Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

Clinical trials for unresectable HCC (uHCC) have mandated excellent underlying liver function. Patients with Child-Pugh (CP) A cirrhosis do not have cirrhosis as their most life-limiting disease. In clinical practice, there are many patients with uHCC who are functionally well yet have CP-B cirrhosis. D'Alessio and colleagues undertook a retrospective evaluation of 202 patients with either CP-A or CP-B cirrhosis who received atezolizumab and bevacizumab as first-line treatment of uHCC. The majority, 154 patients (76%), had CP-A cirrhosis, whereas 48 (24%) had CP-B, including 21 B7, 21 B8, and 6 B9. The authors found that in the overall population, median overall survival (mOS) was 14.9 months (95% CI 13.6-16.3), with patients with CP-A mOS of 16.8 months (95% CI 14.1-23.9), and CP-B mOS of 6.7 months (95% CI 4.3-15.6; P = .0003). Overall response rates (ORR) were comparable, with an ORR of 26% in CP-A and 21% in CP-B, not influenced by Barcelona Clinic Liver Cancer (BCLC) stage, performance status, etiology (viral vs nonviral), portal vein thrombosis (PVT), or extrahepatic spread (P > .05 for all associations). The investigators concluded that atezolizumab and bevacizumab in patients with CP-B was well tolerated, with no relevant difference in terms of clinically significant treatment-related adverse events compared with patients with CP-A.

Shi and colleagues reported a randomized controlled trial of patients with HCC and microvascular invasion (MVI) who underwent suboptimal resection (distance from tumor edge to the cut surface < 1 mm), followed by either stereotactic body radiotherapy (SBRT) or observation. From August 2015 to December 2016, 76 patients with BCLC stage 0/A liver disease, MVI, and no macroscopic vascular invasion were randomized after partial hepatectomy to either observation or SBRT (35 Gy delivered in a week). The 1-, 3-, and 5-year disease free survival (DFS) rates were 92.1%, 65.8%, and 56.1% in the SBRT group vs 76.3%, 36.8%, and 26.3% in the surgery alone group, respectively (P = .005). The 1-, 3-, and 5-year overall survival (OS) rates were 100%, 89.5%, and 75.0% in SBRT group vs 100.0%, 68.4%, and 53.7% in the surgery alone group, respectively (P = .053). The authors concluded that SBRT eradicates residual tumor cells present at the margin and improves surgical outcomes.

Roth and colleagues evaluated the safety and efficacy of transarterial chemoembolization (TACE) in older (> 70 years) patients with intermediate HCC. Out of 271 patients evaluated, 88 were older patients. 20.5% of older patients experienced serious adverse events vs 21.3% of younger patients (P = .87). The predictive factors of serious adverse events were CP stage ≥ B7 (P < .0001), Eastern Cooperative Oncology Group (ECOG) scale ≥ 1 (P = .0019), and Model for End-stage Liver Disease (MELD) score ≥ 9 (P = .0415). The serious adverse event rate was not increased with age (P = .87). The authors concluded that age should not be an exclusionary factor when considering TACE.

A unique ratio of metabolites measured in blood may help supplement a clinical diagnosis of early Alzheimer’s disease (AD), allowing for earlier intervention, early research suggests.

Investigators found that plasma concentrations of 2-aminoethyl dihydrogen phosphate and taurine could distinguish adults with early-stage Alzheimer’s disease from cognitively normal adults.

“Our biomarker for early-stage Alzheimer’s disease represents new thinking and is unique from the amyloid-beta and p-tau molecules that are currently being investigated to diagnose AD,” Sandra Banack, PhD, senior scientist, Brain Chemistry Labs, Jackson, Wyoming, told this news organization.

If further studies pan out, Dr. Banack said this biomarker could “easily be transformed into a test to aid clinical evaluations for Alzheimer’s disease.”

The study was published online in PLOS ONE.
 

New drug target?

The researchers measured concentrations of 2-aminoethyl dihydrogen phosphate and taurine in blood plasma samples in 25 patients (21 men; mean age, 71) with a clinical diagnosis of early-stage Alzheimer’s based on a Clinical Dementia Rating (CDR) score of 0.5, suggesting very mild cognitive impairment, and 25 healthy controls (20 men; mean age, 39).

The concentration of 2-aminoethyl dihydrogen phosphate, normalized by the concentration of taurine, reliably distinguished blood samples of early-stage Alzheimer’s patients from controls in a blinded analysis.

This biomarker “could lead to new understanding of [AD] and lead to new drug candidates,” Dr. Banack told this news organization.

The researchers note that 2-aminoethyl dihydrogen phosphate plays an important role in the structure and function of cellular membranes.

Physiologic effects of increased 2-aminoethyl dihydrogen phosphate concentrations in the blood are not known. However, in one study, concentrations of this molecule were found to be significantly lower in the temporal cortex, frontal cortex, and hippocampus (40%) in patients with Alzheimer’s disease, compared with controls.

“New biomarkers take time before they can be implemented in the clinic. The next step will be to repeat the experiments using a large sample size of AD patient blood samples,” Dr. Banack told this news organization.

The study team is looking to source a larger sample size of AD blood samples to replicate these findings. They are also examining this biomarker relative to other neurodegenerative diseases.

“If verified with larger sample sizes, the quantification of 2-aminoethyl dihydrogen phosphate could potentially assist in the diagnosis of early-stage Alzheimer’s disease when used in conjunction with the patient’s CDR score and other potential AD biomarkers,” Dr. Banack and colleagues say.
 

Caveats, cautionary notes

Commenting on the findings, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the study is “interesting, though very small-scale and very preliminary.”

Dr. Edelmayer said one “major limitation” is that participants did not have their Alzheimer’s diagnosis confirmed with “gold standard biomarkers. They have been diagnosed based only on their cognitive and behavioral symptoms.”

She also cautioned that the study population is not representative – either of the general public or people living with Alzheimer’s disease.

For example, 41 out of all 50 samples are from men, “though we know women are disproportionately impacted by Alzheimer’s.”

“There is a mismatch in the age of the study groups,” Dr. Edelmayer noted. The mean age of controls in the study was 39 and the mean age of people with dementia was 71. Race or ethnicity and other demographic information is also unclear from the article.

“There is an urgent need for simple, inexpensive, noninvasive and easily available diagnostic tools for Alzheimer’s, such as a blood test. A simple blood test for Alzheimer’s would be a great advance for individuals with – and at risk for – the disease, families, doctors, and researchers,” Dr. Edelmayer said.

“Bottom line,” Dr. Edelmayer continued, “these results need to be further tested and verified in long-term, large-scale studies with diverse populations that are representative of those living with Alzheimer’s disease.”

This research was supported by the William Stamps Farish Fund and the Josephine P. & John J. Louis Foundation. Brain Chemistry Labs has applied for a patent related to this research. Dr. Edelmayer has no relevant disclosures.

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

A unique ratio of metabolites measured in blood may help supplement a clinical diagnosis of early Alzheimer’s disease (AD), allowing for earlier intervention, early research suggests.

Investigators found that plasma concentrations of 2-aminoethyl dihydrogen phosphate and taurine could distinguish adults with early-stage Alzheimer’s disease from cognitively normal adults.

“Our biomarker for early-stage Alzheimer’s disease represents new thinking and is unique from the amyloid-beta and p-tau molecules that are currently being investigated to diagnose AD,” Sandra Banack, PhD, senior scientist, Brain Chemistry Labs, Jackson, Wyoming, told this news organization.

If further studies pan out, Dr. Banack said this biomarker could “easily be transformed into a test to aid clinical evaluations for Alzheimer’s disease.”

The study was published online in PLOS ONE.
 

New drug target?

The researchers measured concentrations of 2-aminoethyl dihydrogen phosphate and taurine in blood plasma samples in 25 patients (21 men; mean age, 71) with a clinical diagnosis of early-stage Alzheimer’s based on a Clinical Dementia Rating (CDR) score of 0.5, suggesting very mild cognitive impairment, and 25 healthy controls (20 men; mean age, 39).

The concentration of 2-aminoethyl dihydrogen phosphate, normalized by the concentration of taurine, reliably distinguished blood samples of early-stage Alzheimer’s patients from controls in a blinded analysis.

This biomarker “could lead to new understanding of [AD] and lead to new drug candidates,” Dr. Banack told this news organization.

The researchers note that 2-aminoethyl dihydrogen phosphate plays an important role in the structure and function of cellular membranes.

Physiologic effects of increased 2-aminoethyl dihydrogen phosphate concentrations in the blood are not known. However, in one study, concentrations of this molecule were found to be significantly lower in the temporal cortex, frontal cortex, and hippocampus (40%) in patients with Alzheimer’s disease, compared with controls.

“New biomarkers take time before they can be implemented in the clinic. The next step will be to repeat the experiments using a large sample size of AD patient blood samples,” Dr. Banack told this news organization.

The study team is looking to source a larger sample size of AD blood samples to replicate these findings. They are also examining this biomarker relative to other neurodegenerative diseases.

“If verified with larger sample sizes, the quantification of 2-aminoethyl dihydrogen phosphate could potentially assist in the diagnosis of early-stage Alzheimer’s disease when used in conjunction with the patient’s CDR score and other potential AD biomarkers,” Dr. Banack and colleagues say.
 

Caveats, cautionary notes

Commenting on the findings, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the study is “interesting, though very small-scale and very preliminary.”

Dr. Edelmayer said one “major limitation” is that participants did not have their Alzheimer’s diagnosis confirmed with “gold standard biomarkers. They have been diagnosed based only on their cognitive and behavioral symptoms.”

She also cautioned that the study population is not representative – either of the general public or people living with Alzheimer’s disease.

For example, 41 out of all 50 samples are from men, “though we know women are disproportionately impacted by Alzheimer’s.”

“There is a mismatch in the age of the study groups,” Dr. Edelmayer noted. The mean age of controls in the study was 39 and the mean age of people with dementia was 71. Race or ethnicity and other demographic information is also unclear from the article.

“There is an urgent need for simple, inexpensive, noninvasive and easily available diagnostic tools for Alzheimer’s, such as a blood test. A simple blood test for Alzheimer’s would be a great advance for individuals with – and at risk for – the disease, families, doctors, and researchers,” Dr. Edelmayer said.

“Bottom line,” Dr. Edelmayer continued, “these results need to be further tested and verified in long-term, large-scale studies with diverse populations that are representative of those living with Alzheimer’s disease.”

This research was supported by the William Stamps Farish Fund and the Josephine P. & John J. Louis Foundation. Brain Chemistry Labs has applied for a patent related to this research. Dr. Edelmayer has no relevant disclosures.

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

A unique ratio of metabolites measured in blood may help supplement a clinical diagnosis of early Alzheimer’s disease (AD), allowing for earlier intervention, early research suggests.

Investigators found that plasma concentrations of 2-aminoethyl dihydrogen phosphate and taurine could distinguish adults with early-stage Alzheimer’s disease from cognitively normal adults.

“Our biomarker for early-stage Alzheimer’s disease represents new thinking and is unique from the amyloid-beta and p-tau molecules that are currently being investigated to diagnose AD,” Sandra Banack, PhD, senior scientist, Brain Chemistry Labs, Jackson, Wyoming, told this news organization.

If further studies pan out, Dr. Banack said this biomarker could “easily be transformed into a test to aid clinical evaluations for Alzheimer’s disease.”

The study was published online in PLOS ONE.
 

New drug target?

The researchers measured concentrations of 2-aminoethyl dihydrogen phosphate and taurine in blood plasma samples in 25 patients (21 men; mean age, 71) with a clinical diagnosis of early-stage Alzheimer’s based on a Clinical Dementia Rating (CDR) score of 0.5, suggesting very mild cognitive impairment, and 25 healthy controls (20 men; mean age, 39).

The concentration of 2-aminoethyl dihydrogen phosphate, normalized by the concentration of taurine, reliably distinguished blood samples of early-stage Alzheimer’s patients from controls in a blinded analysis.

This biomarker “could lead to new understanding of [AD] and lead to new drug candidates,” Dr. Banack told this news organization.

The researchers note that 2-aminoethyl dihydrogen phosphate plays an important role in the structure and function of cellular membranes.

Physiologic effects of increased 2-aminoethyl dihydrogen phosphate concentrations in the blood are not known. However, in one study, concentrations of this molecule were found to be significantly lower in the temporal cortex, frontal cortex, and hippocampus (40%) in patients with Alzheimer’s disease, compared with controls.

“New biomarkers take time before they can be implemented in the clinic. The next step will be to repeat the experiments using a large sample size of AD patient blood samples,” Dr. Banack told this news organization.

The study team is looking to source a larger sample size of AD blood samples to replicate these findings. They are also examining this biomarker relative to other neurodegenerative diseases.

“If verified with larger sample sizes, the quantification of 2-aminoethyl dihydrogen phosphate could potentially assist in the diagnosis of early-stage Alzheimer’s disease when used in conjunction with the patient’s CDR score and other potential AD biomarkers,” Dr. Banack and colleagues say.
 

Caveats, cautionary notes

Commenting on the findings, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the study is “interesting, though very small-scale and very preliminary.”

Dr. Edelmayer said one “major limitation” is that participants did not have their Alzheimer’s diagnosis confirmed with “gold standard biomarkers. They have been diagnosed based only on their cognitive and behavioral symptoms.”

She also cautioned that the study population is not representative – either of the general public or people living with Alzheimer’s disease.

For example, 41 out of all 50 samples are from men, “though we know women are disproportionately impacted by Alzheimer’s.”

“There is a mismatch in the age of the study groups,” Dr. Edelmayer noted. The mean age of controls in the study was 39 and the mean age of people with dementia was 71. Race or ethnicity and other demographic information is also unclear from the article.

“There is an urgent need for simple, inexpensive, noninvasive and easily available diagnostic tools for Alzheimer’s, such as a blood test. A simple blood test for Alzheimer’s would be a great advance for individuals with – and at risk for – the disease, families, doctors, and researchers,” Dr. Edelmayer said.

“Bottom line,” Dr. Edelmayer continued, “these results need to be further tested and verified in long-term, large-scale studies with diverse populations that are representative of those living with Alzheimer’s disease.”

This research was supported by the William Stamps Farish Fund and the Josephine P. & John J. Louis Foundation. Brain Chemistry Labs has applied for a patent related to this research. Dr. Edelmayer has no relevant disclosures.

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

The Society for Cardiovascular Angiography and Interventions (SCAI) has issued the first statement on best practices for percutaneous axillary arterial access and training.

The position statement helps fill a gap amid increasing use of transaxillary access as an alternative to the femoral route for large-bore transcatheter aortic valve replacement (TAVR), endovascular aortic repair (EVAR), and mechanical circulatory support.

“The need for alternative access has increased as we are using more and more TAVR for our elderly population, and EVAR has also increased,” writing committee chair Arnold H. Seto, MD, Long Beach VA Health Care System (California) said in an interview. “There’s also a set of patients who require balloon pumps for a prolonged period, and people were using balloon pumps from the axillary approach, which were not custom-designed for that purpose.”

He noted that the evidence base leans heavily on case reports and case series, and that they were approached for guidance by a vendor developing a balloon pump specific to axillary access. “So that helped spur all of us to get together and decide to write up something on this topic, which was developing, but was certainly picking up steam rapidly.”

The statement was published in the Journal of the Society for Cardiovascular Angiography and Interventions, and it reflects the consensus of experts in heart failure, interventional cardiology and radiology, and cardiothoracic and vascular surgery. It reviews anatomic considerations and risks for percutaneous axillary access and suggests techniques for insertion, closure, and complication management.

Although the femoral artery is the most frequent access site for percutaneous large-bore procedures, the document notes that this approach may be limited in 13%-20% of patients because of prior surgeries or severe aortoiliac and/or iliofemoral atherosclerotic disease, tortuosity, or calcification.

“Absolutely, the femoral should be the predominant access site,” Dr. Seto said. Whenever there is a compromised femoral artery, “the axillary artery, which is rarely involved with atherosclerosis, makes for the most optimal alternative access. Other forms of alternative access, including transcaval and transcarotid, are possible but have their own issues and difficulties.”

Axillary access has traditionally been done through an open surgical approach, which allows for direct puncture, primary arterial repair, or placement of a sidearm conduit. Percutaneous transaxillary access avoids a surgical incision and general anesthesia and, theoretically, reduces the risk of infection, he said. It also allows for better mobility for patients, for example, who may have a balloon pump in place for weeks or even a month when waiting for a bridge to transplant.

In terms of technique, key recommendations include:

• Gaining access preferably through the left axillary
• Inserting the needle directly through the pectoralis minor into the second segment of the axillary artery
• Using a shallow-needle angle of 25-30 degrees to improve access success and decrease sheath malformation, kinking, bleeding, or vessel perforation
• Using micropuncture needles to minimize trauma to adjacent tissues
• Abducting the patient’s arm to 45-90 degrees to reduce tortuosity
• Using angiographic and ultrasound techniques to optimize vascular access

The latter point was the one area of debate among the writing committee, Dr. Seto observed. “That is one of the controversies: Should we make ultrasound mandatory? ... Everybody agreed that it can be quite useful and was likely to be useful because of its success in every other access area,” he said. “But in the absence of randomized evidence, we couldn’t make it mandatory or a strong recommendation. We just had to make it one of several options for the operator.”

The document highlights the need for familiarity with potential axillary artery complications and their management, noting that the axillary is more fragile than the femoral artery and, thus, potentially more prone to complications during instrumentation.

Data from the ARMS study in 102 patients undergoing transaxillary access for mechanical hemodynamic support reported 17 procedural complications, including 10 minor access site bleeding events, one stroke, and one pseudoaneurysm. A small study of 25 complex EVAR procedures reported a perioperative access complication rate of 8%, including one axillary artery dissection and one stenosis.

“Despite the brachial plexus being around there, there’s actually rare reports of neurologic injury and certainly none that have been permanent,” Dr. Seto said. “Also, stroke risk is probably more related to your device size and type of device rather than the approach itself.”

A significant amount of the paper is also devoted to training and privileging suggestions with an emphasis on a multidisciplinary team. The writing group recommends graduate medical education programs develop training curricula in percutaneous axillary artery access.

Those already in practice should participate in a formal training program that focuses on axillary artery anatomy, training in large bore access and closure devices, and didactic training in imaging modalities as applied to the axillary artery. Training can occur hands-on or using online simulations.

They also recommend outlining the potential need or role for proctoring and call for ongoing formal professional monitoring programs to evaluate operator outcomes using local or registry data.

“From a privileging standpoint, it was important for hospitals to be equally fair, regardless of the specialty that a requesting practitioner came from,” Dr. Seto said. “In other words, treat the vascular surgeons and interventional cardiologists and radiologists equally in terms of who has the privilege to do transaxillary access.”

The SCAI position statement has been endorsed by the American College of Cardiology, the Heart Failure Society of America, the Society of Interventional Radiology, and the Vascular & Endovascular Surgery Society.

Dr. Seto reported receiving honoraria from Getinge prior to initiation of the document. Disclosures for the rest of the writing group are available with the original article.

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

The Society for Cardiovascular Angiography and Interventions (SCAI) has issued the first statement on best practices for percutaneous axillary arterial access and training.

The position statement helps fill a gap amid increasing use of transaxillary access as an alternative to the femoral route for large-bore transcatheter aortic valve replacement (TAVR), endovascular aortic repair (EVAR), and mechanical circulatory support.

“The need for alternative access has increased as we are using more and more TAVR for our elderly population, and EVAR has also increased,” writing committee chair Arnold H. Seto, MD, Long Beach VA Health Care System (California) said in an interview. “There’s also a set of patients who require balloon pumps for a prolonged period, and people were using balloon pumps from the axillary approach, which were not custom-designed for that purpose.”

He noted that the evidence base leans heavily on case reports and case series, and that they were approached for guidance by a vendor developing a balloon pump specific to axillary access. “So that helped spur all of us to get together and decide to write up something on this topic, which was developing, but was certainly picking up steam rapidly.”

The statement was published in the Journal of the Society for Cardiovascular Angiography and Interventions, and it reflects the consensus of experts in heart failure, interventional cardiology and radiology, and cardiothoracic and vascular surgery. It reviews anatomic considerations and risks for percutaneous axillary access and suggests techniques for insertion, closure, and complication management.

Although the femoral artery is the most frequent access site for percutaneous large-bore procedures, the document notes that this approach may be limited in 13%-20% of patients because of prior surgeries or severe aortoiliac and/or iliofemoral atherosclerotic disease, tortuosity, or calcification.

“Absolutely, the femoral should be the predominant access site,” Dr. Seto said. Whenever there is a compromised femoral artery, “the axillary artery, which is rarely involved with atherosclerosis, makes for the most optimal alternative access. Other forms of alternative access, including transcaval and transcarotid, are possible but have their own issues and difficulties.”

Axillary access has traditionally been done through an open surgical approach, which allows for direct puncture, primary arterial repair, or placement of a sidearm conduit. Percutaneous transaxillary access avoids a surgical incision and general anesthesia and, theoretically, reduces the risk of infection, he said. It also allows for better mobility for patients, for example, who may have a balloon pump in place for weeks or even a month when waiting for a bridge to transplant.

In terms of technique, key recommendations include:

• Gaining access preferably through the left axillary
• Inserting the needle directly through the pectoralis minor into the second segment of the axillary artery
• Using a shallow-needle angle of 25-30 degrees to improve access success and decrease sheath malformation, kinking, bleeding, or vessel perforation
• Using micropuncture needles to minimize trauma to adjacent tissues
• Abducting the patient’s arm to 45-90 degrees to reduce tortuosity
• Using angiographic and ultrasound techniques to optimize vascular access

The latter point was the one area of debate among the writing committee, Dr. Seto observed. “That is one of the controversies: Should we make ultrasound mandatory? ... Everybody agreed that it can be quite useful and was likely to be useful because of its success in every other access area,” he said. “But in the absence of randomized evidence, we couldn’t make it mandatory or a strong recommendation. We just had to make it one of several options for the operator.”

The document highlights the need for familiarity with potential axillary artery complications and their management, noting that the axillary is more fragile than the femoral artery and, thus, potentially more prone to complications during instrumentation.

Data from the ARMS study in 102 patients undergoing transaxillary access for mechanical hemodynamic support reported 17 procedural complications, including 10 minor access site bleeding events, one stroke, and one pseudoaneurysm. A small study of 25 complex EVAR procedures reported a perioperative access complication rate of 8%, including one axillary artery dissection and one stenosis.

“Despite the brachial plexus being around there, there’s actually rare reports of neurologic injury and certainly none that have been permanent,” Dr. Seto said. “Also, stroke risk is probably more related to your device size and type of device rather than the approach itself.”

A significant amount of the paper is also devoted to training and privileging suggestions with an emphasis on a multidisciplinary team. The writing group recommends graduate medical education programs develop training curricula in percutaneous axillary artery access.

Those already in practice should participate in a formal training program that focuses on axillary artery anatomy, training in large bore access and closure devices, and didactic training in imaging modalities as applied to the axillary artery. Training can occur hands-on or using online simulations.

They also recommend outlining the potential need or role for proctoring and call for ongoing formal professional monitoring programs to evaluate operator outcomes using local or registry data.

“From a privileging standpoint, it was important for hospitals to be equally fair, regardless of the specialty that a requesting practitioner came from,” Dr. Seto said. “In other words, treat the vascular surgeons and interventional cardiologists and radiologists equally in terms of who has the privilege to do transaxillary access.”

The SCAI position statement has been endorsed by the American College of Cardiology, the Heart Failure Society of America, the Society of Interventional Radiology, and the Vascular & Endovascular Surgery Society.

Dr. Seto reported receiving honoraria from Getinge prior to initiation of the document. Disclosures for the rest of the writing group are available with the original article.

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

The Society for Cardiovascular Angiography and Interventions (SCAI) has issued the first statement on best practices for percutaneous axillary arterial access and training.

The position statement helps fill a gap amid increasing use of transaxillary access as an alternative to the femoral route for large-bore transcatheter aortic valve replacement (TAVR), endovascular aortic repair (EVAR), and mechanical circulatory support.

“The need for alternative access has increased as we are using more and more TAVR for our elderly population, and EVAR has also increased,” writing committee chair Arnold H. Seto, MD, Long Beach VA Health Care System (California) said in an interview. “There’s also a set of patients who require balloon pumps for a prolonged period, and people were using balloon pumps from the axillary approach, which were not custom-designed for that purpose.”

He noted that the evidence base leans heavily on case reports and case series, and that they were approached for guidance by a vendor developing a balloon pump specific to axillary access. “So that helped spur all of us to get together and decide to write up something on this topic, which was developing, but was certainly picking up steam rapidly.”

The statement was published in the Journal of the Society for Cardiovascular Angiography and Interventions, and it reflects the consensus of experts in heart failure, interventional cardiology and radiology, and cardiothoracic and vascular surgery. It reviews anatomic considerations and risks for percutaneous axillary access and suggests techniques for insertion, closure, and complication management.

Although the femoral artery is the most frequent access site for percutaneous large-bore procedures, the document notes that this approach may be limited in 13%-20% of patients because of prior surgeries or severe aortoiliac and/or iliofemoral atherosclerotic disease, tortuosity, or calcification.

“Absolutely, the femoral should be the predominant access site,” Dr. Seto said. Whenever there is a compromised femoral artery, “the axillary artery, which is rarely involved with atherosclerosis, makes for the most optimal alternative access. Other forms of alternative access, including transcaval and transcarotid, are possible but have their own issues and difficulties.”

Axillary access has traditionally been done through an open surgical approach, which allows for direct puncture, primary arterial repair, or placement of a sidearm conduit. Percutaneous transaxillary access avoids a surgical incision and general anesthesia and, theoretically, reduces the risk of infection, he said. It also allows for better mobility for patients, for example, who may have a balloon pump in place for weeks or even a month when waiting for a bridge to transplant.

In terms of technique, key recommendations include:

• Gaining access preferably through the left axillary
• Inserting the needle directly through the pectoralis minor into the second segment of the axillary artery
• Using a shallow-needle angle of 25-30 degrees to improve access success and decrease sheath malformation, kinking, bleeding, or vessel perforation
• Using micropuncture needles to minimize trauma to adjacent tissues
• Abducting the patient’s arm to 45-90 degrees to reduce tortuosity
• Using angiographic and ultrasound techniques to optimize vascular access

The latter point was the one area of debate among the writing committee, Dr. Seto observed. “That is one of the controversies: Should we make ultrasound mandatory? ... Everybody agreed that it can be quite useful and was likely to be useful because of its success in every other access area,” he said. “But in the absence of randomized evidence, we couldn’t make it mandatory or a strong recommendation. We just had to make it one of several options for the operator.”

The document highlights the need for familiarity with potential axillary artery complications and their management, noting that the axillary is more fragile than the femoral artery and, thus, potentially more prone to complications during instrumentation.

Data from the ARMS study in 102 patients undergoing transaxillary access for mechanical hemodynamic support reported 17 procedural complications, including 10 minor access site bleeding events, one stroke, and one pseudoaneurysm. A small study of 25 complex EVAR procedures reported a perioperative access complication rate of 8%, including one axillary artery dissection and one stenosis.

“Despite the brachial plexus being around there, there’s actually rare reports of neurologic injury and certainly none that have been permanent,” Dr. Seto said. “Also, stroke risk is probably more related to your device size and type of device rather than the approach itself.”

A significant amount of the paper is also devoted to training and privileging suggestions with an emphasis on a multidisciplinary team. The writing group recommends graduate medical education programs develop training curricula in percutaneous axillary artery access.

Those already in practice should participate in a formal training program that focuses on axillary artery anatomy, training in large bore access and closure devices, and didactic training in imaging modalities as applied to the axillary artery. Training can occur hands-on or using online simulations.

They also recommend outlining the potential need or role for proctoring and call for ongoing formal professional monitoring programs to evaluate operator outcomes using local or registry data.

“From a privileging standpoint, it was important for hospitals to be equally fair, regardless of the specialty that a requesting practitioner came from,” Dr. Seto said. “In other words, treat the vascular surgeons and interventional cardiologists and radiologists equally in terms of who has the privilege to do transaxillary access.”

The SCAI position statement has been endorsed by the American College of Cardiology, the Heart Failure Society of America, the Society of Interventional Radiology, and the Vascular & Endovascular Surgery Society.

Dr. Seto reported receiving honoraria from Getinge prior to initiation of the document. Disclosures for the rest of the writing group are available with the original article.

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

The U.S. Food and Drug Administration has approved mavacamten (Camzyos, Bristol Myers Squibb) to improve functional capacity and symptoms in adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (oHCM).

Mavacamten is the first FDA-approved allosteric and reversible inhibitor selective for cardiac myosin that targets the underlying pathophysiology of the genetic disorder. It’s available in 2.5-mg, 5-mg, 10-mg, and 15-mg capsules.

“The approval of Camzyos represents a significant milestone for appropriate symptomatic obstructive HCM patients and their families, who have long awaited a new treatment option for this chronic and progressive disease,” Anjali T. Owens, MD, medical director of the Center for Inherited Cardiac Disease and assistant professor of medicine, University of Pennsylvania, Philadelphia, said in a news release.
 

‘Revolutionary’ change

The approval of mavacamten was based on data from the pivotal EXPLORER-HCM and EXPLORER-LTE (long-term extension) trial of adults with symptomatic NYHA class II-III oHCM.

In EXPLORER-HCM, treatment with mavacamten over 30 weeks led to significant improvement in exercise capacity, left ventricular outflow tract (LVOT) obstruction, NYHA functional class, and health status, as reported by this news organization.

The safety and efficacy findings seen at the end of the blinded, randomized, initial 30-week phase of EXPLORER-LTE were maintained in patients who continued treatment for a median of about 62 weeks.

Mavacamten represents “an almost revolutionary change” for the treatment of oHCM, Maya E. Guglin, MD, professor of clinical medicine and an advanced heart failure physician at Indiana University, Indianapolis, said during a press briefing earlier this month at the American College of Cardiology 2022 Scientific Session earlier this month.

“Until now, there was no good medical treatment for symptomatic oHCM. This will change the landscape, and without question it will change guidelines for treating oHCM,” Dr. Guglin said.

The product information for mavacamten includes a boxed warning citing a risk for heart failure.

Echocardiogram assessments of left ventricular ejection fraction (LVEF) are required before and during treatment.

Starting mavacamten in patients with LVEF below 55% is not recommended and the drug should be interrupted if LVEF falls below 50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status.

Concomitant use of mavacamten with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers can increase the risk for heart failure attributable to systolic dysfunction. Therefore, its use is contraindicated in patients using moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors, and moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers.

Because of the risk for heart failure attributable to systolic dysfunction, mavacamten is only available through the Camzyos Risk Evaluation and Mitigation Strategy (REMS) Program.

Full prescribing information is available online.

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

The U.S. Food and Drug Administration has approved mavacamten (Camzyos, Bristol Myers Squibb) to improve functional capacity and symptoms in adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (oHCM).

Mavacamten is the first FDA-approved allosteric and reversible inhibitor selective for cardiac myosin that targets the underlying pathophysiology of the genetic disorder. It’s available in 2.5-mg, 5-mg, 10-mg, and 15-mg capsules.

“The approval of Camzyos represents a significant milestone for appropriate symptomatic obstructive HCM patients and their families, who have long awaited a new treatment option for this chronic and progressive disease,” Anjali T. Owens, MD, medical director of the Center for Inherited Cardiac Disease and assistant professor of medicine, University of Pennsylvania, Philadelphia, said in a news release.
 

‘Revolutionary’ change

The approval of mavacamten was based on data from the pivotal EXPLORER-HCM and EXPLORER-LTE (long-term extension) trial of adults with symptomatic NYHA class II-III oHCM.

In EXPLORER-HCM, treatment with mavacamten over 30 weeks led to significant improvement in exercise capacity, left ventricular outflow tract (LVOT) obstruction, NYHA functional class, and health status, as reported by this news organization.

The safety and efficacy findings seen at the end of the blinded, randomized, initial 30-week phase of EXPLORER-LTE were maintained in patients who continued treatment for a median of about 62 weeks.

Mavacamten represents “an almost revolutionary change” for the treatment of oHCM, Maya E. Guglin, MD, professor of clinical medicine and an advanced heart failure physician at Indiana University, Indianapolis, said during a press briefing earlier this month at the American College of Cardiology 2022 Scientific Session earlier this month.

“Until now, there was no good medical treatment for symptomatic oHCM. This will change the landscape, and without question it will change guidelines for treating oHCM,” Dr. Guglin said.

The product information for mavacamten includes a boxed warning citing a risk for heart failure.

Echocardiogram assessments of left ventricular ejection fraction (LVEF) are required before and during treatment.

Starting mavacamten in patients with LVEF below 55% is not recommended and the drug should be interrupted if LVEF falls below 50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status.

Concomitant use of mavacamten with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers can increase the risk for heart failure attributable to systolic dysfunction. Therefore, its use is contraindicated in patients using moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors, and moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers.

Because of the risk for heart failure attributable to systolic dysfunction, mavacamten is only available through the Camzyos Risk Evaluation and Mitigation Strategy (REMS) Program.

Full prescribing information is available online.

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

The U.S. Food and Drug Administration has approved mavacamten (Camzyos, Bristol Myers Squibb) to improve functional capacity and symptoms in adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (oHCM).

Mavacamten is the first FDA-approved allosteric and reversible inhibitor selective for cardiac myosin that targets the underlying pathophysiology of the genetic disorder. It’s available in 2.5-mg, 5-mg, 10-mg, and 15-mg capsules.

“The approval of Camzyos represents a significant milestone for appropriate symptomatic obstructive HCM patients and their families, who have long awaited a new treatment option for this chronic and progressive disease,” Anjali T. Owens, MD, medical director of the Center for Inherited Cardiac Disease and assistant professor of medicine, University of Pennsylvania, Philadelphia, said in a news release.
 

‘Revolutionary’ change

The approval of mavacamten was based on data from the pivotal EXPLORER-HCM and EXPLORER-LTE (long-term extension) trial of adults with symptomatic NYHA class II-III oHCM.

In EXPLORER-HCM, treatment with mavacamten over 30 weeks led to significant improvement in exercise capacity, left ventricular outflow tract (LVOT) obstruction, NYHA functional class, and health status, as reported by this news organization.

The safety and efficacy findings seen at the end of the blinded, randomized, initial 30-week phase of EXPLORER-LTE were maintained in patients who continued treatment for a median of about 62 weeks.

Mavacamten represents “an almost revolutionary change” for the treatment of oHCM, Maya E. Guglin, MD, professor of clinical medicine and an advanced heart failure physician at Indiana University, Indianapolis, said during a press briefing earlier this month at the American College of Cardiology 2022 Scientific Session earlier this month.

“Until now, there was no good medical treatment for symptomatic oHCM. This will change the landscape, and without question it will change guidelines for treating oHCM,” Dr. Guglin said.

The product information for mavacamten includes a boxed warning citing a risk for heart failure.

Echocardiogram assessments of left ventricular ejection fraction (LVEF) are required before and during treatment.

Starting mavacamten in patients with LVEF below 55% is not recommended and the drug should be interrupted if LVEF falls below 50% at any visit or if the patient experiences heart failure symptoms or worsening clinical status.

Concomitant use of mavacamten with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers can increase the risk for heart failure attributable to systolic dysfunction. Therefore, its use is contraindicated in patients using moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors, and moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers.

Because of the risk for heart failure attributable to systolic dysfunction, mavacamten is only available through the Camzyos Risk Evaluation and Mitigation Strategy (REMS) Program.

Full prescribing information is available online.

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

Patients implanted with the Medtronic HeartWare ventricular assist device (HVAD) System who develop pump thrombosis could have a welding defect in the internal pump causing the pump to malfunction, the Food and Drug Administration said in a letter to health care professionals. 

Medtronic has sent providers an urgent medical device notice about the pump weld defect and is trying to identify which HVAD pumps are affected.

The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it has been fraught with problems.

This past June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization. 
 

Pump thrombosis

Medtronic has received complaints of suspected pump thrombosis in three patients with the HVAD System.

All three patients presented with one or more of the following signs or symptoms: grinding sound, transient power spikes on log files and high watt alarms, elevated lactate dehydrogenase, and low motor speed resulting in low perfusion or dizziness or lightheadedness.

Inspection of the returned pumps in these three cases identified a malfunction of the internal pump. The pumps were exchanged in all three patients. Two patients died after the pump exchange.

The FDA does not recommend the elective removal of properly functioning systems.

“Decisions about removing or exchanging the Medtronic HVAD System should be made by health care providers and patients on a case-by-case basis, considering the patient’s clinical status and surgical risks,” the agency advised.

Patients who present with one or more of the signs or symptoms of pump thrombosis should be first treated for pump thrombosis.

If symptoms fail to resolve, providers may consider whether the patient is a candidate for pump exchange, heart transplant, or pump explant for recovery, taking into account the patient’s clinical condition and surgical risks.

For patients with any of the signs and symptoms of pump thrombosis, logfiles from the controller should be uploaded to Medtronic.

The FDA is working with Medtronic to monitor for any adverse events related to pump weld defects and ensure patients with the HVAD implant continue to receive appropriate follow-up monitoring.

Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.

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

Patients implanted with the Medtronic HeartWare ventricular assist device (HVAD) System who develop pump thrombosis could have a welding defect in the internal pump causing the pump to malfunction, the Food and Drug Administration said in a letter to health care professionals. 

Medtronic has sent providers an urgent medical device notice about the pump weld defect and is trying to identify which HVAD pumps are affected.

The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it has been fraught with problems.

This past June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization. 
 

Pump thrombosis

Medtronic has received complaints of suspected pump thrombosis in three patients with the HVAD System.

All three patients presented with one or more of the following signs or symptoms: grinding sound, transient power spikes on log files and high watt alarms, elevated lactate dehydrogenase, and low motor speed resulting in low perfusion or dizziness or lightheadedness.

Inspection of the returned pumps in these three cases identified a malfunction of the internal pump. The pumps were exchanged in all three patients. Two patients died after the pump exchange.

The FDA does not recommend the elective removal of properly functioning systems.

“Decisions about removing or exchanging the Medtronic HVAD System should be made by health care providers and patients on a case-by-case basis, considering the patient’s clinical status and surgical risks,” the agency advised.

Patients who present with one or more of the signs or symptoms of pump thrombosis should be first treated for pump thrombosis.

If symptoms fail to resolve, providers may consider whether the patient is a candidate for pump exchange, heart transplant, or pump explant for recovery, taking into account the patient’s clinical condition and surgical risks.

For patients with any of the signs and symptoms of pump thrombosis, logfiles from the controller should be uploaded to Medtronic.

The FDA is working with Medtronic to monitor for any adverse events related to pump weld defects and ensure patients with the HVAD implant continue to receive appropriate follow-up monitoring.

Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.

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

Patients implanted with the Medtronic HeartWare ventricular assist device (HVAD) System who develop pump thrombosis could have a welding defect in the internal pump causing the pump to malfunction, the Food and Drug Administration said in a letter to health care professionals. 

Medtronic has sent providers an urgent medical device notice about the pump weld defect and is trying to identify which HVAD pumps are affected.

The Medtronic HVAD System was approved as a bridge to heart transplantation in 2012. Since then, it has been fraught with problems.

This past June, the company announced it was stopping all sales of the device and advised physicians to stop implanting it, as reported by this news organization. 
 

Pump thrombosis

Medtronic has received complaints of suspected pump thrombosis in three patients with the HVAD System.

All three patients presented with one or more of the following signs or symptoms: grinding sound, transient power spikes on log files and high watt alarms, elevated lactate dehydrogenase, and low motor speed resulting in low perfusion or dizziness or lightheadedness.

Inspection of the returned pumps in these three cases identified a malfunction of the internal pump. The pumps were exchanged in all three patients. Two patients died after the pump exchange.

The FDA does not recommend the elective removal of properly functioning systems.

“Decisions about removing or exchanging the Medtronic HVAD System should be made by health care providers and patients on a case-by-case basis, considering the patient’s clinical status and surgical risks,” the agency advised.

Patients who present with one or more of the signs or symptoms of pump thrombosis should be first treated for pump thrombosis.

If symptoms fail to resolve, providers may consider whether the patient is a candidate for pump exchange, heart transplant, or pump explant for recovery, taking into account the patient’s clinical condition and surgical risks.

For patients with any of the signs and symptoms of pump thrombosis, logfiles from the controller should be uploaded to Medtronic.

The FDA is working with Medtronic to monitor for any adverse events related to pump weld defects and ensure patients with the HVAD implant continue to receive appropriate follow-up monitoring.

Problems related to the Medtronic HVAD System should be reported to the FDA’s MedWatch program.

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

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.

Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).

“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.

This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.

Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”

It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
 

New scanners, new score

DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.

Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.

Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.

The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”

Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).

Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.

For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.

The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.

There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”

What might the future hold?

“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.

Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.

“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”

Dr. Faber and colleagues work was recently published in Rheumatology.

Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.

SAN DIEGO – Among nearly 1,200 single-session facial treatments over 6 years that paired injectable hyaluronic acid filler with lasers, none of the documented adverse events that occurred were directly related to spread of filler or laser treatment of the filled area, results from a single-center, retrospective study showed.

“Data on the safety of pairing single-session treatment with nonablative fractional 1,927-nm thulium and/or 1,550-nm erbium laser and fillers are lacking,” Shirin Bajaj, MD, said during a clinical abstract session at the annual conference of the American Society for Laser Medicine and Surgery. “Anecdotally, we have found this to be completely safe in our high-volume laser center. We typically do fillers first, followed by laser treatment.”

For the study, Dr. Bajaj, a dermatology fellow at the Laser & Skin Surgery Center of New York, and colleagues retrospectively reviewed the charts of 638 patients who had 1,186 single‐session facial treatments with nonablative fractional 1,927-nm thulium and/or 1,550-nm erbium laser (Fraxel DUAL by Solta) and injectable hyaluronic acid filler from August 2015 to June 2021. Safety over the 6-year period was assessed by the adverse events that occurred within the first 4 weeks. The mean age of patients at the time of treatment was 60 years and 95% were female. Fitzpatrick skin types were type 1 (46.1%), type II (48.1%), type III (5.5%), and type IV (0.3%).

Most patients had 1 single‐session treatment (64.3%); the rest had 2 sessions (17.7%), 3 sessions (8%), or 4-18 sessions (10%). Most (91.2%) were treated with the 1,927-nm thulium laser, while 1.8% were treated with the 1,550-nm erbium laser; the mean total energy delivered was 1.3 kilojoules. A small number of patients (7.0%) received treatment with both lasers.

The most common area treated with filler injections were the cheeks and/or tear troughs (85.6%), followed by the perioral area and/or marionette lines (83.7%), temples (31%), nasolabial folds (25.5%), lips (24%), jawline (23.8%), chin (6.5%), forehead (1.4%), glabella and brows (0.5% each), neck (0.3%), and nose (0.1%). One syringe of filler was used in 58.7% of cases, compared with two syringes in 28.7% of cases, three syringes in 9.9% of cases, and four to six syringes in 2.8% of cases.

Dr. Bajaj reported that of the 1,186 single‐session treatments, no adverse events were recorded that were directly related to spread of filler or laser treatment of the filled area, including product migration, unexpected loss of filler volume, vascular occlusion, acute pain, cutaneous necrosis, blindness, and cutaneous burn. There were no hospital or emergency department transfers or admissions and referrals to ENT specialists or ophthalmologists for additional work‐up.

“This is at a busy cosmetic dermatology and plastic surgery practice,” Dr. Bajaj said. “Additional studies may be needed to further validate our findings.”

The study’s lead author was Jordan V. Wang, MD, who is medical research director at the Laser & Skin Surgery Center of New York.

“At most, this retrospective data confirms what we have known for years to be true: that combination treatments with injectables including fillers are safe,” Catherine M. DiGiorgio, MD, a dermatologist who practices at the Boston Center for Facial Rejuvenation, told this news organization. “This is a small study out of a single office, so that is a limitation. However, many dermatologists have performed Fraxel plus filler treatments in the same session daily for the last 10 years without any issues.”

Dr. DiGiorgio was asked to comment on the results and was not an investigator.

Dr. Bajaj reported having no financial disclosures. Dr. Wang reported that he has received grants and/or research funding from ALASTIN Skincare, Cynosure, Lutronic, Novoxel, Sofwave, Solta Medical, Blossom Innovations, Allergan, Accure Acne Inc., and Soliton. Dr. DiGiorgio reported having no relevant disclosures.

SAN DIEGO – Among nearly 1,200 single-session facial treatments over 6 years that paired injectable hyaluronic acid filler with lasers, none of the documented adverse events that occurred were directly related to spread of filler or laser treatment of the filled area, results from a single-center, retrospective study showed.

“Data on the safety of pairing single-session treatment with nonablative fractional 1,927-nm thulium and/or 1,550-nm erbium laser and fillers are lacking,” Shirin Bajaj, MD, said during a clinical abstract session at the annual conference of the American Society for Laser Medicine and Surgery. “Anecdotally, we have found this to be completely safe in our high-volume laser center. We typically do fillers first, followed by laser treatment.”

For the study, Dr. Bajaj, a dermatology fellow at the Laser & Skin Surgery Center of New York, and colleagues retrospectively reviewed the charts of 638 patients who had 1,186 single‐session facial treatments with nonablative fractional 1,927-nm thulium and/or 1,550-nm erbium laser (Fraxel DUAL by Solta) and injectable hyaluronic acid filler from August 2015 to June 2021. Safety over the 6-year period was assessed by the adverse events that occurred within the first 4 weeks. The mean age of patients at the time of treatment was 60 years and 95% were female. Fitzpatrick skin types were type 1 (46.1%), type II (48.1%), type III (5.5%), and type IV (0.3%).

Most patients had 1 single‐session treatment (64.3%); the rest had 2 sessions (17.7%), 3 sessions (8%), or 4-18 sessions (10%). Most (91.2%) were treated with the 1,927-nm thulium laser, while 1.8% were treated with the 1,550-nm erbium laser; the mean total energy delivered was 1.3 kilojoules. A small number of patients (7.0%) received treatment with both lasers.

The most common area treated with filler injections were the cheeks and/or tear troughs (85.6%), followed by the perioral area and/or marionette lines (83.7%), temples (31%), nasolabial folds (25.5%), lips (24%), jawline (23.8%), chin (6.5%), forehead (1.4%), glabella and brows (0.5% each), neck (0.3%), and nose (0.1%). One syringe of filler was used in 58.7% of cases, compared with two syringes in 28.7% of cases, three syringes in 9.9% of cases, and four to six syringes in 2.8% of cases.

Dr. Bajaj reported that of the 1,186 single‐session treatments, no adverse events were recorded that were directly related to spread of filler or laser treatment of the filled area, including product migration, unexpected loss of filler volume, vascular occlusion, acute pain, cutaneous necrosis, blindness, and cutaneous burn. There were no hospital or emergency department transfers or admissions and referrals to ENT specialists or ophthalmologists for additional work‐up.

“This is at a busy cosmetic dermatology and plastic surgery practice,” Dr. Bajaj said. “Additional studies may be needed to further validate our findings.”

The study’s lead author was Jordan V. Wang, MD, who is medical research director at the Laser & Skin Surgery Center of New York.

“At most, this retrospective data confirms what we have known for years to be true: that combination treatments with injectables including fillers are safe,” Catherine M. DiGiorgio, MD, a dermatologist who practices at the Boston Center for Facial Rejuvenation, told this news organization. “This is a small study out of a single office, so that is a limitation. However, many dermatologists have performed Fraxel plus filler treatments in the same session daily for the last 10 years without any issues.”

Dr. DiGiorgio was asked to comment on the results and was not an investigator.

Dr. Bajaj reported having no financial disclosures. Dr. Wang reported that he has received grants and/or research funding from ALASTIN Skincare, Cynosure, Lutronic, Novoxel, Sofwave, Solta Medical, Blossom Innovations, Allergan, Accure Acne Inc., and Soliton. Dr. DiGiorgio reported having no relevant disclosures.

SAN DIEGO – Among nearly 1,200 single-session facial treatments over 6 years that paired injectable hyaluronic acid filler with lasers, none of the documented adverse events that occurred were directly related to spread of filler or laser treatment of the filled area, results from a single-center, retrospective study showed.

“Data on the safety of pairing single-session treatment with nonablative fractional 1,927-nm thulium and/or 1,550-nm erbium laser and fillers are lacking,” Shirin Bajaj, MD, said during a clinical abstract session at the annual conference of the American Society for Laser Medicine and Surgery. “Anecdotally, we have found this to be completely safe in our high-volume laser center. We typically do fillers first, followed by laser treatment.”

For the study, Dr. Bajaj, a dermatology fellow at the Laser & Skin Surgery Center of New York, and colleagues retrospectively reviewed the charts of 638 patients who had 1,186 single‐session facial treatments with nonablative fractional 1,927-nm thulium and/or 1,550-nm erbium laser (Fraxel DUAL by Solta) and injectable hyaluronic acid filler from August 2015 to June 2021. Safety over the 6-year period was assessed by the adverse events that occurred within the first 4 weeks. The mean age of patients at the time of treatment was 60 years and 95% were female. Fitzpatrick skin types were type 1 (46.1%), type II (48.1%), type III (5.5%), and type IV (0.3%).

Most patients had 1 single‐session treatment (64.3%); the rest had 2 sessions (17.7%), 3 sessions (8%), or 4-18 sessions (10%). Most (91.2%) were treated with the 1,927-nm thulium laser, while 1.8% were treated with the 1,550-nm erbium laser; the mean total energy delivered was 1.3 kilojoules. A small number of patients (7.0%) received treatment with both lasers.

The most common area treated with filler injections were the cheeks and/or tear troughs (85.6%), followed by the perioral area and/or marionette lines (83.7%), temples (31%), nasolabial folds (25.5%), lips (24%), jawline (23.8%), chin (6.5%), forehead (1.4%), glabella and brows (0.5% each), neck (0.3%), and nose (0.1%). One syringe of filler was used in 58.7% of cases, compared with two syringes in 28.7% of cases, three syringes in 9.9% of cases, and four to six syringes in 2.8% of cases.

Dr. Bajaj reported that of the 1,186 single‐session treatments, no adverse events were recorded that were directly related to spread of filler or laser treatment of the filled area, including product migration, unexpected loss of filler volume, vascular occlusion, acute pain, cutaneous necrosis, blindness, and cutaneous burn. There were no hospital or emergency department transfers or admissions and referrals to ENT specialists or ophthalmologists for additional work‐up.

“This is at a busy cosmetic dermatology and plastic surgery practice,” Dr. Bajaj said. “Additional studies may be needed to further validate our findings.”

The study’s lead author was Jordan V. Wang, MD, who is medical research director at the Laser & Skin Surgery Center of New York.

“At most, this retrospective data confirms what we have known for years to be true: that combination treatments with injectables including fillers are safe,” Catherine M. DiGiorgio, MD, a dermatologist who practices at the Boston Center for Facial Rejuvenation, told this news organization. “This is a small study out of a single office, so that is a limitation. However, many dermatologists have performed Fraxel plus filler treatments in the same session daily for the last 10 years without any issues.”

Dr. DiGiorgio was asked to comment on the results and was not an investigator.

Dr. Bajaj reported having no financial disclosures. Dr. Wang reported that he has received grants and/or research funding from ALASTIN Skincare, Cynosure, Lutronic, Novoxel, Sofwave, Solta Medical, Blossom Innovations, Allergan, Accure Acne Inc., and Soliton. Dr. DiGiorgio reported having no relevant disclosures.

SAN DIEGO – Combining radiofrequency and targeted ultrasound demonstrated significantly better improvements in the quality of wrinkles and skin laxity in the facial region compared with radiofrequency alone at 3 months, results from a multicenter blinded trial showed.

“We’ve done a lot of work with radiofrequency, and we’ve done a lot of work with ultrasound,” Suneel Chilukuri, MD, said in an interview in advance of a clinical abstract session at the annual conference of the American Society for Laser Medicine and Surgery. “The question becomes, is there truly a difference if we’re combining them together?”

To find out, Dr. Chilukuri, a dermatologist who practices in Houston, Tex., and colleagues conducted an IRB-approved trial of a new device that allows for the delivery of radiofrequency (RF) and targeted ultrasound (TUS) in a single applicator. The device, which is not yet named, has been cleared by the Food and Drug Administration and is expected to be available in the fourth quarter of 2022.

In a single‐blinded study, 21 adults were randomized to receive RF and TUS (group A), while 20 received RF alone (group B). The mean age of patients was 57 years and 38 were women. Patients in each group received four full‐face treatments delivered once per week. Dr. Chilukuri and colleagues used the ElastiMeter to quantitatively measure skin properties at baseline, 1‐month, and 3‐month follow‐up visits. They also took digital photos at each follow-up visit and applied the Fitzpatrick Wrinkle and Elastosis Scale (FWS), and the Global Aesthetic Improvement Scale (GAIS scale) to each one, in addition to performing 3D analysis.

Dr. Chilukuri reported that patients in group A showed superior improvement of skin elasticity compared with those in group B. At 3 months, the preliminary skin elasticity data showed an improvement in the periorbital region by 13.6 N/m (34.7% improvement) and 8.1 N/m (22.2% improvement) in group A and B, respectively. (N/m is a measure of elasticity.)

3D photographs also demonstrated superior results in group A, achieving an improvement of 5.3 points (27.7%) and 4.6 points (24.4%) in wrinkles and skin evenness, respectively. Those in group A achieved marked improvement in both FWS and GAIS scales, compared with their counterparts in group B, he said.

“I think this is going to be one more very useful, versatile tool in our toolbox,” Dr. Chilukuri said of the new device, noting that for both the investigators and the patients, there was greater treatment satisfaction for the areas treated with combined radiofrequency and ultrasound. “It’s something that’s effective, painless, and the treatment time is very short – approximately 10 minutes per side. It’s extremely tolerable and the results were similar to 6-month results I get with fractionated ablative resurfacing, but without the downtime, without the handholding, without any pain.”

Moreover, he added, many patients in the trial have asked to have further treatments “and are on a waiting list for when the product launches.”

He and his colleagues also observed improvements in skin hydration among patients in group A, based on readings from a MoistureMeterSC, which measures skin hydration, a finding that he characterized as “unexpected and interesting.”

Dr. Chilukuri speculated that combining TUS and RF allows for better heat dispersion into the epidermis. “If you get to the proper temperature, which is somewhere between 40 and 42 degrees, and if you can keep it for about 10 minutes, we know that there will be proper stimulation of senescent fibroblasts,” he explained.

“I can’t say that seborrheic keratosis is improved or hyperpigmentation is improved, but the heat generation leads to immediate vasodilation to improve blood flow to treated areas. That results in immediate collagen contraction as well as improved autophagy, removal of age-related cellular debris. With the long term neovascularization, you’re going to see more change with the fibroblast activity leading to collagenesis and elastogenesis.”

Use of the device is not indicated for patients with metal implants in the head and neck region, he noted. “I’d also be cautious about using it in people with melasma as the device’s mechanism is based on heat,” since current scientific evidence shows that heat can worsen melasma, he added. “For now, I recommend caution until we perform a split-face study or develop specific treatment parameters for those patients with melasma.”

“We know that skin tightening is a difficult task for a nonablative, nonsurgical device,” said Murad Alam, MD, professor and vice-chair of dermatology and chief of the section of cutaneous and aesthetic surgery at Northwestern University, Chicago, who was asked to comment on the study.

“The promise is of limited downtime, lack of scars, and minimal discomfort, but we haven’t yet had a home run. As a consequence, there’s a constant effort to develop new and better devices. This study is interesting because it shows that yes, a new and better device might be good, but let’s not overlook the idea of having multiple devices at the same time. The nice thing they’ve shown is that from a safety standpoint, using both radiofrequency and ultrasound was tolerable in terms of safety, discomfort, and downtime.”

BTL Aesthetics, the manufacturer, loaned the device used in the trial. Dr. Chilukuri reported having no other financial conflicts for this study. Dr. Alam reported having no disclosures.

SAN DIEGO – Combining radiofrequency and targeted ultrasound demonstrated significantly better improvements in the quality of wrinkles and skin laxity in the facial region compared with radiofrequency alone at 3 months, results from a multicenter blinded trial showed.

“We’ve done a lot of work with radiofrequency, and we’ve done a lot of work with ultrasound,” Suneel Chilukuri, MD, said in an interview in advance of a clinical abstract session at the annual conference of the American Society for Laser Medicine and Surgery. “The question becomes, is there truly a difference if we’re combining them together?”

To find out, Dr. Chilukuri, a dermatologist who practices in Houston, Tex., and colleagues conducted an IRB-approved trial of a new device that allows for the delivery of radiofrequency (RF) and targeted ultrasound (TUS) in a single applicator. The device, which is not yet named, has been cleared by the Food and Drug Administration and is expected to be available in the fourth quarter of 2022.

In a single‐blinded study, 21 adults were randomized to receive RF and TUS (group A), while 20 received RF alone (group B). The mean age of patients was 57 years and 38 were women. Patients in each group received four full‐face treatments delivered once per week. Dr. Chilukuri and colleagues used the ElastiMeter to quantitatively measure skin properties at baseline, 1‐month, and 3‐month follow‐up visits. They also took digital photos at each follow-up visit and applied the Fitzpatrick Wrinkle and Elastosis Scale (FWS), and the Global Aesthetic Improvement Scale (GAIS scale) to each one, in addition to performing 3D analysis.

Dr. Chilukuri reported that patients in group A showed superior improvement of skin elasticity compared with those in group B. At 3 months, the preliminary skin elasticity data showed an improvement in the periorbital region by 13.6 N/m (34.7% improvement) and 8.1 N/m (22.2% improvement) in group A and B, respectively. (N/m is a measure of elasticity.)

3D photographs also demonstrated superior results in group A, achieving an improvement of 5.3 points (27.7%) and 4.6 points (24.4%) in wrinkles and skin evenness, respectively. Those in group A achieved marked improvement in both FWS and GAIS scales, compared with their counterparts in group B, he said.

“I think this is going to be one more very useful, versatile tool in our toolbox,” Dr. Chilukuri said of the new device, noting that for both the investigators and the patients, there was greater treatment satisfaction for the areas treated with combined radiofrequency and ultrasound. “It’s something that’s effective, painless, and the treatment time is very short – approximately 10 minutes per side. It’s extremely tolerable and the results were similar to 6-month results I get with fractionated ablative resurfacing, but without the downtime, without the handholding, without any pain.”

Moreover, he added, many patients in the trial have asked to have further treatments “and are on a waiting list for when the product launches.”

He and his colleagues also observed improvements in skin hydration among patients in group A, based on readings from a MoistureMeterSC, which measures skin hydration, a finding that he characterized as “unexpected and interesting.”

Dr. Chilukuri speculated that combining TUS and RF allows for better heat dispersion into the epidermis. “If you get to the proper temperature, which is somewhere between 40 and 42 degrees, and if you can keep it for about 10 minutes, we know that there will be proper stimulation of senescent fibroblasts,” he explained.

“I can’t say that seborrheic keratosis is improved or hyperpigmentation is improved, but the heat generation leads to immediate vasodilation to improve blood flow to treated areas. That results in immediate collagen contraction as well as improved autophagy, removal of age-related cellular debris. With the long term neovascularization, you’re going to see more change with the fibroblast activity leading to collagenesis and elastogenesis.”

Use of the device is not indicated for patients with metal implants in the head and neck region, he noted. “I’d also be cautious about using it in people with melasma as the device’s mechanism is based on heat,” since current scientific evidence shows that heat can worsen melasma, he added. “For now, I recommend caution until we perform a split-face study or develop specific treatment parameters for those patients with melasma.”

“We know that skin tightening is a difficult task for a nonablative, nonsurgical device,” said Murad Alam, MD, professor and vice-chair of dermatology and chief of the section of cutaneous and aesthetic surgery at Northwestern University, Chicago, who was asked to comment on the study.

“The promise is of limited downtime, lack of scars, and minimal discomfort, but we haven’t yet had a home run. As a consequence, there’s a constant effort to develop new and better devices. This study is interesting because it shows that yes, a new and better device might be good, but let’s not overlook the idea of having multiple devices at the same time. The nice thing they’ve shown is that from a safety standpoint, using both radiofrequency and ultrasound was tolerable in terms of safety, discomfort, and downtime.”

BTL Aesthetics, the manufacturer, loaned the device used in the trial. Dr. Chilukuri reported having no other financial conflicts for this study. Dr. Alam reported having no disclosures.

SAN DIEGO – Combining radiofrequency and targeted ultrasound demonstrated significantly better improvements in the quality of wrinkles and skin laxity in the facial region compared with radiofrequency alone at 3 months, results from a multicenter blinded trial showed.

“We’ve done a lot of work with radiofrequency, and we’ve done a lot of work with ultrasound,” Suneel Chilukuri, MD, said in an interview in advance of a clinical abstract session at the annual conference of the American Society for Laser Medicine and Surgery. “The question becomes, is there truly a difference if we’re combining them together?”

To find out, Dr. Chilukuri, a dermatologist who practices in Houston, Tex., and colleagues conducted an IRB-approved trial of a new device that allows for the delivery of radiofrequency (RF) and targeted ultrasound (TUS) in a single applicator. The device, which is not yet named, has been cleared by the Food and Drug Administration and is expected to be available in the fourth quarter of 2022.

In a single‐blinded study, 21 adults were randomized to receive RF and TUS (group A), while 20 received RF alone (group B). The mean age of patients was 57 years and 38 were women. Patients in each group received four full‐face treatments delivered once per week. Dr. Chilukuri and colleagues used the ElastiMeter to quantitatively measure skin properties at baseline, 1‐month, and 3‐month follow‐up visits. They also took digital photos at each follow-up visit and applied the Fitzpatrick Wrinkle and Elastosis Scale (FWS), and the Global Aesthetic Improvement Scale (GAIS scale) to each one, in addition to performing 3D analysis.

Dr. Chilukuri reported that patients in group A showed superior improvement of skin elasticity compared with those in group B. At 3 months, the preliminary skin elasticity data showed an improvement in the periorbital region by 13.6 N/m (34.7% improvement) and 8.1 N/m (22.2% improvement) in group A and B, respectively. (N/m is a measure of elasticity.)

3D photographs also demonstrated superior results in group A, achieving an improvement of 5.3 points (27.7%) and 4.6 points (24.4%) in wrinkles and skin evenness, respectively. Those in group A achieved marked improvement in both FWS and GAIS scales, compared with their counterparts in group B, he said.

“I think this is going to be one more very useful, versatile tool in our toolbox,” Dr. Chilukuri said of the new device, noting that for both the investigators and the patients, there was greater treatment satisfaction for the areas treated with combined radiofrequency and ultrasound. “It’s something that’s effective, painless, and the treatment time is very short – approximately 10 minutes per side. It’s extremely tolerable and the results were similar to 6-month results I get with fractionated ablative resurfacing, but without the downtime, without the handholding, without any pain.”

Moreover, he added, many patients in the trial have asked to have further treatments “and are on a waiting list for when the product launches.”

He and his colleagues also observed improvements in skin hydration among patients in group A, based on readings from a MoistureMeterSC, which measures skin hydration, a finding that he characterized as “unexpected and interesting.”

Dr. Chilukuri speculated that combining TUS and RF allows for better heat dispersion into the epidermis. “If you get to the proper temperature, which is somewhere between 40 and 42 degrees, and if you can keep it for about 10 minutes, we know that there will be proper stimulation of senescent fibroblasts,” he explained.

“I can’t say that seborrheic keratosis is improved or hyperpigmentation is improved, but the heat generation leads to immediate vasodilation to improve blood flow to treated areas. That results in immediate collagen contraction as well as improved autophagy, removal of age-related cellular debris. With the long term neovascularization, you’re going to see more change with the fibroblast activity leading to collagenesis and elastogenesis.”

Use of the device is not indicated for patients with metal implants in the head and neck region, he noted. “I’d also be cautious about using it in people with melasma as the device’s mechanism is based on heat,” since current scientific evidence shows that heat can worsen melasma, he added. “For now, I recommend caution until we perform a split-face study or develop specific treatment parameters for those patients with melasma.”

“We know that skin tightening is a difficult task for a nonablative, nonsurgical device,” said Murad Alam, MD, professor and vice-chair of dermatology and chief of the section of cutaneous and aesthetic surgery at Northwestern University, Chicago, who was asked to comment on the study.

“The promise is of limited downtime, lack of scars, and minimal discomfort, but we haven’t yet had a home run. As a consequence, there’s a constant effort to develop new and better devices. This study is interesting because it shows that yes, a new and better device might be good, but let’s not overlook the idea of having multiple devices at the same time. The nice thing they’ve shown is that from a safety standpoint, using both radiofrequency and ultrasound was tolerable in terms of safety, discomfort, and downtime.”

BTL Aesthetics, the manufacturer, loaned the device used in the trial. Dr. Chilukuri reported having no other financial conflicts for this study. Dr. Alam reported having no disclosures.

A new type of genetic test known as a polygenic risk score could change the way clinicians detect and treat chronic illnesses. But to be widely used, genomic findings in large populations first need to be translated into valid clinical tests for individual patients. Then physicians need meaningful interpretations of test data to help make clinical decisions about patient care.

In a study published in Nature Medicine, researchers report details of how they set up a genetic assay for six common diseases and developed explanatory reports to help bridge the gap between science and clinical care.

The assay and reports were created for the GenoVA study, a clinical trial that aims to determine whether polygenic risk scores (PRSs), also known as polygenic scores (PGSs), could be used effectively in a primary care setting. The randomized trial will enroll 1,000 patients at the Veterans Affairs Boston Healthcare System and will follow them for 2 years.

The authors report early data from the new laboratory test. For the 227 participants enrolled so far, 11% had a high risk for atrial fibrillation, 7% were at risk for coronary artery disease, 8% for type 2 diabetes, 6% for colorectal cancer, 15% of men had an increased prostate cancer risk, and 13% of women were at increased risk for breast cancer.

Polygenic scores are promising for informing screening and treatment decisions, with the goal of preventing chronic disease. Jason Vassy, MD, of Brigham and Women’s Hospital and VA Boston, says, “It is important to think of PRS as one risk factor for disease, not a diagnostic test or an indication that an individual will certainly develop the disease.”

He continues, “Most diseases have complex, multifactorial etiologies, and a high PRS is just one piece of the puzzle. PRSs do not replace the traditional risk factors we usually think about in clinical medicine, such as diet and exercise to prevent type 2 diabetes and smoking cessation to lower cardiovascular disease risk.”

Currently, clinical genetic testing is typically performed when a patient is suspected of having a specific disease or a family history of a condition, such as sickle cell disease or breast cancer. Tests for these types of conditions are often monogenic, detecting only select mutations.

PRS tests have the potential to inform clinical decisions years before patients become symptomatic. The PRS testing in this study combines large quantities of genetic information to assess a patient’s risk for multiple conditions. The risk for common chronic conditions can involve hundreds to millions of small genetic variations. Alone, these variations have minimal impact on a person’s risk for disease, but together they can lead to an increased risk for specific conditions.

Certain PRS tests are currently available from direct-to-consumer laboratories, in oncology, and through some clinical trials, but they’re not commonly used in general practice.

Dr. Vassy and colleagues developed and validated PRSs for atrial fibrillation, coronary artery disease, type 2 diabetes, breast cancer, colorectal cancer, and prostate cancer at the Mass General Brigham Laboratory for Molecular Medicine.

The team calculated the final PRS on the basis of individual patient genotyping combined with statistical population models.

In the GenoVA study, adults aged 50-70 years who have no previous history of disease provide saliva or blood for PRS testing at the Boston VA. Participants are stratified by risk result and are randomly assigned to receive test results either immediately or after 24 months.

Enrollees are then followed for 2 years to observe how they and their primary care providers use risk score information and whether any preventive measures or other clinical tests are employed. Guidelines are provided to patients and clinicians throughout the study, along with genetic counseling. Ultimately, the study seeks to determine whether PRS implementation improves health outcomes.

Study participants are from diverse backgrounds: 52% of the first 227 patients report non-White, non-Hispanic ethnicity. To adjust for the fact that most genomic research to date has been based on European populations, researchers used statistical methods to calculate scores across racial groups.
 

Is PRS testing the future of chronic disease prevention?

Genome wide association studies (GWASs) from more inclusive datasets are needed to improve the relevance of PRS across ancestry groups, the authors write.

Dr. Vassy points out that “the risk estimates from GWAS are the underpinnings of the polygenic scores, so a score is only as valid as its original.” Fortunately, he adds, “advances are occurring on multiple fronts, and this will be key to promoting the equitable implementation of polygenic scores. Larger, more diverse cohorts are being recruited for GWAS studies, and more sophisticated, trans-ancestry statistical GWAS methods are being developed to analyze these more diverse data.”

In England, researchers are considering the benefits of using polygenic scores in National Health Service checks for cardiovascular disease, a well-studied area of genetic risk. The new article and the English effort draw from the PGS Catalogue, an open database built by Samuel Lambert, of the University of Cambridge Department of Public Health and Primary Care, and his colleagues to provide scores and methods that can be reused and adapted for clinical use.

He says he’d recommend PRS with confidence to his family members – in particular, certain in-depth cancer assays – “provided [the results] would be interpreted in collaboration with a health care professional who understands genetics (for example, a genetic counselor) with carefully vetted information on the validity and actionability of the test result.”

Mr. Lambert feels it’s important to understand that PRS testing isn’t deterministic. “The risk information is inherently probabilistic and relative (for example, you have a four times higher risk than the average person, but if the disease prevalence is 0.5%, this is a small absolute difference),” he says.

“The PRS also explains a fraction of the variability of risk in the population and thus shouldn’t be used alone but in combination with other established risk factors and tools to predict future risk when they exist,” Mr. Lambert says.

“And thirdly, most current PRS are less accurate in those of non-European ancestry due to a lack of ancestral diversity in the cohorts and datasets that have been used to develop these PRS; special attention must be paid to make sure that the PRS results are valid for the individual,” he adds.

Funding for the study was provided by the NIH National Human Genome Research Institute and NIH, the American Heart Association, the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and Massachusetts General Hospital. Dr. Vassy is an employee of the U.S. Department of Veterans Affairs; the views expressed do not represent those of the VA or the U.S. government. Mr. Lambert is an employee of Cambridge-Baker Systems Genomics Initiative, Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care.

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

A new type of genetic test known as a polygenic risk score could change the way clinicians detect and treat chronic illnesses. But to be widely used, genomic findings in large populations first need to be translated into valid clinical tests for individual patients. Then physicians need meaningful interpretations of test data to help make clinical decisions about patient care.

In a study published in Nature Medicine, researchers report details of how they set up a genetic assay for six common diseases and developed explanatory reports to help bridge the gap between science and clinical care.

The assay and reports were created for the GenoVA study, a clinical trial that aims to determine whether polygenic risk scores (PRSs), also known as polygenic scores (PGSs), could be used effectively in a primary care setting. The randomized trial will enroll 1,000 patients at the Veterans Affairs Boston Healthcare System and will follow them for 2 years.

The authors report early data from the new laboratory test. For the 227 participants enrolled so far, 11% had a high risk for atrial fibrillation, 7% were at risk for coronary artery disease, 8% for type 2 diabetes, 6% for colorectal cancer, 15% of men had an increased prostate cancer risk, and 13% of women were at increased risk for breast cancer.

Polygenic scores are promising for informing screening and treatment decisions, with the goal of preventing chronic disease. Jason Vassy, MD, of Brigham and Women’s Hospital and VA Boston, says, “It is important to think of PRS as one risk factor for disease, not a diagnostic test or an indication that an individual will certainly develop the disease.”

He continues, “Most diseases have complex, multifactorial etiologies, and a high PRS is just one piece of the puzzle. PRSs do not replace the traditional risk factors we usually think about in clinical medicine, such as diet and exercise to prevent type 2 diabetes and smoking cessation to lower cardiovascular disease risk.”

Currently, clinical genetic testing is typically performed when a patient is suspected of having a specific disease or a family history of a condition, such as sickle cell disease or breast cancer. Tests for these types of conditions are often monogenic, detecting only select mutations.

PRS tests have the potential to inform clinical decisions years before patients become symptomatic. The PRS testing in this study combines large quantities of genetic information to assess a patient’s risk for multiple conditions. The risk for common chronic conditions can involve hundreds to millions of small genetic variations. Alone, these variations have minimal impact on a person’s risk for disease, but together they can lead to an increased risk for specific conditions.

Certain PRS tests are currently available from direct-to-consumer laboratories, in oncology, and through some clinical trials, but they’re not commonly used in general practice.

Dr. Vassy and colleagues developed and validated PRSs for atrial fibrillation, coronary artery disease, type 2 diabetes, breast cancer, colorectal cancer, and prostate cancer at the Mass General Brigham Laboratory for Molecular Medicine.

The team calculated the final PRS on the basis of individual patient genotyping combined with statistical population models.

In the GenoVA study, adults aged 50-70 years who have no previous history of disease provide saliva or blood for PRS testing at the Boston VA. Participants are stratified by risk result and are randomly assigned to receive test results either immediately or after 24 months.

Enrollees are then followed for 2 years to observe how they and their primary care providers use risk score information and whether any preventive measures or other clinical tests are employed. Guidelines are provided to patients and clinicians throughout the study, along with genetic counseling. Ultimately, the study seeks to determine whether PRS implementation improves health outcomes.

Study participants are from diverse backgrounds: 52% of the first 227 patients report non-White, non-Hispanic ethnicity. To adjust for the fact that most genomic research to date has been based on European populations, researchers used statistical methods to calculate scores across racial groups.
 

Is PRS testing the future of chronic disease prevention?

Genome wide association studies (GWASs) from more inclusive datasets are needed to improve the relevance of PRS across ancestry groups, the authors write.

Dr. Vassy points out that “the risk estimates from GWAS are the underpinnings of the polygenic scores, so a score is only as valid as its original.” Fortunately, he adds, “advances are occurring on multiple fronts, and this will be key to promoting the equitable implementation of polygenic scores. Larger, more diverse cohorts are being recruited for GWAS studies, and more sophisticated, trans-ancestry statistical GWAS methods are being developed to analyze these more diverse data.”

In England, researchers are considering the benefits of using polygenic scores in National Health Service checks for cardiovascular disease, a well-studied area of genetic risk. The new article and the English effort draw from the PGS Catalogue, an open database built by Samuel Lambert, of the University of Cambridge Department of Public Health and Primary Care, and his colleagues to provide scores and methods that can be reused and adapted for clinical use.

He says he’d recommend PRS with confidence to his family members – in particular, certain in-depth cancer assays – “provided [the results] would be interpreted in collaboration with a health care professional who understands genetics (for example, a genetic counselor) with carefully vetted information on the validity and actionability of the test result.”

Mr. Lambert feels it’s important to understand that PRS testing isn’t deterministic. “The risk information is inherently probabilistic and relative (for example, you have a four times higher risk than the average person, but if the disease prevalence is 0.5%, this is a small absolute difference),” he says.

“The PRS also explains a fraction of the variability of risk in the population and thus shouldn’t be used alone but in combination with other established risk factors and tools to predict future risk when they exist,” Mr. Lambert says.

“And thirdly, most current PRS are less accurate in those of non-European ancestry due to a lack of ancestral diversity in the cohorts and datasets that have been used to develop these PRS; special attention must be paid to make sure that the PRS results are valid for the individual,” he adds.

Funding for the study was provided by the NIH National Human Genome Research Institute and NIH, the American Heart Association, the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and Massachusetts General Hospital. Dr. Vassy is an employee of the U.S. Department of Veterans Affairs; the views expressed do not represent those of the VA or the U.S. government. Mr. Lambert is an employee of Cambridge-Baker Systems Genomics Initiative, Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care.

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

A new type of genetic test known as a polygenic risk score could change the way clinicians detect and treat chronic illnesses. But to be widely used, genomic findings in large populations first need to be translated into valid clinical tests for individual patients. Then physicians need meaningful interpretations of test data to help make clinical decisions about patient care.

In a study published in Nature Medicine, researchers report details of how they set up a genetic assay for six common diseases and developed explanatory reports to help bridge the gap between science and clinical care.

The assay and reports were created for the GenoVA study, a clinical trial that aims to determine whether polygenic risk scores (PRSs), also known as polygenic scores (PGSs), could be used effectively in a primary care setting. The randomized trial will enroll 1,000 patients at the Veterans Affairs Boston Healthcare System and will follow them for 2 years.

The authors report early data from the new laboratory test. For the 227 participants enrolled so far, 11% had a high risk for atrial fibrillation, 7% were at risk for coronary artery disease, 8% for type 2 diabetes, 6% for colorectal cancer, 15% of men had an increased prostate cancer risk, and 13% of women were at increased risk for breast cancer.

Polygenic scores are promising for informing screening and treatment decisions, with the goal of preventing chronic disease. Jason Vassy, MD, of Brigham and Women’s Hospital and VA Boston, says, “It is important to think of PRS as one risk factor for disease, not a diagnostic test or an indication that an individual will certainly develop the disease.”

He continues, “Most diseases have complex, multifactorial etiologies, and a high PRS is just one piece of the puzzle. PRSs do not replace the traditional risk factors we usually think about in clinical medicine, such as diet and exercise to prevent type 2 diabetes and smoking cessation to lower cardiovascular disease risk.”

Currently, clinical genetic testing is typically performed when a patient is suspected of having a specific disease or a family history of a condition, such as sickle cell disease or breast cancer. Tests for these types of conditions are often monogenic, detecting only select mutations.

PRS tests have the potential to inform clinical decisions years before patients become symptomatic. The PRS testing in this study combines large quantities of genetic information to assess a patient’s risk for multiple conditions. The risk for common chronic conditions can involve hundreds to millions of small genetic variations. Alone, these variations have minimal impact on a person’s risk for disease, but together they can lead to an increased risk for specific conditions.

Certain PRS tests are currently available from direct-to-consumer laboratories, in oncology, and through some clinical trials, but they’re not commonly used in general practice.

Dr. Vassy and colleagues developed and validated PRSs for atrial fibrillation, coronary artery disease, type 2 diabetes, breast cancer, colorectal cancer, and prostate cancer at the Mass General Brigham Laboratory for Molecular Medicine.

The team calculated the final PRS on the basis of individual patient genotyping combined with statistical population models.

In the GenoVA study, adults aged 50-70 years who have no previous history of disease provide saliva or blood for PRS testing at the Boston VA. Participants are stratified by risk result and are randomly assigned to receive test results either immediately or after 24 months.

Enrollees are then followed for 2 years to observe how they and their primary care providers use risk score information and whether any preventive measures or other clinical tests are employed. Guidelines are provided to patients and clinicians throughout the study, along with genetic counseling. Ultimately, the study seeks to determine whether PRS implementation improves health outcomes.

Study participants are from diverse backgrounds: 52% of the first 227 patients report non-White, non-Hispanic ethnicity. To adjust for the fact that most genomic research to date has been based on European populations, researchers used statistical methods to calculate scores across racial groups.
 

Is PRS testing the future of chronic disease prevention?

Genome wide association studies (GWASs) from more inclusive datasets are needed to improve the relevance of PRS across ancestry groups, the authors write.

Dr. Vassy points out that “the risk estimates from GWAS are the underpinnings of the polygenic scores, so a score is only as valid as its original.” Fortunately, he adds, “advances are occurring on multiple fronts, and this will be key to promoting the equitable implementation of polygenic scores. Larger, more diverse cohorts are being recruited for GWAS studies, and more sophisticated, trans-ancestry statistical GWAS methods are being developed to analyze these more diverse data.”

In England, researchers are considering the benefits of using polygenic scores in National Health Service checks for cardiovascular disease, a well-studied area of genetic risk. The new article and the English effort draw from the PGS Catalogue, an open database built by Samuel Lambert, of the University of Cambridge Department of Public Health and Primary Care, and his colleagues to provide scores and methods that can be reused and adapted for clinical use.

He says he’d recommend PRS with confidence to his family members – in particular, certain in-depth cancer assays – “provided [the results] would be interpreted in collaboration with a health care professional who understands genetics (for example, a genetic counselor) with carefully vetted information on the validity and actionability of the test result.”

Mr. Lambert feels it’s important to understand that PRS testing isn’t deterministic. “The risk information is inherently probabilistic and relative (for example, you have a four times higher risk than the average person, but if the disease prevalence is 0.5%, this is a small absolute difference),” he says.

“The PRS also explains a fraction of the variability of risk in the population and thus shouldn’t be used alone but in combination with other established risk factors and tools to predict future risk when they exist,” Mr. Lambert says.

“And thirdly, most current PRS are less accurate in those of non-European ancestry due to a lack of ancestral diversity in the cohorts and datasets that have been used to develop these PRS; special attention must be paid to make sure that the PRS results are valid for the individual,” he adds.

Funding for the study was provided by the NIH National Human Genome Research Institute and NIH, the American Heart Association, the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and Massachusetts General Hospital. Dr. Vassy is an employee of the U.S. Department of Veterans Affairs; the views expressed do not represent those of the VA or the U.S. government. Mr. Lambert is an employee of Cambridge-Baker Systems Genomics Initiative, Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care.

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