology, UCL Great Ormond Street Institute of Child Health, and co–senior author, said that it was “really exciting” to think about taking this treatment forward to patients. “If we can improve their symptoms and reduce their risk of getting lymphoproliferative disease this will be a major step forward.”

In addition, the researchers were also able to improve symptoms of the disease in mice with CTLA-4 insufficiency by giving them injections of gene-edited T cells.
 

Technique may help tackle many conditions

The current standard treatment for CTLA-4 insufficiency is a bone marrow transplant to replace the stem cells responsible for producing T cells. However, “transplants are risky” and require high doses of chemotherapy and many weeks in hospital, the authors explained. “Older patients with CTLA-4 insufficiency are typically not well enough to tolerate the transplant procedure.”

Dr. Booth highlighted that the approach has many “positive aspects”. By correcting the patient’s T cells, “we think it can improve many of the symptoms of the disease”, she said, and added that this new approach is much less toxic than a bone marrow transplant. “Collecting the T cells is easier and correcting the T cells is easier. With this approach the amount of time in hospital the patients would need would be far less.”

Emma Morris, PhD, professor of clinical cell and gene therapy and director of UCL’s division of infection and immunity, and co–senior author, said: “Genes that play critical roles in controlling immune responses are not switched on all the time and are very tightly regulated. The technique we have used allows us to leave the natural (endogenous) mechanisms controlling gene expression intact, at the same time as correcting the mistake in the gene itself.”

The researchers explained that, although CTLA-4 insufficiency is rare, the gene editing therapy could be a proof of principle of their approach that could be adapted to tackle other conditions. 

“It’s a way of correcting genetic mutations that could potentially be applicable for other diseases,” suggested Dr. Morris. “The bigger picture is it allows us to correct genes that are dysregulated or overactive, but also allows us to understand much more about gene expression and gene regulation.”

The study was funded by the Wellcome Trust, the Association for Moleculary Pathology, the Medical Research Council, Alzheimer’s Research UK, and the UCLH/UCL NIHR Biomedical Research Centre. Dr. Morris is a founder sharehold of Quell Therapeutics and has received honoraria from Orchard Therapeutics, GlaxoSmithKline, and AstraZeneca. Dr. Booth has performed ad hoc consulting in the past 3 years for SOBI and Novartis and educational material production for SOBI and Chiesi. A patent on the intronic gene editing approach has been filed in the UK. The other authors declared that they have no completing interests.

A version of this article first appeared on Medscape UK.

An “exciting” new gene-editing strategy means those born with a rare inherited disease of the immune system could be treated by repairing a fault in their cells.

Scientists have hailed new research that found faulty cells responsible for the immune system disease CTLA-4 insufficiency can be repaired with a pioneering gene editing technique.

CTLA-4 is a protein produced by T cells that helps to control the activity of the immune system. Most people carry two working copies of the gene responsible for producing CTLA-4, but those who have only one functional copy produce too little of the protein to sufficiently regulate the immune system.

For patients with the condition, CTLA-4 insufficiency causes regulatory T cells to function abnormally, leading to severe autoimmunity. The authors explained that the condition also affects effector T cells and thereby “hampers their immune system’s ‘memory,’ ” meaning patients can “struggle to fight off recurring infections by the same viruses and bacteria.” In some cases, it can also lead to lymphomas.
 

Gene editing to ‘cut’ out faulty genes and ‘paste’ in ‘corrected’ ones

The research, published in Science Translational Medicine, and led by scientists from University College London, demonstrated in human cells and in mice that the cell fault can be repaired.

The scientists used “cut-and-paste” gene-editing techniques. First, they used the CRISPR/Cas9 system to target the faulty gene in human T cells taken from patients with CTLA-4 insufficiency, and then snip the faulty CTLA-4 gene in two. Then, to repair the errors a corrected sequence of DNA – delivered to the cell using a modified virus – was pasted over the faulty part of the gene using a cellular DNA repair mechanism known as homology-directed repair.

The authors explained that this allowed them to “preserve” important sequences within the CTLA-4 gene – known as the intron – that allow it to be switched on and off by the cell only when needed. 

The outcome was “restored levels of CTLA-4 in the cells to those seen in healthy T cells,” the authors said.

Claire Booth, PhD, Mahboubian professor of gene therapy and pediatric immunology, UCL Great Ormond Street Institute of Child Health, and co–senior author, said that it was “really exciting” to think about taking this treatment forward to patients. “If we can improve their symptoms and reduce their risk of getting lymphoproliferative disease this will be a major step forward.”

In addition, the researchers were also able to improve symptoms of the disease in mice with CTLA-4 insufficiency by giving them injections of gene-edited T cells.
 

Technique may help tackle many conditions

The current standard treatment for CTLA-4 insufficiency is a bone marrow transplant to replace the stem cells responsible for producing T cells. However, “transplants are risky” and require high doses of chemotherapy and many weeks in hospital, the authors explained. “Older patients with CTLA-4 insufficiency are typically not well enough to tolerate the transplant procedure.”

Dr. Booth highlighted that the approach has many “positive aspects”. By correcting the patient’s T cells, “we think it can improve many of the symptoms of the disease”, she said, and added that this new approach is much less toxic than a bone marrow transplant. “Collecting the T cells is easier and correcting the T cells is easier. With this approach the amount of time in hospital the patients would need would be far less.”

Emma Morris, PhD, professor of clinical cell and gene therapy and director of UCL’s division of infection and immunity, and co–senior author, said: “Genes that play critical roles in controlling immune responses are not switched on all the time and are very tightly regulated. The technique we have used allows us to leave the natural (endogenous) mechanisms controlling gene expression intact, at the same time as correcting the mistake in the gene itself.”

The researchers explained that, although CTLA-4 insufficiency is rare, the gene editing therapy could be a proof of principle of their approach that could be adapted to tackle other conditions. 

“It’s a way of correcting genetic mutations that could potentially be applicable for other diseases,” suggested Dr. Morris. “The bigger picture is it allows us to correct genes that are dysregulated or overactive, but also allows us to understand much more about gene expression and gene regulation.”

The study was funded by the Wellcome Trust, the Association for Moleculary Pathology, the Medical Research Council, Alzheimer’s Research UK, and the UCLH/UCL NIHR Biomedical Research Centre. Dr. Morris is a founder sharehold of Quell Therapeutics and has received honoraria from Orchard Therapeutics, GlaxoSmithKline, and AstraZeneca. Dr. Booth has performed ad hoc consulting in the past 3 years for SOBI and Novartis and educational material production for SOBI and Chiesi. A patent on the intronic gene editing approach has been filed in the UK. The other authors declared that they have no completing interests.

A version of this article first appeared on Medscape UK.

An “exciting” new gene-editing strategy means those born with a rare inherited disease of the immune system could be treated by repairing a fault in their cells.

Scientists have hailed new research that found faulty cells responsible for the immune system disease CTLA-4 insufficiency can be repaired with a pioneering gene editing technique.

CTLA-4 is a protein produced by T cells that helps to control the activity of the immune system. Most people carry two working copies of the gene responsible for producing CTLA-4, but those who have only one functional copy produce too little of the protein to sufficiently regulate the immune system.

For patients with the condition, CTLA-4 insufficiency causes regulatory T cells to function abnormally, leading to severe autoimmunity. The authors explained that the condition also affects effector T cells and thereby “hampers their immune system’s ‘memory,’ ” meaning patients can “struggle to fight off recurring infections by the same viruses and bacteria.” In some cases, it can also lead to lymphomas.
 

Gene editing to ‘cut’ out faulty genes and ‘paste’ in ‘corrected’ ones

The research, published in Science Translational Medicine, and led by scientists from University College London, demonstrated in human cells and in mice that the cell fault can be repaired.

The scientists used “cut-and-paste” gene-editing techniques. First, they used the CRISPR/Cas9 system to target the faulty gene in human T cells taken from patients with CTLA-4 insufficiency, and then snip the faulty CTLA-4 gene in two. Then, to repair the errors a corrected sequence of DNA – delivered to the cell using a modified virus – was pasted over the faulty part of the gene using a cellular DNA repair mechanism known as homology-directed repair.

The authors explained that this allowed them to “preserve” important sequences within the CTLA-4 gene – known as the intron – that allow it to be switched on and off by the cell only when needed. 

The outcome was “restored levels of CTLA-4 in the cells to those seen in healthy T cells,” the authors said.

Claire Booth, PhD, Mahboubian professor of gene therapy and pediatric immunology, UCL Great Ormond Street Institute of Child Health, and co–senior author, said that it was “really exciting” to think about taking this treatment forward to patients. “If we can improve their symptoms and reduce their risk of getting lymphoproliferative disease this will be a major step forward.”

In addition, the researchers were also able to improve symptoms of the disease in mice with CTLA-4 insufficiency by giving them injections of gene-edited T cells.
 

Technique may help tackle many conditions

The current standard treatment for CTLA-4 insufficiency is a bone marrow transplant to replace the stem cells responsible for producing T cells. However, “transplants are risky” and require high doses of chemotherapy and many weeks in hospital, the authors explained. “Older patients with CTLA-4 insufficiency are typically not well enough to tolerate the transplant procedure.”

Dr. Booth highlighted that the approach has many “positive aspects”. By correcting the patient’s T cells, “we think it can improve many of the symptoms of the disease”, she said, and added that this new approach is much less toxic than a bone marrow transplant. “Collecting the T cells is easier and correcting the T cells is easier. With this approach the amount of time in hospital the patients would need would be far less.”

Emma Morris, PhD, professor of clinical cell and gene therapy and director of UCL’s division of infection and immunity, and co–senior author, said: “Genes that play critical roles in controlling immune responses are not switched on all the time and are very tightly regulated. The technique we have used allows us to leave the natural (endogenous) mechanisms controlling gene expression intact, at the same time as correcting the mistake in the gene itself.”

The researchers explained that, although CTLA-4 insufficiency is rare, the gene editing therapy could be a proof of principle of their approach that could be adapted to tackle other conditions. 

“It’s a way of correcting genetic mutations that could potentially be applicable for other diseases,” suggested Dr. Morris. “The bigger picture is it allows us to correct genes that are dysregulated or overactive, but also allows us to understand much more about gene expression and gene regulation.”

The study was funded by the Wellcome Trust, the Association for Moleculary Pathology, the Medical Research Council, Alzheimer’s Research UK, and the UCLH/UCL NIHR Biomedical Research Centre. Dr. Morris is a founder sharehold of Quell Therapeutics and has received honoraria from Orchard Therapeutics, GlaxoSmithKline, and AstraZeneca. Dr. Booth has performed ad hoc consulting in the past 3 years for SOBI and Novartis and educational material production for SOBI and Chiesi. A patent on the intronic gene editing approach has been filed in the UK. The other authors declared that they have no completing interests.

A version of this article first appeared on Medscape UK.