Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

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

Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

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

Patients with low-risk differentiated thyroid cancer (DTC) undergoing thyroidectomy show no improvements in outcomes with the use of postoperative radioiodine ablation compared to those who do not receive this therapy, suggesting these patients can be spared the previously common treatment.

The study’s take-home message for clinicians should be to “stop systematic radioiodine ablation administration in low-risk thyroid cancer patients,” lead author Sophie Leboulleux, MD, PhD, said in an interview.

The results were first reported at ENDO 2021 and have now been published in the New England Journal of Medicine by Dr. Leboulleux, of the department of nuclear medicine and endocrine oncology, Gustave Roussy Cancer Institute, Villejuif, France, and colleagues.

While American Thyroid Association (ATA) guidelines already indicate that radioiodine ablation is not routinely recommended after thyroidectomy for patients with low-risk thyroid cancer, the guidance is only a “weak recommendation,” supported by “low-quality evidence.”  

However, the new findings should give that level of evidence a much-needed boost, said one expert. “I think the main contribution of this paper is to change the evidence level to ‘high quality,’ therefore making the recommendation ‘strong,’ rather than ‘weak,’ ” David S. Cooper, MD, said in an interview.

Dr. Cooper, professor of medicine and radiology at Johns Hopkins University, Baltimore, wrote an editorial that accompanies Dr. Leboulleux’s study.

The ability to safely spare patients the radioiodine ablation step after thyroidectomy has important benefits in terms of cost and convenience, Dr. Cooper stressed.
 

ESTIMABL2 trial

The new findings are from the prospective, randomized, phase 3 Essai Stimulation Ablation 2 (ESTIMABL2) trial, in which 730 patients at 35 centers in France with low-risk DTC scheduled to undergo thyroidectomy were enrolled between May 2013 and March 2017.

Patients were randomized to receive either postoperative radioiodine ablation (1.1 GBq) after injections of recombinant human thyrotropin (n = 363) or no postoperative radioiodine (n = 367).

Patients were a mean age of 52 years and 83% were women. About 96% had papillary tumors, and pathological tumor node (pTN) stages were mostly pT1b thyroid with a nodal status of N0 or Nx (81.1%). It is these patients in particular in whom retrospective studies of the use of radioiodine ablation have yielded inconsistent results, Dr. Leboulleux and colleagues noted. Hence, their decision to look at this prospectively.

Outcomes were based on the groups’ rates of events, defined as the presence of abnormal foci of radioiodine uptake on whole-body scanning that required treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or increased levels of thyroglobulin or thyroglobulin antibodies.

After a 3-year follow-up, the rates of having no events in both groups were very high – and nearly identical – at 95.6% among those receiving no radioiodine ablation and 95.9% in the radioiodine group, for a between-group difference of –0.3 percentage points, which met the criteria for noninferiority for the no-radioiodine group.

Likewise, the events that did occur were nearly equally split between the no-radioiodine group (16 events, 4.4%) and the radioiodine group (15 events, 4.1%).

Among patients who had events, subsequent treatments, including surgery, radioiodine administration, or both, were necessary for four patients in the no-radioiodine group and 10 in the radioiodine group, and additional treatments were not necessary for the other patients who experienced events.

There were no differences between those who did and did not experience events in terms of molecular alterations, and 50 of the tumors had BRAF mutations, with no significant differences between groups.

Of the adverse events that occurred in 30 patients, none were determined to be related to treatment, and there were no thyroid-related deaths.

The recurrence rates align with the rates observed overall with low-risk thyroid cancer, the authors noted. 

“We observed that less than 5% of the patients in the two groups had events that included abnormal findings on whole-body scanning or neck ultrasonography or elevated levels of thyroglobulin or thyroglobulin antibodies during the first 3 years of follow-up,” they reported.

“This rate is concordant with the definition of low-risk thyroid cancer, and our trial showed that the risk of events was not higher in the absence of postoperative administration of radioiodine.”
 

Patients spared costs, work losses

Dr. Cooper elaborated on the advantages, for patients, of avoiding radioiodine ablation.

For one thing, the recombinant human TSH that is necessary to prepare for radioiodine therapy is very expensive, ranging from $2,000 to $3,000, with patients often having a copay, he explained.

“Patients usually have to take time off work, which is also an expense to society and to them if they don’t get paid for days that they don’t work,” Dr. Cooper added.

A possible study limitation is the question of whether 3 years is an ample follow-up period to detect events. However, Dr. Cooper said he considers the period to be sufficient.

“As the authors point out, most recurrences of thyroid cancer are detected within the first 3-5 years of initial treatment, so ... the 3-year window is still clinically relevant,” he said.

Regarding the study’s inclusion of centers only in France, Dr. Cooper added, “I do not think that this is a study limitation. There is nothing specific about the French population that would lead me to conclude that the results were not generalizable to all populations with low-risk papillary thyroid cancer.”
 

Some continue radioiodine use, but lobectomies add to decline

Despite the mounting evidence of the lack of benefit of radioiodine ablation in low-risk patients, some centers, particularly in Europe, continue the practice, which was standard in the treatment of DTC until relatively recently.

“[While] U.S. guidelines changed in 2015 in favor of no radioiodine in low-risk differentiated thyroid cancer patients, this study should help to change European guidelines,” Dr. Leboulleux said. “The results will help to change practice both in the U.S. and in Europe.”

In addition to awareness of guidelines and new evidence, another reason for the decline in radioiodine ablation for low-risk DTC is the increasing use of thyroid lobectomy, which does not involve the use of radioiodine ablation, rather than total thyroidectomy, Dr. Cooper noted.

“The [new] NEJM paper will hopefully decrease the inappropriate use of radioiodine in low-risk patients even further,” he concluded.

The study received support from the French Ministry of Health through a grant from the National Cancer Institute. The authors have reported no relevant financial relationships.

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

White-to-pink friable plaques occurring acutely in the vulva is concerning for one form of secondary syphilis that affects mucous membranes: condyloma lata.

Known as the great imitator for its variety of clinical presentations, syphilis is a sexually transmitted infection (STI) caused by the spirochete Treponema pallidum. Three to 10 days following contact with the spirochete, a painless ulcer or chancre forms and subsequently resolves—sometimes without notice.

Secondary syphilis develops from hematogenous spread of bacteria taking many forms—most commonly a widespread rash over the whole body of many (although sometimes faint) macules or papules up to about 1 cm in size and haphazardly spread out about every 1 cm. Palms and soles may be affected, even if faintly. Another, less common form of secondary syphilis includes the friable plaques (often in the anogenital area, as pictured) that are highly concentrated with bacteria. These occur 3 to 12 weeks after the appearance of a primary chancre and are variably symptomatic.

The differential diagnosis includes genital warts, vulvar carcinoma, and pemphigus vegetans. The relatively rapid, multifocal presentation helps to separate this disorder from vulvar carcinoma. A biopsy can distinguish the 2. However, diagnosis is better made with serology using nontreponemal tests, such as the rapid plasma reagin (RPR) test. Treponemal tests (assaying immunoglobulin [Ig]M and IgG to Treponema pallidum) are also an option and are very specific. Following this, an RPR titer can help guide treatment. Darkfield microscopy, which can reveal spirochetes directly, isn’t readily available but could be used to diagnose condyloma lata.

Patients who have been given a diagnosis of syphilis should be offered screening for other STIs, including HIV. Anyone who has had sexual contact with the patient within the previous 90 days should be notified, tested, and treated. Patients with primary or secondary syphilis should be treated with 2.4 million units of intramuscular (IM) benzathine penicillin G in a single dose—regardless of whether they test positive for HIV. To exclude tertiary syphilis, a careful neurologic exam should take place at the time of diagnosis and again 6 and 12 months after treatment (sooner if follow-up may be uncertain). Consider treatment failure if RPR titers haven’t fallen fourfold in 12 months. In 2022, the Centers for Disease Control and Prevention released a notice that COVID-19-vaccinated patients may have false-positive RPR titers performed from Bio-Rad Laboratories (BioPlex 2200 Syphilis Total & RPR kit).¹

In this case, the patient tested positive for treponemal antibodies and had an RPR titer of 1:128. She was treated with IM benzathine penicillin with lasting clearance.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

White-to-pink friable plaques occurring acutely in the vulva is concerning for one form of secondary syphilis that affects mucous membranes: condyloma lata.

Known as the great imitator for its variety of clinical presentations, syphilis is a sexually transmitted infection (STI) caused by the spirochete Treponema pallidum. Three to 10 days following contact with the spirochete, a painless ulcer or chancre forms and subsequently resolves—sometimes without notice.

Secondary syphilis develops from hematogenous spread of bacteria taking many forms—most commonly a widespread rash over the whole body of many (although sometimes faint) macules or papules up to about 1 cm in size and haphazardly spread out about every 1 cm. Palms and soles may be affected, even if faintly. Another, less common form of secondary syphilis includes the friable plaques (often in the anogenital area, as pictured) that are highly concentrated with bacteria. These occur 3 to 12 weeks after the appearance of a primary chancre and are variably symptomatic.

The differential diagnosis includes genital warts, vulvar carcinoma, and pemphigus vegetans. The relatively rapid, multifocal presentation helps to separate this disorder from vulvar carcinoma. A biopsy can distinguish the 2. However, diagnosis is better made with serology using nontreponemal tests, such as the rapid plasma reagin (RPR) test. Treponemal tests (assaying immunoglobulin [Ig]M and IgG to Treponema pallidum) are also an option and are very specific. Following this, an RPR titer can help guide treatment. Darkfield microscopy, which can reveal spirochetes directly, isn’t readily available but could be used to diagnose condyloma lata.

Patients who have been given a diagnosis of syphilis should be offered screening for other STIs, including HIV. Anyone who has had sexual contact with the patient within the previous 90 days should be notified, tested, and treated. Patients with primary or secondary syphilis should be treated with 2.4 million units of intramuscular (IM) benzathine penicillin G in a single dose—regardless of whether they test positive for HIV. To exclude tertiary syphilis, a careful neurologic exam should take place at the time of diagnosis and again 6 and 12 months after treatment (sooner if follow-up may be uncertain). Consider treatment failure if RPR titers haven’t fallen fourfold in 12 months. In 2022, the Centers for Disease Control and Prevention released a notice that COVID-19-vaccinated patients may have false-positive RPR titers performed from Bio-Rad Laboratories (BioPlex 2200 Syphilis Total & RPR kit).¹

In this case, the patient tested positive for treponemal antibodies and had an RPR titer of 1:128. She was treated with IM benzathine penicillin with lasting clearance.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

White-to-pink friable plaques occurring acutely in the vulva is concerning for one form of secondary syphilis that affects mucous membranes: condyloma lata.

Known as the great imitator for its variety of clinical presentations, syphilis is a sexually transmitted infection (STI) caused by the spirochete Treponema pallidum. Three to 10 days following contact with the spirochete, a painless ulcer or chancre forms and subsequently resolves—sometimes without notice.

Secondary syphilis develops from hematogenous spread of bacteria taking many forms—most commonly a widespread rash over the whole body of many (although sometimes faint) macules or papules up to about 1 cm in size and haphazardly spread out about every 1 cm. Palms and soles may be affected, even if faintly. Another, less common form of secondary syphilis includes the friable plaques (often in the anogenital area, as pictured) that are highly concentrated with bacteria. These occur 3 to 12 weeks after the appearance of a primary chancre and are variably symptomatic.

The differential diagnosis includes genital warts, vulvar carcinoma, and pemphigus vegetans. The relatively rapid, multifocal presentation helps to separate this disorder from vulvar carcinoma. A biopsy can distinguish the 2. However, diagnosis is better made with serology using nontreponemal tests, such as the rapid plasma reagin (RPR) test. Treponemal tests (assaying immunoglobulin [Ig]M and IgG to Treponema pallidum) are also an option and are very specific. Following this, an RPR titer can help guide treatment. Darkfield microscopy, which can reveal spirochetes directly, isn’t readily available but could be used to diagnose condyloma lata.

Patients who have been given a diagnosis of syphilis should be offered screening for other STIs, including HIV. Anyone who has had sexual contact with the patient within the previous 90 days should be notified, tested, and treated. Patients with primary or secondary syphilis should be treated with 2.4 million units of intramuscular (IM) benzathine penicillin G in a single dose—regardless of whether they test positive for HIV. To exclude tertiary syphilis, a careful neurologic exam should take place at the time of diagnosis and again 6 and 12 months after treatment (sooner if follow-up may be uncertain). Consider treatment failure if RPR titers haven’t fallen fourfold in 12 months. In 2022, the Centers for Disease Control and Prevention released a notice that COVID-19-vaccinated patients may have false-positive RPR titers performed from Bio-Rad Laboratories (BioPlex 2200 Syphilis Total & RPR kit).¹

In this case, the patient tested positive for treponemal antibodies and had an RPR titer of 1:128. She was treated with IM benzathine penicillin with lasting clearance.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Patients who have a rare subtype of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed–Sternberg-like cells (CLL-HRS) may benefit from Hodgkin-directed therapy, based on data from 46 individuals.

Those patients who progress to classic Hodgkin lymphoma (CHL) from CLL/SLL are generally diagnosed based on straightforward pathology and treated with HRS cells in the same way as patients with de novo CHL, wrote lead author Dr. Rebecca L. King, a pathologist at the Mayo Clinic in Rochester, Minn.

However, in a small subset of patients, HRS cells occur in a background of CLL/SLL, in a condition known as CLL-HRS, and these patients do not progress to overt CHL, the researchers wrote.

Given the rarity of CLL-HRS, data on patient management are limited, they noted.

In a retrospective study published in Blood Cancer Journal, researchers reviewed outcome data from 15 adults with CLL-HRS and 31 adults with CLL/SLL who had overtly transformed to CLL-HL. The median age of the participants at the time of CLL-HL or CLL-HRS transformation diagnosis was 72 years; 71% and 87% of the CLL-HL and CLL-HRS patients, respectively, were male.

The median times from CLL to CLL-HL transformation and from CLL to CLL-HRS transformation were 6.6 years and 4.9 years, respectively; the difference was not statistically significant. The phenotypic features of Reed-Sternberg cells and Epstein-Barr virus status were similar in both patient groups. Two patients had biopsies in which both CLL-HRS and CLL-HL were present in the same tissue at initial diagnosis; they were included in the CLL-HL group for clinical analysis and in both groups for pathology analysis.

The median overall survival of CLL-HRS patients was 17.5 months, compared with 33.5 months for CLL-HL patients (P = .24), a nonsignificant difference. However, patients with CLL-HRS who received Hodgkin-directed therapy had a significantly longer median overall survival, compared with those who received CLL-directed therapy (57 months vs. 8.4 months, P = .02).

CLL-directed therapy included rituximab with or without corticosteroids, chemoimmunotherapy, or acalabrutinib; HL-directed therapy included doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine–based treatment; radiotherapy; or BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone).

Histopathology findings showed that CLL-HL patients had a background of mixed inflammation that was distinct from findings in CLL/SLL. CLL-HRS patients had a minimal inflammatory background, compared with CLL-HL cases, but researchers identified rosetting of T cells around the HRS cells in 56% of these patients.

“Our findings suggest that, clinically and pathologically, these patients show a spectrum of findings, and these two entities likely exist on a biologic continuum. Furthermore, our findings suggest that CLL-HRS patients managed with Hodgkin-directed therapy, rather than CLL-directed therapy, may have superior outcomes,” the researchers wrote.

The study findings were limited by several factors, including the retrospective design and the use of data from a single center. Therefore, the results should be validated in other cohorts, the researchers noted. In addition, the study participants were diagnosed over three decades, and management of the condition has significantly improved.

However, the results were strengthened by a review of data by three pathologists who were blinded to the clinical outcomes, they said.

“These findings have important implications for a scenario in which clinical guidelines are lacking and suggest that hematologists treating patients with CLL-HRS should consider HL-directed therapy,” the researchers concluded.

In an interview, Jennifer A. Woyach, MD, a hematologist at Ohio State University, Columbus, commented on the study findings: “Hodgkin transformation and CLL with Hodgkin-like cells likely represent a biologic continuum, and care should be taken to obtain adequate biopsies, so that the diagnosis of Hodgkin transformation can be made when appropriate.”

“Interestingly, the authors noted a trend toward improved survival when CLL with Hodgkin-like cells was treated with standard Hodgkin regimens,” said Dr. Woyach. “With the small patient numbers, this certainly cannot be a general recommendation, but should be considered by treating physicians on a case-by-case basis.”

“While we know that patients with Hodgkin transformation can in many cases be successfully treated with standard Hodgkin regimen, the natural history and optimal treatment for CLL with Hodgkin-like cells have been unknown. This analysis helps understand the biologic difference between these two clinicopathologic entities to understand how to better treat patients,” she noted. Going forward, “it would be extremely helpful to see these data validated by other centers to be sure that these results are reproducible,” Dr. Woyach added.

The study was supported by the Mayo Clinic, Rochester, Minn., and by the Henry J. Predolin Foundation. Lead author Dr. King disclosed research support to her institution from Bristol-Myers Squibb/Celgene. Dr. Woyach had no financial disclosures relevant to this study, but she has received laboratory research funding from Schrodinger and has consulted for AbbVie, Pharmacyclics, Janssen, AstraZeneca, Genentech, Beigene, Loxo, and Newave.
 

This article was updated 3/11/22.

Patients who have a rare subtype of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed–Sternberg-like cells (CLL-HRS) may benefit from Hodgkin-directed therapy, based on data from 46 individuals.

Those patients who progress to classic Hodgkin lymphoma (CHL) from CLL/SLL are generally diagnosed based on straightforward pathology and treated with HRS cells in the same way as patients with de novo CHL, wrote lead author Dr. Rebecca L. King, a pathologist at the Mayo Clinic in Rochester, Minn.

However, in a small subset of patients, HRS cells occur in a background of CLL/SLL, in a condition known as CLL-HRS, and these patients do not progress to overt CHL, the researchers wrote.

Given the rarity of CLL-HRS, data on patient management are limited, they noted.

In a retrospective study published in Blood Cancer Journal, researchers reviewed outcome data from 15 adults with CLL-HRS and 31 adults with CLL/SLL who had overtly transformed to CLL-HL. The median age of the participants at the time of CLL-HL or CLL-HRS transformation diagnosis was 72 years; 71% and 87% of the CLL-HL and CLL-HRS patients, respectively, were male.

The median times from CLL to CLL-HL transformation and from CLL to CLL-HRS transformation were 6.6 years and 4.9 years, respectively; the difference was not statistically significant. The phenotypic features of Reed-Sternberg cells and Epstein-Barr virus status were similar in both patient groups. Two patients had biopsies in which both CLL-HRS and CLL-HL were present in the same tissue at initial diagnosis; they were included in the CLL-HL group for clinical analysis and in both groups for pathology analysis.

The median overall survival of CLL-HRS patients was 17.5 months, compared with 33.5 months for CLL-HL patients (P = .24), a nonsignificant difference. However, patients with CLL-HRS who received Hodgkin-directed therapy had a significantly longer median overall survival, compared with those who received CLL-directed therapy (57 months vs. 8.4 months, P = .02).

CLL-directed therapy included rituximab with or without corticosteroids, chemoimmunotherapy, or acalabrutinib; HL-directed therapy included doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine–based treatment; radiotherapy; or BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone).

Histopathology findings showed that CLL-HL patients had a background of mixed inflammation that was distinct from findings in CLL/SLL. CLL-HRS patients had a minimal inflammatory background, compared with CLL-HL cases, but researchers identified rosetting of T cells around the HRS cells in 56% of these patients.

“Our findings suggest that, clinically and pathologically, these patients show a spectrum of findings, and these two entities likely exist on a biologic continuum. Furthermore, our findings suggest that CLL-HRS patients managed with Hodgkin-directed therapy, rather than CLL-directed therapy, may have superior outcomes,” the researchers wrote.

The study findings were limited by several factors, including the retrospective design and the use of data from a single center. Therefore, the results should be validated in other cohorts, the researchers noted. In addition, the study participants were diagnosed over three decades, and management of the condition has significantly improved.

However, the results were strengthened by a review of data by three pathologists who were blinded to the clinical outcomes, they said.

“These findings have important implications for a scenario in which clinical guidelines are lacking and suggest that hematologists treating patients with CLL-HRS should consider HL-directed therapy,” the researchers concluded.

In an interview, Jennifer A. Woyach, MD, a hematologist at Ohio State University, Columbus, commented on the study findings: “Hodgkin transformation and CLL with Hodgkin-like cells likely represent a biologic continuum, and care should be taken to obtain adequate biopsies, so that the diagnosis of Hodgkin transformation can be made when appropriate.”

“Interestingly, the authors noted a trend toward improved survival when CLL with Hodgkin-like cells was treated with standard Hodgkin regimens,” said Dr. Woyach. “With the small patient numbers, this certainly cannot be a general recommendation, but should be considered by treating physicians on a case-by-case basis.”

“While we know that patients with Hodgkin transformation can in many cases be successfully treated with standard Hodgkin regimen, the natural history and optimal treatment for CLL with Hodgkin-like cells have been unknown. This analysis helps understand the biologic difference between these two clinicopathologic entities to understand how to better treat patients,” she noted. Going forward, “it would be extremely helpful to see these data validated by other centers to be sure that these results are reproducible,” Dr. Woyach added.

The study was supported by the Mayo Clinic, Rochester, Minn., and by the Henry J. Predolin Foundation. Lead author Dr. King disclosed research support to her institution from Bristol-Myers Squibb/Celgene. Dr. Woyach had no financial disclosures relevant to this study, but she has received laboratory research funding from Schrodinger and has consulted for AbbVie, Pharmacyclics, Janssen, AstraZeneca, Genentech, Beigene, Loxo, and Newave.
 

This article was updated 3/11/22.

Patients who have a rare subtype of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with isolated Hodgkin/Reed–Sternberg-like cells (CLL-HRS) may benefit from Hodgkin-directed therapy, based on data from 46 individuals.

Those patients who progress to classic Hodgkin lymphoma (CHL) from CLL/SLL are generally diagnosed based on straightforward pathology and treated with HRS cells in the same way as patients with de novo CHL, wrote lead author Dr. Rebecca L. King, a pathologist at the Mayo Clinic in Rochester, Minn.

However, in a small subset of patients, HRS cells occur in a background of CLL/SLL, in a condition known as CLL-HRS, and these patients do not progress to overt CHL, the researchers wrote.

Given the rarity of CLL-HRS, data on patient management are limited, they noted.

In a retrospective study published in Blood Cancer Journal, researchers reviewed outcome data from 15 adults with CLL-HRS and 31 adults with CLL/SLL who had overtly transformed to CLL-HL. The median age of the participants at the time of CLL-HL or CLL-HRS transformation diagnosis was 72 years; 71% and 87% of the CLL-HL and CLL-HRS patients, respectively, were male.

The median times from CLL to CLL-HL transformation and from CLL to CLL-HRS transformation were 6.6 years and 4.9 years, respectively; the difference was not statistically significant. The phenotypic features of Reed-Sternberg cells and Epstein-Barr virus status were similar in both patient groups. Two patients had biopsies in which both CLL-HRS and CLL-HL were present in the same tissue at initial diagnosis; they were included in the CLL-HL group for clinical analysis and in both groups for pathology analysis.

The median overall survival of CLL-HRS patients was 17.5 months, compared with 33.5 months for CLL-HL patients (P = .24), a nonsignificant difference. However, patients with CLL-HRS who received Hodgkin-directed therapy had a significantly longer median overall survival, compared with those who received CLL-directed therapy (57 months vs. 8.4 months, P = .02).

CLL-directed therapy included rituximab with or without corticosteroids, chemoimmunotherapy, or acalabrutinib; HL-directed therapy included doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, and dacarbazine–based treatment; radiotherapy; or BCVPP (carmustine, cyclophosphamide, vinblastine, procarbazine, and prednisone).

Histopathology findings showed that CLL-HL patients had a background of mixed inflammation that was distinct from findings in CLL/SLL. CLL-HRS patients had a minimal inflammatory background, compared with CLL-HL cases, but researchers identified rosetting of T cells around the HRS cells in 56% of these patients.

“Our findings suggest that, clinically and pathologically, these patients show a spectrum of findings, and these two entities likely exist on a biologic continuum. Furthermore, our findings suggest that CLL-HRS patients managed with Hodgkin-directed therapy, rather than CLL-directed therapy, may have superior outcomes,” the researchers wrote.

The study findings were limited by several factors, including the retrospective design and the use of data from a single center. Therefore, the results should be validated in other cohorts, the researchers noted. In addition, the study participants were diagnosed over three decades, and management of the condition has significantly improved.

However, the results were strengthened by a review of data by three pathologists who were blinded to the clinical outcomes, they said.

“These findings have important implications for a scenario in which clinical guidelines are lacking and suggest that hematologists treating patients with CLL-HRS should consider HL-directed therapy,” the researchers concluded.

In an interview, Jennifer A. Woyach, MD, a hematologist at Ohio State University, Columbus, commented on the study findings: “Hodgkin transformation and CLL with Hodgkin-like cells likely represent a biologic continuum, and care should be taken to obtain adequate biopsies, so that the diagnosis of Hodgkin transformation can be made when appropriate.”

“Interestingly, the authors noted a trend toward improved survival when CLL with Hodgkin-like cells was treated with standard Hodgkin regimens,” said Dr. Woyach. “With the small patient numbers, this certainly cannot be a general recommendation, but should be considered by treating physicians on a case-by-case basis.”

“While we know that patients with Hodgkin transformation can in many cases be successfully treated with standard Hodgkin regimen, the natural history and optimal treatment for CLL with Hodgkin-like cells have been unknown. This analysis helps understand the biologic difference between these two clinicopathologic entities to understand how to better treat patients,” she noted. Going forward, “it would be extremely helpful to see these data validated by other centers to be sure that these results are reproducible,” Dr. Woyach added.

The study was supported by the Mayo Clinic, Rochester, Minn., and by the Henry J. Predolin Foundation. Lead author Dr. King disclosed research support to her institution from Bristol-Myers Squibb/Celgene. Dr. Woyach had no financial disclosures relevant to this study, but she has received laboratory research funding from Schrodinger and has consulted for AbbVie, Pharmacyclics, Janssen, AstraZeneca, Genentech, Beigene, Loxo, and Newave.
 

This article was updated 3/11/22.

Drink a day could age your brain

There are many things we can do daily to improve our health: Exercise, read a book, eat an apple (supposedly). Not drink a glass of red wine. Wait, not drink? That’s right. We were told that a glass of red wine each night was doing something good for our hearts, but it’s doing something bad to our brains: Aging them prematurely.

According to a recent study in Nature Communications, drinking half a pint of beer a day could age the brain of a 50-year-old by 6 months. A pint of beer equaled 2 years of aging and a pint and a half aged participants’ brains by 3.5 years.

Courtesy Debora Cartagena, USCDCP

Compared with people who didn’t drink, those who averaged about two pints of beer or two glasses of wine daily had brains aged 10 years older!

The researchers’ analysis included MRI scans of about 37,000 middle-aged men in the United Kingdom, along with their medical information and drinking habits, Everyday Health reported. They determined volume reductions in two parts of the brain potentially impacted by daily consumption of alcohol: White matter, which controls the senses and communication, and gray matter, which controls cognitive functions such as movement, emotions, and memories.

Normal brain aging is bad enough: Stuff like forgetting why we walked into the kitchen or having a word we want to use on the tips of our tongues. Who knew that happy hour could be speeding up the process?

Bartender, make that mimosa a virgin.
 

A big dose of meta-cine

The metaverse is big news in the tech world. For those who are less technologically inclined or haven’t thrown a few hundred dollars at a clunky virtual reality headset, the metaverse is a vaguely defined artificial reality world, brought to you by Facebo-, excuse us, Meta, where you hang out with people using a virtual avatar and do various activities, all from the comfort of your own home.

Piqsels

That’s not the most helpful definition, if we’re being honest, and that’s partially because the metaverse, as it’s being pushed by companies such as Meta, is very new and kind of a Wild West. No one really knows what it’ll be used for, but that’s not going to stop big business from pushing to secure their own corners of a new and exciting market, and that brings us to CVS, which is looking to become the first pharmacy in the metaverse.

Specifically, the company is looking to provide the entirety of its health care services – nonemergency medical care, wellness programs, nutrition advice, and counseling – to the metaverse. That makes sense. Telemedicine has become big during the pandemic, and bringing that care to the metaverse could work. Probably overcomplicated, since the sort of person who couldn’t figure out a video call to a doctor probably won’t be spending much time in the metaverse, but hey, if they can make it work, more power to them.

Where things get a bit silly is the online store. CVS looking to sell not only NFTs (because of course it is), but also downloadable virtual goods, including “prescription drugs, health, wellness, beauty, and personal care products,” according to the company’s claim to the U.S. Patent Trade Office. What exactly is a downloadable virtual prescription drug? Excellent question. We’re picturing holographic meatloaf, but the true answer is bound to be sillier than anything SpongeBob and friends could conjure.
 

Please don’t eat the winner

Hello friends. LOTME Sports welcomes you to the University of Toledo’s Glass Bowl for the wackiest virtual sporting event since Usain Bolt raced against a cheetah.

Frank_P_AJJ74/Pixabay

Hi, I’m Jim Nantz, and we’re here to witness the brainchild of Toledo physics professor Scott Lee, PhD, who posed an unusual question to his students: Is Usain Bolt faster than a 900-pound dinosaur?

Before we get started, though, I’ve got a quick question for my partner in today’s broadcast, Hall of Fame quarterback Peyton Manning: Why is someone who practices physics called a physicist when someone who practices medicine is known as a physician?

Jim, I’m prepared to talk about how Dr. Lee’s students used the concepts of 1D kinematics – displacement, speed, velocity, and acceleration – to determine if a Jamaican sprinter could beat Dilophosaurus wetherilli in a hypothetical race. Heck, it took me 2 days to be able to pronounce Dilophosaurus wetherilli. Don’t get me started on etymology.

Fair enough, my friend. What else can you tell us?

In his article in The Physics Teacher, Dr. Lee noted that recent musculoskeletal models of vertebrate animals have shown that a dinosaur like Dilophosaurus could run about as fast as Usain Bolt when he set the world record of 9.58 seconds for 100 meters in 2009. You might remember Dilophosaurus from “Jurassic Park.” It was the one that attacked the guy who played Newman on “Seinfeld.”

Fascinating stuff, Peyton, but it looks like the race is about to start. And they’re off! Newton’s second law, which says that acceleration is determined by a combination of mass and force, gives the smaller Bolt an early advantage. The dinosaur takes longer to reach maximum running velocity and crosses the line 2 seconds behind the world’s fastest human. Amazing!

Be sure to tune in again next week, when tennis legend Serena Williams takes the court against a hungry velociraptor.
 

Turning back the egg timer

The idea of getting older can be scary. Wouldn’t it be nice if we could reverse the aging process? Nice, sure, but not possible. Well, it may just be possible for women undergoing assisted reproductive treatment.

Gerd Altmann/Pixabay

It’s generally known that oocytes accumulate DNA damage over time as well, hindering fertility, but a lab in Jerusalem has found a way to reverse the age of eggs.

If you’re wondering how on Earth that was possible, here’s how. Scientists from the Hebrew University of Jerusalem said that they found a previously unknown aging mechanism, which they were able to reverse using antiviral medications, they reported in Aging Cell.

The experiment started on mice eggs, but soon real human eggs were donated. After the procedure, the treated eggs appeared younger, with less of the DNA damage that comes from age. Sperm has not yet been used to test fertility so it is unclear if this will result in something game changing, but the investigators have high hopes.

“Many women are trying to get pregnant aged 40 or over, and we think this could actually increase their level of fertility,” senior investigator Michael Klutstein, PhD, told the Times of Israel. “Within 10 years, we hope to use antiviral drugs to increase fertility among older women.”

We’re counting on you, science! Do your thing!

Drink a day could age your brain

There are many things we can do daily to improve our health: Exercise, read a book, eat an apple (supposedly). Not drink a glass of red wine. Wait, not drink? That’s right. We were told that a glass of red wine each night was doing something good for our hearts, but it’s doing something bad to our brains: Aging them prematurely.

According to a recent study in Nature Communications, drinking half a pint of beer a day could age the brain of a 50-year-old by 6 months. A pint of beer equaled 2 years of aging and a pint and a half aged participants’ brains by 3.5 years.

Courtesy Debora Cartagena, USCDCP

Compared with people who didn’t drink, those who averaged about two pints of beer or two glasses of wine daily had brains aged 10 years older!

The researchers’ analysis included MRI scans of about 37,000 middle-aged men in the United Kingdom, along with their medical information and drinking habits, Everyday Health reported. They determined volume reductions in two parts of the brain potentially impacted by daily consumption of alcohol: White matter, which controls the senses and communication, and gray matter, which controls cognitive functions such as movement, emotions, and memories.

Normal brain aging is bad enough: Stuff like forgetting why we walked into the kitchen or having a word we want to use on the tips of our tongues. Who knew that happy hour could be speeding up the process?

Bartender, make that mimosa a virgin.
 

A big dose of meta-cine

The metaverse is big news in the tech world. For those who are less technologically inclined or haven’t thrown a few hundred dollars at a clunky virtual reality headset, the metaverse is a vaguely defined artificial reality world, brought to you by Facebo-, excuse us, Meta, where you hang out with people using a virtual avatar and do various activities, all from the comfort of your own home.

Piqsels

That’s not the most helpful definition, if we’re being honest, and that’s partially because the metaverse, as it’s being pushed by companies such as Meta, is very new and kind of a Wild West. No one really knows what it’ll be used for, but that’s not going to stop big business from pushing to secure their own corners of a new and exciting market, and that brings us to CVS, which is looking to become the first pharmacy in the metaverse.

Specifically, the company is looking to provide the entirety of its health care services – nonemergency medical care, wellness programs, nutrition advice, and counseling – to the metaverse. That makes sense. Telemedicine has become big during the pandemic, and bringing that care to the metaverse could work. Probably overcomplicated, since the sort of person who couldn’t figure out a video call to a doctor probably won’t be spending much time in the metaverse, but hey, if they can make it work, more power to them.

Where things get a bit silly is the online store. CVS looking to sell not only NFTs (because of course it is), but also downloadable virtual goods, including “prescription drugs, health, wellness, beauty, and personal care products,” according to the company’s claim to the U.S. Patent Trade Office. What exactly is a downloadable virtual prescription drug? Excellent question. We’re picturing holographic meatloaf, but the true answer is bound to be sillier than anything SpongeBob and friends could conjure.
 

Please don’t eat the winner

Hello friends. LOTME Sports welcomes you to the University of Toledo’s Glass Bowl for the wackiest virtual sporting event since Usain Bolt raced against a cheetah.

Frank_P_AJJ74/Pixabay

Hi, I’m Jim Nantz, and we’re here to witness the brainchild of Toledo physics professor Scott Lee, PhD, who posed an unusual question to his students: Is Usain Bolt faster than a 900-pound dinosaur?

Before we get started, though, I’ve got a quick question for my partner in today’s broadcast, Hall of Fame quarterback Peyton Manning: Why is someone who practices physics called a physicist when someone who practices medicine is known as a physician?

Jim, I’m prepared to talk about how Dr. Lee’s students used the concepts of 1D kinematics – displacement, speed, velocity, and acceleration – to determine if a Jamaican sprinter could beat Dilophosaurus wetherilli in a hypothetical race. Heck, it took me 2 days to be able to pronounce Dilophosaurus wetherilli. Don’t get me started on etymology.

Fair enough, my friend. What else can you tell us?

In his article in The Physics Teacher, Dr. Lee noted that recent musculoskeletal models of vertebrate animals have shown that a dinosaur like Dilophosaurus could run about as fast as Usain Bolt when he set the world record of 9.58 seconds for 100 meters in 2009. You might remember Dilophosaurus from “Jurassic Park.” It was the one that attacked the guy who played Newman on “Seinfeld.”

Fascinating stuff, Peyton, but it looks like the race is about to start. And they’re off! Newton’s second law, which says that acceleration is determined by a combination of mass and force, gives the smaller Bolt an early advantage. The dinosaur takes longer to reach maximum running velocity and crosses the line 2 seconds behind the world’s fastest human. Amazing!

Be sure to tune in again next week, when tennis legend Serena Williams takes the court against a hungry velociraptor.
 

Turning back the egg timer

The idea of getting older can be scary. Wouldn’t it be nice if we could reverse the aging process? Nice, sure, but not possible. Well, it may just be possible for women undergoing assisted reproductive treatment.

Gerd Altmann/Pixabay

It’s generally known that oocytes accumulate DNA damage over time as well, hindering fertility, but a lab in Jerusalem has found a way to reverse the age of eggs.

If you’re wondering how on Earth that was possible, here’s how. Scientists from the Hebrew University of Jerusalem said that they found a previously unknown aging mechanism, which they were able to reverse using antiviral medications, they reported in Aging Cell.

The experiment started on mice eggs, but soon real human eggs were donated. After the procedure, the treated eggs appeared younger, with less of the DNA damage that comes from age. Sperm has not yet been used to test fertility so it is unclear if this will result in something game changing, but the investigators have high hopes.

“Many women are trying to get pregnant aged 40 or over, and we think this could actually increase their level of fertility,” senior investigator Michael Klutstein, PhD, told the Times of Israel. “Within 10 years, we hope to use antiviral drugs to increase fertility among older women.”

We’re counting on you, science! Do your thing!

Drink a day could age your brain

There are many things we can do daily to improve our health: Exercise, read a book, eat an apple (supposedly). Not drink a glass of red wine. Wait, not drink? That’s right. We were told that a glass of red wine each night was doing something good for our hearts, but it’s doing something bad to our brains: Aging them prematurely.

According to a recent study in Nature Communications, drinking half a pint of beer a day could age the brain of a 50-year-old by 6 months. A pint of beer equaled 2 years of aging and a pint and a half aged participants’ brains by 3.5 years.

Courtesy Debora Cartagena, USCDCP

Compared with people who didn’t drink, those who averaged about two pints of beer or two glasses of wine daily had brains aged 10 years older!

The researchers’ analysis included MRI scans of about 37,000 middle-aged men in the United Kingdom, along with their medical information and drinking habits, Everyday Health reported. They determined volume reductions in two parts of the brain potentially impacted by daily consumption of alcohol: White matter, which controls the senses and communication, and gray matter, which controls cognitive functions such as movement, emotions, and memories.

Normal brain aging is bad enough: Stuff like forgetting why we walked into the kitchen or having a word we want to use on the tips of our tongues. Who knew that happy hour could be speeding up the process?

Bartender, make that mimosa a virgin.
 

A big dose of meta-cine

The metaverse is big news in the tech world. For those who are less technologically inclined or haven’t thrown a few hundred dollars at a clunky virtual reality headset, the metaverse is a vaguely defined artificial reality world, brought to you by Facebo-, excuse us, Meta, where you hang out with people using a virtual avatar and do various activities, all from the comfort of your own home.

Piqsels

That’s not the most helpful definition, if we’re being honest, and that’s partially because the metaverse, as it’s being pushed by companies such as Meta, is very new and kind of a Wild West. No one really knows what it’ll be used for, but that’s not going to stop big business from pushing to secure their own corners of a new and exciting market, and that brings us to CVS, which is looking to become the first pharmacy in the metaverse.

Specifically, the company is looking to provide the entirety of its health care services – nonemergency medical care, wellness programs, nutrition advice, and counseling – to the metaverse. That makes sense. Telemedicine has become big during the pandemic, and bringing that care to the metaverse could work. Probably overcomplicated, since the sort of person who couldn’t figure out a video call to a doctor probably won’t be spending much time in the metaverse, but hey, if they can make it work, more power to them.

Where things get a bit silly is the online store. CVS looking to sell not only NFTs (because of course it is), but also downloadable virtual goods, including “prescription drugs, health, wellness, beauty, and personal care products,” according to the company’s claim to the U.S. Patent Trade Office. What exactly is a downloadable virtual prescription drug? Excellent question. We’re picturing holographic meatloaf, but the true answer is bound to be sillier than anything SpongeBob and friends could conjure.
 

Please don’t eat the winner

Hello friends. LOTME Sports welcomes you to the University of Toledo’s Glass Bowl for the wackiest virtual sporting event since Usain Bolt raced against a cheetah.

Frank_P_AJJ74/Pixabay

Hi, I’m Jim Nantz, and we’re here to witness the brainchild of Toledo physics professor Scott Lee, PhD, who posed an unusual question to his students: Is Usain Bolt faster than a 900-pound dinosaur?

Before we get started, though, I’ve got a quick question for my partner in today’s broadcast, Hall of Fame quarterback Peyton Manning: Why is someone who practices physics called a physicist when someone who practices medicine is known as a physician?

Jim, I’m prepared to talk about how Dr. Lee’s students used the concepts of 1D kinematics – displacement, speed, velocity, and acceleration – to determine if a Jamaican sprinter could beat Dilophosaurus wetherilli in a hypothetical race. Heck, it took me 2 days to be able to pronounce Dilophosaurus wetherilli. Don’t get me started on etymology.

Fair enough, my friend. What else can you tell us?

In his article in The Physics Teacher, Dr. Lee noted that recent musculoskeletal models of vertebrate animals have shown that a dinosaur like Dilophosaurus could run about as fast as Usain Bolt when he set the world record of 9.58 seconds for 100 meters in 2009. You might remember Dilophosaurus from “Jurassic Park.” It was the one that attacked the guy who played Newman on “Seinfeld.”

Fascinating stuff, Peyton, but it looks like the race is about to start. And they’re off! Newton’s second law, which says that acceleration is determined by a combination of mass and force, gives the smaller Bolt an early advantage. The dinosaur takes longer to reach maximum running velocity and crosses the line 2 seconds behind the world’s fastest human. Amazing!

Be sure to tune in again next week, when tennis legend Serena Williams takes the court against a hungry velociraptor.
 

Turning back the egg timer

The idea of getting older can be scary. Wouldn’t it be nice if we could reverse the aging process? Nice, sure, but not possible. Well, it may just be possible for women undergoing assisted reproductive treatment.

Gerd Altmann/Pixabay

It’s generally known that oocytes accumulate DNA damage over time as well, hindering fertility, but a lab in Jerusalem has found a way to reverse the age of eggs.

If you’re wondering how on Earth that was possible, here’s how. Scientists from the Hebrew University of Jerusalem said that they found a previously unknown aging mechanism, which they were able to reverse using antiviral medications, they reported in Aging Cell.

The experiment started on mice eggs, but soon real human eggs were donated. After the procedure, the treated eggs appeared younger, with less of the DNA damage that comes from age. Sperm has not yet been used to test fertility so it is unclear if this will result in something game changing, but the investigators have high hopes.

“Many women are trying to get pregnant aged 40 or over, and we think this could actually increase their level of fertility,” senior investigator Michael Klutstein, PhD, told the Times of Israel. “Within 10 years, we hope to use antiviral drugs to increase fertility among older women.”

We’re counting on you, science! Do your thing!

Norovirus, as noted above, is now the most common cause of medically attended acute gastroenteritis (AGE) in the United States. Norovirus AGE resembles rotavirus AGE, but a bit heavier on the vomiting. What makes it scary is that it is a low-inoculum infection (as few as 16 virus particles can cause infection), and it survives for prolonged periods in food, 10% chlorinated water, and on environmental surfaces (J Med Virol 2008;80:1468-76); hence, the infamous outbreaks on cruise ships and daycare centers. So a vaccine would be very welcome. The two non-Chinese candidates GI.1/GII.4 vaccines are Takeda’s VLP vaccine and Vaxart’s oral adenovirus vector-based vaccine. 
Takeda’s is injectable. If VLP sounds familiar, VLPs make up the FDA-approved HPV vaccine we use. Two doses of various formulations were tested in a recent phase 2 study of 1- to 3- and 4- to 8-year-olds in Finland, Panama, and Colombia with no safety issues identified. The 1- to 3-year-olds responded somewhat better than 4- to 8-year-olds, and titers remained elevated up to day 210 (Vaccine. 2022 Jun 9;40[26]:3588-96).

A recently as yet unpublished phase 1b trial of Vaxart’s vaccine in 55- to 80-year-olds (NCT04854746) showed a dose-dependent response. IgA mucosal cell responses were similar to those in younger adults. Adverse event profiles were similar between vaccinees and placebo recipients. 

Progress continues for both vaccines, but we await efficacy trials. We are likely still years from a pediatric vaccine. My sense is that an oral vaccine would be more readily accepted into the pediatric schedule, but how to incorporate it and not cause issues with the rotavirus vaccine will need evaluation.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

Norovirus, as noted above, is now the most common cause of medically attended acute gastroenteritis (AGE) in the United States. Norovirus AGE resembles rotavirus AGE, but a bit heavier on the vomiting. What makes it scary is that it is a low-inoculum infection (as few as 16 virus particles can cause infection), and it survives for prolonged periods in food, 10% chlorinated water, and on environmental surfaces (J Med Virol 2008;80:1468-76); hence, the infamous outbreaks on cruise ships and daycare centers. So a vaccine would be very welcome. The two non-Chinese candidates GI.1/GII.4 vaccines are Takeda’s VLP vaccine and Vaxart’s oral adenovirus vector-based vaccine. 
Takeda’s is injectable. If VLP sounds familiar, VLPs make up the FDA-approved HPV vaccine we use. Two doses of various formulations were tested in a recent phase 2 study of 1- to 3- and 4- to 8-year-olds in Finland, Panama, and Colombia with no safety issues identified. The 1- to 3-year-olds responded somewhat better than 4- to 8-year-olds, and titers remained elevated up to day 210 (Vaccine. 2022 Jun 9;40[26]:3588-96).

A recently as yet unpublished phase 1b trial of Vaxart’s vaccine in 55- to 80-year-olds (NCT04854746) showed a dose-dependent response. IgA mucosal cell responses were similar to those in younger adults. Adverse event profiles were similar between vaccinees and placebo recipients. 

Progress continues for both vaccines, but we await efficacy trials. We are likely still years from a pediatric vaccine. My sense is that an oral vaccine would be more readily accepted into the pediatric schedule, but how to incorporate it and not cause issues with the rotavirus vaccine will need evaluation.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

Norovirus, as noted above, is now the most common cause of medically attended acute gastroenteritis (AGE) in the United States. Norovirus AGE resembles rotavirus AGE, but a bit heavier on the vomiting. What makes it scary is that it is a low-inoculum infection (as few as 16 virus particles can cause infection), and it survives for prolonged periods in food, 10% chlorinated water, and on environmental surfaces (J Med Virol 2008;80:1468-76); hence, the infamous outbreaks on cruise ships and daycare centers. So a vaccine would be very welcome. The two non-Chinese candidates GI.1/GII.4 vaccines are Takeda’s VLP vaccine and Vaxart’s oral adenovirus vector-based vaccine. 
Takeda’s is injectable. If VLP sounds familiar, VLPs make up the FDA-approved HPV vaccine we use. Two doses of various formulations were tested in a recent phase 2 study of 1- to 3- and 4- to 8-year-olds in Finland, Panama, and Colombia with no safety issues identified. The 1- to 3-year-olds responded somewhat better than 4- to 8-year-olds, and titers remained elevated up to day 210 (Vaccine. 2022 Jun 9;40[26]:3588-96).

A recently as yet unpublished phase 1b trial of Vaxart’s vaccine in 55- to 80-year-olds (NCT04854746) showed a dose-dependent response. IgA mucosal cell responses were similar to those in younger adults. Adverse event profiles were similar between vaccinees and placebo recipients. 

Progress continues for both vaccines, but we await efficacy trials. We are likely still years from a pediatric vaccine. My sense is that an oral vaccine would be more readily accepted into the pediatric schedule, but how to incorporate it and not cause issues with the rotavirus vaccine will need evaluation.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

In spring 2022 the World Health Organization did release the new guidelines (module 5) for the shorter (4 month) regimen for 3-month- to 16-year-olds with nonsevere pulmonary tuberculosis (TB) limited to one lobe that is also smear-negative and at least presumed to be due to drug-susceptible M. tuberculosis. This regimen is NOT for children with clinically significant airway obstruction, cavitary disease, miliary TB, complex pleural effusion, or peripheral lymph node involvement. The newly recommended regimen consists of 8 weeks as an “intensive phase” (isoniazid, rifampin, pyrazinamide, and ethambutol, per local guidance) followed by 8 weeks of a “continuation phase” (isoniazid and rifampin only). Of note, the Turkova study had shown nearly identical adverse event and adherence rates – 8% and 94% – for both the short- and traditional-length regimens. The onerous multidrug treatment of uncomplicated TB in most children has become less onerous.

Caveat: The newly recommended 4-month schedule (March 2022) of traditional TB drugs is not to be confused with rifapentine-moxifloxacin–based 4-month regimen recommended by the WHO in June 2021 (CDC added guidance February 2022). This rifapentine-based regimen had been okayed for patients 12 years or older weighing at least 40 kg and also with drug-susceptible pulmonary TB, but no extrapulmonary involvement.
The new shorter regimen shows the value of trials in non-U.S. countries. The careful work in Africa and India has borne fruit that makes things easier for families, providers, and public health organizations.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

In spring 2022 the World Health Organization did release the new guidelines (module 5) for the shorter (4 month) regimen for 3-month- to 16-year-olds with nonsevere pulmonary tuberculosis (TB) limited to one lobe that is also smear-negative and at least presumed to be due to drug-susceptible M. tuberculosis. This regimen is NOT for children with clinically significant airway obstruction, cavitary disease, miliary TB, complex pleural effusion, or peripheral lymph node involvement. The newly recommended regimen consists of 8 weeks as an “intensive phase” (isoniazid, rifampin, pyrazinamide, and ethambutol, per local guidance) followed by 8 weeks of a “continuation phase” (isoniazid and rifampin only). Of note, the Turkova study had shown nearly identical adverse event and adherence rates – 8% and 94% – for both the short- and traditional-length regimens. The onerous multidrug treatment of uncomplicated TB in most children has become less onerous.

Caveat: The newly recommended 4-month schedule (March 2022) of traditional TB drugs is not to be confused with rifapentine-moxifloxacin–based 4-month regimen recommended by the WHO in June 2021 (CDC added guidance February 2022). This rifapentine-based regimen had been okayed for patients 12 years or older weighing at least 40 kg and also with drug-susceptible pulmonary TB, but no extrapulmonary involvement.
The new shorter regimen shows the value of trials in non-U.S. countries. The careful work in Africa and India has borne fruit that makes things easier for families, providers, and public health organizations.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

In spring 2022 the World Health Organization did release the new guidelines (module 5) for the shorter (4 month) regimen for 3-month- to 16-year-olds with nonsevere pulmonary tuberculosis (TB) limited to one lobe that is also smear-negative and at least presumed to be due to drug-susceptible M. tuberculosis. This regimen is NOT for children with clinically significant airway obstruction, cavitary disease, miliary TB, complex pleural effusion, or peripheral lymph node involvement. The newly recommended regimen consists of 8 weeks as an “intensive phase” (isoniazid, rifampin, pyrazinamide, and ethambutol, per local guidance) followed by 8 weeks of a “continuation phase” (isoniazid and rifampin only). Of note, the Turkova study had shown nearly identical adverse event and adherence rates – 8% and 94% – for both the short- and traditional-length regimens. The onerous multidrug treatment of uncomplicated TB in most children has become less onerous.

Caveat: The newly recommended 4-month schedule (March 2022) of traditional TB drugs is not to be confused with rifapentine-moxifloxacin–based 4-month regimen recommended by the WHO in June 2021 (CDC added guidance February 2022). This rifapentine-based regimen had been okayed for patients 12 years or older weighing at least 40 kg and also with drug-susceptible pulmonary TB, but no extrapulmonary involvement.
The new shorter regimen shows the value of trials in non-U.S. countries. The careful work in Africa and India has borne fruit that makes things easier for families, providers, and public health organizations.

Christopher J. Harrison, MD, is professor, University of Missouri Kansas City School of Medicine, department of medicine, infectious diseases section, Kansas City. He has no financial conflicts of interest.

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

The standard management for early-stage endometrial cancer involves surgery with hysterectomy, salpingectomy with or without oophorectomy, and staging lymph node sampling. Surgery serves as both a therapeutic and diagnostic intervention because surgical pathology results are in turn used to predict the likelihood of relapse and guide adjuvant therapy decisions. However, in some cases, surgical intervention is not feasible or desired, particularly if fertility preservation is a goal. Fortunately, there are nonsurgical options that are associated with favorable outcomes to offer these patients.

Endometrial cancer is associated with obesity attributable to causative mechanisms that promote endometrial hyperplasia, cellular proliferation, and heightened hormonal and growth factor signaling. Not only does obesity drive the development of endometrial cancer, but it also complicates the treatment of the disease. For example, endometrial cancer staging surgery is less successfully completed through a minimally invasive route as body mass index increases, primarily because of limitations in surgical exposure.¹ In fact, obesity can prevent surgery from being offered through any route. In addition to body habitus, determination of inoperability is also significantly influenced by the presence of coronary artery disease, hypertension, and diabetes.² Given that these comorbidities are more commonly experienced by women who are overweight, obesity creates a perfect storm of causative and complicating factors for optimal treatment.

While surgeons may determine the candidacy of patients for hysterectomy, patients themselves also drive this decision-making, particularly in the case of young patients who desire fertility preservation. Approximately 10% of patients with endometrial cancer are premenopausal, a number that is increasing over time. These women may have experienced infertility prior to their diagnosis, yet still strongly desire the attempt to conceive, particularly if they have suffered from anovulatory menstrual cycles or polycystic ovarian disease. Women with Lynch syndrome are at a higher risk for developing their cancer in premenopausal years. Therefore, it is critical that gynecologic oncologists consider nonsurgical remedies for these women and understand their potential for success.

Certain criteria should be met for women undergoing nonsurgical management of endometrial cancer, particularly if chosen electively for fertility preservation. Diagnosis should be obtained with a curettage specimen (rather than a pipelle) to optimize the accuracy of establishing tumor grade and to “debulk” the endometrial tissue. Pretreatment imaging is necessary to rule out distant metastatic disease. MRI is particularly helpful in approximating the depth of myometrial invasion of the malignancy and is recommended for patients desiring fertility preservation. Patients who have an endometrial cancer that is deeply invasive into the myometrium are poor candidates for fertility preservation and have a higher risk for metastatic disease, particularly to lymph nodes, and treatment decisions (such as surgery, or, if inoperable, radiation which treats nodal basins) should be considered for these women.

Hormonal therapy has long been identified as a highly effective systemic therapy for endometrial cancers, particularly those that are low grade and express estrogen and progesterone receptors. Progesterone can be administered orally in preparations such as megestrol or medroxyprogesterone or “locally” with levonorgestrel-releasing intrauterine devices. Oral preparations are straightforward, typically low-cost agents. Likelihood of success is 50%-75%. However, the systemic side effects of these agents, which include increased venous thromboembolism risk and appetite stimulation, are particularly problematic in this population. Therefore, many providers prefer to place progestin-releasing intrauterine devices to “bypass” these side effects, avoid issues with adherence to dosing, and provide some preventative endometrial coverage after resolution of the cancer. Recent trials have observed elimination of endometrial cancer on repeat sampling in 67%-76% of cases.^3-5 This strategy may be more successful when it is paired with the addition of GnRH agonists.⁴

When hormonal therapy is chosen for primary endometrial cancer treatment, it is typically monitored for efficacy with repeat endometrial samplings, most commonly with pipelle biopsies to avoid displacement of an intrauterine device, though repeat D&C may be more effective in achieving a complete pathologic response to treatment. Most providers recommend resampling the endometrium at 3-month intervals until resolution of the malignancy has been documented, and thereafter if any new bleeding events develop. For women who have demonstrated resolution of carcinoma on repeat sampling, data are lacking to guide decision-making regarding resumption of conception efforts, ongoing surveillance, and completion hysterectomy after they finish childbearing. If malignancy continues to be identified after 6 months of hormonal therapy, consideration should be made of a more definitive treatment (such as surgery, if feasible, or radiation if not). Continued hormonal therapy can also be considered, as delayed responses remain common even 1 year after starting therapy.⁶ If hormonal therapy is prolonged for persistent disease, repeat MRI is recommended at 6 months to document lack of progression.

Radiation, preferably with both intracavitary and external beam treatment, is the most definitive intervention for inoperable early-stage endometrial cancer. Unfortunately, fertility is not preserved with this approach. However, for patients with high-grade tumors that are less likely to express hormone receptors or respond to hormonal therapies, this may be the only treatment option available. Typical treatment courses include 5 weeks of external beam radiation treatments, focused on treating the pelvis as a whole, including occult metastases not identified on imaging. Optimal therapy also includes placement of intracavitary radiation implants, such as Heymans capsules, to concentrate the dose at the uterine fundus, while minimizing toxicity to the adjacent bladder and bowel structures. While definitive radiation is considered inferior to a primary surgical effort, disease-specific survival can be observed in more than 80% of patients treated this way.⁷

While surgery remains the standard intervention for women with early-stage endometrial cancer, hormonal therapy or radiation remain viable options with high rates of success for women who are not surgical candidates or who desire fertility preservation.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Walker JL et al. J Clin Oncol. 2009;27(32):5331-6.

2. Ertel M et al. Ann Surg Oncol. 2021;28(13):8987-95.

3. Janda M et al. Gynecol Oncol. 2021;161(1):143-51.

4. Novikova OV et al. Gynecol Oncol. 2021;161(1):152-9.

5. Westin SN et al. Am J Obstet Gynecol. 2021;224(2):191.e1-15.

6. Cho A et al. Gynecol Oncol. 2021;160(2):413-17.

7. Dutta SW et al. Brachytherapy. 2017;16(3):526-33.

The standard management for early-stage endometrial cancer involves surgery with hysterectomy, salpingectomy with or without oophorectomy, and staging lymph node sampling. Surgery serves as both a therapeutic and diagnostic intervention because surgical pathology results are in turn used to predict the likelihood of relapse and guide adjuvant therapy decisions. However, in some cases, surgical intervention is not feasible or desired, particularly if fertility preservation is a goal. Fortunately, there are nonsurgical options that are associated with favorable outcomes to offer these patients.

Endometrial cancer is associated with obesity attributable to causative mechanisms that promote endometrial hyperplasia, cellular proliferation, and heightened hormonal and growth factor signaling. Not only does obesity drive the development of endometrial cancer, but it also complicates the treatment of the disease. For example, endometrial cancer staging surgery is less successfully completed through a minimally invasive route as body mass index increases, primarily because of limitations in surgical exposure.¹ In fact, obesity can prevent surgery from being offered through any route. In addition to body habitus, determination of inoperability is also significantly influenced by the presence of coronary artery disease, hypertension, and diabetes.² Given that these comorbidities are more commonly experienced by women who are overweight, obesity creates a perfect storm of causative and complicating factors for optimal treatment.

While surgeons may determine the candidacy of patients for hysterectomy, patients themselves also drive this decision-making, particularly in the case of young patients who desire fertility preservation. Approximately 10% of patients with endometrial cancer are premenopausal, a number that is increasing over time. These women may have experienced infertility prior to their diagnosis, yet still strongly desire the attempt to conceive, particularly if they have suffered from anovulatory menstrual cycles or polycystic ovarian disease. Women with Lynch syndrome are at a higher risk for developing their cancer in premenopausal years. Therefore, it is critical that gynecologic oncologists consider nonsurgical remedies for these women and understand their potential for success.

Certain criteria should be met for women undergoing nonsurgical management of endometrial cancer, particularly if chosen electively for fertility preservation. Diagnosis should be obtained with a curettage specimen (rather than a pipelle) to optimize the accuracy of establishing tumor grade and to “debulk” the endometrial tissue. Pretreatment imaging is necessary to rule out distant metastatic disease. MRI is particularly helpful in approximating the depth of myometrial invasion of the malignancy and is recommended for patients desiring fertility preservation. Patients who have an endometrial cancer that is deeply invasive into the myometrium are poor candidates for fertility preservation and have a higher risk for metastatic disease, particularly to lymph nodes, and treatment decisions (such as surgery, or, if inoperable, radiation which treats nodal basins) should be considered for these women.

Hormonal therapy has long been identified as a highly effective systemic therapy for endometrial cancers, particularly those that are low grade and express estrogen and progesterone receptors. Progesterone can be administered orally in preparations such as megestrol or medroxyprogesterone or “locally” with levonorgestrel-releasing intrauterine devices. Oral preparations are straightforward, typically low-cost agents. Likelihood of success is 50%-75%. However, the systemic side effects of these agents, which include increased venous thromboembolism risk and appetite stimulation, are particularly problematic in this population. Therefore, many providers prefer to place progestin-releasing intrauterine devices to “bypass” these side effects, avoid issues with adherence to dosing, and provide some preventative endometrial coverage after resolution of the cancer. Recent trials have observed elimination of endometrial cancer on repeat sampling in 67%-76% of cases.^3-5 This strategy may be more successful when it is paired with the addition of GnRH agonists.⁴

When hormonal therapy is chosen for primary endometrial cancer treatment, it is typically monitored for efficacy with repeat endometrial samplings, most commonly with pipelle biopsies to avoid displacement of an intrauterine device, though repeat D&C may be more effective in achieving a complete pathologic response to treatment. Most providers recommend resampling the endometrium at 3-month intervals until resolution of the malignancy has been documented, and thereafter if any new bleeding events develop. For women who have demonstrated resolution of carcinoma on repeat sampling, data are lacking to guide decision-making regarding resumption of conception efforts, ongoing surveillance, and completion hysterectomy after they finish childbearing. If malignancy continues to be identified after 6 months of hormonal therapy, consideration should be made of a more definitive treatment (such as surgery, if feasible, or radiation if not). Continued hormonal therapy can also be considered, as delayed responses remain common even 1 year after starting therapy.⁶ If hormonal therapy is prolonged for persistent disease, repeat MRI is recommended at 6 months to document lack of progression.

Radiation, preferably with both intracavitary and external beam treatment, is the most definitive intervention for inoperable early-stage endometrial cancer. Unfortunately, fertility is not preserved with this approach. However, for patients with high-grade tumors that are less likely to express hormone receptors or respond to hormonal therapies, this may be the only treatment option available. Typical treatment courses include 5 weeks of external beam radiation treatments, focused on treating the pelvis as a whole, including occult metastases not identified on imaging. Optimal therapy also includes placement of intracavitary radiation implants, such as Heymans capsules, to concentrate the dose at the uterine fundus, while minimizing toxicity to the adjacent bladder and bowel structures. While definitive radiation is considered inferior to a primary surgical effort, disease-specific survival can be observed in more than 80% of patients treated this way.⁷

While surgery remains the standard intervention for women with early-stage endometrial cancer, hormonal therapy or radiation remain viable options with high rates of success for women who are not surgical candidates or who desire fertility preservation.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Walker JL et al. J Clin Oncol. 2009;27(32):5331-6.

2. Ertel M et al. Ann Surg Oncol. 2021;28(13):8987-95.

3. Janda M et al. Gynecol Oncol. 2021;161(1):143-51.

4. Novikova OV et al. Gynecol Oncol. 2021;161(1):152-9.

5. Westin SN et al. Am J Obstet Gynecol. 2021;224(2):191.e1-15.

6. Cho A et al. Gynecol Oncol. 2021;160(2):413-17.

7. Dutta SW et al. Brachytherapy. 2017;16(3):526-33.

The standard management for early-stage endometrial cancer involves surgery with hysterectomy, salpingectomy with or without oophorectomy, and staging lymph node sampling. Surgery serves as both a therapeutic and diagnostic intervention because surgical pathology results are in turn used to predict the likelihood of relapse and guide adjuvant therapy decisions. However, in some cases, surgical intervention is not feasible or desired, particularly if fertility preservation is a goal. Fortunately, there are nonsurgical options that are associated with favorable outcomes to offer these patients.

Endometrial cancer is associated with obesity attributable to causative mechanisms that promote endometrial hyperplasia, cellular proliferation, and heightened hormonal and growth factor signaling. Not only does obesity drive the development of endometrial cancer, but it also complicates the treatment of the disease. For example, endometrial cancer staging surgery is less successfully completed through a minimally invasive route as body mass index increases, primarily because of limitations in surgical exposure.¹ In fact, obesity can prevent surgery from being offered through any route. In addition to body habitus, determination of inoperability is also significantly influenced by the presence of coronary artery disease, hypertension, and diabetes.² Given that these comorbidities are more commonly experienced by women who are overweight, obesity creates a perfect storm of causative and complicating factors for optimal treatment.

While surgeons may determine the candidacy of patients for hysterectomy, patients themselves also drive this decision-making, particularly in the case of young patients who desire fertility preservation. Approximately 10% of patients with endometrial cancer are premenopausal, a number that is increasing over time. These women may have experienced infertility prior to their diagnosis, yet still strongly desire the attempt to conceive, particularly if they have suffered from anovulatory menstrual cycles or polycystic ovarian disease. Women with Lynch syndrome are at a higher risk for developing their cancer in premenopausal years. Therefore, it is critical that gynecologic oncologists consider nonsurgical remedies for these women and understand their potential for success.

Certain criteria should be met for women undergoing nonsurgical management of endometrial cancer, particularly if chosen electively for fertility preservation. Diagnosis should be obtained with a curettage specimen (rather than a pipelle) to optimize the accuracy of establishing tumor grade and to “debulk” the endometrial tissue. Pretreatment imaging is necessary to rule out distant metastatic disease. MRI is particularly helpful in approximating the depth of myometrial invasion of the malignancy and is recommended for patients desiring fertility preservation. Patients who have an endometrial cancer that is deeply invasive into the myometrium are poor candidates for fertility preservation and have a higher risk for metastatic disease, particularly to lymph nodes, and treatment decisions (such as surgery, or, if inoperable, radiation which treats nodal basins) should be considered for these women.

Hormonal therapy has long been identified as a highly effective systemic therapy for endometrial cancers, particularly those that are low grade and express estrogen and progesterone receptors. Progesterone can be administered orally in preparations such as megestrol or medroxyprogesterone or “locally” with levonorgestrel-releasing intrauterine devices. Oral preparations are straightforward, typically low-cost agents. Likelihood of success is 50%-75%. However, the systemic side effects of these agents, which include increased venous thromboembolism risk and appetite stimulation, are particularly problematic in this population. Therefore, many providers prefer to place progestin-releasing intrauterine devices to “bypass” these side effects, avoid issues with adherence to dosing, and provide some preventative endometrial coverage after resolution of the cancer. Recent trials have observed elimination of endometrial cancer on repeat sampling in 67%-76% of cases.^3-5 This strategy may be more successful when it is paired with the addition of GnRH agonists.⁴

When hormonal therapy is chosen for primary endometrial cancer treatment, it is typically monitored for efficacy with repeat endometrial samplings, most commonly with pipelle biopsies to avoid displacement of an intrauterine device, though repeat D&C may be more effective in achieving a complete pathologic response to treatment. Most providers recommend resampling the endometrium at 3-month intervals until resolution of the malignancy has been documented, and thereafter if any new bleeding events develop. For women who have demonstrated resolution of carcinoma on repeat sampling, data are lacking to guide decision-making regarding resumption of conception efforts, ongoing surveillance, and completion hysterectomy after they finish childbearing. If malignancy continues to be identified after 6 months of hormonal therapy, consideration should be made of a more definitive treatment (such as surgery, if feasible, or radiation if not). Continued hormonal therapy can also be considered, as delayed responses remain common even 1 year after starting therapy.⁶ If hormonal therapy is prolonged for persistent disease, repeat MRI is recommended at 6 months to document lack of progression.

Radiation, preferably with both intracavitary and external beam treatment, is the most definitive intervention for inoperable early-stage endometrial cancer. Unfortunately, fertility is not preserved with this approach. However, for patients with high-grade tumors that are less likely to express hormone receptors or respond to hormonal therapies, this may be the only treatment option available. Typical treatment courses include 5 weeks of external beam radiation treatments, focused on treating the pelvis as a whole, including occult metastases not identified on imaging. Optimal therapy also includes placement of intracavitary radiation implants, such as Heymans capsules, to concentrate the dose at the uterine fundus, while minimizing toxicity to the adjacent bladder and bowel structures. While definitive radiation is considered inferior to a primary surgical effort, disease-specific survival can be observed in more than 80% of patients treated this way.⁷

While surgery remains the standard intervention for women with early-stage endometrial cancer, hormonal therapy or radiation remain viable options with high rates of success for women who are not surgical candidates or who desire fertility preservation.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill.

References

1. Walker JL et al. J Clin Oncol. 2009;27(32):5331-6.

2. Ertel M et al. Ann Surg Oncol. 2021;28(13):8987-95.

3. Janda M et al. Gynecol Oncol. 2021;161(1):143-51.

4. Novikova OV et al. Gynecol Oncol. 2021;161(1):152-9.

5. Westin SN et al. Am J Obstet Gynecol. 2021;224(2):191.e1-15.

6. Cho A et al. Gynecol Oncol. 2021;160(2):413-17.

7. Dutta SW et al. Brachytherapy. 2017;16(3):526-33.

David Bennett Sr, the 57-year-old patient with terminal heart disease who became the first person to receive a genetically modified pig heart, has died. He passed away March 8, according to a statement from the University of Maryland Medical Center (UMMC), Baltimore, where the transplant was performed.

Mr. Bennett received the transplant on January 7 and lived for 2 months following the surgery.   

Although not providing the exact cause of his death, UMMC said Mr. Bennett’s condition began deteriorating several days before his death.

When it became clear that he would not recover, he was given compassionate palliative care and was able to communicate with his family during his final hours.

“We are devastated by the loss of Mr. Bennett. He proved to be a brave and noble patient who fought all the way to the end. We extend our sincerest condolences to his family,” Bartley P. Griffith, MD, who performed the transplant, said in the statement.

“We are grateful to Mr. Bennett for his unique and historic role in helping to contribute to a vast array of knowledge to the field of xenotransplantation,” added Muhammad M. Mohiuddin, MD, director of the cardiac xenotransplantation program at University of Maryland School of Medicine.

Before receiving the genetically modified pig heart, Mr. Bennett had required mechanical circulatory support to stay alive but was rejected for standard heart transplantation at UMMC and other centers. He was ineligible for an implanted ventricular assist device due to ventricular arrhythmias.

Following surgery, the transplanted pig heart performed well for several weeks without any signs of rejection. The patient was able to spend time with his family and participate in physical therapy to help regain strength.

“This organ transplant demonstrated for the first time that a genetically modified animal heart can function like a human heart without immediate rejection by the body,” UMMC said in a statement issued 3 days after the surgery.

Thanks to Mr. Bennett, “we have gained invaluable insights learning that the genetically modified pig heart can function well within the human body while the immune system is adequately suppressed,” said Dr. Mohiuddin. “We remain optimistic and plan on continuing our work in future clinical trials.”

The patient’s son, David Bennett Jr, said the family is “profoundly grateful for the life-extending opportunity” provided to his father by the “stellar team” at the University of Maryland School of Medicine and the University of Maryland Medical Center.

“We were able to spend some precious weeks together while he recovered from the transplant surgery, weeks we would not have had without this miraculous effort,” he said.

“We also hope that what was learned from his surgery will benefit future patients and hopefully, one day, end the organ shortage that costs so many lives each year,” he added.

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

David Bennett Sr, the 57-year-old patient with terminal heart disease who became the first person to receive a genetically modified pig heart, has died. He passed away March 8, according to a statement from the University of Maryland Medical Center (UMMC), Baltimore, where the transplant was performed.

Mr. Bennett received the transplant on January 7 and lived for 2 months following the surgery.   

Although not providing the exact cause of his death, UMMC said Mr. Bennett’s condition began deteriorating several days before his death.

When it became clear that he would not recover, he was given compassionate palliative care and was able to communicate with his family during his final hours.

“We are devastated by the loss of Mr. Bennett. He proved to be a brave and noble patient who fought all the way to the end. We extend our sincerest condolences to his family,” Bartley P. Griffith, MD, who performed the transplant, said in the statement.

“We are grateful to Mr. Bennett for his unique and historic role in helping to contribute to a vast array of knowledge to the field of xenotransplantation,” added Muhammad M. Mohiuddin, MD, director of the cardiac xenotransplantation program at University of Maryland School of Medicine.

Before receiving the genetically modified pig heart, Mr. Bennett had required mechanical circulatory support to stay alive but was rejected for standard heart transplantation at UMMC and other centers. He was ineligible for an implanted ventricular assist device due to ventricular arrhythmias.

Following surgery, the transplanted pig heart performed well for several weeks without any signs of rejection. The patient was able to spend time with his family and participate in physical therapy to help regain strength.

“This organ transplant demonstrated for the first time that a genetically modified animal heart can function like a human heart without immediate rejection by the body,” UMMC said in a statement issued 3 days after the surgery.

Thanks to Mr. Bennett, “we have gained invaluable insights learning that the genetically modified pig heart can function well within the human body while the immune system is adequately suppressed,” said Dr. Mohiuddin. “We remain optimistic and plan on continuing our work in future clinical trials.”

The patient’s son, David Bennett Jr, said the family is “profoundly grateful for the life-extending opportunity” provided to his father by the “stellar team” at the University of Maryland School of Medicine and the University of Maryland Medical Center.

“We were able to spend some precious weeks together while he recovered from the transplant surgery, weeks we would not have had without this miraculous effort,” he said.

“We also hope that what was learned from his surgery will benefit future patients and hopefully, one day, end the organ shortage that costs so many lives each year,” he added.

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

David Bennett Sr, the 57-year-old patient with terminal heart disease who became the first person to receive a genetically modified pig heart, has died. He passed away March 8, according to a statement from the University of Maryland Medical Center (UMMC), Baltimore, where the transplant was performed.

Mr. Bennett received the transplant on January 7 and lived for 2 months following the surgery.   

Although not providing the exact cause of his death, UMMC said Mr. Bennett’s condition began deteriorating several days before his death.

When it became clear that he would not recover, he was given compassionate palliative care and was able to communicate with his family during his final hours.

“We are devastated by the loss of Mr. Bennett. He proved to be a brave and noble patient who fought all the way to the end. We extend our sincerest condolences to his family,” Bartley P. Griffith, MD, who performed the transplant, said in the statement.

“We are grateful to Mr. Bennett for his unique and historic role in helping to contribute to a vast array of knowledge to the field of xenotransplantation,” added Muhammad M. Mohiuddin, MD, director of the cardiac xenotransplantation program at University of Maryland School of Medicine.

Before receiving the genetically modified pig heart, Mr. Bennett had required mechanical circulatory support to stay alive but was rejected for standard heart transplantation at UMMC and other centers. He was ineligible for an implanted ventricular assist device due to ventricular arrhythmias.

Following surgery, the transplanted pig heart performed well for several weeks without any signs of rejection. The patient was able to spend time with his family and participate in physical therapy to help regain strength.

“This organ transplant demonstrated for the first time that a genetically modified animal heart can function like a human heart without immediate rejection by the body,” UMMC said in a statement issued 3 days after the surgery.

Thanks to Mr. Bennett, “we have gained invaluable insights learning that the genetically modified pig heart can function well within the human body while the immune system is adequately suppressed,” said Dr. Mohiuddin. “We remain optimistic and plan on continuing our work in future clinical trials.”

The patient’s son, David Bennett Jr, said the family is “profoundly grateful for the life-extending opportunity” provided to his father by the “stellar team” at the University of Maryland School of Medicine and the University of Maryland Medical Center.

“We were able to spend some precious weeks together while he recovered from the transplant surgery, weeks we would not have had without this miraculous effort,” he said.

“We also hope that what was learned from his surgery will benefit future patients and hopefully, one day, end the organ shortage that costs so many lives each year,” he added.

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

A first-ever study of the effect of evidence-based maternity care practices on prenatal breastfeeding intentions in women from low-income U.S. households shows that the use of “baby-friendly steps” during birth hospitalization made it possible for almost half to breastfeed exclusively for 1 month.

Analyses of national data from a longitudinal study of 1,080 women enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) revealed that 47% were able to meet their prenatal intention to breastfeed without formula or other milk for at least 30 days.

The odds of meeting prenatal breastfeeding intentions more than quadrupled when babies received only breast milk (risk ratio, 4.4; 95% confidence interval, 3.4-5.7), the study showed. Breastfeeding within 1 hour of birth was also associated with greater likelihood of breastfeeding success (RR, 1.3; 95% CI, 1.0-1.6).

The study, led by Heather C. Hamner, PhD, MS, MPH, of the National Center for Chronic Disease Prevention and Health Promotion, , Atlanta, was reported online in Pediatrics.

“This study confirms the relationship between experiencing maternity care practices supportive of breastfeeding and meeting one’s breastfeeding intentions, and adds evidence specifically among low-income women, who are known to be at higher risk of not breastfeeding,” the study authors wrote.

Women from low-income households often face additional barriers to meeting their breastfeeding goals, including lack of access to professional lactation services, Dr. Hamner said in an interview. “We want physicians to know how important maternity care practices supportive of breastfeeding are to helping all women achieve their breastfeeding goals. Physicians can be champions for implementation of evidence-based maternity care practices in the hospitals and practices in which they work.”

Dr. Hamner emphasized that physicians need to discuss the importance of breastfeeding with patients and their families, brief them on what to expect in the maternity care setting, and ensure women are connected to lactation resources. The American Academy of Pediatrics is working to increase physician capacity to support breastfeeding through the Physician Engagement and Training Focused on Breastfeeding project.

For the study, Dr. Hamner and colleagues analyzed data from the longitudinal WIC Infant and Toddler Feeding Practices Study-2 (ITFPS-2), which assessed the impact of 6 steps from a 10-step maternity care protocol known as The Ten Steps To Successful Breastfeeding. These steps are part of the worldwide Baby-Friendly Hospital Initiative (BFHI), which has been shown to improve rates of breastfeeding initiation, duration, and exclusivity.

After adjusting for sociodemographic and other factors, the study authors estimated risk ratios for associations between each of six maternity care practices assessed in ITFPS-2 and the success of women who reported an intention to breastfeed exclusively for 1 month. The six steps included initiation of breastfeeding within 1 hour of birth (step 4), showing moms how to breastfeed and maintain lactation (step 5), giving no food or drink other than breast milk unless medically indicated (step 6), rooming-in (step 7), breastfeeding on demand (step 8), and giving no pacifiers (step 9).

The analyses showed that only steps 4 and 6 – initiating breastfeeding at birth and giving only breast milk – remained significantly associated with meeting breastfeeding intentions. The results also revealed a dose-response relationship between the number of baby steps experienced during birth hospitalization and the likelihood of meeting breastfeeding goals, a finding in keeping with previous studies. In women who experienced all six steps, for example, 76% were breastfeeding exclusively at 1 month, compared with 16% of those who experienced zero to two steps.

Although the dose-response relationship did not appear to differ significantly by race or ethnicity, it was driven primarily by a hospital policy of providing infant formula or other supplementation, the study authors found. Notably, 44% of women reported that their infant had been fed something other than breast milk while in the hospital, and about 60% said they stopped breastfeeding earlier than intended.

“This finding reiterates the importance of limiting in-hospital formula or other supplementation of breastfed infants to only those with medical necessity,” Dr. Hamner and colleagues said.

Despite improvements in maternity care practices that promote breastfeeding, including an increase in the number of births occurring in U.S. hospitals with a baby-friendly designation, many women continue to experience significant barriers to breastfeeding, the investigators pointed out. Currently, there are 592 baby-friendly hospitals in the United States, representing 28.29% of annual births.

“I think more hospitals becoming baby friendly would really help,” Mary Franklin, DNP, CNM, assistant professor at Case Western Reserve University, Cleveland, said in an interview. More needs to be done to support women during birth hospitalization and after they return home, so they can continue to breastfeed for “longer than the initial 6 weeks,” added Dr. Franklin, who is also director of the nurse midwifery and women’s health NP program.

The AAP recommends exclusive breastfeeding for about 6 months followed by complementary food introduction and continued breastfeeding through 12 months or beyond.

Like Dr. Hamner, Dr. Franklin emphasized that physicians have an important role to play in the initiation, duration, and exclusivity of breastfeeding. This includes promoting enrichment of the pregnancy experience with prenatal education and increased support from health care providers and peers. At delivery, obstetricians can delay cord clamping to facilitate early breastfeeding. They can also support the elimination of the central nursery in hospitals so that mother and baby stay together from birth. In addition, prescriptions can be written for breast pumps, which are covered by Medicaid.

The study received no outside funding. Dr. Hamner and coauthors disclosed having no potential financial conflicts of interest. Dr. Franklin also disclosed having no financial conflicts of interest.

A first-ever study of the effect of evidence-based maternity care practices on prenatal breastfeeding intentions in women from low-income U.S. households shows that the use of “baby-friendly steps” during birth hospitalization made it possible for almost half to breastfeed exclusively for 1 month.

Analyses of national data from a longitudinal study of 1,080 women enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) revealed that 47% were able to meet their prenatal intention to breastfeed without formula or other milk for at least 30 days.

The odds of meeting prenatal breastfeeding intentions more than quadrupled when babies received only breast milk (risk ratio, 4.4; 95% confidence interval, 3.4-5.7), the study showed. Breastfeeding within 1 hour of birth was also associated with greater likelihood of breastfeeding success (RR, 1.3; 95% CI, 1.0-1.6).

The study, led by Heather C. Hamner, PhD, MS, MPH, of the National Center for Chronic Disease Prevention and Health Promotion, , Atlanta, was reported online in Pediatrics.

“This study confirms the relationship between experiencing maternity care practices supportive of breastfeeding and meeting one’s breastfeeding intentions, and adds evidence specifically among low-income women, who are known to be at higher risk of not breastfeeding,” the study authors wrote.

Women from low-income households often face additional barriers to meeting their breastfeeding goals, including lack of access to professional lactation services, Dr. Hamner said in an interview. “We want physicians to know how important maternity care practices supportive of breastfeeding are to helping all women achieve their breastfeeding goals. Physicians can be champions for implementation of evidence-based maternity care practices in the hospitals and practices in which they work.”

Dr. Hamner emphasized that physicians need to discuss the importance of breastfeeding with patients and their families, brief them on what to expect in the maternity care setting, and ensure women are connected to lactation resources. The American Academy of Pediatrics is working to increase physician capacity to support breastfeeding through the Physician Engagement and Training Focused on Breastfeeding project.

For the study, Dr. Hamner and colleagues analyzed data from the longitudinal WIC Infant and Toddler Feeding Practices Study-2 (ITFPS-2), which assessed the impact of 6 steps from a 10-step maternity care protocol known as The Ten Steps To Successful Breastfeeding. These steps are part of the worldwide Baby-Friendly Hospital Initiative (BFHI), which has been shown to improve rates of breastfeeding initiation, duration, and exclusivity.

After adjusting for sociodemographic and other factors, the study authors estimated risk ratios for associations between each of six maternity care practices assessed in ITFPS-2 and the success of women who reported an intention to breastfeed exclusively for 1 month. The six steps included initiation of breastfeeding within 1 hour of birth (step 4), showing moms how to breastfeed and maintain lactation (step 5), giving no food or drink other than breast milk unless medically indicated (step 6), rooming-in (step 7), breastfeeding on demand (step 8), and giving no pacifiers (step 9).

The analyses showed that only steps 4 and 6 – initiating breastfeeding at birth and giving only breast milk – remained significantly associated with meeting breastfeeding intentions. The results also revealed a dose-response relationship between the number of baby steps experienced during birth hospitalization and the likelihood of meeting breastfeeding goals, a finding in keeping with previous studies. In women who experienced all six steps, for example, 76% were breastfeeding exclusively at 1 month, compared with 16% of those who experienced zero to two steps.

Although the dose-response relationship did not appear to differ significantly by race or ethnicity, it was driven primarily by a hospital policy of providing infant formula or other supplementation, the study authors found. Notably, 44% of women reported that their infant had been fed something other than breast milk while in the hospital, and about 60% said they stopped breastfeeding earlier than intended.

“This finding reiterates the importance of limiting in-hospital formula or other supplementation of breastfed infants to only those with medical necessity,” Dr. Hamner and colleagues said.

Despite improvements in maternity care practices that promote breastfeeding, including an increase in the number of births occurring in U.S. hospitals with a baby-friendly designation, many women continue to experience significant barriers to breastfeeding, the investigators pointed out. Currently, there are 592 baby-friendly hospitals in the United States, representing 28.29% of annual births.

“I think more hospitals becoming baby friendly would really help,” Mary Franklin, DNP, CNM, assistant professor at Case Western Reserve University, Cleveland, said in an interview. More needs to be done to support women during birth hospitalization and after they return home, so they can continue to breastfeed for “longer than the initial 6 weeks,” added Dr. Franklin, who is also director of the nurse midwifery and women’s health NP program.

The AAP recommends exclusive breastfeeding for about 6 months followed by complementary food introduction and continued breastfeeding through 12 months or beyond.

Like Dr. Hamner, Dr. Franklin emphasized that physicians have an important role to play in the initiation, duration, and exclusivity of breastfeeding. This includes promoting enrichment of the pregnancy experience with prenatal education and increased support from health care providers and peers. At delivery, obstetricians can delay cord clamping to facilitate early breastfeeding. They can also support the elimination of the central nursery in hospitals so that mother and baby stay together from birth. In addition, prescriptions can be written for breast pumps, which are covered by Medicaid.

The study received no outside funding. Dr. Hamner and coauthors disclosed having no potential financial conflicts of interest. Dr. Franklin also disclosed having no financial conflicts of interest.

A first-ever study of the effect of evidence-based maternity care practices on prenatal breastfeeding intentions in women from low-income U.S. households shows that the use of “baby-friendly steps” during birth hospitalization made it possible for almost half to breastfeed exclusively for 1 month.

Analyses of national data from a longitudinal study of 1,080 women enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) revealed that 47% were able to meet their prenatal intention to breastfeed without formula or other milk for at least 30 days.

The odds of meeting prenatal breastfeeding intentions more than quadrupled when babies received only breast milk (risk ratio, 4.4; 95% confidence interval, 3.4-5.7), the study showed. Breastfeeding within 1 hour of birth was also associated with greater likelihood of breastfeeding success (RR, 1.3; 95% CI, 1.0-1.6).

The study, led by Heather C. Hamner, PhD, MS, MPH, of the National Center for Chronic Disease Prevention and Health Promotion, , Atlanta, was reported online in Pediatrics.

“This study confirms the relationship between experiencing maternity care practices supportive of breastfeeding and meeting one’s breastfeeding intentions, and adds evidence specifically among low-income women, who are known to be at higher risk of not breastfeeding,” the study authors wrote.

Women from low-income households often face additional barriers to meeting their breastfeeding goals, including lack of access to professional lactation services, Dr. Hamner said in an interview. “We want physicians to know how important maternity care practices supportive of breastfeeding are to helping all women achieve their breastfeeding goals. Physicians can be champions for implementation of evidence-based maternity care practices in the hospitals and practices in which they work.”

Dr. Hamner emphasized that physicians need to discuss the importance of breastfeeding with patients and their families, brief them on what to expect in the maternity care setting, and ensure women are connected to lactation resources. The American Academy of Pediatrics is working to increase physician capacity to support breastfeeding through the Physician Engagement and Training Focused on Breastfeeding project.

For the study, Dr. Hamner and colleagues analyzed data from the longitudinal WIC Infant and Toddler Feeding Practices Study-2 (ITFPS-2), which assessed the impact of 6 steps from a 10-step maternity care protocol known as The Ten Steps To Successful Breastfeeding. These steps are part of the worldwide Baby-Friendly Hospital Initiative (BFHI), which has been shown to improve rates of breastfeeding initiation, duration, and exclusivity.

After adjusting for sociodemographic and other factors, the study authors estimated risk ratios for associations between each of six maternity care practices assessed in ITFPS-2 and the success of women who reported an intention to breastfeed exclusively for 1 month. The six steps included initiation of breastfeeding within 1 hour of birth (step 4), showing moms how to breastfeed and maintain lactation (step 5), giving no food or drink other than breast milk unless medically indicated (step 6), rooming-in (step 7), breastfeeding on demand (step 8), and giving no pacifiers (step 9).

The analyses showed that only steps 4 and 6 – initiating breastfeeding at birth and giving only breast milk – remained significantly associated with meeting breastfeeding intentions. The results also revealed a dose-response relationship between the number of baby steps experienced during birth hospitalization and the likelihood of meeting breastfeeding goals, a finding in keeping with previous studies. In women who experienced all six steps, for example, 76% were breastfeeding exclusively at 1 month, compared with 16% of those who experienced zero to two steps.

Although the dose-response relationship did not appear to differ significantly by race or ethnicity, it was driven primarily by a hospital policy of providing infant formula or other supplementation, the study authors found. Notably, 44% of women reported that their infant had been fed something other than breast milk while in the hospital, and about 60% said they stopped breastfeeding earlier than intended.

“This finding reiterates the importance of limiting in-hospital formula or other supplementation of breastfed infants to only those with medical necessity,” Dr. Hamner and colleagues said.

Despite improvements in maternity care practices that promote breastfeeding, including an increase in the number of births occurring in U.S. hospitals with a baby-friendly designation, many women continue to experience significant barriers to breastfeeding, the investigators pointed out. Currently, there are 592 baby-friendly hospitals in the United States, representing 28.29% of annual births.

“I think more hospitals becoming baby friendly would really help,” Mary Franklin, DNP, CNM, assistant professor at Case Western Reserve University, Cleveland, said in an interview. More needs to be done to support women during birth hospitalization and after they return home, so they can continue to breastfeed for “longer than the initial 6 weeks,” added Dr. Franklin, who is also director of the nurse midwifery and women’s health NP program.

The AAP recommends exclusive breastfeeding for about 6 months followed by complementary food introduction and continued breastfeeding through 12 months or beyond.

Like Dr. Hamner, Dr. Franklin emphasized that physicians have an important role to play in the initiation, duration, and exclusivity of breastfeeding. This includes promoting enrichment of the pregnancy experience with prenatal education and increased support from health care providers and peers. At delivery, obstetricians can delay cord clamping to facilitate early breastfeeding. They can also support the elimination of the central nursery in hospitals so that mother and baby stay together from birth. In addition, prescriptions can be written for breast pumps, which are covered by Medicaid.

The study received no outside funding. Dr. Hamner and coauthors disclosed having no potential financial conflicts of interest. Dr. Franklin also disclosed having no financial conflicts of interest.