Key clinical point: Men vs women with psoriatic arthritis (PsA) experienced significantly improved outcomes with methotrexate+etanercept combination therapy, whereas those with lower body mass index (BMI) experienced better outcomes with no indication of any pattern with treatment received.

Major finding: At week 24, a higher proportion of men vs women receiving methotrexate+etanercept achieved American College of Rheumatology 20% (ACR20; 71.5% vs. 58.3%; P = .0194) and minimal disease activity (MDA; 45.8% vs 25.2%; P = .0003), whereas a higher proportion of patients with a BMI of ≤30 vs >30 kg/m² in all treatment groups achieved MDA (all P < .05) and those in methotrexate+etanercept group achieved ACR20 (P = .0241).

Study details: This was a post hoc analysis of the phase 3 SEAM-PsA trial including 851 methotrexate/biologics naive patients with early PsA who were randomly assigned to receive methotrexate+placebo, etanercept+placebo, or methotrexate+etanercept.

Disclosures: This study was funded by Immunex, a subsidiary of Amgen. Two authors declared being employees of and owned stocks in Amgen. The other authors reported ties with various sources, including Amgen.

Source: Mease PJ et al. Potential impact of sex and body mass index on response to therapy in psoriatic arthritis: Post-hoc analysis of results from the SEAM-PsA trial. J Rheumatol. 2022 (Apr 15). Doi: 10.3899/jrheum.211037

Key clinical point: Men vs women with psoriatic arthritis (PsA) experienced significantly improved outcomes with methotrexate+etanercept combination therapy, whereas those with lower body mass index (BMI) experienced better outcomes with no indication of any pattern with treatment received.

Major finding: At week 24, a higher proportion of men vs women receiving methotrexate+etanercept achieved American College of Rheumatology 20% (ACR20; 71.5% vs. 58.3%; P = .0194) and minimal disease activity (MDA; 45.8% vs 25.2%; P = .0003), whereas a higher proportion of patients with a BMI of ≤30 vs >30 kg/m² in all treatment groups achieved MDA (all P < .05) and those in methotrexate+etanercept group achieved ACR20 (P = .0241).

Study details: This was a post hoc analysis of the phase 3 SEAM-PsA trial including 851 methotrexate/biologics naive patients with early PsA who were randomly assigned to receive methotrexate+placebo, etanercept+placebo, or methotrexate+etanercept.

Disclosures: This study was funded by Immunex, a subsidiary of Amgen. Two authors declared being employees of and owned stocks in Amgen. The other authors reported ties with various sources, including Amgen.

Source: Mease PJ et al. Potential impact of sex and body mass index on response to therapy in psoriatic arthritis: Post-hoc analysis of results from the SEAM-PsA trial. J Rheumatol. 2022 (Apr 15). Doi: 10.3899/jrheum.211037

Key clinical point: Men vs women with psoriatic arthritis (PsA) experienced significantly improved outcomes with methotrexate+etanercept combination therapy, whereas those with lower body mass index (BMI) experienced better outcomes with no indication of any pattern with treatment received.

Major finding: At week 24, a higher proportion of men vs women receiving methotrexate+etanercept achieved American College of Rheumatology 20% (ACR20; 71.5% vs. 58.3%; P = .0194) and minimal disease activity (MDA; 45.8% vs 25.2%; P = .0003), whereas a higher proportion of patients with a BMI of ≤30 vs >30 kg/m² in all treatment groups achieved MDA (all P < .05) and those in methotrexate+etanercept group achieved ACR20 (P = .0241).

Study details: This was a post hoc analysis of the phase 3 SEAM-PsA trial including 851 methotrexate/biologics naive patients with early PsA who were randomly assigned to receive methotrexate+placebo, etanercept+placebo, or methotrexate+etanercept.

Disclosures: This study was funded by Immunex, a subsidiary of Amgen. Two authors declared being employees of and owned stocks in Amgen. The other authors reported ties with various sources, including Amgen.

Source: Mease PJ et al. Potential impact of sex and body mass index on response to therapy in psoriatic arthritis: Post-hoc analysis of results from the SEAM-PsA trial. J Rheumatol. 2022 (Apr 15). Doi: 10.3899/jrheum.211037

Key clinical point: More than one-third of real-world patients with psoriatic arthritis (PsA) who were not in minimal disease activity (MDA) at secukinumab initiation achieved MDA after 6 months of initiating secukinumab along with improvement in other patient-reported outcomes.

Major finding: At 6 months, 36.6% of patients not in MDA at secukinumab initiation achieved MDA and 41.2%, 44.4%, 60.7%, and 75.0% of patients with ≥1 tender joint, ≥1 swollen joint, enthesitis, and dactylitis, respectively, at secukinumab initiation achieved symptom resolution along with improvement in pain, fatigue, and other scores.

Study details: Findings are from an analysis of 100 patients with PsA from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry who initiated secukinumab and maintained the treatment at 6-month follow-up visit.

Disclosures: This study was sponsored by CorEvitas, LLC. Three authors declared being employees of CorEvitas. The other authors reported ties with several sources.

Source: Mease PJ et al. Effectiveness of 6-month use of secukinumab in patients with psoriatic arthritis in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. J Rheumatol. 2022 (Apr 15). Doi: 10.3899/jrheum.211033

Key clinical point: More than one-third of real-world patients with psoriatic arthritis (PsA) who were not in minimal disease activity (MDA) at secukinumab initiation achieved MDA after 6 months of initiating secukinumab along with improvement in other patient-reported outcomes.

Major finding: At 6 months, 36.6% of patients not in MDA at secukinumab initiation achieved MDA and 41.2%, 44.4%, 60.7%, and 75.0% of patients with ≥1 tender joint, ≥1 swollen joint, enthesitis, and dactylitis, respectively, at secukinumab initiation achieved symptom resolution along with improvement in pain, fatigue, and other scores.

Study details: Findings are from an analysis of 100 patients with PsA from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry who initiated secukinumab and maintained the treatment at 6-month follow-up visit.

Disclosures: This study was sponsored by CorEvitas, LLC. Three authors declared being employees of CorEvitas. The other authors reported ties with several sources.

Source: Mease PJ et al. Effectiveness of 6-month use of secukinumab in patients with psoriatic arthritis in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. J Rheumatol. 2022 (Apr 15). Doi: 10.3899/jrheum.211033

Key clinical point: More than one-third of real-world patients with psoriatic arthritis (PsA) who were not in minimal disease activity (MDA) at secukinumab initiation achieved MDA after 6 months of initiating secukinumab along with improvement in other patient-reported outcomes.

Major finding: At 6 months, 36.6% of patients not in MDA at secukinumab initiation achieved MDA and 41.2%, 44.4%, 60.7%, and 75.0% of patients with ≥1 tender joint, ≥1 swollen joint, enthesitis, and dactylitis, respectively, at secukinumab initiation achieved symptom resolution along with improvement in pain, fatigue, and other scores.

Study details: Findings are from an analysis of 100 patients with PsA from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry who initiated secukinumab and maintained the treatment at 6-month follow-up visit.

Disclosures: This study was sponsored by CorEvitas, LLC. Three authors declared being employees of CorEvitas. The other authors reported ties with several sources.

Source: Mease PJ et al. Effectiveness of 6-month use of secukinumab in patients with psoriatic arthritis in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry. J Rheumatol. 2022 (Apr 15). Doi: 10.3899/jrheum.211033

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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

The 2020 explosion that rocked Beirut, killing more than 200, injuring more than 7,000 and causing millions of dollars in damage had a significant impact on the mental health of Lebanese expatriates, leaving many grappling with anxiety, depression, and posttraumatic stress disorder, results of a new survey show.

The findings highlight the importance of considering the well-being of expatriates dealing with adverse events in their home countries, the investigators say.

Dr. Gaëlle Rached

“Everyone, including doctors, should be more sensitive to expatriates around them; we should look out for them especially when their home country is going through a traumatic event,” study investigator Gaëlle Rached, MD, MSc, research postdoctoral fellow, Northwestern University, Chicago, told this news organization.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

A historic explosion

It is estimated that approximately 14 million Lebanese citizens live outside their home country, which is more than double the population of Lebanon. However, the trauma-related mental health of these and other expatriate communities is understudied, said Dr. Rached.

“If you look at the literature, next to no one has examined expatriates’ mental health, and more so in the context of trauma.”

Dr. Rached has personal experience with the event. She was in Beirut on Aug. 4, 2020, when the Lebanese capital was rocked by an explosion attributed to ammonium nitrate stored at the city’s port. It was one of the biggest nonnuclear explosions in history and left hundreds homeless, killed, or injured. Dr. Rached watched as her father was injured and her house destroyed.

She heard anecdotes of Lebanese expatriates, experiencing trauma as a result of the blast. Many were unable to contact friends and loved ones in the wake of the tragedy.

“That prompted us to look at expatriate mental health following this traumatic incident,” she said.

She and her colleagues used various social media platforms to advertise the survey. They also reached out to the International Lebanese Medical Association, which has “a strong base” in the United States, said Dr. Rached.

She was “shocked” at how many expatriates responded. “People really wanted to speak up and express themselves” – whether because of survivor’s guilt or for some other reason, she said.

The survey included 670 adults with Lebanese nationality or who were first generation Lebanese living abroad. The study population had a median age 31 years and 62.2% female, most living in North America or Europe. Over one-third of respondents (270) had been living abroad from 1-5 years but many had been away for more than 20 years.

Study participants completed the Hopkins Symptoms Checklist (HSCL), which screens for anxiety and depression. On this checklist, a score of 1.75 is a typical cutoff value for symptomatic cases.

The investigators found 41.2% of participants scored higher than this threshold. Being younger, female and visiting Lebanon at the time of the blast, were factors associated with higher HSCL scores.
 

No tincture of time

Interestingly, the amount of time since emigrating from Lebanon was unrelated to the score. “Our results show that, no matter how long you’ve been away, you’re prone to the same negative outcome,” said Dr. Rached.

Of the total study population, 268 personally experienced the explosion and/or had close friends or family physically affected by it. These expatriates completed the Post-traumatic Checklist for DSM-5 (PCL-5).

Here, the analysis showed that many of these respondents (57.5%) scored above 33, which is higher than the threshold for probable PTSD. Being female was linked to higher PCL-5 scores.

These findings suggest the mental health of expatriates may be negatively affected by traumatic incidents in their home countries, even if they didn’t witness the event firsthand and have been away from their home country for a long time.

The results may be especially timely as many countries are taking in a flood of refugees fleeing war in Ukraine. However, Dr. Rached said, the findings from her research may not apply to Ukrainians.

“I don’t think the results can be extrapolated, given that the nature of the trauma is a little bit different,” she said, adding that the Beirut blast was “monumental” but it was over quickly. In contrast, there’s no end in sight for the Russian invasion of Ukraine.

Dr. Rached noted the study data are preliminary and limited because there’s no way to determine whether respondents had mental health issues before the blast.
 

Global psychiatrist shortage

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry in Omaha, and incoming chair of the APA’s Council on Communications, said he found the presentation “fascinating on several levels.”

It’s increasingly important for psychiatrists to be “trauma informed,” Dr. Liu told a press briefing highlighting the study. “It’s not just about looking at the biological correlates of illness,” meaning looking at genetic markers etc, “but also looking at the environment in which people live, work, and/or are in therapy or in treatment.”

In a later interview, Dr. Liu said he was impressed by the fact that Dr. Rached, who has “a very deep personal connection to this community,” is using her own personal trauma to help identify others are at risk who may need future care.

Dr. Liu, whose own family sponsors Afghan refugees, said the research underlines the need to ensure training for psychiatrists everywhere to help manage the expatriate population. As it stands, there’s “a huge shortage of psychiatrists around the world,” particularly in countries that have been affected by trauma, said Dr. Liu.

The researchers and Dr. Liu reported no relevant financial relationships.

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

To the Editor:

A 58-year-old man with a pigmented lesion on the left lower eyelid was referred to the oculoplastic clinic by an outside ophthalmologist. The patient had noticed the lesion growing over the course of the last 4 to 5 months. He reported scant amounts of blood and discharge coming from the nose and left eye the week prior, which persisted for 3 days. He had no associated pain or discomfort. A slit-lamp examination revealed a pigmented left lower eyelid lesion measuring 20×15 mm with telangiectasia and an eyelid margin abnormality with no palpable lymphadenopathy. The patient was diagnosed with clinical stage T3N0M0 malignant conjunctival melanoma of the left eyelid based on the American Joint Committee on Cancer classification. It is thought to have originated from conjunctival primary acquired melanosis (PAM). The T3 stage is defined as malignant melanoma with local invasion; the lesion involved the eyelid and puncta as well as canalicular portions of the lacrimal drainage system.¹ The bloody discharge was attributed to the involvement of the canalicular system, which drains tears from the eye to the nose. Melanomas can bleed, so any bloody discharge from the eye also will come through the ipsilateral nasal passage. Oncology evaluated the lesion to help determine the stage, and they found no lymph node involvement or brain, neck, chest, abdominal, or pelvic metastasis by computed tomography and magnetic resonance imaging. Sentinel lymph node biopsy was discussed with head and neck oncology specialists and was ultimately not performed per the recommendation from the Head and Neck Oncology Board; it is not a common modality for managing conjunctival melanoma because it has not been shown to alter morbidity and mortality.

The entire eyelid from the medial canthus to the lateral canthus was removed without touching the pigmented mass to ensure a “no-touch” technique removal of the mass. The no-touch technique primarily is utilized to decrease the likelihood of instrumental seeding of healthy tissues or the vascular system.² This technique focuses on preventing any direct manipulation of the tumor and avoiding an incisional biopsy as well as removal of the tumor en bloc. The margins were cutaneous—3 mm lateral to the lateral canthus, 5 mm below the lid margin, and 3 mm medial to the medial canthus—with dissection of the medial tissue from the orbital rim and lacrimal sac fossa. The lacrimal sac and lower canaliculus were then resected. The conjunctiva 5 mm inferior to the pigmented mass and the entire palpebral conjunctiva was resected to the inferior fornix across the entire palpebral conjunctiva of the lower eyelid (Figure). The eyelid and lacrimal portions were removed as a unit. Essentially, the entire lower eyelid (full thickness), including the lateral canthus, medial canthus, canaliculus, and lacrimal sac, were removed en bloc. The final tumor staging after tissue evaluation by pathology and systemic evaluation by oncology was pT3N0bM0.

A tarsoconjunctival (Hughes) flap from the upper eyelid was used to reconstruct the posterior lamella (tarsus/conjunctiva) of the lower eyelid, and a full-thickness skin graft harvested from the ipsilateral upper eyelid was used to reconstruct the anterior lamella (skin) of the lower eyelid. The reconstruction site was allowed to heal for 4 weeks before severing the tarsoconjunctival graft to allow the separation of the upper and lower eyelids. Adjunctive topical ophthalmic chemotherapy (mitomycin C 0.04%) was started 4 weeks after the last surgery. The medication was applied 4 times daily for 1 week and restarted after the conjunctival erythema and injection subsided, which was approximately 2.5 weeks, on average. The regimen of applying the medication (1 week on and 2.5 weeks off) was completed for 4 cycles. At 1 year follow-up after his diagnosis, the patient was without local recurrence or evidence of systemic metastasis. We plan to have him continue ophthalmic and oncologic evaluation every 3 to 4 months for the next 24 months, and then every 6 months for years 2 through 5.

Ocular melanoma can be further divided into uveal and conjunctival types, both arising from the respective tissue. Melanoma of the conjunctiva commonly arises from PAM with atypia, which is an acquired conjunctival pigmented lesion similar to a skin nevus that has the potential to become dysplastic. In a genetic analysis of 78 conjunctival melanomas, BRAF mutations were identified in 29% (23/78) of tumors, and NRAS mutations were detected in 18% (14/78) of tumors³; however, in our case, there were no BRAF or NRAS mutations detected. In a study of 84,836 cases that included a diagnosis of melanoma, ocular melanoma comprised 5.2% of melanomas, with cutaneous, mucosal, and unknown primary sites totaling the remaining percentage of melanomas. Of 4522 patients with ocular melanomas, 85% had uveal melanomas; 4.8% had conjunctival melanoma; and 10.2% were classified as other—comprised of cornea, not otherwise specified (NOS); retina; lacrimal gland; orbit, NOS; overlapping lesion of the eye; and eye, NOS.⁴ Melanomas of the uvea, including the ciliary body, choroid, and iris, result from a notably different pathogenesis than conjunctival melanoma, with the former being primarily associated with GNAQ and GNA mutations.³ Ciliary body and choroidal melanomas each have a different pathogenesis for occurrence, with choroidal melanoma being mostly from metastasis and ciliary body melanoma from mutations or metastasis.

Pigmented lesions on the conjunctiva or sclera arise from either melanocytes or nonmelanocytes and have a diverse differential diagnosis, including congenital melanosis, conjunctival nevi, PAM or secondary acquired melanosis, or conjunctival melanoma. The diagnosis of uveal melanoma should be based on fundoscopic examination by an experienced clinician. Uveal melanoma is unlike most other cancers in that diagnosis can be by clinical fundoscopic examination alone. Imaging studies such as ultrasound and fluorescein angiography can be performed for prognostication and characterization. Fine needle aspiration biopsy for molecular analysis is becoming more routine, but the results rarely affect the plan of care. Primary treatment of uveal melanoma should strive to preserve vision and prevent metastasis; however, a primary modality has yet to show notable results in decreasing distant disease spread or overall survival. Treatment of the primary tumor should involve consideration of tumor size, location, health of the patient, and patient preference.^1,5

For patients with melanoma arising from the conjunctiva, initial management should focus on local disease control, including wide local excision to avoid seeding, supplemented with cryotherapy and alcohol epitheliectomy to the cornea to ensure local tumor extinction.^2,6 Techniques including enucleation and orbital exenteration historically have been used for treatment of extensive disease, but this approach has not been associated with improvement in mortality and is a cause of notable morbidity.^7,8 Sentinel lymph node biopsy has an established role in the management of cutaneous melanoma, but its use in the setting of conjunctival melanoma is controversial, with studies showing that up to 50% of patients with local recurrence can develop distant metastasis with no evidence of regional lymph node involvement.^9,10 When the tumor is present at the surgical margins or in the case that lesions cannot be fully excised, adjuvant therapy may improve long-term control and prevent recurrence following surgical intervention. Mitomycin C 0.04% is the most commonly used topical chemotherapy agent because it has an established role in the treatment of PAM, but it remains adjuvant therapy for conjunctival melanoma due to the relatively poor outcomes when it is used for primary therapy.¹¹

In one study, recurrence rates for conjunctival melanoma were 26%, 51%, and 65% at 5, 10, and 15 years, respectively.¹² Risk factors for recurrence include increased tumor thickness, incomplete excision, positive margins, surgical excision without adjuvant therapy, and nonlimbal location.¹³ A multivariate analysis of 150 patients showed that the melanoma location not touching the limbus (P=.01) and pathologic evidence of tumor to the lateral margin (P=.02) were related to tumor recurrence, with relative risks (IQR) of 2.3 (1.2-4.6) and 2.9 (1.2-7.1), respectively. Careful surgical planning using wide microsurgical excisional biopsy emphasizing a no-touch technique as well as supplemental alcohol therapy for the cornea and conjunctiva is advised.¹²

To the Editor:

A 58-year-old man with a pigmented lesion on the left lower eyelid was referred to the oculoplastic clinic by an outside ophthalmologist. The patient had noticed the lesion growing over the course of the last 4 to 5 months. He reported scant amounts of blood and discharge coming from the nose and left eye the week prior, which persisted for 3 days. He had no associated pain or discomfort. A slit-lamp examination revealed a pigmented left lower eyelid lesion measuring 20×15 mm with telangiectasia and an eyelid margin abnormality with no palpable lymphadenopathy. The patient was diagnosed with clinical stage T3N0M0 malignant conjunctival melanoma of the left eyelid based on the American Joint Committee on Cancer classification. It is thought to have originated from conjunctival primary acquired melanosis (PAM). The T3 stage is defined as malignant melanoma with local invasion; the lesion involved the eyelid and puncta as well as canalicular portions of the lacrimal drainage system.¹ The bloody discharge was attributed to the involvement of the canalicular system, which drains tears from the eye to the nose. Melanomas can bleed, so any bloody discharge from the eye also will come through the ipsilateral nasal passage. Oncology evaluated the lesion to help determine the stage, and they found no lymph node involvement or brain, neck, chest, abdominal, or pelvic metastasis by computed tomography and magnetic resonance imaging. Sentinel lymph node biopsy was discussed with head and neck oncology specialists and was ultimately not performed per the recommendation from the Head and Neck Oncology Board; it is not a common modality for managing conjunctival melanoma because it has not been shown to alter morbidity and mortality.

The entire eyelid from the medial canthus to the lateral canthus was removed without touching the pigmented mass to ensure a “no-touch” technique removal of the mass. The no-touch technique primarily is utilized to decrease the likelihood of instrumental seeding of healthy tissues or the vascular system.² This technique focuses on preventing any direct manipulation of the tumor and avoiding an incisional biopsy as well as removal of the tumor en bloc. The margins were cutaneous—3 mm lateral to the lateral canthus, 5 mm below the lid margin, and 3 mm medial to the medial canthus—with dissection of the medial tissue from the orbital rim and lacrimal sac fossa. The lacrimal sac and lower canaliculus were then resected. The conjunctiva 5 mm inferior to the pigmented mass and the entire palpebral conjunctiva was resected to the inferior fornix across the entire palpebral conjunctiva of the lower eyelid (Figure). The eyelid and lacrimal portions were removed as a unit. Essentially, the entire lower eyelid (full thickness), including the lateral canthus, medial canthus, canaliculus, and lacrimal sac, were removed en bloc. The final tumor staging after tissue evaluation by pathology and systemic evaluation by oncology was pT3N0bM0.

A tarsoconjunctival (Hughes) flap from the upper eyelid was used to reconstruct the posterior lamella (tarsus/conjunctiva) of the lower eyelid, and a full-thickness skin graft harvested from the ipsilateral upper eyelid was used to reconstruct the anterior lamella (skin) of the lower eyelid. The reconstruction site was allowed to heal for 4 weeks before severing the tarsoconjunctival graft to allow the separation of the upper and lower eyelids. Adjunctive topical ophthalmic chemotherapy (mitomycin C 0.04%) was started 4 weeks after the last surgery. The medication was applied 4 times daily for 1 week and restarted after the conjunctival erythema and injection subsided, which was approximately 2.5 weeks, on average. The regimen of applying the medication (1 week on and 2.5 weeks off) was completed for 4 cycles. At 1 year follow-up after his diagnosis, the patient was without local recurrence or evidence of systemic metastasis. We plan to have him continue ophthalmic and oncologic evaluation every 3 to 4 months for the next 24 months, and then every 6 months for years 2 through 5.

Ocular melanoma can be further divided into uveal and conjunctival types, both arising from the respective tissue. Melanoma of the conjunctiva commonly arises from PAM with atypia, which is an acquired conjunctival pigmented lesion similar to a skin nevus that has the potential to become dysplastic. In a genetic analysis of 78 conjunctival melanomas, BRAF mutations were identified in 29% (23/78) of tumors, and NRAS mutations were detected in 18% (14/78) of tumors³; however, in our case, there were no BRAF or NRAS mutations detected. In a study of 84,836 cases that included a diagnosis of melanoma, ocular melanoma comprised 5.2% of melanomas, with cutaneous, mucosal, and unknown primary sites totaling the remaining percentage of melanomas. Of 4522 patients with ocular melanomas, 85% had uveal melanomas; 4.8% had conjunctival melanoma; and 10.2% were classified as other—comprised of cornea, not otherwise specified (NOS); retina; lacrimal gland; orbit, NOS; overlapping lesion of the eye; and eye, NOS.⁴ Melanomas of the uvea, including the ciliary body, choroid, and iris, result from a notably different pathogenesis than conjunctival melanoma, with the former being primarily associated with GNAQ and GNA mutations.³ Ciliary body and choroidal melanomas each have a different pathogenesis for occurrence, with choroidal melanoma being mostly from metastasis and ciliary body melanoma from mutations or metastasis.

Pigmented lesions on the conjunctiva or sclera arise from either melanocytes or nonmelanocytes and have a diverse differential diagnosis, including congenital melanosis, conjunctival nevi, PAM or secondary acquired melanosis, or conjunctival melanoma. The diagnosis of uveal melanoma should be based on fundoscopic examination by an experienced clinician. Uveal melanoma is unlike most other cancers in that diagnosis can be by clinical fundoscopic examination alone. Imaging studies such as ultrasound and fluorescein angiography can be performed for prognostication and characterization. Fine needle aspiration biopsy for molecular analysis is becoming more routine, but the results rarely affect the plan of care. Primary treatment of uveal melanoma should strive to preserve vision and prevent metastasis; however, a primary modality has yet to show notable results in decreasing distant disease spread or overall survival. Treatment of the primary tumor should involve consideration of tumor size, location, health of the patient, and patient preference.^1,5

For patients with melanoma arising from the conjunctiva, initial management should focus on local disease control, including wide local excision to avoid seeding, supplemented with cryotherapy and alcohol epitheliectomy to the cornea to ensure local tumor extinction.^2,6 Techniques including enucleation and orbital exenteration historically have been used for treatment of extensive disease, but this approach has not been associated with improvement in mortality and is a cause of notable morbidity.^7,8 Sentinel lymph node biopsy has an established role in the management of cutaneous melanoma, but its use in the setting of conjunctival melanoma is controversial, with studies showing that up to 50% of patients with local recurrence can develop distant metastasis with no evidence of regional lymph node involvement.^9,10 When the tumor is present at the surgical margins or in the case that lesions cannot be fully excised, adjuvant therapy may improve long-term control and prevent recurrence following surgical intervention. Mitomycin C 0.04% is the most commonly used topical chemotherapy agent because it has an established role in the treatment of PAM, but it remains adjuvant therapy for conjunctival melanoma due to the relatively poor outcomes when it is used for primary therapy.¹¹

In one study, recurrence rates for conjunctival melanoma were 26%, 51%, and 65% at 5, 10, and 15 years, respectively.¹² Risk factors for recurrence include increased tumor thickness, incomplete excision, positive margins, surgical excision without adjuvant therapy, and nonlimbal location.¹³ A multivariate analysis of 150 patients showed that the melanoma location not touching the limbus (P=.01) and pathologic evidence of tumor to the lateral margin (P=.02) were related to tumor recurrence, with relative risks (IQR) of 2.3 (1.2-4.6) and 2.9 (1.2-7.1), respectively. Careful surgical planning using wide microsurgical excisional biopsy emphasizing a no-touch technique as well as supplemental alcohol therapy for the cornea and conjunctiva is advised.¹²

To the Editor:

A 58-year-old man with a pigmented lesion on the left lower eyelid was referred to the oculoplastic clinic by an outside ophthalmologist. The patient had noticed the lesion growing over the course of the last 4 to 5 months. He reported scant amounts of blood and discharge coming from the nose and left eye the week prior, which persisted for 3 days. He had no associated pain or discomfort. A slit-lamp examination revealed a pigmented left lower eyelid lesion measuring 20×15 mm with telangiectasia and an eyelid margin abnormality with no palpable lymphadenopathy. The patient was diagnosed with clinical stage T3N0M0 malignant conjunctival melanoma of the left eyelid based on the American Joint Committee on Cancer classification. It is thought to have originated from conjunctival primary acquired melanosis (PAM). The T3 stage is defined as malignant melanoma with local invasion; the lesion involved the eyelid and puncta as well as canalicular portions of the lacrimal drainage system.¹ The bloody discharge was attributed to the involvement of the canalicular system, which drains tears from the eye to the nose. Melanomas can bleed, so any bloody discharge from the eye also will come through the ipsilateral nasal passage. Oncology evaluated the lesion to help determine the stage, and they found no lymph node involvement or brain, neck, chest, abdominal, or pelvic metastasis by computed tomography and magnetic resonance imaging. Sentinel lymph node biopsy was discussed with head and neck oncology specialists and was ultimately not performed per the recommendation from the Head and Neck Oncology Board; it is not a common modality for managing conjunctival melanoma because it has not been shown to alter morbidity and mortality.

The entire eyelid from the medial canthus to the lateral canthus was removed without touching the pigmented mass to ensure a “no-touch” technique removal of the mass. The no-touch technique primarily is utilized to decrease the likelihood of instrumental seeding of healthy tissues or the vascular system.² This technique focuses on preventing any direct manipulation of the tumor and avoiding an incisional biopsy as well as removal of the tumor en bloc. The margins were cutaneous—3 mm lateral to the lateral canthus, 5 mm below the lid margin, and 3 mm medial to the medial canthus—with dissection of the medial tissue from the orbital rim and lacrimal sac fossa. The lacrimal sac and lower canaliculus were then resected. The conjunctiva 5 mm inferior to the pigmented mass and the entire palpebral conjunctiva was resected to the inferior fornix across the entire palpebral conjunctiva of the lower eyelid (Figure). The eyelid and lacrimal portions were removed as a unit. Essentially, the entire lower eyelid (full thickness), including the lateral canthus, medial canthus, canaliculus, and lacrimal sac, were removed en bloc. The final tumor staging after tissue evaluation by pathology and systemic evaluation by oncology was pT3N0bM0.

A tarsoconjunctival (Hughes) flap from the upper eyelid was used to reconstruct the posterior lamella (tarsus/conjunctiva) of the lower eyelid, and a full-thickness skin graft harvested from the ipsilateral upper eyelid was used to reconstruct the anterior lamella (skin) of the lower eyelid. The reconstruction site was allowed to heal for 4 weeks before severing the tarsoconjunctival graft to allow the separation of the upper and lower eyelids. Adjunctive topical ophthalmic chemotherapy (mitomycin C 0.04%) was started 4 weeks after the last surgery. The medication was applied 4 times daily for 1 week and restarted after the conjunctival erythema and injection subsided, which was approximately 2.5 weeks, on average. The regimen of applying the medication (1 week on and 2.5 weeks off) was completed for 4 cycles. At 1 year follow-up after his diagnosis, the patient was without local recurrence or evidence of systemic metastasis. We plan to have him continue ophthalmic and oncologic evaluation every 3 to 4 months for the next 24 months, and then every 6 months for years 2 through 5.

Ocular melanoma can be further divided into uveal and conjunctival types, both arising from the respective tissue. Melanoma of the conjunctiva commonly arises from PAM with atypia, which is an acquired conjunctival pigmented lesion similar to a skin nevus that has the potential to become dysplastic. In a genetic analysis of 78 conjunctival melanomas, BRAF mutations were identified in 29% (23/78) of tumors, and NRAS mutations were detected in 18% (14/78) of tumors³; however, in our case, there were no BRAF or NRAS mutations detected. In a study of 84,836 cases that included a diagnosis of melanoma, ocular melanoma comprised 5.2% of melanomas, with cutaneous, mucosal, and unknown primary sites totaling the remaining percentage of melanomas. Of 4522 patients with ocular melanomas, 85% had uveal melanomas; 4.8% had conjunctival melanoma; and 10.2% were classified as other—comprised of cornea, not otherwise specified (NOS); retina; lacrimal gland; orbit, NOS; overlapping lesion of the eye; and eye, NOS.⁴ Melanomas of the uvea, including the ciliary body, choroid, and iris, result from a notably different pathogenesis than conjunctival melanoma, with the former being primarily associated with GNAQ and GNA mutations.³ Ciliary body and choroidal melanomas each have a different pathogenesis for occurrence, with choroidal melanoma being mostly from metastasis and ciliary body melanoma from mutations or metastasis.

Pigmented lesions on the conjunctiva or sclera arise from either melanocytes or nonmelanocytes and have a diverse differential diagnosis, including congenital melanosis, conjunctival nevi, PAM or secondary acquired melanosis, or conjunctival melanoma. The diagnosis of uveal melanoma should be based on fundoscopic examination by an experienced clinician. Uveal melanoma is unlike most other cancers in that diagnosis can be by clinical fundoscopic examination alone. Imaging studies such as ultrasound and fluorescein angiography can be performed for prognostication and characterization. Fine needle aspiration biopsy for molecular analysis is becoming more routine, but the results rarely affect the plan of care. Primary treatment of uveal melanoma should strive to preserve vision and prevent metastasis; however, a primary modality has yet to show notable results in decreasing distant disease spread or overall survival. Treatment of the primary tumor should involve consideration of tumor size, location, health of the patient, and patient preference.^1,5

For patients with melanoma arising from the conjunctiva, initial management should focus on local disease control, including wide local excision to avoid seeding, supplemented with cryotherapy and alcohol epitheliectomy to the cornea to ensure local tumor extinction.^2,6 Techniques including enucleation and orbital exenteration historically have been used for treatment of extensive disease, but this approach has not been associated with improvement in mortality and is a cause of notable morbidity.^7,8 Sentinel lymph node biopsy has an established role in the management of cutaneous melanoma, but its use in the setting of conjunctival melanoma is controversial, with studies showing that up to 50% of patients with local recurrence can develop distant metastasis with no evidence of regional lymph node involvement.^9,10 When the tumor is present at the surgical margins or in the case that lesions cannot be fully excised, adjuvant therapy may improve long-term control and prevent recurrence following surgical intervention. Mitomycin C 0.04% is the most commonly used topical chemotherapy agent because it has an established role in the treatment of PAM, but it remains adjuvant therapy for conjunctival melanoma due to the relatively poor outcomes when it is used for primary therapy.¹¹

In one study, recurrence rates for conjunctival melanoma were 26%, 51%, and 65% at 5, 10, and 15 years, respectively.¹² Risk factors for recurrence include increased tumor thickness, incomplete excision, positive margins, surgical excision without adjuvant therapy, and nonlimbal location.¹³ A multivariate analysis of 150 patients showed that the melanoma location not touching the limbus (P=.01) and pathologic evidence of tumor to the lateral margin (P=.02) were related to tumor recurrence, with relative risks (IQR) of 2.3 (1.2-4.6) and 2.9 (1.2-7.1), respectively. Careful surgical planning using wide microsurgical excisional biopsy emphasizing a no-touch technique as well as supplemental alcohol therapy for the cornea and conjunctiva is advised.¹²

The American Society for Reproductive Medicine’s classification system for müllerian anomalies was the standard until the revision in 2021 by ASRM, which updated and expanded the classification presenting nine classes and imaging criteria: müllerian agenesis, cervical agenesis, unicornuate, uterus didelphys, bicornuate, septate, longitudinal vaginal septum, transverse vaginal septum, and complex anomalies. This month’s article addresses müllerian anomalies from embryology to treatment options.

The early embryo has the capability of developing a wolffian (internal male) or müllerian (internal female) system. Unless anti-müllerian hormone (formerly müllerian-inhibiting substance) is produced, the embryo develops a female reproductive system beginning with two lateral uterine anlagen that fuse in the midline and canalize. Müllerian anomalies occur because of accidents during fusion and canalization (see Table).

The incidence of müllerian anomalies is difficult to discern, given the potential for a normal reproductive outcome precluding an evaluation and based on the population studied. Müllerian anomalies are found in approximately 4.3% of fertile women, 3.5%-8% of infertile patients, 12.3%-13% of those with recurrent pregnancy losses, and 24.5% of patients with miscarriage and infertility. Of the müllerian anomalies, the most common is septate (35%), followed by bicornuate (26%), arcuate (18%), unicornuate (10%), didelphys (8%), and agenesis (3%) (Hum Reprod Update. 2001;7[2]:161; Hum Reprod Update. 2011;17[6]:761-71).

In 20%-30% of patients with müllerian anomalies, particularly in women with a unicornuate uterus, renal anomalies exist that are typically ipsilateral to the absent or rudimentary contralateral uterine horn (J Pediatr Adolesc Gynecol. 2021;34[2]:154-60). As there is no definitive evidence to suggest an association between a septate uterus and renal anomalies, the renal system evaluation can be deferred in this population (Fertil Steril. 2021 Nov;116[5]:1238-52).
 

Diagnosis

2-D ultrasound can be a screen for müllerian anomalies and genitourinary anatomic variants. The diagnostic accuracy of 3-D ultrasound with müllerian anomalies is reported to be 97.6% with sensitivity and specificity of 98.3% and 99.4%, respectively (Hum. Reprod. 2016;31[1]:2-7). As a result, office 3-D has essentially replaced MRI in the diagnosis of müllerian anomalies (Ultrasound Obstet Gynecol. 2015 Nov;46[5]:616-22), with one exception because of the avoidance of a transvaginal probe in the non–sexually active adult and younger adolescent/child. MRI is reserved for diagnosing complex müllerian anomalies or if there is a diagnostic challenge.

Criteria to diagnose müllerian anomalies by radiology begins with the “reference line,” i.e., a line joining both tubal ostia (interostial line). A septate uterus is diagnosed if the distance from the interostial line to the cephalad endometrium is more than 1 cm, otherwise it is considered normal or arcuate based on its appearance. An arcuate uterus has not been associated with impaired reproduction and can be viewed as a normal variant. Alternatively, a bicornuate uterus is diagnosed when the external fundal indentation is more than 1 cm (Fertil Steril. 2021 Nov;116[5]:1238-52).
 

Clinical course

Women with müllerian anomalies may experience pelvic pain and prolonged and/or abnormal bleeding at the time of menarche. While the ability to conceive may not be impaired from müllerian anomalies with the possible exception of the septate uterus, the pregnancy course can be affected, i.e., recurrent pregnancy loss, preterm birth, perinatal mortality, and malpresentation in labor (Reprod Biomed Online. 2014;29[6]:665). In women with septate, bicornuate, and uterine didelphys, fetal growth restriction appears to be increased. Spontaneous abortion rates of 32% and preterm birth rates of 28% have been reported in patients with uterus didelphys (Obstet Gynecol. 1990;75[6]:906).

Special consideration of the unicornuate is given because of the potential for a rudimentary horn that may communicate with the main uterine cavity and/or have functional endometrium which places the woman at risk of an ectopic pregnancy in the smaller horn. Patients with a unicornuate uterus are at higher risk for preterm labor and breech presentation. An obstructed (noncommunicating) functional rudimentary horn is a risk for endometriosis with cyclic pain because of outflow tract obstruction and an ectopic pregnancy prompting consideration for hemihysterectomy based on symptoms.
 

The septate uterus – old dogma revisited

The incidence of uterine septa is approximately 1-15 per 1,000. As the most common müllerian anomaly, the septate uterus has traditionally been associated with an increased risk for spontaneous abortion (21%-44%) and preterm birth (12%-33%). The live birth rate ranges from 50% to 72% (Hum Reprod Update. 2001;7[2]:161-74). A uterine septum is believed to develop as a result of failure of resorption of the tissue connecting the two paramesonephric (müllerian) ducts prior to the 20th embryonic week.

Incising the uterine septum (metroplasty) dates back to 1884 when Ruge described a blind transcervical metroplasty in a woman with two previous miscarriages who, postoperatively, delivered a healthy baby. In the early 1900s, Tompkins reported an abdominal metroplasty (Fertil Stertil. 2021;115:1140-2). The decision to proceed with metroplasty is based on only established observational studies (Fertil Steril. 2016;106:530-40). Until recently, the majority of studies suggested that metroplasty is associated with decreased spontaneous abortion rates and improved obstetrical outcomes. A retrospective case series of 361 patients with a septate uterus who had primary infertility of >2 years’ duration, a history of 1-2 spontaneous abortions, or recurrent pregnancy loss suggested a significant improvement in the live birth rate and reduction in miscarriage (Arch Gynecol Obstet. 2003;268:289-92). A meta-analysis found that the overall pregnancy rate after septum incision was 67.8% and the live-birth rate was 53.5% (J Minim Invas Gynecol. 2013;20:22-42).

Recently, two multinational studies question the prevailing dogma (Fertil Steril. 2021 Sep;116[3]:693-4). Both studies could not demonstrate any increase in live birth rate, reduction in preterm birth, or in pregnancy loss after metroplasty. A significant limitation was the lack of a uniform consensus on the definition of the septate uterus and allowing the discretion of the physician to diagnosis a septum (Hum Reprod. 2020;35:1578-88; Hum Reprod. 2021;36:1260-7).

Hysteroscopic metroplasty is not without complications. Uterine rupture during pregnancy or delivery, while rare, may be linked to significant entry into the myometrium and/or overzealous cauterization and perforation, which emphasizes the importance of appropriate techniques.
 

Conclusion

A diagnosis of müllerian anomalies justifies a comprehensive consultation with the patient given the risk of pregnancy complications. Management of the septate uterus has become controversial. In a patient with infertility, prior pregnancy loss, or poor obstetrical outcome, it is reasonable to consider metroplasty; otherwise, expectant management is an option.

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Email him at [email protected].

The American Society for Reproductive Medicine’s classification system for müllerian anomalies was the standard until the revision in 2021 by ASRM, which updated and expanded the classification presenting nine classes and imaging criteria: müllerian agenesis, cervical agenesis, unicornuate, uterus didelphys, bicornuate, septate, longitudinal vaginal septum, transverse vaginal septum, and complex anomalies. This month’s article addresses müllerian anomalies from embryology to treatment options.

The early embryo has the capability of developing a wolffian (internal male) or müllerian (internal female) system. Unless anti-müllerian hormone (formerly müllerian-inhibiting substance) is produced, the embryo develops a female reproductive system beginning with two lateral uterine anlagen that fuse in the midline and canalize. Müllerian anomalies occur because of accidents during fusion and canalization (see Table).

The incidence of müllerian anomalies is difficult to discern, given the potential for a normal reproductive outcome precluding an evaluation and based on the population studied. Müllerian anomalies are found in approximately 4.3% of fertile women, 3.5%-8% of infertile patients, 12.3%-13% of those with recurrent pregnancy losses, and 24.5% of patients with miscarriage and infertility. Of the müllerian anomalies, the most common is septate (35%), followed by bicornuate (26%), arcuate (18%), unicornuate (10%), didelphys (8%), and agenesis (3%) (Hum Reprod Update. 2001;7[2]:161; Hum Reprod Update. 2011;17[6]:761-71).

In 20%-30% of patients with müllerian anomalies, particularly in women with a unicornuate uterus, renal anomalies exist that are typically ipsilateral to the absent or rudimentary contralateral uterine horn (J Pediatr Adolesc Gynecol. 2021;34[2]:154-60). As there is no definitive evidence to suggest an association between a septate uterus and renal anomalies, the renal system evaluation can be deferred in this population (Fertil Steril. 2021 Nov;116[5]:1238-52).
 

Diagnosis

2-D ultrasound can be a screen for müllerian anomalies and genitourinary anatomic variants. The diagnostic accuracy of 3-D ultrasound with müllerian anomalies is reported to be 97.6% with sensitivity and specificity of 98.3% and 99.4%, respectively (Hum. Reprod. 2016;31[1]:2-7). As a result, office 3-D has essentially replaced MRI in the diagnosis of müllerian anomalies (Ultrasound Obstet Gynecol. 2015 Nov;46[5]:616-22), with one exception because of the avoidance of a transvaginal probe in the non–sexually active adult and younger adolescent/child. MRI is reserved for diagnosing complex müllerian anomalies or if there is a diagnostic challenge.

Criteria to diagnose müllerian anomalies by radiology begins with the “reference line,” i.e., a line joining both tubal ostia (interostial line). A septate uterus is diagnosed if the distance from the interostial line to the cephalad endometrium is more than 1 cm, otherwise it is considered normal or arcuate based on its appearance. An arcuate uterus has not been associated with impaired reproduction and can be viewed as a normal variant. Alternatively, a bicornuate uterus is diagnosed when the external fundal indentation is more than 1 cm (Fertil Steril. 2021 Nov;116[5]:1238-52).
 

Clinical course

Women with müllerian anomalies may experience pelvic pain and prolonged and/or abnormal bleeding at the time of menarche. While the ability to conceive may not be impaired from müllerian anomalies with the possible exception of the septate uterus, the pregnancy course can be affected, i.e., recurrent pregnancy loss, preterm birth, perinatal mortality, and malpresentation in labor (Reprod Biomed Online. 2014;29[6]:665). In women with septate, bicornuate, and uterine didelphys, fetal growth restriction appears to be increased. Spontaneous abortion rates of 32% and preterm birth rates of 28% have been reported in patients with uterus didelphys (Obstet Gynecol. 1990;75[6]:906).

Special consideration of the unicornuate is given because of the potential for a rudimentary horn that may communicate with the main uterine cavity and/or have functional endometrium which places the woman at risk of an ectopic pregnancy in the smaller horn. Patients with a unicornuate uterus are at higher risk for preterm labor and breech presentation. An obstructed (noncommunicating) functional rudimentary horn is a risk for endometriosis with cyclic pain because of outflow tract obstruction and an ectopic pregnancy prompting consideration for hemihysterectomy based on symptoms.
 

The septate uterus – old dogma revisited

The incidence of uterine septa is approximately 1-15 per 1,000. As the most common müllerian anomaly, the septate uterus has traditionally been associated with an increased risk for spontaneous abortion (21%-44%) and preterm birth (12%-33%). The live birth rate ranges from 50% to 72% (Hum Reprod Update. 2001;7[2]:161-74). A uterine septum is believed to develop as a result of failure of resorption of the tissue connecting the two paramesonephric (müllerian) ducts prior to the 20th embryonic week.

Incising the uterine septum (metroplasty) dates back to 1884 when Ruge described a blind transcervical metroplasty in a woman with two previous miscarriages who, postoperatively, delivered a healthy baby. In the early 1900s, Tompkins reported an abdominal metroplasty (Fertil Stertil. 2021;115:1140-2). The decision to proceed with metroplasty is based on only established observational studies (Fertil Steril. 2016;106:530-40). Until recently, the majority of studies suggested that metroplasty is associated with decreased spontaneous abortion rates and improved obstetrical outcomes. A retrospective case series of 361 patients with a septate uterus who had primary infertility of >2 years’ duration, a history of 1-2 spontaneous abortions, or recurrent pregnancy loss suggested a significant improvement in the live birth rate and reduction in miscarriage (Arch Gynecol Obstet. 2003;268:289-92). A meta-analysis found that the overall pregnancy rate after septum incision was 67.8% and the live-birth rate was 53.5% (J Minim Invas Gynecol. 2013;20:22-42).

Recently, two multinational studies question the prevailing dogma (Fertil Steril. 2021 Sep;116[3]:693-4). Both studies could not demonstrate any increase in live birth rate, reduction in preterm birth, or in pregnancy loss after metroplasty. A significant limitation was the lack of a uniform consensus on the definition of the septate uterus and allowing the discretion of the physician to diagnosis a septum (Hum Reprod. 2020;35:1578-88; Hum Reprod. 2021;36:1260-7).

Hysteroscopic metroplasty is not without complications. Uterine rupture during pregnancy or delivery, while rare, may be linked to significant entry into the myometrium and/or overzealous cauterization and perforation, which emphasizes the importance of appropriate techniques.
 

Conclusion

A diagnosis of müllerian anomalies justifies a comprehensive consultation with the patient given the risk of pregnancy complications. Management of the septate uterus has become controversial. In a patient with infertility, prior pregnancy loss, or poor obstetrical outcome, it is reasonable to consider metroplasty; otherwise, expectant management is an option.

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Email him at [email protected].

The American Society for Reproductive Medicine’s classification system for müllerian anomalies was the standard until the revision in 2021 by ASRM, which updated and expanded the classification presenting nine classes and imaging criteria: müllerian agenesis, cervical agenesis, unicornuate, uterus didelphys, bicornuate, septate, longitudinal vaginal septum, transverse vaginal septum, and complex anomalies. This month’s article addresses müllerian anomalies from embryology to treatment options.

The early embryo has the capability of developing a wolffian (internal male) or müllerian (internal female) system. Unless anti-müllerian hormone (formerly müllerian-inhibiting substance) is produced, the embryo develops a female reproductive system beginning with two lateral uterine anlagen that fuse in the midline and canalize. Müllerian anomalies occur because of accidents during fusion and canalization (see Table).

The incidence of müllerian anomalies is difficult to discern, given the potential for a normal reproductive outcome precluding an evaluation and based on the population studied. Müllerian anomalies are found in approximately 4.3% of fertile women, 3.5%-8% of infertile patients, 12.3%-13% of those with recurrent pregnancy losses, and 24.5% of patients with miscarriage and infertility. Of the müllerian anomalies, the most common is septate (35%), followed by bicornuate (26%), arcuate (18%), unicornuate (10%), didelphys (8%), and agenesis (3%) (Hum Reprod Update. 2001;7[2]:161; Hum Reprod Update. 2011;17[6]:761-71).

In 20%-30% of patients with müllerian anomalies, particularly in women with a unicornuate uterus, renal anomalies exist that are typically ipsilateral to the absent or rudimentary contralateral uterine horn (J Pediatr Adolesc Gynecol. 2021;34[2]:154-60). As there is no definitive evidence to suggest an association between a septate uterus and renal anomalies, the renal system evaluation can be deferred in this population (Fertil Steril. 2021 Nov;116[5]:1238-52).
 

Diagnosis

2-D ultrasound can be a screen for müllerian anomalies and genitourinary anatomic variants. The diagnostic accuracy of 3-D ultrasound with müllerian anomalies is reported to be 97.6% with sensitivity and specificity of 98.3% and 99.4%, respectively (Hum. Reprod. 2016;31[1]:2-7). As a result, office 3-D has essentially replaced MRI in the diagnosis of müllerian anomalies (Ultrasound Obstet Gynecol. 2015 Nov;46[5]:616-22), with one exception because of the avoidance of a transvaginal probe in the non–sexually active adult and younger adolescent/child. MRI is reserved for diagnosing complex müllerian anomalies or if there is a diagnostic challenge.

Criteria to diagnose müllerian anomalies by radiology begins with the “reference line,” i.e., a line joining both tubal ostia (interostial line). A septate uterus is diagnosed if the distance from the interostial line to the cephalad endometrium is more than 1 cm, otherwise it is considered normal or arcuate based on its appearance. An arcuate uterus has not been associated with impaired reproduction and can be viewed as a normal variant. Alternatively, a bicornuate uterus is diagnosed when the external fundal indentation is more than 1 cm (Fertil Steril. 2021 Nov;116[5]:1238-52).
 

Clinical course

Women with müllerian anomalies may experience pelvic pain and prolonged and/or abnormal bleeding at the time of menarche. While the ability to conceive may not be impaired from müllerian anomalies with the possible exception of the septate uterus, the pregnancy course can be affected, i.e., recurrent pregnancy loss, preterm birth, perinatal mortality, and malpresentation in labor (Reprod Biomed Online. 2014;29[6]:665). In women with septate, bicornuate, and uterine didelphys, fetal growth restriction appears to be increased. Spontaneous abortion rates of 32% and preterm birth rates of 28% have been reported in patients with uterus didelphys (Obstet Gynecol. 1990;75[6]:906).

Special consideration of the unicornuate is given because of the potential for a rudimentary horn that may communicate with the main uterine cavity and/or have functional endometrium which places the woman at risk of an ectopic pregnancy in the smaller horn. Patients with a unicornuate uterus are at higher risk for preterm labor and breech presentation. An obstructed (noncommunicating) functional rudimentary horn is a risk for endometriosis with cyclic pain because of outflow tract obstruction and an ectopic pregnancy prompting consideration for hemihysterectomy based on symptoms.
 

The septate uterus – old dogma revisited

The incidence of uterine septa is approximately 1-15 per 1,000. As the most common müllerian anomaly, the septate uterus has traditionally been associated with an increased risk for spontaneous abortion (21%-44%) and preterm birth (12%-33%). The live birth rate ranges from 50% to 72% (Hum Reprod Update. 2001;7[2]:161-74). A uterine septum is believed to develop as a result of failure of resorption of the tissue connecting the two paramesonephric (müllerian) ducts prior to the 20th embryonic week.

Incising the uterine septum (metroplasty) dates back to 1884 when Ruge described a blind transcervical metroplasty in a woman with two previous miscarriages who, postoperatively, delivered a healthy baby. In the early 1900s, Tompkins reported an abdominal metroplasty (Fertil Stertil. 2021;115:1140-2). The decision to proceed with metroplasty is based on only established observational studies (Fertil Steril. 2016;106:530-40). Until recently, the majority of studies suggested that metroplasty is associated with decreased spontaneous abortion rates and improved obstetrical outcomes. A retrospective case series of 361 patients with a septate uterus who had primary infertility of >2 years’ duration, a history of 1-2 spontaneous abortions, or recurrent pregnancy loss suggested a significant improvement in the live birth rate and reduction in miscarriage (Arch Gynecol Obstet. 2003;268:289-92). A meta-analysis found that the overall pregnancy rate after septum incision was 67.8% and the live-birth rate was 53.5% (J Minim Invas Gynecol. 2013;20:22-42).

Recently, two multinational studies question the prevailing dogma (Fertil Steril. 2021 Sep;116[3]:693-4). Both studies could not demonstrate any increase in live birth rate, reduction in preterm birth, or in pregnancy loss after metroplasty. A significant limitation was the lack of a uniform consensus on the definition of the septate uterus and allowing the discretion of the physician to diagnosis a septum (Hum Reprod. 2020;35:1578-88; Hum Reprod. 2021;36:1260-7).

Hysteroscopic metroplasty is not without complications. Uterine rupture during pregnancy or delivery, while rare, may be linked to significant entry into the myometrium and/or overzealous cauterization and perforation, which emphasizes the importance of appropriate techniques.
 

Conclusion

A diagnosis of müllerian anomalies justifies a comprehensive consultation with the patient given the risk of pregnancy complications. Management of the septate uterus has become controversial. In a patient with infertility, prior pregnancy loss, or poor obstetrical outcome, it is reasonable to consider metroplasty; otherwise, expectant management is an option.

Dr. Trolice is director of The IVF Center in Winter Park, Fla., and professor of obstetrics and gynecology at the University of Central Florida, Orlando. Email him at [email protected].

A swallowable, vibrating capsule improved symptoms among patients with chronic idiopathic constipation in a phase 3 multicenter, randomized, controlled trial. The method represents a mechanical approach to the treatment of constipation.

The swallowable pill acts by vibrating during passage through the gut, where it is thought to augment colonic biorhythm and peristalsis. Traditional treatments for constipation generally increase motility or secretion.

“That’s how we have been managing constipation since time immemorial. Now we have come up with this novel approach, where there’s a pill that is designed to increase local oscillations, and probably induce local contractions of the colon to mimic what happens normally,” said Satish Rao, MD, PhD, who presented the results of the trial at the annual Digestive Disease Week^® (DDW).

“We’re now seeing that local stimulation works, and the other neat thing seems to be a lack of side effects, which is really a huge plus. I think it will benefit people with both occasional or chronic constipation,” said Dr. Rao, professor of medicine at Medical College of Georgia, Augusta.

The capsules activate for two stimulation cycles, each lasting for about 2 hours. The cycle includes 3 seconds of vibration followed by 16 seconds of rest.

The researchers conducted a study with two active arms and a placebo. It included 312 patients age 22 or older who had an average of between 1 and 2.5 spontaneous bowel movements (SBM) per week.

Treatment lasted for 8 weeks, with patients ingesting a capsule between 9 and 10 p.m. In one treatment group, the device was activated at 6 a.m., and in the other group at about 2 p.m.

The placebo and treatment groups had similar baseline characteristics, except for a longer duration of constipation in the treatment groups (17.9 versus 14.5 years; P = .0253). In an intention-to-treat analysis, the treatment groups were more likely to achieve an increase of one complete SBM per week (39.26% versus 22.15%; P < .0001) and an increase of two complete SBMs per week (22.7% versus 11.41%; P < .0006).

The capsules also improved straining score, stool consistency, and quality of life. There was no significant difference between treatment and placebo groups with respect to bloating or rescue medication use.

The product had few adverse effects. The most common was a vibrating sensation or discomfort (11.0%, versus none in the placebo group).

Dr. Rao expects that the treatment could be widely applicable since many constipation patients don’t gain sufficient benefit from existing treatments, or find side effects intolerable.

Another benefit is that the therapy’s mimicry of natural cycles appears to grant patients more control of bowel movements. Laxatives and other pharmaceutical interventions may prompt the patient to go to the bathroom within an hour or two, but patients in the trial reported bowel movements at predictable times.

However, he noted that the pill is nondissolvable, which would make it contraindicated for patients who have had previous gut surgeries or narrowing of the gut. He noted that the sponsoring company, Vibrant Gastro, expects to obtain Food and Drug Administration approval by the end of 2022.

The results of the study were well received. “I think it’s an exciting new approach for managing patients with chronic constipation. It was a large sample size, and the treatment seems to be well tolerated. It may offer a promising option for patients who have not responded to many other medications,” said Adil E. Bharucha, MD, who comoderated the session where the research was presented.

However, he pointed out that the presentation did not indicate how many of the patients had previously tried other therapies. “We’d like to see the full paper, which will provide a better understanding of the role of this treatment in practice down the road,” said Dr. Bharucha, professor of medicine in the division of gastroenterology and hepatology and director of the office of clinical trials at Mayo Clinic, Rochester, Minn.

The capsule may not work for everyone, said Dr. Bharucha. He suspects that many refractory patients have an issue with pelvic floor muscles, which may restrict stool evacuation. “You wouldn’t expect those people to respond optimally to a laxative and I suspect perhaps not to a capsule, either. I think defecatory disorders are substantially underdiagnosed in patients who don’t respond to laxatives,” said Dr. Bharucha.

Asked why the capsule might benefit patients who don’t improve with laxatives, Dr. Bharucha responded: “I think we need more studies to understand how the capsule works.”

Dr. Rao consults for Vibrant Gastro. Dr. Bharucha has no relevant financial disclosures.

A swallowable, vibrating capsule improved symptoms among patients with chronic idiopathic constipation in a phase 3 multicenter, randomized, controlled trial. The method represents a mechanical approach to the treatment of constipation.

The swallowable pill acts by vibrating during passage through the gut, where it is thought to augment colonic biorhythm and peristalsis. Traditional treatments for constipation generally increase motility or secretion.

“That’s how we have been managing constipation since time immemorial. Now we have come up with this novel approach, where there’s a pill that is designed to increase local oscillations, and probably induce local contractions of the colon to mimic what happens normally,” said Satish Rao, MD, PhD, who presented the results of the trial at the annual Digestive Disease Week^® (DDW).

“We’re now seeing that local stimulation works, and the other neat thing seems to be a lack of side effects, which is really a huge plus. I think it will benefit people with both occasional or chronic constipation,” said Dr. Rao, professor of medicine at Medical College of Georgia, Augusta.

The capsules activate for two stimulation cycles, each lasting for about 2 hours. The cycle includes 3 seconds of vibration followed by 16 seconds of rest.

The researchers conducted a study with two active arms and a placebo. It included 312 patients age 22 or older who had an average of between 1 and 2.5 spontaneous bowel movements (SBM) per week.

Treatment lasted for 8 weeks, with patients ingesting a capsule between 9 and 10 p.m. In one treatment group, the device was activated at 6 a.m., and in the other group at about 2 p.m.

The placebo and treatment groups had similar baseline characteristics, except for a longer duration of constipation in the treatment groups (17.9 versus 14.5 years; P = .0253). In an intention-to-treat analysis, the treatment groups were more likely to achieve an increase of one complete SBM per week (39.26% versus 22.15%; P < .0001) and an increase of two complete SBMs per week (22.7% versus 11.41%; P < .0006).

The capsules also improved straining score, stool consistency, and quality of life. There was no significant difference between treatment and placebo groups with respect to bloating or rescue medication use.

The product had few adverse effects. The most common was a vibrating sensation or discomfort (11.0%, versus none in the placebo group).

Dr. Rao expects that the treatment could be widely applicable since many constipation patients don’t gain sufficient benefit from existing treatments, or find side effects intolerable.

Another benefit is that the therapy’s mimicry of natural cycles appears to grant patients more control of bowel movements. Laxatives and other pharmaceutical interventions may prompt the patient to go to the bathroom within an hour or two, but patients in the trial reported bowel movements at predictable times.

However, he noted that the pill is nondissolvable, which would make it contraindicated for patients who have had previous gut surgeries or narrowing of the gut. He noted that the sponsoring company, Vibrant Gastro, expects to obtain Food and Drug Administration approval by the end of 2022.

The results of the study were well received. “I think it’s an exciting new approach for managing patients with chronic constipation. It was a large sample size, and the treatment seems to be well tolerated. It may offer a promising option for patients who have not responded to many other medications,” said Adil E. Bharucha, MD, who comoderated the session where the research was presented.

However, he pointed out that the presentation did not indicate how many of the patients had previously tried other therapies. “We’d like to see the full paper, which will provide a better understanding of the role of this treatment in practice down the road,” said Dr. Bharucha, professor of medicine in the division of gastroenterology and hepatology and director of the office of clinical trials at Mayo Clinic, Rochester, Minn.

The capsule may not work for everyone, said Dr. Bharucha. He suspects that many refractory patients have an issue with pelvic floor muscles, which may restrict stool evacuation. “You wouldn’t expect those people to respond optimally to a laxative and I suspect perhaps not to a capsule, either. I think defecatory disorders are substantially underdiagnosed in patients who don’t respond to laxatives,” said Dr. Bharucha.

Asked why the capsule might benefit patients who don’t improve with laxatives, Dr. Bharucha responded: “I think we need more studies to understand how the capsule works.”

Dr. Rao consults for Vibrant Gastro. Dr. Bharucha has no relevant financial disclosures.

A swallowable, vibrating capsule improved symptoms among patients with chronic idiopathic constipation in a phase 3 multicenter, randomized, controlled trial. The method represents a mechanical approach to the treatment of constipation.

The swallowable pill acts by vibrating during passage through the gut, where it is thought to augment colonic biorhythm and peristalsis. Traditional treatments for constipation generally increase motility or secretion.

“That’s how we have been managing constipation since time immemorial. Now we have come up with this novel approach, where there’s a pill that is designed to increase local oscillations, and probably induce local contractions of the colon to mimic what happens normally,” said Satish Rao, MD, PhD, who presented the results of the trial at the annual Digestive Disease Week^® (DDW).

“We’re now seeing that local stimulation works, and the other neat thing seems to be a lack of side effects, which is really a huge plus. I think it will benefit people with both occasional or chronic constipation,” said Dr. Rao, professor of medicine at Medical College of Georgia, Augusta.

The capsules activate for two stimulation cycles, each lasting for about 2 hours. The cycle includes 3 seconds of vibration followed by 16 seconds of rest.

The researchers conducted a study with two active arms and a placebo. It included 312 patients age 22 or older who had an average of between 1 and 2.5 spontaneous bowel movements (SBM) per week.

Treatment lasted for 8 weeks, with patients ingesting a capsule between 9 and 10 p.m. In one treatment group, the device was activated at 6 a.m., and in the other group at about 2 p.m.

The placebo and treatment groups had similar baseline characteristics, except for a longer duration of constipation in the treatment groups (17.9 versus 14.5 years; P = .0253). In an intention-to-treat analysis, the treatment groups were more likely to achieve an increase of one complete SBM per week (39.26% versus 22.15%; P < .0001) and an increase of two complete SBMs per week (22.7% versus 11.41%; P < .0006).

The capsules also improved straining score, stool consistency, and quality of life. There was no significant difference between treatment and placebo groups with respect to bloating or rescue medication use.

The product had few adverse effects. The most common was a vibrating sensation or discomfort (11.0%, versus none in the placebo group).

Dr. Rao expects that the treatment could be widely applicable since many constipation patients don’t gain sufficient benefit from existing treatments, or find side effects intolerable.

Another benefit is that the therapy’s mimicry of natural cycles appears to grant patients more control of bowel movements. Laxatives and other pharmaceutical interventions may prompt the patient to go to the bathroom within an hour or two, but patients in the trial reported bowel movements at predictable times.

However, he noted that the pill is nondissolvable, which would make it contraindicated for patients who have had previous gut surgeries or narrowing of the gut. He noted that the sponsoring company, Vibrant Gastro, expects to obtain Food and Drug Administration approval by the end of 2022.

The results of the study were well received. “I think it’s an exciting new approach for managing patients with chronic constipation. It was a large sample size, and the treatment seems to be well tolerated. It may offer a promising option for patients who have not responded to many other medications,” said Adil E. Bharucha, MD, who comoderated the session where the research was presented.

However, he pointed out that the presentation did not indicate how many of the patients had previously tried other therapies. “We’d like to see the full paper, which will provide a better understanding of the role of this treatment in practice down the road,” said Dr. Bharucha, professor of medicine in the division of gastroenterology and hepatology and director of the office of clinical trials at Mayo Clinic, Rochester, Minn.

The capsule may not work for everyone, said Dr. Bharucha. He suspects that many refractory patients have an issue with pelvic floor muscles, which may restrict stool evacuation. “You wouldn’t expect those people to respond optimally to a laxative and I suspect perhaps not to a capsule, either. I think defecatory disorders are substantially underdiagnosed in patients who don’t respond to laxatives,” said Dr. Bharucha.

Asked why the capsule might benefit patients who don’t improve with laxatives, Dr. Bharucha responded: “I think we need more studies to understand how the capsule works.”

Dr. Rao consults for Vibrant Gastro. Dr. Bharucha has no relevant financial disclosures.

To the Editor:

Wolf isotopic response describes the development of a skin disorder at the site of another healed and unrelated skin disease. Skin disorders presenting as isotopic responses have included inflammatory, malignant, granulomatous, and infectious processes. Discoid lupus erythematosus (DLE) is a rare isotopic response. We report a cutaneous lupus erythematosus–like isotopic response that presented at the site of a recent herpes zoster infection in a liver transplant recipient.

A 74-year-old immunocompromised woman was referred to the dermatology clinic for evaluation of a rash on the right leg. She was being treated with maintenance valganciclovir due to cytomegalovirus viremia, as well as tacrolimus, azathioprine, and prednisone following liver transplantation due to autoimmune hepatitis for 8 months prior to presentation. Eighteen days prior to the current presentation, she was clinically diagnosed with herpes zoster. As the grouped vesicles from the herpes zoster resolved, she developed pink scaly papules in the same distribution as the original vesicular eruption.

Physical examination revealed numerous erythematous, 2- to 3-mm, scaly papules that coalesced into small plaques with serous crusts; they originated above the supragluteal cleft and extended rightward in the L3 and L4 dermatomes to the right knee (Figure 1). A 3-mm punch biopsy specimen was obtained from the right anterior thigh. Histologic analysis revealed interface lymphocytic inflammation with squamatization of basal keratinocytes, basement membrane thickening, and follicular plugging by keratin (Figure 2). There was a moderately intense perivascular and periadnexal inflammatory infiltrate of mature lymphocytes with rare eosinophils within the papillary and superficial reticular dermis. There was no evidence of a viral cytopathic effect, and an immunohistochemical stain for varicella-zoster virus protein was negative. The histologic findings were suggestive of cutaneous involvement by DLE. A diagnosis of a cutaneous lupus erythematosus–like Wolf isotopic response was made, and the patient’s rash resolved with the use of triamcinolone cream 0.1% applied twice daily for 2 weeks. At 6-week follow-up, there were postinflammatory pigmentation changes at the sites of the prior rash and persistent postherpetic neuralgia. Recent antinuclear antibody screening was negative, coupled with the patient’s lack of systemic symptoms and quick resolution of rash, indicating that additional testing for systemic lupus was not warranted.

Wolf isotopic response describes the occurrence of a new skin disorder at the site of a previously healed and unrelated skin disorder. The second disease may appear within days to years after the primary disease subsides and is clearly differentiated from the isomorphic response of the Koebner phenomenon, which describes an established skin disorder appearing at a previously uninvolved anatomic site following trauma.¹ As in our case, the initial cutaneous eruption resulting in a subsequent Wolf isotopic response frequently is herpes zoster and less commonly is herpes simplex virus.² The most common reported isotopic response is a granulomatous reaction.² Rare reports of leukemic infiltration, lymphoma, lichen planus, morphea, reactive perforating collagenosis, psoriasis, discoid lupus, lichen simplex chronicus, contact dermatitis, xanthomatous changes, malignant tumors, cutaneous graft-vs-host disease, pityriasis rosea, erythema annulare centrifugum, and other infectious-based isotopic responses exist.^2-6

Our patient presented with Wolf isotopic response that histologically mimicked DLE. A PubMed search of articles indexed for MEDLINE using the terms isotopic response and lupus revealed only 3 cases of cutaneous lupus erythematosus presenting as an isotopic response in the English-language literature. One of those cases occurred in a patient with preexisting systemic lupus erythematosus, making a diagnosis of Koebner isomorphic phenomenon more appropriate than an isotopic response at the site of prior herpes zoster infection.⁷ The remaining 2 cases were clinically defined DLE lesions occurring at sites of prior infection—cutaneous leishmaniasis and herpes zoster—in patients without a prior history of cutaneous or systemic lupus erythematosus.^8,9 The latter case of DLE-like isotopic response occurring after herpes zoster infection was further complicated by local injections at the zoster site for herpes-related local pain. Injection sites are reported as a distinct nidus for Wolf isotopic response.⁹

The pathogenesis of Wolf isotopic response is unclear. Possible explanations include local interactions between persistent viral particles at prior herpes infection sites, vascular injury, neural injury, and an altered immune response.^1,5,6,10 The destruction of sensory nerve fibers by herpesviruses cause the release of neuropeptides that then modulate the local immune system and angiogenic responses.^5,6 Our patient’s immunocompromised state may have further propagated a local altered immune cell infiltrate at the site of the isotopic response. Despite its unclear etiology, Wolf isotopic response should be considered in the differential diagnosis for any patient who presents with a dermatomal eruption at the site of a prior cutaneous infection, particularly after infection with herpes zoster. Treatment with topical or intralesional corticosteroids usually suffices for inflammatory-based isotopic responses with an excellent prognosis.¹¹

We present a case of a cutaneous lupus erythematosus–like isotopic response that occurred at the site of a recent herpes zoster eruption in an immunocompromised patient without prior history of systemic or cutaneous lupus erythematosus. Clinical recognition of Wolf isotopic response is important for accurate histopathologic diagnosis and management. Continued investigation into the underlying pathogenesis should be performed to fully understand and better treat this process.

To the Editor:

Wolf isotopic response describes the development of a skin disorder at the site of another healed and unrelated skin disease. Skin disorders presenting as isotopic responses have included inflammatory, malignant, granulomatous, and infectious processes. Discoid lupus erythematosus (DLE) is a rare isotopic response. We report a cutaneous lupus erythematosus–like isotopic response that presented at the site of a recent herpes zoster infection in a liver transplant recipient.

A 74-year-old immunocompromised woman was referred to the dermatology clinic for evaluation of a rash on the right leg. She was being treated with maintenance valganciclovir due to cytomegalovirus viremia, as well as tacrolimus, azathioprine, and prednisone following liver transplantation due to autoimmune hepatitis for 8 months prior to presentation. Eighteen days prior to the current presentation, she was clinically diagnosed with herpes zoster. As the grouped vesicles from the herpes zoster resolved, she developed pink scaly papules in the same distribution as the original vesicular eruption.

Physical examination revealed numerous erythematous, 2- to 3-mm, scaly papules that coalesced into small plaques with serous crusts; they originated above the supragluteal cleft and extended rightward in the L3 and L4 dermatomes to the right knee (Figure 1). A 3-mm punch biopsy specimen was obtained from the right anterior thigh. Histologic analysis revealed interface lymphocytic inflammation with squamatization of basal keratinocytes, basement membrane thickening, and follicular plugging by keratin (Figure 2). There was a moderately intense perivascular and periadnexal inflammatory infiltrate of mature lymphocytes with rare eosinophils within the papillary and superficial reticular dermis. There was no evidence of a viral cytopathic effect, and an immunohistochemical stain for varicella-zoster virus protein was negative. The histologic findings were suggestive of cutaneous involvement by DLE. A diagnosis of a cutaneous lupus erythematosus–like Wolf isotopic response was made, and the patient’s rash resolved with the use of triamcinolone cream 0.1% applied twice daily for 2 weeks. At 6-week follow-up, there were postinflammatory pigmentation changes at the sites of the prior rash and persistent postherpetic neuralgia. Recent antinuclear antibody screening was negative, coupled with the patient’s lack of systemic symptoms and quick resolution of rash, indicating that additional testing for systemic lupus was not warranted.

Wolf isotopic response describes the occurrence of a new skin disorder at the site of a previously healed and unrelated skin disorder. The second disease may appear within days to years after the primary disease subsides and is clearly differentiated from the isomorphic response of the Koebner phenomenon, which describes an established skin disorder appearing at a previously uninvolved anatomic site following trauma.¹ As in our case, the initial cutaneous eruption resulting in a subsequent Wolf isotopic response frequently is herpes zoster and less commonly is herpes simplex virus.² The most common reported isotopic response is a granulomatous reaction.² Rare reports of leukemic infiltration, lymphoma, lichen planus, morphea, reactive perforating collagenosis, psoriasis, discoid lupus, lichen simplex chronicus, contact dermatitis, xanthomatous changes, malignant tumors, cutaneous graft-vs-host disease, pityriasis rosea, erythema annulare centrifugum, and other infectious-based isotopic responses exist.^2-6

Our patient presented with Wolf isotopic response that histologically mimicked DLE. A PubMed search of articles indexed for MEDLINE using the terms isotopic response and lupus revealed only 3 cases of cutaneous lupus erythematosus presenting as an isotopic response in the English-language literature. One of those cases occurred in a patient with preexisting systemic lupus erythematosus, making a diagnosis of Koebner isomorphic phenomenon more appropriate than an isotopic response at the site of prior herpes zoster infection.⁷ The remaining 2 cases were clinically defined DLE lesions occurring at sites of prior infection—cutaneous leishmaniasis and herpes zoster—in patients without a prior history of cutaneous or systemic lupus erythematosus.^8,9 The latter case of DLE-like isotopic response occurring after herpes zoster infection was further complicated by local injections at the zoster site for herpes-related local pain. Injection sites are reported as a distinct nidus for Wolf isotopic response.⁹

The pathogenesis of Wolf isotopic response is unclear. Possible explanations include local interactions between persistent viral particles at prior herpes infection sites, vascular injury, neural injury, and an altered immune response.^1,5,6,10 The destruction of sensory nerve fibers by herpesviruses cause the release of neuropeptides that then modulate the local immune system and angiogenic responses.^5,6 Our patient’s immunocompromised state may have further propagated a local altered immune cell infiltrate at the site of the isotopic response. Despite its unclear etiology, Wolf isotopic response should be considered in the differential diagnosis for any patient who presents with a dermatomal eruption at the site of a prior cutaneous infection, particularly after infection with herpes zoster. Treatment with topical or intralesional corticosteroids usually suffices for inflammatory-based isotopic responses with an excellent prognosis.¹¹

We present a case of a cutaneous lupus erythematosus–like isotopic response that occurred at the site of a recent herpes zoster eruption in an immunocompromised patient without prior history of systemic or cutaneous lupus erythematosus. Clinical recognition of Wolf isotopic response is important for accurate histopathologic diagnosis and management. Continued investigation into the underlying pathogenesis should be performed to fully understand and better treat this process.

To the Editor:

Wolf isotopic response describes the development of a skin disorder at the site of another healed and unrelated skin disease. Skin disorders presenting as isotopic responses have included inflammatory, malignant, granulomatous, and infectious processes. Discoid lupus erythematosus (DLE) is a rare isotopic response. We report a cutaneous lupus erythematosus–like isotopic response that presented at the site of a recent herpes zoster infection in a liver transplant recipient.

A 74-year-old immunocompromised woman was referred to the dermatology clinic for evaluation of a rash on the right leg. She was being treated with maintenance valganciclovir due to cytomegalovirus viremia, as well as tacrolimus, azathioprine, and prednisone following liver transplantation due to autoimmune hepatitis for 8 months prior to presentation. Eighteen days prior to the current presentation, she was clinically diagnosed with herpes zoster. As the grouped vesicles from the herpes zoster resolved, she developed pink scaly papules in the same distribution as the original vesicular eruption.

Physical examination revealed numerous erythematous, 2- to 3-mm, scaly papules that coalesced into small plaques with serous crusts; they originated above the supragluteal cleft and extended rightward in the L3 and L4 dermatomes to the right knee (Figure 1). A 3-mm punch biopsy specimen was obtained from the right anterior thigh. Histologic analysis revealed interface lymphocytic inflammation with squamatization of basal keratinocytes, basement membrane thickening, and follicular plugging by keratin (Figure 2). There was a moderately intense perivascular and periadnexal inflammatory infiltrate of mature lymphocytes with rare eosinophils within the papillary and superficial reticular dermis. There was no evidence of a viral cytopathic effect, and an immunohistochemical stain for varicella-zoster virus protein was negative. The histologic findings were suggestive of cutaneous involvement by DLE. A diagnosis of a cutaneous lupus erythematosus–like Wolf isotopic response was made, and the patient’s rash resolved with the use of triamcinolone cream 0.1% applied twice daily for 2 weeks. At 6-week follow-up, there were postinflammatory pigmentation changes at the sites of the prior rash and persistent postherpetic neuralgia. Recent antinuclear antibody screening was negative, coupled with the patient’s lack of systemic symptoms and quick resolution of rash, indicating that additional testing for systemic lupus was not warranted.

Wolf isotopic response describes the occurrence of a new skin disorder at the site of a previously healed and unrelated skin disorder. The second disease may appear within days to years after the primary disease subsides and is clearly differentiated from the isomorphic response of the Koebner phenomenon, which describes an established skin disorder appearing at a previously uninvolved anatomic site following trauma.¹ As in our case, the initial cutaneous eruption resulting in a subsequent Wolf isotopic response frequently is herpes zoster and less commonly is herpes simplex virus.² The most common reported isotopic response is a granulomatous reaction.² Rare reports of leukemic infiltration, lymphoma, lichen planus, morphea, reactive perforating collagenosis, psoriasis, discoid lupus, lichen simplex chronicus, contact dermatitis, xanthomatous changes, malignant tumors, cutaneous graft-vs-host disease, pityriasis rosea, erythema annulare centrifugum, and other infectious-based isotopic responses exist.^2-6

Our patient presented with Wolf isotopic response that histologically mimicked DLE. A PubMed search of articles indexed for MEDLINE using the terms isotopic response and lupus revealed only 3 cases of cutaneous lupus erythematosus presenting as an isotopic response in the English-language literature. One of those cases occurred in a patient with preexisting systemic lupus erythematosus, making a diagnosis of Koebner isomorphic phenomenon more appropriate than an isotopic response at the site of prior herpes zoster infection.⁷ The remaining 2 cases were clinically defined DLE lesions occurring at sites of prior infection—cutaneous leishmaniasis and herpes zoster—in patients without a prior history of cutaneous or systemic lupus erythematosus.^8,9 The latter case of DLE-like isotopic response occurring after herpes zoster infection was further complicated by local injections at the zoster site for herpes-related local pain. Injection sites are reported as a distinct nidus for Wolf isotopic response.⁹

The pathogenesis of Wolf isotopic response is unclear. Possible explanations include local interactions between persistent viral particles at prior herpes infection sites, vascular injury, neural injury, and an altered immune response.^1,5,6,10 The destruction of sensory nerve fibers by herpesviruses cause the release of neuropeptides that then modulate the local immune system and angiogenic responses.^5,6 Our patient’s immunocompromised state may have further propagated a local altered immune cell infiltrate at the site of the isotopic response. Despite its unclear etiology, Wolf isotopic response should be considered in the differential diagnosis for any patient who presents with a dermatomal eruption at the site of a prior cutaneous infection, particularly after infection with herpes zoster. Treatment with topical or intralesional corticosteroids usually suffices for inflammatory-based isotopic responses with an excellent prognosis.¹¹

We present a case of a cutaneous lupus erythematosus–like isotopic response that occurred at the site of a recent herpes zoster eruption in an immunocompromised patient without prior history of systemic or cutaneous lupus erythematosus. Clinical recognition of Wolf isotopic response is important for accurate histopathologic diagnosis and management. Continued investigation into the underlying pathogenesis should be performed to fully understand and better treat this process.

Regulators and the nation’s largest physician organization took separate steps in recent days to prepare for expected authorization of use of COVID-19 vaccines in children younger than age 6.

The Food and Drug Administration on May 23 announced its Vaccines and Related Biological Products Advisory Committee will meet June 15 to discuss expanding the use of COVID vaccines from Pfizer and Moderna.

The panel will examine a request from Pfizer and its partner BioNTech for an emergency use authorization (EUA) of its vaccine to cover children ages 6 months through 4 years. The EUA expansion for the Moderna shot would cover children ages 6 months through 5 years, the FDA said.

Many parents and physicians have been urging regulators to clear COVID shots for young children, among whom rates of infection are high.

The American Medical Association in February announced an update of its Current Procedural Terminology (CPT) to prepare for an eventual FDA clearance of the Pfizer-BioNTech shot for children aged 6 months to younger than 5 years. On May 19, the association announced a new CPT update to prepare for FDA clearance for use of the Moderna COVID-19 vaccine for children 6 months through 5 years.

“Extending COVID-19 vaccination protection to approximately 18 million young children will significantly reduce their risk of COVID-19 infection, hospitalization, and death, and give their parents incredible peace of mind,” Gerald Harmon, MD, AMA’s president, said in a statement. “We strongly urge all parents to get their infants and toddlers vaccinated as soon as they are eligible for a COVID-19 vaccine.”

Both the Moderna and the Pfizer-BioNTech COVID vaccines would be given to these young children in low doses.

On May 23, Pfizer announced results from a phase 2/3 trial evaluating a series of three shots of its vaccine in children ages 6 months to younger than 5 years.

Vaccine efficacy, which was a secondary endpoint in this study, was 80.3% in this age group, Pfizer said. The analysis was based on 10 symptomatic cases of COVID-19. The trial’s protocol specifies a formal analysis will be performed when at least 21 cases have accrued from 7 days after the third dose. The company said it would share final data on the effectiveness of the vaccine once the results are available.

Moderna on April 28 issued a statement with details about testing of its vaccine in young children. Vaccine efficacy was estimated at about 51% for children aged 6 months to younger than 2 years and 37% for the children aged 2 years to younger than 6. Paul Burton, MD, Moderna’s chief medical officer, spoke about this rate during a May 1 appearance on CBS’ Face the Nation.

“What it means for parents, for caregivers, is that if they give the Moderna vaccine to these little kids, they would basically cut in half the risk of that child getting symptomatic COVID,” Dr. Burton said in the interview. “Now, the number, 50%, I know is often lower than we are used to seeing with our vaccine, but it’s because this study was conducted during a time of Omicron.”

The FDA’s vaccine advisory committee also will meet on June 14 discuss potential use under an EUA of Moderna’s COVID vaccine for children and teenagers aged 6-17 years. The Pfizer-BioNTech vaccine already is authorized under an EUA for people aged 5 years and older.

The FDA has to date granted both conditional clearances, or EUAs, and regular approvals for COVID vaccines.

EUAs are meant to be temporary, allowing for rapid introduction of medicines in response to public health crises such as the pandemic. The FDA also uses EUAs to provide initial clearances of additional indications for products, as would be the case with the authorizations Moderna and Pfizer-BioNTech are seeking for their COVID vaccines.

Companies that want to continue to sell EUA-cleared products or promote EUA-cleared indications beyond the time of the public health crisis must seek regular approvals.

The FDA cleared the Pfizer-BioNTech and Moderna COVID vaccines under EUAs in December 2020. The agency then granted a regular approval for the Pfizer-BioNTech vaccine for people ages 16 and older in August 2021 based on more robust data. Regular approval for the Moderna vaccine for people ages 18 and older followed in January 2022.
 

Varied reactions among parents

Attitudes in the United States about pediatric COVID vaccines are far from uniform.

The initial uptake has disappointed physicians and researchers, who have been urging wider use of the COVID vaccination among children and teens for whom the FDA already has granted a clearance. Many parents are hesitating to bring their children for the COVID vaccines, according to the Centers for Disease Control and Prevention. Only 35.4% of children ages 5-11 had received at least one dose of a COVID vaccine, CDC staff said during a meeting.

Yet many other parents are demanding this medicine for their young children, urging the FDA to move quickly to clear COVID shots.

A private Facebook group called “Protect Their Future: A Call to Action for COVID Vaccines in Kids <5” boasts about 6,200 members. Many parents and physicians have used Twitter in recent months to press for a speedy review of COVID vaccines for the youngest children, often using the hashtag #immunizeunder5s. A group called Protect Their Future, which uses @ImmunizeUnder5s as its Twitter handle, had 5,288 followers as of the afternoon of May 23.

A special panel of the House of Representatives, the Select Subcommittee on the Coronavirus Crisis, on May 23 joined those tweeting about the need to soon authorize COVID vaccines for very young children.

“Parents have been waiting many months for vaccines for their young children,” the subcommittee tweeted. “They deserve to hear from @US_FDA why this lengthy process has been in children’s best interests.”

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

Regulators and the nation’s largest physician organization took separate steps in recent days to prepare for expected authorization of use of COVID-19 vaccines in children younger than age 6.

The Food and Drug Administration on May 23 announced its Vaccines and Related Biological Products Advisory Committee will meet June 15 to discuss expanding the use of COVID vaccines from Pfizer and Moderna.

The panel will examine a request from Pfizer and its partner BioNTech for an emergency use authorization (EUA) of its vaccine to cover children ages 6 months through 4 years. The EUA expansion for the Moderna shot would cover children ages 6 months through 5 years, the FDA said.

Many parents and physicians have been urging regulators to clear COVID shots for young children, among whom rates of infection are high.

The American Medical Association in February announced an update of its Current Procedural Terminology (CPT) to prepare for an eventual FDA clearance of the Pfizer-BioNTech shot for children aged 6 months to younger than 5 years. On May 19, the association announced a new CPT update to prepare for FDA clearance for use of the Moderna COVID-19 vaccine for children 6 months through 5 years.

“Extending COVID-19 vaccination protection to approximately 18 million young children will significantly reduce their risk of COVID-19 infection, hospitalization, and death, and give their parents incredible peace of mind,” Gerald Harmon, MD, AMA’s president, said in a statement. “We strongly urge all parents to get their infants and toddlers vaccinated as soon as they are eligible for a COVID-19 vaccine.”

Both the Moderna and the Pfizer-BioNTech COVID vaccines would be given to these young children in low doses.

On May 23, Pfizer announced results from a phase 2/3 trial evaluating a series of three shots of its vaccine in children ages 6 months to younger than 5 years.

Vaccine efficacy, which was a secondary endpoint in this study, was 80.3% in this age group, Pfizer said. The analysis was based on 10 symptomatic cases of COVID-19. The trial’s protocol specifies a formal analysis will be performed when at least 21 cases have accrued from 7 days after the third dose. The company said it would share final data on the effectiveness of the vaccine once the results are available.

Moderna on April 28 issued a statement with details about testing of its vaccine in young children. Vaccine efficacy was estimated at about 51% for children aged 6 months to younger than 2 years and 37% for the children aged 2 years to younger than 6. Paul Burton, MD, Moderna’s chief medical officer, spoke about this rate during a May 1 appearance on CBS’ Face the Nation.

“What it means for parents, for caregivers, is that if they give the Moderna vaccine to these little kids, they would basically cut in half the risk of that child getting symptomatic COVID,” Dr. Burton said in the interview. “Now, the number, 50%, I know is often lower than we are used to seeing with our vaccine, but it’s because this study was conducted during a time of Omicron.”

The FDA’s vaccine advisory committee also will meet on June 14 discuss potential use under an EUA of Moderna’s COVID vaccine for children and teenagers aged 6-17 years. The Pfizer-BioNTech vaccine already is authorized under an EUA for people aged 5 years and older.

The FDA has to date granted both conditional clearances, or EUAs, and regular approvals for COVID vaccines.

EUAs are meant to be temporary, allowing for rapid introduction of medicines in response to public health crises such as the pandemic. The FDA also uses EUAs to provide initial clearances of additional indications for products, as would be the case with the authorizations Moderna and Pfizer-BioNTech are seeking for their COVID vaccines.

Companies that want to continue to sell EUA-cleared products or promote EUA-cleared indications beyond the time of the public health crisis must seek regular approvals.

The FDA cleared the Pfizer-BioNTech and Moderna COVID vaccines under EUAs in December 2020. The agency then granted a regular approval for the Pfizer-BioNTech vaccine for people ages 16 and older in August 2021 based on more robust data. Regular approval for the Moderna vaccine for people ages 18 and older followed in January 2022.
 

Varied reactions among parents

Attitudes in the United States about pediatric COVID vaccines are far from uniform.

The initial uptake has disappointed physicians and researchers, who have been urging wider use of the COVID vaccination among children and teens for whom the FDA already has granted a clearance. Many parents are hesitating to bring their children for the COVID vaccines, according to the Centers for Disease Control and Prevention. Only 35.4% of children ages 5-11 had received at least one dose of a COVID vaccine, CDC staff said during a meeting.

Yet many other parents are demanding this medicine for their young children, urging the FDA to move quickly to clear COVID shots.

A private Facebook group called “Protect Their Future: A Call to Action for COVID Vaccines in Kids <5” boasts about 6,200 members. Many parents and physicians have used Twitter in recent months to press for a speedy review of COVID vaccines for the youngest children, often using the hashtag #immunizeunder5s. A group called Protect Their Future, which uses @ImmunizeUnder5s as its Twitter handle, had 5,288 followers as of the afternoon of May 23.

A special panel of the House of Representatives, the Select Subcommittee on the Coronavirus Crisis, on May 23 joined those tweeting about the need to soon authorize COVID vaccines for very young children.

“Parents have been waiting many months for vaccines for their young children,” the subcommittee tweeted. “They deserve to hear from @US_FDA why this lengthy process has been in children’s best interests.”

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

Regulators and the nation’s largest physician organization took separate steps in recent days to prepare for expected authorization of use of COVID-19 vaccines in children younger than age 6.

The Food and Drug Administration on May 23 announced its Vaccines and Related Biological Products Advisory Committee will meet June 15 to discuss expanding the use of COVID vaccines from Pfizer and Moderna.

The panel will examine a request from Pfizer and its partner BioNTech for an emergency use authorization (EUA) of its vaccine to cover children ages 6 months through 4 years. The EUA expansion for the Moderna shot would cover children ages 6 months through 5 years, the FDA said.

Many parents and physicians have been urging regulators to clear COVID shots for young children, among whom rates of infection are high.

The American Medical Association in February announced an update of its Current Procedural Terminology (CPT) to prepare for an eventual FDA clearance of the Pfizer-BioNTech shot for children aged 6 months to younger than 5 years. On May 19, the association announced a new CPT update to prepare for FDA clearance for use of the Moderna COVID-19 vaccine for children 6 months through 5 years.

“Extending COVID-19 vaccination protection to approximately 18 million young children will significantly reduce their risk of COVID-19 infection, hospitalization, and death, and give their parents incredible peace of mind,” Gerald Harmon, MD, AMA’s president, said in a statement. “We strongly urge all parents to get their infants and toddlers vaccinated as soon as they are eligible for a COVID-19 vaccine.”

Both the Moderna and the Pfizer-BioNTech COVID vaccines would be given to these young children in low doses.

On May 23, Pfizer announced results from a phase 2/3 trial evaluating a series of three shots of its vaccine in children ages 6 months to younger than 5 years.

Vaccine efficacy, which was a secondary endpoint in this study, was 80.3% in this age group, Pfizer said. The analysis was based on 10 symptomatic cases of COVID-19. The trial’s protocol specifies a formal analysis will be performed when at least 21 cases have accrued from 7 days after the third dose. The company said it would share final data on the effectiveness of the vaccine once the results are available.

Moderna on April 28 issued a statement with details about testing of its vaccine in young children. Vaccine efficacy was estimated at about 51% for children aged 6 months to younger than 2 years and 37% for the children aged 2 years to younger than 6. Paul Burton, MD, Moderna’s chief medical officer, spoke about this rate during a May 1 appearance on CBS’ Face the Nation.

“What it means for parents, for caregivers, is that if they give the Moderna vaccine to these little kids, they would basically cut in half the risk of that child getting symptomatic COVID,” Dr. Burton said in the interview. “Now, the number, 50%, I know is often lower than we are used to seeing with our vaccine, but it’s because this study was conducted during a time of Omicron.”

The FDA’s vaccine advisory committee also will meet on June 14 discuss potential use under an EUA of Moderna’s COVID vaccine for children and teenagers aged 6-17 years. The Pfizer-BioNTech vaccine already is authorized under an EUA for people aged 5 years and older.

The FDA has to date granted both conditional clearances, or EUAs, and regular approvals for COVID vaccines.

EUAs are meant to be temporary, allowing for rapid introduction of medicines in response to public health crises such as the pandemic. The FDA also uses EUAs to provide initial clearances of additional indications for products, as would be the case with the authorizations Moderna and Pfizer-BioNTech are seeking for their COVID vaccines.

Companies that want to continue to sell EUA-cleared products or promote EUA-cleared indications beyond the time of the public health crisis must seek regular approvals.

The FDA cleared the Pfizer-BioNTech and Moderna COVID vaccines under EUAs in December 2020. The agency then granted a regular approval for the Pfizer-BioNTech vaccine for people ages 16 and older in August 2021 based on more robust data. Regular approval for the Moderna vaccine for people ages 18 and older followed in January 2022.
 

Varied reactions among parents

Attitudes in the United States about pediatric COVID vaccines are far from uniform.

The initial uptake has disappointed physicians and researchers, who have been urging wider use of the COVID vaccination among children and teens for whom the FDA already has granted a clearance. Many parents are hesitating to bring their children for the COVID vaccines, according to the Centers for Disease Control and Prevention. Only 35.4% of children ages 5-11 had received at least one dose of a COVID vaccine, CDC staff said during a meeting.

Yet many other parents are demanding this medicine for their young children, urging the FDA to move quickly to clear COVID shots.

A private Facebook group called “Protect Their Future: A Call to Action for COVID Vaccines in Kids <5” boasts about 6,200 members. Many parents and physicians have used Twitter in recent months to press for a speedy review of COVID vaccines for the youngest children, often using the hashtag #immunizeunder5s. A group called Protect Their Future, which uses @ImmunizeUnder5s as its Twitter handle, had 5,288 followers as of the afternoon of May 23.

A special panel of the House of Representatives, the Select Subcommittee on the Coronavirus Crisis, on May 23 joined those tweeting about the need to soon authorize COVID vaccines for very young children.

“Parents have been waiting many months for vaccines for their young children,” the subcommittee tweeted. “They deserve to hear from @US_FDA why this lengthy process has been in children’s best interests.”

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

Intravenous thrombolysis (IVT) for acute stroke appears safe for patients who have recently received direct oral anticoagulant (DOAC) therapy, a new observational study suggests, prompting researchers to ask whether guidelines that restrict its use should be updated.

Researchers found that DOAC users were significantly less likely to develop symptomatic intracerebral hemorrhage (sICH) after IVT, and there was no difference in functional independence at 3 months, compared with patients who received IVT but who did not receive DOAC.

“At the moment, the guidelines really pose a barrier and stop sign in front of the most important medical reperfusion therapy, which is thrombolysis,” said principal investigator Jan Purrucker, MD, professor of neurology at Heidelberg University Hospital.

“The main question we have to answer is, is IVT safe in patients with acute ischemic stroke who were pretreated with direct oral anticoagulants or not?”

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022, Lyon, France.
 

A ‘daily clinical problem’

As many as 20% of patients with atrial fibrillation experience ischemic stroke while receiving DOAC therapy. Reperfusion therapy with intravenous alteplase is considered standard of care for acute ischemic stroke, but current guidelines recommend against the use of IVT for patients who have recently received a DOAC, owing to safety concerns that researchers say are not backed by strong clinical evidence.

A recent study found no significant difference in sICH among patients who received IV alteplase for acute ischemic stroke within 7 days of receiving therapy with non–vitamin K antagonist oral anticoagulants.

“In our daily clinical practice, we face a lot of patients who have received oral anticoagulation, many with atrial fibrillation, but a lot of other indicators as well, and they suffer from ischemic stroke,” Dr. Purrucker said. “They usually are ineligible for medical reperfusion therapy because of quite strict guideline recommendations at the moment. This is a daily clinical problem.”

Dr. Purrucker and colleagues in New Zealand and Switzerland launched an international, observational, multicenter cohort study to examine the issue.

Researchers collected data on patients with ischemic stroke who had last received DOAC therapy 48 hours or less before the event or whose last intake was unknown and who had received IVT. They included 20,448 patients, 830 of whom were receiving DOAC therapy at the time of stroke onset.

Among the DOAC users, 30% received DOAC reversal prior to IVT, 27% had their DOAC level measured, and 42% received IVT without reversal treatment or knowledge of DOAC levels.

Overall, 4.5% of patients developed sICH. Compared with the control group, DOAC users were half as likely to develop sICH (adjusted odds ratio, 0.47; P = .003).

There was no significant difference between groups in independent outcome at 3 months, defined as a Modified Rankin Scale score of 1 to 3 (aOR, 1.21; 95% confidence interval, 0.99-1.49).

This finding held across patient subgroups, including patients for whom selection methods differed and patients with very recent intake of less than 12 hours.

“The question is whether we are so confident in these data that we would change our clinical practice now,” Dr. Purrucker said.
 

Infrastructure needed

While the findings are promising, more data are needed to strengthen the argument for revising current IVT guidelines, said Ho-Yan Yvonne Chun, PhD, honorary senior clinical lecturer with the Centre for Clinical Brain Sciences at the University of Edinburgh and a consultant in stroke medicine for NHS Lothian and Borders General Hospital, who commented on the findings.

“The study sample are a highly selected group of patients from selected centers that have the infrastructure to offer DOAC level checking and DOAC reversal,” Dr. Chun said. “The selected centers are not representative of the majority of hospitals that offer IVT to stroke patients with acute stroke.”

Most hospitals lack the equipment necessary to test DOAC levels and don’t have immediate access to DOAC reversal agents, Dr. Chun said. In those centers, she added, the administration of IVT could be delayed, which might affect clinical outcomes.

“Infrastructure needs to be in place to ensure timely delivery of IVT to these patients,” Dr. Chun added. “This means that in real-world practice, hospitals need to have right logistical pathway in place in order to provide timely DOAC level checking and DOAC reversal agents.”

Dr. Chun added that “large pragmatic clinical trials, preferably multicentered, are needed to provide the definitive evidence on the safety and effectiveness of using these approaches to select patients with prior DOAC use for IVT.”

But such a study may not be feasible, Dr. Purrucker said. Among the hurdles he noted are the large sample size needed for such a trial, uncertainty regarding funding, and patient selection bias, resulting from the fact that such studies would likely exclude patients eligible for mechanical thrombectomy or those eligible for reversal treatment.

In light of earlier studies, including preclinical data that support the safety of DOACs in IVT, and these new data, Dr. Purrucker said he hopes a change in guidelines might be taken up in the future.

“But it should be good academic practice to first let the results be externally evaluated, for example, during the manuscript submission process,” he said. “But once published, guideline working groups will have to evaluate the recent and new evidence and might reconsider previous recommendations.”

The study received no commercial funding. Dr. Purrucker and Dr. Chun reported no relevant financial relationships.

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

Intravenous thrombolysis (IVT) for acute stroke appears safe for patients who have recently received direct oral anticoagulant (DOAC) therapy, a new observational study suggests, prompting researchers to ask whether guidelines that restrict its use should be updated.

Researchers found that DOAC users were significantly less likely to develop symptomatic intracerebral hemorrhage (sICH) after IVT, and there was no difference in functional independence at 3 months, compared with patients who received IVT but who did not receive DOAC.

“At the moment, the guidelines really pose a barrier and stop sign in front of the most important medical reperfusion therapy, which is thrombolysis,” said principal investigator Jan Purrucker, MD, professor of neurology at Heidelberg University Hospital.

“The main question we have to answer is, is IVT safe in patients with acute ischemic stroke who were pretreated with direct oral anticoagulants or not?”

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022, Lyon, France.
 

A ‘daily clinical problem’

As many as 20% of patients with atrial fibrillation experience ischemic stroke while receiving DOAC therapy. Reperfusion therapy with intravenous alteplase is considered standard of care for acute ischemic stroke, but current guidelines recommend against the use of IVT for patients who have recently received a DOAC, owing to safety concerns that researchers say are not backed by strong clinical evidence.

A recent study found no significant difference in sICH among patients who received IV alteplase for acute ischemic stroke within 7 days of receiving therapy with non–vitamin K antagonist oral anticoagulants.

“In our daily clinical practice, we face a lot of patients who have received oral anticoagulation, many with atrial fibrillation, but a lot of other indicators as well, and they suffer from ischemic stroke,” Dr. Purrucker said. “They usually are ineligible for medical reperfusion therapy because of quite strict guideline recommendations at the moment. This is a daily clinical problem.”

Dr. Purrucker and colleagues in New Zealand and Switzerland launched an international, observational, multicenter cohort study to examine the issue.

Researchers collected data on patients with ischemic stroke who had last received DOAC therapy 48 hours or less before the event or whose last intake was unknown and who had received IVT. They included 20,448 patients, 830 of whom were receiving DOAC therapy at the time of stroke onset.

Among the DOAC users, 30% received DOAC reversal prior to IVT, 27% had their DOAC level measured, and 42% received IVT without reversal treatment or knowledge of DOAC levels.

Overall, 4.5% of patients developed sICH. Compared with the control group, DOAC users were half as likely to develop sICH (adjusted odds ratio, 0.47; P = .003).

There was no significant difference between groups in independent outcome at 3 months, defined as a Modified Rankin Scale score of 1 to 3 (aOR, 1.21; 95% confidence interval, 0.99-1.49).

This finding held across patient subgroups, including patients for whom selection methods differed and patients with very recent intake of less than 12 hours.

“The question is whether we are so confident in these data that we would change our clinical practice now,” Dr. Purrucker said.
 

Infrastructure needed

While the findings are promising, more data are needed to strengthen the argument for revising current IVT guidelines, said Ho-Yan Yvonne Chun, PhD, honorary senior clinical lecturer with the Centre for Clinical Brain Sciences at the University of Edinburgh and a consultant in stroke medicine for NHS Lothian and Borders General Hospital, who commented on the findings.

“The study sample are a highly selected group of patients from selected centers that have the infrastructure to offer DOAC level checking and DOAC reversal,” Dr. Chun said. “The selected centers are not representative of the majority of hospitals that offer IVT to stroke patients with acute stroke.”

Most hospitals lack the equipment necessary to test DOAC levels and don’t have immediate access to DOAC reversal agents, Dr. Chun said. In those centers, she added, the administration of IVT could be delayed, which might affect clinical outcomes.

“Infrastructure needs to be in place to ensure timely delivery of IVT to these patients,” Dr. Chun added. “This means that in real-world practice, hospitals need to have right logistical pathway in place in order to provide timely DOAC level checking and DOAC reversal agents.”

Dr. Chun added that “large pragmatic clinical trials, preferably multicentered, are needed to provide the definitive evidence on the safety and effectiveness of using these approaches to select patients with prior DOAC use for IVT.”

But such a study may not be feasible, Dr. Purrucker said. Among the hurdles he noted are the large sample size needed for such a trial, uncertainty regarding funding, and patient selection bias, resulting from the fact that such studies would likely exclude patients eligible for mechanical thrombectomy or those eligible for reversal treatment.

In light of earlier studies, including preclinical data that support the safety of DOACs in IVT, and these new data, Dr. Purrucker said he hopes a change in guidelines might be taken up in the future.

“But it should be good academic practice to first let the results be externally evaluated, for example, during the manuscript submission process,” he said. “But once published, guideline working groups will have to evaluate the recent and new evidence and might reconsider previous recommendations.”

The study received no commercial funding. Dr. Purrucker and Dr. Chun reported no relevant financial relationships.

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

Intravenous thrombolysis (IVT) for acute stroke appears safe for patients who have recently received direct oral anticoagulant (DOAC) therapy, a new observational study suggests, prompting researchers to ask whether guidelines that restrict its use should be updated.

Researchers found that DOAC users were significantly less likely to develop symptomatic intracerebral hemorrhage (sICH) after IVT, and there was no difference in functional independence at 3 months, compared with patients who received IVT but who did not receive DOAC.

“At the moment, the guidelines really pose a barrier and stop sign in front of the most important medical reperfusion therapy, which is thrombolysis,” said principal investigator Jan Purrucker, MD, professor of neurology at Heidelberg University Hospital.

“The main question we have to answer is, is IVT safe in patients with acute ischemic stroke who were pretreated with direct oral anticoagulants or not?”

The findings were presented at the European Stroke Organisation Conference (ESOC) 2022, Lyon, France.
 

A ‘daily clinical problem’

As many as 20% of patients with atrial fibrillation experience ischemic stroke while receiving DOAC therapy. Reperfusion therapy with intravenous alteplase is considered standard of care for acute ischemic stroke, but current guidelines recommend against the use of IVT for patients who have recently received a DOAC, owing to safety concerns that researchers say are not backed by strong clinical evidence.

A recent study found no significant difference in sICH among patients who received IV alteplase for acute ischemic stroke within 7 days of receiving therapy with non–vitamin K antagonist oral anticoagulants.

“In our daily clinical practice, we face a lot of patients who have received oral anticoagulation, many with atrial fibrillation, but a lot of other indicators as well, and they suffer from ischemic stroke,” Dr. Purrucker said. “They usually are ineligible for medical reperfusion therapy because of quite strict guideline recommendations at the moment. This is a daily clinical problem.”

Dr. Purrucker and colleagues in New Zealand and Switzerland launched an international, observational, multicenter cohort study to examine the issue.

Researchers collected data on patients with ischemic stroke who had last received DOAC therapy 48 hours or less before the event or whose last intake was unknown and who had received IVT. They included 20,448 patients, 830 of whom were receiving DOAC therapy at the time of stroke onset.

Among the DOAC users, 30% received DOAC reversal prior to IVT, 27% had their DOAC level measured, and 42% received IVT without reversal treatment or knowledge of DOAC levels.

Overall, 4.5% of patients developed sICH. Compared with the control group, DOAC users were half as likely to develop sICH (adjusted odds ratio, 0.47; P = .003).

There was no significant difference between groups in independent outcome at 3 months, defined as a Modified Rankin Scale score of 1 to 3 (aOR, 1.21; 95% confidence interval, 0.99-1.49).

This finding held across patient subgroups, including patients for whom selection methods differed and patients with very recent intake of less than 12 hours.

“The question is whether we are so confident in these data that we would change our clinical practice now,” Dr. Purrucker said.
 

Infrastructure needed

While the findings are promising, more data are needed to strengthen the argument for revising current IVT guidelines, said Ho-Yan Yvonne Chun, PhD, honorary senior clinical lecturer with the Centre for Clinical Brain Sciences at the University of Edinburgh and a consultant in stroke medicine for NHS Lothian and Borders General Hospital, who commented on the findings.

“The study sample are a highly selected group of patients from selected centers that have the infrastructure to offer DOAC level checking and DOAC reversal,” Dr. Chun said. “The selected centers are not representative of the majority of hospitals that offer IVT to stroke patients with acute stroke.”

Most hospitals lack the equipment necessary to test DOAC levels and don’t have immediate access to DOAC reversal agents, Dr. Chun said. In those centers, she added, the administration of IVT could be delayed, which might affect clinical outcomes.

“Infrastructure needs to be in place to ensure timely delivery of IVT to these patients,” Dr. Chun added. “This means that in real-world practice, hospitals need to have right logistical pathway in place in order to provide timely DOAC level checking and DOAC reversal agents.”

Dr. Chun added that “large pragmatic clinical trials, preferably multicentered, are needed to provide the definitive evidence on the safety and effectiveness of using these approaches to select patients with prior DOAC use for IVT.”

But such a study may not be feasible, Dr. Purrucker said. Among the hurdles he noted are the large sample size needed for such a trial, uncertainty regarding funding, and patient selection bias, resulting from the fact that such studies would likely exclude patients eligible for mechanical thrombectomy or those eligible for reversal treatment.

In light of earlier studies, including preclinical data that support the safety of DOACs in IVT, and these new data, Dr. Purrucker said he hopes a change in guidelines might be taken up in the future.

“But it should be good academic practice to first let the results be externally evaluated, for example, during the manuscript submission process,” he said. “But once published, guideline working groups will have to evaluate the recent and new evidence and might reconsider previous recommendations.”

The study received no commercial funding. Dr. Purrucker and Dr. Chun reported no relevant financial relationships.

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

A federal sting operation led to the recent conviction of a Texas physician assistant on charges of illegally prescribing a total of $3 million in drugs to patients at two “pill mill” clinics in Houston and helping others do the same.

The May 20 conviction of Charles Thompson, 76, of Houston, was based on charges of distributing more than 1.2 million opioid pills to thousands of individuals posing as patients at two pain management clinics, according to the U.S. Department of Justice.

Thompson’s conviction was the latest legal action in a string of cases involving the operation, including a doctor convicted in March who worked with Thompson at the West Parker Medical Clinic. Internist James Pierre, MD, 52, faces charges of unlawfully prescribing more than $1 million worth of opioid hydrocodone, according to federal officials.

Thompson also worked at Priority Wellness Clinic. Six people have pled guilty in connection with their conduct at West Parker or Priority Wellness, the justice department reported.

From June 2015 through July 2016, while Thompson was at West Parker, he helped Dr. Pierre unlawfully prescribe hydrocodone and the muscle relaxant carisoprodol, a combination of controlled substances for pain management known as the “Las Vegas cocktail,” to people in the sting operations pretending to be patients, authorities stated.

Thompson also distributed unlawful prescriptions for carisoprodol. So-called “runners” brought numerous people to pose as patients at West Parker and paid the clinic about $220 to $500 in cash for each visit that resulted in prescriptions for dangerous drugs. Throughout the scheme, West Parker pocketed about $1.75 million from prescriptions; Thompson was paid more than $208,000.

According to authorities, Thompson also helped others illegally prescribe controlled substances, including hydrocodone and oxycodone, from May to July 2017 at Priority Wellness, which opened in December 2016 after West Parker closed.

Priority Wellness reportedly operated as a pill mill similar to West Parker’s. Runners brought people posing as patients to Priority Wellness and paid the clinic between $300 and $600. The cost depended on whether the purported patient received a prescription for hydrocodone or oxycodone, almost always prescribed in combination with carisoprodol, authorities said. Throughout the scheme, Priority Wellness made about $1.1 million, and Thompson made between $700 and $900 a day.

He was convicted of one count of conspiracy to unlawfully distribute and dispense controlled substances and seven counts of unlawfully distributing and dispensing controlled substances in connection with his conduct at West Parker. For his conduct at Priority Wellness, he was convicted of one count of conspiracy to unlawfully distribute and dispense controlled substances and one count of unlawfully distributing and dispensing controlled substances.

He faces up to 20 years in prison for each count of conviction with sentencing scheduled for Oct. 3.

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

A federal sting operation led to the recent conviction of a Texas physician assistant on charges of illegally prescribing a total of $3 million in drugs to patients at two “pill mill” clinics in Houston and helping others do the same.

The May 20 conviction of Charles Thompson, 76, of Houston, was based on charges of distributing more than 1.2 million opioid pills to thousands of individuals posing as patients at two pain management clinics, according to the U.S. Department of Justice.

Thompson’s conviction was the latest legal action in a string of cases involving the operation, including a doctor convicted in March who worked with Thompson at the West Parker Medical Clinic. Internist James Pierre, MD, 52, faces charges of unlawfully prescribing more than $1 million worth of opioid hydrocodone, according to federal officials.

Thompson also worked at Priority Wellness Clinic. Six people have pled guilty in connection with their conduct at West Parker or Priority Wellness, the justice department reported.

From June 2015 through July 2016, while Thompson was at West Parker, he helped Dr. Pierre unlawfully prescribe hydrocodone and the muscle relaxant carisoprodol, a combination of controlled substances for pain management known as the “Las Vegas cocktail,” to people in the sting operations pretending to be patients, authorities stated.

Thompson also distributed unlawful prescriptions for carisoprodol. So-called “runners” brought numerous people to pose as patients at West Parker and paid the clinic about $220 to $500 in cash for each visit that resulted in prescriptions for dangerous drugs. Throughout the scheme, West Parker pocketed about $1.75 million from prescriptions; Thompson was paid more than $208,000.

According to authorities, Thompson also helped others illegally prescribe controlled substances, including hydrocodone and oxycodone, from May to July 2017 at Priority Wellness, which opened in December 2016 after West Parker closed.

Priority Wellness reportedly operated as a pill mill similar to West Parker’s. Runners brought people posing as patients to Priority Wellness and paid the clinic between $300 and $600. The cost depended on whether the purported patient received a prescription for hydrocodone or oxycodone, almost always prescribed in combination with carisoprodol, authorities said. Throughout the scheme, Priority Wellness made about $1.1 million, and Thompson made between $700 and $900 a day.

He was convicted of one count of conspiracy to unlawfully distribute and dispense controlled substances and seven counts of unlawfully distributing and dispensing controlled substances in connection with his conduct at West Parker. For his conduct at Priority Wellness, he was convicted of one count of conspiracy to unlawfully distribute and dispense controlled substances and one count of unlawfully distributing and dispensing controlled substances.

He faces up to 20 years in prison for each count of conviction with sentencing scheduled for Oct. 3.

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

A federal sting operation led to the recent conviction of a Texas physician assistant on charges of illegally prescribing a total of $3 million in drugs to patients at two “pill mill” clinics in Houston and helping others do the same.

The May 20 conviction of Charles Thompson, 76, of Houston, was based on charges of distributing more than 1.2 million opioid pills to thousands of individuals posing as patients at two pain management clinics, according to the U.S. Department of Justice.

Thompson’s conviction was the latest legal action in a string of cases involving the operation, including a doctor convicted in March who worked with Thompson at the West Parker Medical Clinic. Internist James Pierre, MD, 52, faces charges of unlawfully prescribing more than $1 million worth of opioid hydrocodone, according to federal officials.

Thompson also worked at Priority Wellness Clinic. Six people have pled guilty in connection with their conduct at West Parker or Priority Wellness, the justice department reported.

From June 2015 through July 2016, while Thompson was at West Parker, he helped Dr. Pierre unlawfully prescribe hydrocodone and the muscle relaxant carisoprodol, a combination of controlled substances for pain management known as the “Las Vegas cocktail,” to people in the sting operations pretending to be patients, authorities stated.

Thompson also distributed unlawful prescriptions for carisoprodol. So-called “runners” brought numerous people to pose as patients at West Parker and paid the clinic about $220 to $500 in cash for each visit that resulted in prescriptions for dangerous drugs. Throughout the scheme, West Parker pocketed about $1.75 million from prescriptions; Thompson was paid more than $208,000.

According to authorities, Thompson also helped others illegally prescribe controlled substances, including hydrocodone and oxycodone, from May to July 2017 at Priority Wellness, which opened in December 2016 after West Parker closed.

Priority Wellness reportedly operated as a pill mill similar to West Parker’s. Runners brought people posing as patients to Priority Wellness and paid the clinic between $300 and $600. The cost depended on whether the purported patient received a prescription for hydrocodone or oxycodone, almost always prescribed in combination with carisoprodol, authorities said. Throughout the scheme, Priority Wellness made about $1.1 million, and Thompson made between $700 and $900 a day.

He was convicted of one count of conspiracy to unlawfully distribute and dispense controlled substances and seven counts of unlawfully distributing and dispensing controlled substances in connection with his conduct at West Parker. For his conduct at Priority Wellness, he was convicted of one count of conspiracy to unlawfully distribute and dispense controlled substances and one count of unlawfully distributing and dispensing controlled substances.

He faces up to 20 years in prison for each count of conviction with sentencing scheduled for Oct. 3.

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