New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

New treatment strategies in clinical trials show promise in reducing the tapering time of glucocorticoids (GCs) or possibly even replacing the use of GCs. Selective GC receptor agonists and modulators and GC plus hydroxysteroid dehydrogenase inhibitor combination therapy are some of the approaches under consideration.

“There is growing observational data that confirms the GC-sparing effect seen in some of these clinical trials in real-world data,” said Sebastian E. Sattui, MD, assistant professor of medicine and director of the Vasculitis Center at the University of Pittsburgh Medical Center, Pittsburgh.

GC minimization is an important goal, “and the data emerging from these trials should be reassuring for rheumatology providers,” Dr. Sattui said.

HSD-1 Inhibitors Under Study

11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is a tissue-specific intracellular modulator of GC action that’s been trialed for a number of rheumatic conditions. “HSD-1 deficiency or inhibition has been consistently associated with reduced GC side effects in mouse and human,” wrote the authors of a study testing the coadministration of HSD-1 inhibitor SPI-62 (clofutriben) with prednisolone in patients with polymyalgia rheumatica (PMR) to measure its impact on efficacy and toxicity.

Lead study author David Katz, PhD, chief scientific officer at Sparrow Pharmaceuticals, presented results at the at the annual European Congress of Rheumatology.

GCs are often the first-line therapy with PMR. However, it’s very difficult for patients to stop taking GCs once they start taking them. The study included patients with PMR who were taking 10 mg/d prednisolone and didn’t require a dose increase. For the study, they continued prednisolone without dose reduction for 4 weeks, receiving either SPI-62 6 mg/d or a matching placebo for 2 weeks.

During SPI-62 treatment, researchers in sequential cohorts maintained daily prednisolone doses at 10 mg, adjusted to 15 mg or adjusted to 20 mg.

A 10-mg dose of prednisolone combined with 6 mg of SPI-62 demonstrated less efficacy compared with placebo but improved upon prednisolone toxicities such as bone formation and resorption biomarkers, lipidemia, and insulin resistance. Doubling the dose to 20 mg prednisolone combined with SPI-62 achieved similar efficacy and maintained improvement of prednisolone toxicity markers.

“In patients with PMR, when we double the dose of prednisolone during coadministration with a potent HSD-1 inhibitor, we are able to have similar stability of symptoms, physical function, and systemic inflammation. At the same time, we are able to show improvements on biomarkers of bone turnover and insulin resistance,” Dr. Katz informed the EULAR 2024 audience.

An ongoing phase 2 clinical trial is testing SPI-62 in patients with endogenous Cushing syndrome. “It’s a longer-term trial, so we’re able to see at least an individual patient’s more clinical outcomes such as reversal of Cushing’s-associated myopathy and the ability of patients to discontinue all of their antidiabetic medications and yet still have good glycemic control,” he said.

Another research team from the United Kingdom explored whether AZD4017, an inhibitor of human 11ß-HSD1, could mitigate GC effects. The researchers randomly assigned 32 healthy male volunteers to AZD4017 or placebo, along with prednisolone. They reported a worsening of hepatic insulin sensitivity in the placebo group but not in the AZD4017 group, and protective effects of AZD4017 on markers of lipid metabolism and bone turnover, as well as lowered nighttime blood pressure. The results signified that coadministration of AZD4017 with prednisolone in men could be a way to reduce GC side effects.

In a Japanese phase 1/2 study, 11ß-HSD1 inhibitor S-707106 proved useful as an insulin sensitizer and antisarcopenic and anti-obesity medication in 16 patients with Cushing syndrome and autonomous cortisol secretion.
 

Novel Antitumor Necrosis Factor (TNF) Antibody Plus GC Receptor Modulator Conjugate

A novel antibody-drug conjugate comprising the anti-TNF monoclonal antibody adalimumab (ABBV-3373) linked to a GC receptor modulator shows promise as a GC alternative.

A notable 2022 study authored by Frank Buttgereit, MD, and other researchers assessed its safety and efficacy in a randomized, double-blind, active-controlled, proof-of-concept trial.

ABBV-3373 “was designed to potentially allow precise targeting of activated immune cells while significantly dampening inflammation and minimizing the systemic side effects associated with glucocorticoids,” according to AbbVie, its manufacturer.

A total of 48 adults with moderate to severe rheumatoid arthritis receiving background methotrexate were randomized to receive either ABBV-3373 (n = 31) or adalimumab (n = 17). The novel drug at 12 weeks showed a −2.65 reduction in the Disease Activity Score in 28 joints using C-reactive protein, compared with −2.13 for adalimumab. Researchers also predicted ABBV-3373 to be more effective than adalimumab based on in-trial and historical adalimumab data.

“We have great expectations for this molecule,” said Giovanni Adami, MD, PhD, a rheumatologist at the University of Verona, Verona, Italy, who has coauthored several studies on the use of GCs. Plans are underway for a phase 3 study with ABBV-3373.
 

C5a and Interleukin (IL)-6 Receptor Inhibitors as GC-Sparing Drugs

Investigators in a 2021 paper explored whether the C5a receptor inhibitor avacopan could effectively treat patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis without the need for daily GCs, following treatment with either cyclophosphamide or rituximab. They randomized 331 patients to receive avacopan or prednisone given on a tapering schedule for 20 weeks (60 mg/d tapered to discontinuation by week 21). “Avacopan was noninferior but not superior to prednisone taper with respect to remission at week 26 and was superior to prednisone taper with respect to sustained remission at week 52,” the investigators summarized.

A longer trial should test avacopan’s safety and durability in patients with ANCA-associated vasculitis, they recommended.

Sarilumab, a human monoclonal antibody that binds IL-6 receptor alpha and blocks the IL-6 pathway, yielded good results in the phase 3 SAPHYR trial as an alternative for patients with PMR who relapse while tapering prednisone therapy.

Researchers in the SAPHYR trial randomly assigned 118 patients 1:1 to receive a twice-monthly subcutaneous injection of sarilumab over 52 weeks plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. Patients in each group received a tapered GC dose initially at 15 mg/d for 2 weeks in a blinded fashion to control for disease at baseline.

Sarilumab effectively sustained remission in patients, significantly reducing the GC dose compared with placebo.

Disease flare after clinical remission took place in 57% of patients in the placebo group, vs 24% in the sarilumab group. “The placebo-treated patients had a fairly traditional 52-week GC taper. The patients treated with sarilumab had a very rapid GC taper,” said lead study author Robert Spiera, MD, director of the Scleroderma, Vasculitis and Myositis Center at the Hospital for Special Surgery, New York City.

In his own practice, Dr. Spiera often treats his patients with new-onset PMR with a fairly rapid GC taper, akin to what was used in SAPHYR, recognizing that a portion of these patients can be successfully treated with a relatively brief course of GCs, although the majority will need to have “rescue” therapy for flares with that approach.

Hospital for Special Surgery

A version of this article appeared on Medscape.com.

Hi, everyone. I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

A few months ago, my health system added a clinical decision support function to our electronic health record to reduce inappropriate ordering of vitamin D levels. Clinicians are now required to select from a list of approved indications or diagnoses (including a history of vitamin D deficiency) before ordering the test.

Although I don’t know yet whether this process has had the desired effect, I felt that it was long overdue. Several years ago, I wrote an editorial that questioned the dramatic increase in vitamin D testing given the uncertainty about what level is adequate for good health and clinical trials showing that supplementing people with lower levels has no benefits for a variety of medical conditions. A more recent review of prospective studies of vitamin D supplements concluded that most correlations between vitamin D levels and outcomes in common and high-mortality conditions are unlikely to be causal.

A new Endocrine Society guideline recommends against routine measurement of vitamin D levels in healthy individuals. The guideline reinforces my current practice of not screening for vitamin D deficiency except in special situations, such as an individual with dark skin who works the night shift and rarely goes outdoors during daytime hours. But I haven’t been offering empirical vitamin D supplements to the four at-risk groups identified by the Endocrine Society: children, adults older than 75 years, pregnant patients, and adults with prediabetes. The evidence behind these recommendations merits a closer look.

In exclusively or primarily breastfed infants, I follow the American Academy of Pediatrics recommendation to prescribe a daily supplement containing 400 IU of vitamin D. However, the Endocrine Society found evidence from several studies conducted in other countries that continuing supplementation throughout childhood reduces the risk for rickets and possibly reduces the incidence of respiratory infections, with few adverse effects.

Many older women, and some older men, choose to take a calcium and vitamin D supplement for bone health, even though there is scant evidence that doing so prevents fractures in community-dwelling adults without osteoporosis. The Endocrine Society’s meta-analysis, however, found that 1000 adults aged 75 years or older who took an average of 900 IU of vitamin D daily for 2 years could expect to experience six fewer deaths than an identical group not taking supplements.

A typical prenatal vitamin contains 400 IU of vitamin D. Placebo-controlled trials reviewed by the Endocrine Society that gave an average of 2500 IU daily found statistically insignificant reductions in preeclampsia, intrauterine death, preterm birth, small for gestation age birth, and neonatal deaths.

Finally, the Endocrine Society’s recommendation for adults with prediabetes was based on 11 trials (three conducted in the United States) that tested a daily average of 3500 IU and found a slightly lower risk for progression to diabetes (24 fewer diagnoses of type 2 diabetes per 1000 persons) in the group who took supplements.

Of the four groups highlighted by the guideline, the strongest case for vitamin D supplements is in older adults — it’s hard to argue with lower mortality, even if the difference is small. Therefore, I will start suggesting that my patients over age 75 take a daily vitamin D supplement containing at least 800 IU if they aren’t already doing so.

On the other hand, I don’t plan to change my approach to pregnant patients (whose benefits in studies could have been due to chance), children after age 1 year (studies of children in other countries with different nutritional status may not apply to the United States), or adults with prediabetes (where we already have proven lifestyle interventions with much greater effects). In these cases, either I am unconvinced that the data support benefits for my patients, or I feel that the benefits of vitamin D supplements are small enough to be outweighed by potential harms, such as increased kidney stones.

Kenneth W. Lin, Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed no relevant financial relationships.

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

Hi, everyone. I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

A few months ago, my health system added a clinical decision support function to our electronic health record to reduce inappropriate ordering of vitamin D levels. Clinicians are now required to select from a list of approved indications or diagnoses (including a history of vitamin D deficiency) before ordering the test.

Although I don’t know yet whether this process has had the desired effect, I felt that it was long overdue. Several years ago, I wrote an editorial that questioned the dramatic increase in vitamin D testing given the uncertainty about what level is adequate for good health and clinical trials showing that supplementing people with lower levels has no benefits for a variety of medical conditions. A more recent review of prospective studies of vitamin D supplements concluded that most correlations between vitamin D levels and outcomes in common and high-mortality conditions are unlikely to be causal.

A new Endocrine Society guideline recommends against routine measurement of vitamin D levels in healthy individuals. The guideline reinforces my current practice of not screening for vitamin D deficiency except in special situations, such as an individual with dark skin who works the night shift and rarely goes outdoors during daytime hours. But I haven’t been offering empirical vitamin D supplements to the four at-risk groups identified by the Endocrine Society: children, adults older than 75 years, pregnant patients, and adults with prediabetes. The evidence behind these recommendations merits a closer look.

In exclusively or primarily breastfed infants, I follow the American Academy of Pediatrics recommendation to prescribe a daily supplement containing 400 IU of vitamin D. However, the Endocrine Society found evidence from several studies conducted in other countries that continuing supplementation throughout childhood reduces the risk for rickets and possibly reduces the incidence of respiratory infections, with few adverse effects.

Many older women, and some older men, choose to take a calcium and vitamin D supplement for bone health, even though there is scant evidence that doing so prevents fractures in community-dwelling adults without osteoporosis. The Endocrine Society’s meta-analysis, however, found that 1000 adults aged 75 years or older who took an average of 900 IU of vitamin D daily for 2 years could expect to experience six fewer deaths than an identical group not taking supplements.

A typical prenatal vitamin contains 400 IU of vitamin D. Placebo-controlled trials reviewed by the Endocrine Society that gave an average of 2500 IU daily found statistically insignificant reductions in preeclampsia, intrauterine death, preterm birth, small for gestation age birth, and neonatal deaths.

Finally, the Endocrine Society’s recommendation for adults with prediabetes was based on 11 trials (three conducted in the United States) that tested a daily average of 3500 IU and found a slightly lower risk for progression to diabetes (24 fewer diagnoses of type 2 diabetes per 1000 persons) in the group who took supplements.

Of the four groups highlighted by the guideline, the strongest case for vitamin D supplements is in older adults — it’s hard to argue with lower mortality, even if the difference is small. Therefore, I will start suggesting that my patients over age 75 take a daily vitamin D supplement containing at least 800 IU if they aren’t already doing so.

On the other hand, I don’t plan to change my approach to pregnant patients (whose benefits in studies could have been due to chance), children after age 1 year (studies of children in other countries with different nutritional status may not apply to the United States), or adults with prediabetes (where we already have proven lifestyle interventions with much greater effects). In these cases, either I am unconvinced that the data support benefits for my patients, or I feel that the benefits of vitamin D supplements are small enough to be outweighed by potential harms, such as increased kidney stones.

Kenneth W. Lin, Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed no relevant financial relationships.

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

Hi, everyone. I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

A few months ago, my health system added a clinical decision support function to our electronic health record to reduce inappropriate ordering of vitamin D levels. Clinicians are now required to select from a list of approved indications or diagnoses (including a history of vitamin D deficiency) before ordering the test.

Although I don’t know yet whether this process has had the desired effect, I felt that it was long overdue. Several years ago, I wrote an editorial that questioned the dramatic increase in vitamin D testing given the uncertainty about what level is adequate for good health and clinical trials showing that supplementing people with lower levels has no benefits for a variety of medical conditions. A more recent review of prospective studies of vitamin D supplements concluded that most correlations between vitamin D levels and outcomes in common and high-mortality conditions are unlikely to be causal.

A new Endocrine Society guideline recommends against routine measurement of vitamin D levels in healthy individuals. The guideline reinforces my current practice of not screening for vitamin D deficiency except in special situations, such as an individual with dark skin who works the night shift and rarely goes outdoors during daytime hours. But I haven’t been offering empirical vitamin D supplements to the four at-risk groups identified by the Endocrine Society: children, adults older than 75 years, pregnant patients, and adults with prediabetes. The evidence behind these recommendations merits a closer look.

In exclusively or primarily breastfed infants, I follow the American Academy of Pediatrics recommendation to prescribe a daily supplement containing 400 IU of vitamin D. However, the Endocrine Society found evidence from several studies conducted in other countries that continuing supplementation throughout childhood reduces the risk for rickets and possibly reduces the incidence of respiratory infections, with few adverse effects.

Many older women, and some older men, choose to take a calcium and vitamin D supplement for bone health, even though there is scant evidence that doing so prevents fractures in community-dwelling adults without osteoporosis. The Endocrine Society’s meta-analysis, however, found that 1000 adults aged 75 years or older who took an average of 900 IU of vitamin D daily for 2 years could expect to experience six fewer deaths than an identical group not taking supplements.

A typical prenatal vitamin contains 400 IU of vitamin D. Placebo-controlled trials reviewed by the Endocrine Society that gave an average of 2500 IU daily found statistically insignificant reductions in preeclampsia, intrauterine death, preterm birth, small for gestation age birth, and neonatal deaths.

Finally, the Endocrine Society’s recommendation for adults with prediabetes was based on 11 trials (three conducted in the United States) that tested a daily average of 3500 IU and found a slightly lower risk for progression to diabetes (24 fewer diagnoses of type 2 diabetes per 1000 persons) in the group who took supplements.

Of the four groups highlighted by the guideline, the strongest case for vitamin D supplements is in older adults — it’s hard to argue with lower mortality, even if the difference is small. Therefore, I will start suggesting that my patients over age 75 take a daily vitamin D supplement containing at least 800 IU if they aren’t already doing so.

On the other hand, I don’t plan to change my approach to pregnant patients (whose benefits in studies could have been due to chance), children after age 1 year (studies of children in other countries with different nutritional status may not apply to the United States), or adults with prediabetes (where we already have proven lifestyle interventions with much greater effects). In these cases, either I am unconvinced that the data support benefits for my patients, or I feel that the benefits of vitamin D supplements are small enough to be outweighed by potential harms, such as increased kidney stones.

Kenneth W. Lin, Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed no relevant financial relationships.

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

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The health consequences of excess visceral fat tissue are well known. But there is another type of fat accumulation in the body that increases the risk for type 2 diabetes and cardiovascular diseases. In Molecular Aspects of Medicine, researchers warned that the dangers arising from intramuscular fat tissue are often underestimated.

“Everyone knows the dangers of abdominal fat or that the deposition of fat in the coronary arteries can cause a heart attack,” said lead author Osvaldo Contreras, PhD, from the School of Clinical Medicine at the University of New South Wales in Sydney, Australia. “But hardly anyone has ever heard of fat accumulation in skeletal muscles, even though they are associated with a whole range of life-threatening diseases.” 

“The work emphasizes that muscles are not only good for standing, walking, or lifting a box. They are metabolically active, produce hormones, communicate in the body, and can positively or negatively affect a person’s health,” Yurdagül Zopf, MD, PhD, professor of integrative medicine specializing in nutritional medicine and director of the Hector Center for Nutrition, Exercise, and Sports at the University Hospital Erlangen, Erlangen, Germany, said in an interview.
 

Associated With Diseases

Increased intramuscular fat is found in various conditions where muscle mass is increasingly lost and replaced by fat and connective tissue. Intramuscular fat has been observed, for example, in patients with chronic muscle diseases, sarcopenia, hormonal disorders, and metabolic diseases such as insulin resistance and type 2 diabetes, as well as in patients with cardiovascular problems such as hypertension and heart failure.

Fat accumulation in the muscles, like all fat deposits in the body, can result from an unhealthy lifestyle with excessive calorie intake and, especially, lack of exercise. “If the body has more energy available than it can use, it will initially store it as subcutaneous fat,” said Dr. Zopf. “Once these storage capacities are depleted, more and more visceral fat is deposited, and then more and more fat is stored in the organs and the muscles.”

Movement plays a particularly important role in intramuscular fat. “We know that the less physically active someone is, the higher the risk that fat will be stored in the muscles,” said Dr. Zopf.
 

Arising From Injuries

Unlike other fat tissues in the body, intramuscular fat can also accumulate in higher amounts when there are injuries to the muscles. The group led by Dr. Contreras and lead author Marcelo Flores-Opazo from the Universidad de O’Higgins in Rancagua, Chile, emphasized the role of fibroadipogenic progenitor (FAP) cells in their review. “FAPs play a crucial role in preserving and repairing muscle tissue injuries. They can differentiate into fibroblasts and adipocytes and are responsible for depositing fat and connective tissue in response to muscle injuries.”

Studies suggest that exercise can prevent FAPs from differentiating into fat and connective tissue cells. Metformin can achieve a similar effect in vitro. Dr. Contreras and colleagues hope that drug-based ways to reduce muscle fat will emerge in the future.

But how do you determine whether a patient has too much intramuscular fat? Although MRI and CT can be used for quantification, these are not routine examinations. There is currently no simple way to determine the fat content in muscles, according to the authors. The study authors hope that advances in molecular testing, imaging, and biopsies will improve diagnostic capabilities in the future.
 

Training Crucial

Until then, Dr. Contreras and colleagues advise close monitoring of one’s body weight and the maintenance of a healthy lifestyle. Excessive fat accumulation in the muscles can be prevented and reversed through adequate exercise and healthy nutrition, they emphasized. 

The important message is that these measures are possible. “With healthy nutrition and exercise, excess fat can be reduced. We have observed a reduction in muscle fat in obese individuals with just two sessions of 15-minute high-intensity workouts per week,” Dr. Zopf reported, citing her own research. The more obese a person is and the higher the inflammation in the body, the more likely additional medication may be needed.

Dr. Zopf also pointed out a peculiarity of intramuscular fat tissue. “Muscle fat can only be trained off.” A fatty liver or too much fat under the skin can be combated well with a diet, but muscles are different. “For that, you have to exercise to counteract the inflammatory cascade in the muscles.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Proposed clinical criteria for a memory loss disorder that is often misdiagnosed as Alzheimer’s disease (AD) have been published.

The new criteria for limbic-predominant amnestic neurodegenerative syndrome (LANS) provide a framework for neurologists and other experts to classify the condition and offer a more precise diagnosis and potential treatments.

“In our clinical work, we see patients whose memory symptoms appear to mimic Alzheimer’s disease, but when you look at their brain imaging or biomarkers, it’s clear they don’t have Alzheimer’s. Until now, there has not been a specific medical diagnosis to point to, but now we can offer them some answers,” senior investigator David T. Jones, MD, said in a release.

The proposed criteria and the research behind it were published online in Brain Communications and will be presented at the Alzheimer›s Association International Conference in Philadelphia.
 

Already in Use

Predominant limbic degeneration has been linked to various underlying etiologies, older age, predominant impairment of episodic memory, and slow clinical progression, the investigators noted. However, they added, the neurologic syndrome associated with predominant limbic degeneration is undefined.

Developing clinical criteria and validating them “is critical to distinguish such a syndrome from those originating from neocortical degeneration, which may differ in underlying etiology, disease course, and therapeutic needs,” the investigators wrote.

The newly proposed clinical criteria apply to LANS, which is “highly associated with limbic-predominant age-related TDP-43 encephalopathy but also other pathologic entities.”

The criteria incorporate core, standard, and advanced features including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of endocortical degeneration, and low likelihood of neocortical tau with highest, high, moderate, and low degrees of certainty.

“A detailed history of the clinical symptoms, which may be supported by neuropsychological testing, with the observation of disproportionate hippocampal atrophy and limbic degeneration on MRI/FDG yields a high confidence in a diagnosis of LANS, where the most likely symptom-driving proteinopathy is TDP-43 and not Alzheimer’s associated proteins,” the first author, Nick Corriveau-Lecavalier, PhD, assistant professor of neurology and psychology at Mayo Clinic, Rochester, Minnesota, told this news organization.

To validate the criteria, the investigators screened autopsied patients from Mayo Clinic and Alzheimer’s Disease Neuroimaging Initiative cohorts and applied the criteria to those with a predominant amnestic syndrome and those who had AD neuropathologic change, limbic-predominant age-related TDP-43 encephalopathy, or both pathologies at autopsy.

“The criteria effectively categorized these cases, with Alzheimer’s disease having the lowest likelihoods, limbic-predominant age-related TDP-43 encephalopathy patients having the highest likelihoods, and patients with both pathologies having intermediate likelihoods,” the investigators reported.

“Patients with high likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods,” they added.

Dr. Corriveau-Lecavalier said the team is currently analyzing longitudinal cognitive and imaging trajectories in LANS over several years. “This will help us better understand how LANS and Alzheimer’s differ in their sequence of symptoms over time.”

It is important to understand that memory symptoms in old age are not “unequivocally” driven by Alzheimer’s and that LANS progresses more slowly and has a better prognosis than AD, he noted.

In addition, in vivo markers of TDP-43 are “on the horizon and can hopefully make their way to human research settings soon. This will help better understand the underlying molecular etiologies causing LANS and associated symptoms,” he said.

Dr. Corriveau-Lecavalier said the LANS criteria are ready for clinical use by experts in neurologic care. These criteria can be used to inform not only diagnosis but also prognosis, where this syndrome is associated with slow and mild progression and a memory-dominant profile.

He added that “the new criteria are also routinely used in our practice to make decisions about anti-amyloid treatment eligibility.”

Commenting on the research for this news organization, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the research “exemplifies the great need to develop objective criteria for diagnosis and staging of Alzheimer’s and all other types of dementia and to create an integrated biological and clinical staging scheme that can be used effectively by physicians.”

“Advances in biomarkers will help to differentiate all types of dementia when incorporated into the diagnostic workup, but until those tools are available, a more succinct clinical criteria for diagnosis can be used to support a more personalized medicine approach to treatment, care, and enrollment into clinical studies,” said Dr. Edelmayer, who wasn’t involved in the research.

The research was funded in part by the National Institutes of Health and by the Robert Wood Johnson Foundation, the Elsie & Marvin Dekelboum Family Foundation, the Liston Family Foundation, the Edson Family, the Gerald A. and Henrietta Rauenhorst Foundation, and the Foundation Dr Corinne Schuler. Dr. Corriveau-Lecavalier and Dr. Edelmayer had no relevant conflicts of interest.

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

Proposed clinical criteria for a memory loss disorder that is often misdiagnosed as Alzheimer’s disease (AD) have been published.

The new criteria for limbic-predominant amnestic neurodegenerative syndrome (LANS) provide a framework for neurologists and other experts to classify the condition and offer a more precise diagnosis and potential treatments.

“In our clinical work, we see patients whose memory symptoms appear to mimic Alzheimer’s disease, but when you look at their brain imaging or biomarkers, it’s clear they don’t have Alzheimer’s. Until now, there has not been a specific medical diagnosis to point to, but now we can offer them some answers,” senior investigator David T. Jones, MD, said in a release.

The proposed criteria and the research behind it were published online in Brain Communications and will be presented at the Alzheimer›s Association International Conference in Philadelphia.
 

Already in Use

Predominant limbic degeneration has been linked to various underlying etiologies, older age, predominant impairment of episodic memory, and slow clinical progression, the investigators noted. However, they added, the neurologic syndrome associated with predominant limbic degeneration is undefined.

Developing clinical criteria and validating them “is critical to distinguish such a syndrome from those originating from neocortical degeneration, which may differ in underlying etiology, disease course, and therapeutic needs,” the investigators wrote.

The newly proposed clinical criteria apply to LANS, which is “highly associated with limbic-predominant age-related TDP-43 encephalopathy but also other pathologic entities.”

The criteria incorporate core, standard, and advanced features including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of endocortical degeneration, and low likelihood of neocortical tau with highest, high, moderate, and low degrees of certainty.

“A detailed history of the clinical symptoms, which may be supported by neuropsychological testing, with the observation of disproportionate hippocampal atrophy and limbic degeneration on MRI/FDG yields a high confidence in a diagnosis of LANS, where the most likely symptom-driving proteinopathy is TDP-43 and not Alzheimer’s associated proteins,” the first author, Nick Corriveau-Lecavalier, PhD, assistant professor of neurology and psychology at Mayo Clinic, Rochester, Minnesota, told this news organization.

To validate the criteria, the investigators screened autopsied patients from Mayo Clinic and Alzheimer’s Disease Neuroimaging Initiative cohorts and applied the criteria to those with a predominant amnestic syndrome and those who had AD neuropathologic change, limbic-predominant age-related TDP-43 encephalopathy, or both pathologies at autopsy.

“The criteria effectively categorized these cases, with Alzheimer’s disease having the lowest likelihoods, limbic-predominant age-related TDP-43 encephalopathy patients having the highest likelihoods, and patients with both pathologies having intermediate likelihoods,” the investigators reported.

“Patients with high likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods,” they added.

Dr. Corriveau-Lecavalier said the team is currently analyzing longitudinal cognitive and imaging trajectories in LANS over several years. “This will help us better understand how LANS and Alzheimer’s differ in their sequence of symptoms over time.”

It is important to understand that memory symptoms in old age are not “unequivocally” driven by Alzheimer’s and that LANS progresses more slowly and has a better prognosis than AD, he noted.

In addition, in vivo markers of TDP-43 are “on the horizon and can hopefully make their way to human research settings soon. This will help better understand the underlying molecular etiologies causing LANS and associated symptoms,” he said.

Dr. Corriveau-Lecavalier said the LANS criteria are ready for clinical use by experts in neurologic care. These criteria can be used to inform not only diagnosis but also prognosis, where this syndrome is associated with slow and mild progression and a memory-dominant profile.

He added that “the new criteria are also routinely used in our practice to make decisions about anti-amyloid treatment eligibility.”

Commenting on the research for this news organization, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the research “exemplifies the great need to develop objective criteria for diagnosis and staging of Alzheimer’s and all other types of dementia and to create an integrated biological and clinical staging scheme that can be used effectively by physicians.”

“Advances in biomarkers will help to differentiate all types of dementia when incorporated into the diagnostic workup, but until those tools are available, a more succinct clinical criteria for diagnosis can be used to support a more personalized medicine approach to treatment, care, and enrollment into clinical studies,” said Dr. Edelmayer, who wasn’t involved in the research.

The research was funded in part by the National Institutes of Health and by the Robert Wood Johnson Foundation, the Elsie & Marvin Dekelboum Family Foundation, the Liston Family Foundation, the Edson Family, the Gerald A. and Henrietta Rauenhorst Foundation, and the Foundation Dr Corinne Schuler. Dr. Corriveau-Lecavalier and Dr. Edelmayer had no relevant conflicts of interest.

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

Proposed clinical criteria for a memory loss disorder that is often misdiagnosed as Alzheimer’s disease (AD) have been published.

The new criteria for limbic-predominant amnestic neurodegenerative syndrome (LANS) provide a framework for neurologists and other experts to classify the condition and offer a more precise diagnosis and potential treatments.

“In our clinical work, we see patients whose memory symptoms appear to mimic Alzheimer’s disease, but when you look at their brain imaging or biomarkers, it’s clear they don’t have Alzheimer’s. Until now, there has not been a specific medical diagnosis to point to, but now we can offer them some answers,” senior investigator David T. Jones, MD, said in a release.

The proposed criteria and the research behind it were published online in Brain Communications and will be presented at the Alzheimer›s Association International Conference in Philadelphia.
 

Already in Use

Predominant limbic degeneration has been linked to various underlying etiologies, older age, predominant impairment of episodic memory, and slow clinical progression, the investigators noted. However, they added, the neurologic syndrome associated with predominant limbic degeneration is undefined.

Developing clinical criteria and validating them “is critical to distinguish such a syndrome from those originating from neocortical degeneration, which may differ in underlying etiology, disease course, and therapeutic needs,” the investigators wrote.

The newly proposed clinical criteria apply to LANS, which is “highly associated with limbic-predominant age-related TDP-43 encephalopathy but also other pathologic entities.”

The criteria incorporate core, standard, and advanced features including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of endocortical degeneration, and low likelihood of neocortical tau with highest, high, moderate, and low degrees of certainty.

“A detailed history of the clinical symptoms, which may be supported by neuropsychological testing, with the observation of disproportionate hippocampal atrophy and limbic degeneration on MRI/FDG yields a high confidence in a diagnosis of LANS, where the most likely symptom-driving proteinopathy is TDP-43 and not Alzheimer’s associated proteins,” the first author, Nick Corriveau-Lecavalier, PhD, assistant professor of neurology and psychology at Mayo Clinic, Rochester, Minnesota, told this news organization.

To validate the criteria, the investigators screened autopsied patients from Mayo Clinic and Alzheimer’s Disease Neuroimaging Initiative cohorts and applied the criteria to those with a predominant amnestic syndrome and those who had AD neuropathologic change, limbic-predominant age-related TDP-43 encephalopathy, or both pathologies at autopsy.

“The criteria effectively categorized these cases, with Alzheimer’s disease having the lowest likelihoods, limbic-predominant age-related TDP-43 encephalopathy patients having the highest likelihoods, and patients with both pathologies having intermediate likelihoods,” the investigators reported.

“Patients with high likelihoods had a milder and slower clinical course and more severe temporo-limbic degeneration compared to those with low likelihoods,” they added.

Dr. Corriveau-Lecavalier said the team is currently analyzing longitudinal cognitive and imaging trajectories in LANS over several years. “This will help us better understand how LANS and Alzheimer’s differ in their sequence of symptoms over time.”

It is important to understand that memory symptoms in old age are not “unequivocally” driven by Alzheimer’s and that LANS progresses more slowly and has a better prognosis than AD, he noted.

In addition, in vivo markers of TDP-43 are “on the horizon and can hopefully make their way to human research settings soon. This will help better understand the underlying molecular etiologies causing LANS and associated symptoms,” he said.

Dr. Corriveau-Lecavalier said the LANS criteria are ready for clinical use by experts in neurologic care. These criteria can be used to inform not only diagnosis but also prognosis, where this syndrome is associated with slow and mild progression and a memory-dominant profile.

He added that “the new criteria are also routinely used in our practice to make decisions about anti-amyloid treatment eligibility.”

Commenting on the research for this news organization, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the research “exemplifies the great need to develop objective criteria for diagnosis and staging of Alzheimer’s and all other types of dementia and to create an integrated biological and clinical staging scheme that can be used effectively by physicians.”

“Advances in biomarkers will help to differentiate all types of dementia when incorporated into the diagnostic workup, but until those tools are available, a more succinct clinical criteria for diagnosis can be used to support a more personalized medicine approach to treatment, care, and enrollment into clinical studies,” said Dr. Edelmayer, who wasn’t involved in the research.

The research was funded in part by the National Institutes of Health and by the Robert Wood Johnson Foundation, the Elsie & Marvin Dekelboum Family Foundation, the Liston Family Foundation, the Edson Family, the Gerald A. and Henrietta Rauenhorst Foundation, and the Foundation Dr Corinne Schuler. Dr. Corriveau-Lecavalier and Dr. Edelmayer had no relevant conflicts of interest.

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

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

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

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

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

Compared with traditional replacement valves, sutureless valves placed through minimally invasive cardiac surgery have less data supporting their use but offer unique features that might make them the preferred option for certain patients, reported specialists.

Two valves placed by minimally invasive surgery received regulatory approval 8 years ago, but they are not widely used to this day.

The sutureless device known as Perceval (Corcym) and a rapidly deployed device called Intuity (Edwards Lifesciences) are used as an alternative to surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). But despite being commercially available since 2016, the devices are still not being used much.

The devices are not discussed in substantial detail in either the joint guidelines from the American College of Cardiology and American Heart Association issued in 2020 or guidelines from the European Society of Cardiology issued in 2022.

Cristiano Spadaccio, MD, PhD, a cardiothoracic surgeon associated with Lancashire Cardiac Centre in Blackpool, England, and his colleagues reviewed the small number of studies evaluating the alternate approach to “make the cardiology world aware” of alternatives “that can relieve the surgical burden by minimizing the implantation time and length of the operation,” he said.

The comprehensive review is published in the Journal of the American College of Cardiology.
 

A Neglected Alternative

The sutureless Perceval device is held in place by a stent frame that self-expands. The Intuity device also relies primarily on its framework to anchor the valve in place but does involve three sutures. Both devices are still referred to as sutureless in the new review of them.

Only a small number of centers perform minimally invasive cardiac surgeries, and the main advantage of the devices — rapid deployment — has been eroded with the advent of automated knotting which has significantly reduced the time to implant and sutured valve.

The underuse of these devices is largely caused by the limited amount of comparative and prospective data, said Dr. Spadaccio. “The entire literature on sutureless aortic valve replacement with the exception of one randomized controlled trial is observational.”

That trial, PERSIST-AVR, found that the sutureless valves were just as good as conventional ones when it comes to major adverse cardiovascular events including all-cause death, myocardial infarction, stroke, or valve reintervention at 1 year.

In a subanalysis limited to patients who had isolated aortic valve replacement, the sutureless procedure was associated with lower adverse events (5.2% vs 10.8%) at the cost of a higher rate of pacemaker implantation (11% vs 1.6%).

There are also multiple retrospective studies and registries that have generated observational data comparing sutureless aortic valve replacement with SAVR and TAVR in various patient populations, said Dr. Spadaccio, and the review was based on more than a dozen studies published since 2015. Long-term follow-up data for sutureless aortic valve replacements, which now exceeds 10 years, suggest rates of structural valve deterioration and reintervention have been acceptably low.

The minimally invasive procedures have other advantages too. For example, relative to the greater trauma associated with open heart surgery, minimally invasive surgeries typically involve faster recovery, an advantage likely to appeal to many patients who are candidates for either.
 

Quicker Recovery

Collectively, these data suggest that sutureless aortic valve replacement might be a reasonable or even a more appropriate alternative to either SAVR or TAVR when considering specific patient characteristics and goals, according to the review, which included an algorithm identifying specifically where sutureless aortic valve replacement fits with SAVR and TAVR.

“The algorithm is based on different clinical scenarios and reflects current guidelines for SAVR,” said Dr. Spadaccio. For example, current guidelines identify SAVR as preferred in patients younger than 65 years and in older patients with a low Society of Thoracic Surgeons (STS) score, but there are many instances in which sutureless aortic valve replacement might be more attractive, such as in those also undergoing mitral valve repair, coronary artery bypass grafting, or another surgical procedure.

Dr. Spadaccio said that the STS score should not be considered in isolation when evaluating a patient for SAVR or TAVR. Other features such as mobility, frailty score, and comorbid liver or renal disease should also be considered when discussing the three options with patients. As a result, the algorithm emphasizes a detailed evaluation of patient characteristics in selecting one procedure over another.

“The treatment should be really tailored on the individual patient basis,” said Dr. Spadaccio.

Dr. Spadaccio acknowledged that there is a need for more comparative trials, particularly in regard to sutureless aortic valve replacement as an alternative to TAVR. “I really think that a 1:1 RCT on sutureless aortic valve replacement vs TAVR could give better answers to all of these interrogatives.”

But despite the limitations outlined in this review, Dr. Spadaccio and colleagues challenged the perception that current data are not sufficient to allow clinicians to consider sutureless aortic valve replacement in the mix of options.
 

A Viable Option

This comprehensive summary of what is known about sutureless aortic valve replacement compared with the other options addresses an important knowledge gap, said S. Chris Malaisrie, MD, a cardiac surgeon at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

He said he agrees this option has unique qualities. “Minimally invasive surgery has been largely ignored by guideline writers, but patients certainly demand options that are less invasive than standard open heart surgery. Sutureless and rapid deployment valves facilitate minimally invasive surgery and offer an advantageous option for younger patients.”

Dr. Malaisrie said the review is generating discussion about a potentially valuable option within the cardiology community. And that is exactly what Dr. Spadaccio was hoping for. “This paper was meant to educate as much as possible on these details to assist and inform decision-making,” he said.

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

Pyoderma faciale, also known as rosacea fulminans, is a rare and severe form of rosacea that primarily affects women between the ages of 15 and 46. It typically presents with a sudden onset of papules, pustules, cysts, painful inflammatory nodules, and erythema on the centrofacial areas. The etiology is unknown but has been speculated to be hormone-related as it is more common in women and can be triggered by acute changes such as stress or medications.

Because of overlapping symptoms with other conditions, an accurate clinical assessment is crucial. Typically, there are no comedones and about half of the patients have a history of acne. Some cases have shown a possible link between pyoderma faciale with inflammatory bowel disease, thyroid disease and liver disease, highlighting the importance of considering these associations in treatment decisions.

Treatment options for pyoderma faciale include isotretinoin, corticosteroids, dapsone, and antibiotics such as doxycycline. Isotretinoin is usually the first-line treatment, with dapsone reserved for cases where other methods have failed. Despite concerns about isotretinoin exacerbating inflammatory bowel disease (IBD), there has been at least one reported case where a patient with ulcerative colitis who had pyoderma faciale that was successfully treated with isotretinoin with no adverse effects.

Mallory Towe, MS, and Donna Bilu Martin, MD

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Angileri L et al. J Dermatolog Treat. 2021 Feb;32(1):110-3. doi: 10.1080/09546634.2019.1628175.

Coutinho JC et al. An Bras Dermatol. 2016 Sep-Oct;91(5 suppl 1):151-3. doi: 10.1590/abd1806-4841.20164943.

Rosen T and Unkefer RP. Cutis. 1999 Aug;64(2):107-9.

Pyoderma faciale, also known as rosacea fulminans, is a rare and severe form of rosacea that primarily affects women between the ages of 15 and 46. It typically presents with a sudden onset of papules, pustules, cysts, painful inflammatory nodules, and erythema on the centrofacial areas. The etiology is unknown but has been speculated to be hormone-related as it is more common in women and can be triggered by acute changes such as stress or medications.

Because of overlapping symptoms with other conditions, an accurate clinical assessment is crucial. Typically, there are no comedones and about half of the patients have a history of acne. Some cases have shown a possible link between pyoderma faciale with inflammatory bowel disease, thyroid disease and liver disease, highlighting the importance of considering these associations in treatment decisions.

Treatment options for pyoderma faciale include isotretinoin, corticosteroids, dapsone, and antibiotics such as doxycycline. Isotretinoin is usually the first-line treatment, with dapsone reserved for cases where other methods have failed. Despite concerns about isotretinoin exacerbating inflammatory bowel disease (IBD), there has been at least one reported case where a patient with ulcerative colitis who had pyoderma faciale that was successfully treated with isotretinoin with no adverse effects.

Mallory Towe, MS, and Donna Bilu Martin, MD

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Angileri L et al. J Dermatolog Treat. 2021 Feb;32(1):110-3. doi: 10.1080/09546634.2019.1628175.

Coutinho JC et al. An Bras Dermatol. 2016 Sep-Oct;91(5 suppl 1):151-3. doi: 10.1590/abd1806-4841.20164943.

Rosen T and Unkefer RP. Cutis. 1999 Aug;64(2):107-9.

Pyoderma faciale, also known as rosacea fulminans, is a rare and severe form of rosacea that primarily affects women between the ages of 15 and 46. It typically presents with a sudden onset of papules, pustules, cysts, painful inflammatory nodules, and erythema on the centrofacial areas. The etiology is unknown but has been speculated to be hormone-related as it is more common in women and can be triggered by acute changes such as stress or medications.

Because of overlapping symptoms with other conditions, an accurate clinical assessment is crucial. Typically, there are no comedones and about half of the patients have a history of acne. Some cases have shown a possible link between pyoderma faciale with inflammatory bowel disease, thyroid disease and liver disease, highlighting the importance of considering these associations in treatment decisions.

Treatment options for pyoderma faciale include isotretinoin, corticosteroids, dapsone, and antibiotics such as doxycycline. Isotretinoin is usually the first-line treatment, with dapsone reserved for cases where other methods have failed. Despite concerns about isotretinoin exacerbating inflammatory bowel disease (IBD), there has been at least one reported case where a patient with ulcerative colitis who had pyoderma faciale that was successfully treated with isotretinoin with no adverse effects.

Mallory Towe, MS, and Donna Bilu Martin, MD

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Angileri L et al. J Dermatolog Treat. 2021 Feb;32(1):110-3. doi: 10.1080/09546634.2019.1628175.

Coutinho JC et al. An Bras Dermatol. 2016 Sep-Oct;91(5 suppl 1):151-3. doi: 10.1590/abd1806-4841.20164943.

Rosen T and Unkefer RP. Cutis. 1999 Aug;64(2):107-9.

High blood pressure is an established risk factor for neurodegeneration and cognitive decline. Long-standing evidence shows that treating hypertension can reduce its vascular consequences, but whether that is true for neurodegeneration is less clear.

Valentin Fuster, MD, president of Mount Sinai Fuster Heart Hospital in New York City, told this news organization. “There is no question in the literature that untreated high blood pressure may lead to dementia,” he said. “The open question is whether treating blood pressure is sufficient to decrease or stop the progress of dementia.”

Studies are mixed, but recent research suggests that addressing hypertension does affect the risk for dementia. A secondary analysis of the China Rural Hypertension Control Project reported at the American Heart Association (AHA) Scientific Sessions in 2023 but not yet published showed that the 4-year blood pressure–lowering program in adults aged 40 or older significantly reduced the risk for all-cause dementia and cognitive impairment.

Similarly, a post hoc analysis of the SPRINT MIND trial found that participants aged 50 or older who underwent intensive (< 120 mm Hg) vs standard (< 140 mm Hg) blood pressure lowering had a lower rate of probable dementia or mild cognitive impairment.

Other studies pointing to a benefit included a pooled individual participant analysis of five randomized controlled trials, which found class I evidence to support antihypertensive treatment to reduce the risk for incident dementia, and an earlier systematic review and meta-analysis of the association of blood pressure lowering with newly diagnosed dementia or cognitive impairment.
 

How It Might Work

Some possible mechanisms underlying the connection have emerged.

“Vascular disease caused by hypertension is clearly implicated in one form of dementia, called vascular cognitive impairment and dementia,” Andrew Moran, MD, PhD, associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons in New York City, told this news organization. “This category includes dementia following a stroke caused by uncontrolled hypertension.” 

“At the same time, we now know that hypertension and other vascular risk factors can also contribute, along with other factors, to developing Alzheimer dementia,” he said. “Even without causing clinically evident stroke, vascular disease from hypertension can lead to subtle damage to the brain via ischemia, microhemorrhage, and atrophy.”

“It is well known that hypertension affects the vasculature, and the vasculature of the brain is not spared,” agreed Eileen Handberg, PhD, ARNP, a member of the Hypertension Workgroup at the American College of Cardiology (ACC) and a professor of medicine and director of the Cardiovascular Clinical Trials Program in the University of Florida, Gainesville, Florida. “Combine this with other mechanisms like inflammation and endothelial dysfunction, and add amyloid accumulation, and there is a deterioration in vascular beds leading to decreased cerebral blood flow,” she said.

Treating hypertension likely helps lower dementia risk through “a combination of reduced risk of stroke and also benefits on blood flow, blood vessel health, and reduction in neurodegeneration,” suggested Mitchell S.V. Elkind, MD, chief clinical science officer and past president of the AHA and a professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City. “Midlife blood pressure elevations are associated with deposition of amyloid in the brain, so controlling blood pressure may reduce amyloid deposits and neurodegeneration.”
 

Time in Range or Treat to Target?

With respect to dementia risk, does treating hypertension to a specific target make a difference, or is it the time spent in a healthy blood pressure range? 

“Observational studies and a post hoc analysis of the SPRINT MIND trial suggest that more time spent in a healthy blood pressure range or more stable blood pressure are associated with lower dementia risk,” Dr. Moran said. Citing results of the CHRC program and SPRINT MIND trial, he suggested that while a dose-response effect (the lower the blood pressure, the lower the dementia risk) hasn’t been definitively demonstrated, it is likely the case.

In his practice, Dr. Moran follows ACC/AHA guidelines and prescribes antihypertensives to get blood pressure below 130/80 mm Hg in individuals with hypertension who have other high-risk factors (cardiovascular disease, diabetes, chronic kidney disease, or high risk for these conditions). “The treatment rule for people with hypertension without these other risk factors is less clear — lowering blood pressure below 140/90 mm Hg is a must; I will discuss with patients whether to go lower than that.”

“The relative contributions of time in range versus treating to a target for blood pressure require further study,” said Dr. Elkind. “It is likely that the cumulative effect of blood pressure over time has a big role to play — and it does seem clear that midlife blood pressure is even more important than blood pressure late in life.”

That said, he added, “In general and all things being equal, I would treat to a blood pressure of < 120/80 mmHg,” given the SPRINT trial findings of greater benefits when treating to this systolic blood pressure goal. “Of course, if patients have side effects such as lightheadedness or dizziness or other medical conditions that require a higher target, then one would need to adjust the treatment targets.”

According to Dr. Fuster, targets should not be the focus because they vary. For example, the ACC/AHA guidelines use < 130/80 mm Hg, whereas the European Society of Hypertension guidelines and those of the American Academy of Family Physicians specify < 140/90 mm Hg and include age-based criteria. Because there are no studies comparing the outcomes of one set of guidelines vs another, Dr. Fuster thinks the focus should be on starting treatment as early as possible to prevent hypertension leading to dementia.

He pointed to the ongoing PESA trial, which uses brain MRI and other tests to characterize longitudinal associations among cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in asymptomatic individuals aged 40-54. Most did not have hypertension at baseline.

A recently published analysis of a subcohort of 370 PESA participants found that those with persistent high cardiovascular risk and subclinical carotid atherosclerosis already had signs of brain metabolic decline, “suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life,” wrote the investigators.
 

Is It Ever Too Late?

If starting hypertension treatment in midlife can help reduce the risk for cognitive impairment later, can treating later in life also help? “It’s theoretically possible, but it has to be proven,” Dr. Fuster said. “There are no data on whether there’s less chance to prevent the development of dementia if you start treating hypertension at age 70, for example. And we have no idea whether hypertension treatment will prevent progression in those who already have dementia.”

“Treating high blood pressure in older adults could affect the course of further progressive cognitive decline by improving vascular health and preventing strokes, which likely exacerbate nonvascular dementia,” Dr. Elkind suggested. “Most people with dementia have a combination of vascular and nonvascular dementia, so treating reversible causes wherever possible makes a difference.”

Dr. Elkind treats older patients with this in mind, he said, “even though most of the evidence points to the fact that it is blood pressure in middle age, not older age, that seems to have the biggest impact on later-life cognitive decline and dementia.” Like Dr. Fuster, he said, “the best strategy is to identify and treat blood pressure in midlife, before damage to the brain has advanced.”

Dr. Moran noted, “The latest science on dementia causes suggests it is difficult to draw a border between vascular and nonvascular dementia. So, as a practical matter, healthcare providers should consider that hypertension treatment is one of the best ways to prevent any category of dementia. This dementia prevention is added to the well-known benefits of hypertension treatment to prevent heart attacks, strokes, and kidney disease: ‘Healthy heart, healthy brain.’ ”

“Our BP [blood pressure] control rates overall are still abysmal,” Dr. Handberg added. Currently around one in four US adults with hypertension have it under control. Studies have shown that blood pressure control rates of 70%-80% are achievable, she said. “We can’t let patient or provider inertia continue.”

Dr. Handberg, Dr. Elkind, Dr. Moran, and Dr. Fuster declared no relevant conflicts of interest.

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

High blood pressure is an established risk factor for neurodegeneration and cognitive decline. Long-standing evidence shows that treating hypertension can reduce its vascular consequences, but whether that is true for neurodegeneration is less clear.

Valentin Fuster, MD, president of Mount Sinai Fuster Heart Hospital in New York City, told this news organization. “There is no question in the literature that untreated high blood pressure may lead to dementia,” he said. “The open question is whether treating blood pressure is sufficient to decrease or stop the progress of dementia.”

Studies are mixed, but recent research suggests that addressing hypertension does affect the risk for dementia. A secondary analysis of the China Rural Hypertension Control Project reported at the American Heart Association (AHA) Scientific Sessions in 2023 but not yet published showed that the 4-year blood pressure–lowering program in adults aged 40 or older significantly reduced the risk for all-cause dementia and cognitive impairment.

Similarly, a post hoc analysis of the SPRINT MIND trial found that participants aged 50 or older who underwent intensive (< 120 mm Hg) vs standard (< 140 mm Hg) blood pressure lowering had a lower rate of probable dementia or mild cognitive impairment.

Other studies pointing to a benefit included a pooled individual participant analysis of five randomized controlled trials, which found class I evidence to support antihypertensive treatment to reduce the risk for incident dementia, and an earlier systematic review and meta-analysis of the association of blood pressure lowering with newly diagnosed dementia or cognitive impairment.
 

How It Might Work

Some possible mechanisms underlying the connection have emerged.

“Vascular disease caused by hypertension is clearly implicated in one form of dementia, called vascular cognitive impairment and dementia,” Andrew Moran, MD, PhD, associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons in New York City, told this news organization. “This category includes dementia following a stroke caused by uncontrolled hypertension.” 

“At the same time, we now know that hypertension and other vascular risk factors can also contribute, along with other factors, to developing Alzheimer dementia,” he said. “Even without causing clinically evident stroke, vascular disease from hypertension can lead to subtle damage to the brain via ischemia, microhemorrhage, and atrophy.”

“It is well known that hypertension affects the vasculature, and the vasculature of the brain is not spared,” agreed Eileen Handberg, PhD, ARNP, a member of the Hypertension Workgroup at the American College of Cardiology (ACC) and a professor of medicine and director of the Cardiovascular Clinical Trials Program in the University of Florida, Gainesville, Florida. “Combine this with other mechanisms like inflammation and endothelial dysfunction, and add amyloid accumulation, and there is a deterioration in vascular beds leading to decreased cerebral blood flow,” she said.

Treating hypertension likely helps lower dementia risk through “a combination of reduced risk of stroke and also benefits on blood flow, blood vessel health, and reduction in neurodegeneration,” suggested Mitchell S.V. Elkind, MD, chief clinical science officer and past president of the AHA and a professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City. “Midlife blood pressure elevations are associated with deposition of amyloid in the brain, so controlling blood pressure may reduce amyloid deposits and neurodegeneration.”
 

Time in Range or Treat to Target?

With respect to dementia risk, does treating hypertension to a specific target make a difference, or is it the time spent in a healthy blood pressure range? 

“Observational studies and a post hoc analysis of the SPRINT MIND trial suggest that more time spent in a healthy blood pressure range or more stable blood pressure are associated with lower dementia risk,” Dr. Moran said. Citing results of the CHRC program and SPRINT MIND trial, he suggested that while a dose-response effect (the lower the blood pressure, the lower the dementia risk) hasn’t been definitively demonstrated, it is likely the case.

In his practice, Dr. Moran follows ACC/AHA guidelines and prescribes antihypertensives to get blood pressure below 130/80 mm Hg in individuals with hypertension who have other high-risk factors (cardiovascular disease, diabetes, chronic kidney disease, or high risk for these conditions). “The treatment rule for people with hypertension without these other risk factors is less clear — lowering blood pressure below 140/90 mm Hg is a must; I will discuss with patients whether to go lower than that.”

“The relative contributions of time in range versus treating to a target for blood pressure require further study,” said Dr. Elkind. “It is likely that the cumulative effect of blood pressure over time has a big role to play — and it does seem clear that midlife blood pressure is even more important than blood pressure late in life.”

That said, he added, “In general and all things being equal, I would treat to a blood pressure of < 120/80 mmHg,” given the SPRINT trial findings of greater benefits when treating to this systolic blood pressure goal. “Of course, if patients have side effects such as lightheadedness or dizziness or other medical conditions that require a higher target, then one would need to adjust the treatment targets.”

According to Dr. Fuster, targets should not be the focus because they vary. For example, the ACC/AHA guidelines use < 130/80 mm Hg, whereas the European Society of Hypertension guidelines and those of the American Academy of Family Physicians specify < 140/90 mm Hg and include age-based criteria. Because there are no studies comparing the outcomes of one set of guidelines vs another, Dr. Fuster thinks the focus should be on starting treatment as early as possible to prevent hypertension leading to dementia.

He pointed to the ongoing PESA trial, which uses brain MRI and other tests to characterize longitudinal associations among cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in asymptomatic individuals aged 40-54. Most did not have hypertension at baseline.

A recently published analysis of a subcohort of 370 PESA participants found that those with persistent high cardiovascular risk and subclinical carotid atherosclerosis already had signs of brain metabolic decline, “suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life,” wrote the investigators.
 

Is It Ever Too Late?

If starting hypertension treatment in midlife can help reduce the risk for cognitive impairment later, can treating later in life also help? “It’s theoretically possible, but it has to be proven,” Dr. Fuster said. “There are no data on whether there’s less chance to prevent the development of dementia if you start treating hypertension at age 70, for example. And we have no idea whether hypertension treatment will prevent progression in those who already have dementia.”

“Treating high blood pressure in older adults could affect the course of further progressive cognitive decline by improving vascular health and preventing strokes, which likely exacerbate nonvascular dementia,” Dr. Elkind suggested. “Most people with dementia have a combination of vascular and nonvascular dementia, so treating reversible causes wherever possible makes a difference.”

Dr. Elkind treats older patients with this in mind, he said, “even though most of the evidence points to the fact that it is blood pressure in middle age, not older age, that seems to have the biggest impact on later-life cognitive decline and dementia.” Like Dr. Fuster, he said, “the best strategy is to identify and treat blood pressure in midlife, before damage to the brain has advanced.”

Dr. Moran noted, “The latest science on dementia causes suggests it is difficult to draw a border between vascular and nonvascular dementia. So, as a practical matter, healthcare providers should consider that hypertension treatment is one of the best ways to prevent any category of dementia. This dementia prevention is added to the well-known benefits of hypertension treatment to prevent heart attacks, strokes, and kidney disease: ‘Healthy heart, healthy brain.’ ”

“Our BP [blood pressure] control rates overall are still abysmal,” Dr. Handberg added. Currently around one in four US adults with hypertension have it under control. Studies have shown that blood pressure control rates of 70%-80% are achievable, she said. “We can’t let patient or provider inertia continue.”

Dr. Handberg, Dr. Elkind, Dr. Moran, and Dr. Fuster declared no relevant conflicts of interest.

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

High blood pressure is an established risk factor for neurodegeneration and cognitive decline. Long-standing evidence shows that treating hypertension can reduce its vascular consequences, but whether that is true for neurodegeneration is less clear.

Valentin Fuster, MD, president of Mount Sinai Fuster Heart Hospital in New York City, told this news organization. “There is no question in the literature that untreated high blood pressure may lead to dementia,” he said. “The open question is whether treating blood pressure is sufficient to decrease or stop the progress of dementia.”

Studies are mixed, but recent research suggests that addressing hypertension does affect the risk for dementia. A secondary analysis of the China Rural Hypertension Control Project reported at the American Heart Association (AHA) Scientific Sessions in 2023 but not yet published showed that the 4-year blood pressure–lowering program in adults aged 40 or older significantly reduced the risk for all-cause dementia and cognitive impairment.

Similarly, a post hoc analysis of the SPRINT MIND trial found that participants aged 50 or older who underwent intensive (< 120 mm Hg) vs standard (< 140 mm Hg) blood pressure lowering had a lower rate of probable dementia or mild cognitive impairment.

Other studies pointing to a benefit included a pooled individual participant analysis of five randomized controlled trials, which found class I evidence to support antihypertensive treatment to reduce the risk for incident dementia, and an earlier systematic review and meta-analysis of the association of blood pressure lowering with newly diagnosed dementia or cognitive impairment.
 

How It Might Work

Some possible mechanisms underlying the connection have emerged.

“Vascular disease caused by hypertension is clearly implicated in one form of dementia, called vascular cognitive impairment and dementia,” Andrew Moran, MD, PhD, associate professor of medicine at Columbia University Vagelos College of Physicians and Surgeons in New York City, told this news organization. “This category includes dementia following a stroke caused by uncontrolled hypertension.” 

“At the same time, we now know that hypertension and other vascular risk factors can also contribute, along with other factors, to developing Alzheimer dementia,” he said. “Even without causing clinically evident stroke, vascular disease from hypertension can lead to subtle damage to the brain via ischemia, microhemorrhage, and atrophy.”

“It is well known that hypertension affects the vasculature, and the vasculature of the brain is not spared,” agreed Eileen Handberg, PhD, ARNP, a member of the Hypertension Workgroup at the American College of Cardiology (ACC) and a professor of medicine and director of the Cardiovascular Clinical Trials Program in the University of Florida, Gainesville, Florida. “Combine this with other mechanisms like inflammation and endothelial dysfunction, and add amyloid accumulation, and there is a deterioration in vascular beds leading to decreased cerebral blood flow,” she said.

Treating hypertension likely helps lower dementia risk through “a combination of reduced risk of stroke and also benefits on blood flow, blood vessel health, and reduction in neurodegeneration,” suggested Mitchell S.V. Elkind, MD, chief clinical science officer and past president of the AHA and a professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City. “Midlife blood pressure elevations are associated with deposition of amyloid in the brain, so controlling blood pressure may reduce amyloid deposits and neurodegeneration.”
 

Time in Range or Treat to Target?

With respect to dementia risk, does treating hypertension to a specific target make a difference, or is it the time spent in a healthy blood pressure range? 

“Observational studies and a post hoc analysis of the SPRINT MIND trial suggest that more time spent in a healthy blood pressure range or more stable blood pressure are associated with lower dementia risk,” Dr. Moran said. Citing results of the CHRC program and SPRINT MIND trial, he suggested that while a dose-response effect (the lower the blood pressure, the lower the dementia risk) hasn’t been definitively demonstrated, it is likely the case.

In his practice, Dr. Moran follows ACC/AHA guidelines and prescribes antihypertensives to get blood pressure below 130/80 mm Hg in individuals with hypertension who have other high-risk factors (cardiovascular disease, diabetes, chronic kidney disease, or high risk for these conditions). “The treatment rule for people with hypertension without these other risk factors is less clear — lowering blood pressure below 140/90 mm Hg is a must; I will discuss with patients whether to go lower than that.”

“The relative contributions of time in range versus treating to a target for blood pressure require further study,” said Dr. Elkind. “It is likely that the cumulative effect of blood pressure over time has a big role to play — and it does seem clear that midlife blood pressure is even more important than blood pressure late in life.”

That said, he added, “In general and all things being equal, I would treat to a blood pressure of < 120/80 mmHg,” given the SPRINT trial findings of greater benefits when treating to this systolic blood pressure goal. “Of course, if patients have side effects such as lightheadedness or dizziness or other medical conditions that require a higher target, then one would need to adjust the treatment targets.”

According to Dr. Fuster, targets should not be the focus because they vary. For example, the ACC/AHA guidelines use < 130/80 mm Hg, whereas the European Society of Hypertension guidelines and those of the American Academy of Family Physicians specify < 140/90 mm Hg and include age-based criteria. Because there are no studies comparing the outcomes of one set of guidelines vs another, Dr. Fuster thinks the focus should be on starting treatment as early as possible to prevent hypertension leading to dementia.

He pointed to the ongoing PESA trial, which uses brain MRI and other tests to characterize longitudinal associations among cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in asymptomatic individuals aged 40-54. Most did not have hypertension at baseline.

A recently published analysis of a subcohort of 370 PESA participants found that those with persistent high cardiovascular risk and subclinical carotid atherosclerosis already had signs of brain metabolic decline, “suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life,” wrote the investigators.
 

Is It Ever Too Late?

If starting hypertension treatment in midlife can help reduce the risk for cognitive impairment later, can treating later in life also help? “It’s theoretically possible, but it has to be proven,” Dr. Fuster said. “There are no data on whether there’s less chance to prevent the development of dementia if you start treating hypertension at age 70, for example. And we have no idea whether hypertension treatment will prevent progression in those who already have dementia.”

“Treating high blood pressure in older adults could affect the course of further progressive cognitive decline by improving vascular health and preventing strokes, which likely exacerbate nonvascular dementia,” Dr. Elkind suggested. “Most people with dementia have a combination of vascular and nonvascular dementia, so treating reversible causes wherever possible makes a difference.”

Dr. Elkind treats older patients with this in mind, he said, “even though most of the evidence points to the fact that it is blood pressure in middle age, not older age, that seems to have the biggest impact on later-life cognitive decline and dementia.” Like Dr. Fuster, he said, “the best strategy is to identify and treat blood pressure in midlife, before damage to the brain has advanced.”

Dr. Moran noted, “The latest science on dementia causes suggests it is difficult to draw a border between vascular and nonvascular dementia. So, as a practical matter, healthcare providers should consider that hypertension treatment is one of the best ways to prevent any category of dementia. This dementia prevention is added to the well-known benefits of hypertension treatment to prevent heart attacks, strokes, and kidney disease: ‘Healthy heart, healthy brain.’ ”

“Our BP [blood pressure] control rates overall are still abysmal,” Dr. Handberg added. Currently around one in four US adults with hypertension have it under control. Studies have shown that blood pressure control rates of 70%-80% are achievable, she said. “We can’t let patient or provider inertia continue.”

Dr. Handberg, Dr. Elkind, Dr. Moran, and Dr. Fuster declared no relevant conflicts of interest.

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

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

TORONTO — Dermatologists should prescribe emergency contraception (EC) to adolescent patients being treated with isotretinoin for acne.

That was one of the main messages from Andrea L. Zaenglein, MD, professor of dermatology and pediatrics, Penn State University, Hershey, who discussed hormonal therapies for pediatric acne at the annual meeting of the Society for Pediatric Dermatology.

Many doctors are reluctant to prescribe EC, which refers to contraceptive methods used to prevent unintended pregnancy after unprotected sexual intercourse or contraceptive failure, whether that’s from discomfort with EC or lack of training, Dr. Zaenglein said in an interview.

Isotretinoin, a retinoid marketed as Accutane and other brand names, is an effective treatment for acne but carries serious teratogenicity risks; the iPLEDGE Risk Evaluation and Mitigation Strategy is designed to manage this risk and minimize fetal exposure. Yet from 2011 to 2017, 210-310 pregnancies per year were reported to the Food and Drug Administration, according to a 2019 study.

There is a knowledge gap regarding EC among dermatologists who prescribe isotretinoin, which “is perpetuated by the iPLEDGE program because it is inadequate in guiding clinicians or educating patients about the use of EC,” Dr. Zaenglein and colleagues wrote in a recently published viewpoint on EC prescribing in patients on isotretinoin.

Types of EC include oral levonorgestrel (plan B), available over the counter; oral ulipristal acetate (ella), which requires a prescription; and the copper/hormonal intrauterine device.

Not all teens taking isotretinoin can be trusted to be sexually abstinent. Dr. Zaenglein cited research showing 39% of female high school students have had sexual relations. “In my opinion, these patients should have emergency contraception prescribed to them as a backup,” she said.

Dr. Zaenglein believes there’s a fair amount of “misunderstanding” about EC, with many people thinking it’s an abortion pill. “It’s a totally different medicine. This is contraception; if you’re pregnant, it’s not going to affect your fetus.”

Outgoing SPD President Sheilagh Maguiness, MD, professor of dermatology and pediatrics, University of Minnesota, Minneapolis, agreed that Dr. Zaenglein raised an important issue. “She has identified a practice gap and a knowledge gap that we need to address,” she said in an interview.

When discussing contraception with female patients taking isotretinoin, assume they’re sexually active or could be, Dr. Zaenglein told meeting attendees. Be explicit about the risks to the fetus and consider their past compliance.
 

Complex Disorder

During her presentation, Dr. Zaenglein described acne as a “very complex, multifactorial inflammatory disorder” of the skin. It involves four steps: Increased sebum production, hyperkeratinization, Cutibacterium acnes, and inflammation. External factors such as diet, genes, and the environment play a role.

“But at the heart of all of it is androgens; if you didn’t have androgens, you wouldn’t have acne.” That’s why some acne treatments block androgen receptors.

Clinicians are increasingly using one such therapy, spironolactone, to treat acne in female adolescents. Dr. Zaenglein referred to a Mayo Clinic study of 80 patients (mean age, 19 years), who had moderate to severe acne treated with a mean dose of 100 mg/day, that found 80% had improvement with a favorable side effect profile. This included nearly 23% who had a complete response (90% or more) and 36% who had a partial response (more than 50%); 20% had no response.

However, response rates are higher in adults, said Dr. Zaenglein, noting that spironolactone works “much better” in adult women.

Side effects of spironolactone can include menstrual disturbances, breast enlargement and tenderness, and premenstrual syndrome–like symptoms.

Dermatologists should also consider combined oral contraceptives (COCs) in their adolescent patients with acne. These have an estrogen component as well as a progestin component.

They have proven effectiveness for acne in adolescents, yet a US survey of 170 dermatology residents found only 60% felt comfortable prescribing them to healthy adolescents. The survey also found only 62% of respondents felt adequately trained on the efficacy of COCs, and 42% felt adequately trained on their safety.

Contraindications for COCs include thrombosis, migraine with aura, lupus, seizures, and hypertension. Complex valvular heart disease and liver tumors also need to be ruled out, said Dr. Zaenglein. One of the “newer concerns” with COCs is depression. “There’s biological plausibility because, obviously, hormones impact the brain.”
 

Preventing Drug Interactions

Before prescribing hormonal therapy, clinicians should carry out an acne assessment, aimed in part at preventing drug interactions. “The one we mostly have to watch out for is rifampin,” an antibiotic that could interact with COCs, said Dr. Zaenglein.

The herbal supplement St John’s Wort can reduce the efficacy of COCs. “You also want to make sure that they’re not on any medicines that will increase potassium, such as ACE inhibitors,” said Dr. Zaenglein. But tetracyclines, ampicillin, or metronidazole are usually “all okay” when combined with COCs.

It’s important to get baseline blood pressure levels and to check these along with weight on a regular basis, she added.

Always Consider PCOS

Before starting hormonal therapy, she advises dermatologists to “always consider” polycystic ovary syndrome (PCOS), a condition that’s “probably much underdiagnosed.” Acne is common in adolescents with PCOS. She suggests using a PCOS checklist, a reminder to ask about irregular periods, hirsutism, signs of insulin resistance such as increased body mass index, a history of premature adrenarche, and a family history of PCOS, said Dr. Zaenglein, noting that a person with a sibling who has PCOS has about a 40% chance of developing the condition.

“We play an important role in getting kids diagnosed at an early age so that we can make interventions because the impact of the metabolic syndrome can have lifelong effects on their cardiovascular system, as well as infertility.”

Dr. Zaenglein is a member of the American Academy of Dermatology (AAD) Acne Guidelines work group, the immediate past president of the American Acne and Rosacea Society, a member of the AAD iPLEDGE work group, co–editor in chief of Pediatric Dermatology, an advisory board member of Ortho Dermatologics, and a consultant for Church & Dwight. Dr. Maguiness had no relevant conflicts of interest.

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

Within the next few years, patients will go to their primary care facility for a medical problem. They’ll be greeted by a nonhuman who speaks in the language of their choice. Based upon the initial interview, which will be taken in note form, the patient will be diagnosed, and a prescription called into the pharmacy. They’ll pay the robot at a reception kiosk, and their meds will be delivered via driverless car.

Or so suggests Allan Stewart, MD, medical director and chief of cardiothoracic surgery at HCA Florida Mercy Hospital in Miami.

The writing is on the wall. Artificial intelligence (AI) is only going to play a more significant role in healthcare, and the entire patient experience will be much different in the next 5 years, he said.

If that sounds far too futuristic, buckle up. AI is already here and being used by most medical specialties. However, it’s primary care that stands to gain the most from this technology — right now — thanks to its ability to radically streamline patient care.
 

Seeing the Doctor and His or Her AI Assistant

AI is making doctors’ work lives easier, whether the technology helps with risk prevention and intervention or closing care gaps. It can also triage patient complaints, monitor patients remotely, or even perform digital health coaching to keep patients on track with their lifestyle regimens or monitor their health conditions.

Each of these AI components enables primary care physicians to reduce some of the paperwork requirements of their jobs and do what they were trained to do — listen and assess patients. Doctors currently spend 12 hours on average each week submitting prior authorization requests, according to an American Medical Association survey.

“Primary care can be overwhelming, especially today, with the advent of electronic records and data,” said Davin Lundquist, MD, a family medicine physician and chief medical officer at Augmedix, an automated medical documentation company that provides tools to reduce clinician burnout. “The amount of data we have to go through to try to get a complete and clear picture of our patients can be overwhelming on top of the referrals, administrative burdens, and regulatory requirements, which seem to be focused on the primary care space,” Dr. Lundquist said.

With an AI assist, primary care physicians can reduce their prep and pre-charting time, lessen the time needed for paperwork outside of clinic hours, and streamline information, including access to lab results, radiology reports, and consults.

“AI is already helping doctors manage their practices, make differential diagnoses, and input progress notes or histories,” said Dr. Stewart.

In Seattle, Ford Parsons, MD, chief of operational analytics at Providence Hospitals in Seattle, has been leading a generative AI project that recently developed a tool called Provaria to prioritize incoming messages from patients. The tool ensures that those with more urgent needs get immediate attention, and it supports the personnel who lead the responses.

The process begins with Provaria reviewing patient messages to ensure those with more urgent needs, such as a mental health crisis, get immediate attention instead of answering messages in the order they were received.

Provaria also provides resources to help responding staff craft a reply. If a patient’s message cites back pain, for example, the system might suggest a referral to a physical therapist, include a link to that department, and prompt the staff to ask about red flags that indicate a more urgent situation.

After an initial rollout, Providence recently deployed Provaria to manage the messages for all 4000 of its primary care, family medicine, and internal medicine providers. The system has reviewed and categorized more than 500,000 messages so far.

“This is another example where AI can increase the human connection in healthcare,” Dr. Parsons said. “That’s the opposite of what others are saying, but by using AI, you can automate the stuff that isn’t critical that doctors have wound up doing.”
 

AI Helps Foster Better Person-to-Person Communication

In recent years, the first thing most doctors do when they enter the exam room with a patient is log into the in-room computer and start to take notes — which can be off-putting to patients.

Now devices can ease this process, such as PLAUD, an AI voice recognition device that attaches to a cell phone. Just the size of a credit card, the device enables conversations to be easily recorded. It not only streamlines note-taking but also enables a physician to listen intently to a patient’s concerns instead of furiously jotting down notes.

“That device is already helping transcribe conversations into notes and then into a patient’s electronic medical record,” Dr. Stewart said. “This helps save doctors the work of having to input patient information.”
 

AI Can’t Be a Compassionate Human

The one thing AI can’t do is show compassion, at least not yet. The someday “vision” when a robot will gather intel about a patient’s symptoms and even offer a diagnosis does have some downsides. There is no replacement for human interaction, especially in the case of dire health news.

“If you have signs of a metastatic cancer and a nonhuman is delivering this news, there’s no way AI can share this news with compassion,” said Dr. Stewart.

For now, AI is becoming instrumental in helping reduce the number of extra demands on primary care doctors, as well as physicians in other specialties, so that they can continue focusing on what matters — healing patients.
 

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

Within the next few years, patients will go to their primary care facility for a medical problem. They’ll be greeted by a nonhuman who speaks in the language of their choice. Based upon the initial interview, which will be taken in note form, the patient will be diagnosed, and a prescription called into the pharmacy. They’ll pay the robot at a reception kiosk, and their meds will be delivered via driverless car.

Or so suggests Allan Stewart, MD, medical director and chief of cardiothoracic surgery at HCA Florida Mercy Hospital in Miami.

The writing is on the wall. Artificial intelligence (AI) is only going to play a more significant role in healthcare, and the entire patient experience will be much different in the next 5 years, he said.

If that sounds far too futuristic, buckle up. AI is already here and being used by most medical specialties. However, it’s primary care that stands to gain the most from this technology — right now — thanks to its ability to radically streamline patient care.
 

Seeing the Doctor and His or Her AI Assistant

AI is making doctors’ work lives easier, whether the technology helps with risk prevention and intervention or closing care gaps. It can also triage patient complaints, monitor patients remotely, or even perform digital health coaching to keep patients on track with their lifestyle regimens or monitor their health conditions.

Each of these AI components enables primary care physicians to reduce some of the paperwork requirements of their jobs and do what they were trained to do — listen and assess patients. Doctors currently spend 12 hours on average each week submitting prior authorization requests, according to an American Medical Association survey.

“Primary care can be overwhelming, especially today, with the advent of electronic records and data,” said Davin Lundquist, MD, a family medicine physician and chief medical officer at Augmedix, an automated medical documentation company that provides tools to reduce clinician burnout. “The amount of data we have to go through to try to get a complete and clear picture of our patients can be overwhelming on top of the referrals, administrative burdens, and regulatory requirements, which seem to be focused on the primary care space,” Dr. Lundquist said.

With an AI assist, primary care physicians can reduce their prep and pre-charting time, lessen the time needed for paperwork outside of clinic hours, and streamline information, including access to lab results, radiology reports, and consults.

“AI is already helping doctors manage their practices, make differential diagnoses, and input progress notes or histories,” said Dr. Stewart.

In Seattle, Ford Parsons, MD, chief of operational analytics at Providence Hospitals in Seattle, has been leading a generative AI project that recently developed a tool called Provaria to prioritize incoming messages from patients. The tool ensures that those with more urgent needs get immediate attention, and it supports the personnel who lead the responses.

The process begins with Provaria reviewing patient messages to ensure those with more urgent needs, such as a mental health crisis, get immediate attention instead of answering messages in the order they were received.

Provaria also provides resources to help responding staff craft a reply. If a patient’s message cites back pain, for example, the system might suggest a referral to a physical therapist, include a link to that department, and prompt the staff to ask about red flags that indicate a more urgent situation.

After an initial rollout, Providence recently deployed Provaria to manage the messages for all 4000 of its primary care, family medicine, and internal medicine providers. The system has reviewed and categorized more than 500,000 messages so far.

“This is another example where AI can increase the human connection in healthcare,” Dr. Parsons said. “That’s the opposite of what others are saying, but by using AI, you can automate the stuff that isn’t critical that doctors have wound up doing.”
 

AI Helps Foster Better Person-to-Person Communication

In recent years, the first thing most doctors do when they enter the exam room with a patient is log into the in-room computer and start to take notes — which can be off-putting to patients.

Now devices can ease this process, such as PLAUD, an AI voice recognition device that attaches to a cell phone. Just the size of a credit card, the device enables conversations to be easily recorded. It not only streamlines note-taking but also enables a physician to listen intently to a patient’s concerns instead of furiously jotting down notes.

“That device is already helping transcribe conversations into notes and then into a patient’s electronic medical record,” Dr. Stewart said. “This helps save doctors the work of having to input patient information.”
 

AI Can’t Be a Compassionate Human

The one thing AI can’t do is show compassion, at least not yet. The someday “vision” when a robot will gather intel about a patient’s symptoms and even offer a diagnosis does have some downsides. There is no replacement for human interaction, especially in the case of dire health news.

“If you have signs of a metastatic cancer and a nonhuman is delivering this news, there’s no way AI can share this news with compassion,” said Dr. Stewart.

For now, AI is becoming instrumental in helping reduce the number of extra demands on primary care doctors, as well as physicians in other specialties, so that they can continue focusing on what matters — healing patients.
 

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

Within the next few years, patients will go to their primary care facility for a medical problem. They’ll be greeted by a nonhuman who speaks in the language of their choice. Based upon the initial interview, which will be taken in note form, the patient will be diagnosed, and a prescription called into the pharmacy. They’ll pay the robot at a reception kiosk, and their meds will be delivered via driverless car.

Or so suggests Allan Stewart, MD, medical director and chief of cardiothoracic surgery at HCA Florida Mercy Hospital in Miami.

The writing is on the wall. Artificial intelligence (AI) is only going to play a more significant role in healthcare, and the entire patient experience will be much different in the next 5 years, he said.

If that sounds far too futuristic, buckle up. AI is already here and being used by most medical specialties. However, it’s primary care that stands to gain the most from this technology — right now — thanks to its ability to radically streamline patient care.
 

Seeing the Doctor and His or Her AI Assistant

AI is making doctors’ work lives easier, whether the technology helps with risk prevention and intervention or closing care gaps. It can also triage patient complaints, monitor patients remotely, or even perform digital health coaching to keep patients on track with their lifestyle regimens or monitor their health conditions.

Each of these AI components enables primary care physicians to reduce some of the paperwork requirements of their jobs and do what they were trained to do — listen and assess patients. Doctors currently spend 12 hours on average each week submitting prior authorization requests, according to an American Medical Association survey.

“Primary care can be overwhelming, especially today, with the advent of electronic records and data,” said Davin Lundquist, MD, a family medicine physician and chief medical officer at Augmedix, an automated medical documentation company that provides tools to reduce clinician burnout. “The amount of data we have to go through to try to get a complete and clear picture of our patients can be overwhelming on top of the referrals, administrative burdens, and regulatory requirements, which seem to be focused on the primary care space,” Dr. Lundquist said.

With an AI assist, primary care physicians can reduce their prep and pre-charting time, lessen the time needed for paperwork outside of clinic hours, and streamline information, including access to lab results, radiology reports, and consults.

“AI is already helping doctors manage their practices, make differential diagnoses, and input progress notes or histories,” said Dr. Stewart.

In Seattle, Ford Parsons, MD, chief of operational analytics at Providence Hospitals in Seattle, has been leading a generative AI project that recently developed a tool called Provaria to prioritize incoming messages from patients. The tool ensures that those with more urgent needs get immediate attention, and it supports the personnel who lead the responses.

The process begins with Provaria reviewing patient messages to ensure those with more urgent needs, such as a mental health crisis, get immediate attention instead of answering messages in the order they were received.

Provaria also provides resources to help responding staff craft a reply. If a patient’s message cites back pain, for example, the system might suggest a referral to a physical therapist, include a link to that department, and prompt the staff to ask about red flags that indicate a more urgent situation.

After an initial rollout, Providence recently deployed Provaria to manage the messages for all 4000 of its primary care, family medicine, and internal medicine providers. The system has reviewed and categorized more than 500,000 messages so far.

“This is another example where AI can increase the human connection in healthcare,” Dr. Parsons said. “That’s the opposite of what others are saying, but by using AI, you can automate the stuff that isn’t critical that doctors have wound up doing.”
 

AI Helps Foster Better Person-to-Person Communication

In recent years, the first thing most doctors do when they enter the exam room with a patient is log into the in-room computer and start to take notes — which can be off-putting to patients.

Now devices can ease this process, such as PLAUD, an AI voice recognition device that attaches to a cell phone. Just the size of a credit card, the device enables conversations to be easily recorded. It not only streamlines note-taking but also enables a physician to listen intently to a patient’s concerns instead of furiously jotting down notes.

“That device is already helping transcribe conversations into notes and then into a patient’s electronic medical record,” Dr. Stewart said. “This helps save doctors the work of having to input patient information.”
 

AI Can’t Be a Compassionate Human

The one thing AI can’t do is show compassion, at least not yet. The someday “vision” when a robot will gather intel about a patient’s symptoms and even offer a diagnosis does have some downsides. There is no replacement for human interaction, especially in the case of dire health news.

“If you have signs of a metastatic cancer and a nonhuman is delivering this news, there’s no way AI can share this news with compassion,” said Dr. Stewart.

For now, AI is becoming instrumental in helping reduce the number of extra demands on primary care doctors, as well as physicians in other specialties, so that they can continue focusing on what matters — healing patients.
 

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