Cardiovascular-related deaths increased dramatically in 2020, marking the largest single-year increase since 2015 and surpassing the previous record from 2003, according to the American Heart Association’s 2023 Statistical Update.

During the first year of the COVID-19 pandemic, the largest increases in cardiovascular disease (CVD) deaths were seen among Asian, Black, and Hispanic people.

“We thought we had been improving as a country with respect to CVD deaths over the past few decades,” Connie Tsao, MD, chair of the AHA Statistical Update writing committee, told this news organization.

Since 2020, however, those trends have changed. Dr. Tsao, a staff cardiologist at Beth Israel Deaconess Medical Center and assistant professor of medicine at Harvard Medical School, both in Boston, noted the firsthand experience that many clinicians had in seeing the shift.

“We observed this sharp rise in age-adjusted CVD deaths, which corresponds to the COVID-19 pandemic,” she said. “Those of us health care providers knew from the overfull hospitals and ICUs that clearly COVID took a toll, particularly in those with cardiovascular risk factors.”

The AHA Statistical Update was published online in the journal Circulation.
 

Data on deaths

Each year, the American Heart Association and National Institutes of Health report the latest statistics related to heart disease, stroke, and cardiovascular risk factors. The 2023 update includes additional information about pandemic-related data.

Overall, the number of people who died from cardiovascular disease increased during the first year of the pandemic, rising from 876,613 in 2019 to 928,741 in 2020. This topped the previous high of 910,000 in 2003.

In addition, the age-adjusted mortality rate increased for the first time in several years, Dr. Tsao said, by a “fairly substantial” 4.6%. The age-adjusted mortality rate incorporates the variability in the aging population from year to year, accounting for higher death rates among older people.

“Even though our total number of deaths has been slowly increasing over the past decade, we have seen a decline each year in our age-adjusted rates – until 2020,” she said. “I think that is very indicative of what has been going on within our country – and the world – in light of people of all ages being impacted by the COVID-19 pandemic, especially before vaccines were available to slow the spread.”

The largest increases in CVD-related deaths occurred among Asian, Black, and Hispanic people, who were most heavily affected during the first year of the pandemic.

“People from communities of color were among those most highly impacted, especially early on, often due to a disproportionate burden of cardiovascular risk factors, such as hypertension and obesity,” Michelle Albert, MD, MPH, president of AHA and a professor of medicine at the University of California, San Francisco, said in a statement.

Dr. Albert, who is also the director of UCSF’s Center for the Study of Adversity and Cardiovascular Disease, does research on health equity and noted the disparities seen in the 2020 numbers. “Additionally, there are socioeconomic considerations, as well as the ongoing impact of structural racism on multiple factors, including limiting the ability to access quality health care,” she said.
 

Additional considerations

In a special commentary, the Statistical Update writing committee pointed to the need to track data for other underrepresented communities, including LGBTQ people and those living in rural or urban areas. The authors outlined several ways to better understand the effects of identity and social determinants of health, as well as strategies to reduce cardiovascular-related disparities.

“This year’s writing group made a concerted effort to gather information on specific social factors related to health risk and outcomes, including sexual orientation, gender identity, urbanization, and socioeconomic position,” Dr. Tsao said. “However, the data are lacking because these communities are grossly underrepresented in clinical and epidemiological research.”

For the next several years, the AHA Statistical Update will likely include more insights about the effects of the COVID-19 pandemic, as well as ongoing disparities.

“For sure, we will be continuing to see the effects of the pandemic for years to come,” Dr. Tsao said. “Recognition of the disparities in outcomes among vulnerable groups should be a call to action among health care providers and researchers, administration, and policy leaders to investigate the reasons and make changes to reverse these trends.”

The statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee.

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

Cardiovascular-related deaths increased dramatically in 2020, marking the largest single-year increase since 2015 and surpassing the previous record from 2003, according to the American Heart Association’s 2023 Statistical Update.

During the first year of the COVID-19 pandemic, the largest increases in cardiovascular disease (CVD) deaths were seen among Asian, Black, and Hispanic people.

“We thought we had been improving as a country with respect to CVD deaths over the past few decades,” Connie Tsao, MD, chair of the AHA Statistical Update writing committee, told this news organization.

Since 2020, however, those trends have changed. Dr. Tsao, a staff cardiologist at Beth Israel Deaconess Medical Center and assistant professor of medicine at Harvard Medical School, both in Boston, noted the firsthand experience that many clinicians had in seeing the shift.

“We observed this sharp rise in age-adjusted CVD deaths, which corresponds to the COVID-19 pandemic,” she said. “Those of us health care providers knew from the overfull hospitals and ICUs that clearly COVID took a toll, particularly in those with cardiovascular risk factors.”

The AHA Statistical Update was published online in the journal Circulation.
 

Data on deaths

Each year, the American Heart Association and National Institutes of Health report the latest statistics related to heart disease, stroke, and cardiovascular risk factors. The 2023 update includes additional information about pandemic-related data.

Overall, the number of people who died from cardiovascular disease increased during the first year of the pandemic, rising from 876,613 in 2019 to 928,741 in 2020. This topped the previous high of 910,000 in 2003.

In addition, the age-adjusted mortality rate increased for the first time in several years, Dr. Tsao said, by a “fairly substantial” 4.6%. The age-adjusted mortality rate incorporates the variability in the aging population from year to year, accounting for higher death rates among older people.

“Even though our total number of deaths has been slowly increasing over the past decade, we have seen a decline each year in our age-adjusted rates – until 2020,” she said. “I think that is very indicative of what has been going on within our country – and the world – in light of people of all ages being impacted by the COVID-19 pandemic, especially before vaccines were available to slow the spread.”

The largest increases in CVD-related deaths occurred among Asian, Black, and Hispanic people, who were most heavily affected during the first year of the pandemic.

“People from communities of color were among those most highly impacted, especially early on, often due to a disproportionate burden of cardiovascular risk factors, such as hypertension and obesity,” Michelle Albert, MD, MPH, president of AHA and a professor of medicine at the University of California, San Francisco, said in a statement.

Dr. Albert, who is also the director of UCSF’s Center for the Study of Adversity and Cardiovascular Disease, does research on health equity and noted the disparities seen in the 2020 numbers. “Additionally, there are socioeconomic considerations, as well as the ongoing impact of structural racism on multiple factors, including limiting the ability to access quality health care,” she said.
 

Additional considerations

In a special commentary, the Statistical Update writing committee pointed to the need to track data for other underrepresented communities, including LGBTQ people and those living in rural or urban areas. The authors outlined several ways to better understand the effects of identity and social determinants of health, as well as strategies to reduce cardiovascular-related disparities.

“This year’s writing group made a concerted effort to gather information on specific social factors related to health risk and outcomes, including sexual orientation, gender identity, urbanization, and socioeconomic position,” Dr. Tsao said. “However, the data are lacking because these communities are grossly underrepresented in clinical and epidemiological research.”

For the next several years, the AHA Statistical Update will likely include more insights about the effects of the COVID-19 pandemic, as well as ongoing disparities.

“For sure, we will be continuing to see the effects of the pandemic for years to come,” Dr. Tsao said. “Recognition of the disparities in outcomes among vulnerable groups should be a call to action among health care providers and researchers, administration, and policy leaders to investigate the reasons and make changes to reverse these trends.”

The statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee.

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

Cardiovascular-related deaths increased dramatically in 2020, marking the largest single-year increase since 2015 and surpassing the previous record from 2003, according to the American Heart Association’s 2023 Statistical Update.

During the first year of the COVID-19 pandemic, the largest increases in cardiovascular disease (CVD) deaths were seen among Asian, Black, and Hispanic people.

“We thought we had been improving as a country with respect to CVD deaths over the past few decades,” Connie Tsao, MD, chair of the AHA Statistical Update writing committee, told this news organization.

Since 2020, however, those trends have changed. Dr. Tsao, a staff cardiologist at Beth Israel Deaconess Medical Center and assistant professor of medicine at Harvard Medical School, both in Boston, noted the firsthand experience that many clinicians had in seeing the shift.

“We observed this sharp rise in age-adjusted CVD deaths, which corresponds to the COVID-19 pandemic,” she said. “Those of us health care providers knew from the overfull hospitals and ICUs that clearly COVID took a toll, particularly in those with cardiovascular risk factors.”

The AHA Statistical Update was published online in the journal Circulation.
 

Data on deaths

Each year, the American Heart Association and National Institutes of Health report the latest statistics related to heart disease, stroke, and cardiovascular risk factors. The 2023 update includes additional information about pandemic-related data.

Overall, the number of people who died from cardiovascular disease increased during the first year of the pandemic, rising from 876,613 in 2019 to 928,741 in 2020. This topped the previous high of 910,000 in 2003.

In addition, the age-adjusted mortality rate increased for the first time in several years, Dr. Tsao said, by a “fairly substantial” 4.6%. The age-adjusted mortality rate incorporates the variability in the aging population from year to year, accounting for higher death rates among older people.

“Even though our total number of deaths has been slowly increasing over the past decade, we have seen a decline each year in our age-adjusted rates – until 2020,” she said. “I think that is very indicative of what has been going on within our country – and the world – in light of people of all ages being impacted by the COVID-19 pandemic, especially before vaccines were available to slow the spread.”

The largest increases in CVD-related deaths occurred among Asian, Black, and Hispanic people, who were most heavily affected during the first year of the pandemic.

“People from communities of color were among those most highly impacted, especially early on, often due to a disproportionate burden of cardiovascular risk factors, such as hypertension and obesity,” Michelle Albert, MD, MPH, president of AHA and a professor of medicine at the University of California, San Francisco, said in a statement.

Dr. Albert, who is also the director of UCSF’s Center for the Study of Adversity and Cardiovascular Disease, does research on health equity and noted the disparities seen in the 2020 numbers. “Additionally, there are socioeconomic considerations, as well as the ongoing impact of structural racism on multiple factors, including limiting the ability to access quality health care,” she said.
 

Additional considerations

In a special commentary, the Statistical Update writing committee pointed to the need to track data for other underrepresented communities, including LGBTQ people and those living in rural or urban areas. The authors outlined several ways to better understand the effects of identity and social determinants of health, as well as strategies to reduce cardiovascular-related disparities.

“This year’s writing group made a concerted effort to gather information on specific social factors related to health risk and outcomes, including sexual orientation, gender identity, urbanization, and socioeconomic position,” Dr. Tsao said. “However, the data are lacking because these communities are grossly underrepresented in clinical and epidemiological research.”

For the next several years, the AHA Statistical Update will likely include more insights about the effects of the COVID-19 pandemic, as well as ongoing disparities.

“For sure, we will be continuing to see the effects of the pandemic for years to come,” Dr. Tsao said. “Recognition of the disparities in outcomes among vulnerable groups should be a call to action among health care providers and researchers, administration, and policy leaders to investigate the reasons and make changes to reverse these trends.”

The statistical update was prepared by a volunteer writing group on behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee.

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

An experimental psychedelic tryptamine combined with supportive therapy is associated with improvements in moderate to severe major depressive disorder (MDD), new research suggests.

Top-line results from a phase 2a study of SPL026 (intravenous N,N-Dimethyltryptamine [DMT]) showed a 57% remission rate 3 months after participants received a single dose of the drug, the developer reports.

Small Pharma noted in a press release that this is the first placebo-controlled efficacy trial of a short-duration psychedelic for depression completed to date.

Investigators reported significant improvement in depression symptoms 2 weeks after dosing, which was the primary endpoint, and the improvement persisted at week 12.

“We now have the first evidence that SPL026 DMT, combined with supportive therapy, may be effective for people suffering from MDD,” chief investigator David Erritzoe, MD, PhD, clinical psychiatrist at Imperial College London, said in a statement.

“For patients who are unfortunate to experience little benefit from existing antidepressants, the potential for rapid and durable relief from a single treatment, as shown in this trial, is very promising,” Dr. Erritzoe added.
 

Randomized trial results

The blinded, randomized, placebo-controlled, two-staged phase 2a study included 34 patients with moderate to severe MDD. Those who were taking pharmacological antidepressant medication at baseline stopped taking the medication prior to dosing with SPL026.

Patients received a placebo (n = 17) or active treatment (n = 17). The latter consisted of a short IV infusion of 21.5 mg of SPL026, resulting in a 20- to 30-minute psychedelic experience, and supportive therapy.

The dose was selected based on data analysis from the company’s phase 1 study in healthy volunteers.

Efficacy was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) to measure changes in MDD symptoms.

Two weeks after dosing, those receiving the novel therapy showed a significant reduction in depressive symptoms, demonstrating a –7.4-point difference versus the placebo group in MADRS score (P = .02).

Analysis of key secondary endpoints showed a rapid onset of antidepressant effect 1 week post-dose, with a statistically significant difference in MADRS score between the active and placebo groups of –10.8 points (P = .002).
 

Next steps?

All participants were subsequently enrolled into an open-label phase of the trial where they received a single dose of SPL026 with supportive therapy. They were then followed for a further 12 weeks.

In the open-label phase, patients who received at least one active dose of SPL026 with supportive therapy reported a durable improvement in depression symptoms.

No apparent difference in antidepressant effect was observed between a one- or two-dose regimen of SPL026.

“SPL026 with supportive therapy was shown to have a significant antidepressant effect that was rapid and durable,” Carol Routledge, PhD, chief medical and scientific officer at Small Pharma, said in the statement.

Small Pharma

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

An experimental psychedelic tryptamine combined with supportive therapy is associated with improvements in moderate to severe major depressive disorder (MDD), new research suggests.

Top-line results from a phase 2a study of SPL026 (intravenous N,N-Dimethyltryptamine [DMT]) showed a 57% remission rate 3 months after participants received a single dose of the drug, the developer reports.

Small Pharma noted in a press release that this is the first placebo-controlled efficacy trial of a short-duration psychedelic for depression completed to date.

Investigators reported significant improvement in depression symptoms 2 weeks after dosing, which was the primary endpoint, and the improvement persisted at week 12.

“We now have the first evidence that SPL026 DMT, combined with supportive therapy, may be effective for people suffering from MDD,” chief investigator David Erritzoe, MD, PhD, clinical psychiatrist at Imperial College London, said in a statement.

“For patients who are unfortunate to experience little benefit from existing antidepressants, the potential for rapid and durable relief from a single treatment, as shown in this trial, is very promising,” Dr. Erritzoe added.
 

Randomized trial results

The blinded, randomized, placebo-controlled, two-staged phase 2a study included 34 patients with moderate to severe MDD. Those who were taking pharmacological antidepressant medication at baseline stopped taking the medication prior to dosing with SPL026.

Patients received a placebo (n = 17) or active treatment (n = 17). The latter consisted of a short IV infusion of 21.5 mg of SPL026, resulting in a 20- to 30-minute psychedelic experience, and supportive therapy.

The dose was selected based on data analysis from the company’s phase 1 study in healthy volunteers.

Efficacy was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) to measure changes in MDD symptoms.

Two weeks after dosing, those receiving the novel therapy showed a significant reduction in depressive symptoms, demonstrating a –7.4-point difference versus the placebo group in MADRS score (P = .02).

Analysis of key secondary endpoints showed a rapid onset of antidepressant effect 1 week post-dose, with a statistically significant difference in MADRS score between the active and placebo groups of –10.8 points (P = .002).
 

Next steps?

All participants were subsequently enrolled into an open-label phase of the trial where they received a single dose of SPL026 with supportive therapy. They were then followed for a further 12 weeks.

In the open-label phase, patients who received at least one active dose of SPL026 with supportive therapy reported a durable improvement in depression symptoms.

No apparent difference in antidepressant effect was observed between a one- or two-dose regimen of SPL026.

“SPL026 with supportive therapy was shown to have a significant antidepressant effect that was rapid and durable,” Carol Routledge, PhD, chief medical and scientific officer at Small Pharma, said in the statement.

Small Pharma

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

An experimental psychedelic tryptamine combined with supportive therapy is associated with improvements in moderate to severe major depressive disorder (MDD), new research suggests.

Top-line results from a phase 2a study of SPL026 (intravenous N,N-Dimethyltryptamine [DMT]) showed a 57% remission rate 3 months after participants received a single dose of the drug, the developer reports.

Small Pharma noted in a press release that this is the first placebo-controlled efficacy trial of a short-duration psychedelic for depression completed to date.

Investigators reported significant improvement in depression symptoms 2 weeks after dosing, which was the primary endpoint, and the improvement persisted at week 12.

“We now have the first evidence that SPL026 DMT, combined with supportive therapy, may be effective for people suffering from MDD,” chief investigator David Erritzoe, MD, PhD, clinical psychiatrist at Imperial College London, said in a statement.

“For patients who are unfortunate to experience little benefit from existing antidepressants, the potential for rapid and durable relief from a single treatment, as shown in this trial, is very promising,” Dr. Erritzoe added.
 

Randomized trial results

The blinded, randomized, placebo-controlled, two-staged phase 2a study included 34 patients with moderate to severe MDD. Those who were taking pharmacological antidepressant medication at baseline stopped taking the medication prior to dosing with SPL026.

Patients received a placebo (n = 17) or active treatment (n = 17). The latter consisted of a short IV infusion of 21.5 mg of SPL026, resulting in a 20- to 30-minute psychedelic experience, and supportive therapy.

The dose was selected based on data analysis from the company’s phase 1 study in healthy volunteers.

Efficacy was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) to measure changes in MDD symptoms.

Two weeks after dosing, those receiving the novel therapy showed a significant reduction in depressive symptoms, demonstrating a –7.4-point difference versus the placebo group in MADRS score (P = .02).

Analysis of key secondary endpoints showed a rapid onset of antidepressant effect 1 week post-dose, with a statistically significant difference in MADRS score between the active and placebo groups of –10.8 points (P = .002).
 

Next steps?

All participants were subsequently enrolled into an open-label phase of the trial where they received a single dose of SPL026 with supportive therapy. They were then followed for a further 12 weeks.

In the open-label phase, patients who received at least one active dose of SPL026 with supportive therapy reported a durable improvement in depression symptoms.

No apparent difference in antidepressant effect was observed between a one- or two-dose regimen of SPL026.

“SPL026 with supportive therapy was shown to have a significant antidepressant effect that was rapid and durable,” Carol Routledge, PhD, chief medical and scientific officer at Small Pharma, said in the statement.

Small Pharma

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

Roughly 4 decades after she first started menstruating, Elizabeth Flanagan finally underwent surgery to repair damage wreaked on her body by endometriosis. She’d spent years struggling with a variety of seemingly random symptoms, from migraines to excruciatingly painful periods to fatigue and irritable bowel syndrome. She’d worried about abnormal labs, including “extremely high” ANA, creatinine, and BUN blood test results that had been out of normal range for more than 10 years.

She was diagnosed with endometriosis in 2016, at age 47, after surgery to remove an ovarian cyst. Still, it took 5 more years before she landed in the office of a surgeon with the proper training to excise the lesions that continued to cause her so much anguish. That physician, Matthew Siedhoff, MD, at Cedars-Sinai Medical Center in Los Angeles, explained why her creatinine and BUN results were so far out of range: The endometriosis was impinging on her ureters.

The appointment left Ms. Flanagan with a range of emotions. “I was shocked that no doctor had identified this before, relieved knowing that I was finally in the hands of an expert who understood my condition, and saddened by the dearth of knowledge and proper treatment of endometriosis,” she wrote in an email.

Although the disease afflicts at least 1 out of every 10 women, endometriosis remains a conundrum for patients and their physicians. It often masquerades as other problems, from mental health issues such as anxiety and depression to physical issues such as irritable bowel syndrome. It often coexists with autoimmune conditions. Short of performing surgery, it can be a diagnosis of exclusion. And the existing, state-of-the-art treatment – hormone therapy that shuts down the reproductive system – doesn’t work for every woman every time.

“It is no wonder that it takes 10 years on average, from the time someone has symptoms of endometriosis, until they get a definitive diagnosis,” said Hugh Taylor, MD, chair of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn. “It’s a combination of [physicians] not taking painful menses seriously and getting distracted by all these other manifestations of the disease throughout the whole body.”

Endometriosis, he said, “is a whole-body disease.”

But recent genetic research offers the tantalizing prospect of new diagnostic tools and treatments. In 5-10 years, scientists say, physicians may be able to diagnose the disease with a simple blood test, and treat it, for example, by preventing a gene receptor from initiating a cascade of inflammatory effects, or crafting treatments tailored to the molecular makeup of a patient’s disease.

“Tomorrow’s therapies will target specifically the molecular defects of endometriosis and be nonhormonal,” Dr. Taylor said.

Guidelines published last year by the European Society of Human Reproduction and Embryology detail the latest standards for diagnosis and treatment of endometriosis.

According to the guidelines, physicians should consider the diagnosis of endometriosis in individuals presenting with the following cyclical and noncyclical signs and symptoms: dysmenorrhea, deep dyspareunia, dysuria, dyschezia, painful rectal bleeding or hematuria, shoulder tip pain, catamenial pneumothorax, cyclical cough/hemoptysis/chest pain, cyclical scar swelling, and pain, fatigue, and infertility.

A clinical exam should be considered, as well as imaging such as ultrasound and/or MRI, the guidelines state, although negative findings should not rule out a diagnosis. Laparoscopy is also an option, particularly for patients who desire a definitive diagnosis or cannot be diagnosed any other way, “although negative histology [of endometriotic lesions] does not entirely rule out the disease,” the guidelines state.

To treat the pain associated with endometriosis, the guidelines advise, as a first-line therapy, beginning with NSAIDs and combined hormonal contraceptives (in oral, vaginal, or transdermal form). Another option is progesterone, including progesterone-only contraceptives, with a recommendation to prescribe a levonorgestrel-releasing intrauterine system or an etonogestrel-releasing subdermal implant to reduce endometriosis-associated pain.

However, progestins and low-dose oral contraceptives are “unsuccessful in a third of women,” Dr. Taylor and his coauthors wrote in a paper published in 2021 in The Lancet.

Until recently, the gold standard for second-line treatment of endometriosis was oral gonadotropin-releasing hormone (GnRH) agonists. These manage the disease by inducing medical menopause – they downregulate pituitary GnRH receptors to create a hypoestrogenic state characterized by low serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). GnRH agonists may be administered nasally, or through daily, monthly, or trimonthly injections. But the Food and Drug Administration advises that, when used for longer than 6 months, GnRH agonists be paired with add-back hormone replacement therapy to reduce the risk of bone loss associated with the plunge in hormone levels. Also, treatment may not be appropriate for patients who, when suddenly forced into menopause, suffer from bothersome symptoms.

The latest treatment, GnRH antagonists, are new options for patients who either do not respond adequately to progestins and low-dose contraceptives or develop progesterone resistance, and want to avoid some of the risks and/or symptoms associated with GnRH agonists. Two advantages of GnRH antagonists for patients, Dr. Taylor said, are that they have a fast onset of action and are oral rather than injectable.

“These drugs [GnRH antagonists] cause competitive blockage of the GnRH receptor and hence dose-dependently suppress production of FSH and LH and inhibit secretion of ovarian steroid hormones without inducing a flare-up effect,” Belgian physicians and researchers Jacques Donnez, MD, and Marie-Madeleine Dolmans, MD, PhD, wrote in a paper published last year in the Journal of Clinical Medicine. “The mechanism is different from that of the GnRH agonist which, after a first phase of stimulation, desensitizes GnRH receptors, leading to full suppression of LH and FSH production and subsequently to complete suppression of [estrogen] to levels similar to those observed after bilateral oophorectomy.”

Patients who took Elagolix, the first oral nonpeptide GnRH antagonist available for the treatment of moderate to severe endometriosis-associated pain, had fewer vasomotor side effects and less bone density loss than those on the GnRH agonist leuprorelin, according to a 2018 study in Obstetrics and Gynecology. However, without add-back hormone-replacement therapy, GnRH antagonist use may need to be limited to 24 months, because of loss of bone density, a study in Cell Reports Medicine reported in 2022.

Attempting to explain the pathogenesis of endometriosis, and frustrated by the shortcomings of currently available therapies, researchers have turned to genetics for insight. A team of scientists led by Thomas Tapmeier, PhD, now a senior research fellow at Monash University in Australia, and Prof. Krina Zondervan at the University of Oxford, ran genetic analyses of families with a history of endometriosis, as well as rhesus macaques that spontaneously developed endometriosis. The research, published in Science Translational Medicine, identified NPSR1, the gene encoding neuropeptide S receptor 1, as one commonly associated with endometriosis. In trials with mouse models, they found that the NPSR1 inhibitor SHA 68R was able to reduce endometriosis-related inflammation and pain.

“It’s important to stress that there is no single gene that is responsible for endometriosis,” Dr. Tapmeier said in an interview. “This gene just has a higher frequency in people with endometriosis.”

The next step, then, would be to try to find a compound that would inhibit NPSR1 at some point, or a competitor to the ligand that binds to the receptor and blocks it, he said.

“We’re currently looking at compounds that might be able to inhibit the receptor signaling,” he said.

Such a therapy could potentially reduce the symptoms of endometriosis without interfering with the menstrual cycle and without introducing hormones that cause undesirable side effects in some patients.

“This might be a way to treat the pain and inflammation that goes with endometriosis, as well as leaving the possibility of pregnancy open,” he said.

Other researchers are searching for biomarkers of the disease, both to provide a definitive, nonsurgical diagnostic tool, and for potential, individualized treatment.

In a study published in Nature Genetics, researchers at Cedars-Sinai created a “cellular atlas” of endometriosis by analyzing nearly 400,000 individual cells from 21 patients, some of whom had the disease and some of whom did not. A new technology, single-cell genomics, allowed the scientists to profile the multiple cell types contributing to the disease.

“So the initial question we wanted to ask was about understanding how the cells look in endometriosis, compared to endometrium,” said Kate Lawrenson, PhD, an associate professor in the department of obstetrics and gynecology at Cedars-Sinai, and co–senior author of the study. “We know that they resemble the cells of the womb, but we really don’t understand if they behave the same. We had a good inkling that they would behave differently.”

It turned out they did: Cells of endometriosis interacted atypically with female hormones, compared with cells in the uterus, Dr. Lawrenson said.

“That helps us understand how, even when patients take contraceptive pills, which is a commonly prescribed therapy, it doesn’t always work, or sometimes it stops working after a while,” she said. The next step for researchers, she said, will be to pinpoint the specific causes of these altered interactions.

Meanwhile, the current research also points to diagnostic possibilities. “We were quite excited to see that multiple cell types and endometriosis are upregulating the same sets of genes,” she said. “That makes us optimistic that hopefully there are some protein gene products that are being made in abundance, and hopefully we can detect them in the blood stream. It might be that we could use that information to develop new biomarkers, or even risk stratification tools.”

In the future, a simple blood test could identify signs of endometriosis in at-risk patients and get them “fast-tracked to a specialist for evaluation,” she said. “Whereas now, they might go from PCP to gynecologist to a different gynecologist over the course of 5-10 years before they get that referral.”

This discovery, that endometrial cells use genes differently and cross-talk with nearby cells differently, presents new treatment possibilities. Maybe we can physically block how cells interact with nearby cells, Dr. Lawrenson said. One model for doing that, she said, would be antibody-based therapy, similar to the therapies now changing the treatment of cancer.

What’s most exciting, looking ahead 5-10 years, is that treatment for endometriosis in the future may be significantly more individualized, and less hormone-based, than it is today.

“What we need for endometriosis is more options for patients and something that is tailored to the molecular makeup of their disease rather than a process of trial and error,” she said.

Roughly 4 decades after she first started menstruating, Elizabeth Flanagan finally underwent surgery to repair damage wreaked on her body by endometriosis. She’d spent years struggling with a variety of seemingly random symptoms, from migraines to excruciatingly painful periods to fatigue and irritable bowel syndrome. She’d worried about abnormal labs, including “extremely high” ANA, creatinine, and BUN blood test results that had been out of normal range for more than 10 years.

She was diagnosed with endometriosis in 2016, at age 47, after surgery to remove an ovarian cyst. Still, it took 5 more years before she landed in the office of a surgeon with the proper training to excise the lesions that continued to cause her so much anguish. That physician, Matthew Siedhoff, MD, at Cedars-Sinai Medical Center in Los Angeles, explained why her creatinine and BUN results were so far out of range: The endometriosis was impinging on her ureters.

The appointment left Ms. Flanagan with a range of emotions. “I was shocked that no doctor had identified this before, relieved knowing that I was finally in the hands of an expert who understood my condition, and saddened by the dearth of knowledge and proper treatment of endometriosis,” she wrote in an email.

Although the disease afflicts at least 1 out of every 10 women, endometriosis remains a conundrum for patients and their physicians. It often masquerades as other problems, from mental health issues such as anxiety and depression to physical issues such as irritable bowel syndrome. It often coexists with autoimmune conditions. Short of performing surgery, it can be a diagnosis of exclusion. And the existing, state-of-the-art treatment – hormone therapy that shuts down the reproductive system – doesn’t work for every woman every time.

“It is no wonder that it takes 10 years on average, from the time someone has symptoms of endometriosis, until they get a definitive diagnosis,” said Hugh Taylor, MD, chair of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn. “It’s a combination of [physicians] not taking painful menses seriously and getting distracted by all these other manifestations of the disease throughout the whole body.”

Endometriosis, he said, “is a whole-body disease.”

But recent genetic research offers the tantalizing prospect of new diagnostic tools and treatments. In 5-10 years, scientists say, physicians may be able to diagnose the disease with a simple blood test, and treat it, for example, by preventing a gene receptor from initiating a cascade of inflammatory effects, or crafting treatments tailored to the molecular makeup of a patient’s disease.

“Tomorrow’s therapies will target specifically the molecular defects of endometriosis and be nonhormonal,” Dr. Taylor said.

Guidelines published last year by the European Society of Human Reproduction and Embryology detail the latest standards for diagnosis and treatment of endometriosis.

According to the guidelines, physicians should consider the diagnosis of endometriosis in individuals presenting with the following cyclical and noncyclical signs and symptoms: dysmenorrhea, deep dyspareunia, dysuria, dyschezia, painful rectal bleeding or hematuria, shoulder tip pain, catamenial pneumothorax, cyclical cough/hemoptysis/chest pain, cyclical scar swelling, and pain, fatigue, and infertility.

A clinical exam should be considered, as well as imaging such as ultrasound and/or MRI, the guidelines state, although negative findings should not rule out a diagnosis. Laparoscopy is also an option, particularly for patients who desire a definitive diagnosis or cannot be diagnosed any other way, “although negative histology [of endometriotic lesions] does not entirely rule out the disease,” the guidelines state.

To treat the pain associated with endometriosis, the guidelines advise, as a first-line therapy, beginning with NSAIDs and combined hormonal contraceptives (in oral, vaginal, or transdermal form). Another option is progesterone, including progesterone-only contraceptives, with a recommendation to prescribe a levonorgestrel-releasing intrauterine system or an etonogestrel-releasing subdermal implant to reduce endometriosis-associated pain.

However, progestins and low-dose oral contraceptives are “unsuccessful in a third of women,” Dr. Taylor and his coauthors wrote in a paper published in 2021 in The Lancet.

Until recently, the gold standard for second-line treatment of endometriosis was oral gonadotropin-releasing hormone (GnRH) agonists. These manage the disease by inducing medical menopause – they downregulate pituitary GnRH receptors to create a hypoestrogenic state characterized by low serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). GnRH agonists may be administered nasally, or through daily, monthly, or trimonthly injections. But the Food and Drug Administration advises that, when used for longer than 6 months, GnRH agonists be paired with add-back hormone replacement therapy to reduce the risk of bone loss associated with the plunge in hormone levels. Also, treatment may not be appropriate for patients who, when suddenly forced into menopause, suffer from bothersome symptoms.

The latest treatment, GnRH antagonists, are new options for patients who either do not respond adequately to progestins and low-dose contraceptives or develop progesterone resistance, and want to avoid some of the risks and/or symptoms associated with GnRH agonists. Two advantages of GnRH antagonists for patients, Dr. Taylor said, are that they have a fast onset of action and are oral rather than injectable.

“These drugs [GnRH antagonists] cause competitive blockage of the GnRH receptor and hence dose-dependently suppress production of FSH and LH and inhibit secretion of ovarian steroid hormones without inducing a flare-up effect,” Belgian physicians and researchers Jacques Donnez, MD, and Marie-Madeleine Dolmans, MD, PhD, wrote in a paper published last year in the Journal of Clinical Medicine. “The mechanism is different from that of the GnRH agonist which, after a first phase of stimulation, desensitizes GnRH receptors, leading to full suppression of LH and FSH production and subsequently to complete suppression of [estrogen] to levels similar to those observed after bilateral oophorectomy.”

Patients who took Elagolix, the first oral nonpeptide GnRH antagonist available for the treatment of moderate to severe endometriosis-associated pain, had fewer vasomotor side effects and less bone density loss than those on the GnRH agonist leuprorelin, according to a 2018 study in Obstetrics and Gynecology. However, without add-back hormone-replacement therapy, GnRH antagonist use may need to be limited to 24 months, because of loss of bone density, a study in Cell Reports Medicine reported in 2022.

Attempting to explain the pathogenesis of endometriosis, and frustrated by the shortcomings of currently available therapies, researchers have turned to genetics for insight. A team of scientists led by Thomas Tapmeier, PhD, now a senior research fellow at Monash University in Australia, and Prof. Krina Zondervan at the University of Oxford, ran genetic analyses of families with a history of endometriosis, as well as rhesus macaques that spontaneously developed endometriosis. The research, published in Science Translational Medicine, identified NPSR1, the gene encoding neuropeptide S receptor 1, as one commonly associated with endometriosis. In trials with mouse models, they found that the NPSR1 inhibitor SHA 68R was able to reduce endometriosis-related inflammation and pain.

“It’s important to stress that there is no single gene that is responsible for endometriosis,” Dr. Tapmeier said in an interview. “This gene just has a higher frequency in people with endometriosis.”

The next step, then, would be to try to find a compound that would inhibit NPSR1 at some point, or a competitor to the ligand that binds to the receptor and blocks it, he said.

“We’re currently looking at compounds that might be able to inhibit the receptor signaling,” he said.

Such a therapy could potentially reduce the symptoms of endometriosis without interfering with the menstrual cycle and without introducing hormones that cause undesirable side effects in some patients.

“This might be a way to treat the pain and inflammation that goes with endometriosis, as well as leaving the possibility of pregnancy open,” he said.

Other researchers are searching for biomarkers of the disease, both to provide a definitive, nonsurgical diagnostic tool, and for potential, individualized treatment.

In a study published in Nature Genetics, researchers at Cedars-Sinai created a “cellular atlas” of endometriosis by analyzing nearly 400,000 individual cells from 21 patients, some of whom had the disease and some of whom did not. A new technology, single-cell genomics, allowed the scientists to profile the multiple cell types contributing to the disease.

“So the initial question we wanted to ask was about understanding how the cells look in endometriosis, compared to endometrium,” said Kate Lawrenson, PhD, an associate professor in the department of obstetrics and gynecology at Cedars-Sinai, and co–senior author of the study. “We know that they resemble the cells of the womb, but we really don’t understand if they behave the same. We had a good inkling that they would behave differently.”

It turned out they did: Cells of endometriosis interacted atypically with female hormones, compared with cells in the uterus, Dr. Lawrenson said.

“That helps us understand how, even when patients take contraceptive pills, which is a commonly prescribed therapy, it doesn’t always work, or sometimes it stops working after a while,” she said. The next step for researchers, she said, will be to pinpoint the specific causes of these altered interactions.

Meanwhile, the current research also points to diagnostic possibilities. “We were quite excited to see that multiple cell types and endometriosis are upregulating the same sets of genes,” she said. “That makes us optimistic that hopefully there are some protein gene products that are being made in abundance, and hopefully we can detect them in the blood stream. It might be that we could use that information to develop new biomarkers, or even risk stratification tools.”

In the future, a simple blood test could identify signs of endometriosis in at-risk patients and get them “fast-tracked to a specialist for evaluation,” she said. “Whereas now, they might go from PCP to gynecologist to a different gynecologist over the course of 5-10 years before they get that referral.”

This discovery, that endometrial cells use genes differently and cross-talk with nearby cells differently, presents new treatment possibilities. Maybe we can physically block how cells interact with nearby cells, Dr. Lawrenson said. One model for doing that, she said, would be antibody-based therapy, similar to the therapies now changing the treatment of cancer.

What’s most exciting, looking ahead 5-10 years, is that treatment for endometriosis in the future may be significantly more individualized, and less hormone-based, than it is today.

“What we need for endometriosis is more options for patients and something that is tailored to the molecular makeup of their disease rather than a process of trial and error,” she said.

Roughly 4 decades after she first started menstruating, Elizabeth Flanagan finally underwent surgery to repair damage wreaked on her body by endometriosis. She’d spent years struggling with a variety of seemingly random symptoms, from migraines to excruciatingly painful periods to fatigue and irritable bowel syndrome. She’d worried about abnormal labs, including “extremely high” ANA, creatinine, and BUN blood test results that had been out of normal range for more than 10 years.

She was diagnosed with endometriosis in 2016, at age 47, after surgery to remove an ovarian cyst. Still, it took 5 more years before she landed in the office of a surgeon with the proper training to excise the lesions that continued to cause her so much anguish. That physician, Matthew Siedhoff, MD, at Cedars-Sinai Medical Center in Los Angeles, explained why her creatinine and BUN results were so far out of range: The endometriosis was impinging on her ureters.

The appointment left Ms. Flanagan with a range of emotions. “I was shocked that no doctor had identified this before, relieved knowing that I was finally in the hands of an expert who understood my condition, and saddened by the dearth of knowledge and proper treatment of endometriosis,” she wrote in an email.

Although the disease afflicts at least 1 out of every 10 women, endometriosis remains a conundrum for patients and their physicians. It often masquerades as other problems, from mental health issues such as anxiety and depression to physical issues such as irritable bowel syndrome. It often coexists with autoimmune conditions. Short of performing surgery, it can be a diagnosis of exclusion. And the existing, state-of-the-art treatment – hormone therapy that shuts down the reproductive system – doesn’t work for every woman every time.

“It is no wonder that it takes 10 years on average, from the time someone has symptoms of endometriosis, until they get a definitive diagnosis,” said Hugh Taylor, MD, chair of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn. “It’s a combination of [physicians] not taking painful menses seriously and getting distracted by all these other manifestations of the disease throughout the whole body.”

Endometriosis, he said, “is a whole-body disease.”

But recent genetic research offers the tantalizing prospect of new diagnostic tools and treatments. In 5-10 years, scientists say, physicians may be able to diagnose the disease with a simple blood test, and treat it, for example, by preventing a gene receptor from initiating a cascade of inflammatory effects, or crafting treatments tailored to the molecular makeup of a patient’s disease.

“Tomorrow’s therapies will target specifically the molecular defects of endometriosis and be nonhormonal,” Dr. Taylor said.

Guidelines published last year by the European Society of Human Reproduction and Embryology detail the latest standards for diagnosis and treatment of endometriosis.

According to the guidelines, physicians should consider the diagnosis of endometriosis in individuals presenting with the following cyclical and noncyclical signs and symptoms: dysmenorrhea, deep dyspareunia, dysuria, dyschezia, painful rectal bleeding or hematuria, shoulder tip pain, catamenial pneumothorax, cyclical cough/hemoptysis/chest pain, cyclical scar swelling, and pain, fatigue, and infertility.

A clinical exam should be considered, as well as imaging such as ultrasound and/or MRI, the guidelines state, although negative findings should not rule out a diagnosis. Laparoscopy is also an option, particularly for patients who desire a definitive diagnosis or cannot be diagnosed any other way, “although negative histology [of endometriotic lesions] does not entirely rule out the disease,” the guidelines state.

To treat the pain associated with endometriosis, the guidelines advise, as a first-line therapy, beginning with NSAIDs and combined hormonal contraceptives (in oral, vaginal, or transdermal form). Another option is progesterone, including progesterone-only contraceptives, with a recommendation to prescribe a levonorgestrel-releasing intrauterine system or an etonogestrel-releasing subdermal implant to reduce endometriosis-associated pain.

However, progestins and low-dose oral contraceptives are “unsuccessful in a third of women,” Dr. Taylor and his coauthors wrote in a paper published in 2021 in The Lancet.

Until recently, the gold standard for second-line treatment of endometriosis was oral gonadotropin-releasing hormone (GnRH) agonists. These manage the disease by inducing medical menopause – they downregulate pituitary GnRH receptors to create a hypoestrogenic state characterized by low serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). GnRH agonists may be administered nasally, or through daily, monthly, or trimonthly injections. But the Food and Drug Administration advises that, when used for longer than 6 months, GnRH agonists be paired with add-back hormone replacement therapy to reduce the risk of bone loss associated with the plunge in hormone levels. Also, treatment may not be appropriate for patients who, when suddenly forced into menopause, suffer from bothersome symptoms.

The latest treatment, GnRH antagonists, are new options for patients who either do not respond adequately to progestins and low-dose contraceptives or develop progesterone resistance, and want to avoid some of the risks and/or symptoms associated with GnRH agonists. Two advantages of GnRH antagonists for patients, Dr. Taylor said, are that they have a fast onset of action and are oral rather than injectable.

“These drugs [GnRH antagonists] cause competitive blockage of the GnRH receptor and hence dose-dependently suppress production of FSH and LH and inhibit secretion of ovarian steroid hormones without inducing a flare-up effect,” Belgian physicians and researchers Jacques Donnez, MD, and Marie-Madeleine Dolmans, MD, PhD, wrote in a paper published last year in the Journal of Clinical Medicine. “The mechanism is different from that of the GnRH agonist which, after a first phase of stimulation, desensitizes GnRH receptors, leading to full suppression of LH and FSH production and subsequently to complete suppression of [estrogen] to levels similar to those observed after bilateral oophorectomy.”

Patients who took Elagolix, the first oral nonpeptide GnRH antagonist available for the treatment of moderate to severe endometriosis-associated pain, had fewer vasomotor side effects and less bone density loss than those on the GnRH agonist leuprorelin, according to a 2018 study in Obstetrics and Gynecology. However, without add-back hormone-replacement therapy, GnRH antagonist use may need to be limited to 24 months, because of loss of bone density, a study in Cell Reports Medicine reported in 2022.

Attempting to explain the pathogenesis of endometriosis, and frustrated by the shortcomings of currently available therapies, researchers have turned to genetics for insight. A team of scientists led by Thomas Tapmeier, PhD, now a senior research fellow at Monash University in Australia, and Prof. Krina Zondervan at the University of Oxford, ran genetic analyses of families with a history of endometriosis, as well as rhesus macaques that spontaneously developed endometriosis. The research, published in Science Translational Medicine, identified NPSR1, the gene encoding neuropeptide S receptor 1, as one commonly associated with endometriosis. In trials with mouse models, they found that the NPSR1 inhibitor SHA 68R was able to reduce endometriosis-related inflammation and pain.

“It’s important to stress that there is no single gene that is responsible for endometriosis,” Dr. Tapmeier said in an interview. “This gene just has a higher frequency in people with endometriosis.”

The next step, then, would be to try to find a compound that would inhibit NPSR1 at some point, or a competitor to the ligand that binds to the receptor and blocks it, he said.

“We’re currently looking at compounds that might be able to inhibit the receptor signaling,” he said.

Such a therapy could potentially reduce the symptoms of endometriosis without interfering with the menstrual cycle and without introducing hormones that cause undesirable side effects in some patients.

“This might be a way to treat the pain and inflammation that goes with endometriosis, as well as leaving the possibility of pregnancy open,” he said.

Other researchers are searching for biomarkers of the disease, both to provide a definitive, nonsurgical diagnostic tool, and for potential, individualized treatment.

In a study published in Nature Genetics, researchers at Cedars-Sinai created a “cellular atlas” of endometriosis by analyzing nearly 400,000 individual cells from 21 patients, some of whom had the disease and some of whom did not. A new technology, single-cell genomics, allowed the scientists to profile the multiple cell types contributing to the disease.

“So the initial question we wanted to ask was about understanding how the cells look in endometriosis, compared to endometrium,” said Kate Lawrenson, PhD, an associate professor in the department of obstetrics and gynecology at Cedars-Sinai, and co–senior author of the study. “We know that they resemble the cells of the womb, but we really don’t understand if they behave the same. We had a good inkling that they would behave differently.”

It turned out they did: Cells of endometriosis interacted atypically with female hormones, compared with cells in the uterus, Dr. Lawrenson said.

“That helps us understand how, even when patients take contraceptive pills, which is a commonly prescribed therapy, it doesn’t always work, or sometimes it stops working after a while,” she said. The next step for researchers, she said, will be to pinpoint the specific causes of these altered interactions.

Meanwhile, the current research also points to diagnostic possibilities. “We were quite excited to see that multiple cell types and endometriosis are upregulating the same sets of genes,” she said. “That makes us optimistic that hopefully there are some protein gene products that are being made in abundance, and hopefully we can detect them in the blood stream. It might be that we could use that information to develop new biomarkers, or even risk stratification tools.”

In the future, a simple blood test could identify signs of endometriosis in at-risk patients and get them “fast-tracked to a specialist for evaluation,” she said. “Whereas now, they might go from PCP to gynecologist to a different gynecologist over the course of 5-10 years before they get that referral.”

This discovery, that endometrial cells use genes differently and cross-talk with nearby cells differently, presents new treatment possibilities. Maybe we can physically block how cells interact with nearby cells, Dr. Lawrenson said. One model for doing that, she said, would be antibody-based therapy, similar to the therapies now changing the treatment of cancer.

What’s most exciting, looking ahead 5-10 years, is that treatment for endometriosis in the future may be significantly more individualized, and less hormone-based, than it is today.

“What we need for endometriosis is more options for patients and something that is tailored to the molecular makeup of their disease rather than a process of trial and error,” she said.

Did you know you can honor a family member, friend, or colleague through a gift to the AGA Research Foundation? Your gift will honor a loved one and support the AGA Research Awards Program, while giving you a tax benefit.

• Giving now or later. Any charitable gift can be made in honor or memory of someone.
• A gift today. An outright gift will help fund the AGA Research Awards Program. Your gift will assist in furthering basic digestive disease research, which can ultimately advance research into all digestive diseases. The financial benefits include an income tax deduction and possible elimination of capital gains tax.
• A gift through your will or living trust. You can include a bequest in your will or living trust stating that a specific asset, certain dollar amount, or more commonly a percentage of your estate will pass to the AGA Research Foundation at your death in honor of your loved one.
• Named opportunities. Individuals interested in receiving name recognition for a listed AGA Institute program can do so by contributing a new, unrestricted gift to the AGA Research Foundation. The gift can be payable over five years. Endowed opportunities are also available.

Your next step

An honorary gift is a wonderful way to acknowledge someone’s vision for the future. To learn more about ways to recognize your honoree, visit our website.

Did you know you can honor a family member, friend, or colleague through a gift to the AGA Research Foundation? Your gift will honor a loved one and support the AGA Research Awards Program, while giving you a tax benefit.

• Giving now or later. Any charitable gift can be made in honor or memory of someone.
• A gift today. An outright gift will help fund the AGA Research Awards Program. Your gift will assist in furthering basic digestive disease research, which can ultimately advance research into all digestive diseases. The financial benefits include an income tax deduction and possible elimination of capital gains tax.
• A gift through your will or living trust. You can include a bequest in your will or living trust stating that a specific asset, certain dollar amount, or more commonly a percentage of your estate will pass to the AGA Research Foundation at your death in honor of your loved one.
• Named opportunities. Individuals interested in receiving name recognition for a listed AGA Institute program can do so by contributing a new, unrestricted gift to the AGA Research Foundation. The gift can be payable over five years. Endowed opportunities are also available.

Your next step

An honorary gift is a wonderful way to acknowledge someone’s vision for the future. To learn more about ways to recognize your honoree, visit our website.

Did you know you can honor a family member, friend, or colleague through a gift to the AGA Research Foundation? Your gift will honor a loved one and support the AGA Research Awards Program, while giving you a tax benefit.

• Giving now or later. Any charitable gift can be made in honor or memory of someone.
• A gift today. An outright gift will help fund the AGA Research Awards Program. Your gift will assist in furthering basic digestive disease research, which can ultimately advance research into all digestive diseases. The financial benefits include an income tax deduction and possible elimination of capital gains tax.
• A gift through your will or living trust. You can include a bequest in your will or living trust stating that a specific asset, certain dollar amount, or more commonly a percentage of your estate will pass to the AGA Research Foundation at your death in honor of your loved one.
• Named opportunities. Individuals interested in receiving name recognition for a listed AGA Institute program can do so by contributing a new, unrestricted gift to the AGA Research Foundation. The gift can be payable over five years. Endowed opportunities are also available.

Your next step

An honorary gift is a wonderful way to acknowledge someone’s vision for the future. To learn more about ways to recognize your honoree, visit our website.

Sticks and stones may break my bones, but clots will never hurt me

You’ve probably seen “Ghostbusters” or at least heard the theme song. Maybe you even know about the Discovery Channel’s “Mythbusters.” But now there’s a new buster in town, and it eats platitudes for breakfast: Meet Cliche-busters, LOTME’s new recurring feature.

This week, Cliche-busters takes on “Two wrongs don’t make a right.” Yum.

We start with blood clots, which are bad. Doctors go to a lot of trouble to get rid of the things because they are dangerous. A blood clot, then, is a bodily function gone wrong.

Tornadoes are also bad. Out there in the world, these violently rotating columns of air can destroy buildings, toss large objects long distances, and inspire mediocre action movies. They are examples of nature gone wrong.

Seemingly, these two wrongs – blood clots and tornadoes – are not about to make a right. Has Cliche-busters bitten off more than it can chew?

Not according to Xiaoning Jiang of North Carolina State University, Raleigh, and his team of researchers. They’ve figured out a way to use a tiny ultrasonic tornado to break down clots in the brain. “Our new work uses vortex ultrasound, where the ultrasound waves have a helical wavefront. In other words, the ultrasound is swirling as it moves forward,” he said in a statement from the university.

Xiaoning Jiang and Chengzhi Shi

Their new tool’s single transducer is small enough to fit in a catheter, and its “vortex ultrasound-induced shear force has the potential to break down clots safely and improve the efficacy of thrombolysis,” they explained in the open-access journal Research.

The investigators used cow blood in a 3D-printed model of the cerebral venous sinus for the proof-of-concept study and were able to dissolve an acute blood clot in less than 30 minutes, compared with the 15-30 hours needed with a pharmaceutical intervention, according to the written statement.

Can you hear the sound of two wrongs making a right? We can, and that closes the curtain on this cliche.
 

With age does not come wisdom

We’ve all met this person before. The sort of person who takes a 10-minute IQ test on a shifty-looking website and then proceeds to brag about a 180 IQ until the heat death of the universe. The one who worships at the altar of Mensa. Yeah, that guy. They’re never as smart as they think they are, but they’ll never, ever admit it.

It’s not exactly a secret that IQ as a measurement of intelligence is highly overrated. A lot of scientists doubt we should bother measuring it at all. That said, a higher IQ is associated with greater success in academic and financial endeavors, so it’s not absolutely worthless. And if we’re stuck with it, we may as well study it.

That brings us neatly to new research published in Brain and Behavior. Most studies into IQ and self-estimated intelligence have focused on younger adults, and the author of this study was curious if the stereotype of young men inflating their IQ, a stereotype backed up by research, persisted into older adulthood. So she conducted a survey of 159 younger adults and 152 older adults to find out.

Wavebreakmedia Ltd/Thinkstock

The results in younger adults were not surprising: Younger men overestimated their actual IQ by 5-15 points, which tracks with previous research. We’re in for a bit of a surprise with the older adults, though, because the older men were more humble about their intelligence, with their estimation falling in line with their actual IQ. Older women, however, not so much. In fact, they overestimated their intelligence just as much as the younger men.

In addition, older women who perceived themselves as more attractive reported the highest self-estimated intelligence of all. That isn’t how intelligence works, but honestly, if Grandma’s out and about thinking she looks good and has the brains to go and win “Jeopardy!” do you really have the heart to tell her otherwise?
 

Fight temptation with empathy … and shoes

Relationships are tough. They all go through their respective ups and downs, but what happens when one person is feeling so down in the partnership that cheating comes to mind? Is there any way to stop it from happening?

Rawpixel

Well, a recent study suggests that there is, and it’s as simple as putting yourself in the other person’s shoes. By observing 408 heterosexual, monogamous participants in a series of experiments, psychologists in Israel and New York found that practicing empathy and “perspective taking” doesn’t necessarily stop people from cheating but it does reduces the desire.

People cheat on their significant others for many different reasons – men for a lack of sexual needs being met and women for shortfalls regarding emotional needs – but prioritizing the other person’s perspective gives the idea of being unfaithful a different view and could make one act differently, the investigators said.

Perspective taking also promotes other positive attributes to the relationship, such as the promotion of compassion and the feeling of being understood, lead author Gurit Birnbaum of Reichman University in Herzliya, Israel, said in a written statement. These things ultimately help couples navigate the rough patches and strengthen bonds, making them even less likely to cheat.

The researchers noted that even people in satisfying relationships do cheat, but this approach does encourage people to stop and think before they act. It could ultimately prevent what might be a huge mistake.

Think before they act. Hmm, that’s kind of like look before they leap, right? Sounds like a job for the Cliche-busters.

Sticks and stones may break my bones, but clots will never hurt me

You’ve probably seen “Ghostbusters” or at least heard the theme song. Maybe you even know about the Discovery Channel’s “Mythbusters.” But now there’s a new buster in town, and it eats platitudes for breakfast: Meet Cliche-busters, LOTME’s new recurring feature.

This week, Cliche-busters takes on “Two wrongs don’t make a right.” Yum.

We start with blood clots, which are bad. Doctors go to a lot of trouble to get rid of the things because they are dangerous. A blood clot, then, is a bodily function gone wrong.

Tornadoes are also bad. Out there in the world, these violently rotating columns of air can destroy buildings, toss large objects long distances, and inspire mediocre action movies. They are examples of nature gone wrong.

Seemingly, these two wrongs – blood clots and tornadoes – are not about to make a right. Has Cliche-busters bitten off more than it can chew?

Not according to Xiaoning Jiang of North Carolina State University, Raleigh, and his team of researchers. They’ve figured out a way to use a tiny ultrasonic tornado to break down clots in the brain. “Our new work uses vortex ultrasound, where the ultrasound waves have a helical wavefront. In other words, the ultrasound is swirling as it moves forward,” he said in a statement from the university.

Xiaoning Jiang and Chengzhi Shi

Their new tool’s single transducer is small enough to fit in a catheter, and its “vortex ultrasound-induced shear force has the potential to break down clots safely and improve the efficacy of thrombolysis,” they explained in the open-access journal Research.

The investigators used cow blood in a 3D-printed model of the cerebral venous sinus for the proof-of-concept study and were able to dissolve an acute blood clot in less than 30 minutes, compared with the 15-30 hours needed with a pharmaceutical intervention, according to the written statement.

Can you hear the sound of two wrongs making a right? We can, and that closes the curtain on this cliche.
 

With age does not come wisdom

We’ve all met this person before. The sort of person who takes a 10-minute IQ test on a shifty-looking website and then proceeds to brag about a 180 IQ until the heat death of the universe. The one who worships at the altar of Mensa. Yeah, that guy. They’re never as smart as they think they are, but they’ll never, ever admit it.

It’s not exactly a secret that IQ as a measurement of intelligence is highly overrated. A lot of scientists doubt we should bother measuring it at all. That said, a higher IQ is associated with greater success in academic and financial endeavors, so it’s not absolutely worthless. And if we’re stuck with it, we may as well study it.

That brings us neatly to new research published in Brain and Behavior. Most studies into IQ and self-estimated intelligence have focused on younger adults, and the author of this study was curious if the stereotype of young men inflating their IQ, a stereotype backed up by research, persisted into older adulthood. So she conducted a survey of 159 younger adults and 152 older adults to find out.

Wavebreakmedia Ltd/Thinkstock

The results in younger adults were not surprising: Younger men overestimated their actual IQ by 5-15 points, which tracks with previous research. We’re in for a bit of a surprise with the older adults, though, because the older men were more humble about their intelligence, with their estimation falling in line with their actual IQ. Older women, however, not so much. In fact, they overestimated their intelligence just as much as the younger men.

In addition, older women who perceived themselves as more attractive reported the highest self-estimated intelligence of all. That isn’t how intelligence works, but honestly, if Grandma’s out and about thinking she looks good and has the brains to go and win “Jeopardy!” do you really have the heart to tell her otherwise?
 

Fight temptation with empathy … and shoes

Relationships are tough. They all go through their respective ups and downs, but what happens when one person is feeling so down in the partnership that cheating comes to mind? Is there any way to stop it from happening?

Rawpixel

Well, a recent study suggests that there is, and it’s as simple as putting yourself in the other person’s shoes. By observing 408 heterosexual, monogamous participants in a series of experiments, psychologists in Israel and New York found that practicing empathy and “perspective taking” doesn’t necessarily stop people from cheating but it does reduces the desire.

People cheat on their significant others for many different reasons – men for a lack of sexual needs being met and women for shortfalls regarding emotional needs – but prioritizing the other person’s perspective gives the idea of being unfaithful a different view and could make one act differently, the investigators said.

Perspective taking also promotes other positive attributes to the relationship, such as the promotion of compassion and the feeling of being understood, lead author Gurit Birnbaum of Reichman University in Herzliya, Israel, said in a written statement. These things ultimately help couples navigate the rough patches and strengthen bonds, making them even less likely to cheat.

The researchers noted that even people in satisfying relationships do cheat, but this approach does encourage people to stop and think before they act. It could ultimately prevent what might be a huge mistake.

Think before they act. Hmm, that’s kind of like look before they leap, right? Sounds like a job for the Cliche-busters.

Sticks and stones may break my bones, but clots will never hurt me

You’ve probably seen “Ghostbusters” or at least heard the theme song. Maybe you even know about the Discovery Channel’s “Mythbusters.” But now there’s a new buster in town, and it eats platitudes for breakfast: Meet Cliche-busters, LOTME’s new recurring feature.

This week, Cliche-busters takes on “Two wrongs don’t make a right.” Yum.

We start with blood clots, which are bad. Doctors go to a lot of trouble to get rid of the things because they are dangerous. A blood clot, then, is a bodily function gone wrong.

Tornadoes are also bad. Out there in the world, these violently rotating columns of air can destroy buildings, toss large objects long distances, and inspire mediocre action movies. They are examples of nature gone wrong.

Seemingly, these two wrongs – blood clots and tornadoes – are not about to make a right. Has Cliche-busters bitten off more than it can chew?

Not according to Xiaoning Jiang of North Carolina State University, Raleigh, and his team of researchers. They’ve figured out a way to use a tiny ultrasonic tornado to break down clots in the brain. “Our new work uses vortex ultrasound, where the ultrasound waves have a helical wavefront. In other words, the ultrasound is swirling as it moves forward,” he said in a statement from the university.

Xiaoning Jiang and Chengzhi Shi

Their new tool’s single transducer is small enough to fit in a catheter, and its “vortex ultrasound-induced shear force has the potential to break down clots safely and improve the efficacy of thrombolysis,” they explained in the open-access journal Research.

The investigators used cow blood in a 3D-printed model of the cerebral venous sinus for the proof-of-concept study and were able to dissolve an acute blood clot in less than 30 minutes, compared with the 15-30 hours needed with a pharmaceutical intervention, according to the written statement.

Can you hear the sound of two wrongs making a right? We can, and that closes the curtain on this cliche.
 

With age does not come wisdom

We’ve all met this person before. The sort of person who takes a 10-minute IQ test on a shifty-looking website and then proceeds to brag about a 180 IQ until the heat death of the universe. The one who worships at the altar of Mensa. Yeah, that guy. They’re never as smart as they think they are, but they’ll never, ever admit it.

It’s not exactly a secret that IQ as a measurement of intelligence is highly overrated. A lot of scientists doubt we should bother measuring it at all. That said, a higher IQ is associated with greater success in academic and financial endeavors, so it’s not absolutely worthless. And if we’re stuck with it, we may as well study it.

That brings us neatly to new research published in Brain and Behavior. Most studies into IQ and self-estimated intelligence have focused on younger adults, and the author of this study was curious if the stereotype of young men inflating their IQ, a stereotype backed up by research, persisted into older adulthood. So she conducted a survey of 159 younger adults and 152 older adults to find out.

Wavebreakmedia Ltd/Thinkstock

The results in younger adults were not surprising: Younger men overestimated their actual IQ by 5-15 points, which tracks with previous research. We’re in for a bit of a surprise with the older adults, though, because the older men were more humble about their intelligence, with their estimation falling in line with their actual IQ. Older women, however, not so much. In fact, they overestimated their intelligence just as much as the younger men.

In addition, older women who perceived themselves as more attractive reported the highest self-estimated intelligence of all. That isn’t how intelligence works, but honestly, if Grandma’s out and about thinking she looks good and has the brains to go and win “Jeopardy!” do you really have the heart to tell her otherwise?
 

Fight temptation with empathy … and shoes

Relationships are tough. They all go through their respective ups and downs, but what happens when one person is feeling so down in the partnership that cheating comes to mind? Is there any way to stop it from happening?

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Well, a recent study suggests that there is, and it’s as simple as putting yourself in the other person’s shoes. By observing 408 heterosexual, monogamous participants in a series of experiments, psychologists in Israel and New York found that practicing empathy and “perspective taking” doesn’t necessarily stop people from cheating but it does reduces the desire.

People cheat on their significant others for many different reasons – men for a lack of sexual needs being met and women for shortfalls regarding emotional needs – but prioritizing the other person’s perspective gives the idea of being unfaithful a different view and could make one act differently, the investigators said.

Perspective taking also promotes other positive attributes to the relationship, such as the promotion of compassion and the feeling of being understood, lead author Gurit Birnbaum of Reichman University in Herzliya, Israel, said in a written statement. These things ultimately help couples navigate the rough patches and strengthen bonds, making them even less likely to cheat.

The researchers noted that even people in satisfying relationships do cheat, but this approach does encourage people to stop and think before they act. It could ultimately prevent what might be a huge mistake.

Think before they act. Hmm, that’s kind of like look before they leap, right? Sounds like a job for the Cliche-busters.

AURORA, COLO. – A combination of two over-the-counter herbal extracts – curcumin and qing dai – induced remissions in a significant proportion of patients with active ulcerative colitis (UC) in a small placebo-controlled trial.

Among 42 patients randomized on a 2:1 basis to receive either an enteric-coated pill containing 3 g of curcumin and qing-dai (CurQD) or placebo for 8 weeks, 43% of those assigned to receive the combination met the co-primary endpoint of a significant reduction in disease activity and objective evidence of response, compared with 8% of those assigned to placebo, reported Shomron Ben-Horin, MD, of Sheba Medical Center in Tel Aviv, Israel, and colleagues.

“In this randomized multicenter placebo-controlled trial, combination CurQD was found effective for inducing remission in active UC patients, including biologic-experienced patients,” they wrote in a scientific poster presented at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
 

Nice spice

Curcumin is a polyphenolic compound derived from the spice turmeric that has been shown to have antioxidative and anti-inflammatory properties. Qing-dai (QD), also known as indigo naturalis, has been used in traditional Chinese medicine as an anti-inflammatory. Both agents are available over the counter in the United States, and have been on the market in Israel as a combination since 2016, said coauthor Nir Salomon, a certified herbalist at Sheba Medical Center.

Neil Osterweil/MDedge News

“What we have here is a combination of these two compounds that are specifically sourced – the gut-directed curcumin, which we developed, and the specifically-sourced QD, and we use them in a specific protocol with a formulation suitable for moderate to severe disease,” he said in an interview.

Mr. Salomon and colleagues in Israel and in Athens, Greece, tested CurQD in a two-part trial. The first part was a 4-week open-label study of CurQD in 10 patients with active UC defined by a Simple Clinical Colitis Activity Index (SCCAI) score of 5 or greater and a modified Mayo endoscopic subscore of 2 or greater.

Part 2 was the placebo-controlled trial described before, with 42 patients with active UC. For 49% of these patients immunomodulatory and/or biologic therapies had failed to induce or maintain remissions.

A total of 43% of patients assigned to CurQD met the primary combined endpoint of a reduction in SCCAI of at least 3 points and objective evidence of response, consisting of either a Mayo endoscopic subscore improvement of 1 or greater, or at least 50% reduction in calprotectin.

In all, 85.7% of patients assigned to CurQD had a clinical response, compared with 30.7% of those assigned to placebo (P < .001).

In addition, 75% of patients on CurQD had endoscopic improvement, compared with 20% on placebo (P = .036), and more patients on the combined supplement had at least 50% reductions in calprotectin levels (46.4% vs. 15.4%, respectively), although the difference did not reach statistical significance.

Patients randomized to CurQD had significantly better resolution of rectal bleeding by day 12 (P value not shown).

Eight additional weeks of maintenance on curcumin alone resulted in 93% retention at week 16 of clinical response, 80% retention of remissions, and 40% maintenance of clinical biomarker responses.

CurQD, but not placebo, was associated with activation of the aryl-hydrocarbon receptor (AhR) pathway. AhR is a nuclear receptor that has been implicated as a mediator of inflammatory bowel disease.

“Induction of AhR merits further study as [a] potential treatment target in active UC,” the investigators wrote.
 

Small molecule

“This is a very promising and nicely conducted trial. Previously there are separate trials both determining potential mechanisms of action as well as efficacy of curcumin and Qing Dai separately in this population. This is a nice study that uses the combination in patients with mild to moderate UC,” said Ashwin N. Ananthakrishnan, MBBS, MPH, a gastroenterology physician and researcher at Massachusetts General Hospital in Boston.

“Immunosuppressive treatments are very effective in our patients with IBD but there remains concern (particularly for patients) about the consequences of immunosuppression including risk of treatment associated cancer. Thus, there is a lot of interest in rigorous studies of nonimmunosuppressive treatments that may still be effective in relieving objective inflammation (apart from just symptomatic improvement). This study provides a nice evidence base for that. There remain multiple limitations including small sample size, potential generalizability to other populations, and importantly whether the efficacy is driven by curcumin or Qing Dai,” he said in reply to a request for independent commentary.

Dr. Ananthakrishnan was not involved in the study.

“This is great work! We are also studying Qing Dai/indigo naturalis and have developed a single small molecule that works similarly to this therapy,” Matt Davidson, PhD, of Azora Therapeutics in Encino, Calif., said in an online chat section of the meeting website.

In a separate scientific poster presented at the meeting, Dr. Davidson and Julie Saiki, PhD, also from Azora, reported that their company is developing a novel synthetic small molecule prodrug of indirubin, an AhR agonist derived from indigo that is purported to maximize colonic exposure while minimizing systemic exposure.

In mouse models of colitis, oral administration of the prodrug significantly reduced Disease Activity Index and weight loss similar in magnitude to the active compound indirubin, they reported.

The study was supported by Sheba Medical Center. Mr. Salomon disclosed speaking fees from various companies and has received consulting fees and has an equity position in EvNature, the manufacturer of CurQD. Dr. Ananthakrishnan reported having no disclosures relative to the study. Dr. Davidson is CEO and cofounder of Avora Therapeutics.

AURORA, COLO. – A combination of two over-the-counter herbal extracts – curcumin and qing dai – induced remissions in a significant proportion of patients with active ulcerative colitis (UC) in a small placebo-controlled trial.

Among 42 patients randomized on a 2:1 basis to receive either an enteric-coated pill containing 3 g of curcumin and qing-dai (CurQD) or placebo for 8 weeks, 43% of those assigned to receive the combination met the co-primary endpoint of a significant reduction in disease activity and objective evidence of response, compared with 8% of those assigned to placebo, reported Shomron Ben-Horin, MD, of Sheba Medical Center in Tel Aviv, Israel, and colleagues.

“In this randomized multicenter placebo-controlled trial, combination CurQD was found effective for inducing remission in active UC patients, including biologic-experienced patients,” they wrote in a scientific poster presented at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
 

Nice spice

Curcumin is a polyphenolic compound derived from the spice turmeric that has been shown to have antioxidative and anti-inflammatory properties. Qing-dai (QD), also known as indigo naturalis, has been used in traditional Chinese medicine as an anti-inflammatory. Both agents are available over the counter in the United States, and have been on the market in Israel as a combination since 2016, said coauthor Nir Salomon, a certified herbalist at Sheba Medical Center.

Neil Osterweil/MDedge News

“What we have here is a combination of these two compounds that are specifically sourced – the gut-directed curcumin, which we developed, and the specifically-sourced QD, and we use them in a specific protocol with a formulation suitable for moderate to severe disease,” he said in an interview.

Mr. Salomon and colleagues in Israel and in Athens, Greece, tested CurQD in a two-part trial. The first part was a 4-week open-label study of CurQD in 10 patients with active UC defined by a Simple Clinical Colitis Activity Index (SCCAI) score of 5 or greater and a modified Mayo endoscopic subscore of 2 or greater.

Part 2 was the placebo-controlled trial described before, with 42 patients with active UC. For 49% of these patients immunomodulatory and/or biologic therapies had failed to induce or maintain remissions.

A total of 43% of patients assigned to CurQD met the primary combined endpoint of a reduction in SCCAI of at least 3 points and objective evidence of response, consisting of either a Mayo endoscopic subscore improvement of 1 or greater, or at least 50% reduction in calprotectin.

In all, 85.7% of patients assigned to CurQD had a clinical response, compared with 30.7% of those assigned to placebo (P < .001).

In addition, 75% of patients on CurQD had endoscopic improvement, compared with 20% on placebo (P = .036), and more patients on the combined supplement had at least 50% reductions in calprotectin levels (46.4% vs. 15.4%, respectively), although the difference did not reach statistical significance.

Patients randomized to CurQD had significantly better resolution of rectal bleeding by day 12 (P value not shown).

Eight additional weeks of maintenance on curcumin alone resulted in 93% retention at week 16 of clinical response, 80% retention of remissions, and 40% maintenance of clinical biomarker responses.

CurQD, but not placebo, was associated with activation of the aryl-hydrocarbon receptor (AhR) pathway. AhR is a nuclear receptor that has been implicated as a mediator of inflammatory bowel disease.

“Induction of AhR merits further study as [a] potential treatment target in active UC,” the investigators wrote.
 

Small molecule

“This is a very promising and nicely conducted trial. Previously there are separate trials both determining potential mechanisms of action as well as efficacy of curcumin and Qing Dai separately in this population. This is a nice study that uses the combination in patients with mild to moderate UC,” said Ashwin N. Ananthakrishnan, MBBS, MPH, a gastroenterology physician and researcher at Massachusetts General Hospital in Boston.

“Immunosuppressive treatments are very effective in our patients with IBD but there remains concern (particularly for patients) about the consequences of immunosuppression including risk of treatment associated cancer. Thus, there is a lot of interest in rigorous studies of nonimmunosuppressive treatments that may still be effective in relieving objective inflammation (apart from just symptomatic improvement). This study provides a nice evidence base for that. There remain multiple limitations including small sample size, potential generalizability to other populations, and importantly whether the efficacy is driven by curcumin or Qing Dai,” he said in reply to a request for independent commentary.

Dr. Ananthakrishnan was not involved in the study.

“This is great work! We are also studying Qing Dai/indigo naturalis and have developed a single small molecule that works similarly to this therapy,” Matt Davidson, PhD, of Azora Therapeutics in Encino, Calif., said in an online chat section of the meeting website.

In a separate scientific poster presented at the meeting, Dr. Davidson and Julie Saiki, PhD, also from Azora, reported that their company is developing a novel synthetic small molecule prodrug of indirubin, an AhR agonist derived from indigo that is purported to maximize colonic exposure while minimizing systemic exposure.

In mouse models of colitis, oral administration of the prodrug significantly reduced Disease Activity Index and weight loss similar in magnitude to the active compound indirubin, they reported.

The study was supported by Sheba Medical Center. Mr. Salomon disclosed speaking fees from various companies and has received consulting fees and has an equity position in EvNature, the manufacturer of CurQD. Dr. Ananthakrishnan reported having no disclosures relative to the study. Dr. Davidson is CEO and cofounder of Avora Therapeutics.

AURORA, COLO. – A combination of two over-the-counter herbal extracts – curcumin and qing dai – induced remissions in a significant proportion of patients with active ulcerative colitis (UC) in a small placebo-controlled trial.

Among 42 patients randomized on a 2:1 basis to receive either an enteric-coated pill containing 3 g of curcumin and qing-dai (CurQD) or placebo for 8 weeks, 43% of those assigned to receive the combination met the co-primary endpoint of a significant reduction in disease activity and objective evidence of response, compared with 8% of those assigned to placebo, reported Shomron Ben-Horin, MD, of Sheba Medical Center in Tel Aviv, Israel, and colleagues.

“In this randomized multicenter placebo-controlled trial, combination CurQD was found effective for inducing remission in active UC patients, including biologic-experienced patients,” they wrote in a scientific poster presented at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.
 

Nice spice

Curcumin is a polyphenolic compound derived from the spice turmeric that has been shown to have antioxidative and anti-inflammatory properties. Qing-dai (QD), also known as indigo naturalis, has been used in traditional Chinese medicine as an anti-inflammatory. Both agents are available over the counter in the United States, and have been on the market in Israel as a combination since 2016, said coauthor Nir Salomon, a certified herbalist at Sheba Medical Center.

Neil Osterweil/MDedge News

“What we have here is a combination of these two compounds that are specifically sourced – the gut-directed curcumin, which we developed, and the specifically-sourced QD, and we use them in a specific protocol with a formulation suitable for moderate to severe disease,” he said in an interview.

Mr. Salomon and colleagues in Israel and in Athens, Greece, tested CurQD in a two-part trial. The first part was a 4-week open-label study of CurQD in 10 patients with active UC defined by a Simple Clinical Colitis Activity Index (SCCAI) score of 5 or greater and a modified Mayo endoscopic subscore of 2 or greater.

Part 2 was the placebo-controlled trial described before, with 42 patients with active UC. For 49% of these patients immunomodulatory and/or biologic therapies had failed to induce or maintain remissions.

A total of 43% of patients assigned to CurQD met the primary combined endpoint of a reduction in SCCAI of at least 3 points and objective evidence of response, consisting of either a Mayo endoscopic subscore improvement of 1 or greater, or at least 50% reduction in calprotectin.

In all, 85.7% of patients assigned to CurQD had a clinical response, compared with 30.7% of those assigned to placebo (P < .001).

In addition, 75% of patients on CurQD had endoscopic improvement, compared with 20% on placebo (P = .036), and more patients on the combined supplement had at least 50% reductions in calprotectin levels (46.4% vs. 15.4%, respectively), although the difference did not reach statistical significance.

Patients randomized to CurQD had significantly better resolution of rectal bleeding by day 12 (P value not shown).

Eight additional weeks of maintenance on curcumin alone resulted in 93% retention at week 16 of clinical response, 80% retention of remissions, and 40% maintenance of clinical biomarker responses.

CurQD, but not placebo, was associated with activation of the aryl-hydrocarbon receptor (AhR) pathway. AhR is a nuclear receptor that has been implicated as a mediator of inflammatory bowel disease.

“Induction of AhR merits further study as [a] potential treatment target in active UC,” the investigators wrote.
 

Small molecule

“This is a very promising and nicely conducted trial. Previously there are separate trials both determining potential mechanisms of action as well as efficacy of curcumin and Qing Dai separately in this population. This is a nice study that uses the combination in patients with mild to moderate UC,” said Ashwin N. Ananthakrishnan, MBBS, MPH, a gastroenterology physician and researcher at Massachusetts General Hospital in Boston.

“Immunosuppressive treatments are very effective in our patients with IBD but there remains concern (particularly for patients) about the consequences of immunosuppression including risk of treatment associated cancer. Thus, there is a lot of interest in rigorous studies of nonimmunosuppressive treatments that may still be effective in relieving objective inflammation (apart from just symptomatic improvement). This study provides a nice evidence base for that. There remain multiple limitations including small sample size, potential generalizability to other populations, and importantly whether the efficacy is driven by curcumin or Qing Dai,” he said in reply to a request for independent commentary.

Dr. Ananthakrishnan was not involved in the study.

“This is great work! We are also studying Qing Dai/indigo naturalis and have developed a single small molecule that works similarly to this therapy,” Matt Davidson, PhD, of Azora Therapeutics in Encino, Calif., said in an online chat section of the meeting website.

In a separate scientific poster presented at the meeting, Dr. Davidson and Julie Saiki, PhD, also from Azora, reported that their company is developing a novel synthetic small molecule prodrug of indirubin, an AhR agonist derived from indigo that is purported to maximize colonic exposure while minimizing systemic exposure.

In mouse models of colitis, oral administration of the prodrug significantly reduced Disease Activity Index and weight loss similar in magnitude to the active compound indirubin, they reported.

The study was supported by Sheba Medical Center. Mr. Salomon disclosed speaking fees from various companies and has received consulting fees and has an equity position in EvNature, the manufacturer of CurQD. Dr. Ananthakrishnan reported having no disclosures relative to the study. Dr. Davidson is CEO and cofounder of Avora Therapeutics.

A 12-month program of moderate to vigorous exercise reduced the risk of type 2 diabetes by approximately 50% in adults with obesity over 10 years, according to a new analysis of a study.

“Physical exercise combined with diet restriction has been proven to be effective in prevention of diabetes. However, the long-term effect of exercise on prevention of diabetes, and the difference of exercise intensity in prevention of diabetes have not been well studied,” said corresponding author Xiaoying Li, MD, of Zhongshan Hospital, Fudan University, Shanghai, in an interview.

In the research letter published in JAMA Internal Medicine, Dr. Li and colleagues analyzed the results of a study of 220 adults with central obesity and nonalcoholic fatty liver disease, but no incident diabetes, randomized to a 12-month program of vigorous exercise (73 patients), moderate aerobic exercise (73 patients) or no exercise (74 patients).

A total of 208 participants completed the 1-year intervention; of these, 195 and 178 remained to provide data at 2 years and 10 years, respectively. The mean age of the participants was 53.9 years, 32.3% were male, and the mean waist circumference was 96.1 cm at baseline.

The cumulative incidence of type 2 diabetes in the vigorous exercise, moderate exercise, and nonexercise groups was 2.1 per 100 person-years 1.9 per 100 person-years, and 4.1 per 100 person-years, respectively, over the 10-year follow-up period. This translated to a reduction in type 2 diabetes risk of 49% in the vigorous exercise group and 53% in the moderate exercise group compared with the nonexercise group.

In addition, individuals in the vigorous and moderate exercise groups significantly reduced their HbA1c and waist circumference compared with the nonexercisers. Levels of plasma fasting glucose and weight regain were lower in both exercise groups compared with nonexercisers, but these differences were not significant.

The exercise intervention was described in a 2016 study, which was also published in JAMA Internal Medicine. That study’s purpose was to compare the effects of exercise on patients with nonalcoholic fatty liver disease. Participants were coached and supervised for their exercise programs. The program for the vigorous group involved jogging for 150 minutes per week at 65%-80% of maximum heart rate for 6 months and brisk walking 150 minutes per week at 45%-55% of maximum heart rate for another 6 months. The program for the moderate exercise group involved brisk walking 150 minutes per week for 12 months.

Both exercise groups showed a trend towards higher levels of leisure time physical activity after 10 years compared with the nonexercise groups, although the difference was not significant.

The main limitation of the study was that incident prediabetes was not prespecified, which may have led to some confounding, the researchers noted. In addition, the participants were highly supervised for a 12-month program only. However, the results support the long-term value of physical exercise as a method of obesity management and to delay progression to type 2 diabetes in obese individuals, they said. Vigorous and moderate aerobic exercise programs could be implemented for this patient population, they concluded.

“Surprisingly, our findings demonstrated that a 12-month vigorous aerobic exercise or moderate aerobic exercise could significantly reduce the risk of incident diabetes by 50% over the 10-year follow-up,” Dr. Li said in an interview. The results suggest that physical exercise for some period of time can produce a long-term beneficial effect in prevention of type 2 diabetes, he said.

Potential barriers to the routine use of an exercise intervention in patients with obesity include the unwillingness of this population to engage in vigorous exercise, and the potential for musculoskeletal injury, said Dr. Li. In these cases, obese patients should be encouraged to pursue moderate exercise, Dr. Li said.

Looking ahead, more research is needed to examine the potential mechanism behind the effect of exercise on diabetes prevention, said Dr. Li.

Findings fill gap in long-term outcome data

The current study is important because of the long-term follow-up data, said Jill Kanaley, PhD, professor and interim chair of nutrition and exercise physiology at the University of Missouri, in an interview. “We seldom follow up on our training studies, thus it is important to see if there is any long-term impact of these interventions,” she said.

Dr. Kanaley said she was surprised to see the residual benefits of the exercise intervention 10 years later.

“We often wonder how long the impact of the exercise training will stay with someone so that they continue to exercise and watch their weight; this study seems to indicate that there is an educational component that stays with them,” she said.

The main clinical takeaway from the current study was the minimal weight gain over time, Dr. Kanaley said.

Although time may be a barrier to the routine use of an exercise intervention, patients have to realize that they can usually find the time, especially given the multiple benefits, said Dr. Kanaley. “The exercise interventions provide more benefits than just weight control and glucose levels,” she said.

“The 30-60 minutes of exercise does not have to come all at the same time,” Dr. Kanaley noted. “It could be three 15-minute bouts of exercise/physical activity to get their 45 minutes in,” she noted. Exercise does not have to be heavy vigorous exercise, even walking is beneficial, she said. For people who complain of boredom with an exercise routine, Dr. Kanaley encourages mixing it up, with activities such as different exercise classes, running, or walking on a different day of any given week.

Although the current study was conducted in China, the findings may translate to a U.S. population, Dr. Kanaley said in an interview. However, “frequently our Western diet is less healthy than the traditional Chinese diet. This may have provided an immeasurable benefit to these subjects,” although study participants did not make specific adjustments to their diets, she said.  

Additional research is needed to confirm the findings, said Dr. Kanaley. “Ideally, the study should be repeated in a population with a Western diet,” she noted.

Next steps for research include maintenance of activity

Evidence on the long-term benefits of exercise programs is limited, said Amanda Paluch, PhD, a physical activity epidemiologist at the University of Massachusetts, Amherst, in an interview.

“Chronic diseases such as diabetes can take years to develop, so understanding these important health outcomes requires years of follow-up. This study followed their study participants for 10 years, which gives us a nice glimpse of the long-term benefits of exercise training on diabetes prevention,” she said.

Data from previous observational studies of individuals’ current activity levels (without an intervention) suggest that adults who are more physically active have a lower risk of diabetes over time, said Dr. Paluch. However, the current study is one of the few with rigorous exercise interventions with extensive follow-up on diabetes risk, and it provides important evidence that a 12-month structured exercise program in inactive adults with obesity can result in meaningful long-term health benefits by lowering the risk of diabetes, she said.

“The individuals in the current study participated in a structured exercise program where their exercise sessions were supervised and coached,” Dr. Paluch noted. “Having a personalized coach may not be within the budget or time constraints for many people,” she said. Her message to clinicians for their patients: “When looking to start an exercise routine, identify an activity you enjoy and find feasible to fit into your existing life and schedule,” she said.

“Although this study was conducted in China, the results are meaningful for the U.S. population, as we would expect the physiological benefit of exercise to be consistent across various populations,” Dr. Paluch said. “However, there are certainly differences across countries at the individual level to the larger community-wide level that may influence a person’s ability to maintain physical activity and prevent diabetes, so replicating similar studies in other countries, including the U.S., would be of value.” 

“Additionally, we need more research on how to encourage maintenance of physical activity in the long-term, after the initial exercise program is over,” she said.

“From this current study, we cannot tease out whether diabetes risk is reduced because of the 12-month exercise intervention or the benefit is from maintaining physical activity regularly over the 10 years of follow-up, or a combination of the two,” said Dr. Paluch. Future studies should consider teasing out participants who were only active during the exercise intervention, then ceased being active vs. participants who continued with vigorous activity long-term, she said.

The study was supported by the National Nature Science Foundation, the National Key Research and Development Program of China, and the Shanghai Municipal Science and Technology Major Project. The researchers, Dr. Kanaley, and Dr. Paluch had no financial conflicts to disclose.

A 12-month program of moderate to vigorous exercise reduced the risk of type 2 diabetes by approximately 50% in adults with obesity over 10 years, according to a new analysis of a study.

“Physical exercise combined with diet restriction has been proven to be effective in prevention of diabetes. However, the long-term effect of exercise on prevention of diabetes, and the difference of exercise intensity in prevention of diabetes have not been well studied,” said corresponding author Xiaoying Li, MD, of Zhongshan Hospital, Fudan University, Shanghai, in an interview.

In the research letter published in JAMA Internal Medicine, Dr. Li and colleagues analyzed the results of a study of 220 adults with central obesity and nonalcoholic fatty liver disease, but no incident diabetes, randomized to a 12-month program of vigorous exercise (73 patients), moderate aerobic exercise (73 patients) or no exercise (74 patients).

A total of 208 participants completed the 1-year intervention; of these, 195 and 178 remained to provide data at 2 years and 10 years, respectively. The mean age of the participants was 53.9 years, 32.3% were male, and the mean waist circumference was 96.1 cm at baseline.

The cumulative incidence of type 2 diabetes in the vigorous exercise, moderate exercise, and nonexercise groups was 2.1 per 100 person-years 1.9 per 100 person-years, and 4.1 per 100 person-years, respectively, over the 10-year follow-up period. This translated to a reduction in type 2 diabetes risk of 49% in the vigorous exercise group and 53% in the moderate exercise group compared with the nonexercise group.

In addition, individuals in the vigorous and moderate exercise groups significantly reduced their HbA1c and waist circumference compared with the nonexercisers. Levels of plasma fasting glucose and weight regain were lower in both exercise groups compared with nonexercisers, but these differences were not significant.

The exercise intervention was described in a 2016 study, which was also published in JAMA Internal Medicine. That study’s purpose was to compare the effects of exercise on patients with nonalcoholic fatty liver disease. Participants were coached and supervised for their exercise programs. The program for the vigorous group involved jogging for 150 minutes per week at 65%-80% of maximum heart rate for 6 months and brisk walking 150 minutes per week at 45%-55% of maximum heart rate for another 6 months. The program for the moderate exercise group involved brisk walking 150 minutes per week for 12 months.

Both exercise groups showed a trend towards higher levels of leisure time physical activity after 10 years compared with the nonexercise groups, although the difference was not significant.

The main limitation of the study was that incident prediabetes was not prespecified, which may have led to some confounding, the researchers noted. In addition, the participants were highly supervised for a 12-month program only. However, the results support the long-term value of physical exercise as a method of obesity management and to delay progression to type 2 diabetes in obese individuals, they said. Vigorous and moderate aerobic exercise programs could be implemented for this patient population, they concluded.

“Surprisingly, our findings demonstrated that a 12-month vigorous aerobic exercise or moderate aerobic exercise could significantly reduce the risk of incident diabetes by 50% over the 10-year follow-up,” Dr. Li said in an interview. The results suggest that physical exercise for some period of time can produce a long-term beneficial effect in prevention of type 2 diabetes, he said.

Potential barriers to the routine use of an exercise intervention in patients with obesity include the unwillingness of this population to engage in vigorous exercise, and the potential for musculoskeletal injury, said Dr. Li. In these cases, obese patients should be encouraged to pursue moderate exercise, Dr. Li said.

Looking ahead, more research is needed to examine the potential mechanism behind the effect of exercise on diabetes prevention, said Dr. Li.

Findings fill gap in long-term outcome data

The current study is important because of the long-term follow-up data, said Jill Kanaley, PhD, professor and interim chair of nutrition and exercise physiology at the University of Missouri, in an interview. “We seldom follow up on our training studies, thus it is important to see if there is any long-term impact of these interventions,” she said.

Dr. Kanaley said she was surprised to see the residual benefits of the exercise intervention 10 years later.

“We often wonder how long the impact of the exercise training will stay with someone so that they continue to exercise and watch their weight; this study seems to indicate that there is an educational component that stays with them,” she said.

The main clinical takeaway from the current study was the minimal weight gain over time, Dr. Kanaley said.

Although time may be a barrier to the routine use of an exercise intervention, patients have to realize that they can usually find the time, especially given the multiple benefits, said Dr. Kanaley. “The exercise interventions provide more benefits than just weight control and glucose levels,” she said.

“The 30-60 minutes of exercise does not have to come all at the same time,” Dr. Kanaley noted. “It could be three 15-minute bouts of exercise/physical activity to get their 45 minutes in,” she noted. Exercise does not have to be heavy vigorous exercise, even walking is beneficial, she said. For people who complain of boredom with an exercise routine, Dr. Kanaley encourages mixing it up, with activities such as different exercise classes, running, or walking on a different day of any given week.

Although the current study was conducted in China, the findings may translate to a U.S. population, Dr. Kanaley said in an interview. However, “frequently our Western diet is less healthy than the traditional Chinese diet. This may have provided an immeasurable benefit to these subjects,” although study participants did not make specific adjustments to their diets, she said.  

Additional research is needed to confirm the findings, said Dr. Kanaley. “Ideally, the study should be repeated in a population with a Western diet,” she noted.

Next steps for research include maintenance of activity

Evidence on the long-term benefits of exercise programs is limited, said Amanda Paluch, PhD, a physical activity epidemiologist at the University of Massachusetts, Amherst, in an interview.

“Chronic diseases such as diabetes can take years to develop, so understanding these important health outcomes requires years of follow-up. This study followed their study participants for 10 years, which gives us a nice glimpse of the long-term benefits of exercise training on diabetes prevention,” she said.

Data from previous observational studies of individuals’ current activity levels (without an intervention) suggest that adults who are more physically active have a lower risk of diabetes over time, said Dr. Paluch. However, the current study is one of the few with rigorous exercise interventions with extensive follow-up on diabetes risk, and it provides important evidence that a 12-month structured exercise program in inactive adults with obesity can result in meaningful long-term health benefits by lowering the risk of diabetes, she said.

“The individuals in the current study participated in a structured exercise program where their exercise sessions were supervised and coached,” Dr. Paluch noted. “Having a personalized coach may not be within the budget or time constraints for many people,” she said. Her message to clinicians for their patients: “When looking to start an exercise routine, identify an activity you enjoy and find feasible to fit into your existing life and schedule,” she said.

“Although this study was conducted in China, the results are meaningful for the U.S. population, as we would expect the physiological benefit of exercise to be consistent across various populations,” Dr. Paluch said. “However, there are certainly differences across countries at the individual level to the larger community-wide level that may influence a person’s ability to maintain physical activity and prevent diabetes, so replicating similar studies in other countries, including the U.S., would be of value.” 

“Additionally, we need more research on how to encourage maintenance of physical activity in the long-term, after the initial exercise program is over,” she said.

“From this current study, we cannot tease out whether diabetes risk is reduced because of the 12-month exercise intervention or the benefit is from maintaining physical activity regularly over the 10 years of follow-up, or a combination of the two,” said Dr. Paluch. Future studies should consider teasing out participants who were only active during the exercise intervention, then ceased being active vs. participants who continued with vigorous activity long-term, she said.

The study was supported by the National Nature Science Foundation, the National Key Research and Development Program of China, and the Shanghai Municipal Science and Technology Major Project. The researchers, Dr. Kanaley, and Dr. Paluch had no financial conflicts to disclose.

A 12-month program of moderate to vigorous exercise reduced the risk of type 2 diabetes by approximately 50% in adults with obesity over 10 years, according to a new analysis of a study.

“Physical exercise combined with diet restriction has been proven to be effective in prevention of diabetes. However, the long-term effect of exercise on prevention of diabetes, and the difference of exercise intensity in prevention of diabetes have not been well studied,” said corresponding author Xiaoying Li, MD, of Zhongshan Hospital, Fudan University, Shanghai, in an interview.

In the research letter published in JAMA Internal Medicine, Dr. Li and colleagues analyzed the results of a study of 220 adults with central obesity and nonalcoholic fatty liver disease, but no incident diabetes, randomized to a 12-month program of vigorous exercise (73 patients), moderate aerobic exercise (73 patients) or no exercise (74 patients).

A total of 208 participants completed the 1-year intervention; of these, 195 and 178 remained to provide data at 2 years and 10 years, respectively. The mean age of the participants was 53.9 years, 32.3% were male, and the mean waist circumference was 96.1 cm at baseline.

The cumulative incidence of type 2 diabetes in the vigorous exercise, moderate exercise, and nonexercise groups was 2.1 per 100 person-years 1.9 per 100 person-years, and 4.1 per 100 person-years, respectively, over the 10-year follow-up period. This translated to a reduction in type 2 diabetes risk of 49% in the vigorous exercise group and 53% in the moderate exercise group compared with the nonexercise group.

In addition, individuals in the vigorous and moderate exercise groups significantly reduced their HbA1c and waist circumference compared with the nonexercisers. Levels of plasma fasting glucose and weight regain were lower in both exercise groups compared with nonexercisers, but these differences were not significant.

The exercise intervention was described in a 2016 study, which was also published in JAMA Internal Medicine. That study’s purpose was to compare the effects of exercise on patients with nonalcoholic fatty liver disease. Participants were coached and supervised for their exercise programs. The program for the vigorous group involved jogging for 150 minutes per week at 65%-80% of maximum heart rate for 6 months and brisk walking 150 minutes per week at 45%-55% of maximum heart rate for another 6 months. The program for the moderate exercise group involved brisk walking 150 minutes per week for 12 months.

Both exercise groups showed a trend towards higher levels of leisure time physical activity after 10 years compared with the nonexercise groups, although the difference was not significant.

The main limitation of the study was that incident prediabetes was not prespecified, which may have led to some confounding, the researchers noted. In addition, the participants were highly supervised for a 12-month program only. However, the results support the long-term value of physical exercise as a method of obesity management and to delay progression to type 2 diabetes in obese individuals, they said. Vigorous and moderate aerobic exercise programs could be implemented for this patient population, they concluded.

“Surprisingly, our findings demonstrated that a 12-month vigorous aerobic exercise or moderate aerobic exercise could significantly reduce the risk of incident diabetes by 50% over the 10-year follow-up,” Dr. Li said in an interview. The results suggest that physical exercise for some period of time can produce a long-term beneficial effect in prevention of type 2 diabetes, he said.

Potential barriers to the routine use of an exercise intervention in patients with obesity include the unwillingness of this population to engage in vigorous exercise, and the potential for musculoskeletal injury, said Dr. Li. In these cases, obese patients should be encouraged to pursue moderate exercise, Dr. Li said.

Looking ahead, more research is needed to examine the potential mechanism behind the effect of exercise on diabetes prevention, said Dr. Li.

Findings fill gap in long-term outcome data

The current study is important because of the long-term follow-up data, said Jill Kanaley, PhD, professor and interim chair of nutrition and exercise physiology at the University of Missouri, in an interview. “We seldom follow up on our training studies, thus it is important to see if there is any long-term impact of these interventions,” she said.

Dr. Kanaley said she was surprised to see the residual benefits of the exercise intervention 10 years later.

“We often wonder how long the impact of the exercise training will stay with someone so that they continue to exercise and watch their weight; this study seems to indicate that there is an educational component that stays with them,” she said.

The main clinical takeaway from the current study was the minimal weight gain over time, Dr. Kanaley said.

Although time may be a barrier to the routine use of an exercise intervention, patients have to realize that they can usually find the time, especially given the multiple benefits, said Dr. Kanaley. “The exercise interventions provide more benefits than just weight control and glucose levels,” she said.

“The 30-60 minutes of exercise does not have to come all at the same time,” Dr. Kanaley noted. “It could be three 15-minute bouts of exercise/physical activity to get their 45 minutes in,” she noted. Exercise does not have to be heavy vigorous exercise, even walking is beneficial, she said. For people who complain of boredom with an exercise routine, Dr. Kanaley encourages mixing it up, with activities such as different exercise classes, running, or walking on a different day of any given week.

Although the current study was conducted in China, the findings may translate to a U.S. population, Dr. Kanaley said in an interview. However, “frequently our Western diet is less healthy than the traditional Chinese diet. This may have provided an immeasurable benefit to these subjects,” although study participants did not make specific adjustments to their diets, she said.  

Additional research is needed to confirm the findings, said Dr. Kanaley. “Ideally, the study should be repeated in a population with a Western diet,” she noted.

Next steps for research include maintenance of activity

Evidence on the long-term benefits of exercise programs is limited, said Amanda Paluch, PhD, a physical activity epidemiologist at the University of Massachusetts, Amherst, in an interview.

“Chronic diseases such as diabetes can take years to develop, so understanding these important health outcomes requires years of follow-up. This study followed their study participants for 10 years, which gives us a nice glimpse of the long-term benefits of exercise training on diabetes prevention,” she said.

Data from previous observational studies of individuals’ current activity levels (without an intervention) suggest that adults who are more physically active have a lower risk of diabetes over time, said Dr. Paluch. However, the current study is one of the few with rigorous exercise interventions with extensive follow-up on diabetes risk, and it provides important evidence that a 12-month structured exercise program in inactive adults with obesity can result in meaningful long-term health benefits by lowering the risk of diabetes, she said.

“The individuals in the current study participated in a structured exercise program where their exercise sessions were supervised and coached,” Dr. Paluch noted. “Having a personalized coach may not be within the budget or time constraints for many people,” she said. Her message to clinicians for their patients: “When looking to start an exercise routine, identify an activity you enjoy and find feasible to fit into your existing life and schedule,” she said.

“Although this study was conducted in China, the results are meaningful for the U.S. population, as we would expect the physiological benefit of exercise to be consistent across various populations,” Dr. Paluch said. “However, there are certainly differences across countries at the individual level to the larger community-wide level that may influence a person’s ability to maintain physical activity and prevent diabetes, so replicating similar studies in other countries, including the U.S., would be of value.” 

“Additionally, we need more research on how to encourage maintenance of physical activity in the long-term, after the initial exercise program is over,” she said.

“From this current study, we cannot tease out whether diabetes risk is reduced because of the 12-month exercise intervention or the benefit is from maintaining physical activity regularly over the 10 years of follow-up, or a combination of the two,” said Dr. Paluch. Future studies should consider teasing out participants who were only active during the exercise intervention, then ceased being active vs. participants who continued with vigorous activity long-term, she said.

The study was supported by the National Nature Science Foundation, the National Key Research and Development Program of China, and the Shanghai Municipal Science and Technology Major Project. The researchers, Dr. Kanaley, and Dr. Paluch had no financial conflicts to disclose.

Running does not appear to cause sustained wear and tear of healthy knee cartilage, with research suggesting that the small, short-term changes to cartilage after a run reverse within hours.

A systematic review and meta-analysis published in the most recent issue of Osteoarthritis and Cartilage presents the findings involving 396 adults, which compared the “before” and “after” state of healthy knee cartilage in runners.

pojoslaw/Thinkstock

Running is often thought to be detrimental to joint health, wrote Sally Coburn, PhD candidate at the La Trobe Sport & Exercise Medicine Research Centre at La Trobe University in Melbourne and coauthors, but this perception is not supported by evidence.

For the analysis, the researchers included studies that looked at either knee or hip cartilage using MRI to assess its size, shape, structure, and/or composition both in the 48 hours before a single bout of running and in the 48 hours after. The analysis aimed to include adults with or at risk of osteoarthritis, but only 57 of the 446 knees in the analysis fit these criteria.

In studies where participants underwent MRI within 20 minutes of running, there was an immediate postrun decrease in the volume of cartilage, ranging from –3.3% for weight-bearing femoral cartilage to –4.1% for tibial cartilage volume. This also revealed a decrease in T1 and T2 relaxation times, which are specialized MRI measures that reflect the composition of cartilage and which can indicate a breakdown of cartilage structure in the case of diseases such as arthritis.

Reversal of short-term cartilage changes

However, within 48 hours of the run, data from studies that repeated the MRIs more than once after the initial prerun scan suggested these changes reversed back to prerun levels.

“We were able to pool delayed T2 relaxation time measures from studies that repeated scans of the same participants 60 minutes and 91 minutes post-run and found no effect of running on tibiofemoral joint cartilage composition,” the authors write.

For example, one study in marathon runners found no difference in cartilage thickness in the tibiofemoral joint between baseline and at 2-10 hours and 12 hours after the marathon. Another showed the immediate post-run decrease in patellofemoral joint cartilage thickness had reverted back to prerun levels when the scan was repeated 24 hours after the run.

“The changes are very minimal and not inconsistent with what’s expected for your cartilage which is functioning normally,” Ms. Coburn told this news organization.

Sparse data in people with osteoarthritis

The authors said there were not enough data from individuals with osteoarthritis to be able to pool and quantify their cartilage changes. However, one study in the analysis found that cartilage lesions in people considered at risk of osteoarthritis because of prior anterior cruciate ligament reconstruction were unchanged after running.

Another suggested that the decrease in femoral cartilage volume recorded at 15 minutes persisted at 45 minutes, while a separate study found significantly increased T2 relaxation times at 45 minutes after a run in those with knee osteoarthritis but not in those without osteoarthritis.

Senior author Adam Culvenor, PhD, senior research fellow at the La Trobe Centre, said their analysis suggested running was healthy, with small changes in cartilage that resolve quickly, but “we really don’t know yet if running is safe for people with osteoarthritis,” he said. “We need much more work in that space.”

Overall, the study evidence was rated as being of low certainty, which Dr. Coburn said was related to the small numbers in each study, which in turn relates to the cost and logistical challenges of the specialized MRI scan used.

“Study of a repeated exposure over a long duration of time on a disease that has a long natural history, like osteoarthritis, is challenging in that most funding agencies will not fund studies longer than 5 years,” Grace Hsiao-Wei Lo, MD, of the department of immunology, allergy, and rheumatology at the Baylor College of Medicine in Houston, said in an email.

Dr. Lo, who was not involved with this review and meta-analysis, said there are still concerns about the effect of running on knee osteoarthritis among those with the disease, although there are some data to suggest that among those who self-select to run, there are no negative outcomes for the knee.

An accompanying editorial noted that research into the effect of running on those with osteoarthritis was still in its infancy. “This would help to guide clinical practice on how to support people with osteoarthritis, with regard to accessing the health benefits of running participation,” write Jean-Francois Esculier, PT, PhD, from the University of British Columbia, Vancouver, and Christian Barton, PhD, with the La Trobe Centre, pointing out there were a lack of evidence-based clinical recommendations for people with osteoarthritis who want to start or continue running.

It’s a question that PhD candidate Michaela Khan, MSc, is trying to answer at the University of British Columbia. “Our lab did a pilot study for my current study now, and they found that osteoarthritic cartilage took a little bit longer to recover than their healthy counterparts,” Ms. Khan said. Her research is suggesting that people with osteoarthritis not only can run, but even those with severe disease, who might be candidates for knee replacement, can run long distances.

Commenting on the analysis, Ms. Khan said the main take-home message was that healthy cartilage seems to recover after running, and that there is not an ongoing effect of ‘wear and tear.’

“That’s changing the narrative that if you keep running, it will wear away your cartilage, it’ll hurt your knees,” she said. “Now, we have a good synthesis of scientific evidence to prove maybe otherwise.”

Ms. Coburn and Dr. Culvenor report grant support from the National Health & Medical Research Council of Australia, and another author reports grant support from the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors, as well as Dr. Lo and Ms. Khan, report relevant financial relationships.
 

Running does not appear to cause sustained wear and tear of healthy knee cartilage, with research suggesting that the small, short-term changes to cartilage after a run reverse within hours.

A systematic review and meta-analysis published in the most recent issue of Osteoarthritis and Cartilage presents the findings involving 396 adults, which compared the “before” and “after” state of healthy knee cartilage in runners.

pojoslaw/Thinkstock

Running is often thought to be detrimental to joint health, wrote Sally Coburn, PhD candidate at the La Trobe Sport & Exercise Medicine Research Centre at La Trobe University in Melbourne and coauthors, but this perception is not supported by evidence.

For the analysis, the researchers included studies that looked at either knee or hip cartilage using MRI to assess its size, shape, structure, and/or composition both in the 48 hours before a single bout of running and in the 48 hours after. The analysis aimed to include adults with or at risk of osteoarthritis, but only 57 of the 446 knees in the analysis fit these criteria.

In studies where participants underwent MRI within 20 minutes of running, there was an immediate postrun decrease in the volume of cartilage, ranging from –3.3% for weight-bearing femoral cartilage to –4.1% for tibial cartilage volume. This also revealed a decrease in T1 and T2 relaxation times, which are specialized MRI measures that reflect the composition of cartilage and which can indicate a breakdown of cartilage structure in the case of diseases such as arthritis.

Reversal of short-term cartilage changes

However, within 48 hours of the run, data from studies that repeated the MRIs more than once after the initial prerun scan suggested these changes reversed back to prerun levels.

“We were able to pool delayed T2 relaxation time measures from studies that repeated scans of the same participants 60 minutes and 91 minutes post-run and found no effect of running on tibiofemoral joint cartilage composition,” the authors write.

For example, one study in marathon runners found no difference in cartilage thickness in the tibiofemoral joint between baseline and at 2-10 hours and 12 hours after the marathon. Another showed the immediate post-run decrease in patellofemoral joint cartilage thickness had reverted back to prerun levels when the scan was repeated 24 hours after the run.

“The changes are very minimal and not inconsistent with what’s expected for your cartilage which is functioning normally,” Ms. Coburn told this news organization.

Sparse data in people with osteoarthritis

The authors said there were not enough data from individuals with osteoarthritis to be able to pool and quantify their cartilage changes. However, one study in the analysis found that cartilage lesions in people considered at risk of osteoarthritis because of prior anterior cruciate ligament reconstruction were unchanged after running.

Another suggested that the decrease in femoral cartilage volume recorded at 15 minutes persisted at 45 minutes, while a separate study found significantly increased T2 relaxation times at 45 minutes after a run in those with knee osteoarthritis but not in those without osteoarthritis.

Senior author Adam Culvenor, PhD, senior research fellow at the La Trobe Centre, said their analysis suggested running was healthy, with small changes in cartilage that resolve quickly, but “we really don’t know yet if running is safe for people with osteoarthritis,” he said. “We need much more work in that space.”

Overall, the study evidence was rated as being of low certainty, which Dr. Coburn said was related to the small numbers in each study, which in turn relates to the cost and logistical challenges of the specialized MRI scan used.

“Study of a repeated exposure over a long duration of time on a disease that has a long natural history, like osteoarthritis, is challenging in that most funding agencies will not fund studies longer than 5 years,” Grace Hsiao-Wei Lo, MD, of the department of immunology, allergy, and rheumatology at the Baylor College of Medicine in Houston, said in an email.

Dr. Lo, who was not involved with this review and meta-analysis, said there are still concerns about the effect of running on knee osteoarthritis among those with the disease, although there are some data to suggest that among those who self-select to run, there are no negative outcomes for the knee.

An accompanying editorial noted that research into the effect of running on those with osteoarthritis was still in its infancy. “This would help to guide clinical practice on how to support people with osteoarthritis, with regard to accessing the health benefits of running participation,” write Jean-Francois Esculier, PT, PhD, from the University of British Columbia, Vancouver, and Christian Barton, PhD, with the La Trobe Centre, pointing out there were a lack of evidence-based clinical recommendations for people with osteoarthritis who want to start or continue running.

It’s a question that PhD candidate Michaela Khan, MSc, is trying to answer at the University of British Columbia. “Our lab did a pilot study for my current study now, and they found that osteoarthritic cartilage took a little bit longer to recover than their healthy counterparts,” Ms. Khan said. Her research is suggesting that people with osteoarthritis not only can run, but even those with severe disease, who might be candidates for knee replacement, can run long distances.

Commenting on the analysis, Ms. Khan said the main take-home message was that healthy cartilage seems to recover after running, and that there is not an ongoing effect of ‘wear and tear.’

“That’s changing the narrative that if you keep running, it will wear away your cartilage, it’ll hurt your knees,” she said. “Now, we have a good synthesis of scientific evidence to prove maybe otherwise.”

Ms. Coburn and Dr. Culvenor report grant support from the National Health & Medical Research Council of Australia, and another author reports grant support from the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors, as well as Dr. Lo and Ms. Khan, report relevant financial relationships.
 

Running does not appear to cause sustained wear and tear of healthy knee cartilage, with research suggesting that the small, short-term changes to cartilage after a run reverse within hours.

A systematic review and meta-analysis published in the most recent issue of Osteoarthritis and Cartilage presents the findings involving 396 adults, which compared the “before” and “after” state of healthy knee cartilage in runners.

pojoslaw/Thinkstock

Running is often thought to be detrimental to joint health, wrote Sally Coburn, PhD candidate at the La Trobe Sport & Exercise Medicine Research Centre at La Trobe University in Melbourne and coauthors, but this perception is not supported by evidence.

For the analysis, the researchers included studies that looked at either knee or hip cartilage using MRI to assess its size, shape, structure, and/or composition both in the 48 hours before a single bout of running and in the 48 hours after. The analysis aimed to include adults with or at risk of osteoarthritis, but only 57 of the 446 knees in the analysis fit these criteria.

In studies where participants underwent MRI within 20 minutes of running, there was an immediate postrun decrease in the volume of cartilage, ranging from –3.3% for weight-bearing femoral cartilage to –4.1% for tibial cartilage volume. This also revealed a decrease in T1 and T2 relaxation times, which are specialized MRI measures that reflect the composition of cartilage and which can indicate a breakdown of cartilage structure in the case of diseases such as arthritis.

Reversal of short-term cartilage changes

However, within 48 hours of the run, data from studies that repeated the MRIs more than once after the initial prerun scan suggested these changes reversed back to prerun levels.

“We were able to pool delayed T2 relaxation time measures from studies that repeated scans of the same participants 60 minutes and 91 minutes post-run and found no effect of running on tibiofemoral joint cartilage composition,” the authors write.

For example, one study in marathon runners found no difference in cartilage thickness in the tibiofemoral joint between baseline and at 2-10 hours and 12 hours after the marathon. Another showed the immediate post-run decrease in patellofemoral joint cartilage thickness had reverted back to prerun levels when the scan was repeated 24 hours after the run.

“The changes are very minimal and not inconsistent with what’s expected for your cartilage which is functioning normally,” Ms. Coburn told this news organization.

Sparse data in people with osteoarthritis

The authors said there were not enough data from individuals with osteoarthritis to be able to pool and quantify their cartilage changes. However, one study in the analysis found that cartilage lesions in people considered at risk of osteoarthritis because of prior anterior cruciate ligament reconstruction were unchanged after running.

Another suggested that the decrease in femoral cartilage volume recorded at 15 minutes persisted at 45 minutes, while a separate study found significantly increased T2 relaxation times at 45 minutes after a run in those with knee osteoarthritis but not in those without osteoarthritis.

Senior author Adam Culvenor, PhD, senior research fellow at the La Trobe Centre, said their analysis suggested running was healthy, with small changes in cartilage that resolve quickly, but “we really don’t know yet if running is safe for people with osteoarthritis,” he said. “We need much more work in that space.”

Overall, the study evidence was rated as being of low certainty, which Dr. Coburn said was related to the small numbers in each study, which in turn relates to the cost and logistical challenges of the specialized MRI scan used.

“Study of a repeated exposure over a long duration of time on a disease that has a long natural history, like osteoarthritis, is challenging in that most funding agencies will not fund studies longer than 5 years,” Grace Hsiao-Wei Lo, MD, of the department of immunology, allergy, and rheumatology at the Baylor College of Medicine in Houston, said in an email.

Dr. Lo, who was not involved with this review and meta-analysis, said there are still concerns about the effect of running on knee osteoarthritis among those with the disease, although there are some data to suggest that among those who self-select to run, there are no negative outcomes for the knee.

An accompanying editorial noted that research into the effect of running on those with osteoarthritis was still in its infancy. “This would help to guide clinical practice on how to support people with osteoarthritis, with regard to accessing the health benefits of running participation,” write Jean-Francois Esculier, PT, PhD, from the University of British Columbia, Vancouver, and Christian Barton, PhD, with the La Trobe Centre, pointing out there were a lack of evidence-based clinical recommendations for people with osteoarthritis who want to start or continue running.

It’s a question that PhD candidate Michaela Khan, MSc, is trying to answer at the University of British Columbia. “Our lab did a pilot study for my current study now, and they found that osteoarthritic cartilage took a little bit longer to recover than their healthy counterparts,” Ms. Khan said. Her research is suggesting that people with osteoarthritis not only can run, but even those with severe disease, who might be candidates for knee replacement, can run long distances.

Commenting on the analysis, Ms. Khan said the main take-home message was that healthy cartilage seems to recover after running, and that there is not an ongoing effect of ‘wear and tear.’

“That’s changing the narrative that if you keep running, it will wear away your cartilage, it’ll hurt your knees,” she said. “Now, we have a good synthesis of scientific evidence to prove maybe otherwise.”

Ms. Coburn and Dr. Culvenor report grant support from the National Health & Medical Research Council of Australia, and another author reports grant support from the U.S. National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors, as well as Dr. Lo and Ms. Khan, report relevant financial relationships.
 

AURORA, COLO. – Perianal Crohn’s disease with fistula is notoriously difficult to treat and can make patients’ lives miserable, but a new, minimally invasive approach involving local injection of mesenchymal stem cells is both safe and, in a significant proportion of patients, highly effective, according to a colorectal surgeon.

“It’s a really debilitating phenotype, a spectrum of phenotypes,” Amy Lightner, MD, of the Cleveland Clinic said at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

Although some patients have minimal symptoms, others may require multiple setons to aid in drainage and healing, while others may require fistulotomy, endorectal advancement flap, intersphincteric fistula tract (LIFT) procedure, diversion, or proctectomy.

“Why is it so difficult to treat? Well, part of it is that this is an anatomic defect, and this is why 90% of patients will come to the operating room and will see their surgeons on a frequent basis. The other part of that is that we have medical therapies to treat these fistulas but they’re really largely ineffective, because there is that anatomical defect, the hole there that needs to be closed,” Dr. Lightner said.

Up to 20% of patients may require a permanent stoma, and an additional 20% may require temporary fecal diversion.

Mesenchymal stem cells (MSC) are derived from bone marrow, fat stores, or umbilical cord tissues. Unlike embryonic stem cells, which have the ability to metamorphose into a multitude of other cell types, mesenchymal stem cells are differentiated “adult” cells.

They work by secreting anti-inflammatory cytokines and recruiting immune cells to stimulate tissue repair and healing. The cells are delivered in a minimally invasive outpatient setting, and there is no risk of incontinence compared with more invasive procedures such as fistulotomy or advancement flaps.
 

Effective and safe

MSCs were first used in Spain in 2003 to successfully treat a young women with a complex fistula with five perianal tracts converging into a rectovaginal fistula. The investigators injected a single dose of 9 x 10⁶ MSCs into the site, and the fistula healed within 3 months.

Since then in multiple clinical trials involving more than 400 patients, injection of MSCs has resulted in fistula closure and complete healing by 8-12 weeks in 50%-85% of patients, Dr. Lightner said.

The treatment effect is also durable, she said, pointing to data from the ADMIRE-CD study, in which 51.5% of Crohn’s disease patients with treatment-refractory complex perianal fistula were healed at 24 weeks following injection of adipose-derived stem cells, compared with 35.6% of controls. At 1 year of follow-up, respective rates of healing were 56.3% vs. 38.6%.

Dr. Lightner also cited a case report of a patient whose fistula remained healed 4 years after receiving MSCs for refractory perianal Crohn’s fistulas.

Although MSCs are derived from healthy donors, they do not bear cellular surface antigens that would instigate a destructive host immune response, and to date, there have been no reports from clinical trials of systemic infections or complications. The most frequently reported adverse events have been injection-site pain in about 12%-15% of patients, and perianal abscess in 5%-13%, with similar frequencies in treatment and control groups.

Dr. Lightner and colleagues are currently exploring additional indications for stem cell therapy with MSCs, including other complex fistula phenotypes, intestinal Crohn’s disease, and ulcerative colitis.
 

Other approaches

In a separate presentation, James D. Lewis, MD, MSCE, of the University of Pennsylvania in Philadelphia talked about what would be needed to achieve a “medical moonshot” with the goal of curing inflammatory bowel disease (IBD), and touched on hematopoietic stem cell transplants as a potential option for patients with chronic, severe, and intractable disease.

One of his patients was a woman in her 60s who was diagnosed with stricturing and penetrating Crohn’s disease in her 30s, with the disease involving the ileum and entire colon. She had previously undergone three small bowel resections and a partial colon resection, and had never experienced remission despite taking steroids, azathioprine, methotrexate, four anti-TNF drugs, ustekinumab (Stelara), and vedolizumab (Entyvio).

Following an autologous hematopoietic stem cell transplant, she had a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of 0. Her course was complicated by demand ischemia and acute kidney injury.

An IBD specialist who was not involved in either study commented in an interview that both MSCs and stem cell transplants show promise for treatment-refractory IBD,

“Both approaches are very promising, but stem cell transplants for IBD haven’t been formally studied yet so the data aren’t as strong, but there is promise for the future,” said Berkeley N. Limketkai, MD, PhD, from the University of California, Los Angeles.

“The challenges, however, are also the morbidity associated with actually undergoing such procedures,” he continued. Short- and long-term morbidities associated with hematopoietic stem cell transplants may include mucositis; hemorrhagic cystitis; prolonged, severe pancytopenia; infection; graft-versus-host disease; graft failure; pulmonary complications, veno-occlusive disease of the liver; and thrombotic microangiopathy.

Dr. Limketkai said that over time as the protocols for stem cell transplants in IBD improve, the benefits for select patients may more clearly outweigh the risks.

Dr. Lightner’s work is supported by the Leona M. and Harry B. Helmsley Charitable Trust and the American Society of Colon and Rectal Surgery. She disclosed consulting fees from Boomerang Medical, Mesoblast Limited, Ossium Health, and Takeda Pharmaceuticals USA. Dr. Lewis’ work is supported by grants from the National Institutes of Health, and from AbbVie, Takeda, Janssen, and Nestlé Health Science. He has also served as a consultant to and data safety monitoring board member for several entities. Dr. Limketkai disclosed consulting for Azora Therapeutics.

AURORA, COLO. – Perianal Crohn’s disease with fistula is notoriously difficult to treat and can make patients’ lives miserable, but a new, minimally invasive approach involving local injection of mesenchymal stem cells is both safe and, in a significant proportion of patients, highly effective, according to a colorectal surgeon.

“It’s a really debilitating phenotype, a spectrum of phenotypes,” Amy Lightner, MD, of the Cleveland Clinic said at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

Although some patients have minimal symptoms, others may require multiple setons to aid in drainage and healing, while others may require fistulotomy, endorectal advancement flap, intersphincteric fistula tract (LIFT) procedure, diversion, or proctectomy.

“Why is it so difficult to treat? Well, part of it is that this is an anatomic defect, and this is why 90% of patients will come to the operating room and will see their surgeons on a frequent basis. The other part of that is that we have medical therapies to treat these fistulas but they’re really largely ineffective, because there is that anatomical defect, the hole there that needs to be closed,” Dr. Lightner said.

Up to 20% of patients may require a permanent stoma, and an additional 20% may require temporary fecal diversion.

Mesenchymal stem cells (MSC) are derived from bone marrow, fat stores, or umbilical cord tissues. Unlike embryonic stem cells, which have the ability to metamorphose into a multitude of other cell types, mesenchymal stem cells are differentiated “adult” cells.

They work by secreting anti-inflammatory cytokines and recruiting immune cells to stimulate tissue repair and healing. The cells are delivered in a minimally invasive outpatient setting, and there is no risk of incontinence compared with more invasive procedures such as fistulotomy or advancement flaps.
 

Effective and safe

MSCs were first used in Spain in 2003 to successfully treat a young women with a complex fistula with five perianal tracts converging into a rectovaginal fistula. The investigators injected a single dose of 9 x 10⁶ MSCs into the site, and the fistula healed within 3 months.

Since then in multiple clinical trials involving more than 400 patients, injection of MSCs has resulted in fistula closure and complete healing by 8-12 weeks in 50%-85% of patients, Dr. Lightner said.

The treatment effect is also durable, she said, pointing to data from the ADMIRE-CD study, in which 51.5% of Crohn’s disease patients with treatment-refractory complex perianal fistula were healed at 24 weeks following injection of adipose-derived stem cells, compared with 35.6% of controls. At 1 year of follow-up, respective rates of healing were 56.3% vs. 38.6%.

Dr. Lightner also cited a case report of a patient whose fistula remained healed 4 years after receiving MSCs for refractory perianal Crohn’s fistulas.

Although MSCs are derived from healthy donors, they do not bear cellular surface antigens that would instigate a destructive host immune response, and to date, there have been no reports from clinical trials of systemic infections or complications. The most frequently reported adverse events have been injection-site pain in about 12%-15% of patients, and perianal abscess in 5%-13%, with similar frequencies in treatment and control groups.

Dr. Lightner and colleagues are currently exploring additional indications for stem cell therapy with MSCs, including other complex fistula phenotypes, intestinal Crohn’s disease, and ulcerative colitis.
 

Other approaches

In a separate presentation, James D. Lewis, MD, MSCE, of the University of Pennsylvania in Philadelphia talked about what would be needed to achieve a “medical moonshot” with the goal of curing inflammatory bowel disease (IBD), and touched on hematopoietic stem cell transplants as a potential option for patients with chronic, severe, and intractable disease.

One of his patients was a woman in her 60s who was diagnosed with stricturing and penetrating Crohn’s disease in her 30s, with the disease involving the ileum and entire colon. She had previously undergone three small bowel resections and a partial colon resection, and had never experienced remission despite taking steroids, azathioprine, methotrexate, four anti-TNF drugs, ustekinumab (Stelara), and vedolizumab (Entyvio).

Following an autologous hematopoietic stem cell transplant, she had a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of 0. Her course was complicated by demand ischemia and acute kidney injury.

An IBD specialist who was not involved in either study commented in an interview that both MSCs and stem cell transplants show promise for treatment-refractory IBD,

“Both approaches are very promising, but stem cell transplants for IBD haven’t been formally studied yet so the data aren’t as strong, but there is promise for the future,” said Berkeley N. Limketkai, MD, PhD, from the University of California, Los Angeles.

“The challenges, however, are also the morbidity associated with actually undergoing such procedures,” he continued. Short- and long-term morbidities associated with hematopoietic stem cell transplants may include mucositis; hemorrhagic cystitis; prolonged, severe pancytopenia; infection; graft-versus-host disease; graft failure; pulmonary complications, veno-occlusive disease of the liver; and thrombotic microangiopathy.

Dr. Limketkai said that over time as the protocols for stem cell transplants in IBD improve, the benefits for select patients may more clearly outweigh the risks.

Dr. Lightner’s work is supported by the Leona M. and Harry B. Helmsley Charitable Trust and the American Society of Colon and Rectal Surgery. She disclosed consulting fees from Boomerang Medical, Mesoblast Limited, Ossium Health, and Takeda Pharmaceuticals USA. Dr. Lewis’ work is supported by grants from the National Institutes of Health, and from AbbVie, Takeda, Janssen, and Nestlé Health Science. He has also served as a consultant to and data safety monitoring board member for several entities. Dr. Limketkai disclosed consulting for Azora Therapeutics.

AURORA, COLO. – Perianal Crohn’s disease with fistula is notoriously difficult to treat and can make patients’ lives miserable, but a new, minimally invasive approach involving local injection of mesenchymal stem cells is both safe and, in a significant proportion of patients, highly effective, according to a colorectal surgeon.

“It’s a really debilitating phenotype, a spectrum of phenotypes,” Amy Lightner, MD, of the Cleveland Clinic said at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

Although some patients have minimal symptoms, others may require multiple setons to aid in drainage and healing, while others may require fistulotomy, endorectal advancement flap, intersphincteric fistula tract (LIFT) procedure, diversion, or proctectomy.

“Why is it so difficult to treat? Well, part of it is that this is an anatomic defect, and this is why 90% of patients will come to the operating room and will see their surgeons on a frequent basis. The other part of that is that we have medical therapies to treat these fistulas but they’re really largely ineffective, because there is that anatomical defect, the hole there that needs to be closed,” Dr. Lightner said.

Up to 20% of patients may require a permanent stoma, and an additional 20% may require temporary fecal diversion.

Mesenchymal stem cells (MSC) are derived from bone marrow, fat stores, or umbilical cord tissues. Unlike embryonic stem cells, which have the ability to metamorphose into a multitude of other cell types, mesenchymal stem cells are differentiated “adult” cells.

They work by secreting anti-inflammatory cytokines and recruiting immune cells to stimulate tissue repair and healing. The cells are delivered in a minimally invasive outpatient setting, and there is no risk of incontinence compared with more invasive procedures such as fistulotomy or advancement flaps.
 

Effective and safe

MSCs were first used in Spain in 2003 to successfully treat a young women with a complex fistula with five perianal tracts converging into a rectovaginal fistula. The investigators injected a single dose of 9 x 10⁶ MSCs into the site, and the fistula healed within 3 months.

Since then in multiple clinical trials involving more than 400 patients, injection of MSCs has resulted in fistula closure and complete healing by 8-12 weeks in 50%-85% of patients, Dr. Lightner said.

The treatment effect is also durable, she said, pointing to data from the ADMIRE-CD study, in which 51.5% of Crohn’s disease patients with treatment-refractory complex perianal fistula were healed at 24 weeks following injection of adipose-derived stem cells, compared with 35.6% of controls. At 1 year of follow-up, respective rates of healing were 56.3% vs. 38.6%.

Dr. Lightner also cited a case report of a patient whose fistula remained healed 4 years after receiving MSCs for refractory perianal Crohn’s fistulas.

Although MSCs are derived from healthy donors, they do not bear cellular surface antigens that would instigate a destructive host immune response, and to date, there have been no reports from clinical trials of systemic infections or complications. The most frequently reported adverse events have been injection-site pain in about 12%-15% of patients, and perianal abscess in 5%-13%, with similar frequencies in treatment and control groups.

Dr. Lightner and colleagues are currently exploring additional indications for stem cell therapy with MSCs, including other complex fistula phenotypes, intestinal Crohn’s disease, and ulcerative colitis.
 

Other approaches

In a separate presentation, James D. Lewis, MD, MSCE, of the University of Pennsylvania in Philadelphia talked about what would be needed to achieve a “medical moonshot” with the goal of curing inflammatory bowel disease (IBD), and touched on hematopoietic stem cell transplants as a potential option for patients with chronic, severe, and intractable disease.

One of his patients was a woman in her 60s who was diagnosed with stricturing and penetrating Crohn’s disease in her 30s, with the disease involving the ileum and entire colon. She had previously undergone three small bowel resections and a partial colon resection, and had never experienced remission despite taking steroids, azathioprine, methotrexate, four anti-TNF drugs, ustekinumab (Stelara), and vedolizumab (Entyvio).

Following an autologous hematopoietic stem cell transplant, she had a Simple Endoscopic Score for Crohn’s Disease (SES-CD) of 0. Her course was complicated by demand ischemia and acute kidney injury.

An IBD specialist who was not involved in either study commented in an interview that both MSCs and stem cell transplants show promise for treatment-refractory IBD,

“Both approaches are very promising, but stem cell transplants for IBD haven’t been formally studied yet so the data aren’t as strong, but there is promise for the future,” said Berkeley N. Limketkai, MD, PhD, from the University of California, Los Angeles.

“The challenges, however, are also the morbidity associated with actually undergoing such procedures,” he continued. Short- and long-term morbidities associated with hematopoietic stem cell transplants may include mucositis; hemorrhagic cystitis; prolonged, severe pancytopenia; infection; graft-versus-host disease; graft failure; pulmonary complications, veno-occlusive disease of the liver; and thrombotic microangiopathy.

Dr. Limketkai said that over time as the protocols for stem cell transplants in IBD improve, the benefits for select patients may more clearly outweigh the risks.

Dr. Lightner’s work is supported by the Leona M. and Harry B. Helmsley Charitable Trust and the American Society of Colon and Rectal Surgery. She disclosed consulting fees from Boomerang Medical, Mesoblast Limited, Ossium Health, and Takeda Pharmaceuticals USA. Dr. Lewis’ work is supported by grants from the National Institutes of Health, and from AbbVie, Takeda, Janssen, and Nestlé Health Science. He has also served as a consultant to and data safety monitoring board member for several entities. Dr. Limketkai disclosed consulting for Azora Therapeutics.

The drug overdose death rate in the United States climbed 376% from 2001 to 2021, with much of that increase occurring in the last 2 years, according to the National Center for Heath Statistics.

The 376% represents the change in age-adjusted overdose deaths per 100,000 population, which went from 6.9 in 2001 to 32.4 in 2021, as the total number of deaths rose from 19,394 to 106,699 (450%) over that time period, the NCHS said in a recent data brief. That total made 2021 the first year ever with more than 100,000 overdose deaths.

Since the age-adjusted rate stood at 21.6 per 100,000 in 2019, that means 42% of the total increase over 20 years actually occurred in 2020 and 2021. The number of deaths increased by about 36,000 over those 2 years, accounting for 41% of the total annual increase from 2001 to 2021, based on data from the National Vital Statistics System mortality files.

The overdose death rate was significantly higher for males than females for all of the years from 2001 to 2021, with males seeing an increase from 9.0 to 45.1 per 100,000 and females going from 4.6 to 19.6 deaths per 100,000. In the single year from 2020 to 2021, the age-adjusted rate was up by 14% for males and 15% for females, the mortality-file data show.

Analysis by age showed an even larger effect in some groups from 2020 to 2021. Drug overdose deaths jumped 28% among adults aged 65 years and older, more than any other group, and by 21% in those aged 55-64 years, according to the NCHS.

The only age group for which deaths didn’t increase significantly from 2020 to 2021 was 15- to 24-year-olds, whose rate rose by just 3%. The age group with the highest rate in both 2020 and 2021, however, was the 35- to 44-year-olds: 53.9 and 62.0 overdose deaths per 100,000, respectively, for an increase of 15%, the NCHS said in the report.

The drugs now involved in overdose deaths are most often opioids, a change from 2001. That year, opioids were involved in 49% of all overdose deaths, but by 2021 that share had increased to 75%. The trend for opioid-related deaths almost matches that of overall deaths over the 20-year span, and the significantly increasing trend that began for all overdose deaths in 2013 closely follows that of synthetic opioids such as fentanyl and tramadol, the report shows.

Overdose deaths involving cocaine and psychostimulants such as methamphetamine, amphetamine, and methylphenidate also show similar increases. The cocaine-related death rate rose 22% from 2020 to 2021 and is up by 421% since 2012, while the corresponding increases for psychostimulant deaths were 33% and 2,400%, the NCHS said.

The drug overdose death rate in the United States climbed 376% from 2001 to 2021, with much of that increase occurring in the last 2 years, according to the National Center for Heath Statistics.

The 376% represents the change in age-adjusted overdose deaths per 100,000 population, which went from 6.9 in 2001 to 32.4 in 2021, as the total number of deaths rose from 19,394 to 106,699 (450%) over that time period, the NCHS said in a recent data brief. That total made 2021 the first year ever with more than 100,000 overdose deaths.

Since the age-adjusted rate stood at 21.6 per 100,000 in 2019, that means 42% of the total increase over 20 years actually occurred in 2020 and 2021. The number of deaths increased by about 36,000 over those 2 years, accounting for 41% of the total annual increase from 2001 to 2021, based on data from the National Vital Statistics System mortality files.

The overdose death rate was significantly higher for males than females for all of the years from 2001 to 2021, with males seeing an increase from 9.0 to 45.1 per 100,000 and females going from 4.6 to 19.6 deaths per 100,000. In the single year from 2020 to 2021, the age-adjusted rate was up by 14% for males and 15% for females, the mortality-file data show.

Analysis by age showed an even larger effect in some groups from 2020 to 2021. Drug overdose deaths jumped 28% among adults aged 65 years and older, more than any other group, and by 21% in those aged 55-64 years, according to the NCHS.

The only age group for which deaths didn’t increase significantly from 2020 to 2021 was 15- to 24-year-olds, whose rate rose by just 3%. The age group with the highest rate in both 2020 and 2021, however, was the 35- to 44-year-olds: 53.9 and 62.0 overdose deaths per 100,000, respectively, for an increase of 15%, the NCHS said in the report.

The drugs now involved in overdose deaths are most often opioids, a change from 2001. That year, opioids were involved in 49% of all overdose deaths, but by 2021 that share had increased to 75%. The trend for opioid-related deaths almost matches that of overall deaths over the 20-year span, and the significantly increasing trend that began for all overdose deaths in 2013 closely follows that of synthetic opioids such as fentanyl and tramadol, the report shows.

Overdose deaths involving cocaine and psychostimulants such as methamphetamine, amphetamine, and methylphenidate also show similar increases. The cocaine-related death rate rose 22% from 2020 to 2021 and is up by 421% since 2012, while the corresponding increases for psychostimulant deaths were 33% and 2,400%, the NCHS said.

The drug overdose death rate in the United States climbed 376% from 2001 to 2021, with much of that increase occurring in the last 2 years, according to the National Center for Heath Statistics.

The 376% represents the change in age-adjusted overdose deaths per 100,000 population, which went from 6.9 in 2001 to 32.4 in 2021, as the total number of deaths rose from 19,394 to 106,699 (450%) over that time period, the NCHS said in a recent data brief. That total made 2021 the first year ever with more than 100,000 overdose deaths.

Since the age-adjusted rate stood at 21.6 per 100,000 in 2019, that means 42% of the total increase over 20 years actually occurred in 2020 and 2021. The number of deaths increased by about 36,000 over those 2 years, accounting for 41% of the total annual increase from 2001 to 2021, based on data from the National Vital Statistics System mortality files.

The overdose death rate was significantly higher for males than females for all of the years from 2001 to 2021, with males seeing an increase from 9.0 to 45.1 per 100,000 and females going from 4.6 to 19.6 deaths per 100,000. In the single year from 2020 to 2021, the age-adjusted rate was up by 14% for males and 15% for females, the mortality-file data show.

Analysis by age showed an even larger effect in some groups from 2020 to 2021. Drug overdose deaths jumped 28% among adults aged 65 years and older, more than any other group, and by 21% in those aged 55-64 years, according to the NCHS.

The only age group for which deaths didn’t increase significantly from 2020 to 2021 was 15- to 24-year-olds, whose rate rose by just 3%. The age group with the highest rate in both 2020 and 2021, however, was the 35- to 44-year-olds: 53.9 and 62.0 overdose deaths per 100,000, respectively, for an increase of 15%, the NCHS said in the report.

The drugs now involved in overdose deaths are most often opioids, a change from 2001. That year, opioids were involved in 49% of all overdose deaths, but by 2021 that share had increased to 75%. The trend for opioid-related deaths almost matches that of overall deaths over the 20-year span, and the significantly increasing trend that began for all overdose deaths in 2013 closely follows that of synthetic opioids such as fentanyl and tramadol, the report shows.

Overdose deaths involving cocaine and psychostimulants such as methamphetamine, amphetamine, and methylphenidate also show similar increases. The cocaine-related death rate rose 22% from 2020 to 2021 and is up by 421% since 2012, while the corresponding increases for psychostimulant deaths were 33% and 2,400%, the NCHS said.