When a child presents with café au lait macules, when is genetic testing for neurofibromatosis type 1 (NF1) advised?

According to Peter Kannu, MB, ChB, DCH, PhD, a definitive diagnosis of NF1 can be made in most children using National Institutes of Health criteria published in 1988, which include the presence of two of the following:

• Six or more café au lait macules over 5 mm in diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals
• Two or more neurofibromas of any type or one plexiform neurofibroma
• Freckling in the axillary or inguinal regions
• Two or more Lisch nodules
• Optic glioma
• A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudarthrosis
• Having a first-degree relative with NF1

For example, in the case of an 8-year-old child who presents with multiple café au lait macules, axillary and inguinal freckling, Lisch nodules, and an optic glioma, “the diagnosis is secure and genetic testing is not going to change clinical management or surveillance,” Dr. Kannu, a clinical geneticist at the University of Alberta, Edmonton, said during the annual meeting of the Society for Pediatric Dermatology. “The only reason for genetic testing in this situation is so that we know the mutation in order to inform reproductive risk counseling in the future.”

However, while a diagnosis of NF1 may be suspected in a 6- to 12-month-old presenting with only café au lait macules, “the diagnosis is not secure because the clinical criteria cannot be met. In this situation, a genetic test can speed up the diagnosis,” he added. “Or, if the test is negative, it can decrease your suspicion for NF1 and you wouldn’t refer the child on to an NF1 screening clinic for intensive surveillance.”

Dr. Kannu based his remarks largely on his 5 years working at the multidisciplinary Genodermatoses Clinic at the Hospital for Sick Children, Toronto. Founded in 2015, the clinic is a “one-stop shop” designed to reduce the wait time for diagnosis and management and the number of hospital visits. The team – composed of a dermatologist, medical geneticist, genetic counselor, residents, and fellows – meets to review the charts of each patient before the appointment, and decides on a preliminary management plan. All children are then seen by one of the trainees in the clinic who devises a differential diagnosis that is presented to staff physicians, at which point genetic testing is decided on. A genetics counselor handles follow-up for those who do have genetic testing.

In 2018, Dr. Kannu and colleagues conducted an informal review of 300 patients who had been seen in the clinic. The mean age at referral was about 6 years, 51% were female, and the top three referral sources were pediatricians (51%), dermatologists (18%), and family physicians (18%). Of the 300 children, 84 (28%) were confirmed to have a diagnosis of NF1. Two patients were diagnosed with NF2 and 5% of the total cohort was diagnosed with mosaic NF1 (MNF1), “which is higher than what you would expect based on the incidence of MNF1 in the literature,” he said.

He separates genetic tests for NF1 into one of two categories: Conventional testing, which is offered by most labs in North America; and comprehensive testing, which is offered by the medical genomics lab at the University of Alabama at Birmingham. Conventional testing focuses on the exons, “the protein coding regions of the gene where most of the mutations lie,” he said. “The test also sequences about 20 base pairs or so of the intron exon boundary and may pick up some intronic mutations. But this test will not detect anything that’s hidden deep in the intronic region.”

Comprehensive testing, meanwhile, checks for mutations in both introns and exons.

Dr. Kannu and colleagues published a case of a paraspinal ganglioneuroma in the proband of a large family with mild cutaneous manifestations of NF1, carrying a deep NF1 intronic mutation. “The clinicians were suspicious that this was NF1, rightly so. The diagnosis was only confirmed after we sent samples to the University of Alabama lab where the deep intronic mutation was found,” he said.

The other situation where conventional genetic testing may be negative is in the case of MNF1, where there “are mutations in some cells but not all cells,” Dr. Kannu explained. “It may only be present in the melanocytes of the skin but not present in the lymphocytes in the blood. Mosaicism is characterized by the regional distribution of pigmentary or other NF1 associated findings. Mosaicism may be detected in the blood if it’s more than 20%. Anything less than that is not detected with conventional genetic testing using DNA from blood and requires extracting DNA from a punch biopsy sample of a café au lait macule.”

The differential diagnosis of café au lait macules includes several conditions associated mutations in the RAS pathway. “Neurofibromin is a key signal of molecules which regulates the activation of RAS,” Dr. Kannu said. “A close binding partner of NF1 is SPRED 1. We know that mutations in this gene cause Legius syndrome, a condition which presents with multiple café au lait macules.”

Two key receptors in the RAS pathway include EGFR and KITL, he continued. Mutations in the EGFR receptor cause a rare condition known as neonatal skin and bowel disease, while mutations in the KITL receptor cause familial progressive hyperpigmentation with or without hypopigmentation. “Looking into the pathway and focusing downstream of RAS, we have genes such as RAF and CBL, which are mutated in Noonan syndrome,” he said. “Further along in the pathway you have mutations in PTEN, which cause Cowden syndrome, and mutations in TSC1 and TSC2, which cause tuberous sclerosis. Mutations in any of these genes can also present with café au lait macules.”

During a question-and-answer session Dr. Kannu was asked to comment about revised diagnostic criteria for NF1 based on an international consensus recommendation, such as changes in the eye that require a formal opthalmologic examination, which were recently published.

“We are understanding more about the phenotype,” he said. “If you fulfill diagnostic criteria for NF1, the main reasons for doing genetic testing are, one, if the family wants to know that information, and two, it informs our reproductive risk counseling. Genotype-phenotype correlations do exist in NF1 but they’re not very robust, so that information is not clinically useful.”

Dr. Kannu disclosed that he has been an advisory board member for Ipsen, Novartis, and Alexion. He has also been a primary investigator for QED and Clementia.

[email protected]

When a child presents with café au lait macules, when is genetic testing for neurofibromatosis type 1 (NF1) advised?

According to Peter Kannu, MB, ChB, DCH, PhD, a definitive diagnosis of NF1 can be made in most children using National Institutes of Health criteria published in 1988, which include the presence of two of the following:

• Six or more café au lait macules over 5 mm in diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals
• Two or more neurofibromas of any type or one plexiform neurofibroma
• Freckling in the axillary or inguinal regions
• Two or more Lisch nodules
• Optic glioma
• A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudarthrosis
• Having a first-degree relative with NF1

For example, in the case of an 8-year-old child who presents with multiple café au lait macules, axillary and inguinal freckling, Lisch nodules, and an optic glioma, “the diagnosis is secure and genetic testing is not going to change clinical management or surveillance,” Dr. Kannu, a clinical geneticist at the University of Alberta, Edmonton, said during the annual meeting of the Society for Pediatric Dermatology. “The only reason for genetic testing in this situation is so that we know the mutation in order to inform reproductive risk counseling in the future.”

However, while a diagnosis of NF1 may be suspected in a 6- to 12-month-old presenting with only café au lait macules, “the diagnosis is not secure because the clinical criteria cannot be met. In this situation, a genetic test can speed up the diagnosis,” he added. “Or, if the test is negative, it can decrease your suspicion for NF1 and you wouldn’t refer the child on to an NF1 screening clinic for intensive surveillance.”

Dr. Kannu based his remarks largely on his 5 years working at the multidisciplinary Genodermatoses Clinic at the Hospital for Sick Children, Toronto. Founded in 2015, the clinic is a “one-stop shop” designed to reduce the wait time for diagnosis and management and the number of hospital visits. The team – composed of a dermatologist, medical geneticist, genetic counselor, residents, and fellows – meets to review the charts of each patient before the appointment, and decides on a preliminary management plan. All children are then seen by one of the trainees in the clinic who devises a differential diagnosis that is presented to staff physicians, at which point genetic testing is decided on. A genetics counselor handles follow-up for those who do have genetic testing.

In 2018, Dr. Kannu and colleagues conducted an informal review of 300 patients who had been seen in the clinic. The mean age at referral was about 6 years, 51% were female, and the top three referral sources were pediatricians (51%), dermatologists (18%), and family physicians (18%). Of the 300 children, 84 (28%) were confirmed to have a diagnosis of NF1. Two patients were diagnosed with NF2 and 5% of the total cohort was diagnosed with mosaic NF1 (MNF1), “which is higher than what you would expect based on the incidence of MNF1 in the literature,” he said.

He separates genetic tests for NF1 into one of two categories: Conventional testing, which is offered by most labs in North America; and comprehensive testing, which is offered by the medical genomics lab at the University of Alabama at Birmingham. Conventional testing focuses on the exons, “the protein coding regions of the gene where most of the mutations lie,” he said. “The test also sequences about 20 base pairs or so of the intron exon boundary and may pick up some intronic mutations. But this test will not detect anything that’s hidden deep in the intronic region.”

Comprehensive testing, meanwhile, checks for mutations in both introns and exons.

Dr. Kannu and colleagues published a case of a paraspinal ganglioneuroma in the proband of a large family with mild cutaneous manifestations of NF1, carrying a deep NF1 intronic mutation. “The clinicians were suspicious that this was NF1, rightly so. The diagnosis was only confirmed after we sent samples to the University of Alabama lab where the deep intronic mutation was found,” he said.

The other situation where conventional genetic testing may be negative is in the case of MNF1, where there “are mutations in some cells but not all cells,” Dr. Kannu explained. “It may only be present in the melanocytes of the skin but not present in the lymphocytes in the blood. Mosaicism is characterized by the regional distribution of pigmentary or other NF1 associated findings. Mosaicism may be detected in the blood if it’s more than 20%. Anything less than that is not detected with conventional genetic testing using DNA from blood and requires extracting DNA from a punch biopsy sample of a café au lait macule.”

The differential diagnosis of café au lait macules includes several conditions associated mutations in the RAS pathway. “Neurofibromin is a key signal of molecules which regulates the activation of RAS,” Dr. Kannu said. “A close binding partner of NF1 is SPRED 1. We know that mutations in this gene cause Legius syndrome, a condition which presents with multiple café au lait macules.”

Two key receptors in the RAS pathway include EGFR and KITL, he continued. Mutations in the EGFR receptor cause a rare condition known as neonatal skin and bowel disease, while mutations in the KITL receptor cause familial progressive hyperpigmentation with or without hypopigmentation. “Looking into the pathway and focusing downstream of RAS, we have genes such as RAF and CBL, which are mutated in Noonan syndrome,” he said. “Further along in the pathway you have mutations in PTEN, which cause Cowden syndrome, and mutations in TSC1 and TSC2, which cause tuberous sclerosis. Mutations in any of these genes can also present with café au lait macules.”

During a question-and-answer session Dr. Kannu was asked to comment about revised diagnostic criteria for NF1 based on an international consensus recommendation, such as changes in the eye that require a formal opthalmologic examination, which were recently published.

“We are understanding more about the phenotype,” he said. “If you fulfill diagnostic criteria for NF1, the main reasons for doing genetic testing are, one, if the family wants to know that information, and two, it informs our reproductive risk counseling. Genotype-phenotype correlations do exist in NF1 but they’re not very robust, so that information is not clinically useful.”

Dr. Kannu disclosed that he has been an advisory board member for Ipsen, Novartis, and Alexion. He has also been a primary investigator for QED and Clementia.

[email protected]

When a child presents with café au lait macules, when is genetic testing for neurofibromatosis type 1 (NF1) advised?

According to Peter Kannu, MB, ChB, DCH, PhD, a definitive diagnosis of NF1 can be made in most children using National Institutes of Health criteria published in 1988, which include the presence of two of the following:

• Six or more café au lait macules over 5 mm in diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals
• Two or more neurofibromas of any type or one plexiform neurofibroma
• Freckling in the axillary or inguinal regions
• Two or more Lisch nodules
• Optic glioma
• A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudarthrosis
• Having a first-degree relative with NF1

For example, in the case of an 8-year-old child who presents with multiple café au lait macules, axillary and inguinal freckling, Lisch nodules, and an optic glioma, “the diagnosis is secure and genetic testing is not going to change clinical management or surveillance,” Dr. Kannu, a clinical geneticist at the University of Alberta, Edmonton, said during the annual meeting of the Society for Pediatric Dermatology. “The only reason for genetic testing in this situation is so that we know the mutation in order to inform reproductive risk counseling in the future.”

However, while a diagnosis of NF1 may be suspected in a 6- to 12-month-old presenting with only café au lait macules, “the diagnosis is not secure because the clinical criteria cannot be met. In this situation, a genetic test can speed up the diagnosis,” he added. “Or, if the test is negative, it can decrease your suspicion for NF1 and you wouldn’t refer the child on to an NF1 screening clinic for intensive surveillance.”

Dr. Kannu based his remarks largely on his 5 years working at the multidisciplinary Genodermatoses Clinic at the Hospital for Sick Children, Toronto. Founded in 2015, the clinic is a “one-stop shop” designed to reduce the wait time for diagnosis and management and the number of hospital visits. The team – composed of a dermatologist, medical geneticist, genetic counselor, residents, and fellows – meets to review the charts of each patient before the appointment, and decides on a preliminary management plan. All children are then seen by one of the trainees in the clinic who devises a differential diagnosis that is presented to staff physicians, at which point genetic testing is decided on. A genetics counselor handles follow-up for those who do have genetic testing.

In 2018, Dr. Kannu and colleagues conducted an informal review of 300 patients who had been seen in the clinic. The mean age at referral was about 6 years, 51% were female, and the top three referral sources were pediatricians (51%), dermatologists (18%), and family physicians (18%). Of the 300 children, 84 (28%) were confirmed to have a diagnosis of NF1. Two patients were diagnosed with NF2 and 5% of the total cohort was diagnosed with mosaic NF1 (MNF1), “which is higher than what you would expect based on the incidence of MNF1 in the literature,” he said.

He separates genetic tests for NF1 into one of two categories: Conventional testing, which is offered by most labs in North America; and comprehensive testing, which is offered by the medical genomics lab at the University of Alabama at Birmingham. Conventional testing focuses on the exons, “the protein coding regions of the gene where most of the mutations lie,” he said. “The test also sequences about 20 base pairs or so of the intron exon boundary and may pick up some intronic mutations. But this test will not detect anything that’s hidden deep in the intronic region.”

Comprehensive testing, meanwhile, checks for mutations in both introns and exons.

Dr. Kannu and colleagues published a case of a paraspinal ganglioneuroma in the proband of a large family with mild cutaneous manifestations of NF1, carrying a deep NF1 intronic mutation. “The clinicians were suspicious that this was NF1, rightly so. The diagnosis was only confirmed after we sent samples to the University of Alabama lab where the deep intronic mutation was found,” he said.

The other situation where conventional genetic testing may be negative is in the case of MNF1, where there “are mutations in some cells but not all cells,” Dr. Kannu explained. “It may only be present in the melanocytes of the skin but not present in the lymphocytes in the blood. Mosaicism is characterized by the regional distribution of pigmentary or other NF1 associated findings. Mosaicism may be detected in the blood if it’s more than 20%. Anything less than that is not detected with conventional genetic testing using DNA from blood and requires extracting DNA from a punch biopsy sample of a café au lait macule.”

The differential diagnosis of café au lait macules includes several conditions associated mutations in the RAS pathway. “Neurofibromin is a key signal of molecules which regulates the activation of RAS,” Dr. Kannu said. “A close binding partner of NF1 is SPRED 1. We know that mutations in this gene cause Legius syndrome, a condition which presents with multiple café au lait macules.”

Two key receptors in the RAS pathway include EGFR and KITL, he continued. Mutations in the EGFR receptor cause a rare condition known as neonatal skin and bowel disease, while mutations in the KITL receptor cause familial progressive hyperpigmentation with or without hypopigmentation. “Looking into the pathway and focusing downstream of RAS, we have genes such as RAF and CBL, which are mutated in Noonan syndrome,” he said. “Further along in the pathway you have mutations in PTEN, which cause Cowden syndrome, and mutations in TSC1 and TSC2, which cause tuberous sclerosis. Mutations in any of these genes can also present with café au lait macules.”

During a question-and-answer session Dr. Kannu was asked to comment about revised diagnostic criteria for NF1 based on an international consensus recommendation, such as changes in the eye that require a formal opthalmologic examination, which were recently published.

“We are understanding more about the phenotype,” he said. “If you fulfill diagnostic criteria for NF1, the main reasons for doing genetic testing are, one, if the family wants to know that information, and two, it informs our reproductive risk counseling. Genotype-phenotype correlations do exist in NF1 but they’re not very robust, so that information is not clinically useful.”

Dr. Kannu disclosed that he has been an advisory board member for Ipsen, Novartis, and Alexion. He has also been a primary investigator for QED and Clementia.

[email protected]

It’s not necessary to completely eradicate all Clostridioides difficile to successfully treat recurrent C. difficile infections with fecal microbiota transplant (FMT), according to a study presented online July 12 at the European Congress of Clinical Microbiology & Infectious Diseases.

C. difficile colonization persisted for 3 weeks after FMT in about one-quarter of patients, but it’s not clear whether this is a persistent infection, a newly acquired infection, or partial persistence of a mixed infection, said Elisabeth Terveer, MD, a medical microbiologist at Leiden (the Netherlands) University Medical Center. In addition, “82% of patients with detectable C. diff do not relapse, so it’s absolutely not necessary for a cure,” she said.

Several mechanisms explain why FMT is a highly effective therapy for recurrent C. difficile infections, including restoration of bacterial metabolism in the gut, immune modulation, and direct competition between bacteria, Dr. Terveer said, but it’s less clear whether eradication of C. difficile spores is among these mechanisms. 

Between May 2016 and April 2020, the researchers analyzed fecal samples from 84 patients who took vancomycin for at least 4 days before undergoing FMT. The researchers took fecal samples from patients before FMT and 3 weeks after FMT to culture them and the donor samples for presence of C. difficile, and they assessed clinical outcomes at 3 weeks and 6 months after FMT.

After antibiotic treatment but prior to FMT, 19% of patients (n = 16) still had a toxigenic C. difficile culture while the other 81% had a negative culture. None of the donor samples had a positive C. difficile culture. After FMT treatment, five patients who had a positive pre-FMT culture remained positive, and the other 11 were negative. Among the 81% of patients (n = 68) who had a negative culture just before FMT, 22 had a positive culture and 46 had a negative culture after FMT. Overall, 26% of patients post FMT had a positive C. difficile culture, a finding that was 10-fold higher than another study that assessed C. difficile with PCR testing, Dr. Terveer said.

The clinical cure rate after FMT was 94%, and five patients had relapses within 2 months of their FMT. These relapses were more prevalent in patients with a positive C. difficile culture prior to FMT (odds ratio [OR], 7.6; P = .045) and a positive C. difficile culture after FMT (OR, 13.6; P = .016). Still, 82% of patients who had a positive C. difficile culture post FMT remained clinically cured 2 months later.

It’s unclear why 19% of patients had a positive culture after their antibiotic pretreatment prior to FMT, Dr. Terveer said, but it may be because the pretreatment was of such a short duration.

“I think the advice should be: Give a full anti–C. diff antibiotic course to treat the C. diff infection, and then give FMT afterward to restore the microbiota and prevent further relapses,” Dr. Terveer told attendees.

Dimitri Drekonja, MD, chief of the Minneapolis VA Infectious Disease Section, said the findings were not necessarily surprising, but it would have been interesting for the researchers to have conducted DNA sequencing of the patients’ fecal samples post FMT to see what the biological diversity looked like.

“One school of thought has been that you have to repopulate the normal diverse microbiota of the colon” with FMT, and the other “is that you need to get rid of the C. diff that›s there,” Dr. Drekonja, who was not involved in the study, said in an interview. “I think more people think it’s the diverse microbiota because if it’s just getting rid of C. diff, we can get do that with antibiotics – but that gets rid of the other organisms.”

As long as you have a diverse microbiota post FMT, Dr. Drekonja said, then “having a few residual organisms, even if they get magnified in the culture process, is probably not that big a deal.”

But there’s a third school of thought that Dr. Drekonja said he himself falls into: “I don’t really care how it works, just that in well-done trials, it does work.” As long as large, robust, well-blinded trials show that FMT works, “I’m open to all sorts of ideas of what the mechanism is,” he said. “The main thing is that it does or doesn’t work.”

These findings basically reinforce current guidance not to test patients’ stools if they are asymptomatic, Dr. Drekonja said. In the past, clinicians sometimes tested patients’ stool after therapy to ensure the C. difficile was eradicated, regardless of whether the patient had symptoms of infection, he said.

“We’ve since become much more attuned that there are lots of people who have detectable C. diff in their stool without any symptoms,” whether detectable by culture or PCR, Dr. Drekonja said. “Generally, if you’re doing well and you’re not having diarrhea, don’t test, and if someone does test and finds it, pretend you didn’t see the test,” he advised. “This is a big part of diagnostic stewardship, which is: You don’t go testing people who are doing well.”

The Netherlands Donor Feces Bank used in the research is funded by a grant from Vedanta Biosciences. Dr. Drekonja had no disclosures.

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

It’s not necessary to completely eradicate all Clostridioides difficile to successfully treat recurrent C. difficile infections with fecal microbiota transplant (FMT), according to a study presented online July 12 at the European Congress of Clinical Microbiology & Infectious Diseases.

C. difficile colonization persisted for 3 weeks after FMT in about one-quarter of patients, but it’s not clear whether this is a persistent infection, a newly acquired infection, or partial persistence of a mixed infection, said Elisabeth Terveer, MD, a medical microbiologist at Leiden (the Netherlands) University Medical Center. In addition, “82% of patients with detectable C. diff do not relapse, so it’s absolutely not necessary for a cure,” she said.

Several mechanisms explain why FMT is a highly effective therapy for recurrent C. difficile infections, including restoration of bacterial metabolism in the gut, immune modulation, and direct competition between bacteria, Dr. Terveer said, but it’s less clear whether eradication of C. difficile spores is among these mechanisms. 

Between May 2016 and April 2020, the researchers analyzed fecal samples from 84 patients who took vancomycin for at least 4 days before undergoing FMT. The researchers took fecal samples from patients before FMT and 3 weeks after FMT to culture them and the donor samples for presence of C. difficile, and they assessed clinical outcomes at 3 weeks and 6 months after FMT.

After antibiotic treatment but prior to FMT, 19% of patients (n = 16) still had a toxigenic C. difficile culture while the other 81% had a negative culture. None of the donor samples had a positive C. difficile culture. After FMT treatment, five patients who had a positive pre-FMT culture remained positive, and the other 11 were negative. Among the 81% of patients (n = 68) who had a negative culture just before FMT, 22 had a positive culture and 46 had a negative culture after FMT. Overall, 26% of patients post FMT had a positive C. difficile culture, a finding that was 10-fold higher than another study that assessed C. difficile with PCR testing, Dr. Terveer said.

The clinical cure rate after FMT was 94%, and five patients had relapses within 2 months of their FMT. These relapses were more prevalent in patients with a positive C. difficile culture prior to FMT (odds ratio [OR], 7.6; P = .045) and a positive C. difficile culture after FMT (OR, 13.6; P = .016). Still, 82% of patients who had a positive C. difficile culture post FMT remained clinically cured 2 months later.

It’s unclear why 19% of patients had a positive culture after their antibiotic pretreatment prior to FMT, Dr. Terveer said, but it may be because the pretreatment was of such a short duration.

“I think the advice should be: Give a full anti–C. diff antibiotic course to treat the C. diff infection, and then give FMT afterward to restore the microbiota and prevent further relapses,” Dr. Terveer told attendees.

Dimitri Drekonja, MD, chief of the Minneapolis VA Infectious Disease Section, said the findings were not necessarily surprising, but it would have been interesting for the researchers to have conducted DNA sequencing of the patients’ fecal samples post FMT to see what the biological diversity looked like.

“One school of thought has been that you have to repopulate the normal diverse microbiota of the colon” with FMT, and the other “is that you need to get rid of the C. diff that›s there,” Dr. Drekonja, who was not involved in the study, said in an interview. “I think more people think it’s the diverse microbiota because if it’s just getting rid of C. diff, we can get do that with antibiotics – but that gets rid of the other organisms.”

As long as you have a diverse microbiota post FMT, Dr. Drekonja said, then “having a few residual organisms, even if they get magnified in the culture process, is probably not that big a deal.”

But there’s a third school of thought that Dr. Drekonja said he himself falls into: “I don’t really care how it works, just that in well-done trials, it does work.” As long as large, robust, well-blinded trials show that FMT works, “I’m open to all sorts of ideas of what the mechanism is,” he said. “The main thing is that it does or doesn’t work.”

These findings basically reinforce current guidance not to test patients’ stools if they are asymptomatic, Dr. Drekonja said. In the past, clinicians sometimes tested patients’ stool after therapy to ensure the C. difficile was eradicated, regardless of whether the patient had symptoms of infection, he said.

“We’ve since become much more attuned that there are lots of people who have detectable C. diff in their stool without any symptoms,” whether detectable by culture or PCR, Dr. Drekonja said. “Generally, if you’re doing well and you’re not having diarrhea, don’t test, and if someone does test and finds it, pretend you didn’t see the test,” he advised. “This is a big part of diagnostic stewardship, which is: You don’t go testing people who are doing well.”

The Netherlands Donor Feces Bank used in the research is funded by a grant from Vedanta Biosciences. Dr. Drekonja had no disclosures.

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

It’s not necessary to completely eradicate all Clostridioides difficile to successfully treat recurrent C. difficile infections with fecal microbiota transplant (FMT), according to a study presented online July 12 at the European Congress of Clinical Microbiology & Infectious Diseases.

C. difficile colonization persisted for 3 weeks after FMT in about one-quarter of patients, but it’s not clear whether this is a persistent infection, a newly acquired infection, or partial persistence of a mixed infection, said Elisabeth Terveer, MD, a medical microbiologist at Leiden (the Netherlands) University Medical Center. In addition, “82% of patients with detectable C. diff do not relapse, so it’s absolutely not necessary for a cure,” she said.

Several mechanisms explain why FMT is a highly effective therapy for recurrent C. difficile infections, including restoration of bacterial metabolism in the gut, immune modulation, and direct competition between bacteria, Dr. Terveer said, but it’s less clear whether eradication of C. difficile spores is among these mechanisms. 

Between May 2016 and April 2020, the researchers analyzed fecal samples from 84 patients who took vancomycin for at least 4 days before undergoing FMT. The researchers took fecal samples from patients before FMT and 3 weeks after FMT to culture them and the donor samples for presence of C. difficile, and they assessed clinical outcomes at 3 weeks and 6 months after FMT.

After antibiotic treatment but prior to FMT, 19% of patients (n = 16) still had a toxigenic C. difficile culture while the other 81% had a negative culture. None of the donor samples had a positive C. difficile culture. After FMT treatment, five patients who had a positive pre-FMT culture remained positive, and the other 11 were negative. Among the 81% of patients (n = 68) who had a negative culture just before FMT, 22 had a positive culture and 46 had a negative culture after FMT. Overall, 26% of patients post FMT had a positive C. difficile culture, a finding that was 10-fold higher than another study that assessed C. difficile with PCR testing, Dr. Terveer said.

The clinical cure rate after FMT was 94%, and five patients had relapses within 2 months of their FMT. These relapses were more prevalent in patients with a positive C. difficile culture prior to FMT (odds ratio [OR], 7.6; P = .045) and a positive C. difficile culture after FMT (OR, 13.6; P = .016). Still, 82% of patients who had a positive C. difficile culture post FMT remained clinically cured 2 months later.

It’s unclear why 19% of patients had a positive culture after their antibiotic pretreatment prior to FMT, Dr. Terveer said, but it may be because the pretreatment was of such a short duration.

“I think the advice should be: Give a full anti–C. diff antibiotic course to treat the C. diff infection, and then give FMT afterward to restore the microbiota and prevent further relapses,” Dr. Terveer told attendees.

Dimitri Drekonja, MD, chief of the Minneapolis VA Infectious Disease Section, said the findings were not necessarily surprising, but it would have been interesting for the researchers to have conducted DNA sequencing of the patients’ fecal samples post FMT to see what the biological diversity looked like.

“One school of thought has been that you have to repopulate the normal diverse microbiota of the colon” with FMT, and the other “is that you need to get rid of the C. diff that›s there,” Dr. Drekonja, who was not involved in the study, said in an interview. “I think more people think it’s the diverse microbiota because if it’s just getting rid of C. diff, we can get do that with antibiotics – but that gets rid of the other organisms.”

As long as you have a diverse microbiota post FMT, Dr. Drekonja said, then “having a few residual organisms, even if they get magnified in the culture process, is probably not that big a deal.”

But there’s a third school of thought that Dr. Drekonja said he himself falls into: “I don’t really care how it works, just that in well-done trials, it does work.” As long as large, robust, well-blinded trials show that FMT works, “I’m open to all sorts of ideas of what the mechanism is,” he said. “The main thing is that it does or doesn’t work.”

These findings basically reinforce current guidance not to test patients’ stools if they are asymptomatic, Dr. Drekonja said. In the past, clinicians sometimes tested patients’ stool after therapy to ensure the C. difficile was eradicated, regardless of whether the patient had symptoms of infection, he said.

“We’ve since become much more attuned that there are lots of people who have detectable C. diff in their stool without any symptoms,” whether detectable by culture or PCR, Dr. Drekonja said. “Generally, if you’re doing well and you’re not having diarrhea, don’t test, and if someone does test and finds it, pretend you didn’t see the test,” he advised. “This is a big part of diagnostic stewardship, which is: You don’t go testing people who are doing well.”

The Netherlands Donor Feces Bank used in the research is funded by a grant from Vedanta Biosciences. Dr. Drekonja had no disclosures.

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

For the sixth consecutive year, the Mayo Clinic in Rochester, Minn., claimed the No. 1 spot in the annual honor roll of best hospitals published July 27 by U.S. News & World Report.
 

This year’s expanded report debuts new ratings for seven “important procedures and conditions to help patients, in consultation with their doctors, narrow down their choice of hospital based on the specific type of care they need,” Ben Harder, managing editor and chief of health analysis, said in a news release.

With new ratings for myocardial infarction, stroke, hip fracture, and back surgery (spinal fusion), the report now ranks 17 procedures and conditions.

Also new to the 2021 report, which marks the 32nd edition, is a look at racial disparities in health care and the inclusion of health equity measures alongside the hospital rankings.

The new measures examine whether the patients each hospital has treated reflect the racial and ethnic diversity of the surrounding community, among other aspects of health equity.

“At roughly four out of five hospitals, we found that the community’s minority residents were underrepresented among patients receiving services such as joint replacement, cancer surgery and common heart procedures,” Mr. Harder said.

“Against this backdrop, however, we found important exceptions – hospitals that provide care to a disproportionate share of their community’s minority residents. These metrics are just a beginning; we aim to expand on our measurement of health equity in the future,” Mr. Harder added.

Mayo and Cleveland Clinic remain tops

Following the Mayo Clinic, the Cleveland Clinic once again takes the No. 2 spot in the magazine’s latest annual honor roll of best hospitals, which highlights hospitals that deliver exceptional treatment across multiple areas of care.

UCLA Medical Center, Los Angeles, holds the No. 3 spot in 2021. In 2020, UCLA Medical Center and New York–Presbyterian Hospital–Columbia and Cornell, New York, sat in a tie at No. 4.

In 2021, Johns Hopkins Hospital, Baltimore, which held the No. 3 spot in 2020, drops to No. 4, while Massachusetts General Hospital in Boston takes the No. 5 spot, up from No. 6 in 2020.

Rounding out the top 10 (in order) are Cedars-Sinai Medical Center, Los Angeles; New York–Presbyterian Hospital–Columbia and Cornell, New York; NYU Langone Hospitals, New York; UCSF Medical Center, San Francisco; and Northwestern Memorial Hospital, Chicago.
 

2021-2022 Best Hospitals honor roll

1. Mayo Clinic, Rochester, Minn.

2. Cleveland Clinic, Cleveland

3. UCLA Medical Center, Los Angeles

4. Johns Hopkins Hospital, Baltimore

5. Massachusetts General Hospital, Boston

6. Cedars-Sinai Medical Center, San Francisco

7. New York–Presbyterian Hospital–Columbia and Cornell, New York

8. NYU Langone Hospitals, New York

9. UCSF Medical Center, San Francisco

10. Northwestern Memorial Hospital, Chicago

11. University of Michigan Hospitals–Michigan Medicine, Ann Arbor.

12. Stanford Health Care–Stanford Hospital, Palo Alto, Calif.

13. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia

14. Brigham and Women’s Hospital, Boston

15. Mayo Clinic–Phoenix, Phoenix

16. Houston Methodist Hospital, Houston

17. (tie) Barnes-Jewish Hospital, St. Louis

17. (tie) Mount Sinai Hospital, New York Rush University Medical Center, Chicago

19. Rush University Medical Center, Chicago

20. Vanderbilt University Medical Center, Nashville, Tenn.

For the 2021-2022 rankings and ratings, the magazine compared more than 4,750 hospitals nationwide in 15 specialties and 17 procedures and conditions.

At least 2,039 hospitals received a high performance rating in at least one of the services rated; 11 hospitals received high performance in all 17. A total of 175 hospitals were nationally ranked in at least one specialty

For specialty rankings, the University of Texas MD Anderson Cancer Center continues to hold the No. 1 spot in cancer care, the Hospital for Special Surgery continues to be No. 1 in orthopedics, and the Cleveland Clinic continues to be No. 1 in cardiology and heart surgery.
 

Top five for cancer

1. University of Texas MD Anderson Cancer Center, Houston

2. Memorial Sloan Kettering Cancer Center, New York

3. Mayo Clinic, Rochester, Minn.

4. Dana-Farber/Brigham & Women’s Cancer Center, Boston

5. Cleveland Clinic, Cleveland

Top five for cardiology and heart surgery

1. Cleveland Clinic, Cleveland

2. Mayo Clinic, Rochester, Minn.

3. Cedars-Sinai Medical Center, Los Angeles

4. New York–Presbyterian Hospital–Columbia and Cornell, New York

5. NYU Langone Hospitals, New York

Top five for orthopedics

1. Hospital for Special Surgery, New York

2. Mayo Clinic, Rochester, Minn.

3. Cedars-Sinai Medical Center, Los Angeles

4. NYU Langone Orthopedic Hospital, New York

5. UCLA Medical Center, Los Angeles

The magazine noted that data for the 2021-2022 Best Hospitals rankings and ratings were not affected by the COVID-19 pandemic, which began after the end of the data collection period.

The methodologies used in determining the rankings are based largely on objective measures, such as risk-adjusted survival, discharge-to-home rates, volume, and quality of nursing, among other care-related indicators.

The full report is available online.

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

For the sixth consecutive year, the Mayo Clinic in Rochester, Minn., claimed the No. 1 spot in the annual honor roll of best hospitals published July 27 by U.S. News & World Report.
 

This year’s expanded report debuts new ratings for seven “important procedures and conditions to help patients, in consultation with their doctors, narrow down their choice of hospital based on the specific type of care they need,” Ben Harder, managing editor and chief of health analysis, said in a news release.

With new ratings for myocardial infarction, stroke, hip fracture, and back surgery (spinal fusion), the report now ranks 17 procedures and conditions.

Also new to the 2021 report, which marks the 32nd edition, is a look at racial disparities in health care and the inclusion of health equity measures alongside the hospital rankings.

The new measures examine whether the patients each hospital has treated reflect the racial and ethnic diversity of the surrounding community, among other aspects of health equity.

“At roughly four out of five hospitals, we found that the community’s minority residents were underrepresented among patients receiving services such as joint replacement, cancer surgery and common heart procedures,” Mr. Harder said.

“Against this backdrop, however, we found important exceptions – hospitals that provide care to a disproportionate share of their community’s minority residents. These metrics are just a beginning; we aim to expand on our measurement of health equity in the future,” Mr. Harder added.

Mayo and Cleveland Clinic remain tops

Following the Mayo Clinic, the Cleveland Clinic once again takes the No. 2 spot in the magazine’s latest annual honor roll of best hospitals, which highlights hospitals that deliver exceptional treatment across multiple areas of care.

UCLA Medical Center, Los Angeles, holds the No. 3 spot in 2021. In 2020, UCLA Medical Center and New York–Presbyterian Hospital–Columbia and Cornell, New York, sat in a tie at No. 4.

In 2021, Johns Hopkins Hospital, Baltimore, which held the No. 3 spot in 2020, drops to No. 4, while Massachusetts General Hospital in Boston takes the No. 5 spot, up from No. 6 in 2020.

Rounding out the top 10 (in order) are Cedars-Sinai Medical Center, Los Angeles; New York–Presbyterian Hospital–Columbia and Cornell, New York; NYU Langone Hospitals, New York; UCSF Medical Center, San Francisco; and Northwestern Memorial Hospital, Chicago.
 

2021-2022 Best Hospitals honor roll

1. Mayo Clinic, Rochester, Minn.

2. Cleveland Clinic, Cleveland

3. UCLA Medical Center, Los Angeles

4. Johns Hopkins Hospital, Baltimore

5. Massachusetts General Hospital, Boston

6. Cedars-Sinai Medical Center, San Francisco

7. New York–Presbyterian Hospital–Columbia and Cornell, New York

8. NYU Langone Hospitals, New York

9. UCSF Medical Center, San Francisco

10. Northwestern Memorial Hospital, Chicago

11. University of Michigan Hospitals–Michigan Medicine, Ann Arbor.

12. Stanford Health Care–Stanford Hospital, Palo Alto, Calif.

13. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia

14. Brigham and Women’s Hospital, Boston

15. Mayo Clinic–Phoenix, Phoenix

16. Houston Methodist Hospital, Houston

17. (tie) Barnes-Jewish Hospital, St. Louis

17. (tie) Mount Sinai Hospital, New York Rush University Medical Center, Chicago

19. Rush University Medical Center, Chicago

20. Vanderbilt University Medical Center, Nashville, Tenn.

For the 2021-2022 rankings and ratings, the magazine compared more than 4,750 hospitals nationwide in 15 specialties and 17 procedures and conditions.

At least 2,039 hospitals received a high performance rating in at least one of the services rated; 11 hospitals received high performance in all 17. A total of 175 hospitals were nationally ranked in at least one specialty

For specialty rankings, the University of Texas MD Anderson Cancer Center continues to hold the No. 1 spot in cancer care, the Hospital for Special Surgery continues to be No. 1 in orthopedics, and the Cleveland Clinic continues to be No. 1 in cardiology and heart surgery.
 

Top five for cancer

1. University of Texas MD Anderson Cancer Center, Houston

2. Memorial Sloan Kettering Cancer Center, New York

3. Mayo Clinic, Rochester, Minn.

4. Dana-Farber/Brigham & Women’s Cancer Center, Boston

5. Cleveland Clinic, Cleveland

Top five for cardiology and heart surgery

1. Cleveland Clinic, Cleveland

2. Mayo Clinic, Rochester, Minn.

3. Cedars-Sinai Medical Center, Los Angeles

4. New York–Presbyterian Hospital–Columbia and Cornell, New York

5. NYU Langone Hospitals, New York

Top five for orthopedics

1. Hospital for Special Surgery, New York

2. Mayo Clinic, Rochester, Minn.

3. Cedars-Sinai Medical Center, Los Angeles

4. NYU Langone Orthopedic Hospital, New York

5. UCLA Medical Center, Los Angeles

The magazine noted that data for the 2021-2022 Best Hospitals rankings and ratings were not affected by the COVID-19 pandemic, which began after the end of the data collection period.

The methodologies used in determining the rankings are based largely on objective measures, such as risk-adjusted survival, discharge-to-home rates, volume, and quality of nursing, among other care-related indicators.

The full report is available online.

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

For the sixth consecutive year, the Mayo Clinic in Rochester, Minn., claimed the No. 1 spot in the annual honor roll of best hospitals published July 27 by U.S. News & World Report.
 

This year’s expanded report debuts new ratings for seven “important procedures and conditions to help patients, in consultation with their doctors, narrow down their choice of hospital based on the specific type of care they need,” Ben Harder, managing editor and chief of health analysis, said in a news release.

With new ratings for myocardial infarction, stroke, hip fracture, and back surgery (spinal fusion), the report now ranks 17 procedures and conditions.

Also new to the 2021 report, which marks the 32nd edition, is a look at racial disparities in health care and the inclusion of health equity measures alongside the hospital rankings.

The new measures examine whether the patients each hospital has treated reflect the racial and ethnic diversity of the surrounding community, among other aspects of health equity.

“At roughly four out of five hospitals, we found that the community’s minority residents were underrepresented among patients receiving services such as joint replacement, cancer surgery and common heart procedures,” Mr. Harder said.

“Against this backdrop, however, we found important exceptions – hospitals that provide care to a disproportionate share of their community’s minority residents. These metrics are just a beginning; we aim to expand on our measurement of health equity in the future,” Mr. Harder added.

Mayo and Cleveland Clinic remain tops

Following the Mayo Clinic, the Cleveland Clinic once again takes the No. 2 spot in the magazine’s latest annual honor roll of best hospitals, which highlights hospitals that deliver exceptional treatment across multiple areas of care.

UCLA Medical Center, Los Angeles, holds the No. 3 spot in 2021. In 2020, UCLA Medical Center and New York–Presbyterian Hospital–Columbia and Cornell, New York, sat in a tie at No. 4.

In 2021, Johns Hopkins Hospital, Baltimore, which held the No. 3 spot in 2020, drops to No. 4, while Massachusetts General Hospital in Boston takes the No. 5 spot, up from No. 6 in 2020.

Rounding out the top 10 (in order) are Cedars-Sinai Medical Center, Los Angeles; New York–Presbyterian Hospital–Columbia and Cornell, New York; NYU Langone Hospitals, New York; UCSF Medical Center, San Francisco; and Northwestern Memorial Hospital, Chicago.
 

2021-2022 Best Hospitals honor roll

1. Mayo Clinic, Rochester, Minn.

2. Cleveland Clinic, Cleveland

3. UCLA Medical Center, Los Angeles

4. Johns Hopkins Hospital, Baltimore

5. Massachusetts General Hospital, Boston

6. Cedars-Sinai Medical Center, San Francisco

7. New York–Presbyterian Hospital–Columbia and Cornell, New York

8. NYU Langone Hospitals, New York

9. UCSF Medical Center, San Francisco

10. Northwestern Memorial Hospital, Chicago

11. University of Michigan Hospitals–Michigan Medicine, Ann Arbor.

12. Stanford Health Care–Stanford Hospital, Palo Alto, Calif.

13. Hospitals of the University of Pennsylvania–Penn Presbyterian, Philadelphia

14. Brigham and Women’s Hospital, Boston

15. Mayo Clinic–Phoenix, Phoenix

16. Houston Methodist Hospital, Houston

17. (tie) Barnes-Jewish Hospital, St. Louis

17. (tie) Mount Sinai Hospital, New York Rush University Medical Center, Chicago

19. Rush University Medical Center, Chicago

20. Vanderbilt University Medical Center, Nashville, Tenn.

For the 2021-2022 rankings and ratings, the magazine compared more than 4,750 hospitals nationwide in 15 specialties and 17 procedures and conditions.

At least 2,039 hospitals received a high performance rating in at least one of the services rated; 11 hospitals received high performance in all 17. A total of 175 hospitals were nationally ranked in at least one specialty

For specialty rankings, the University of Texas MD Anderson Cancer Center continues to hold the No. 1 spot in cancer care, the Hospital for Special Surgery continues to be No. 1 in orthopedics, and the Cleveland Clinic continues to be No. 1 in cardiology and heart surgery.
 

Top five for cancer

1. University of Texas MD Anderson Cancer Center, Houston

2. Memorial Sloan Kettering Cancer Center, New York

3. Mayo Clinic, Rochester, Minn.

4. Dana-Farber/Brigham & Women’s Cancer Center, Boston

5. Cleveland Clinic, Cleveland

Top five for cardiology and heart surgery

1. Cleveland Clinic, Cleveland

2. Mayo Clinic, Rochester, Minn.

3. Cedars-Sinai Medical Center, Los Angeles

4. New York–Presbyterian Hospital–Columbia and Cornell, New York

5. NYU Langone Hospitals, New York

Top five for orthopedics

1. Hospital for Special Surgery, New York

2. Mayo Clinic, Rochester, Minn.

3. Cedars-Sinai Medical Center, Los Angeles

4. NYU Langone Orthopedic Hospital, New York

5. UCLA Medical Center, Los Angeles

The magazine noted that data for the 2021-2022 Best Hospitals rankings and ratings were not affected by the COVID-19 pandemic, which began after the end of the data collection period.

The methodologies used in determining the rankings are based largely on objective measures, such as risk-adjusted survival, discharge-to-home rates, volume, and quality of nursing, among other care-related indicators.

The full report is available online.

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

As COVID-19 cases, hospitalizations, and deaths mount again across the country, the American Medical Association (AMA), the American Nursing Association, and 54 other medical and allied healthcare associations released a joint statement calling on “all health care and long-term care employers” to require their workers to receive the COVID-19 vaccine.

This injunction, issued July 26, covers everyone in healthcare, Emanuel Ezekiel, MD, PhD, chair of the department of medical ethics and health policy at the University of Pennsylvania, Philadelphia, and the organizer of the joint statement, said in an interview.

That includes not only hospitals, but also physician offices, ambulatory surgery centers, home care agencies, skilled nursing facilities, pharmacies, laboratories, and imaging centers, he said.

The exhortation to get vaccinated also extends to federal and state healthcare facilities, including those of the military health system — TRICARE and the Department of Veterans Affairs — which instituted a mandate the same day.

The American Hospital Association (AHA) and other hospital groups recently said they supported hospitals and health systems that required their personnel to get vaccinated. Several dozen healthcare organizations have already done so, including some of the nation’s largest health systems.

A substantial fraction of U.S. healthcare workers have not yet gotten vaccinated, although how many are unvaccinated is unclear. An analysis by WebMD and Medscape Medical News estimated that 25% of hospital workers who had contact with patients were unvaccinated at the end of May.

More than 38% of nursing workers were not fully vaccinated by July 11, according to an analysis of Centers for Medicare & Medicaid Services data by LeadingAge, which was cited by the Washington Post. And more than 40% of nursing home employees have not been fully vaccinated, according to the Centers for Disease Control and Prevention.

The joint statement did not give any indication of how many employees of physician practices have failed to get COVID shots. However, a recent AMA survey shows that 96% of physicians have been fully vaccinated.
 

Ethical commitment

The main reason for vaccine mandates, according to the healthcare associations’ statement, is “the ethical commitment to put patients as well as residents of long-term care facilities first and take all steps necessary to ensure their health and well-being.”

In addition, the statement noted, vaccination can protect healthcare workers and their families from getting COVID-19.

The statement also pointed out that many healthcare and long-term care organizations already require vaccinations for influenza, hepatitis B, and pertussis.

Workers who have certain medical conditions should be exempt from the vaccination mandates, the statement added.

While recognizing the “historical mistrust of health care institutions” among some healthcare workers, the statement said, “We must continue to address workers’ concerns, engage with marginalized populations, and work with trusted messengers to improve vaccine acceptance.”

There has been some skepticism about the legality of requiring healthcare workers to get vaccinated as a condition of employment, partly because the U.S. Food and Drug Administration has not yet fully authorized any of the COVID-19 vaccines.

But in June, a federal judge turned down a legal challenge to Houston Methodist’s vaccination mandate.

“It is critical that all people in the health care workforce get vaccinated against COVID-19 for the safety of our patients and our colleagues. With more than 300 million doses administered in the United States and nearly 4 billion doses administered worldwide, we know the vaccines are safe and highly effective at preventing severe illness and death from COVID-19.

“Increased vaccinations among health care personnel will not only reduce the spread of COVID-19 but also reduce the harmful toll this virus is taking within the health care workforce and those we are striving to serve,” Susan Bailey, MD, immediate past president of the AMA, said in a news release.

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

As COVID-19 cases, hospitalizations, and deaths mount again across the country, the American Medical Association (AMA), the American Nursing Association, and 54 other medical and allied healthcare associations released a joint statement calling on “all health care and long-term care employers” to require their workers to receive the COVID-19 vaccine.

This injunction, issued July 26, covers everyone in healthcare, Emanuel Ezekiel, MD, PhD, chair of the department of medical ethics and health policy at the University of Pennsylvania, Philadelphia, and the organizer of the joint statement, said in an interview.

That includes not only hospitals, but also physician offices, ambulatory surgery centers, home care agencies, skilled nursing facilities, pharmacies, laboratories, and imaging centers, he said.

The exhortation to get vaccinated also extends to federal and state healthcare facilities, including those of the military health system — TRICARE and the Department of Veterans Affairs — which instituted a mandate the same day.

The American Hospital Association (AHA) and other hospital groups recently said they supported hospitals and health systems that required their personnel to get vaccinated. Several dozen healthcare organizations have already done so, including some of the nation’s largest health systems.

A substantial fraction of U.S. healthcare workers have not yet gotten vaccinated, although how many are unvaccinated is unclear. An analysis by WebMD and Medscape Medical News estimated that 25% of hospital workers who had contact with patients were unvaccinated at the end of May.

More than 38% of nursing workers were not fully vaccinated by July 11, according to an analysis of Centers for Medicare & Medicaid Services data by LeadingAge, which was cited by the Washington Post. And more than 40% of nursing home employees have not been fully vaccinated, according to the Centers for Disease Control and Prevention.

The joint statement did not give any indication of how many employees of physician practices have failed to get COVID shots. However, a recent AMA survey shows that 96% of physicians have been fully vaccinated.
 

Ethical commitment

The main reason for vaccine mandates, according to the healthcare associations’ statement, is “the ethical commitment to put patients as well as residents of long-term care facilities first and take all steps necessary to ensure their health and well-being.”

In addition, the statement noted, vaccination can protect healthcare workers and their families from getting COVID-19.

The statement also pointed out that many healthcare and long-term care organizations already require vaccinations for influenza, hepatitis B, and pertussis.

Workers who have certain medical conditions should be exempt from the vaccination mandates, the statement added.

While recognizing the “historical mistrust of health care institutions” among some healthcare workers, the statement said, “We must continue to address workers’ concerns, engage with marginalized populations, and work with trusted messengers to improve vaccine acceptance.”

There has been some skepticism about the legality of requiring healthcare workers to get vaccinated as a condition of employment, partly because the U.S. Food and Drug Administration has not yet fully authorized any of the COVID-19 vaccines.

But in June, a federal judge turned down a legal challenge to Houston Methodist’s vaccination mandate.

“It is critical that all people in the health care workforce get vaccinated against COVID-19 for the safety of our patients and our colleagues. With more than 300 million doses administered in the United States and nearly 4 billion doses administered worldwide, we know the vaccines are safe and highly effective at preventing severe illness and death from COVID-19.

“Increased vaccinations among health care personnel will not only reduce the spread of COVID-19 but also reduce the harmful toll this virus is taking within the health care workforce and those we are striving to serve,” Susan Bailey, MD, immediate past president of the AMA, said in a news release.

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

As COVID-19 cases, hospitalizations, and deaths mount again across the country, the American Medical Association (AMA), the American Nursing Association, and 54 other medical and allied healthcare associations released a joint statement calling on “all health care and long-term care employers” to require their workers to receive the COVID-19 vaccine.

This injunction, issued July 26, covers everyone in healthcare, Emanuel Ezekiel, MD, PhD, chair of the department of medical ethics and health policy at the University of Pennsylvania, Philadelphia, and the organizer of the joint statement, said in an interview.

That includes not only hospitals, but also physician offices, ambulatory surgery centers, home care agencies, skilled nursing facilities, pharmacies, laboratories, and imaging centers, he said.

The exhortation to get vaccinated also extends to federal and state healthcare facilities, including those of the military health system — TRICARE and the Department of Veterans Affairs — which instituted a mandate the same day.

The American Hospital Association (AHA) and other hospital groups recently said they supported hospitals and health systems that required their personnel to get vaccinated. Several dozen healthcare organizations have already done so, including some of the nation’s largest health systems.

A substantial fraction of U.S. healthcare workers have not yet gotten vaccinated, although how many are unvaccinated is unclear. An analysis by WebMD and Medscape Medical News estimated that 25% of hospital workers who had contact with patients were unvaccinated at the end of May.

More than 38% of nursing workers were not fully vaccinated by July 11, according to an analysis of Centers for Medicare & Medicaid Services data by LeadingAge, which was cited by the Washington Post. And more than 40% of nursing home employees have not been fully vaccinated, according to the Centers for Disease Control and Prevention.

The joint statement did not give any indication of how many employees of physician practices have failed to get COVID shots. However, a recent AMA survey shows that 96% of physicians have been fully vaccinated.
 

Ethical commitment

The main reason for vaccine mandates, according to the healthcare associations’ statement, is “the ethical commitment to put patients as well as residents of long-term care facilities first and take all steps necessary to ensure their health and well-being.”

In addition, the statement noted, vaccination can protect healthcare workers and their families from getting COVID-19.

The statement also pointed out that many healthcare and long-term care organizations already require vaccinations for influenza, hepatitis B, and pertussis.

Workers who have certain medical conditions should be exempt from the vaccination mandates, the statement added.

While recognizing the “historical mistrust of health care institutions” among some healthcare workers, the statement said, “We must continue to address workers’ concerns, engage with marginalized populations, and work with trusted messengers to improve vaccine acceptance.”

There has been some skepticism about the legality of requiring healthcare workers to get vaccinated as a condition of employment, partly because the U.S. Food and Drug Administration has not yet fully authorized any of the COVID-19 vaccines.

But in June, a federal judge turned down a legal challenge to Houston Methodist’s vaccination mandate.

“It is critical that all people in the health care workforce get vaccinated against COVID-19 for the safety of our patients and our colleagues. With more than 300 million doses administered in the United States and nearly 4 billion doses administered worldwide, we know the vaccines are safe and highly effective at preventing severe illness and death from COVID-19.

“Increased vaccinations among health care personnel will not only reduce the spread of COVID-19 but also reduce the harmful toll this virus is taking within the health care workforce and those we are striving to serve,” Susan Bailey, MD, immediate past president of the AMA, said in a news release.

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

I don’t see anyone under 18. After all, I’m not a child neurologist.

People will occasionally argue with this policy, claiming that it’s too rigid. Why not 17½? I know that some adult neurologists do see teenagers.

But not me. It’s easier to just have a solid line and stick by it.

So, by habit, I often note someone’s birthday on the schedule to make sure they’re old enough to see me. And, over the years, this has made me realize the passage of time more than a lot of things.

Not much changes in my office. I’ve been in the same building since 2013, had the same furniture for longer, and the same staff since 2004. So it’s easy to lose track of how long I’ve been doing this.

But when I started out I didn’t see anyone born after 1979. Today that’s crept up to 2003. How the hell did that happen?

With that came the even more sobering realization that my kids are now all old enough to be my patients.

Time flies by in this world. You do the same thing day in and day out, and suddenly you’re 20 years older and starting to think about retirement.

We all see ourselves in the mirror each day, but rarely notice the changes. Watching patients grow older, seeing the minimum birth year for them advance, even being surprised when a drug I thought had just come out is now generic – those are the reminders of time’s passage that get my attention at work.

Not that it’s a bad thing. Time will go on, whether we want it to or not. After 20 years I still enjoy this job, and it allows me to support my family. I can’t ask for much more than that.

But each morning I scan through the names and birthdays on my schedule, and am amazed when I think about how clearly I remember my first day of medical school, college, and even high school like it had just happened.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I don’t see anyone under 18. After all, I’m not a child neurologist.

People will occasionally argue with this policy, claiming that it’s too rigid. Why not 17½? I know that some adult neurologists do see teenagers.

But not me. It’s easier to just have a solid line and stick by it.

So, by habit, I often note someone’s birthday on the schedule to make sure they’re old enough to see me. And, over the years, this has made me realize the passage of time more than a lot of things.

Not much changes in my office. I’ve been in the same building since 2013, had the same furniture for longer, and the same staff since 2004. So it’s easy to lose track of how long I’ve been doing this.

But when I started out I didn’t see anyone born after 1979. Today that’s crept up to 2003. How the hell did that happen?

With that came the even more sobering realization that my kids are now all old enough to be my patients.

Time flies by in this world. You do the same thing day in and day out, and suddenly you’re 20 years older and starting to think about retirement.

We all see ourselves in the mirror each day, but rarely notice the changes. Watching patients grow older, seeing the minimum birth year for them advance, even being surprised when a drug I thought had just come out is now generic – those are the reminders of time’s passage that get my attention at work.

Not that it’s a bad thing. Time will go on, whether we want it to or not. After 20 years I still enjoy this job, and it allows me to support my family. I can’t ask for much more than that.

But each morning I scan through the names and birthdays on my schedule, and am amazed when I think about how clearly I remember my first day of medical school, college, and even high school like it had just happened.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I don’t see anyone under 18. After all, I’m not a child neurologist.

People will occasionally argue with this policy, claiming that it’s too rigid. Why not 17½? I know that some adult neurologists do see teenagers.

But not me. It’s easier to just have a solid line and stick by it.

So, by habit, I often note someone’s birthday on the schedule to make sure they’re old enough to see me. And, over the years, this has made me realize the passage of time more than a lot of things.

Not much changes in my office. I’ve been in the same building since 2013, had the same furniture for longer, and the same staff since 2004. So it’s easy to lose track of how long I’ve been doing this.

But when I started out I didn’t see anyone born after 1979. Today that’s crept up to 2003. How the hell did that happen?

With that came the even more sobering realization that my kids are now all old enough to be my patients.

Time flies by in this world. You do the same thing day in and day out, and suddenly you’re 20 years older and starting to think about retirement.

We all see ourselves in the mirror each day, but rarely notice the changes. Watching patients grow older, seeing the minimum birth year for them advance, even being surprised when a drug I thought had just come out is now generic – those are the reminders of time’s passage that get my attention at work.

Not that it’s a bad thing. Time will go on, whether we want it to or not. After 20 years I still enjoy this job, and it allows me to support my family. I can’t ask for much more than that.

But each morning I scan through the names and birthdays on my schedule, and am amazed when I think about how clearly I remember my first day of medical school, college, and even high school like it had just happened.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The Diagnosis: Hidradenocarcinoma

An excisional biopsy revealed a neoplasm in the dermis with focal invasion into the adjacent soft tissue (Figure 1). The tumor consisted of sheets of cells with cytoplasmic vacuoles and ductal differentiation (Figure 2), as well as cells with mild atypia, mild pleomorphism, rare mitotic figures, and abundant pale cytoplasm. Immunohistochemical staining was positive for cytokeratin (CK) 5, CK7, CK20, CK AE1/AE3, and p63 (Figure 3). The culmination of features including the large tumor size, immunohistochemical staining pattern, and mild pleomorphism with focal invasion into the soft tissue supported the diagnosis of hidradenocarcinoma.

Hidradenocarcinoma is an exceedingly rare malignant tumor of eccrine and/or apocrine origin.¹ It accounts for less than 0.001% of all tumors and 1 of 13,000 skin biopsies.² It usually arises in the head and neck region and most commonly affects older adults aged 50 to 70 years.³ The size of hidradenocarcinomas can vary; however, they typically are large, often growing to be greater than 5 cm in diameter.² It tends to be an aggressive tumor that generally spreads to regional lymph nodes and distant viscera.⁴ Although it most commonly arises de novo, it may occasionally derive from a benign hidradenoma.¹ The diagnosis of hidradenocarcinoma is made based on the tumor’s morphologic and pathologic characteristics. Histologically, it is characterized by an infiltrative and invasive proliferation of lobules made of large clear cells with atypical mitotic figures and nuclear pleomorphism as well as immunohistochemical features displaying various positive markers, such as carcinoembryonic antigen, epithelial membrane antigen, S-100 protein, and CKs AE1/AE3 and 5/6.² Invasion of the adjacent soft tissue can be present and helps to confirm the diagnosis.

The differential diagnosis for hidradenocarcinoma primarily is the benign hidradenoma, which is similar both clinically and histologically with a few important differences. Hidradenocarcinomas often are larger and ulcerated. Histologically, they usually are more pleomorphic with the presence of mitotic figures in clear cells and tend to invade locally into the surrounding soft tissue. Other similar lesions such as spiradenoma, Merkel cell carcinoma, lymphangioma, cutaneous Crohn disease, tumors metastatic to the skin, and metastatic clear cell carcinomas originating from other organs also are included in the differential diagnosis.²

Spiradenomas are dermal tumors originating from the sweat glands. They typically present as bluish, painful, solitary nodules on the ventral surfaces of the upper body, though multiple nodules also are reported.⁵ Spiradenomas manifest as a central constellation of pale large cells surrounded by small, dark, basaloid cells containing hyperchromatic nuclei. The microscopic appearance of the blue basaloid cells contrasts with the clear cells seen in hidradenoma.⁵

Merkel cell carcinoma is a cutaneous neuroendocrine tumor affecting elderly or immunosuppressed individuals. It arises in sun-exposed areas and often is associated with Merkel cell polyomavirus infection. The histologic features display small and round cells that stain positive for CK8, CK18, CK19, and CK20 but stain negative for CK7, a marker that often is positive in hidradenocarcinoma.⁶

Lymphangioma, particularly cavernous lymphangioma, may resemble the gross appearance of hidradenoma/ hidradenocarcinoma. It usually presents as irregular clear blue papules and nodules in the skin and subcutaneous tissue.⁷ The key histopathologic finding in this tumor is the endothelium-lined channels that stain positive for D2-40, a lymphatic endothelium marker.^7,8

Cutaneous Crohn disease is classified as noncaseating granulomatous skin lesions that are noncontinuous with the gastrointestinal tract.⁹ Clinical presentations in addition to skin edema include erythematous plaques, ulcerations, and erosions. Histopathology reveals sterile noncaseating granulomas made of Langerhans giant cells, epithelioid histocytes, and plasma cells.⁹

Metastatic clear cell carcinomas, such as renal cell carcinoma, can be differentiated by a history of primary carcinoma, demonstration of histologic vascular stroma, and other features related to metastatic clear cell carcinoma.²

There are no well-established therapeutic guidelines for hidradenocarcinoma. Wide local excision with margins greater than 2 cm is the preferred initial treatment and often is performed in conjunction with sentinel lymph node biopsy. External beam radiotherapy and adjunctive chemotherapy have been used for tumors that could not be surgically cleared. However, the efficacy of these treatments has not been well established.² Targeted therapies recently have emerged as an alternative treatment choice for hidradenocarcinoma due to the utilization of immunohistochemical and genomic testing. The discovery of specific gene mutations or the expression of hormonal receptors in this tumor have paved the way for targeting HER2-expressing hidradenocarcinomas with trastuzumab and those expressing estrogen receptor with the estrogen receptor inhibitor tamoxifen.¹ Epidermal growth factor receptor inhibitors and PI3K/Akt/mTOR (phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin) pathway inhibitors also have been used to target various signal transduction pathways.²

Wide excision with 2.5-cm margins was performed on our patient, and a positron emission tomography– computed tomography scan revealed no metastatic disease. She declined sentinel lymph node biopsy and additional treatment. Due to the risk for recurrence, she was monitored closely with skin examinations and positron emission tomography–computed tomography every 3 months for the first year and every 6 months thereafter. Thus far, she has had no evidence of local or regional recurrence.

The Diagnosis: Hidradenocarcinoma

An excisional biopsy revealed a neoplasm in the dermis with focal invasion into the adjacent soft tissue (Figure 1). The tumor consisted of sheets of cells with cytoplasmic vacuoles and ductal differentiation (Figure 2), as well as cells with mild atypia, mild pleomorphism, rare mitotic figures, and abundant pale cytoplasm. Immunohistochemical staining was positive for cytokeratin (CK) 5, CK7, CK20, CK AE1/AE3, and p63 (Figure 3). The culmination of features including the large tumor size, immunohistochemical staining pattern, and mild pleomorphism with focal invasion into the soft tissue supported the diagnosis of hidradenocarcinoma.

Hidradenocarcinoma is an exceedingly rare malignant tumor of eccrine and/or apocrine origin.¹ It accounts for less than 0.001% of all tumors and 1 of 13,000 skin biopsies.² It usually arises in the head and neck region and most commonly affects older adults aged 50 to 70 years.³ The size of hidradenocarcinomas can vary; however, they typically are large, often growing to be greater than 5 cm in diameter.² It tends to be an aggressive tumor that generally spreads to regional lymph nodes and distant viscera.⁴ Although it most commonly arises de novo, it may occasionally derive from a benign hidradenoma.¹ The diagnosis of hidradenocarcinoma is made based on the tumor’s morphologic and pathologic characteristics. Histologically, it is characterized by an infiltrative and invasive proliferation of lobules made of large clear cells with atypical mitotic figures and nuclear pleomorphism as well as immunohistochemical features displaying various positive markers, such as carcinoembryonic antigen, epithelial membrane antigen, S-100 protein, and CKs AE1/AE3 and 5/6.² Invasion of the adjacent soft tissue can be present and helps to confirm the diagnosis.

The differential diagnosis for hidradenocarcinoma primarily is the benign hidradenoma, which is similar both clinically and histologically with a few important differences. Hidradenocarcinomas often are larger and ulcerated. Histologically, they usually are more pleomorphic with the presence of mitotic figures in clear cells and tend to invade locally into the surrounding soft tissue. Other similar lesions such as spiradenoma, Merkel cell carcinoma, lymphangioma, cutaneous Crohn disease, tumors metastatic to the skin, and metastatic clear cell carcinomas originating from other organs also are included in the differential diagnosis.²

Spiradenomas are dermal tumors originating from the sweat glands. They typically present as bluish, painful, solitary nodules on the ventral surfaces of the upper body, though multiple nodules also are reported.⁵ Spiradenomas manifest as a central constellation of pale large cells surrounded by small, dark, basaloid cells containing hyperchromatic nuclei. The microscopic appearance of the blue basaloid cells contrasts with the clear cells seen in hidradenoma.⁵

Merkel cell carcinoma is a cutaneous neuroendocrine tumor affecting elderly or immunosuppressed individuals. It arises in sun-exposed areas and often is associated with Merkel cell polyomavirus infection. The histologic features display small and round cells that stain positive for CK8, CK18, CK19, and CK20 but stain negative for CK7, a marker that often is positive in hidradenocarcinoma.⁶

Lymphangioma, particularly cavernous lymphangioma, may resemble the gross appearance of hidradenoma/ hidradenocarcinoma. It usually presents as irregular clear blue papules and nodules in the skin and subcutaneous tissue.⁷ The key histopathologic finding in this tumor is the endothelium-lined channels that stain positive for D2-40, a lymphatic endothelium marker.^7,8

Cutaneous Crohn disease is classified as noncaseating granulomatous skin lesions that are noncontinuous with the gastrointestinal tract.⁹ Clinical presentations in addition to skin edema include erythematous plaques, ulcerations, and erosions. Histopathology reveals sterile noncaseating granulomas made of Langerhans giant cells, epithelioid histocytes, and plasma cells.⁹

Metastatic clear cell carcinomas, such as renal cell carcinoma, can be differentiated by a history of primary carcinoma, demonstration of histologic vascular stroma, and other features related to metastatic clear cell carcinoma.²

There are no well-established therapeutic guidelines for hidradenocarcinoma. Wide local excision with margins greater than 2 cm is the preferred initial treatment and often is performed in conjunction with sentinel lymph node biopsy. External beam radiotherapy and adjunctive chemotherapy have been used for tumors that could not be surgically cleared. However, the efficacy of these treatments has not been well established.² Targeted therapies recently have emerged as an alternative treatment choice for hidradenocarcinoma due to the utilization of immunohistochemical and genomic testing. The discovery of specific gene mutations or the expression of hormonal receptors in this tumor have paved the way for targeting HER2-expressing hidradenocarcinomas with trastuzumab and those expressing estrogen receptor with the estrogen receptor inhibitor tamoxifen.¹ Epidermal growth factor receptor inhibitors and PI3K/Akt/mTOR (phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin) pathway inhibitors also have been used to target various signal transduction pathways.²

Wide excision with 2.5-cm margins was performed on our patient, and a positron emission tomography– computed tomography scan revealed no metastatic disease. She declined sentinel lymph node biopsy and additional treatment. Due to the risk for recurrence, she was monitored closely with skin examinations and positron emission tomography–computed tomography every 3 months for the first year and every 6 months thereafter. Thus far, she has had no evidence of local or regional recurrence.

The Diagnosis: Hidradenocarcinoma

An excisional biopsy revealed a neoplasm in the dermis with focal invasion into the adjacent soft tissue (Figure 1). The tumor consisted of sheets of cells with cytoplasmic vacuoles and ductal differentiation (Figure 2), as well as cells with mild atypia, mild pleomorphism, rare mitotic figures, and abundant pale cytoplasm. Immunohistochemical staining was positive for cytokeratin (CK) 5, CK7, CK20, CK AE1/AE3, and p63 (Figure 3). The culmination of features including the large tumor size, immunohistochemical staining pattern, and mild pleomorphism with focal invasion into the soft tissue supported the diagnosis of hidradenocarcinoma.

Hidradenocarcinoma is an exceedingly rare malignant tumor of eccrine and/or apocrine origin.¹ It accounts for less than 0.001% of all tumors and 1 of 13,000 skin biopsies.² It usually arises in the head and neck region and most commonly affects older adults aged 50 to 70 years.³ The size of hidradenocarcinomas can vary; however, they typically are large, often growing to be greater than 5 cm in diameter.² It tends to be an aggressive tumor that generally spreads to regional lymph nodes and distant viscera.⁴ Although it most commonly arises de novo, it may occasionally derive from a benign hidradenoma.¹ The diagnosis of hidradenocarcinoma is made based on the tumor’s morphologic and pathologic characteristics. Histologically, it is characterized by an infiltrative and invasive proliferation of lobules made of large clear cells with atypical mitotic figures and nuclear pleomorphism as well as immunohistochemical features displaying various positive markers, such as carcinoembryonic antigen, epithelial membrane antigen, S-100 protein, and CKs AE1/AE3 and 5/6.² Invasion of the adjacent soft tissue can be present and helps to confirm the diagnosis.

The differential diagnosis for hidradenocarcinoma primarily is the benign hidradenoma, which is similar both clinically and histologically with a few important differences. Hidradenocarcinomas often are larger and ulcerated. Histologically, they usually are more pleomorphic with the presence of mitotic figures in clear cells and tend to invade locally into the surrounding soft tissue. Other similar lesions such as spiradenoma, Merkel cell carcinoma, lymphangioma, cutaneous Crohn disease, tumors metastatic to the skin, and metastatic clear cell carcinomas originating from other organs also are included in the differential diagnosis.²

Spiradenomas are dermal tumors originating from the sweat glands. They typically present as bluish, painful, solitary nodules on the ventral surfaces of the upper body, though multiple nodules also are reported.⁵ Spiradenomas manifest as a central constellation of pale large cells surrounded by small, dark, basaloid cells containing hyperchromatic nuclei. The microscopic appearance of the blue basaloid cells contrasts with the clear cells seen in hidradenoma.⁵

Merkel cell carcinoma is a cutaneous neuroendocrine tumor affecting elderly or immunosuppressed individuals. It arises in sun-exposed areas and often is associated with Merkel cell polyomavirus infection. The histologic features display small and round cells that stain positive for CK8, CK18, CK19, and CK20 but stain negative for CK7, a marker that often is positive in hidradenocarcinoma.⁶

Lymphangioma, particularly cavernous lymphangioma, may resemble the gross appearance of hidradenoma/ hidradenocarcinoma. It usually presents as irregular clear blue papules and nodules in the skin and subcutaneous tissue.⁷ The key histopathologic finding in this tumor is the endothelium-lined channels that stain positive for D2-40, a lymphatic endothelium marker.^7,8

Cutaneous Crohn disease is classified as noncaseating granulomatous skin lesions that are noncontinuous with the gastrointestinal tract.⁹ Clinical presentations in addition to skin edema include erythematous plaques, ulcerations, and erosions. Histopathology reveals sterile noncaseating granulomas made of Langerhans giant cells, epithelioid histocytes, and plasma cells.⁹

Metastatic clear cell carcinomas, such as renal cell carcinoma, can be differentiated by a history of primary carcinoma, demonstration of histologic vascular stroma, and other features related to metastatic clear cell carcinoma.²

There are no well-established therapeutic guidelines for hidradenocarcinoma. Wide local excision with margins greater than 2 cm is the preferred initial treatment and often is performed in conjunction with sentinel lymph node biopsy. External beam radiotherapy and adjunctive chemotherapy have been used for tumors that could not be surgically cleared. However, the efficacy of these treatments has not been well established.² Targeted therapies recently have emerged as an alternative treatment choice for hidradenocarcinoma due to the utilization of immunohistochemical and genomic testing. The discovery of specific gene mutations or the expression of hormonal receptors in this tumor have paved the way for targeting HER2-expressing hidradenocarcinomas with trastuzumab and those expressing estrogen receptor with the estrogen receptor inhibitor tamoxifen.¹ Epidermal growth factor receptor inhibitors and PI3K/Akt/mTOR (phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin) pathway inhibitors also have been used to target various signal transduction pathways.²

Wide excision with 2.5-cm margins was performed on our patient, and a positron emission tomography– computed tomography scan revealed no metastatic disease. She declined sentinel lymph node biopsy and additional treatment. Due to the risk for recurrence, she was monitored closely with skin examinations and positron emission tomography–computed tomography every 3 months for the first year and every 6 months thereafter. Thus far, she has had no evidence of local or regional recurrence.

In type 2 diabetes (T2D), a greater degree of hyperlipidemia and hypertension, although not hyperglycemia, was associated with measurable cognitive impairment even among patients with only a 4-year mean disease duration, according to a substudy of the GRADE trial.

The association of these cardiovascular (CV) risk factors with impairments in cognition has been reported before, but the findings are notable because the mean duration of T2D was short in a relatively healthy study population, reported a multicenter team of investigators.

The relative impairments in cognitive function “may not be clinically significant given the very small size of the differences,” conceded the authors of this study, led by José A. Luchsinger, MD, but they are consistent with previous reports of the same association in older patients with a longer duration of diabetes. In other words, the data suggest the risk of cognitive loss from CV risk factors in T2D patients begins early.

“A potential explanation for the small differences, compared with those previously reported, is that the GRADE cohort is relatively young with a healthier cardiovascular profile and shorter diabetes duration compared with other studies,” reported the investigators, whose results were published online July 20, 2021, in Diabetes Care.
 

99% complete cognitive assessments

In the GRADE (Glycemia Reduction Approaches in Diabetes: Comparative Effectiveness) trial, 5,018 (99.4%) of the 5,047 enrolled patients completed a battery of cognitive assessments at baseline. Patients were excluded from this study if they had any major CV event in the previous year, if they had T2D for more than 10 years, if they had significant renal impairment, and if they had any history of stage 3 or greater heart failure. Their mean age was 56.7 years.

By cross-sectional analysis, cognitive evaluations, including the Digit Symbol Substitution Test (DSST) and the Spanish English Verbal Learning Test, were evaluated in relation to baseline LDL cholesterol levels, systolic and diastolic blood pressure, hemoglobin A1c, and statin use.

Unlike previous studies in T2D patients, no relationship was observed between cognitive function and A1c level at baseline. However, LDL cholesterol greater than 100 mg/dL was associated with cognitive impairment as measured with the DSST after adjustment for age, sex, education, and general health. The mean difference relative to LDL cholesterol below 70 mg/dL was only 1.8 points, but this was highly significant (P < .001).

Similarly, significant but modest cognitive impairment on DSST score after adjustment for variables were seen for those with a systolic BP between 120 mg and <140 mg relative to either <120 mm Hg or at least 140 mm Hg (P = .014). The same was seen for diastolic BPs of 80 to <90 when compared with either <80 mm Hg or to 90 mm Hg or higher (P = .01).

For those taking statins versus no statins at baseline, there was a 1.4-point mean advantage in DSST score after adjusting for variables (P < .001).

Modest cognitive impairments recorded

Again, the absolute mean differences in the DSST cognitive scores, despite their statistical significance, were modest, according to the authors. In general, the mean difference was rarely greater than 2.0 points and often 1.0 point or less. The authors acknowledged that these changes are of an uncertain clinical significance, but they considered the findings consistent with the association of CV risk factors with cognitive deficits in older T2DM patients or T2DM patients with longer duration of disease.

One difference between this GRADE substudy and previous studies was the lack of an association between cognitive impairment and hyperglycemia. In the ACCORD trial for example, increased levels of blood glycemia were associated with lower performance on numerous tests of cognitive function.

In the Diabetes Control and Complications Trial (DCCT), poorer glycemic control was related to poorer performance on tests of executive function.

Both of those studies also linked hypertension and hyperlipidemia with cognitive deficits, but given that patients in ACCORD had T2DM of substantially longer duration and those in DCCT were older, “it seems reasonable to speculate that, in patients with diabetes duration of less than 10 years, the association between hyperglycemia and cognitive performance may not yet be evident,” the GRADE authors reported.
 

GRADE trial compares drugs in four classes

The GRADE trial was conducted to compare four classes of T2D therapies for long-term glycemic control as expressed by A1c control over time. The results of the trial, presented recently at the 2021 annual scientific sessions of the American Diabetes Association, found that insulin glargine and the glucagonlike peptide–1 receptor agonist liraglutide performed best on the primary endpoint of maintaining A1c below 7.0%. Both performed significantly better than the sulfonylurea glimepiride and the dipeptidyl peptidase–4 inhibitor sitagliptin.

This substudy of baseline cognitive function in the relatively large GRADE trial provided a unique opportunity to evaluate the impact of CV risk factors in patients with T2D of relatively short duration.

While the data support the adverse impact of inadequately controlled modifiable risk factors on cognitive function in T2D patients, David R. Matthews, DPhil, BM, BCh, emeritus professor of diabetes medicine at the University of Oxford (England), noted that the association was weak and advised a cautious interpretation.

“The effect size is very small indeed. The data are found as a subset of multiple testing,” he said in an interview. He suggested the associations might be the result of “data farming,” and he emphasized that the relationships between these risk factors and cognitive deficits are associations that do not imply causation.

Nevertheless, and despite their unclear clinical implications, Dr. Matthews said that these data might still have a message.

“It is another reminder that for many reasons we all need to be alert to the need for lowering hyperlipidemia and hypertension to normal levels – the benefits may not just be limited to cardiovascular outcome,” Dr. Matthews stated.

The lead author of the study, Dr. Luchsinger, also cautioned against overinterpreting the data.

While the data show that “lipid and blood pressure control within recommended guidelines are associated with marginally better cognitive function in patients with type 2 diabetes of less than 5 years duration on average,” he added that “the study is limited by its cross-sectional nature.”

He indicated that further analysis will be helpful in assessing the implications.

“Longitudinal analyses of the same group of individuals will be conducted next year,” noted Dr. Luchsinger, associate professor of medicine and epidemiology, Columbia University Medical Center, New York.

Dr. Luchsinger reported financial relationships with vTv therapeutics. Dr. Matthews reported no potential conflicts of interest.

In type 2 diabetes (T2D), a greater degree of hyperlipidemia and hypertension, although not hyperglycemia, was associated with measurable cognitive impairment even among patients with only a 4-year mean disease duration, according to a substudy of the GRADE trial.

The association of these cardiovascular (CV) risk factors with impairments in cognition has been reported before, but the findings are notable because the mean duration of T2D was short in a relatively healthy study population, reported a multicenter team of investigators.

The relative impairments in cognitive function “may not be clinically significant given the very small size of the differences,” conceded the authors of this study, led by José A. Luchsinger, MD, but they are consistent with previous reports of the same association in older patients with a longer duration of diabetes. In other words, the data suggest the risk of cognitive loss from CV risk factors in T2D patients begins early.

“A potential explanation for the small differences, compared with those previously reported, is that the GRADE cohort is relatively young with a healthier cardiovascular profile and shorter diabetes duration compared with other studies,” reported the investigators, whose results were published online July 20, 2021, in Diabetes Care.
 

99% complete cognitive assessments

In the GRADE (Glycemia Reduction Approaches in Diabetes: Comparative Effectiveness) trial, 5,018 (99.4%) of the 5,047 enrolled patients completed a battery of cognitive assessments at baseline. Patients were excluded from this study if they had any major CV event in the previous year, if they had T2D for more than 10 years, if they had significant renal impairment, and if they had any history of stage 3 or greater heart failure. Their mean age was 56.7 years.

By cross-sectional analysis, cognitive evaluations, including the Digit Symbol Substitution Test (DSST) and the Spanish English Verbal Learning Test, were evaluated in relation to baseline LDL cholesterol levels, systolic and diastolic blood pressure, hemoglobin A1c, and statin use.

Unlike previous studies in T2D patients, no relationship was observed between cognitive function and A1c level at baseline. However, LDL cholesterol greater than 100 mg/dL was associated with cognitive impairment as measured with the DSST after adjustment for age, sex, education, and general health. The mean difference relative to LDL cholesterol below 70 mg/dL was only 1.8 points, but this was highly significant (P < .001).

Similarly, significant but modest cognitive impairment on DSST score after adjustment for variables were seen for those with a systolic BP between 120 mg and <140 mg relative to either <120 mm Hg or at least 140 mm Hg (P = .014). The same was seen for diastolic BPs of 80 to <90 when compared with either <80 mm Hg or to 90 mm Hg or higher (P = .01).

For those taking statins versus no statins at baseline, there was a 1.4-point mean advantage in DSST score after adjusting for variables (P < .001).

Modest cognitive impairments recorded

Again, the absolute mean differences in the DSST cognitive scores, despite their statistical significance, were modest, according to the authors. In general, the mean difference was rarely greater than 2.0 points and often 1.0 point or less. The authors acknowledged that these changes are of an uncertain clinical significance, but they considered the findings consistent with the association of CV risk factors with cognitive deficits in older T2DM patients or T2DM patients with longer duration of disease.

One difference between this GRADE substudy and previous studies was the lack of an association between cognitive impairment and hyperglycemia. In the ACCORD trial for example, increased levels of blood glycemia were associated with lower performance on numerous tests of cognitive function.

In the Diabetes Control and Complications Trial (DCCT), poorer glycemic control was related to poorer performance on tests of executive function.

Both of those studies also linked hypertension and hyperlipidemia with cognitive deficits, but given that patients in ACCORD had T2DM of substantially longer duration and those in DCCT were older, “it seems reasonable to speculate that, in patients with diabetes duration of less than 10 years, the association between hyperglycemia and cognitive performance may not yet be evident,” the GRADE authors reported.
 

GRADE trial compares drugs in four classes

The GRADE trial was conducted to compare four classes of T2D therapies for long-term glycemic control as expressed by A1c control over time. The results of the trial, presented recently at the 2021 annual scientific sessions of the American Diabetes Association, found that insulin glargine and the glucagonlike peptide–1 receptor agonist liraglutide performed best on the primary endpoint of maintaining A1c below 7.0%. Both performed significantly better than the sulfonylurea glimepiride and the dipeptidyl peptidase–4 inhibitor sitagliptin.

This substudy of baseline cognitive function in the relatively large GRADE trial provided a unique opportunity to evaluate the impact of CV risk factors in patients with T2D of relatively short duration.

While the data support the adverse impact of inadequately controlled modifiable risk factors on cognitive function in T2D patients, David R. Matthews, DPhil, BM, BCh, emeritus professor of diabetes medicine at the University of Oxford (England), noted that the association was weak and advised a cautious interpretation.

“The effect size is very small indeed. The data are found as a subset of multiple testing,” he said in an interview. He suggested the associations might be the result of “data farming,” and he emphasized that the relationships between these risk factors and cognitive deficits are associations that do not imply causation.

Nevertheless, and despite their unclear clinical implications, Dr. Matthews said that these data might still have a message.

“It is another reminder that for many reasons we all need to be alert to the need for lowering hyperlipidemia and hypertension to normal levels – the benefits may not just be limited to cardiovascular outcome,” Dr. Matthews stated.

The lead author of the study, Dr. Luchsinger, also cautioned against overinterpreting the data.

While the data show that “lipid and blood pressure control within recommended guidelines are associated with marginally better cognitive function in patients with type 2 diabetes of less than 5 years duration on average,” he added that “the study is limited by its cross-sectional nature.”

He indicated that further analysis will be helpful in assessing the implications.

“Longitudinal analyses of the same group of individuals will be conducted next year,” noted Dr. Luchsinger, associate professor of medicine and epidemiology, Columbia University Medical Center, New York.

Dr. Luchsinger reported financial relationships with vTv therapeutics. Dr. Matthews reported no potential conflicts of interest.

In type 2 diabetes (T2D), a greater degree of hyperlipidemia and hypertension, although not hyperglycemia, was associated with measurable cognitive impairment even among patients with only a 4-year mean disease duration, according to a substudy of the GRADE trial.

The association of these cardiovascular (CV) risk factors with impairments in cognition has been reported before, but the findings are notable because the mean duration of T2D was short in a relatively healthy study population, reported a multicenter team of investigators.

The relative impairments in cognitive function “may not be clinically significant given the very small size of the differences,” conceded the authors of this study, led by José A. Luchsinger, MD, but they are consistent with previous reports of the same association in older patients with a longer duration of diabetes. In other words, the data suggest the risk of cognitive loss from CV risk factors in T2D patients begins early.

“A potential explanation for the small differences, compared with those previously reported, is that the GRADE cohort is relatively young with a healthier cardiovascular profile and shorter diabetes duration compared with other studies,” reported the investigators, whose results were published online July 20, 2021, in Diabetes Care.
 

99% complete cognitive assessments

In the GRADE (Glycemia Reduction Approaches in Diabetes: Comparative Effectiveness) trial, 5,018 (99.4%) of the 5,047 enrolled patients completed a battery of cognitive assessments at baseline. Patients were excluded from this study if they had any major CV event in the previous year, if they had T2D for more than 10 years, if they had significant renal impairment, and if they had any history of stage 3 or greater heart failure. Their mean age was 56.7 years.

By cross-sectional analysis, cognitive evaluations, including the Digit Symbol Substitution Test (DSST) and the Spanish English Verbal Learning Test, were evaluated in relation to baseline LDL cholesterol levels, systolic and diastolic blood pressure, hemoglobin A1c, and statin use.

Unlike previous studies in T2D patients, no relationship was observed between cognitive function and A1c level at baseline. However, LDL cholesterol greater than 100 mg/dL was associated with cognitive impairment as measured with the DSST after adjustment for age, sex, education, and general health. The mean difference relative to LDL cholesterol below 70 mg/dL was only 1.8 points, but this was highly significant (P < .001).

Similarly, significant but modest cognitive impairment on DSST score after adjustment for variables were seen for those with a systolic BP between 120 mg and <140 mg relative to either <120 mm Hg or at least 140 mm Hg (P = .014). The same was seen for diastolic BPs of 80 to <90 when compared with either <80 mm Hg or to 90 mm Hg or higher (P = .01).

For those taking statins versus no statins at baseline, there was a 1.4-point mean advantage in DSST score after adjusting for variables (P < .001).

Modest cognitive impairments recorded

Again, the absolute mean differences in the DSST cognitive scores, despite their statistical significance, were modest, according to the authors. In general, the mean difference was rarely greater than 2.0 points and often 1.0 point or less. The authors acknowledged that these changes are of an uncertain clinical significance, but they considered the findings consistent with the association of CV risk factors with cognitive deficits in older T2DM patients or T2DM patients with longer duration of disease.

One difference between this GRADE substudy and previous studies was the lack of an association between cognitive impairment and hyperglycemia. In the ACCORD trial for example, increased levels of blood glycemia were associated with lower performance on numerous tests of cognitive function.

In the Diabetes Control and Complications Trial (DCCT), poorer glycemic control was related to poorer performance on tests of executive function.

Both of those studies also linked hypertension and hyperlipidemia with cognitive deficits, but given that patients in ACCORD had T2DM of substantially longer duration and those in DCCT were older, “it seems reasonable to speculate that, in patients with diabetes duration of less than 10 years, the association between hyperglycemia and cognitive performance may not yet be evident,” the GRADE authors reported.
 

GRADE trial compares drugs in four classes

The GRADE trial was conducted to compare four classes of T2D therapies for long-term glycemic control as expressed by A1c control over time. The results of the trial, presented recently at the 2021 annual scientific sessions of the American Diabetes Association, found that insulin glargine and the glucagonlike peptide–1 receptor agonist liraglutide performed best on the primary endpoint of maintaining A1c below 7.0%. Both performed significantly better than the sulfonylurea glimepiride and the dipeptidyl peptidase–4 inhibitor sitagliptin.

This substudy of baseline cognitive function in the relatively large GRADE trial provided a unique opportunity to evaluate the impact of CV risk factors in patients with T2D of relatively short duration.

While the data support the adverse impact of inadequately controlled modifiable risk factors on cognitive function in T2D patients, David R. Matthews, DPhil, BM, BCh, emeritus professor of diabetes medicine at the University of Oxford (England), noted that the association was weak and advised a cautious interpretation.

“The effect size is very small indeed. The data are found as a subset of multiple testing,” he said in an interview. He suggested the associations might be the result of “data farming,” and he emphasized that the relationships between these risk factors and cognitive deficits are associations that do not imply causation.

Nevertheless, and despite their unclear clinical implications, Dr. Matthews said that these data might still have a message.

“It is another reminder that for many reasons we all need to be alert to the need for lowering hyperlipidemia and hypertension to normal levels – the benefits may not just be limited to cardiovascular outcome,” Dr. Matthews stated.

The lead author of the study, Dr. Luchsinger, also cautioned against overinterpreting the data.

While the data show that “lipid and blood pressure control within recommended guidelines are associated with marginally better cognitive function in patients with type 2 diabetes of less than 5 years duration on average,” he added that “the study is limited by its cross-sectional nature.”

He indicated that further analysis will be helpful in assessing the implications.

“Longitudinal analyses of the same group of individuals will be conducted next year,” noted Dr. Luchsinger, associate professor of medicine and epidemiology, Columbia University Medical Center, New York.

Dr. Luchsinger reported financial relationships with vTv therapeutics. Dr. Matthews reported no potential conflicts of interest.

In most patients with psoriatic arthritis (PsA), the musculoskeletal manifestations occur after the onset of cutaneous manifestations. The mechanisms underlying the triggering of joint disease is still not well understood, one burning question is whether early and effective treatment of cutaneous psoriasis will reduce the incidence of PsA. In a retrospective non-randomised study, Gisondi et al compared the incidence rates of PsA in patients with chronic plaque psoriasis receiving either continuous treatment with a biologic disease modifying anti-rheumatic drugs (bDMARD- infliximab, etanercept, adalimumab, ustekinumab and secukinumab) for at least 5 years (n=234, 1584 person-year of follow-up) or at least three courses of narrow band ultraviolet B (nb-UVB) phototherapy (n=230, 1478 person-year of follow-up). bDMARDs treatment was associated with a lower risk of incident PsA (adjusted hazard ratio 0.27, 95% Confidence Interval 0.11–0.66). However, analysis after propensity score matching found no significant difference between treatment with bDMARDs and nb-UVB phototherapy and the risk of incident PsA. Prospective studies are required to answer this important question. Interestingly, nail psoriasis was associated with higher risk of PsA, confirming previous observations.

Due to lack of disease activity biomarkers clinical assessment of disease activity in PsA patients with concomitant fibromyalgia can be challenging. Ultrasound (US) may however be useful in providing objective assessment of disease activity. Polachek et al compared 42 patients with PsA and coexisting fibromyalgia syndrome (FMS) (satisfying CASPAR criteria and the 2016 fibromyalgia classification criteria) to 114 PsA patients without FMS (satisfying CASPAR criteria alone). All patients underwent detailed US evaluation including 52 joints, 40 tendons and 14 entheses, and a scores for synovitis, tenosynovitis and enthesitis were summed to obtain a final US disease activity score for each patient. Those with FMS had higher scores of composite clinical disease activity indices. However, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with composite indices in PsA patients without FMS but not in PsA patients with FMS. Thus, US is a tool that can be employed to determine PsA disease activity in patients with concomitant FMS. However, the scanning protocol as described is time consuming. A shortened protocol as well as training of rheumatologists and radiologists for reliably assessing synovitis, tenosynovitis and enthesitis is required before US can be feasibly and reliably used in clinical practice.

IL-23 inhibitors were not found to be efficacious in the treatment of axial spondyloarthritis. It is not clear whether these inhibitors improve axial disease in PsA patients, and if indeed axial PsA is distinct from primary axial spondyloarthritis. In a post-hoc analyses of the DISCOVER 1 and DISCOVER 2 studies that included 312 patients with PsA with imaging-confirmed sacroiliitis randomly assigned to either placebo (n=118), guselkumab Q4 (n=103), or Q8 (n=91), Mease et al demonstrated that at week 24, guselkumab Q4 and Q8 groups vs placebo showed higher least-squares mean changes in BASDAI (−2.7 and −2.7 vs −1.3; P less than .0001) and ASDAS (−1.4 and −1.4 vs −0.7; P less than .0001) scores, which were maintained until week 52. Thus, Guselkumab may improve axial PsA. However, axial PsA has not yet been formally defined, and BASDAI and ASDAS are not specific for axial PsA. Once axial PsA is defined, prospective randomised clinical trials with associated MRI studies will be required to determine if IL-23 inhibitors improve symptoms of axial PsA.

In most patients with psoriatic arthritis (PsA), the musculoskeletal manifestations occur after the onset of cutaneous manifestations. The mechanisms underlying the triggering of joint disease is still not well understood, one burning question is whether early and effective treatment of cutaneous psoriasis will reduce the incidence of PsA. In a retrospective non-randomised study, Gisondi et al compared the incidence rates of PsA in patients with chronic plaque psoriasis receiving either continuous treatment with a biologic disease modifying anti-rheumatic drugs (bDMARD- infliximab, etanercept, adalimumab, ustekinumab and secukinumab) for at least 5 years (n=234, 1584 person-year of follow-up) or at least three courses of narrow band ultraviolet B (nb-UVB) phototherapy (n=230, 1478 person-year of follow-up). bDMARDs treatment was associated with a lower risk of incident PsA (adjusted hazard ratio 0.27, 95% Confidence Interval 0.11–0.66). However, analysis after propensity score matching found no significant difference between treatment with bDMARDs and nb-UVB phototherapy and the risk of incident PsA. Prospective studies are required to answer this important question. Interestingly, nail psoriasis was associated with higher risk of PsA, confirming previous observations.

Due to lack of disease activity biomarkers clinical assessment of disease activity in PsA patients with concomitant fibromyalgia can be challenging. Ultrasound (US) may however be useful in providing objective assessment of disease activity. Polachek et al compared 42 patients with PsA and coexisting fibromyalgia syndrome (FMS) (satisfying CASPAR criteria and the 2016 fibromyalgia classification criteria) to 114 PsA patients without FMS (satisfying CASPAR criteria alone). All patients underwent detailed US evaluation including 52 joints, 40 tendons and 14 entheses, and a scores for synovitis, tenosynovitis and enthesitis were summed to obtain a final US disease activity score for each patient. Those with FMS had higher scores of composite clinical disease activity indices. However, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with composite indices in PsA patients without FMS but not in PsA patients with FMS. Thus, US is a tool that can be employed to determine PsA disease activity in patients with concomitant FMS. However, the scanning protocol as described is time consuming. A shortened protocol as well as training of rheumatologists and radiologists for reliably assessing synovitis, tenosynovitis and enthesitis is required before US can be feasibly and reliably used in clinical practice.

IL-23 inhibitors were not found to be efficacious in the treatment of axial spondyloarthritis. It is not clear whether these inhibitors improve axial disease in PsA patients, and if indeed axial PsA is distinct from primary axial spondyloarthritis. In a post-hoc analyses of the DISCOVER 1 and DISCOVER 2 studies that included 312 patients with PsA with imaging-confirmed sacroiliitis randomly assigned to either placebo (n=118), guselkumab Q4 (n=103), or Q8 (n=91), Mease et al demonstrated that at week 24, guselkumab Q4 and Q8 groups vs placebo showed higher least-squares mean changes in BASDAI (−2.7 and −2.7 vs −1.3; P less than .0001) and ASDAS (−1.4 and −1.4 vs −0.7; P less than .0001) scores, which were maintained until week 52. Thus, Guselkumab may improve axial PsA. However, axial PsA has not yet been formally defined, and BASDAI and ASDAS are not specific for axial PsA. Once axial PsA is defined, prospective randomised clinical trials with associated MRI studies will be required to determine if IL-23 inhibitors improve symptoms of axial PsA.

In most patients with psoriatic arthritis (PsA), the musculoskeletal manifestations occur after the onset of cutaneous manifestations. The mechanisms underlying the triggering of joint disease is still not well understood, one burning question is whether early and effective treatment of cutaneous psoriasis will reduce the incidence of PsA. In a retrospective non-randomised study, Gisondi et al compared the incidence rates of PsA in patients with chronic plaque psoriasis receiving either continuous treatment with a biologic disease modifying anti-rheumatic drugs (bDMARD- infliximab, etanercept, adalimumab, ustekinumab and secukinumab) for at least 5 years (n=234, 1584 person-year of follow-up) or at least three courses of narrow band ultraviolet B (nb-UVB) phototherapy (n=230, 1478 person-year of follow-up). bDMARDs treatment was associated with a lower risk of incident PsA (adjusted hazard ratio 0.27, 95% Confidence Interval 0.11–0.66). However, analysis after propensity score matching found no significant difference between treatment with bDMARDs and nb-UVB phototherapy and the risk of incident PsA. Prospective studies are required to answer this important question. Interestingly, nail psoriasis was associated with higher risk of PsA, confirming previous observations.

Due to lack of disease activity biomarkers clinical assessment of disease activity in PsA patients with concomitant fibromyalgia can be challenging. Ultrasound (US) may however be useful in providing objective assessment of disease activity. Polachek et al compared 42 patients with PsA and coexisting fibromyalgia syndrome (FMS) (satisfying CASPAR criteria and the 2016 fibromyalgia classification criteria) to 114 PsA patients without FMS (satisfying CASPAR criteria alone). All patients underwent detailed US evaluation including 52 joints, 40 tendons and 14 entheses, and a scores for synovitis, tenosynovitis and enthesitis were summed to obtain a final US disease activity score for each patient. Those with FMS had higher scores of composite clinical disease activity indices. However, the total US score and its subcategories were similar for those with and without FMS. The total US score significantly correlated with composite indices in PsA patients without FMS but not in PsA patients with FMS. Thus, US is a tool that can be employed to determine PsA disease activity in patients with concomitant FMS. However, the scanning protocol as described is time consuming. A shortened protocol as well as training of rheumatologists and radiologists for reliably assessing synovitis, tenosynovitis and enthesitis is required before US can be feasibly and reliably used in clinical practice.

IL-23 inhibitors were not found to be efficacious in the treatment of axial spondyloarthritis. It is not clear whether these inhibitors improve axial disease in PsA patients, and if indeed axial PsA is distinct from primary axial spondyloarthritis. In a post-hoc analyses of the DISCOVER 1 and DISCOVER 2 studies that included 312 patients with PsA with imaging-confirmed sacroiliitis randomly assigned to either placebo (n=118), guselkumab Q4 (n=103), or Q8 (n=91), Mease et al demonstrated that at week 24, guselkumab Q4 and Q8 groups vs placebo showed higher least-squares mean changes in BASDAI (−2.7 and −2.7 vs −1.3; P less than .0001) and ASDAS (−1.4 and −1.4 vs −0.7; P less than .0001) scores, which were maintained until week 52. Thus, Guselkumab may improve axial PsA. However, axial PsA has not yet been formally defined, and BASDAI and ASDAS are not specific for axial PsA. Once axial PsA is defined, prospective randomised clinical trials with associated MRI studies will be required to determine if IL-23 inhibitors improve symptoms of axial PsA.

Key clinical point: Among patients with psoriatic arthritis (PsA), risk for major adverse cardiovascular events (MACEs) was higher in those who initiated interleukin (IL)12/23 and IL17 inhibitors vs tumor necrosis factor (TNF) inhibitors. However, risk for MACEs was not different among new-users of TNF inhibitors or apremilast.

Major finding: Overall, 51 MACEs (crude incidence rate, 3.4/1,000 patient-years) were observed. The risk of MACEs was higher (P less than .0001) with IL12/23 (weighted hazard ratio [wHR], 2.0; 95% confidence interval [CI], 1.3-3.0) and IL17 (wHR, 1.9; 95% CI, 1.2-3.0) inhibitors but not with apremilast (wHR, 1.3; 95% CI, 0.8-2.2) vs TNF inhibitors.

Study details: Findings are from a nationwide PsA cohort without a history of cardiovascular diseases involving 9,510 new users of biological disease-modifying anti-rheumatic drugs (TNF inhibitor, n=7289; IL12/23 inhibitor, n=1058; IL17 inhibitor, n=1,163) and 1,885 new users of apremilast.

Disclosures: The study did not receive any funding. P Claudepierre reported receiving consulting fees from and being an investigator for various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Vegas LP et al. Rheumatology. 2021 Jul 9. doi: 10.1093/rheumatology/keab522.

Key clinical point: Among patients with psoriatic arthritis (PsA), risk for major adverse cardiovascular events (MACEs) was higher in those who initiated interleukin (IL)12/23 and IL17 inhibitors vs tumor necrosis factor (TNF) inhibitors. However, risk for MACEs was not different among new-users of TNF inhibitors or apremilast.

Major finding: Overall, 51 MACEs (crude incidence rate, 3.4/1,000 patient-years) were observed. The risk of MACEs was higher (P less than .0001) with IL12/23 (weighted hazard ratio [wHR], 2.0; 95% confidence interval [CI], 1.3-3.0) and IL17 (wHR, 1.9; 95% CI, 1.2-3.0) inhibitors but not with apremilast (wHR, 1.3; 95% CI, 0.8-2.2) vs TNF inhibitors.

Study details: Findings are from a nationwide PsA cohort without a history of cardiovascular diseases involving 9,510 new users of biological disease-modifying anti-rheumatic drugs (TNF inhibitor, n=7289; IL12/23 inhibitor, n=1058; IL17 inhibitor, n=1,163) and 1,885 new users of apremilast.

Disclosures: The study did not receive any funding. P Claudepierre reported receiving consulting fees from and being an investigator for various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Vegas LP et al. Rheumatology. 2021 Jul 9. doi: 10.1093/rheumatology/keab522.

Key clinical point: Among patients with psoriatic arthritis (PsA), risk for major adverse cardiovascular events (MACEs) was higher in those who initiated interleukin (IL)12/23 and IL17 inhibitors vs tumor necrosis factor (TNF) inhibitors. However, risk for MACEs was not different among new-users of TNF inhibitors or apremilast.

Major finding: Overall, 51 MACEs (crude incidence rate, 3.4/1,000 patient-years) were observed. The risk of MACEs was higher (P less than .0001) with IL12/23 (weighted hazard ratio [wHR], 2.0; 95% confidence interval [CI], 1.3-3.0) and IL17 (wHR, 1.9; 95% CI, 1.2-3.0) inhibitors but not with apremilast (wHR, 1.3; 95% CI, 0.8-2.2) vs TNF inhibitors.

Study details: Findings are from a nationwide PsA cohort without a history of cardiovascular diseases involving 9,510 new users of biological disease-modifying anti-rheumatic drugs (TNF inhibitor, n=7289; IL12/23 inhibitor, n=1058; IL17 inhibitor, n=1,163) and 1,885 new users of apremilast.

Disclosures: The study did not receive any funding. P Claudepierre reported receiving consulting fees from and being an investigator for various pharmaceutical companies. Other authors declared no conflicts of interest.

Source: Vegas LP et al. Rheumatology. 2021 Jul 9. doi: 10.1093/rheumatology/keab522.

Key clinical point: The drug survival rate was good for the first biological disease-modifying antirheumatic drug (bDMARD) in patients with psoriatic arthritis (PsA). Moreover, female sex may be a predisposing risk factor for flares and therapeutic switches.

Major finding: Overall, 44.32% of patients switched to another bDMARD. The mean time to first bDMARD discontinuation was 72 months. Overall, the drug survival rate in patients treated with antitumor necrosis factor-α and anti-interleukin (IL)-12/23 or anti-IL17 was 75% at 2 years and 60% at 5 years without a significant difference between the biological agents (P = .66). Female sex was associated with a higher risk for first bDMARD discontinuation (hazard ratio, 2.39; 95% confidence interval, 1.50-3.81).

Study details: The data come from a 15-year, monocentric, real-life study involving 264 patients with PsA who received biologics treatment.

Disclosures: The study reported no external funding. R Ramonda and A Doria reported receiving honoraria and speaker fees from Novartis, AbbVie, Pfizer, MSD, and Janssen. All the other authors declared no conflicts of interest.

Source: Lorenzin M et al. Clin Rheumatol. 2021 Jun 16. doi: 10.1007/s10067-021-05799-0.

Key clinical point: The drug survival rate was good for the first biological disease-modifying antirheumatic drug (bDMARD) in patients with psoriatic arthritis (PsA). Moreover, female sex may be a predisposing risk factor for flares and therapeutic switches.

Major finding: Overall, 44.32% of patients switched to another bDMARD. The mean time to first bDMARD discontinuation was 72 months. Overall, the drug survival rate in patients treated with antitumor necrosis factor-α and anti-interleukin (IL)-12/23 or anti-IL17 was 75% at 2 years and 60% at 5 years without a significant difference between the biological agents (P = .66). Female sex was associated with a higher risk for first bDMARD discontinuation (hazard ratio, 2.39; 95% confidence interval, 1.50-3.81).

Study details: The data come from a 15-year, monocentric, real-life study involving 264 patients with PsA who received biologics treatment.

Disclosures: The study reported no external funding. R Ramonda and A Doria reported receiving honoraria and speaker fees from Novartis, AbbVie, Pfizer, MSD, and Janssen. All the other authors declared no conflicts of interest.

Source: Lorenzin M et al. Clin Rheumatol. 2021 Jun 16. doi: 10.1007/s10067-021-05799-0.

Key clinical point: The drug survival rate was good for the first biological disease-modifying antirheumatic drug (bDMARD) in patients with psoriatic arthritis (PsA). Moreover, female sex may be a predisposing risk factor for flares and therapeutic switches.

Major finding: Overall, 44.32% of patients switched to another bDMARD. The mean time to first bDMARD discontinuation was 72 months. Overall, the drug survival rate in patients treated with antitumor necrosis factor-α and anti-interleukin (IL)-12/23 or anti-IL17 was 75% at 2 years and 60% at 5 years without a significant difference between the biological agents (P = .66). Female sex was associated with a higher risk for first bDMARD discontinuation (hazard ratio, 2.39; 95% confidence interval, 1.50-3.81).

Study details: The data come from a 15-year, monocentric, real-life study involving 264 patients with PsA who received biologics treatment.

Disclosures: The study reported no external funding. R Ramonda and A Doria reported receiving honoraria and speaker fees from Novartis, AbbVie, Pfizer, MSD, and Janssen. All the other authors declared no conflicts of interest.

Source: Lorenzin M et al. Clin Rheumatol. 2021 Jun 16. doi: 10.1007/s10067-021-05799-0.