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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Compelling case for skipping RT in some early breast cancers
Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy.
(1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03).
Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.
“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said.
This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.”
Results of the PROSPECT trial were published online on December 5 in The Lancet.
PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.
The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates.
Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort.
Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years.
At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%).
The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.
Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.
PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said.
The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.
Risk Tolerance and Personal Preferences
Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”
He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”
Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”
Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy.
(1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03).
Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.
“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said.
This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.”
Results of the PROSPECT trial were published online on December 5 in The Lancet.
PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.
The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates.
Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort.
Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years.
At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%).
The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.
Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.
PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said.
The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.
Risk Tolerance and Personal Preferences
Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”
He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”
Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”
Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Results of the PROSPECT trial provide compelling evidence that high-quality preoperative MRI in combination with postoperative analysis of pathologic features can identify a substantial subset of women with localized early breast cancer who could safely skip radiation therapy.
(1%) at 5 years, reported lead investigator Gregory Bruce Mann, MBBS, PhD, of The Royal Women’s Hospital, Melbourne, Australia, at the San Antonio Breast Cancer Symposium (abstract PS02-03).
Additionally, women who skipped radiation had superior health-related quality of life relative to peers who underwent the treatment and, quite unexpectedly, their fear of cancer recurrence was “dramatically reduced,” Dr, Mann said in an interview.
“The hypothesis was that less treatment [would] lead to more fear of cancer recurrence” because patients would worry that they hadn’t received standard treatment, “but patients who omitted RT actually had less fear of cancer recurrence,” he said.
This may come down to positive perceptions about tailored care and trust, he explained. “If the patient got the impression that the doctor wasn’t worried about recurrence, then the patient wasn’t worried. If they trusted you and you had that relationship with the patient, they were less likely to experience a fear of recurrence.”
Results of the PROSPECT trial were published online on December 5 in The Lancet.
PROSPECT was a prospective, nonrandomized study that evaluated whether preoperative bilateral contrast-enhanced 3-Tesla breast MRI and postoperative tumor pathology could identify patients with “truly localized” disease who might feasibly skip radiation therapy after breast-conserving surgery.
The researchers hypothesised that radiation therapy reduces local recurrence risk by treating occult synchronous disease that has not been identified by conventional imaging techniques. Exclusion of such occult disease using preoperative MRI, in association with low-risk pathology, could define a group of patients with early breast cancer in whom radiation can be omitted without substantially compromising local recurrence rates.
Women aged 50 years or older with cT1N0 non–triple-negative breast cancer were eligible for the trial. Among 443 patients, preoperative MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%) of the total cohort.
Patients with apparently unifocal cancer had breast-conserving surgery and, if pT1N0 or N1mi, did not undergo radiation therapy (group 1: 201 women). Standard treatment including radiation therapy was offered to the others (group 2: 242 women). All women were recommended for systemic therapy. The primary endpoint was the ipsilateral invasive recurrence rate at 5 years, with follow-up to continue to 10 years.
At a median follow-up of 5.4 years, the ipsilateral invasive recurrence rate in group 1 was exceedingly low — just 1.0% (upper 95% CI, 5.4%) — with one local recurrence at 4.5 years and a second at 7.5 years. In group 2, local recurrence at 5 years was also low, at 1.7% (upper 95% CI, 6.1%).
The only case of distant metastasis in the entire cohort was genetically distinct from the index cancer.
Omitting radiation therapy led to better health-related quality of life and functional and cosmetic outcomes, and the women viewed not having radiation as highly acceptable and appropriate treatment, not undertreatment.
PROSPECT has defined a role for “very high quality” preoperative MRI in identifying patients who can be considered for deintensified treatment, Dr. Mann said.
The findings need to be replicated in multicenter, international trials, “and that’s what we are working on,” he added.
Risk Tolerance and Personal Preferences
Writing in a comment for The Lancet, Lior Z. Braunstein, MD, with Memorial Sloan Kettering Cancer Center in New York, says that overall, PROSPECT and comparable trials of radiation therapy omission, “rather than setting uniform clinical practice, will empower patients to delineate their individual risk tolerance and personal preferences.”
He notes, however, that “the use of preoperative MRI among patients at low risk remains somewhat controversial. Indeed, the MRI intervention in PROSPECT was not entirely benign, prompting nearly 200 biopsies and five of the nine observed mastectomies.”
Dr. Braunstein concludes that with numerous approaches to risk profiling, “informed patients might very reasonably choose differing paths. Indeed, it is precisely this individualized approach to breast cancer management that has long been the promise of personalized medicine — PROSPECT adds laudably to that tradition.”
Funding for the trial was provided by Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation. Dr. Mann and Dr. Braunstein have no relevant disclosures.Megan Brooks has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM SABCS 2023
Sleep disorders linked to increased mortality risk in epilepsy
ORLANDO — , new research shows.
SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.
“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.
She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.
The findings were presented at the annual meeting of the American Epilepsy Society (AES).
The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.
The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.
They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
SUDEP Inventory
Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.
Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).
Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).
The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.
From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
Powerful Study
Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.
“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.
Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.
Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.
Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ORLANDO — , new research shows.
SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.
“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.
She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.
The findings were presented at the annual meeting of the American Epilepsy Society (AES).
The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.
The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.
They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
SUDEP Inventory
Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.
Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).
Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).
The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.
From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
Powerful Study
Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.
“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.
Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.
Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.
Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
ORLANDO — , new research shows.
SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.
“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.
She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.
The findings were presented at the annual meeting of the American Epilepsy Society (AES).
The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.
The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.
They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
SUDEP Inventory
Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.
Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).
Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).
The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.
From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
Powerful Study
Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.
“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.
Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.
Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.
Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM AES 2023
Pulmonary arterial hypertension: Promising results for investigational agents and catheter-based denervation
PHILADELPHIA — Promise that the unmet need for more effective pulmonary artery hypertension treatments may soon be met was in strong evidence in research into three strategies presented at this year’s recent American Heart Association scientific sessions; one was based on an ancient Chinese herb epimedium (yin yang huo or horny goat weed) commonly used for treating sexual dysfunction and directly related to the phosphodiesterase inhibitors sildenafil, vardenafil, and tadalafil (sold as Viagra, Levitra, and Cialis). A second studied sotatercept, an investigational, potential first-in-class activin signaling inhibitor biologic, and a third evaluated physically ablating the baroreceptor nerves that stimulate vasoconstriction of the pulmonary artery via catheter-based techniques.
Until as recently as the late 1970s, a pulmonary arterial hypertension diagnosis was a uniformly fatal one.1 While associated with pulmonary and right ventricle remodeling, and leads toward heart failure and death. The complex underlying pathogenesis was divided into six groups by the 6th World Symposium on Pulmonary Hypertension (WSPH) in 2018, and includes as its most common features pulmonary artery endothelial cell dysfunction, pulmonary artery smooth muscle cell proliferation and migration, and dysregulated fibroblast activity leading to dysregulated vasoconstriction, micro and in-situ vascular thrombosis, vascular fibrosis and pathogenic remodeling of pulmonary vessels.1 The threshold mean arterial pressure (mPAP) for pulmonary arterial hypertension was defined by the 6th [WSPH] at mPAP ≥ 20 mm Hg, twice the upper limit of a normal mPAP of 14.0 ± 3.3 mm Hg as reported by Kovacs et al. in 2018.2
Pathways for current therapies
Current drugs for pulmonary arterial hypertension focus on three signaling pathways, including the endothelin receptor, prostacyclin and nitric oxide pathways, stated Zhi-Cheng Jing, MD, professor of medicine, head of the cardiology department at Peking Union Medical College Hospital, Peking, China. While the phosphodiesterase 5 inhibitors sildenafil and tadalafil, which target the nitric oxide pathway, came into wide use after Food and Drug Administration approval, the need for higher PDE5-selectivity remains, Dr. Jing said. Structurally modified from the active ingredient in epimedium, TPN171H is an investigational PDE5 inhibitor which has shown several favorable features: a greater PDE5 selectivity than both sildenafil and tadalafil in vitro, an ability to decrease right ventricular systolic pressure and alleviate arterial remodeling in animal studies, and safety and tolerability in healthy human subjects.
The current randomized, double-blind, placebo-and active-controlled phase IIa study assessed the hemodynamic impact of a single oral dose of TPN171H in 60 pulmonary arterial hypertension patients (mean age ~34 years, 83.3% female), all with negative vasodilation test results and in WHO class 2 or 3. Only patients aged 18-75 years with group 1 pulmonary arterial hypertension of idiopathic, connective tissue disorder, or repaired congenital heart defects etiology were included. Patients were divided into six groups: placebo, TPN171H at 2.5, 5, and 10 milligrams, and tadalafil at 20 and 40 milligrams.
For the primary endpoint of maximum decrease in pulmonary vascular resistance (PVR), significant reductions vs. placebo were found only for the TPN171H 5-mg group (–41.2% vs. –24.4%; P = .008) and for the 20-mg (–39.8%) and 40-mg (–37.6%) tadalafil groups (both P < .05). What was not seen in the tadalafil groups, but was evident in the TPN171H 5-mg group, was a significant reduction in the secondary endpoint of PVR/SVR (systolic vascular resistance) at 2, 3, and 5 hours (all P < .05). “As we know,” Dr. Jing said in an interview, “the PDE5 inhibitor functions as a vasodilator, having an impact on both pulmonary circulation and systemic circulation. So, to evaluate the selectivity for pulmonary circulation is crucial when exploring a novel drug for pulmonary arterial hypertension. The change of PVR/SVR ratio from baseline is an indicator for selectivity for pulmonary circulation and implies that TPN171H has good PDE5 selectivity in the pulmonary vasculature,” Dr. Jing said.
TPN171H was well tolerated with no serious adverse effects (vomiting 10% and headache 10% were most common with no discontinuations).
TGF-signaling pathway
A meta-analysis of randomized controlled trials of sotatercept, an investigational fusion protein under priority FDA review that modulates the TGF-beta superfamily signaling pathway, looked at PVR, pulmonary arterial pressure (PAP), right arterial pressure (RAP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). A literature search by corresponding author Vamsikalyan Borra, MD, Knapp Medical Center, Weslaco, Texas, and colleagues identified two trials (STELLAR and PULSAR) comprising 429 patients with pulmonary arterial hypertension. The experimental arms (sotatercept) had 237 patients (mean age ~49 years, ~82% female) and the placebo arm had 192 patients (mean age ~47 years, ~80% female).
A pooled analysis showed significant reductions with sotatercept in PVR (standardization mean difference [SMD] = –1.00, 95% confidence interval [CI] = –1.2, –.79, P < .001), PAP (SMD = –1.34, 95% CI = 1.6, –1.08, P < .001), RAP (SMD = –0.66, 95% CI = –0.93, –0.39, P < .001), and the levels of NT-proBNP (SMD = –0.64, 95% CI = –1.01, –0.27, P < .001) at 24 weeks from baseline. The sotatercept safety profile was favorable, with lower overall incidence of adverse events (84.8% vs. 87.5%) and fewer adverse events leading to death (0.4% vs. 3.1%) compared with placebo. Further investigation is needed, however, according to Dr. Borra, into the higher frequency of reported thrombocytopenia (71.7% vs. 20.8%) with sotatercept. “Our findings,” Dr. Borra said in a poster session, “suggest that sotatercept is an effective treatment option for pulmonary arterial hypertension, with the potential to improve both pulmonary and cardiac function.”
Denervation technique
Catheter-based ablation techniques, most commonly using thermal energy, target the afferent and efferent fibers of the baroreceptor reflex in the main pulmonary artery trunk and bifurcation involved in elevated pulmonary artery pressure. Mounica Vorla, MD, Carle Foundation Hospital, Urbana, Illinois, and colleagues conducted an updated systematic review and meta-analysis of the safety and efficacy of pulmonary artery denervation (PADN) for pulmonary arterial hypertension in seven clinical trials with 506 patients with moderate-severe pulmonary arterial hypertension conducted from 2013 to 2022.
Compared with placebo, PADN treatment was associated with a significant reduction in mean pulmonary artery pressure (weighted mean difference [WMD] = –6.9 mm Hg; 95% CI = –9.7, –4.1; P < .01; I2 = 61) and pulmonary vascular resistance (WMD = –3.2; 95% CI = –5.4, –0.9; P = .005). PADN improvements in cardiac output were also statistically significant (WMD = 0.3; 95% CI = 0.07, 0.6; P = .012), with numerical improvement in 6-minute walking distance (WMD = 67.7; 95% CI = –3.73, 139.2; P = .06) in the PADN group. Side effects were less common in the PADN group as compared with the placebo group, Dr. Vorla reported. She concluded, “This updated meta-analysis supports PADN as a safe and efficacious therapy for severe pulmonary arterial hypertension.” The authors noted limitations imposed by the small sample size, large data heterogeneity, and medium-quality literature. Larger randomized, controlled trials with clinical endpoints comparing PADN with optimal medical therapy are needed, they stated.
References
1. Shah AJ et al. New Drugs and Therapies in Pulmonary Arterial Hypertension. Int J Mol Sci. 2023 Mar 19;24(6):5850. doi: 10.3390/ijms24065850. PMID: 36982922; PMCID: PMC10058689.
2. Kovacs G et al. Pulmonary Vascular Involvement in Chronic Obstructive Pulmonary Disease. Is There a Pulmonary Vascular Phenotype? Am J Respir Crit Care Med. 2018 Oct 15;198(8):1000-11. doi: 10.1164/rccm.201801-0095PP. PMID: 29746142.
PHILADELPHIA — Promise that the unmet need for more effective pulmonary artery hypertension treatments may soon be met was in strong evidence in research into three strategies presented at this year’s recent American Heart Association scientific sessions; one was based on an ancient Chinese herb epimedium (yin yang huo or horny goat weed) commonly used for treating sexual dysfunction and directly related to the phosphodiesterase inhibitors sildenafil, vardenafil, and tadalafil (sold as Viagra, Levitra, and Cialis). A second studied sotatercept, an investigational, potential first-in-class activin signaling inhibitor biologic, and a third evaluated physically ablating the baroreceptor nerves that stimulate vasoconstriction of the pulmonary artery via catheter-based techniques.
Until as recently as the late 1970s, a pulmonary arterial hypertension diagnosis was a uniformly fatal one.1 While associated with pulmonary and right ventricle remodeling, and leads toward heart failure and death. The complex underlying pathogenesis was divided into six groups by the 6th World Symposium on Pulmonary Hypertension (WSPH) in 2018, and includes as its most common features pulmonary artery endothelial cell dysfunction, pulmonary artery smooth muscle cell proliferation and migration, and dysregulated fibroblast activity leading to dysregulated vasoconstriction, micro and in-situ vascular thrombosis, vascular fibrosis and pathogenic remodeling of pulmonary vessels.1 The threshold mean arterial pressure (mPAP) for pulmonary arterial hypertension was defined by the 6th [WSPH] at mPAP ≥ 20 mm Hg, twice the upper limit of a normal mPAP of 14.0 ± 3.3 mm Hg as reported by Kovacs et al. in 2018.2
Pathways for current therapies
Current drugs for pulmonary arterial hypertension focus on three signaling pathways, including the endothelin receptor, prostacyclin and nitric oxide pathways, stated Zhi-Cheng Jing, MD, professor of medicine, head of the cardiology department at Peking Union Medical College Hospital, Peking, China. While the phosphodiesterase 5 inhibitors sildenafil and tadalafil, which target the nitric oxide pathway, came into wide use after Food and Drug Administration approval, the need for higher PDE5-selectivity remains, Dr. Jing said. Structurally modified from the active ingredient in epimedium, TPN171H is an investigational PDE5 inhibitor which has shown several favorable features: a greater PDE5 selectivity than both sildenafil and tadalafil in vitro, an ability to decrease right ventricular systolic pressure and alleviate arterial remodeling in animal studies, and safety and tolerability in healthy human subjects.
The current randomized, double-blind, placebo-and active-controlled phase IIa study assessed the hemodynamic impact of a single oral dose of TPN171H in 60 pulmonary arterial hypertension patients (mean age ~34 years, 83.3% female), all with negative vasodilation test results and in WHO class 2 or 3. Only patients aged 18-75 years with group 1 pulmonary arterial hypertension of idiopathic, connective tissue disorder, or repaired congenital heart defects etiology were included. Patients were divided into six groups: placebo, TPN171H at 2.5, 5, and 10 milligrams, and tadalafil at 20 and 40 milligrams.
For the primary endpoint of maximum decrease in pulmonary vascular resistance (PVR), significant reductions vs. placebo were found only for the TPN171H 5-mg group (–41.2% vs. –24.4%; P = .008) and for the 20-mg (–39.8%) and 40-mg (–37.6%) tadalafil groups (both P < .05). What was not seen in the tadalafil groups, but was evident in the TPN171H 5-mg group, was a significant reduction in the secondary endpoint of PVR/SVR (systolic vascular resistance) at 2, 3, and 5 hours (all P < .05). “As we know,” Dr. Jing said in an interview, “the PDE5 inhibitor functions as a vasodilator, having an impact on both pulmonary circulation and systemic circulation. So, to evaluate the selectivity for pulmonary circulation is crucial when exploring a novel drug for pulmonary arterial hypertension. The change of PVR/SVR ratio from baseline is an indicator for selectivity for pulmonary circulation and implies that TPN171H has good PDE5 selectivity in the pulmonary vasculature,” Dr. Jing said.
TPN171H was well tolerated with no serious adverse effects (vomiting 10% and headache 10% were most common with no discontinuations).
TGF-signaling pathway
A meta-analysis of randomized controlled trials of sotatercept, an investigational fusion protein under priority FDA review that modulates the TGF-beta superfamily signaling pathway, looked at PVR, pulmonary arterial pressure (PAP), right arterial pressure (RAP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). A literature search by corresponding author Vamsikalyan Borra, MD, Knapp Medical Center, Weslaco, Texas, and colleagues identified two trials (STELLAR and PULSAR) comprising 429 patients with pulmonary arterial hypertension. The experimental arms (sotatercept) had 237 patients (mean age ~49 years, ~82% female) and the placebo arm had 192 patients (mean age ~47 years, ~80% female).
A pooled analysis showed significant reductions with sotatercept in PVR (standardization mean difference [SMD] = –1.00, 95% confidence interval [CI] = –1.2, –.79, P < .001), PAP (SMD = –1.34, 95% CI = 1.6, –1.08, P < .001), RAP (SMD = –0.66, 95% CI = –0.93, –0.39, P < .001), and the levels of NT-proBNP (SMD = –0.64, 95% CI = –1.01, –0.27, P < .001) at 24 weeks from baseline. The sotatercept safety profile was favorable, with lower overall incidence of adverse events (84.8% vs. 87.5%) and fewer adverse events leading to death (0.4% vs. 3.1%) compared with placebo. Further investigation is needed, however, according to Dr. Borra, into the higher frequency of reported thrombocytopenia (71.7% vs. 20.8%) with sotatercept. “Our findings,” Dr. Borra said in a poster session, “suggest that sotatercept is an effective treatment option for pulmonary arterial hypertension, with the potential to improve both pulmonary and cardiac function.”
Denervation technique
Catheter-based ablation techniques, most commonly using thermal energy, target the afferent and efferent fibers of the baroreceptor reflex in the main pulmonary artery trunk and bifurcation involved in elevated pulmonary artery pressure. Mounica Vorla, MD, Carle Foundation Hospital, Urbana, Illinois, and colleagues conducted an updated systematic review and meta-analysis of the safety and efficacy of pulmonary artery denervation (PADN) for pulmonary arterial hypertension in seven clinical trials with 506 patients with moderate-severe pulmonary arterial hypertension conducted from 2013 to 2022.
Compared with placebo, PADN treatment was associated with a significant reduction in mean pulmonary artery pressure (weighted mean difference [WMD] = –6.9 mm Hg; 95% CI = –9.7, –4.1; P < .01; I2 = 61) and pulmonary vascular resistance (WMD = –3.2; 95% CI = –5.4, –0.9; P = .005). PADN improvements in cardiac output were also statistically significant (WMD = 0.3; 95% CI = 0.07, 0.6; P = .012), with numerical improvement in 6-minute walking distance (WMD = 67.7; 95% CI = –3.73, 139.2; P = .06) in the PADN group. Side effects were less common in the PADN group as compared with the placebo group, Dr. Vorla reported. She concluded, “This updated meta-analysis supports PADN as a safe and efficacious therapy for severe pulmonary arterial hypertension.” The authors noted limitations imposed by the small sample size, large data heterogeneity, and medium-quality literature. Larger randomized, controlled trials with clinical endpoints comparing PADN with optimal medical therapy are needed, they stated.
References
1. Shah AJ et al. New Drugs and Therapies in Pulmonary Arterial Hypertension. Int J Mol Sci. 2023 Mar 19;24(6):5850. doi: 10.3390/ijms24065850. PMID: 36982922; PMCID: PMC10058689.
2. Kovacs G et al. Pulmonary Vascular Involvement in Chronic Obstructive Pulmonary Disease. Is There a Pulmonary Vascular Phenotype? Am J Respir Crit Care Med. 2018 Oct 15;198(8):1000-11. doi: 10.1164/rccm.201801-0095PP. PMID: 29746142.
PHILADELPHIA — Promise that the unmet need for more effective pulmonary artery hypertension treatments may soon be met was in strong evidence in research into three strategies presented at this year’s recent American Heart Association scientific sessions; one was based on an ancient Chinese herb epimedium (yin yang huo or horny goat weed) commonly used for treating sexual dysfunction and directly related to the phosphodiesterase inhibitors sildenafil, vardenafil, and tadalafil (sold as Viagra, Levitra, and Cialis). A second studied sotatercept, an investigational, potential first-in-class activin signaling inhibitor biologic, and a third evaluated physically ablating the baroreceptor nerves that stimulate vasoconstriction of the pulmonary artery via catheter-based techniques.
Until as recently as the late 1970s, a pulmonary arterial hypertension diagnosis was a uniformly fatal one.1 While associated with pulmonary and right ventricle remodeling, and leads toward heart failure and death. The complex underlying pathogenesis was divided into six groups by the 6th World Symposium on Pulmonary Hypertension (WSPH) in 2018, and includes as its most common features pulmonary artery endothelial cell dysfunction, pulmonary artery smooth muscle cell proliferation and migration, and dysregulated fibroblast activity leading to dysregulated vasoconstriction, micro and in-situ vascular thrombosis, vascular fibrosis and pathogenic remodeling of pulmonary vessels.1 The threshold mean arterial pressure (mPAP) for pulmonary arterial hypertension was defined by the 6th [WSPH] at mPAP ≥ 20 mm Hg, twice the upper limit of a normal mPAP of 14.0 ± 3.3 mm Hg as reported by Kovacs et al. in 2018.2
Pathways for current therapies
Current drugs for pulmonary arterial hypertension focus on three signaling pathways, including the endothelin receptor, prostacyclin and nitric oxide pathways, stated Zhi-Cheng Jing, MD, professor of medicine, head of the cardiology department at Peking Union Medical College Hospital, Peking, China. While the phosphodiesterase 5 inhibitors sildenafil and tadalafil, which target the nitric oxide pathway, came into wide use after Food and Drug Administration approval, the need for higher PDE5-selectivity remains, Dr. Jing said. Structurally modified from the active ingredient in epimedium, TPN171H is an investigational PDE5 inhibitor which has shown several favorable features: a greater PDE5 selectivity than both sildenafil and tadalafil in vitro, an ability to decrease right ventricular systolic pressure and alleviate arterial remodeling in animal studies, and safety and tolerability in healthy human subjects.
The current randomized, double-blind, placebo-and active-controlled phase IIa study assessed the hemodynamic impact of a single oral dose of TPN171H in 60 pulmonary arterial hypertension patients (mean age ~34 years, 83.3% female), all with negative vasodilation test results and in WHO class 2 or 3. Only patients aged 18-75 years with group 1 pulmonary arterial hypertension of idiopathic, connective tissue disorder, or repaired congenital heart defects etiology were included. Patients were divided into six groups: placebo, TPN171H at 2.5, 5, and 10 milligrams, and tadalafil at 20 and 40 milligrams.
For the primary endpoint of maximum decrease in pulmonary vascular resistance (PVR), significant reductions vs. placebo were found only for the TPN171H 5-mg group (–41.2% vs. –24.4%; P = .008) and for the 20-mg (–39.8%) and 40-mg (–37.6%) tadalafil groups (both P < .05). What was not seen in the tadalafil groups, but was evident in the TPN171H 5-mg group, was a significant reduction in the secondary endpoint of PVR/SVR (systolic vascular resistance) at 2, 3, and 5 hours (all P < .05). “As we know,” Dr. Jing said in an interview, “the PDE5 inhibitor functions as a vasodilator, having an impact on both pulmonary circulation and systemic circulation. So, to evaluate the selectivity for pulmonary circulation is crucial when exploring a novel drug for pulmonary arterial hypertension. The change of PVR/SVR ratio from baseline is an indicator for selectivity for pulmonary circulation and implies that TPN171H has good PDE5 selectivity in the pulmonary vasculature,” Dr. Jing said.
TPN171H was well tolerated with no serious adverse effects (vomiting 10% and headache 10% were most common with no discontinuations).
TGF-signaling pathway
A meta-analysis of randomized controlled trials of sotatercept, an investigational fusion protein under priority FDA review that modulates the TGF-beta superfamily signaling pathway, looked at PVR, pulmonary arterial pressure (PAP), right arterial pressure (RAP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). A literature search by corresponding author Vamsikalyan Borra, MD, Knapp Medical Center, Weslaco, Texas, and colleagues identified two trials (STELLAR and PULSAR) comprising 429 patients with pulmonary arterial hypertension. The experimental arms (sotatercept) had 237 patients (mean age ~49 years, ~82% female) and the placebo arm had 192 patients (mean age ~47 years, ~80% female).
A pooled analysis showed significant reductions with sotatercept in PVR (standardization mean difference [SMD] = –1.00, 95% confidence interval [CI] = –1.2, –.79, P < .001), PAP (SMD = –1.34, 95% CI = 1.6, –1.08, P < .001), RAP (SMD = –0.66, 95% CI = –0.93, –0.39, P < .001), and the levels of NT-proBNP (SMD = –0.64, 95% CI = –1.01, –0.27, P < .001) at 24 weeks from baseline. The sotatercept safety profile was favorable, with lower overall incidence of adverse events (84.8% vs. 87.5%) and fewer adverse events leading to death (0.4% vs. 3.1%) compared with placebo. Further investigation is needed, however, according to Dr. Borra, into the higher frequency of reported thrombocytopenia (71.7% vs. 20.8%) with sotatercept. “Our findings,” Dr. Borra said in a poster session, “suggest that sotatercept is an effective treatment option for pulmonary arterial hypertension, with the potential to improve both pulmonary and cardiac function.”
Denervation technique
Catheter-based ablation techniques, most commonly using thermal energy, target the afferent and efferent fibers of the baroreceptor reflex in the main pulmonary artery trunk and bifurcation involved in elevated pulmonary artery pressure. Mounica Vorla, MD, Carle Foundation Hospital, Urbana, Illinois, and colleagues conducted an updated systematic review and meta-analysis of the safety and efficacy of pulmonary artery denervation (PADN) for pulmonary arterial hypertension in seven clinical trials with 506 patients with moderate-severe pulmonary arterial hypertension conducted from 2013 to 2022.
Compared with placebo, PADN treatment was associated with a significant reduction in mean pulmonary artery pressure (weighted mean difference [WMD] = –6.9 mm Hg; 95% CI = –9.7, –4.1; P < .01; I2 = 61) and pulmonary vascular resistance (WMD = –3.2; 95% CI = –5.4, –0.9; P = .005). PADN improvements in cardiac output were also statistically significant (WMD = 0.3; 95% CI = 0.07, 0.6; P = .012), with numerical improvement in 6-minute walking distance (WMD = 67.7; 95% CI = –3.73, 139.2; P = .06) in the PADN group. Side effects were less common in the PADN group as compared with the placebo group, Dr. Vorla reported. She concluded, “This updated meta-analysis supports PADN as a safe and efficacious therapy for severe pulmonary arterial hypertension.” The authors noted limitations imposed by the small sample size, large data heterogeneity, and medium-quality literature. Larger randomized, controlled trials with clinical endpoints comparing PADN with optimal medical therapy are needed, they stated.
References
1. Shah AJ et al. New Drugs and Therapies in Pulmonary Arterial Hypertension. Int J Mol Sci. 2023 Mar 19;24(6):5850. doi: 10.3390/ijms24065850. PMID: 36982922; PMCID: PMC10058689.
2. Kovacs G et al. Pulmonary Vascular Involvement in Chronic Obstructive Pulmonary Disease. Is There a Pulmonary Vascular Phenotype? Am J Respir Crit Care Med. 2018 Oct 15;198(8):1000-11. doi: 10.1164/rccm.201801-0095PP. PMID: 29746142.
FROM AHA 2023
Hematology is in the Brodsky family’s blood
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
In interviews, Robert and Max Brodsky spoke about the appeal of hematology and the threads that unite them with family members who came before. The elder Brodsky also talked about the work that’s made him the proudest during his year-long presidency at ASH.
Robert A. Brodsky is professor of medicine and director of hematology at Johns Hopkins University, Baltimore. He is stepping down as ASH president at its annual meeting in San Diego, December 9-12. Here are excerpts from our conversation:
Q: What drew your dad into medicine?
Dr. Robert A. Brodsky: He was going through his medical training at the University of Pennsylvania, then the Vietnam War came, and he served at the National Institutes of Health in what they referred to as the Yellow Berets. He got very interested in retroviruses and viruses that lead to cancer, which was a foreign idea at the time. This led him into hematology, stem cells, and myeloproliferative disorders.
He had a very successful career in hematology and just loved it. He performed the first bone marrow transplant in the tristate area of Pennsylvania, Delaware, and New Jersey.
Q: What did he like about hematology specifically?
Dr. Robert A. Brodsky: It’s a fascinating field, probably the most scientific area of medicine. It’s so easy to access blood and bone marrow. You can grow it, you can look at it, you can see it. It’s hard to do that with a lung, heart, kidney, or brain. Even back then, they could translate some of the science. What really drew him to hematology — and me, for that matter — was looking at a blood smear or bone marrow and being able to make a diagnosis. The other thing is the personal aspect. Hematologists tend to like the long-term relationships that they develop with their patients over the years.
Q: What were the biggest transformations in hematology during his career?
Dr. Robert A. Brodsky: Bone marrow transplant had the biggest impact, and it’s an area he really pioneered. He was very much involved in some of the early bone marrow transplants and was very close with Dr. George W. Santos, who was at Johns Hopkins and one of the big pioneers in that area as well. To be able to take marrow from related donors, get it to grow without the patient rejecting it, and cure a disease, was really huge. When he started doing this, patients had no other option. To see patients be cured was incredibly satisfying to him.
Q: How did you end up following your father into hematology?
Dr. Robert A. Brodsky: My brother Jeff, who’s a surgeon and older than me, knew he was going into medicine — probably about 3 hours after he was born. I came to it late. I was a political science major as an undergrad and really trying to figure out what I wanted to do. In my sophomore year, I decided I wanted to give this a shot. My dad worked very hard, long hours, but you could tell he loved what he did. And he was never absent, always involved in our lives and still made time for everyone. At some level, that must have had an influence on me.
Q: What has changed in hematology over your 30-plus years in medicine?
A: When I look back at when I was a fellow, it’s just mind-boggling how many lethal or life-threatening diseases are now pretty easy to treat. I studied disorders like aplastic anemia, which was very fatal. Without treatment, patients would die within a year. Now, over 95% are cured. Another classic examples is chronic myeloid leukemia disorder. Back when I was a fellow, the median survival for CML was maybe 4 to 6 years. Now, Kareem Abdul Jabbar has had this[for about 15 years]. Also a lot of hematologic malignancies are being cured with immunotherapy approaches. We’ve figured out the pathophysiology of a lot of diseases, and there are incredible genetic diagnostic assays.
Q: What was your father’s relationship with ASH?
Dr. Robert A. Brodsky: The first ASH meeting was 1958 in Atlantic City, New Jersey. There were 300 hematologists there, and my dad was one of them. We’re going to have over 30,000 people in San Diego, which is a record, and another 5,000 or 6,000 virtually.
Q: As ASH president, what are your biggest accomplishments when it comes to addressing the shortage of hematologists and other issues?
Dr. Robert A. Brodsky: ASH is investing $19 million to develop fellowships with a focus on hematology.* This is going to put lots of new hematologists into the workforce over the next 5 to 10 years. We’ve also been working on the Maintenance of Certification [MOC] process to make it less onerous on physicians. It’s really a bad process, and it’s not just ASH [that’s complaining], it’s all of medicine. We’re hearing this from GI, endocrine, renal and the general internists.
[In a September 2023 letter to the American Board of Internal Medicine’s president and chief officer, Dr. Brodsky wrote that “ASH continues to support the importance of lifelong learning for hematologists via a program that is evidence-based, relevant to one’s practice, and transparent; however, these three basic requirements are not met by the current ABIM MOC program.” ASH is calling for a new and reformed MOC program.]
Q: What convinced ASH to expand its journals by adding Blood Neoplasia and Blood Vessels, Thrombosis & Hemostasis?
Dr. Robert A. Brodsky: ASH has two flagship journals right now, Blood and Blood Advances, and they’re both very competitive, high-impact journals. It turns out there’s not enough room to publish all the new science, and they end up rejecting the majority of the submissions that come to them. We decided to keep these journals in the ASH family because there’s some fantastic clinical trials and science that would be going elsewhere.
Dr. Brodsky’s sons both have medical degrees: Brett Brodsky, DO, is a resident at Virginia Commonwealth University who plans to become a sports medicine specialist, and Max Brodsky, MD, is a second-year fellow in hematology at Johns Hopkins University.
In an interview, Max Brodsky, MD, talked about the roots of his family’s dedication to caring for others.
Q: What drew you to hematology?
Dr. Max Brodsky: I’ve watched both my dad and my grandfather be leaders in the field as both physicians and scientists, and that was very inspirational for me to see. And I went to a medical school [Drexel University College of Medicine] that my dad went to and where my grandfather was on faculty. That was like walking in their footsteps in a major way.
Q: What do you hope to focus on as a hematologist?
Dr. Max Brodsky: I’m still working through that, but I am really interested in thrombotic thrombocytopenic purpura. Patients used to not be able to survive their initial episodes, but now we have good treatments and are able to follow them as outpatients. With this whole cohort of patients that are surviving, we’re seeing that they have more health problems — more heart disease, more strokes and kidney disease. There’s a whole growing field exploring how to treat these patients for their lifespan.
Q: How do you deal with the reality that more of your patients will die than in some other medical fields?
Dr. Max Brodsky: It is challenging, but I also see those moments as opportunities to support patients and families. I’m good at connecting to patients and families who are in scary situations. I’ve always had that skill of putting people at ease, making people feel calm, knowing that they can trust me, and I have their best interests in mind.
Q: Why do you think your family is so committed to medicine?
Dr. Max Brodsky: We’re Jewish, and looking to help the world is one of the main core values of Judaism. The Torah expects us to make this world better. Actually, my great-grandfather Max, whom I’m named after, used to dig tunnels to help people escape Ukraine and get to freedom. He was always looking to help others as well. My great-grandmother was shot crossing the border escaping from Ukraine, and he carried her the whole way to the boat. They lived in very poor West Philadelphia and poured everything into my grandfather. He became a great doctor, and his sons and his grandchildren are in medicine today.
*Correction, 12/11: A previous version of this story misstated the amount of ASH’s $19 million investment in developing fellowships with a focus on hematology.
FROM ASH 2023
What’s new in acne treatment?
NEW YORK — New treatments for acne, including the recent FDA approval of a topical gel that combines an antibiotic, a retinoid, and an antimicrobial agent, and reports on the safe use of lasers in people with darker skin types, were presented at the annual Mount Sinai Winter Symposium – Advances in Medical and Surgical Dermatology.
“Patients want clear skin and many don’t care how they get there. I see patients who have been on minocycline [a broad-spectrum antibiotic] for 2 years; this is really not the best way to treat our patients,” said Joshua Zeichner, MD, associate professor of dermatology at the Icahn School of Medicine at Mount Sinai Hospital, New York, who reviewed the current state of acne treatments at the meeting.
Patients often do not care about the risk of developing antibiotic resistance, he noted, citing a survey (funded by Almirall and presented at a previous conference), which found that less than 10% of adult patients or caregivers of patients being treated for acne were moderately or extremely worried about antibiotics compared with more than 65% of the clinicians. But despite their concerns, nearly 60% of clinicians surveyed reported prescribing broad-spectrum antibiotics “most” or “all of the time,” he said.
Dr. Zeichner said that patients’ short-term wishes overriding dermatologists’ own concerns can lead to antibiotic resistance, with a negative impact on patients’ microbiomes. He encouraged prescribers to incorporate sarecycline and other narrow spectrum antibiotics into their practice as part of antibiotic stewardship. These drugs have less of an impact on the gut microbiome than broad spectrum antibiotics, while targeting the patient’s acne.
Dr. Zeichner noted that “acne is more than a 12-week disease,” but manufacturers of acne treatments can only market information based on what is in the product labeling, which usually includes 12-week results. Yet, for many acne treatments, “as you continue treating over time, you’re seeing much better improvements,” he said.
As an example, he referred to data from an unpublished phase 4 Galderma study. Patients aged 17-35 years with acne and scarring who were treated with trifarotene cream demonstrated about a 52% rate of success in acne clearance as measured by the Investigator Global Assessment (IGA) at 24 weeks, up from 31.4% at 12 weeks, highlighting the need to consider long-term data, which is helpful for patients to know, he said.
Dr. Zeichner noted that many patients and their caregivers are enthusiastic about the idea of treatment that does not involve pharmaceuticals and that these options, while not “silver bullets,” are available and advancing.
These include light-based devices. He referred to a 7-week, open label efficacy and safety study of a photo-pneumatic device with broadband light (Strata Skin Sciences). This device uses thermal heat to target and destroy Cutibacterium acnes and reduce sebum production and has a vacuum feature that removes occlusive material from the pilosebaceous unit, which he said “leads directly to a reduction in acne lesions.”
Of note is the fact that the device’ filters out visible wavelength light, which minimizes absorption by melanin in the epidermis that can damage darker skin, making the treatment safe for most skin types. In the study of patients with mild to moderate facial acne, aged 12-40 years, treatment resulted in significant reductions in mean inflammatory and noninflammatory lesion counts, and mean IGA score at day 49 compared with baseline.
Similarly, Dr. Zeichner presented a 2022 study demonstrating the use of higher spectrum lasers (a 1726-nm [nanometer] laser) to shrink sebaceous glands and reduce sebum production to treat acne. In addition, lasers that operate at such a high frequency do not cause hyperpigmentation in individuals with darker skin types, he said.
Dr. Zeichner disclosed that he is an advisor, consultant, or speaker for AbbVie, Allergan, Arcutis, Beiersdorf, Dermavant, Galderma, Kenvue, L’Oreal, Ortho, Pfizer, Regeneron, UCB, and Sun.
A version of this article first appeared on Medscape.com.
NEW YORK — New treatments for acne, including the recent FDA approval of a topical gel that combines an antibiotic, a retinoid, and an antimicrobial agent, and reports on the safe use of lasers in people with darker skin types, were presented at the annual Mount Sinai Winter Symposium – Advances in Medical and Surgical Dermatology.
“Patients want clear skin and many don’t care how they get there. I see patients who have been on minocycline [a broad-spectrum antibiotic] for 2 years; this is really not the best way to treat our patients,” said Joshua Zeichner, MD, associate professor of dermatology at the Icahn School of Medicine at Mount Sinai Hospital, New York, who reviewed the current state of acne treatments at the meeting.
Patients often do not care about the risk of developing antibiotic resistance, he noted, citing a survey (funded by Almirall and presented at a previous conference), which found that less than 10% of adult patients or caregivers of patients being treated for acne were moderately or extremely worried about antibiotics compared with more than 65% of the clinicians. But despite their concerns, nearly 60% of clinicians surveyed reported prescribing broad-spectrum antibiotics “most” or “all of the time,” he said.
Dr. Zeichner said that patients’ short-term wishes overriding dermatologists’ own concerns can lead to antibiotic resistance, with a negative impact on patients’ microbiomes. He encouraged prescribers to incorporate sarecycline and other narrow spectrum antibiotics into their practice as part of antibiotic stewardship. These drugs have less of an impact on the gut microbiome than broad spectrum antibiotics, while targeting the patient’s acne.
Dr. Zeichner noted that “acne is more than a 12-week disease,” but manufacturers of acne treatments can only market information based on what is in the product labeling, which usually includes 12-week results. Yet, for many acne treatments, “as you continue treating over time, you’re seeing much better improvements,” he said.
As an example, he referred to data from an unpublished phase 4 Galderma study. Patients aged 17-35 years with acne and scarring who were treated with trifarotene cream demonstrated about a 52% rate of success in acne clearance as measured by the Investigator Global Assessment (IGA) at 24 weeks, up from 31.4% at 12 weeks, highlighting the need to consider long-term data, which is helpful for patients to know, he said.
Dr. Zeichner noted that many patients and their caregivers are enthusiastic about the idea of treatment that does not involve pharmaceuticals and that these options, while not “silver bullets,” are available and advancing.
These include light-based devices. He referred to a 7-week, open label efficacy and safety study of a photo-pneumatic device with broadband light (Strata Skin Sciences). This device uses thermal heat to target and destroy Cutibacterium acnes and reduce sebum production and has a vacuum feature that removes occlusive material from the pilosebaceous unit, which he said “leads directly to a reduction in acne lesions.”
Of note is the fact that the device’ filters out visible wavelength light, which minimizes absorption by melanin in the epidermis that can damage darker skin, making the treatment safe for most skin types. In the study of patients with mild to moderate facial acne, aged 12-40 years, treatment resulted in significant reductions in mean inflammatory and noninflammatory lesion counts, and mean IGA score at day 49 compared with baseline.
Similarly, Dr. Zeichner presented a 2022 study demonstrating the use of higher spectrum lasers (a 1726-nm [nanometer] laser) to shrink sebaceous glands and reduce sebum production to treat acne. In addition, lasers that operate at such a high frequency do not cause hyperpigmentation in individuals with darker skin types, he said.
Dr. Zeichner disclosed that he is an advisor, consultant, or speaker for AbbVie, Allergan, Arcutis, Beiersdorf, Dermavant, Galderma, Kenvue, L’Oreal, Ortho, Pfizer, Regeneron, UCB, and Sun.
A version of this article first appeared on Medscape.com.
NEW YORK — New treatments for acne, including the recent FDA approval of a topical gel that combines an antibiotic, a retinoid, and an antimicrobial agent, and reports on the safe use of lasers in people with darker skin types, were presented at the annual Mount Sinai Winter Symposium – Advances in Medical and Surgical Dermatology.
“Patients want clear skin and many don’t care how they get there. I see patients who have been on minocycline [a broad-spectrum antibiotic] for 2 years; this is really not the best way to treat our patients,” said Joshua Zeichner, MD, associate professor of dermatology at the Icahn School of Medicine at Mount Sinai Hospital, New York, who reviewed the current state of acne treatments at the meeting.
Patients often do not care about the risk of developing antibiotic resistance, he noted, citing a survey (funded by Almirall and presented at a previous conference), which found that less than 10% of adult patients or caregivers of patients being treated for acne were moderately or extremely worried about antibiotics compared with more than 65% of the clinicians. But despite their concerns, nearly 60% of clinicians surveyed reported prescribing broad-spectrum antibiotics “most” or “all of the time,” he said.
Dr. Zeichner said that patients’ short-term wishes overriding dermatologists’ own concerns can lead to antibiotic resistance, with a negative impact on patients’ microbiomes. He encouraged prescribers to incorporate sarecycline and other narrow spectrum antibiotics into their practice as part of antibiotic stewardship. These drugs have less of an impact on the gut microbiome than broad spectrum antibiotics, while targeting the patient’s acne.
Dr. Zeichner noted that “acne is more than a 12-week disease,” but manufacturers of acne treatments can only market information based on what is in the product labeling, which usually includes 12-week results. Yet, for many acne treatments, “as you continue treating over time, you’re seeing much better improvements,” he said.
As an example, he referred to data from an unpublished phase 4 Galderma study. Patients aged 17-35 years with acne and scarring who were treated with trifarotene cream demonstrated about a 52% rate of success in acne clearance as measured by the Investigator Global Assessment (IGA) at 24 weeks, up from 31.4% at 12 weeks, highlighting the need to consider long-term data, which is helpful for patients to know, he said.
Dr. Zeichner noted that many patients and their caregivers are enthusiastic about the idea of treatment that does not involve pharmaceuticals and that these options, while not “silver bullets,” are available and advancing.
These include light-based devices. He referred to a 7-week, open label efficacy and safety study of a photo-pneumatic device with broadband light (Strata Skin Sciences). This device uses thermal heat to target and destroy Cutibacterium acnes and reduce sebum production and has a vacuum feature that removes occlusive material from the pilosebaceous unit, which he said “leads directly to a reduction in acne lesions.”
Of note is the fact that the device’ filters out visible wavelength light, which minimizes absorption by melanin in the epidermis that can damage darker skin, making the treatment safe for most skin types. In the study of patients with mild to moderate facial acne, aged 12-40 years, treatment resulted in significant reductions in mean inflammatory and noninflammatory lesion counts, and mean IGA score at day 49 compared with baseline.
Similarly, Dr. Zeichner presented a 2022 study demonstrating the use of higher spectrum lasers (a 1726-nm [nanometer] laser) to shrink sebaceous glands and reduce sebum production to treat acne. In addition, lasers that operate at such a high frequency do not cause hyperpigmentation in individuals with darker skin types, he said.
Dr. Zeichner disclosed that he is an advisor, consultant, or speaker for AbbVie, Allergan, Arcutis, Beiersdorf, Dermavant, Galderma, Kenvue, L’Oreal, Ortho, Pfizer, Regeneron, UCB, and Sun.
A version of this article first appeared on Medscape.com.
ASH 2023: Equity, Sickle Cell, and Real-Life Outcomes
Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH, added that insight into actual patient experiences also will be a major theme at ASH 2023.
“There is a huge growth in research on outcomes and focusing on using real-world data and how important that is,” Dr. Dunbar said. “Academic research and hematology is really focusing on patient-reported outcomes and how care is delivered in a real-world setting – actually looking at what matters to patients. Are they alive in a certain number of years? And how are they feeling?”
As an example, Dr. Dunbar pointed to an abstract that examined clinical databases in Canada and found that real-world outcomes in multiple myeloma treatments were much worse than those in the original clinical trials for the therapies. Patients reached relapse 44% faster and their overall survival was 75% worse.
In the media briefing, ASH chair of communications Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami, noted that patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated.”
Dr. Dunbar agreed, noting that “patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects. They might stay on the drug for longer, or they have nurses who are always encouraging them of how to make it through a toxicity.”
Hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly,” she said.
Another highlighted study linked worse outcomes in African-Americans with pediatric acute myeloid leukemia to genetic traits that are more common in that population. The traits “likely explain at least in part the worst outcomes in Black patients in prior studies and on some regimens,” Dr. Dunbar said.
She added that the findings emphasize how testing for genetic variants and biomarkers that impact outcomes should be performed “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity.”
ASH President Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, Baltimore, highlighted an abstract that reported on the use of AI as a clinical decision support tool to differentiate two easily confused conditions — prefibrotic primary myelofibrosis and essential thrombocythemia.
AI “is a tool that’s going to help pathologists make more accurate and faster diagnoses,” he said. He also spotlighted an abstract about the use of “social media listening” to understand the experiences of patients with SCD and their caregivers. “There can be a lot of misuse and waste of time with social media, but they used this in a way to try and gain insight as to what’s really important to the patients and the caregiver.”
Also, in regard to SCD, Dr. Dunbar pointed to a study that reports on outcomes in patients who received lovotibeglogene autotemcel (lovo-cel) gene therapy for up to 60 months. Both this treatment and a CRISPR-based therapy called exa-cel “appear to result in comparable very impressive efficacy in terms of pain crises and organ dysfunction,” she said. “The hurdle is going to be figuring out how to deliver what will be very expensive and complicated therapies — but likely curative — therapies to patients.”
Another study to be presented at ASH — coauthored by Dr. Brodsky — shows promising results from reduced-intensity haploidentical bone marrow transplantation in adults with severe SCD. Results were similar to those seen with bone marrow from matched siblings, Dr. Sekeres said.
He added that more clarity is needed about new treatment options for SCD, perhaps through a “randomized trial where patients upfront get a haploidentical bone marrow transplant or fully matched bone marrow transplant. Then other patients are randomized to some of these other, newer technology therapies, and we follow them over time. We’re looking not only for overall survival but complications of the therapy itself and how many patients relapse from the treatment.”
Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH, added that insight into actual patient experiences also will be a major theme at ASH 2023.
“There is a huge growth in research on outcomes and focusing on using real-world data and how important that is,” Dr. Dunbar said. “Academic research and hematology is really focusing on patient-reported outcomes and how care is delivered in a real-world setting – actually looking at what matters to patients. Are they alive in a certain number of years? And how are they feeling?”
As an example, Dr. Dunbar pointed to an abstract that examined clinical databases in Canada and found that real-world outcomes in multiple myeloma treatments were much worse than those in the original clinical trials for the therapies. Patients reached relapse 44% faster and their overall survival was 75% worse.
In the media briefing, ASH chair of communications Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami, noted that patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated.”
Dr. Dunbar agreed, noting that “patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects. They might stay on the drug for longer, or they have nurses who are always encouraging them of how to make it through a toxicity.”
Hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly,” she said.
Another highlighted study linked worse outcomes in African-Americans with pediatric acute myeloid leukemia to genetic traits that are more common in that population. The traits “likely explain at least in part the worst outcomes in Black patients in prior studies and on some regimens,” Dr. Dunbar said.
She added that the findings emphasize how testing for genetic variants and biomarkers that impact outcomes should be performed “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity.”
ASH President Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, Baltimore, highlighted an abstract that reported on the use of AI as a clinical decision support tool to differentiate two easily confused conditions — prefibrotic primary myelofibrosis and essential thrombocythemia.
AI “is a tool that’s going to help pathologists make more accurate and faster diagnoses,” he said. He also spotlighted an abstract about the use of “social media listening” to understand the experiences of patients with SCD and their caregivers. “There can be a lot of misuse and waste of time with social media, but they used this in a way to try and gain insight as to what’s really important to the patients and the caregiver.”
Also, in regard to SCD, Dr. Dunbar pointed to a study that reports on outcomes in patients who received lovotibeglogene autotemcel (lovo-cel) gene therapy for up to 60 months. Both this treatment and a CRISPR-based therapy called exa-cel “appear to result in comparable very impressive efficacy in terms of pain crises and organ dysfunction,” she said. “The hurdle is going to be figuring out how to deliver what will be very expensive and complicated therapies — but likely curative — therapies to patients.”
Another study to be presented at ASH — coauthored by Dr. Brodsky — shows promising results from reduced-intensity haploidentical bone marrow transplantation in adults with severe SCD. Results were similar to those seen with bone marrow from matched siblings, Dr. Sekeres said.
He added that more clarity is needed about new treatment options for SCD, perhaps through a “randomized trial where patients upfront get a haploidentical bone marrow transplant or fully matched bone marrow transplant. Then other patients are randomized to some of these other, newer technology therapies, and we follow them over time. We’re looking not only for overall survival but complications of the therapy itself and how many patients relapse from the treatment.”
Cynthia E. Dunbar, MD, chief of the Translational Stem Cell Biology Branch at the National Heart, Lung, and Blood Institute and secretary of ASH, added that insight into actual patient experiences also will be a major theme at ASH 2023.
“There is a huge growth in research on outcomes and focusing on using real-world data and how important that is,” Dr. Dunbar said. “Academic research and hematology is really focusing on patient-reported outcomes and how care is delivered in a real-world setting – actually looking at what matters to patients. Are they alive in a certain number of years? And how are they feeling?”
As an example, Dr. Dunbar pointed to an abstract that examined clinical databases in Canada and found that real-world outcomes in multiple myeloma treatments were much worse than those in the original clinical trials for the therapies. Patients reached relapse 44% faster and their overall survival was 75% worse.
In the media briefing, ASH chair of communications Mikkael A. Sekeres, MD, MS, of the Sylvester Comprehensive Cancer Center at the University of Miami, noted that patients in these types of clinical trials “are just these pristine specimens of human beings except for the cancer that’s being treated.”
Dr. Dunbar agreed, noting that “patients who are able to enroll in clinical trials are more likely to be able to show up at the treatment center at the right time and for every dose, have transportation, and afford drugs to prevent side effects. They might stay on the drug for longer, or they have nurses who are always encouraging them of how to make it through a toxicity.”
Hematologists and patients should consider randomized controlled trials to be “the best possible outcome, and perhaps adjust their thinking if an individual patient is older, sicker, or less able to follow a regimen exactly,” she said.
Another highlighted study linked worse outcomes in African-Americans with pediatric acute myeloid leukemia to genetic traits that are more common in that population. The traits “likely explain at least in part the worst outcomes in Black patients in prior studies and on some regimens,” Dr. Dunbar said.
She added that the findings emphasize how testing for genetic variants and biomarkers that impact outcomes should be performed “instead of assuming that a certain dose should be given simply based on perceived or reported race or ethnicity.”
ASH President Robert A. Brodsky, MD, of Johns Hopkins University School of Medicine, Baltimore, highlighted an abstract that reported on the use of AI as a clinical decision support tool to differentiate two easily confused conditions — prefibrotic primary myelofibrosis and essential thrombocythemia.
AI “is a tool that’s going to help pathologists make more accurate and faster diagnoses,” he said. He also spotlighted an abstract about the use of “social media listening” to understand the experiences of patients with SCD and their caregivers. “There can be a lot of misuse and waste of time with social media, but they used this in a way to try and gain insight as to what’s really important to the patients and the caregiver.”
Also, in regard to SCD, Dr. Dunbar pointed to a study that reports on outcomes in patients who received lovotibeglogene autotemcel (lovo-cel) gene therapy for up to 60 months. Both this treatment and a CRISPR-based therapy called exa-cel “appear to result in comparable very impressive efficacy in terms of pain crises and organ dysfunction,” she said. “The hurdle is going to be figuring out how to deliver what will be very expensive and complicated therapies — but likely curative — therapies to patients.”
Another study to be presented at ASH — coauthored by Dr. Brodsky — shows promising results from reduced-intensity haploidentical bone marrow transplantation in adults with severe SCD. Results were similar to those seen with bone marrow from matched siblings, Dr. Sekeres said.
He added that more clarity is needed about new treatment options for SCD, perhaps through a “randomized trial where patients upfront get a haploidentical bone marrow transplant or fully matched bone marrow transplant. Then other patients are randomized to some of these other, newer technology therapies, and we follow them over time. We’re looking not only for overall survival but complications of the therapy itself and how many patients relapse from the treatment.”
AT ASH 2023
Fewer than 1 out of 4 patients with HCV-related liver cancer receive antivirals
, and rates aren’t much better for patients seen by specialists, based on a retrospective analysis of private insurance claims.
The study also showed that patients receiving DAAs lived significantly longer, emphasizing the importance of prescribing these medications to all eligible patients, reported principal investigator Mindie H. Nguyen, MD, AGAF,, of Stanford University Medical Center, Palo Alto, California, and colleagues.
“Prior studies have shown evidence of improved survival among HCV-related HCC patients who received DAA treatment, but not much is known about the current DAA utilization among these patients in the general US population,” said lead author Leslie Y. Kam, MD, a postdoctoral scholar in gastroenterology at Stanford Medicine, who presented the findings in November at the annual meeting of the American Association for the Study of Liver Diseases.
To generate real-world data, the investigators analyzed medical records from 3922 patients in Optum’s Clinformatics Data Mart Database. All patients had private medical insurance and received care for HCV-related HCC between 2015 and 2021.
“Instead of using institutional databases which tend to bias toward highly specialized tertiary care center patients, our study uses a large, national sample of HCV-HCC patients that represents real-world DAA treatment rates and survival outcomes,” Dr. Kam said in a written comment.
Within this cohort, fewer than one out of four patients (23.5%) received DAA, a rate that Dr. Kam called “dismally low.”
Patients with either compensated or decompensated cirrhosis had higher treatment rates than those without cirrhosis (24.2% or 24.5%, respectively, vs. 16.2%; P = .001). The investigators noted that more than half of the patients had decompensated cirrhosis, suggesting that HCV-related HCC was diagnosed late in the disease course.
Receiving care from a gastroenterologist or infectious disease physician also was associated with a higher treatment rate. Patients managed by a gastroenterologist alone had a treatment rate of 27.0%, while those who received care from a gastroenterologist or infectious disease doctor alongside an oncologist had a treatment rate of 25.6%, versus just 9.4% for those who received care from an oncologist alone, and 12.4% among those who did not see a specialist of any kind (P = .005).
These findings highlight “the need for a multidisciplinary approach to care in this population,” Dr. Kam suggested.
Echoing previous research, DAAs were associated with extended survival. A significantly greater percentage of patients who received DAA were alive after 5 years, compared with patients who did not receive DAA (47.2% vs. 35.2%; P less than .001). After adjustment for comorbidities, HCC treatment, race/ethnicity, sex, and age, DAAs were associated with a 39% reduction in risk of death (adjusted hazard ratio, 0.61; 0.53-0.69; P less than .001).
“There were also racial ethnic disparities in patient survival whether patients received DAA or not, with Black patients having worse survival,” Dr. Kam said. “As such, our study highlights that awareness of HCV remains low as does the use of DAA treatment. Therefore, culturally appropriate efforts to improve awareness of HCV must continue among the general public and health care workers as well as efforts to provide point of care accurate and rapid screening tests for HCV so that DAA treatment can be initiated in a timely manner for eligible patients. Continual education on the use of DAA treatment is also needed.”
Robert John Fontana, MD, AGAF, professor of medicine and transplant hepatologist at the University of Michigan, Ann Arbor, described the findings as “frustrating,” and “not the kind of stuff I like to hear about.
“Treatment rates are so low,” Dr. Fontana said, noting that even among gastroenterologists and infectious disease doctors, who should be well-versed in DAAs, antivirals were prescribed less than 30% of the time.
In an interview, Dr. Fontana highlighted the benefits of DAAs, including their ease-of-use and effectiveness.
“Hepatitis C was the leading reason that we had to do liver transplants in the United States for years,” he said. “Then once these really amazing drugs called direct-acting antivirals came out, they changed the landscape very quickly. It really was a game changer for my whole practice, and, nationally, the practice of transplant.”
Yet, this study and others suggest that these practice-altering agents are being underutilized, Dr. Fontana said. A variety of reasons could explain suboptimal usage, he suggested, including lack of awareness among medical professionals and the public, the recency of DAA approvals, low HCV testing rates, lack of symptoms in HCV-positive patients, and medication costs.
This latter barrier, at least, is dissolving, Dr. Fontana said. Some payers initially restricted which providers could prescribe DAAs, but now the economic consensus has swung in their favor, since curing patients of HCV brings significant health care savings down the line. This financial advantage—theoretically multiplied across 4-5 million Americans living with HCV—has bolstered a multi-institutional effort toward universal HCV screening, with testing recommended at least once in every person’s lifetime.
“It’s highly cost effective,” Dr. Fontana said. “Even though the drugs are super expensive, you will reduce cost by preventing the people streaming towards liver cancer or streaming towards liver transplant. That’s why all the professional societies—the USPSTF, the CDC—they all say, ‘OK, screen everyone.’ ”
Screening may be getting easier soon, Dr. Fontana predicted, as at-home HCV-testing kits are on the horizon, with development and adoption likely accelerated by the success of at-home viral testing during the COVID-19 pandemic.
Beyond broader screening, Dr. Fontana suggested that greater awareness of DAAs is needed both within and beyond the medical community.
He advised health care providers who don’t yet feel comfortable diagnosing or treating HCV to refer to their local specialist.
“That’s the main message,” Dr. Fontana said. “I’m always eternally hopeful that every little message helps.”
The investigators and Dr. Fontana disclosed no conflicts of interest.
, and rates aren’t much better for patients seen by specialists, based on a retrospective analysis of private insurance claims.
The study also showed that patients receiving DAAs lived significantly longer, emphasizing the importance of prescribing these medications to all eligible patients, reported principal investigator Mindie H. Nguyen, MD, AGAF,, of Stanford University Medical Center, Palo Alto, California, and colleagues.
“Prior studies have shown evidence of improved survival among HCV-related HCC patients who received DAA treatment, but not much is known about the current DAA utilization among these patients in the general US population,” said lead author Leslie Y. Kam, MD, a postdoctoral scholar in gastroenterology at Stanford Medicine, who presented the findings in November at the annual meeting of the American Association for the Study of Liver Diseases.
To generate real-world data, the investigators analyzed medical records from 3922 patients in Optum’s Clinformatics Data Mart Database. All patients had private medical insurance and received care for HCV-related HCC between 2015 and 2021.
“Instead of using institutional databases which tend to bias toward highly specialized tertiary care center patients, our study uses a large, national sample of HCV-HCC patients that represents real-world DAA treatment rates and survival outcomes,” Dr. Kam said in a written comment.
Within this cohort, fewer than one out of four patients (23.5%) received DAA, a rate that Dr. Kam called “dismally low.”
Patients with either compensated or decompensated cirrhosis had higher treatment rates than those without cirrhosis (24.2% or 24.5%, respectively, vs. 16.2%; P = .001). The investigators noted that more than half of the patients had decompensated cirrhosis, suggesting that HCV-related HCC was diagnosed late in the disease course.
Receiving care from a gastroenterologist or infectious disease physician also was associated with a higher treatment rate. Patients managed by a gastroenterologist alone had a treatment rate of 27.0%, while those who received care from a gastroenterologist or infectious disease doctor alongside an oncologist had a treatment rate of 25.6%, versus just 9.4% for those who received care from an oncologist alone, and 12.4% among those who did not see a specialist of any kind (P = .005).
These findings highlight “the need for a multidisciplinary approach to care in this population,” Dr. Kam suggested.
Echoing previous research, DAAs were associated with extended survival. A significantly greater percentage of patients who received DAA were alive after 5 years, compared with patients who did not receive DAA (47.2% vs. 35.2%; P less than .001). After adjustment for comorbidities, HCC treatment, race/ethnicity, sex, and age, DAAs were associated with a 39% reduction in risk of death (adjusted hazard ratio, 0.61; 0.53-0.69; P less than .001).
“There were also racial ethnic disparities in patient survival whether patients received DAA or not, with Black patients having worse survival,” Dr. Kam said. “As such, our study highlights that awareness of HCV remains low as does the use of DAA treatment. Therefore, culturally appropriate efforts to improve awareness of HCV must continue among the general public and health care workers as well as efforts to provide point of care accurate and rapid screening tests for HCV so that DAA treatment can be initiated in a timely manner for eligible patients. Continual education on the use of DAA treatment is also needed.”
Robert John Fontana, MD, AGAF, professor of medicine and transplant hepatologist at the University of Michigan, Ann Arbor, described the findings as “frustrating,” and “not the kind of stuff I like to hear about.
“Treatment rates are so low,” Dr. Fontana said, noting that even among gastroenterologists and infectious disease doctors, who should be well-versed in DAAs, antivirals were prescribed less than 30% of the time.
In an interview, Dr. Fontana highlighted the benefits of DAAs, including their ease-of-use and effectiveness.
“Hepatitis C was the leading reason that we had to do liver transplants in the United States for years,” he said. “Then once these really amazing drugs called direct-acting antivirals came out, they changed the landscape very quickly. It really was a game changer for my whole practice, and, nationally, the practice of transplant.”
Yet, this study and others suggest that these practice-altering agents are being underutilized, Dr. Fontana said. A variety of reasons could explain suboptimal usage, he suggested, including lack of awareness among medical professionals and the public, the recency of DAA approvals, low HCV testing rates, lack of symptoms in HCV-positive patients, and medication costs.
This latter barrier, at least, is dissolving, Dr. Fontana said. Some payers initially restricted which providers could prescribe DAAs, but now the economic consensus has swung in their favor, since curing patients of HCV brings significant health care savings down the line. This financial advantage—theoretically multiplied across 4-5 million Americans living with HCV—has bolstered a multi-institutional effort toward universal HCV screening, with testing recommended at least once in every person’s lifetime.
“It’s highly cost effective,” Dr. Fontana said. “Even though the drugs are super expensive, you will reduce cost by preventing the people streaming towards liver cancer or streaming towards liver transplant. That’s why all the professional societies—the USPSTF, the CDC—they all say, ‘OK, screen everyone.’ ”
Screening may be getting easier soon, Dr. Fontana predicted, as at-home HCV-testing kits are on the horizon, with development and adoption likely accelerated by the success of at-home viral testing during the COVID-19 pandemic.
Beyond broader screening, Dr. Fontana suggested that greater awareness of DAAs is needed both within and beyond the medical community.
He advised health care providers who don’t yet feel comfortable diagnosing or treating HCV to refer to their local specialist.
“That’s the main message,” Dr. Fontana said. “I’m always eternally hopeful that every little message helps.”
The investigators and Dr. Fontana disclosed no conflicts of interest.
, and rates aren’t much better for patients seen by specialists, based on a retrospective analysis of private insurance claims.
The study also showed that patients receiving DAAs lived significantly longer, emphasizing the importance of prescribing these medications to all eligible patients, reported principal investigator Mindie H. Nguyen, MD, AGAF,, of Stanford University Medical Center, Palo Alto, California, and colleagues.
“Prior studies have shown evidence of improved survival among HCV-related HCC patients who received DAA treatment, but not much is known about the current DAA utilization among these patients in the general US population,” said lead author Leslie Y. Kam, MD, a postdoctoral scholar in gastroenterology at Stanford Medicine, who presented the findings in November at the annual meeting of the American Association for the Study of Liver Diseases.
To generate real-world data, the investigators analyzed medical records from 3922 patients in Optum’s Clinformatics Data Mart Database. All patients had private medical insurance and received care for HCV-related HCC between 2015 and 2021.
“Instead of using institutional databases which tend to bias toward highly specialized tertiary care center patients, our study uses a large, national sample of HCV-HCC patients that represents real-world DAA treatment rates and survival outcomes,” Dr. Kam said in a written comment.
Within this cohort, fewer than one out of four patients (23.5%) received DAA, a rate that Dr. Kam called “dismally low.”
Patients with either compensated or decompensated cirrhosis had higher treatment rates than those without cirrhosis (24.2% or 24.5%, respectively, vs. 16.2%; P = .001). The investigators noted that more than half of the patients had decompensated cirrhosis, suggesting that HCV-related HCC was diagnosed late in the disease course.
Receiving care from a gastroenterologist or infectious disease physician also was associated with a higher treatment rate. Patients managed by a gastroenterologist alone had a treatment rate of 27.0%, while those who received care from a gastroenterologist or infectious disease doctor alongside an oncologist had a treatment rate of 25.6%, versus just 9.4% for those who received care from an oncologist alone, and 12.4% among those who did not see a specialist of any kind (P = .005).
These findings highlight “the need for a multidisciplinary approach to care in this population,” Dr. Kam suggested.
Echoing previous research, DAAs were associated with extended survival. A significantly greater percentage of patients who received DAA were alive after 5 years, compared with patients who did not receive DAA (47.2% vs. 35.2%; P less than .001). After adjustment for comorbidities, HCC treatment, race/ethnicity, sex, and age, DAAs were associated with a 39% reduction in risk of death (adjusted hazard ratio, 0.61; 0.53-0.69; P less than .001).
“There were also racial ethnic disparities in patient survival whether patients received DAA or not, with Black patients having worse survival,” Dr. Kam said. “As such, our study highlights that awareness of HCV remains low as does the use of DAA treatment. Therefore, culturally appropriate efforts to improve awareness of HCV must continue among the general public and health care workers as well as efforts to provide point of care accurate and rapid screening tests for HCV so that DAA treatment can be initiated in a timely manner for eligible patients. Continual education on the use of DAA treatment is also needed.”
Robert John Fontana, MD, AGAF, professor of medicine and transplant hepatologist at the University of Michigan, Ann Arbor, described the findings as “frustrating,” and “not the kind of stuff I like to hear about.
“Treatment rates are so low,” Dr. Fontana said, noting that even among gastroenterologists and infectious disease doctors, who should be well-versed in DAAs, antivirals were prescribed less than 30% of the time.
In an interview, Dr. Fontana highlighted the benefits of DAAs, including their ease-of-use and effectiveness.
“Hepatitis C was the leading reason that we had to do liver transplants in the United States for years,” he said. “Then once these really amazing drugs called direct-acting antivirals came out, they changed the landscape very quickly. It really was a game changer for my whole practice, and, nationally, the practice of transplant.”
Yet, this study and others suggest that these practice-altering agents are being underutilized, Dr. Fontana said. A variety of reasons could explain suboptimal usage, he suggested, including lack of awareness among medical professionals and the public, the recency of DAA approvals, low HCV testing rates, lack of symptoms in HCV-positive patients, and medication costs.
This latter barrier, at least, is dissolving, Dr. Fontana said. Some payers initially restricted which providers could prescribe DAAs, but now the economic consensus has swung in their favor, since curing patients of HCV brings significant health care savings down the line. This financial advantage—theoretically multiplied across 4-5 million Americans living with HCV—has bolstered a multi-institutional effort toward universal HCV screening, with testing recommended at least once in every person’s lifetime.
“It’s highly cost effective,” Dr. Fontana said. “Even though the drugs are super expensive, you will reduce cost by preventing the people streaming towards liver cancer or streaming towards liver transplant. That’s why all the professional societies—the USPSTF, the CDC—they all say, ‘OK, screen everyone.’ ”
Screening may be getting easier soon, Dr. Fontana predicted, as at-home HCV-testing kits are on the horizon, with development and adoption likely accelerated by the success of at-home viral testing during the COVID-19 pandemic.
Beyond broader screening, Dr. Fontana suggested that greater awareness of DAAs is needed both within and beyond the medical community.
He advised health care providers who don’t yet feel comfortable diagnosing or treating HCV to refer to their local specialist.
“That’s the main message,” Dr. Fontana said. “I’m always eternally hopeful that every little message helps.”
The investigators and Dr. Fontana disclosed no conflicts of interest.
AT THE LIVER MEETING
Taste and smell changes linked with worse QOL and cognition in cirrhosis, renal failure
than those who do not exhibit these sensory changes, according to investigators.
Clinicians should screen for changes in taste and smell among patients at risk of cognitive changes, and offer nutritional interventions to support body weight and QOL, reported principal investigator Jasmohan S. Bajaj, MD, AGAF, of Virginia Commonwealth University, Richmond, and colleagues.
“Cirrhosis is linked with poor nutrition, which could partly be due to anorexia in hepatic encephalopathy (HE) and coexistent renal failure,” the investigators wrote in their abstract, which Dr. Bajaj presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“We wanted to measure how changes in the brain in cirrhosis affect patients’ abilities to smell and taste, and study how that affects their quality of life,” Dr. Bajaj said in a written comment.
To this end, the investigators conducted an observational study involving 59 participants, among whom 22 were healthy, 21 had cirrhosis, and 16 had renal failure requiring dialysis.
“Prior studies individually have shown changes in taste and smell for these two organ failures,” Dr. Bajaj said. “We studied them together as well and linked these to quality of life and individual cognitive tests.”
Of note, individuals with past or current COVID-19, or with current or recent alcohol or tobacco use, were excluded.
Compared with healthy individuals, participants with cirrhosis or renal failure had significantly worse performance on a taste discrimination test, with perceptions of sweet and sour most affected.
Cognitive measurement with Psychometric Hepatic Encephalopathy Score (PHES) and Stroop tests showed that scores were worse for patients with disease than those without. Taste discrimination significantly correlated with both cognitive test scores, regardless of HE or dialysis, whereas smell only correlated with the Stroop test.
Multivariable analysis revealed that better PHES scores and smell discrimination were linked with better taste discrimination. Similarly, better PHES scores and taste discrimination contributed to better smell discrimination. Eating impairment was associated with worse Stroop scores and worse olfactory-related QOL, suggesting that sensory changes, cognitive changes, and eating behaviors were all correlated.
“Health care providers ought to be alert to changes in patients’ eating habits, diet and weight as their liver and kidney disease worsen and as their brain function changes,” Dr. Bajaj said. “Nutritionists and others may be able to assist patients with a healthy diet and suggest ways to improve patients’ reports of their quality of life. Taste and smell are just a few aspects of the complicated assessment of health-related quality of life, brain dysfunction, and nutritional compromise in cirrhosis. We need to be mindful to not just focus on these aspects but to individualize care.”
Adrian M. Di Bisceglie, MD, hepatologist and emeritus professor of internal medicine at Saint Louis University, said the study was “well done,” and called the findings “an interesting little tidbit” that would probably not change his practice as a physician, but could be valuable for designing nutritional interventions.
In an interview, Dr. Di Bisceglie explained that a well-balanced diet with adequate caloric intake can help slow the muscle wasting that occurs with the condition, but creating a tasty menu can be challenging when patients are asked to restrict their sodium intake as a means of reducing fluid retention.
“Salt contributes substantially to the enjoyment of food,” Dr. Di Bisceglie said.
Although the study did not specifically report the salt level in patients’ diets, Dr. Di Bisceglie said the findings highlight the need for low-salt strategies to improve palatability. For example, he suggested increasing umami, or savory flavor, as this can be accomplished without adding a significant amount of salt.
When asked if changes in taste or smell might be used as simple screening tools to detect cognitive impairment in patients with cirrhosis, Dr. Di Bisceglie said that this might be “possible,” but is probably unnecessary.
“There is an easy bedside test that we’ve been using for decades [to predict hepatic encephalopathy], which is reading,” Dr. Di Bisceglie said, noting that patients with cognitive deficits often describe reading paragraphs repeatedly without comprehending what they have read.
The investigators and Dr. Di Bisceglie disclosed no conflicts of interest.
than those who do not exhibit these sensory changes, according to investigators.
Clinicians should screen for changes in taste and smell among patients at risk of cognitive changes, and offer nutritional interventions to support body weight and QOL, reported principal investigator Jasmohan S. Bajaj, MD, AGAF, of Virginia Commonwealth University, Richmond, and colleagues.
“Cirrhosis is linked with poor nutrition, which could partly be due to anorexia in hepatic encephalopathy (HE) and coexistent renal failure,” the investigators wrote in their abstract, which Dr. Bajaj presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“We wanted to measure how changes in the brain in cirrhosis affect patients’ abilities to smell and taste, and study how that affects their quality of life,” Dr. Bajaj said in a written comment.
To this end, the investigators conducted an observational study involving 59 participants, among whom 22 were healthy, 21 had cirrhosis, and 16 had renal failure requiring dialysis.
“Prior studies individually have shown changes in taste and smell for these two organ failures,” Dr. Bajaj said. “We studied them together as well and linked these to quality of life and individual cognitive tests.”
Of note, individuals with past or current COVID-19, or with current or recent alcohol or tobacco use, were excluded.
Compared with healthy individuals, participants with cirrhosis or renal failure had significantly worse performance on a taste discrimination test, with perceptions of sweet and sour most affected.
Cognitive measurement with Psychometric Hepatic Encephalopathy Score (PHES) and Stroop tests showed that scores were worse for patients with disease than those without. Taste discrimination significantly correlated with both cognitive test scores, regardless of HE or dialysis, whereas smell only correlated with the Stroop test.
Multivariable analysis revealed that better PHES scores and smell discrimination were linked with better taste discrimination. Similarly, better PHES scores and taste discrimination contributed to better smell discrimination. Eating impairment was associated with worse Stroop scores and worse olfactory-related QOL, suggesting that sensory changes, cognitive changes, and eating behaviors were all correlated.
“Health care providers ought to be alert to changes in patients’ eating habits, diet and weight as their liver and kidney disease worsen and as their brain function changes,” Dr. Bajaj said. “Nutritionists and others may be able to assist patients with a healthy diet and suggest ways to improve patients’ reports of their quality of life. Taste and smell are just a few aspects of the complicated assessment of health-related quality of life, brain dysfunction, and nutritional compromise in cirrhosis. We need to be mindful to not just focus on these aspects but to individualize care.”
Adrian M. Di Bisceglie, MD, hepatologist and emeritus professor of internal medicine at Saint Louis University, said the study was “well done,” and called the findings “an interesting little tidbit” that would probably not change his practice as a physician, but could be valuable for designing nutritional interventions.
In an interview, Dr. Di Bisceglie explained that a well-balanced diet with adequate caloric intake can help slow the muscle wasting that occurs with the condition, but creating a tasty menu can be challenging when patients are asked to restrict their sodium intake as a means of reducing fluid retention.
“Salt contributes substantially to the enjoyment of food,” Dr. Di Bisceglie said.
Although the study did not specifically report the salt level in patients’ diets, Dr. Di Bisceglie said the findings highlight the need for low-salt strategies to improve palatability. For example, he suggested increasing umami, or savory flavor, as this can be accomplished without adding a significant amount of salt.
When asked if changes in taste or smell might be used as simple screening tools to detect cognitive impairment in patients with cirrhosis, Dr. Di Bisceglie said that this might be “possible,” but is probably unnecessary.
“There is an easy bedside test that we’ve been using for decades [to predict hepatic encephalopathy], which is reading,” Dr. Di Bisceglie said, noting that patients with cognitive deficits often describe reading paragraphs repeatedly without comprehending what they have read.
The investigators and Dr. Di Bisceglie disclosed no conflicts of interest.
than those who do not exhibit these sensory changes, according to investigators.
Clinicians should screen for changes in taste and smell among patients at risk of cognitive changes, and offer nutritional interventions to support body weight and QOL, reported principal investigator Jasmohan S. Bajaj, MD, AGAF, of Virginia Commonwealth University, Richmond, and colleagues.
“Cirrhosis is linked with poor nutrition, which could partly be due to anorexia in hepatic encephalopathy (HE) and coexistent renal failure,” the investigators wrote in their abstract, which Dr. Bajaj presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“We wanted to measure how changes in the brain in cirrhosis affect patients’ abilities to smell and taste, and study how that affects their quality of life,” Dr. Bajaj said in a written comment.
To this end, the investigators conducted an observational study involving 59 participants, among whom 22 were healthy, 21 had cirrhosis, and 16 had renal failure requiring dialysis.
“Prior studies individually have shown changes in taste and smell for these two organ failures,” Dr. Bajaj said. “We studied them together as well and linked these to quality of life and individual cognitive tests.”
Of note, individuals with past or current COVID-19, or with current or recent alcohol or tobacco use, were excluded.
Compared with healthy individuals, participants with cirrhosis or renal failure had significantly worse performance on a taste discrimination test, with perceptions of sweet and sour most affected.
Cognitive measurement with Psychometric Hepatic Encephalopathy Score (PHES) and Stroop tests showed that scores were worse for patients with disease than those without. Taste discrimination significantly correlated with both cognitive test scores, regardless of HE or dialysis, whereas smell only correlated with the Stroop test.
Multivariable analysis revealed that better PHES scores and smell discrimination were linked with better taste discrimination. Similarly, better PHES scores and taste discrimination contributed to better smell discrimination. Eating impairment was associated with worse Stroop scores and worse olfactory-related QOL, suggesting that sensory changes, cognitive changes, and eating behaviors were all correlated.
“Health care providers ought to be alert to changes in patients’ eating habits, diet and weight as their liver and kidney disease worsen and as their brain function changes,” Dr. Bajaj said. “Nutritionists and others may be able to assist patients with a healthy diet and suggest ways to improve patients’ reports of their quality of life. Taste and smell are just a few aspects of the complicated assessment of health-related quality of life, brain dysfunction, and nutritional compromise in cirrhosis. We need to be mindful to not just focus on these aspects but to individualize care.”
Adrian M. Di Bisceglie, MD, hepatologist and emeritus professor of internal medicine at Saint Louis University, said the study was “well done,” and called the findings “an interesting little tidbit” that would probably not change his practice as a physician, but could be valuable for designing nutritional interventions.
In an interview, Dr. Di Bisceglie explained that a well-balanced diet with adequate caloric intake can help slow the muscle wasting that occurs with the condition, but creating a tasty menu can be challenging when patients are asked to restrict their sodium intake as a means of reducing fluid retention.
“Salt contributes substantially to the enjoyment of food,” Dr. Di Bisceglie said.
Although the study did not specifically report the salt level in patients’ diets, Dr. Di Bisceglie said the findings highlight the need for low-salt strategies to improve palatability. For example, he suggested increasing umami, or savory flavor, as this can be accomplished without adding a significant amount of salt.
When asked if changes in taste or smell might be used as simple screening tools to detect cognitive impairment in patients with cirrhosis, Dr. Di Bisceglie said that this might be “possible,” but is probably unnecessary.
“There is an easy bedside test that we’ve been using for decades [to predict hepatic encephalopathy], which is reading,” Dr. Di Bisceglie said, noting that patients with cognitive deficits often describe reading paragraphs repeatedly without comprehending what they have read.
The investigators and Dr. Di Bisceglie disclosed no conflicts of interest.
AT THE LIVER MEETING
COVID livers are safe for transplant
, based on a national study with the longest follow-up to date.
Using livers from deceased patients with COVID-19 could be an opportunity expand organ availability, reported principal investigator Nadim Mahmud, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Findings were presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“During the COVID-19 pandemic, a few centers trialed transplanting solid organs from COVID-19 positive donors with promising initial results,” presenting author Roy X. Wang, MD, of the University of Pennsylvania, said in a written comment. “However, these were smaller experiences with short follow-up that were not exclusively focused on liver transplantation. We wanted to explore the safety of liver transplantation from COVID-19 positive donors using a large national dataset with the longest follow up time to date.”
The dataset included 13,096 COVID-negative donors and 299 COVID-positive donors who died between July 2020 and July 2022, with cases and controls matched via propensity scoring. COVID-positive donors were significantly more likely to be younger and have died of brain death. Beyond this difference in age, no significant demographic differences were detected.
After 1 year of follow-up, no statistically significant differences in patient survival (subhazard ratio, 1.11; log-rank P = .70) or allograft survival (hazard ratio, 1.44; log-rank P = .14) were detected when comparing livers transplanted from positive versus negative donors.
“Our findings support and expand upon the results from earlier studies,” Dr. Wang concluded. “Liver transplant from COVID-19-positive donors has acceptable short-term outcomes and may represent an opportunity to expand organ access.”
Still, more work is needed to assess other clinical metrics and long-term outcomes, he added.
“While we were able to show similar patient and graft survival post-transplant between COVID-19-positive and negative donors, rates of other complications were not investigated such as episodes of rejection, liver injury, and hospitalizations,” Dr. Wang said. “Due to data limitations, we are only able to report on outcomes up to 1 year post transplant. Additional investigation will be needed to continue monitoring future outcomes and identifying any differences between recipients of COVID-19-positive and negative donors.”
Timucin Taner, MD, PhD, division chair of transplant surgery at Mayo Clinic, Rochester, Minnesota, said the study is important because it reaffirms the majority opinion among transplant physicians: These livers are safe.
In an interview, Dr. Taner suggested that Dr. Wang’s call for longer term data is “mostly science speak,” since 1 year of follow-up should be sufficient to determine liver viability.
“If a liver from a COVID-19 donor behaved well for a year, then chances are it’s not going to behave badly [later on] because of the virus at the time of donation,” Dr. Taner said.
He said the reported trends in usage of COVID-positive livers reflect early hesitancy that waned with rising vaccination rates, and recognition that the virus could not be spread via liver donation.
“To date, the only transmission [of SARS-CoV-2] from a transplant has been from a lung transplant,” Dr. Taner said, “and that was back in the days that we didn’t know about this. Other organs don’t transmit the disease, so they are easily usable.”
These new data should further increase confidence among both health care providers and patients, he added.
“[This study is] reassuring to the patients on the waitlist that these organs are very safe to use,” Dr. Taner said. “We as the transplant society are comfortable using them without any hesitation.”
The investigators and Dr. Taner disclosed no conflicts of interest.
, based on a national study with the longest follow-up to date.
Using livers from deceased patients with COVID-19 could be an opportunity expand organ availability, reported principal investigator Nadim Mahmud, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Findings were presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“During the COVID-19 pandemic, a few centers trialed transplanting solid organs from COVID-19 positive donors with promising initial results,” presenting author Roy X. Wang, MD, of the University of Pennsylvania, said in a written comment. “However, these were smaller experiences with short follow-up that were not exclusively focused on liver transplantation. We wanted to explore the safety of liver transplantation from COVID-19 positive donors using a large national dataset with the longest follow up time to date.”
The dataset included 13,096 COVID-negative donors and 299 COVID-positive donors who died between July 2020 and July 2022, with cases and controls matched via propensity scoring. COVID-positive donors were significantly more likely to be younger and have died of brain death. Beyond this difference in age, no significant demographic differences were detected.
After 1 year of follow-up, no statistically significant differences in patient survival (subhazard ratio, 1.11; log-rank P = .70) or allograft survival (hazard ratio, 1.44; log-rank P = .14) were detected when comparing livers transplanted from positive versus negative donors.
“Our findings support and expand upon the results from earlier studies,” Dr. Wang concluded. “Liver transplant from COVID-19-positive donors has acceptable short-term outcomes and may represent an opportunity to expand organ access.”
Still, more work is needed to assess other clinical metrics and long-term outcomes, he added.
“While we were able to show similar patient and graft survival post-transplant between COVID-19-positive and negative donors, rates of other complications were not investigated such as episodes of rejection, liver injury, and hospitalizations,” Dr. Wang said. “Due to data limitations, we are only able to report on outcomes up to 1 year post transplant. Additional investigation will be needed to continue monitoring future outcomes and identifying any differences between recipients of COVID-19-positive and negative donors.”
Timucin Taner, MD, PhD, division chair of transplant surgery at Mayo Clinic, Rochester, Minnesota, said the study is important because it reaffirms the majority opinion among transplant physicians: These livers are safe.
In an interview, Dr. Taner suggested that Dr. Wang’s call for longer term data is “mostly science speak,” since 1 year of follow-up should be sufficient to determine liver viability.
“If a liver from a COVID-19 donor behaved well for a year, then chances are it’s not going to behave badly [later on] because of the virus at the time of donation,” Dr. Taner said.
He said the reported trends in usage of COVID-positive livers reflect early hesitancy that waned with rising vaccination rates, and recognition that the virus could not be spread via liver donation.
“To date, the only transmission [of SARS-CoV-2] from a transplant has been from a lung transplant,” Dr. Taner said, “and that was back in the days that we didn’t know about this. Other organs don’t transmit the disease, so they are easily usable.”
These new data should further increase confidence among both health care providers and patients, he added.
“[This study is] reassuring to the patients on the waitlist that these organs are very safe to use,” Dr. Taner said. “We as the transplant society are comfortable using them without any hesitation.”
The investigators and Dr. Taner disclosed no conflicts of interest.
, based on a national study with the longest follow-up to date.
Using livers from deceased patients with COVID-19 could be an opportunity expand organ availability, reported principal investigator Nadim Mahmud, MD, of the University of Pennsylvania, Philadelphia, and colleagues.
Findings were presented in November at the annual meeting of the American Association for the Study of Liver Diseases.
“During the COVID-19 pandemic, a few centers trialed transplanting solid organs from COVID-19 positive donors with promising initial results,” presenting author Roy X. Wang, MD, of the University of Pennsylvania, said in a written comment. “However, these were smaller experiences with short follow-up that were not exclusively focused on liver transplantation. We wanted to explore the safety of liver transplantation from COVID-19 positive donors using a large national dataset with the longest follow up time to date.”
The dataset included 13,096 COVID-negative donors and 299 COVID-positive donors who died between July 2020 and July 2022, with cases and controls matched via propensity scoring. COVID-positive donors were significantly more likely to be younger and have died of brain death. Beyond this difference in age, no significant demographic differences were detected.
After 1 year of follow-up, no statistically significant differences in patient survival (subhazard ratio, 1.11; log-rank P = .70) or allograft survival (hazard ratio, 1.44; log-rank P = .14) were detected when comparing livers transplanted from positive versus negative donors.
“Our findings support and expand upon the results from earlier studies,” Dr. Wang concluded. “Liver transplant from COVID-19-positive donors has acceptable short-term outcomes and may represent an opportunity to expand organ access.”
Still, more work is needed to assess other clinical metrics and long-term outcomes, he added.
“While we were able to show similar patient and graft survival post-transplant between COVID-19-positive and negative donors, rates of other complications were not investigated such as episodes of rejection, liver injury, and hospitalizations,” Dr. Wang said. “Due to data limitations, we are only able to report on outcomes up to 1 year post transplant. Additional investigation will be needed to continue monitoring future outcomes and identifying any differences between recipients of COVID-19-positive and negative donors.”
Timucin Taner, MD, PhD, division chair of transplant surgery at Mayo Clinic, Rochester, Minnesota, said the study is important because it reaffirms the majority opinion among transplant physicians: These livers are safe.
In an interview, Dr. Taner suggested that Dr. Wang’s call for longer term data is “mostly science speak,” since 1 year of follow-up should be sufficient to determine liver viability.
“If a liver from a COVID-19 donor behaved well for a year, then chances are it’s not going to behave badly [later on] because of the virus at the time of donation,” Dr. Taner said.
He said the reported trends in usage of COVID-positive livers reflect early hesitancy that waned with rising vaccination rates, and recognition that the virus could not be spread via liver donation.
“To date, the only transmission [of SARS-CoV-2] from a transplant has been from a lung transplant,” Dr. Taner said, “and that was back in the days that we didn’t know about this. Other organs don’t transmit the disease, so they are easily usable.”
These new data should further increase confidence among both health care providers and patients, he added.
“[This study is] reassuring to the patients on the waitlist that these organs are very safe to use,” Dr. Taner said. “We as the transplant society are comfortable using them without any hesitation.”
The investigators and Dr. Taner disclosed no conflicts of interest.
AT THE LIVER MEETING
More than one-third of adults in the US could have NAFLD by 2050
, according to investigators.
These findings suggest that health care systems should prepare for “large increases” in cases of hepatocellular carcinoma (HCC) and need for liver transplants, reported lead author Phuc Le, PhD, MPH, of the Cleveland Clinic, and colleagues.
“Following the alarming rise in prevalence of obesity and diabetes, NAFLD is projected to become the leading indication for liver transplant in the United States in the next decade,” Dr. Le and colleagues wrote in their abstract for the annual meeting of the American Association for the Study of Liver Diseases. “A better understanding of the clinical burden associated with NAFLD will enable health systems to prepare to meet this imminent demand from patients.”
To this end, Dr. Le and colleagues developed an agent-based state transition model to predict future prevalence of NAFLD and associated outcomes.
In the first part of the model, the investigators simulated population growth in the United States using Census Bureau data, including new births and immigration, from the year 2000 onward. The second part of the model simulated natural progression of NAFLD in adults via 14 associated conditions and events, including steatosis, nonalcoholic steatohepatitis (NASH), HCC, liver transplants, liver-related mortality, and others.
By first comparing simulated findings with actual findings between 2000 and 2018, the investigators confirmed that their model could reliably predict the intended epidemiological parameters.
Next, they turned their model toward the future.
It predicted that the prevalence of NAFLD among US adults will rise from 27.8% in 2020 to 34.3% in 2050. Over the same timeframe, prevalence of NASH is predicted to increase from 20.0% to 21.8%, proportion of NAFLD cases developing cirrhosis is expected to increase from 1.9% to 3.1%, and liver-related mortality is estimated to rise from 0.4% to 1% of all deaths.
The model also predicted that the burden of HCC will increase from 10,400 to 19,300 new cases per year, while liver transplant burden will more than double, from 1,700 to 4,200 transplants per year.
“Our model forecasts substantial clinical burden of NAFLD over the next three decades,” Dr. Le said in a virtual press conference. “And in the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant.”
During the press conference, Norah Terrault, MD, president of the AASLD from the University of Southern California, Los Angeles, noted that all of the reported outcomes, including increasing rates of liver cancer, cirrhosis, and transplants are “potentially preventable.”
Dr. Terrault went on to suggest ways of combating this increasing burden of NAFLD, which she referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), the name now recommended by the AASLD.
“There’s no way we’re going to be able to transplant our way out of this,” Dr. Terrault said. “We need to be bringing greater awareness both to patients, as well as to providers about how we seek out the diagnosis. And we need to bring greater awareness to the population around the things that contribute to MASLD.”
Rates of obesity and diabetes continue to rise, Dr. Terrault said, explaining why MASLD is more common than ever. To counteract these trends, she called for greater awareness of driving factors, such as dietary choices and sedentary lifestyle.
“These are all really important messages that we want to get out to the population, and are really the cornerstones for how we approach the management of patients who have MASLD,” Dr. Terrault said.
In discussion with Dr. Terrault, Dr. Le agreed that increased education may help stem the rising tide of disease, while treatment advances could also increase the odds of a brighter future.
“If we improve our management of NAFLD, or NAFLD-related comorbidities, and if we can develop an effective treatment for NAFLD, then obviously the future would not be so dark,” Dr. Le said, noting promising phase 3 data that would be presented at the meeting. “We are hopeful that the future of disease burden will not be as bad as our model predicts.”
The study was funded by the Agency for Healthcare Research and Quality. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings suggest that health care systems should prepare for “large increases” in cases of hepatocellular carcinoma (HCC) and need for liver transplants, reported lead author Phuc Le, PhD, MPH, of the Cleveland Clinic, and colleagues.
“Following the alarming rise in prevalence of obesity and diabetes, NAFLD is projected to become the leading indication for liver transplant in the United States in the next decade,” Dr. Le and colleagues wrote in their abstract for the annual meeting of the American Association for the Study of Liver Diseases. “A better understanding of the clinical burden associated with NAFLD will enable health systems to prepare to meet this imminent demand from patients.”
To this end, Dr. Le and colleagues developed an agent-based state transition model to predict future prevalence of NAFLD and associated outcomes.
In the first part of the model, the investigators simulated population growth in the United States using Census Bureau data, including new births and immigration, from the year 2000 onward. The second part of the model simulated natural progression of NAFLD in adults via 14 associated conditions and events, including steatosis, nonalcoholic steatohepatitis (NASH), HCC, liver transplants, liver-related mortality, and others.
By first comparing simulated findings with actual findings between 2000 and 2018, the investigators confirmed that their model could reliably predict the intended epidemiological parameters.
Next, they turned their model toward the future.
It predicted that the prevalence of NAFLD among US adults will rise from 27.8% in 2020 to 34.3% in 2050. Over the same timeframe, prevalence of NASH is predicted to increase from 20.0% to 21.8%, proportion of NAFLD cases developing cirrhosis is expected to increase from 1.9% to 3.1%, and liver-related mortality is estimated to rise from 0.4% to 1% of all deaths.
The model also predicted that the burden of HCC will increase from 10,400 to 19,300 new cases per year, while liver transplant burden will more than double, from 1,700 to 4,200 transplants per year.
“Our model forecasts substantial clinical burden of NAFLD over the next three decades,” Dr. Le said in a virtual press conference. “And in the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant.”
During the press conference, Norah Terrault, MD, president of the AASLD from the University of Southern California, Los Angeles, noted that all of the reported outcomes, including increasing rates of liver cancer, cirrhosis, and transplants are “potentially preventable.”
Dr. Terrault went on to suggest ways of combating this increasing burden of NAFLD, which she referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), the name now recommended by the AASLD.
“There’s no way we’re going to be able to transplant our way out of this,” Dr. Terrault said. “We need to be bringing greater awareness both to patients, as well as to providers about how we seek out the diagnosis. And we need to bring greater awareness to the population around the things that contribute to MASLD.”
Rates of obesity and diabetes continue to rise, Dr. Terrault said, explaining why MASLD is more common than ever. To counteract these trends, she called for greater awareness of driving factors, such as dietary choices and sedentary lifestyle.
“These are all really important messages that we want to get out to the population, and are really the cornerstones for how we approach the management of patients who have MASLD,” Dr. Terrault said.
In discussion with Dr. Terrault, Dr. Le agreed that increased education may help stem the rising tide of disease, while treatment advances could also increase the odds of a brighter future.
“If we improve our management of NAFLD, or NAFLD-related comorbidities, and if we can develop an effective treatment for NAFLD, then obviously the future would not be so dark,” Dr. Le said, noting promising phase 3 data that would be presented at the meeting. “We are hopeful that the future of disease burden will not be as bad as our model predicts.”
The study was funded by the Agency for Healthcare Research and Quality. The investigators disclosed no conflicts of interest.
, according to investigators.
These findings suggest that health care systems should prepare for “large increases” in cases of hepatocellular carcinoma (HCC) and need for liver transplants, reported lead author Phuc Le, PhD, MPH, of the Cleveland Clinic, and colleagues.
“Following the alarming rise in prevalence of obesity and diabetes, NAFLD is projected to become the leading indication for liver transplant in the United States in the next decade,” Dr. Le and colleagues wrote in their abstract for the annual meeting of the American Association for the Study of Liver Diseases. “A better understanding of the clinical burden associated with NAFLD will enable health systems to prepare to meet this imminent demand from patients.”
To this end, Dr. Le and colleagues developed an agent-based state transition model to predict future prevalence of NAFLD and associated outcomes.
In the first part of the model, the investigators simulated population growth in the United States using Census Bureau data, including new births and immigration, from the year 2000 onward. The second part of the model simulated natural progression of NAFLD in adults via 14 associated conditions and events, including steatosis, nonalcoholic steatohepatitis (NASH), HCC, liver transplants, liver-related mortality, and others.
By first comparing simulated findings with actual findings between 2000 and 2018, the investigators confirmed that their model could reliably predict the intended epidemiological parameters.
Next, they turned their model toward the future.
It predicted that the prevalence of NAFLD among US adults will rise from 27.8% in 2020 to 34.3% in 2050. Over the same timeframe, prevalence of NASH is predicted to increase from 20.0% to 21.8%, proportion of NAFLD cases developing cirrhosis is expected to increase from 1.9% to 3.1%, and liver-related mortality is estimated to rise from 0.4% to 1% of all deaths.
The model also predicted that the burden of HCC will increase from 10,400 to 19,300 new cases per year, while liver transplant burden will more than double, from 1,700 to 4,200 transplants per year.
“Our model forecasts substantial clinical burden of NAFLD over the next three decades,” Dr. Le said in a virtual press conference. “And in the absence of effective treatments, health systems should plan for large increases in the number of liver cancer cases and the need for liver transplant.”
During the press conference, Norah Terrault, MD, president of the AASLD from the University of Southern California, Los Angeles, noted that all of the reported outcomes, including increasing rates of liver cancer, cirrhosis, and transplants are “potentially preventable.”
Dr. Terrault went on to suggest ways of combating this increasing burden of NAFLD, which she referred to as metabolic dysfunction–associated steatotic liver disease (MASLD), the name now recommended by the AASLD.
“There’s no way we’re going to be able to transplant our way out of this,” Dr. Terrault said. “We need to be bringing greater awareness both to patients, as well as to providers about how we seek out the diagnosis. And we need to bring greater awareness to the population around the things that contribute to MASLD.”
Rates of obesity and diabetes continue to rise, Dr. Terrault said, explaining why MASLD is more common than ever. To counteract these trends, she called for greater awareness of driving factors, such as dietary choices and sedentary lifestyle.
“These are all really important messages that we want to get out to the population, and are really the cornerstones for how we approach the management of patients who have MASLD,” Dr. Terrault said.
In discussion with Dr. Terrault, Dr. Le agreed that increased education may help stem the rising tide of disease, while treatment advances could also increase the odds of a brighter future.
“If we improve our management of NAFLD, or NAFLD-related comorbidities, and if we can develop an effective treatment for NAFLD, then obviously the future would not be so dark,” Dr. Le said, noting promising phase 3 data that would be presented at the meeting. “We are hopeful that the future of disease burden will not be as bad as our model predicts.”
The study was funded by the Agency for Healthcare Research and Quality. The investigators disclosed no conflicts of interest.
AT THE LIVER MEETING