As the Vascular Annual Meeting approaches, we hope you are gearing up for a great few days of vascular programming, networking, receptions and fun! We invite you to share meeting details with your peers and colleagues on social media to generate excitement and increase attendance. To help you do this, we've put together a social media kit with directions, example posts and images you may use to spread the word about VAM. Start posting with directions listed here.

As the Vascular Annual Meeting approaches, we hope you are gearing up for a great few days of vascular programming, networking, receptions and fun! We invite you to share meeting details with your peers and colleagues on social media to generate excitement and increase attendance. To help you do this, we've put together a social media kit with directions, example posts and images you may use to spread the word about VAM. Start posting with directions listed here.

As the Vascular Annual Meeting approaches, we hope you are gearing up for a great few days of vascular programming, networking, receptions and fun! We invite you to share meeting details with your peers and colleagues on social media to generate excitement and increase attendance. To help you do this, we've put together a social media kit with directions, example posts and images you may use to spread the word about VAM. Start posting with directions listed here.

A community has opened specifically for our PA Section members on SVSConnect. This community is meant to provide a private space for vascular PAs to engage and collaborate with one another. Members will be able to have in depth discussions surrounding important issues including case complications and surgical procedures, research projects, wellness topics and much more. If you haven’t logged into SVSConnect yet, what are you waiting for? All you need are your SVS log in credentials to get started. Email [email protected] or call 312-334-2300 with questions. Sign in here.

A community has opened specifically for our PA Section members on SVSConnect. This community is meant to provide a private space for vascular PAs to engage and collaborate with one another. Members will be able to have in depth discussions surrounding important issues including case complications and surgical procedures, research projects, wellness topics and much more. If you haven’t logged into SVSConnect yet, what are you waiting for? All you need are your SVS log in credentials to get started. Email [email protected] or call 312-334-2300 with questions. Sign in here.

A community has opened specifically for our PA Section members on SVSConnect. This community is meant to provide a private space for vascular PAs to engage and collaborate with one another. Members will be able to have in depth discussions surrounding important issues including case complications and surgical procedures, research projects, wellness topics and much more. If you haven’t logged into SVSConnect yet, what are you waiting for? All you need are your SVS log in credentials to get started. Email [email protected] or call 312-334-2300 with questions. Sign in here.

Requirements for starting a vascular surgery training program have been lightened – you no longer need to have a general surgery residency at your institution and faculty requirements are in review. Because of this, SVS members are available to encourage and assist with the formation of new vascular surgery training programs. From 9:30 a.m. to 10:30 a.m. on Friday, June 14, at the Vascular Annual Meeting, an information session will be held for those interested in establishing a vascular training program. If you’re heading to the meeting in June, stop by National Harbor 4 Room at the Gaylord National to hear more about this. Register for VAM today.

Requirements for starting a vascular surgery training program have been lightened – you no longer need to have a general surgery residency at your institution and faculty requirements are in review. Because of this, SVS members are available to encourage and assist with the formation of new vascular surgery training programs. From 9:30 a.m. to 10:30 a.m. on Friday, June 14, at the Vascular Annual Meeting, an information session will be held for those interested in establishing a vascular training program. If you’re heading to the meeting in June, stop by National Harbor 4 Room at the Gaylord National to hear more about this. Register for VAM today.

Requirements for starting a vascular surgery training program have been lightened – you no longer need to have a general surgery residency at your institution and faculty requirements are in review. Because of this, SVS members are available to encourage and assist with the formation of new vascular surgery training programs. From 9:30 a.m. to 10:30 a.m. on Friday, June 14, at the Vascular Annual Meeting, an information session will be held for those interested in establishing a vascular training program. If you’re heading to the meeting in June, stop by National Harbor 4 Room at the Gaylord National to hear more about this. Register for VAM today.

SAN DIEGO – Ethnicity influences the effect of body mass index on metabolic syndrome and other obesity-associated diseases, results from a large survey of national data showed.

Doug Brunk/MDedge News

“It appears that not all components of metabolic syndrome directly correlate with visceral fat,” lead study author Patrick Chen, DO, said at the annual Digestive Disease Week.

According to Dr. Chen, a gastroenterology fellow at Wright State University, Dayton, Ohio, the prevalence of obesity in the United States increased from 30.5% in 2000 to 39.6% in 2015, a condition that costs the U.S. medical system $150 billion each year and is associated with 19% of all deaths. “We also know that abdominal visceral fat is more associated with mortality and cardiac events than overall adiposity, while visceral fat contributes to nonalcoholic fatty liver disease and metabolic syndrome,” he said.

For Asian populations, the World Health Organization has set body mass indexes of 23 kg/m² for overweight and 27.5 kg/m² for obesity. “This has led to an ongoing debate as to whether we should be adopting regional anthropometric criteria based on race-unique risk factors,” Dr. Chen said. “Despite all of these association studies, the mechanisms are still undergoing research and still unknown to this day.”

For the current analysis, he and his colleagues assessed the prevalence of type 2 diabetes, hypertension, and hyperlipidemia and the impact of increasing BMI among racial groups in the United States. They drew from the National Ambulatory Medical Care Survey from 2011 to 2015 to collect and compare data on patient race, BMI, and the prevalence of type 2 diabetes, hypertension, and dyslipidemia, and used SPSS software for chi-square analysis. They excluded patients under the age of 18, those with type 1 diabetes, those with no listed race, and Native American populations, “since there were too few patients for meaningful analysis,” he said.

The 69,949 patients in the analysis included 57,448 whites, 9,281 African Americans, and 2,142 Asians. The majority (64,091) were listed as non-Hispanic, while 5,858 were listed as Hispanic. The mean age of the study population ranged from 49 to 55 years. African Americans had the highest mean BMI (31 kg/m²), followed by whites (29 kg/m²) and Asians (25 kg/m²). Meanwhile, both Hispanics and non-Hispanics had a mean BMI of 29 kg/m².

Dr. Chen reported that African Americans (19.3%) and Asians (18.5%) had a higher prevalence of type 2 diabetes compared with whites (13.4%; P less than .001), while Hispanics had a higher prevalence of type 2 diabetes compared with non-Hispanics (18.9% vs. 13.9%; P less than .001). At the same time, African Americans had a higher prevalence of hypertension (49.6%) compared with whites (38.2%) and Asians (37.9%; P less than .001 for both associations), while non-Hispanics had a higher prevalence of hypertension compared with Hispanics (40.4% vs. 33.1%; P less than .001). Asians had a higher prevalence of hyperlipidemia (28.4%) compared with whites (25.6%; P = .004); both groups had a higher prevalence compared with African Americans (21.9%, P less than .001). Hispanics had a lower prevalence of hyperlipidemia compared with non-Hispanics (23.6% vs. 25.1%; P = .005).

“Diabetes, hypertension, and hyperlipidemia likely have different mechanisms that lead to different race’s predisposition to these diseases,” Dr. Chen concluded. “This study supports that regional anthropometric criteria should be done based on ethnicity-specific risk factors. Some food for thought is whether we need to change our screening guidelines for conditions like diabetes for Asian patients and hypertension in African American patients. We should also consider ethnicity when we look for NAFLD. Overall, continued research is needed to explain these correlations.”

The researchers reported having no financial disclosures.

[email protected]

SOURCE: Chen P et al. DDW 2019, Abstract 447.

SAN DIEGO – Ethnicity influences the effect of body mass index on metabolic syndrome and other obesity-associated diseases, results from a large survey of national data showed.

Doug Brunk/MDedge News

“It appears that not all components of metabolic syndrome directly correlate with visceral fat,” lead study author Patrick Chen, DO, said at the annual Digestive Disease Week.

According to Dr. Chen, a gastroenterology fellow at Wright State University, Dayton, Ohio, the prevalence of obesity in the United States increased from 30.5% in 2000 to 39.6% in 2015, a condition that costs the U.S. medical system $150 billion each year and is associated with 19% of all deaths. “We also know that abdominal visceral fat is more associated with mortality and cardiac events than overall adiposity, while visceral fat contributes to nonalcoholic fatty liver disease and metabolic syndrome,” he said.

For Asian populations, the World Health Organization has set body mass indexes of 23 kg/m² for overweight and 27.5 kg/m² for obesity. “This has led to an ongoing debate as to whether we should be adopting regional anthropometric criteria based on race-unique risk factors,” Dr. Chen said. “Despite all of these association studies, the mechanisms are still undergoing research and still unknown to this day.”

For the current analysis, he and his colleagues assessed the prevalence of type 2 diabetes, hypertension, and hyperlipidemia and the impact of increasing BMI among racial groups in the United States. They drew from the National Ambulatory Medical Care Survey from 2011 to 2015 to collect and compare data on patient race, BMI, and the prevalence of type 2 diabetes, hypertension, and dyslipidemia, and used SPSS software for chi-square analysis. They excluded patients under the age of 18, those with type 1 diabetes, those with no listed race, and Native American populations, “since there were too few patients for meaningful analysis,” he said.

The 69,949 patients in the analysis included 57,448 whites, 9,281 African Americans, and 2,142 Asians. The majority (64,091) were listed as non-Hispanic, while 5,858 were listed as Hispanic. The mean age of the study population ranged from 49 to 55 years. African Americans had the highest mean BMI (31 kg/m²), followed by whites (29 kg/m²) and Asians (25 kg/m²). Meanwhile, both Hispanics and non-Hispanics had a mean BMI of 29 kg/m².

Dr. Chen reported that African Americans (19.3%) and Asians (18.5%) had a higher prevalence of type 2 diabetes compared with whites (13.4%; P less than .001), while Hispanics had a higher prevalence of type 2 diabetes compared with non-Hispanics (18.9% vs. 13.9%; P less than .001). At the same time, African Americans had a higher prevalence of hypertension (49.6%) compared with whites (38.2%) and Asians (37.9%; P less than .001 for both associations), while non-Hispanics had a higher prevalence of hypertension compared with Hispanics (40.4% vs. 33.1%; P less than .001). Asians had a higher prevalence of hyperlipidemia (28.4%) compared with whites (25.6%; P = .004); both groups had a higher prevalence compared with African Americans (21.9%, P less than .001). Hispanics had a lower prevalence of hyperlipidemia compared with non-Hispanics (23.6% vs. 25.1%; P = .005).

“Diabetes, hypertension, and hyperlipidemia likely have different mechanisms that lead to different race’s predisposition to these diseases,” Dr. Chen concluded. “This study supports that regional anthropometric criteria should be done based on ethnicity-specific risk factors. Some food for thought is whether we need to change our screening guidelines for conditions like diabetes for Asian patients and hypertension in African American patients. We should also consider ethnicity when we look for NAFLD. Overall, continued research is needed to explain these correlations.”

The researchers reported having no financial disclosures.

[email protected]

SOURCE: Chen P et al. DDW 2019, Abstract 447.

SAN DIEGO – Ethnicity influences the effect of body mass index on metabolic syndrome and other obesity-associated diseases, results from a large survey of national data showed.

Doug Brunk/MDedge News

“It appears that not all components of metabolic syndrome directly correlate with visceral fat,” lead study author Patrick Chen, DO, said at the annual Digestive Disease Week.

According to Dr. Chen, a gastroenterology fellow at Wright State University, Dayton, Ohio, the prevalence of obesity in the United States increased from 30.5% in 2000 to 39.6% in 2015, a condition that costs the U.S. medical system $150 billion each year and is associated with 19% of all deaths. “We also know that abdominal visceral fat is more associated with mortality and cardiac events than overall adiposity, while visceral fat contributes to nonalcoholic fatty liver disease and metabolic syndrome,” he said.

For Asian populations, the World Health Organization has set body mass indexes of 23 kg/m² for overweight and 27.5 kg/m² for obesity. “This has led to an ongoing debate as to whether we should be adopting regional anthropometric criteria based on race-unique risk factors,” Dr. Chen said. “Despite all of these association studies, the mechanisms are still undergoing research and still unknown to this day.”

For the current analysis, he and his colleagues assessed the prevalence of type 2 diabetes, hypertension, and hyperlipidemia and the impact of increasing BMI among racial groups in the United States. They drew from the National Ambulatory Medical Care Survey from 2011 to 2015 to collect and compare data on patient race, BMI, and the prevalence of type 2 diabetes, hypertension, and dyslipidemia, and used SPSS software for chi-square analysis. They excluded patients under the age of 18, those with type 1 diabetes, those with no listed race, and Native American populations, “since there were too few patients for meaningful analysis,” he said.

The 69,949 patients in the analysis included 57,448 whites, 9,281 African Americans, and 2,142 Asians. The majority (64,091) were listed as non-Hispanic, while 5,858 were listed as Hispanic. The mean age of the study population ranged from 49 to 55 years. African Americans had the highest mean BMI (31 kg/m²), followed by whites (29 kg/m²) and Asians (25 kg/m²). Meanwhile, both Hispanics and non-Hispanics had a mean BMI of 29 kg/m².

Dr. Chen reported that African Americans (19.3%) and Asians (18.5%) had a higher prevalence of type 2 diabetes compared with whites (13.4%; P less than .001), while Hispanics had a higher prevalence of type 2 diabetes compared with non-Hispanics (18.9% vs. 13.9%; P less than .001). At the same time, African Americans had a higher prevalence of hypertension (49.6%) compared with whites (38.2%) and Asians (37.9%; P less than .001 for both associations), while non-Hispanics had a higher prevalence of hypertension compared with Hispanics (40.4% vs. 33.1%; P less than .001). Asians had a higher prevalence of hyperlipidemia (28.4%) compared with whites (25.6%; P = .004); both groups had a higher prevalence compared with African Americans (21.9%, P less than .001). Hispanics had a lower prevalence of hyperlipidemia compared with non-Hispanics (23.6% vs. 25.1%; P = .005).

“Diabetes, hypertension, and hyperlipidemia likely have different mechanisms that lead to different race’s predisposition to these diseases,” Dr. Chen concluded. “This study supports that regional anthropometric criteria should be done based on ethnicity-specific risk factors. Some food for thought is whether we need to change our screening guidelines for conditions like diabetes for Asian patients and hypertension in African American patients. We should also consider ethnicity when we look for NAFLD. Overall, continued research is needed to explain these correlations.”

The researchers reported having no financial disclosures.

[email protected]

SOURCE: Chen P et al. DDW 2019, Abstract 447.

The FVIII/W (factor VIII:C/von Willebrand factor antigen) ratio appears to be a reliable biological marker to predict recovery and/or relapse in patients with acquired hemophilia A, according to a retrospective analysis.

Marc Trossaert, MD, PhD, of the CHU de Nantes, France, and colleagues conducted a retrospective analysis of 64 consecutive patients diagnosed with acquired hemophilia A over a period of 15 years (2000-2015). Data were obtained from institutional databases at the Toulouse and Nantes university hospitals in France.

Data collected included patient demographics, comorbidities, biological factors, and information related to immunosuppressive therapy. The findings of the study were published in Haemophilia.

To ascertain normal parameters and uses of the FVIII/W ratio, the team assessed FVIII:C and VWF:Ag levels of 40 healthy individuals and normal parameters of the ratio were defined using these levels.

Among the 64 patients with acquired hemophilia A who were enrolled in the study, 55 patients achieved complete remission. Of that group, 44 patients did not relapse. Researchers had follow-up data of at least 1 year for 22 of these patients. They found that the FVIII/W ratio remained within normal parameters for all 22 patients.

Researchers had follow-up data on 5 of the 11 patients who relapsed during the study period. For 4 of the patients, a decrease of FVIII/W ratio was the first indicator of relapse. In the fifth patient, an abnormal activated partial thromboplastin time (aPTT) displayed before the changes were observed in the FVIII/W ratio.

Dr. Trossaert and his colleagues acknowledged that a key limitation of the study was the retrospective design.

“We cannot eliminate the fact that in these patients less frequent testing may have influenced the chance of seeing a low FVIII/W ratio,” they wrote.

The biomarker now needs to be studied in larger cohorts, the researchers suggested.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Trossaert M et al. Haemophilia. 2019 May 2. doi: 10.1111/hae.13752.

The FVIII/W (factor VIII:C/von Willebrand factor antigen) ratio appears to be a reliable biological marker to predict recovery and/or relapse in patients with acquired hemophilia A, according to a retrospective analysis.

Marc Trossaert, MD, PhD, of the CHU de Nantes, France, and colleagues conducted a retrospective analysis of 64 consecutive patients diagnosed with acquired hemophilia A over a period of 15 years (2000-2015). Data were obtained from institutional databases at the Toulouse and Nantes university hospitals in France.

Data collected included patient demographics, comorbidities, biological factors, and information related to immunosuppressive therapy. The findings of the study were published in Haemophilia.

To ascertain normal parameters and uses of the FVIII/W ratio, the team assessed FVIII:C and VWF:Ag levels of 40 healthy individuals and normal parameters of the ratio were defined using these levels.

Among the 64 patients with acquired hemophilia A who were enrolled in the study, 55 patients achieved complete remission. Of that group, 44 patients did not relapse. Researchers had follow-up data of at least 1 year for 22 of these patients. They found that the FVIII/W ratio remained within normal parameters for all 22 patients.

Researchers had follow-up data on 5 of the 11 patients who relapsed during the study period. For 4 of the patients, a decrease of FVIII/W ratio was the first indicator of relapse. In the fifth patient, an abnormal activated partial thromboplastin time (aPTT) displayed before the changes were observed in the FVIII/W ratio.

Dr. Trossaert and his colleagues acknowledged that a key limitation of the study was the retrospective design.

“We cannot eliminate the fact that in these patients less frequent testing may have influenced the chance of seeing a low FVIII/W ratio,” they wrote.

The biomarker now needs to be studied in larger cohorts, the researchers suggested.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Trossaert M et al. Haemophilia. 2019 May 2. doi: 10.1111/hae.13752.

The FVIII/W (factor VIII:C/von Willebrand factor antigen) ratio appears to be a reliable biological marker to predict recovery and/or relapse in patients with acquired hemophilia A, according to a retrospective analysis.

Marc Trossaert, MD, PhD, of the CHU de Nantes, France, and colleagues conducted a retrospective analysis of 64 consecutive patients diagnosed with acquired hemophilia A over a period of 15 years (2000-2015). Data were obtained from institutional databases at the Toulouse and Nantes university hospitals in France.

Data collected included patient demographics, comorbidities, biological factors, and information related to immunosuppressive therapy. The findings of the study were published in Haemophilia.

To ascertain normal parameters and uses of the FVIII/W ratio, the team assessed FVIII:C and VWF:Ag levels of 40 healthy individuals and normal parameters of the ratio were defined using these levels.

Among the 64 patients with acquired hemophilia A who were enrolled in the study, 55 patients achieved complete remission. Of that group, 44 patients did not relapse. Researchers had follow-up data of at least 1 year for 22 of these patients. They found that the FVIII/W ratio remained within normal parameters for all 22 patients.

Researchers had follow-up data on 5 of the 11 patients who relapsed during the study period. For 4 of the patients, a decrease of FVIII/W ratio was the first indicator of relapse. In the fifth patient, an abnormal activated partial thromboplastin time (aPTT) displayed before the changes were observed in the FVIII/W ratio.

Dr. Trossaert and his colleagues acknowledged that a key limitation of the study was the retrospective design.

“We cannot eliminate the fact that in these patients less frequent testing may have influenced the chance of seeing a low FVIII/W ratio,” they wrote.

The biomarker now needs to be studied in larger cohorts, the researchers suggested.

No funding sources were reported. The authors reported having no conflicts of interest.

SOURCE: Trossaert M et al. Haemophilia. 2019 May 2. doi: 10.1111/hae.13752.

NASHVILLE, TENN. – A targeted next-generation sequencing panel rapidly identifies both germline and somatic Lynch syndrome pathogenic mutations in women with – or at risk for – endometrial cancer, according to findings in a prospective patient cohort.

Sharon Worcester/MDedge News

The findings, which also suggest that the incidence of Lynch syndrome among endometrial cancer patients is higher than previously recognized, have “immediate and major implications for the individual patient with endometrial cancer ... and implications for related family members,” Maria Mercedes M. Padron, MD, reported during an e-poster session at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

Of 71 patients included in the study, 67 were undergoing endometrial cancer treatment and 7 (3 among those undergoing endometrial cancer treatment and 4 who did not have endometrial cancer) were known to have Lynch syndrome.

Of the 67 undergoing treatment, 22 (33%) were identified by the direct sequencing panel as having Lynch syndrome mutations, and of those, 7 (10%) had mutations classified as high confidence inactivating mutations in either MLH1, MSH6, PMS2, or MSH2 genes, said Dr. Padron, a research scholar at Icahn School of Medicine at Mount Sinai, New York. The remaining 15 patients had rare mutations and met previously defined phenotypic criteria for Lynch syndrome pathogenicity, she reported.

The sequencing panel–based results were compared with commercially available gene tests, including immunohistochemistry (IHC) and microsatellite instability testing (MSI); 10 patients were identified by IHC to have loss of nuclear mismatch repair (MMR) protein expression, and 8 of those were Lynch syndrome mutation positive. In addition, two patients were MSI-high, and both of those were Lynch syndrome mutation positive.

Thus, two Lynch syndrome patients were missed by direct sequencing, noted Dr. Padron.

However, an additional 10 patients who were not identified as having Lynch syndrome by IHC and MSI testing were potentially identified as such using the sequencing panel, Dr. Padron said, noting that “the pathogenicity of these additional variants needs to be defined.”

Lynch syndrome is a hereditary cancer syndrome caused by germline mutations in DNA MMR genes; it is the third most common malignancy in women and it confers an increased risk of several types of cancer, including colorectal, ovarian, gastric, and endometrial cancer, among others.

“It is estimated that 3% to 5% of endometrial cancers will arise from Lynch syndrome,” Dr. Padron explained during the poster session.

Because the presence of Lynch syndrome directly affects immediate clinical management and future risk-reducing and surveillance strategies for patients and at-risk family members, screening is recommended in all women with endometrial cancer, she added, noting, however, that “the optimum screening method has yet to be established.”

The sequencing panel evaluated in this study – Swift’s Accel-Amplicon Plus Lynch Syndrome Panel – requires only low input amounts of DNA, and in an earlier test using 10 control samples, it exhibited greater than 90% on-target and coverage uniformity. The work flow allowed for data analysis within 2 days, Dr. Padron noted.

The panel then was tested in the current cohort of patients who were referred to a gynecology oncology clinic for either treatment of endometrial cancer or for evaluation of risk for endometrial cancer.

Germline/tumor DNA was isolated and 10 ng DNA was used for targeted exon-level hotspot coverage of MLH1, MSH2, MSH6, and PMS2.

The findings suggest that the prevalence of Lynch syndrome may be six to seven times greater than previously estimated, Dr. Padron said during the poster presentation.

“If confirmed, this would have huge implications for our patients and health care system,” she said, adding that the ability to perform and analyze the sequencing within 48 hours of sample collection using a very low DNA input also was of note.

Taken together, “the findings of this study support future larger studies that can be performed concurrently with current standard of care technologies,” she and her colleagues concluded, noting that such studies would better determine more robust estimates of the prevalence of Lynch syndrome in women with endometrial cancer, help define improved standard-of-care guidelines, and provide future guidance for possible universal/targeted screening programs – all with the goal of improving the clinical care of women.

Dr. Padron reported having no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – A targeted next-generation sequencing panel rapidly identifies both germline and somatic Lynch syndrome pathogenic mutations in women with – or at risk for – endometrial cancer, according to findings in a prospective patient cohort.

Sharon Worcester/MDedge News

The findings, which also suggest that the incidence of Lynch syndrome among endometrial cancer patients is higher than previously recognized, have “immediate and major implications for the individual patient with endometrial cancer ... and implications for related family members,” Maria Mercedes M. Padron, MD, reported during an e-poster session at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

Of 71 patients included in the study, 67 were undergoing endometrial cancer treatment and 7 (3 among those undergoing endometrial cancer treatment and 4 who did not have endometrial cancer) were known to have Lynch syndrome.

Of the 67 undergoing treatment, 22 (33%) were identified by the direct sequencing panel as having Lynch syndrome mutations, and of those, 7 (10%) had mutations classified as high confidence inactivating mutations in either MLH1, MSH6, PMS2, or MSH2 genes, said Dr. Padron, a research scholar at Icahn School of Medicine at Mount Sinai, New York. The remaining 15 patients had rare mutations and met previously defined phenotypic criteria for Lynch syndrome pathogenicity, she reported.

The sequencing panel–based results were compared with commercially available gene tests, including immunohistochemistry (IHC) and microsatellite instability testing (MSI); 10 patients were identified by IHC to have loss of nuclear mismatch repair (MMR) protein expression, and 8 of those were Lynch syndrome mutation positive. In addition, two patients were MSI-high, and both of those were Lynch syndrome mutation positive.

Thus, two Lynch syndrome patients were missed by direct sequencing, noted Dr. Padron.

However, an additional 10 patients who were not identified as having Lynch syndrome by IHC and MSI testing were potentially identified as such using the sequencing panel, Dr. Padron said, noting that “the pathogenicity of these additional variants needs to be defined.”

Lynch syndrome is a hereditary cancer syndrome caused by germline mutations in DNA MMR genes; it is the third most common malignancy in women and it confers an increased risk of several types of cancer, including colorectal, ovarian, gastric, and endometrial cancer, among others.

“It is estimated that 3% to 5% of endometrial cancers will arise from Lynch syndrome,” Dr. Padron explained during the poster session.

Because the presence of Lynch syndrome directly affects immediate clinical management and future risk-reducing and surveillance strategies for patients and at-risk family members, screening is recommended in all women with endometrial cancer, she added, noting, however, that “the optimum screening method has yet to be established.”

The sequencing panel evaluated in this study – Swift’s Accel-Amplicon Plus Lynch Syndrome Panel – requires only low input amounts of DNA, and in an earlier test using 10 control samples, it exhibited greater than 90% on-target and coverage uniformity. The work flow allowed for data analysis within 2 days, Dr. Padron noted.

The panel then was tested in the current cohort of patients who were referred to a gynecology oncology clinic for either treatment of endometrial cancer or for evaluation of risk for endometrial cancer.

Germline/tumor DNA was isolated and 10 ng DNA was used for targeted exon-level hotspot coverage of MLH1, MSH2, MSH6, and PMS2.

The findings suggest that the prevalence of Lynch syndrome may be six to seven times greater than previously estimated, Dr. Padron said during the poster presentation.

“If confirmed, this would have huge implications for our patients and health care system,” she said, adding that the ability to perform and analyze the sequencing within 48 hours of sample collection using a very low DNA input also was of note.

Taken together, “the findings of this study support future larger studies that can be performed concurrently with current standard of care technologies,” she and her colleagues concluded, noting that such studies would better determine more robust estimates of the prevalence of Lynch syndrome in women with endometrial cancer, help define improved standard-of-care guidelines, and provide future guidance for possible universal/targeted screening programs – all with the goal of improving the clinical care of women.

Dr. Padron reported having no relevant financial disclosures.

[email protected]

NASHVILLE, TENN. – A targeted next-generation sequencing panel rapidly identifies both germline and somatic Lynch syndrome pathogenic mutations in women with – or at risk for – endometrial cancer, according to findings in a prospective patient cohort.

Sharon Worcester/MDedge News

The findings, which also suggest that the incidence of Lynch syndrome among endometrial cancer patients is higher than previously recognized, have “immediate and major implications for the individual patient with endometrial cancer ... and implications for related family members,” Maria Mercedes M. Padron, MD, reported during an e-poster session at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists.

Of 71 patients included in the study, 67 were undergoing endometrial cancer treatment and 7 (3 among those undergoing endometrial cancer treatment and 4 who did not have endometrial cancer) were known to have Lynch syndrome.

Of the 67 undergoing treatment, 22 (33%) were identified by the direct sequencing panel as having Lynch syndrome mutations, and of those, 7 (10%) had mutations classified as high confidence inactivating mutations in either MLH1, MSH6, PMS2, or MSH2 genes, said Dr. Padron, a research scholar at Icahn School of Medicine at Mount Sinai, New York. The remaining 15 patients had rare mutations and met previously defined phenotypic criteria for Lynch syndrome pathogenicity, she reported.

The sequencing panel–based results were compared with commercially available gene tests, including immunohistochemistry (IHC) and microsatellite instability testing (MSI); 10 patients were identified by IHC to have loss of nuclear mismatch repair (MMR) protein expression, and 8 of those were Lynch syndrome mutation positive. In addition, two patients were MSI-high, and both of those were Lynch syndrome mutation positive.

Thus, two Lynch syndrome patients were missed by direct sequencing, noted Dr. Padron.

However, an additional 10 patients who were not identified as having Lynch syndrome by IHC and MSI testing were potentially identified as such using the sequencing panel, Dr. Padron said, noting that “the pathogenicity of these additional variants needs to be defined.”

Lynch syndrome is a hereditary cancer syndrome caused by germline mutations in DNA MMR genes; it is the third most common malignancy in women and it confers an increased risk of several types of cancer, including colorectal, ovarian, gastric, and endometrial cancer, among others.

“It is estimated that 3% to 5% of endometrial cancers will arise from Lynch syndrome,” Dr. Padron explained during the poster session.

Because the presence of Lynch syndrome directly affects immediate clinical management and future risk-reducing and surveillance strategies for patients and at-risk family members, screening is recommended in all women with endometrial cancer, she added, noting, however, that “the optimum screening method has yet to be established.”

The sequencing panel evaluated in this study – Swift’s Accel-Amplicon Plus Lynch Syndrome Panel – requires only low input amounts of DNA, and in an earlier test using 10 control samples, it exhibited greater than 90% on-target and coverage uniformity. The work flow allowed for data analysis within 2 days, Dr. Padron noted.

The panel then was tested in the current cohort of patients who were referred to a gynecology oncology clinic for either treatment of endometrial cancer or for evaluation of risk for endometrial cancer.

Germline/tumor DNA was isolated and 10 ng DNA was used for targeted exon-level hotspot coverage of MLH1, MSH2, MSH6, and PMS2.

The findings suggest that the prevalence of Lynch syndrome may be six to seven times greater than previously estimated, Dr. Padron said during the poster presentation.

“If confirmed, this would have huge implications for our patients and health care system,” she said, adding that the ability to perform and analyze the sequencing within 48 hours of sample collection using a very low DNA input also was of note.

Taken together, “the findings of this study support future larger studies that can be performed concurrently with current standard of care technologies,” she and her colleagues concluded, noting that such studies would better determine more robust estimates of the prevalence of Lynch syndrome in women with endometrial cancer, help define improved standard-of-care guidelines, and provide future guidance for possible universal/targeted screening programs – all with the goal of improving the clinical care of women.

Dr. Padron reported having no relevant financial disclosures.

[email protected]

Adolescents and adults had similar weight loss after bariatric surgery, but diabetes and hypertension reoccurred more often in the older cohort, according to two related studies of 5-year outcomes after Roux-en-Y gastric bypass.

However, despite adolescents’ better outcomes for diabetes and hypertension, their rate of abdominal reoperations was significantly higher during the 5-year follow-up period, and at 2 years post surgery, they were found to have low ferritin levels. The rates of death were similar in the two groups at 5 years.

“We have documented similar and durable weight loss after gastric bypass in adolescents and adults, but important differences between these cohorts were observed in specific health outcomes,” wrote Thomas H. Inge, MD, PhD, of the University of Colorado at Denver, Aurora, and his coauthors. The study was published in the New England Journal of Medicine.

To evaluate and compare outcomes after bariatric surgery, the researchers undertook the Teen–Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study and the LABS study. The two were related but independent observational studies of postsurgery patient cohorts. The Teen-LABS study included 161 adolescents with severe obesity, and the LABS study included 396 adults who reported becoming obese during adolescence.

At 5-year follow-up, there was no significant difference in mean percentage weight change between adolescents (−26%; 95% confidence interval, −29 to −23) and adults (−29%; 95% CI, −31 to −27; P = .08). Adolescents were more likely than were adults to have remission of type 2 diabetes (86% vs. 53%, respectively; risk ratio, 1.27; 95% CI, 1.03 to 1.57; P = .03) as well as hypertension (68% vs. 41%; risk ratio, 1.51; 95% CI, 1.21 to 1.88; P less than .001).

In addition, 20% of adolescents and 16% of adults underwent intra-abdominal procedures within 5 years of surgery, with cholecystectomy being the most common, followed by surgery for bowel obstruction or hernia repair, and gastrostomy. At 2 years, ferritin levels were lower in adolescents than in adults (48% of patients vs. 29%, respectively). Five-year ferritin levels were not assessed.

In all, three adolescents (1.9%) and seven adults (1.8%) died over the 5-year period. Among the adolescents, one patient with type 1 diabetes died 3 years after surgery from complications after a hypoglycemic episode, and the other two deaths, both 4 years after surgery, were consistent with overdose. Among the adults, three of the deaths occurred within 3 weeks of surgery and were related to gastric bypass, two were of indeterminate cause (at 11 months and 5 years after surgery), one was by suicide at 3 years, and one was from colon cancer at 4 years.

The authors acknowledged the limitations of their study, including its observational design, low counts for some of the outcomes, and a lack of nonsurgical controls. They also noted potential unmeasured biases in the adult cohort, including the effects of weight cycling and inaccuracies in recalling adolescent weight issues.

The study and several of its authors were supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants, honoraria, and consulting fees from medical technology and pharmaceutical companies.

SOURCE: Inge TH et al. N Engl J Med. 2019 May 16. doi: 10.1056/NEJMoa1813909.

Adolescents and adults had similar weight loss after bariatric surgery, but diabetes and hypertension reoccurred more often in the older cohort, according to two related studies of 5-year outcomes after Roux-en-Y gastric bypass.

However, despite adolescents’ better outcomes for diabetes and hypertension, their rate of abdominal reoperations was significantly higher during the 5-year follow-up period, and at 2 years post surgery, they were found to have low ferritin levels. The rates of death were similar in the two groups at 5 years.

“We have documented similar and durable weight loss after gastric bypass in adolescents and adults, but important differences between these cohorts were observed in specific health outcomes,” wrote Thomas H. Inge, MD, PhD, of the University of Colorado at Denver, Aurora, and his coauthors. The study was published in the New England Journal of Medicine.

To evaluate and compare outcomes after bariatric surgery, the researchers undertook the Teen–Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study and the LABS study. The two were related but independent observational studies of postsurgery patient cohorts. The Teen-LABS study included 161 adolescents with severe obesity, and the LABS study included 396 adults who reported becoming obese during adolescence.

At 5-year follow-up, there was no significant difference in mean percentage weight change between adolescents (−26%; 95% confidence interval, −29 to −23) and adults (−29%; 95% CI, −31 to −27; P = .08). Adolescents were more likely than were adults to have remission of type 2 diabetes (86% vs. 53%, respectively; risk ratio, 1.27; 95% CI, 1.03 to 1.57; P = .03) as well as hypertension (68% vs. 41%; risk ratio, 1.51; 95% CI, 1.21 to 1.88; P less than .001).

In addition, 20% of adolescents and 16% of adults underwent intra-abdominal procedures within 5 years of surgery, with cholecystectomy being the most common, followed by surgery for bowel obstruction or hernia repair, and gastrostomy. At 2 years, ferritin levels were lower in adolescents than in adults (48% of patients vs. 29%, respectively). Five-year ferritin levels were not assessed.

In all, three adolescents (1.9%) and seven adults (1.8%) died over the 5-year period. Among the adolescents, one patient with type 1 diabetes died 3 years after surgery from complications after a hypoglycemic episode, and the other two deaths, both 4 years after surgery, were consistent with overdose. Among the adults, three of the deaths occurred within 3 weeks of surgery and were related to gastric bypass, two were of indeterminate cause (at 11 months and 5 years after surgery), one was by suicide at 3 years, and one was from colon cancer at 4 years.

The authors acknowledged the limitations of their study, including its observational design, low counts for some of the outcomes, and a lack of nonsurgical controls. They also noted potential unmeasured biases in the adult cohort, including the effects of weight cycling and inaccuracies in recalling adolescent weight issues.

The study and several of its authors were supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants, honoraria, and consulting fees from medical technology and pharmaceutical companies.

SOURCE: Inge TH et al. N Engl J Med. 2019 May 16. doi: 10.1056/NEJMoa1813909.

Adolescents and adults had similar weight loss after bariatric surgery, but diabetes and hypertension reoccurred more often in the older cohort, according to two related studies of 5-year outcomes after Roux-en-Y gastric bypass.

However, despite adolescents’ better outcomes for diabetes and hypertension, their rate of abdominal reoperations was significantly higher during the 5-year follow-up period, and at 2 years post surgery, they were found to have low ferritin levels. The rates of death were similar in the two groups at 5 years.

“We have documented similar and durable weight loss after gastric bypass in adolescents and adults, but important differences between these cohorts were observed in specific health outcomes,” wrote Thomas H. Inge, MD, PhD, of the University of Colorado at Denver, Aurora, and his coauthors. The study was published in the New England Journal of Medicine.

To evaluate and compare outcomes after bariatric surgery, the researchers undertook the Teen–Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study and the LABS study. The two were related but independent observational studies of postsurgery patient cohorts. The Teen-LABS study included 161 adolescents with severe obesity, and the LABS study included 396 adults who reported becoming obese during adolescence.

At 5-year follow-up, there was no significant difference in mean percentage weight change between adolescents (−26%; 95% confidence interval, −29 to −23) and adults (−29%; 95% CI, −31 to −27; P = .08). Adolescents were more likely than were adults to have remission of type 2 diabetes (86% vs. 53%, respectively; risk ratio, 1.27; 95% CI, 1.03 to 1.57; P = .03) as well as hypertension (68% vs. 41%; risk ratio, 1.51; 95% CI, 1.21 to 1.88; P less than .001).

In addition, 20% of adolescents and 16% of adults underwent intra-abdominal procedures within 5 years of surgery, with cholecystectomy being the most common, followed by surgery for bowel obstruction or hernia repair, and gastrostomy. At 2 years, ferritin levels were lower in adolescents than in adults (48% of patients vs. 29%, respectively). Five-year ferritin levels were not assessed.

In all, three adolescents (1.9%) and seven adults (1.8%) died over the 5-year period. Among the adolescents, one patient with type 1 diabetes died 3 years after surgery from complications after a hypoglycemic episode, and the other two deaths, both 4 years after surgery, were consistent with overdose. Among the adults, three of the deaths occurred within 3 weeks of surgery and were related to gastric bypass, two were of indeterminate cause (at 11 months and 5 years after surgery), one was by suicide at 3 years, and one was from colon cancer at 4 years.

The authors acknowledged the limitations of their study, including its observational design, low counts for some of the outcomes, and a lack of nonsurgical controls. They also noted potential unmeasured biases in the adult cohort, including the effects of weight cycling and inaccuracies in recalling adolescent weight issues.

The study and several of its authors were supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases. Several authors reported receiving grants, honoraria, and consulting fees from medical technology and pharmaceutical companies.

SOURCE: Inge TH et al. N Engl J Med. 2019 May 16. doi: 10.1056/NEJMoa1813909.

SAN FRANCISCO – Some physicians are uncomfortable providing mental health care to patients with intellectual disability (ID) because many of the patients’ communications skills are limited. But many resources are available that can help.

In this video, Nita V. Bhatt, MD, MPH, interviews Julie P. Gentile, MD, about some of those resources and discusses how to approach psychiatric treatment interventions for patients with ID.

In addition to the DSM-5, Dr. Gentile said the National Association for the Dually Diagnosed has published the Diagnostic Manual – Intellectual Disability. Another resource is a practical reference manual originally proposed by one of Dr. Gentile’s residents.

“He came into my office for supervision one day and said, ‘You know, there’s all these nuances for psychiatric treatment in this patient population. So we should write a practice, quick reference manual to help clinicians who aren’t able to spend as much time concentrate on this patient population.’ ”

As a result, several residents and faculty members formed a team to produce an 18-chapter book published this year by Springer called the Guide to Intellectual Disabilities: A Clinical Handbook.

Dr. Bhatt is a staff psychiatrist at Twin Valley Behavioral Healthcare, the state psychiatric hospital in Columbus, Ohio. Dr. Gentile is professor and chair of the department of psychiatry at Wright State in Dayton. She is also serves as project director of Ohio’s Telepsychiatry Project for Intellectual Disability and has been awarded more than $7 million in grant funding to support her projects in the field of ID.

Dr. Gentile’s work has been funded by the Ohio Department of Developmental Disabilities and the Ohio Department of Mental Health and Addiction Services.
 

[email protected]

SAN FRANCISCO – Some physicians are uncomfortable providing mental health care to patients with intellectual disability (ID) because many of the patients’ communications skills are limited. But many resources are available that can help.

In this video, Nita V. Bhatt, MD, MPH, interviews Julie P. Gentile, MD, about some of those resources and discusses how to approach psychiatric treatment interventions for patients with ID.

In addition to the DSM-5, Dr. Gentile said the National Association for the Dually Diagnosed has published the Diagnostic Manual – Intellectual Disability. Another resource is a practical reference manual originally proposed by one of Dr. Gentile’s residents.

“He came into my office for supervision one day and said, ‘You know, there’s all these nuances for psychiatric treatment in this patient population. So we should write a practice, quick reference manual to help clinicians who aren’t able to spend as much time concentrate on this patient population.’ ”

As a result, several residents and faculty members formed a team to produce an 18-chapter book published this year by Springer called the Guide to Intellectual Disabilities: A Clinical Handbook.

Dr. Bhatt is a staff psychiatrist at Twin Valley Behavioral Healthcare, the state psychiatric hospital in Columbus, Ohio. Dr. Gentile is professor and chair of the department of psychiatry at Wright State in Dayton. She is also serves as project director of Ohio’s Telepsychiatry Project for Intellectual Disability and has been awarded more than $7 million in grant funding to support her projects in the field of ID.

Dr. Gentile’s work has been funded by the Ohio Department of Developmental Disabilities and the Ohio Department of Mental Health and Addiction Services.
 

[email protected]

SAN FRANCISCO – Some physicians are uncomfortable providing mental health care to patients with intellectual disability (ID) because many of the patients’ communications skills are limited. But many resources are available that can help.

In this video, Nita V. Bhatt, MD, MPH, interviews Julie P. Gentile, MD, about some of those resources and discusses how to approach psychiatric treatment interventions for patients with ID.

In addition to the DSM-5, Dr. Gentile said the National Association for the Dually Diagnosed has published the Diagnostic Manual – Intellectual Disability. Another resource is a practical reference manual originally proposed by one of Dr. Gentile’s residents.

“He came into my office for supervision one day and said, ‘You know, there’s all these nuances for psychiatric treatment in this patient population. So we should write a practice, quick reference manual to help clinicians who aren’t able to spend as much time concentrate on this patient population.’ ”

As a result, several residents and faculty members formed a team to produce an 18-chapter book published this year by Springer called the Guide to Intellectual Disabilities: A Clinical Handbook.

Dr. Bhatt is a staff psychiatrist at Twin Valley Behavioral Healthcare, the state psychiatric hospital in Columbus, Ohio. Dr. Gentile is professor and chair of the department of psychiatry at Wright State in Dayton. She is also serves as project director of Ohio’s Telepsychiatry Project for Intellectual Disability and has been awarded more than $7 million in grant funding to support her projects in the field of ID.

Dr. Gentile’s work has been funded by the Ohio Department of Developmental Disabilities and the Ohio Department of Mental Health and Addiction Services.
 

[email protected]

In a commentary issued on May 6, the Food and Drug Administration stated that “with sunscreens now being used with greater frequency, in larger amounts, and by broader populations, it is more important than ever to ensure that sunscreens are safe and effective for daily, lifelong use.” The statement coincided with the publication of the randomized study, “Effect of sunscreen application under maximal use conditions on plasma concentrations of sunscreen active ingredients,” by Matta et al. of the FDA and others in JAMA (2019 May 6. doi: 10.1001/jama.2019.5586). A maximal usage trial examines the systemic absorption of a topical drug when used according to the guidelines given for the product’s maximum usage. In this study, adult participants were randomized to one of four commercially available sunscreen products: spray 1 (n = 6), spray 2 (n = 6), a lotion (n = 6), and a cream (n = 6). Two mg of sunscreen per 1 cm² was applied to 75% of body surface area four times per day for 4 days, and blood samples were collected from each individual over 7 days.

Plasma concentrations of the four active ingredients tested – avobenzone, oxybenzone, octocrylene, and ecamsule – were above 0.5 ng/mL. The FDA’s guidance for industry and proposed rule on OTC sunscreens state that active ingredients with systemic absorption at 0.5 ng/mL or higher or with possible safety concerns need to undergo further nonclinical toxicology assessment to evaluate risk of systemic carcinogenicity, developmental/reproductive abnormalities, or other adverse effects.

Absorption of some sunscreen ingredients has been detected in other studies. Despite systemic absorption, two active ingredients – zinc oxide and titanium dioxide – have been found by the FDA to be generally recognized as safe and effective. But for 12 other active ingredients (cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone), there are insufficient data to make a “generally recognized as safe and effective” determination; thus, more data have been requested from the manufacturers. While physical blocking sunscreens have improved in their UV-blocking ability without compromising cosmesis over the past several years, some sunscreens containing chemical blockers are able to achieve higher SPFs with good cosmesis when applied to the skin.

Our skin acts as the ultimate barrier between ourselves and the environment, and it is not uncommon for substances to be blocked, absorbed, or excreted from the skin. Absorption of an ingredient through the skin and into the body does not indicate that the ingredient is unsafe. Rather, findings such as these call for further testing and research to determine the safety of that ingredient with repeated use. Per the FDA, such testing is part of the standard premarket safety evaluation of most chronically administered drugs with appreciable systemic absorption.

In February 2019, the FDA’s proposed rule was issued to “update regulatory requirements for most sunscreen products in the United States,” with the goal of bringing OTC sunscreens “up to date with the latest scientific standards,” according to the FDA May 6 commentary. “As part of this rule, the FDA is asking industry and other interested parties for additional safety data on the 12 active sunscreen ingredients currently available in marketed products” mentioned previously. These rules are being put into place to address the “key data gap” for these 12 ingredients, which is “understanding whether, and to what extent the ingredient is absorbed into the body after topical application.”

More research in this area is needed, but studies have linked these ingredients to harming coral by bleaching, disease, and damage to DNA, and also to decreasing fertility in fish, impairing algae growth, inducing defects in mussel and sea urchin young, and accumulating in the tissues of dolphins. According to NASA, as much as 27% of monitored reef formation have already been lost and over the following 32 years, 32% more are at risk. Reefs cover a mere 0.2% of the ocean’s floor, but it is estimated that reefs are home to and protect nearly 1 million species of fish, invertebrates, and algae.

In early May, Rep. Tulsi Gabbard (D-Hawaii) and Sen. Tim Ryan (D-Ohio) introduced legislation known as the Oxybenzone and Octinoxate Impact Study Act of 2019 (H.R. 2588) to require the Environmental Protection Agency to study the impact of those two chemicals on human health and the environment and to provide findings to Congress and the public within 18 months.

The importance of sun protection and prevention of sunburns is paramount. We know that multiple sunburn events during childhood double a child’s risk of developing skin cancer later in life, and skin cancer is the most common cancer diagnosed in the United States, with 5 million cases treated every year. One in five Americans will develop skin cancer by age 70 years.

As a Mohs and a cosmetic dermatologic surgeon, I appreciate the unquestionable protective effects of sunscreen products with regards to skin cancer, dyspigmentation, solar elastosis, and rhytids associated with photoaging. We can applaud the FDA for improving testing and regulation of OTC ingredients, including those in sunscreen. These types of studies are important and monumental in ensuring that we are utilizing the right type of ingredients to protect our patients, our oceans, and our reefs.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References

• Matta MK et al. JAMA. 2019 May 6. doi: 10.1001/jama.2019.5586.
• Shedding new light on sunscreen absorption, by Janet Woodcock, MD, director, Center for Drug Evaluation and Research, and Theresa M. Michele, MD, director, CDER’s Division of Nonprescription Drug Products, Office of New Drugs
• Food and Drug Administration. Sunscreen drug products for over-the-counter human use: Proposed rule. Fed Regist. 2019;84(38):6204-75.
• Schlumpf M et al. Chemosphere. 2010 Nov;81(10):1171-83.
• Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.

In a commentary issued on May 6, the Food and Drug Administration stated that “with sunscreens now being used with greater frequency, in larger amounts, and by broader populations, it is more important than ever to ensure that sunscreens are safe and effective for daily, lifelong use.” The statement coincided with the publication of the randomized study, “Effect of sunscreen application under maximal use conditions on plasma concentrations of sunscreen active ingredients,” by Matta et al. of the FDA and others in JAMA (2019 May 6. doi: 10.1001/jama.2019.5586). A maximal usage trial examines the systemic absorption of a topical drug when used according to the guidelines given for the product’s maximum usage. In this study, adult participants were randomized to one of four commercially available sunscreen products: spray 1 (n = 6), spray 2 (n = 6), a lotion (n = 6), and a cream (n = 6). Two mg of sunscreen per 1 cm² was applied to 75% of body surface area four times per day for 4 days, and blood samples were collected from each individual over 7 days.

Plasma concentrations of the four active ingredients tested – avobenzone, oxybenzone, octocrylene, and ecamsule – were above 0.5 ng/mL. The FDA’s guidance for industry and proposed rule on OTC sunscreens state that active ingredients with systemic absorption at 0.5 ng/mL or higher or with possible safety concerns need to undergo further nonclinical toxicology assessment to evaluate risk of systemic carcinogenicity, developmental/reproductive abnormalities, or other adverse effects.

Absorption of some sunscreen ingredients has been detected in other studies. Despite systemic absorption, two active ingredients – zinc oxide and titanium dioxide – have been found by the FDA to be generally recognized as safe and effective. But for 12 other active ingredients (cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone), there are insufficient data to make a “generally recognized as safe and effective” determination; thus, more data have been requested from the manufacturers. While physical blocking sunscreens have improved in their UV-blocking ability without compromising cosmesis over the past several years, some sunscreens containing chemical blockers are able to achieve higher SPFs with good cosmesis when applied to the skin.

Our skin acts as the ultimate barrier between ourselves and the environment, and it is not uncommon for substances to be blocked, absorbed, or excreted from the skin. Absorption of an ingredient through the skin and into the body does not indicate that the ingredient is unsafe. Rather, findings such as these call for further testing and research to determine the safety of that ingredient with repeated use. Per the FDA, such testing is part of the standard premarket safety evaluation of most chronically administered drugs with appreciable systemic absorption.

In February 2019, the FDA’s proposed rule was issued to “update regulatory requirements for most sunscreen products in the United States,” with the goal of bringing OTC sunscreens “up to date with the latest scientific standards,” according to the FDA May 6 commentary. “As part of this rule, the FDA is asking industry and other interested parties for additional safety data on the 12 active sunscreen ingredients currently available in marketed products” mentioned previously. These rules are being put into place to address the “key data gap” for these 12 ingredients, which is “understanding whether, and to what extent the ingredient is absorbed into the body after topical application.”

More research in this area is needed, but studies have linked these ingredients to harming coral by bleaching, disease, and damage to DNA, and also to decreasing fertility in fish, impairing algae growth, inducing defects in mussel and sea urchin young, and accumulating in the tissues of dolphins. According to NASA, as much as 27% of monitored reef formation have already been lost and over the following 32 years, 32% more are at risk. Reefs cover a mere 0.2% of the ocean’s floor, but it is estimated that reefs are home to and protect nearly 1 million species of fish, invertebrates, and algae.

In early May, Rep. Tulsi Gabbard (D-Hawaii) and Sen. Tim Ryan (D-Ohio) introduced legislation known as the Oxybenzone and Octinoxate Impact Study Act of 2019 (H.R. 2588) to require the Environmental Protection Agency to study the impact of those two chemicals on human health and the environment and to provide findings to Congress and the public within 18 months.

The importance of sun protection and prevention of sunburns is paramount. We know that multiple sunburn events during childhood double a child’s risk of developing skin cancer later in life, and skin cancer is the most common cancer diagnosed in the United States, with 5 million cases treated every year. One in five Americans will develop skin cancer by age 70 years.

As a Mohs and a cosmetic dermatologic surgeon, I appreciate the unquestionable protective effects of sunscreen products with regards to skin cancer, dyspigmentation, solar elastosis, and rhytids associated with photoaging. We can applaud the FDA for improving testing and regulation of OTC ingredients, including those in sunscreen. These types of studies are important and monumental in ensuring that we are utilizing the right type of ingredients to protect our patients, our oceans, and our reefs.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References

• Matta MK et al. JAMA. 2019 May 6. doi: 10.1001/jama.2019.5586.
• Shedding new light on sunscreen absorption, by Janet Woodcock, MD, director, Center for Drug Evaluation and Research, and Theresa M. Michele, MD, director, CDER’s Division of Nonprescription Drug Products, Office of New Drugs
• Food and Drug Administration. Sunscreen drug products for over-the-counter human use: Proposed rule. Fed Regist. 2019;84(38):6204-75.
• Schlumpf M et al. Chemosphere. 2010 Nov;81(10):1171-83.
• Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.

In a commentary issued on May 6, the Food and Drug Administration stated that “with sunscreens now being used with greater frequency, in larger amounts, and by broader populations, it is more important than ever to ensure that sunscreens are safe and effective for daily, lifelong use.” The statement coincided with the publication of the randomized study, “Effect of sunscreen application under maximal use conditions on plasma concentrations of sunscreen active ingredients,” by Matta et al. of the FDA and others in JAMA (2019 May 6. doi: 10.1001/jama.2019.5586). A maximal usage trial examines the systemic absorption of a topical drug when used according to the guidelines given for the product’s maximum usage. In this study, adult participants were randomized to one of four commercially available sunscreen products: spray 1 (n = 6), spray 2 (n = 6), a lotion (n = 6), and a cream (n = 6). Two mg of sunscreen per 1 cm² was applied to 75% of body surface area four times per day for 4 days, and blood samples were collected from each individual over 7 days.

Plasma concentrations of the four active ingredients tested – avobenzone, oxybenzone, octocrylene, and ecamsule – were above 0.5 ng/mL. The FDA’s guidance for industry and proposed rule on OTC sunscreens state that active ingredients with systemic absorption at 0.5 ng/mL or higher or with possible safety concerns need to undergo further nonclinical toxicology assessment to evaluate risk of systemic carcinogenicity, developmental/reproductive abnormalities, or other adverse effects.

Absorption of some sunscreen ingredients has been detected in other studies. Despite systemic absorption, two active ingredients – zinc oxide and titanium dioxide – have been found by the FDA to be generally recognized as safe and effective. But for 12 other active ingredients (cinoxate, dioxybenzone, ensulizole, homosalate, meradimate, octinoxate, octisalate, octocrylene, padimate O, sulisobenzone, oxybenzone, and avobenzone), there are insufficient data to make a “generally recognized as safe and effective” determination; thus, more data have been requested from the manufacturers. While physical blocking sunscreens have improved in their UV-blocking ability without compromising cosmesis over the past several years, some sunscreens containing chemical blockers are able to achieve higher SPFs with good cosmesis when applied to the skin.

Our skin acts as the ultimate barrier between ourselves and the environment, and it is not uncommon for substances to be blocked, absorbed, or excreted from the skin. Absorption of an ingredient through the skin and into the body does not indicate that the ingredient is unsafe. Rather, findings such as these call for further testing and research to determine the safety of that ingredient with repeated use. Per the FDA, such testing is part of the standard premarket safety evaluation of most chronically administered drugs with appreciable systemic absorption.

In February 2019, the FDA’s proposed rule was issued to “update regulatory requirements for most sunscreen products in the United States,” with the goal of bringing OTC sunscreens “up to date with the latest scientific standards,” according to the FDA May 6 commentary. “As part of this rule, the FDA is asking industry and other interested parties for additional safety data on the 12 active sunscreen ingredients currently available in marketed products” mentioned previously. These rules are being put into place to address the “key data gap” for these 12 ingredients, which is “understanding whether, and to what extent the ingredient is absorbed into the body after topical application.”

More research in this area is needed, but studies have linked these ingredients to harming coral by bleaching, disease, and damage to DNA, and also to decreasing fertility in fish, impairing algae growth, inducing defects in mussel and sea urchin young, and accumulating in the tissues of dolphins. According to NASA, as much as 27% of monitored reef formation have already been lost and over the following 32 years, 32% more are at risk. Reefs cover a mere 0.2% of the ocean’s floor, but it is estimated that reefs are home to and protect nearly 1 million species of fish, invertebrates, and algae.

In early May, Rep. Tulsi Gabbard (D-Hawaii) and Sen. Tim Ryan (D-Ohio) introduced legislation known as the Oxybenzone and Octinoxate Impact Study Act of 2019 (H.R. 2588) to require the Environmental Protection Agency to study the impact of those two chemicals on human health and the environment and to provide findings to Congress and the public within 18 months.

The importance of sun protection and prevention of sunburns is paramount. We know that multiple sunburn events during childhood double a child’s risk of developing skin cancer later in life, and skin cancer is the most common cancer diagnosed in the United States, with 5 million cases treated every year. One in five Americans will develop skin cancer by age 70 years.

As a Mohs and a cosmetic dermatologic surgeon, I appreciate the unquestionable protective effects of sunscreen products with regards to skin cancer, dyspigmentation, solar elastosis, and rhytids associated with photoaging. We can applaud the FDA for improving testing and regulation of OTC ingredients, including those in sunscreen. These types of studies are important and monumental in ensuring that we are utilizing the right type of ingredients to protect our patients, our oceans, and our reefs.

Dr. Wesley and Dr. Talakoub are co-contributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Wesley. Write to them at [email protected]. They had no relevant disclosures.

References

• Matta MK et al. JAMA. 2019 May 6. doi: 10.1001/jama.2019.5586.
• Shedding new light on sunscreen absorption, by Janet Woodcock, MD, director, Center for Drug Evaluation and Research, and Theresa M. Michele, MD, director, CDER’s Division of Nonprescription Drug Products, Office of New Drugs
• Food and Drug Administration. Sunscreen drug products for over-the-counter human use: Proposed rule. Fed Regist. 2019;84(38):6204-75.
• Schlumpf M et al. Chemosphere. 2010 Nov;81(10):1171-83.
• Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.

Background: Acute variceal bleeding remains the most severe and life-threatening complication of portal hypertension in cirrhotic patients. Several small studies have shown improved outcomes with p-TIPS without worsening of hepatic encephalopathy or other adverse events.

Dr. Imber is an assistant professor in the division of hospital medicine, University of New Mexico.
 

Background: Acute variceal bleeding remains the most severe and life-threatening complication of portal hypertension in cirrhotic patients. Several small studies have shown improved outcomes with p-TIPS without worsening of hepatic encephalopathy or other adverse events.

Dr. Imber is an assistant professor in the division of hospital medicine, University of New Mexico.
 

Background: Acute variceal bleeding remains the most severe and life-threatening complication of portal hypertension in cirrhotic patients. Several small studies have shown improved outcomes with p-TIPS without worsening of hepatic encephalopathy or other adverse events.

Dr. Imber is an assistant professor in the division of hospital medicine, University of New Mexico.