Promising New Approaches for Testicular and Prostate Cancer

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References
  1. Risk factors for testicular cancer. American Cancer Society. Updated May 17, 2018. Accessed December 15, 2022. https://www.cancer.org/cancer/testicular-cancer/causes-risks-prevention/risk-factors.html
  2. Chovanec M, Cheng L. BMJ. 2022;379:e070499. doi:10.1136/bmj-2022-070499
  3. Tavares NT et al. J Pathol. 2022. doi:10.1002/path.6037
  4. Bryant AK et al. JAMA Oncol. 2022;e224319. doi:10.1001/jamaoncol.2022.4319
  5. Kabasakal L et al. Nucl Med Commun. 2017;38(2):149-155. doi:10.1097/MNM.0000000000000617
  6. Sartor O et al; VISION Investigators. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322
  7. Rowe SP et al. Annu Rev Med. 2019;70:461-477. doi:10.1146/annurev-med-062117-073027
  8. Pomykala KL et al. Eur Urol Oncol. 2022;S2588-9311(22)00177-8. doi:10.1016/j.euo.2022.10.007
  9. Keam SJ. Mol Diagn Ther. 2022;26(4):467-475. doi:10.1007/s40291-022-00594-2
  10. Lovejoy LA et al. Mil Med. 2022:usac297. doi:10.1093/milmed/usac297
  11. Smith ZL et al. Med Clin North Am. 2018;102(2):251-264. doi:10.1016/j.mcna.2017.10.003
  12. Hohnloser JH et al. Eur J Med Res.1996;1(11):509-514.
  13. Johns Hopkins Medicine website. Testicular Cancer tumor Markers. Accessed December 2022. https://www.hopkinsmedicine.org/health/conditions-and-diseases/testicular-cancer/testicular-cancer-tumor-markers
  14. Webber BJ et al. J Occup Environ Med. 2022;64(1):71-78. doi:10.1097/JOM.0000000000002353
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Bruce Montgomery, MD
Medicine and Oncology,
University of Washington
Fred Hutchinson Cancer Center
VA Puget Sound HCS
Seattle, WA

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Medicine and Oncology,
University of Washington
Fred Hutchinson Cancer Center
VA Puget Sound HCS
Seattle, WA

References
  1. Risk factors for testicular cancer. American Cancer Society. Updated May 17, 2018. Accessed December 15, 2022. https://www.cancer.org/cancer/testicular-cancer/causes-risks-prevention/risk-factors.html
  2. Chovanec M, Cheng L. BMJ. 2022;379:e070499. doi:10.1136/bmj-2022-070499
  3. Tavares NT et al. J Pathol. 2022. doi:10.1002/path.6037
  4. Bryant AK et al. JAMA Oncol. 2022;e224319. doi:10.1001/jamaoncol.2022.4319
  5. Kabasakal L et al. Nucl Med Commun. 2017;38(2):149-155. doi:10.1097/MNM.0000000000000617
  6. Sartor O et al; VISION Investigators. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322
  7. Rowe SP et al. Annu Rev Med. 2019;70:461-477. doi:10.1146/annurev-med-062117-073027
  8. Pomykala KL et al. Eur Urol Oncol. 2022;S2588-9311(22)00177-8. doi:10.1016/j.euo.2022.10.007
  9. Keam SJ. Mol Diagn Ther. 2022;26(4):467-475. doi:10.1007/s40291-022-00594-2
  10. Lovejoy LA et al. Mil Med. 2022:usac297. doi:10.1093/milmed/usac297
  11. Smith ZL et al. Med Clin North Am. 2018;102(2):251-264. doi:10.1016/j.mcna.2017.10.003
  12. Hohnloser JH et al. Eur J Med Res.1996;1(11):509-514.
  13. Johns Hopkins Medicine website. Testicular Cancer tumor Markers. Accessed December 2022. https://www.hopkinsmedicine.org/health/conditions-and-diseases/testicular-cancer/testicular-cancer-tumor-markers
  14. Webber BJ et al. J Occup Environ Med. 2022;64(1):71-78. doi:10.1097/JOM.0000000000002353
References
  1. Risk factors for testicular cancer. American Cancer Society. Updated May 17, 2018. Accessed December 15, 2022. https://www.cancer.org/cancer/testicular-cancer/causes-risks-prevention/risk-factors.html
  2. Chovanec M, Cheng L. BMJ. 2022;379:e070499. doi:10.1136/bmj-2022-070499
  3. Tavares NT et al. J Pathol. 2022. doi:10.1002/path.6037
  4. Bryant AK et al. JAMA Oncol. 2022;e224319. doi:10.1001/jamaoncol.2022.4319
  5. Kabasakal L et al. Nucl Med Commun. 2017;38(2):149-155. doi:10.1097/MNM.0000000000000617
  6. Sartor O et al; VISION Investigators. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322
  7. Rowe SP et al. Annu Rev Med. 2019;70:461-477. doi:10.1146/annurev-med-062117-073027
  8. Pomykala KL et al. Eur Urol Oncol. 2022;S2588-9311(22)00177-8. doi:10.1016/j.euo.2022.10.007
  9. Keam SJ. Mol Diagn Ther. 2022;26(4):467-475. doi:10.1007/s40291-022-00594-2
  10. Lovejoy LA et al. Mil Med. 2022:usac297. doi:10.1093/milmed/usac297
  11. Smith ZL et al. Med Clin North Am. 2018;102(2):251-264. doi:10.1016/j.mcna.2017.10.003
  12. Hohnloser JH et al. Eur J Med Res.1996;1(11):509-514.
  13. Johns Hopkins Medicine website. Testicular Cancer tumor Markers. Accessed December 2022. https://www.hopkinsmedicine.org/health/conditions-and-diseases/testicular-cancer/testicular-cancer-tumor-markers
  14. Webber BJ et al. J Occup Environ Med. 2022;64(1):71-78. doi:10.1097/JOM.0000000000002353
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Although testicular cancer is rare, it is most common in boys and men between 15 and 34 years of age—the age range of many active-duty military members. Risk factors include a personal history of an undescended testicle or prior testicular cancer, a family history of testicular cancer, HIV infection, having Klinefelter disease, age, and race.1

Treatment for testicular cancer can involve surgery, radiation, or chemotherapy. For patients with metastatic testicular cancer, the development of cisplatin-based chemotherapy has made this one of the most curable malignancies of any type.2,3 Advances in the treatment of men with testicular cancer continue to be made. A recently described serum biomarker,  miR-371a-3p, is more sensitive for detecting the presence of subclinical disease than those currently used and is poised to be in clinical use shortly.3 New approaches to treatment, including high-dose therapy and drugs targeting the epigenetic regulation of testicular cancer, continue to be explored. Prostate cancer, on the other hand, is the second most common cancer in men worldwide.4 The use of prostate-specific antigen (PSA) screening for the detection of prostate cancer has been controversial in the United States for years. Because the US Preventive Services Task Force recommended against PSA screening, PSA screening rates decreased in the VHA and across the United States from 2005 to 2019.

A recent study was conducted within the VHA to determine whether the lower PSA screening rates had an impact on the occurrence of metastatic prostate cancer in VHA patients. The results showed that facilities with higher PSA screening rates had lower rates of metastatic prostate cancer; conversely, higher long-term nonscreening rates were associated with higher metastatic prostate cancer diagnosis rates for patients within the VHA system.4

These results strongly suggest that PSA screening does aid in the early detection and reduction of the development of prostate cancer. New imaging and treatments for prostate cancer are also available and have shown promise for patients. Prostate-specific membrane antigen (PSMA) imaging can effectively detect prostate cancer that has spread at earlier time points and help with informed decision-making for treatment. Where available, PSMA positron emission tomography/computed tomography (PET/CT) is preferred over other forms of noninvasive diagnostic imaging for staging before local therapy and for detection of sites of recurrence after local therapy because of its greater sensitivity at low PSA levels.5
Lutetium Lu 177 vipivotide tetraxetan (Pluvicto), the newest FDA-approved drug for treating prostate cancer, is an IV radioligand therapy that delivers β-particle radiation to PSMA-expressing cells.6 It can target prostate cancer cells without affecting most normal tissues in patients with the use of imaging to confirm radionuclide binding.The use of Lutetium in men with advanced prostate cancer improved survival compared with the standard of care.6,7 Strategies for early detection of these 2 cancers affecting veterans should include testicular self-examination for the presence of any masses and the use of the PSA test should be considered for the early detection of prostate cancer in the appropriate patient.

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Lung Cancer Screening in Veterans

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Lung Cancer Screening in Veterans
References
  1. Spalluto LB et al. J Am Coll Radiol. 2021;18(6):809-819. doi:10.1016/j.jacr.2020.12.010
  2. Lewis JA et al. JNCI Cancer Spectr. 2020;4(5):pkaa053. doi:10.1093/jncics/pkaa053
  3. Wallace C. Largest-ever lung cancer screening study reveals ways to increase screening outreach. Medical University of South Carolina. November 22, 2022. Accessed January 4, 202 https://hollingscancercenter.musc.edu/news/archive/2022/11/22/largest-ever-lung-cancer-screening-study-reveals-ways-to-increase-screening-outreach
  4. Screening facts & figures. Go2 For Lung Cancer. 2022. Accessed January 4, 2023. https://go2.org/risk-early-detection/screening-facts-figures/
  5. Dyer O. BMJ. 2021;372:n698. doi:10.1136/bmj.n698
  6. Boudreau JH et al. Chest. 2021;160(1):358-367. doi:10.1016/j.chest.2021.02.016
  7. Maurice NM, Tanner NT. Semin Oncol. 2022;S0093-7754(22)00041-0. doi:10.1053/j.seminoncol.2022.06.001
  8. Rusher TN et al. Fed Pract. 2022;39(suppl 2):S48-S51. doi:10.12788/fp.0269
  9. Núñez ER et al. JAMA Netw Open. 2021;4(7):e2116233. doi:10.1001/jamanetworkopen.2021.16233
  10. Lake M et al. BMC Cancer. 2020;20(1):561. doi:1186/s12885-020-06923-0
Author and Disclosure Information

Apar Kishor Ganti, MD, MS
Doctor and Mrs. D. Leon UNMC Research
Fund Chair in Internal Medicine
Staff Physician, VA Nebraska-Western Iowa Health Care System
Professor of Medicine, Division of Oncology-Hematology
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Associate Director of Clinical Research, Fred & Pamela Buffett Cancer Center
University of Nebraska Medical Center
Omaha, NE

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University of Nebraska Medical Center
Omaha, NE

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Apar Kishor Ganti, MD, MS
Doctor and Mrs. D. Leon UNMC Research
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Professor of Medicine, Division of Oncology-Hematology
Professor (Courtesy) of Biochemistry and Molecular Biology
Associate Director of Clinical Research, Fred & Pamela Buffett Cancer Center
University of Nebraska Medical Center
Omaha, NE

References
  1. Spalluto LB et al. J Am Coll Radiol. 2021;18(6):809-819. doi:10.1016/j.jacr.2020.12.010
  2. Lewis JA et al. JNCI Cancer Spectr. 2020;4(5):pkaa053. doi:10.1093/jncics/pkaa053
  3. Wallace C. Largest-ever lung cancer screening study reveals ways to increase screening outreach. Medical University of South Carolina. November 22, 2022. Accessed January 4, 202 https://hollingscancercenter.musc.edu/news/archive/2022/11/22/largest-ever-lung-cancer-screening-study-reveals-ways-to-increase-screening-outreach
  4. Screening facts & figures. Go2 For Lung Cancer. 2022. Accessed January 4, 2023. https://go2.org/risk-early-detection/screening-facts-figures/
  5. Dyer O. BMJ. 2021;372:n698. doi:10.1136/bmj.n698
  6. Boudreau JH et al. Chest. 2021;160(1):358-367. doi:10.1016/j.chest.2021.02.016
  7. Maurice NM, Tanner NT. Semin Oncol. 2022;S0093-7754(22)00041-0. doi:10.1053/j.seminoncol.2022.06.001
  8. Rusher TN et al. Fed Pract. 2022;39(suppl 2):S48-S51. doi:10.12788/fp.0269
  9. Núñez ER et al. JAMA Netw Open. 2021;4(7):e2116233. doi:10.1001/jamanetworkopen.2021.16233
  10. Lake M et al. BMC Cancer. 2020;20(1):561. doi:1186/s12885-020-06923-0
References
  1. Spalluto LB et al. J Am Coll Radiol. 2021;18(6):809-819. doi:10.1016/j.jacr.2020.12.010
  2. Lewis JA et al. JNCI Cancer Spectr. 2020;4(5):pkaa053. doi:10.1093/jncics/pkaa053
  3. Wallace C. Largest-ever lung cancer screening study reveals ways to increase screening outreach. Medical University of South Carolina. November 22, 2022. Accessed January 4, 202 https://hollingscancercenter.musc.edu/news/archive/2022/11/22/largest-ever-lung-cancer-screening-study-reveals-ways-to-increase-screening-outreach
  4. Screening facts & figures. Go2 For Lung Cancer. 2022. Accessed January 4, 2023. https://go2.org/risk-early-detection/screening-facts-figures/
  5. Dyer O. BMJ. 2021;372:n698. doi:10.1136/bmj.n698
  6. Boudreau JH et al. Chest. 2021;160(1):358-367. doi:10.1016/j.chest.2021.02.016
  7. Maurice NM, Tanner NT. Semin Oncol. 2022;S0093-7754(22)00041-0. doi:10.1053/j.seminoncol.2022.06.001
  8. Rusher TN et al. Fed Pract. 2022;39(suppl 2):S48-S51. doi:10.12788/fp.0269
  9. Núñez ER et al. JAMA Netw Open. 2021;4(7):e2116233. doi:10.1001/jamanetworkopen.2021.16233
  10. Lake M et al. BMC Cancer. 2020;20(1):561. doi:1186/s12885-020-06923-0
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In the United States and among veterans, lung cancer has the highest rate of cancer-related mortality. Earlier detection and increased screening of high-risk individuals can improve the overall survival rate.1  With the broadening of the USPSTF lung cancer screening guidelines, in 2020 an estimated 15 million people in the United States—including at least 900,000 veterans—were eligible for lung cancer screening by CT.2,3 However, only 5% of those eligible were screened.4,5 One reason for this vast discrepancy is uneven access. Estimates in 2021 were that <20% of eligible veterans have undergone lung cancer screening because of problems accessing it in rural areas.6

Implementing the expanded USPSTF guidelines is key to maximizing screening among underserved populations, such as those in rural areas who may lack access to nearby health care, as well as racial and ethnic minorities.1  A study of one VAMCs standardization of screening practices found that radiologists were more likely to adapt to these changes than primary care clinicians, suggesting a need to better understand differences in health care professional practices and priorities to universally improve screening rates across the VA.

An important question will always be how many high-risk veterans are being screened for lung cancer? To ensure proper care, it is important to understand the characteristics of clinicians who provide screening based on setting and clinical areas of expertise. Where are they, who are they, and how do our most vulnerable populations gain access? Access is critical, particularly among clinicians who typically provide screening to those underserved populations.

Although lung cancer screening rates have increased over the years, overall, utilization remains low, even though data show a 20% reduction in lung cancer mortality with adherence to yearly CT screening. Looking at these rates helps us understand the need to intervene to increase lung cancer screening rates.8  Guidelines have been an essential component when it comes to outcomes related to screenings. Through programs implemented by the VHA, the goal is to improve the uptake and quality of lung cancer screening and optimize the practice and access for all veterans.For clinicians, future work should evaluate lung cancer screening programs with high vs low rates of adherence to identify and publicize best practices for timely, appropriate follow-up. Although adherence rates remain low regardless of race, further research, particularly among Black veterans, is encouraged to address delayed follow-up and to create culturally competent and inclusive lung cancer screening programs.10

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AGA Research Scholar Awards advance the GI field

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The AGA Research Foundation plays an important role in medical research by providing grants to young scientists at a critical time in their careers. AGA’s flagship award is the Research Scholar Award (RSA), which provides career development support for young investigators in gastroenterology and hepatology research.

The AGA Research Awards program has a significant impact on digestive disease research.

  • More than $58 million has been awarded in research grants.
  • More than 1,000 scientists have been awarded grants.
  • Over the first 30 years of the Research Scholar Awards program, 57% of RSA recipients subsequently received at least one NIH R01 award, with 5 years on average between the RSA and first R01. Collectively, this group of investigators has secured 280 distinct R01 or equivalent awards.

Funded by the generosity of donors, the AGA Research Foundation’s research award program ensures that we are building a community of researchers whose work serves the greater community and benefits patients.

“In order to produce truly innovative work at the forefront of current discoveries, donations to research in GI are essential and cannot be replaced by other funding sources,” states Kathleen Curtius, PhD, MS, 2022 AGA Foundation Research Scholar Award recipient.

Join others in supporting the AGA Research Foundation. You will ensure that young researchers have opportunities to continue their lifesaving work. Your tax-deductible contribution supports the Foundation’s research award program, including the RSA, which ensures that studies are funded, discoveries are made, and patients are treated.

To learn more or to make a contribution, visit www.foundation.gastro.org.

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The AGA Research Foundation plays an important role in medical research by providing grants to young scientists at a critical time in their careers. AGA’s flagship award is the Research Scholar Award (RSA), which provides career development support for young investigators in gastroenterology and hepatology research.

The AGA Research Awards program has a significant impact on digestive disease research.

  • More than $58 million has been awarded in research grants.
  • More than 1,000 scientists have been awarded grants.
  • Over the first 30 years of the Research Scholar Awards program, 57% of RSA recipients subsequently received at least one NIH R01 award, with 5 years on average between the RSA and first R01. Collectively, this group of investigators has secured 280 distinct R01 or equivalent awards.

Funded by the generosity of donors, the AGA Research Foundation’s research award program ensures that we are building a community of researchers whose work serves the greater community and benefits patients.

“In order to produce truly innovative work at the forefront of current discoveries, donations to research in GI are essential and cannot be replaced by other funding sources,” states Kathleen Curtius, PhD, MS, 2022 AGA Foundation Research Scholar Award recipient.

Join others in supporting the AGA Research Foundation. You will ensure that young researchers have opportunities to continue their lifesaving work. Your tax-deductible contribution supports the Foundation’s research award program, including the RSA, which ensures that studies are funded, discoveries are made, and patients are treated.

To learn more or to make a contribution, visit www.foundation.gastro.org.

The AGA Research Foundation plays an important role in medical research by providing grants to young scientists at a critical time in their careers. AGA’s flagship award is the Research Scholar Award (RSA), which provides career development support for young investigators in gastroenterology and hepatology research.

The AGA Research Awards program has a significant impact on digestive disease research.

  • More than $58 million has been awarded in research grants.
  • More than 1,000 scientists have been awarded grants.
  • Over the first 30 years of the Research Scholar Awards program, 57% of RSA recipients subsequently received at least one NIH R01 award, with 5 years on average between the RSA and first R01. Collectively, this group of investigators has secured 280 distinct R01 or equivalent awards.

Funded by the generosity of donors, the AGA Research Foundation’s research award program ensures that we are building a community of researchers whose work serves the greater community and benefits patients.

“In order to produce truly innovative work at the forefront of current discoveries, donations to research in GI are essential and cannot be replaced by other funding sources,” states Kathleen Curtius, PhD, MS, 2022 AGA Foundation Research Scholar Award recipient.

Join others in supporting the AGA Research Foundation. You will ensure that young researchers have opportunities to continue their lifesaving work. Your tax-deductible contribution supports the Foundation’s research award program, including the RSA, which ensures that studies are funded, discoveries are made, and patients are treated.

To learn more or to make a contribution, visit www.foundation.gastro.org.

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Exposure-Related Cancers: A Look at the PACT Act

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References
  1. US Department of Veterans Affairs. PACT Act. Updated November 4, 2022. Accessed January 4, 2023. https://www.publichealth.va.gov/exposures/benefits/PACT_Act.asp
  2. The White House. FACT SHEET: President Biden signs the PACT Act and delivers on his promise to America’s veterans. August 10, 202 Accessed January 10, 2023. https://www.whitehouse.gov/briefing-room/statements-releases/2022/08/10/fact-sheet-president-biden-signs-the-pact-act-and-delivers-on-his-promise-to-americas-veterans/
  3. US House of Representatives. Honoring our promise to address Comprehensive Toxics Act of 2021. Title I – Expansion of health care eligibility for toxic exposed veterans. House report 117-249. February 22, 2022. Accessed January 19, 202 https://www.govinfo.gov/content/pkg/CRPT-117hrpt249/html/CRPT-117hrpt249-pt1.htm
  4. VA News. Cancer Moonshot week of action sees VA deploying new clinical pathways. Updated December 7, 2022. Accessed January 19, 2023. https://news.va.gov/111925/cancer-moonshot-clinical-pathways/
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References
  1. US Department of Veterans Affairs. PACT Act. Updated November 4, 2022. Accessed January 4, 2023. https://www.publichealth.va.gov/exposures/benefits/PACT_Act.asp
  2. The White House. FACT SHEET: President Biden signs the PACT Act and delivers on his promise to America’s veterans. August 10, 202 Accessed January 10, 2023. https://www.whitehouse.gov/briefing-room/statements-releases/2022/08/10/fact-sheet-president-biden-signs-the-pact-act-and-delivers-on-his-promise-to-americas-veterans/
  3. US House of Representatives. Honoring our promise to address Comprehensive Toxics Act of 2021. Title I – Expansion of health care eligibility for toxic exposed veterans. House report 117-249. February 22, 2022. Accessed January 19, 202 https://www.govinfo.gov/content/pkg/CRPT-117hrpt249/html/CRPT-117hrpt249-pt1.htm
  4. VA News. Cancer Moonshot week of action sees VA deploying new clinical pathways. Updated December 7, 2022. Accessed January 19, 2023. https://news.va.gov/111925/cancer-moonshot-clinical-pathways/
References
  1. US Department of Veterans Affairs. PACT Act. Updated November 4, 2022. Accessed January 4, 2023. https://www.publichealth.va.gov/exposures/benefits/PACT_Act.asp
  2. The White House. FACT SHEET: President Biden signs the PACT Act and delivers on his promise to America’s veterans. August 10, 202 Accessed January 10, 2023. https://www.whitehouse.gov/briefing-room/statements-releases/2022/08/10/fact-sheet-president-biden-signs-the-pact-act-and-delivers-on-his-promise-to-americas-veterans/
  3. US House of Representatives. Honoring our promise to address Comprehensive Toxics Act of 2021. Title I – Expansion of health care eligibility for toxic exposed veterans. House report 117-249. February 22, 2022. Accessed January 19, 202 https://www.govinfo.gov/content/pkg/CRPT-117hrpt249/html/CRPT-117hrpt249-pt1.htm
  4. VA News. Cancer Moonshot week of action sees VA deploying new clinical pathways. Updated December 7, 2022. Accessed January 19, 2023. https://news.va.gov/111925/cancer-moonshot-clinical-pathways/
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In August 2022, Congress passed the Sergeant First Class Heath Robinson Honoring our Promise to Address Comprehensive Toxics Act, known as the PACT Act. This new law signified the most expansive extension of VA health care and benefits in more than 30 years for veterans who were exposed to burn pits and other toxic substances during their service.1,2 In addition to striving for better care, the PACT Act also requires the VA to conduct new studies to better understand health trends in post-9/11 veterans and those who served in the Gulf War, and directs the Secretary of Veterans Affairs to develop a 5-year strategic plan on toxic exposure–related research.2

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New definition for iron deficiency in CV disease proposed

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A cohort study of patients with pulmonary hypertension (PH) has questioned the guideline definition of iron deficiency and the criteria used to identify and potentially treat it, with implications that may extend to cardiovascular disease in general.

In the study involving more than 900 patients with PH, investigators at seven U.S. centers determined the prevalence of iron deficiency by two separate definitions and assessed its associations with functional measures and quality of life (QoL) scores.

An iron deficiency definition used conventionally in heart failure (HF) – ferritin less than 100 g/mL or 100-299 ng/mL with transferrin saturation (TSAT) less than 20% – failed to discriminate patients with reduced peak oxygen consumption (peakVO2), 6-minute walk test (6MWT) results, and QoL scores on the 36-item Short Form Survey (SF-36).

But an alternative definition for iron deficiency, simply a TSAT less than 21%, did predict such patients with reduced peakVO2, 6MWT, and QoL. It was also associated with an increased mortality risk. The study was published in the European Heart Journal.

“A low TSAT, less than 21%, is key in the pathophysiology of iron deficiency in pulmonary hypertension” and is associated with those important clinical and functional characteristics, lead author Pieter Martens MD, PhD, said in an interview. The study “underscores the importance of these criteria in future intervention studies in the field of pulmonary hypertension testing iron therapies.”

A broader implication is that “we should revise how we define iron deficiency in heart failure and cardiovascular disease in general and how we select patients for iron therapies,” said Dr. Martens, of the Heart, Vascular & Thoracic Institute of the Cleveland Clinic.
 

Iron’s role in pulmonary vascular disease

“Iron deficiency is associated with an energetic deficit, especially in high energy–demanding tissue, leading to early skeletal muscle acidification and diminished left and right ventricular (RV) contractile reserve during exercise,” the published report states. It can lead to “maladaptive RV remodeling,” which is a “hallmark feature” predictive of morbidity and mortality in patients with pulmonary vascular disease (PVD).

Some studies have suggested that iron deficiency is a common comorbidity in patients with PVD, their estimates of its prevalence ranging widely due in part to the “absence of a uniform definition,” write the authors.

Dr. Martens said the current study was conducted partly in response to the increasingly common observation that the HF-associated definition of iron deficiency “has limitations.” Yet, “without validation in the field of pulmonary hypertension, the 2022 pulmonary hypertension guidelines endorse this definition.”

As iron deficiency is a causal risk factor for HF progression, Dr. Martens added, the HF field has “taught us the importance of using validated definitions for iron deficiency when selecting patients for iron treatment in randomized controlled trials.”

Moreover, some evidence suggests that iron deficiency by some definitions may be associated with diminished exercise capacity and QoL in patients with PVD, which are associations that have not been confirmed in large studies, the report notes.

Therefore, it continues, the study sought to “determine and validate” the optimal definition of iron deficiency in patients with PVD; document its prevalence; and explore associations between iron deficiency and exercise capacity, QoL, and cardiac and pulmonary vascular remodeling.
 

 

 

Evaluating definitions of iron deficiency

The prospective study, called PVDOMICS, entered 1,195 subjects with available iron levels. After exclusion of 38 patients with sarcoidosis, myeloproliferative disease, or hemoglobinopathy, there remained 693 patients with “overt” PH, 225 with a milder form of PH who served as PVD comparators, and 90 age-, sex-, race/ethnicity- matched “healthy” adults who served as controls.

According to the conventional HF definition of iron deficiency – that is, ferritin 100-299 ng/mL and TSAT less than 20% – the prevalences were 74% in patients with overt PH and 72% of those “across the PVD spectrum.”

But by that definition, iron deficient and non-iron deficient patients didn’t differ significantly in peakVO2, 6MWT distance, or SF-36 physical component scores.

In contrast, patients meeting the alternative definition of iron deficiency of TSAT less than 21% showed significantly reduced functional and QoL measures, compared with those with TSAT greater than or equal to 21%.



The group with TSAT less than 21% also showed significantly more RV remodeling at cardiac MRI, compared with those who had TSAT greater than or equal to 21%, but their invasively measured pulmonary vascular resistance was comparable.

Of note, those with TSAT less than 21% also showed significantly increased all-cause mortality (hazard ratio, 1.63; 95% confidence interval, 1.13-2.34; P = .009) after adjustment for age, sex, hemoglobin, and natriuretic peptide levels.

“Proper validation of the definition of iron deficiency is important for prognostication,” the published report states, “but also for providing a working definition that can be used to identify suitable patients for inclusion in randomized controlled trials” of drugs for iron deficiency.

Additionally, the finding that TSAT less than 21% points to patients with diminished functional and exercise capacity is “consistent with more recent studies in the field of heart failure” that suggest “functional abnormalities and adverse cardiac remodeling are worse in patients with a low TSAT.” Indeed, the report states, such treatment effects have been “the most convincing” in HF trials.
 

Broader implications

An accompanying editorial agrees that the study’s implications apply well beyond PH. It highlights that iron deficiency is common in PH, while such PH is “not substantially different from the problem in patients with heart failure, chronic kidney disease, and cardiovascular disease in general,” lead editorialist John G.F. Cleland, MD, PhD, University of Glasgow, said in an interview. “It’s also common as people get older, even in those without these diseases.”

Dr. Cleland said the anemia definition currently used in cardiovascular research and practice is based on a hemoglobin concentration below the 5th percentile of age and sex in primarily young, healthy people, and not on its association with clinical outcomes.

“We recently analyzed data on a large population in the United Kingdom with a broad range of cardiovascular diseases and found that unless anemia is severe, [other] markers of iron deficiency are usually not measured,” he said. A low hemoglobin and TSAT, but not low ferritin levels, are associated with worse prognosis.

Dr. Cleland agreed that the HF-oriented definition is “poor,” with profound implications for the conduct of clinical trials. “If the definition of iron deficiency lacks specificity, then clinical trials will include many patients without iron deficiency who are unlikely to benefit from and might be harmed by IV iron.” Inclusion of such patients may also “dilute” any benefit that might emerge and render the outcome inaccurate.

But if the definition of iron deficiency lacks sensitivity, “then in clinical practice, many patients with iron deficiency may be denied a simple and effective treatment.”

Measuring serum iron could potentially be useful, but it’s usually not done in randomized trials “especially since taking an iron tablet can give a temporary ‘blip’ in serum iron,” Dr. Cleland said. “So TSAT is a reasonable compromise.” He said he “looks forward” to any further data on serum iron as a way of assessing iron deficiency and anemia.
 

 

 

Half full vs. half empty

Dr. Cleland likened the question of whom to treat with iron supplementation as a “glass half full versus half empty” clinical dilemma. “One approach is to give iron to everyone unless there’s evidence that they’re overloaded,” he said, “while the other is to withhold iron from everyone unless there’s evidence that they’re iron depleted.”

Recent evidence from the IRONMAN trial suggested that its patients with HF who received intravenous iron were less likely to be hospitalized for infections, particularly COVID-19, than a usual-care group. The treatment may also help reduce frailty.

“So should we be offering IV iron specifically to people considered iron deficient, or should we be ensuring that everyone over age 70 get iron supplements?” Dr. Cleland mused rhetorically. On a cautionary note, he added, perhaps iron supplementation will be harmful if it’s not necessary.

Dr. Cleland proposed “focusing for the moment on people who are iron deficient but investigating the possibility that we are being overly restrictive and should be giving iron to a much broader population.” That course, however, would require large population-based studies.

“We need more experience,” Dr. Cleland said, “to make sure that the benefits outweigh any risks before we can just give iron to everyone.”

Dr. Martens has received consultancy fees from AstraZeneca, Abbott, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Novartis, Novo Nordisk, and Vifor Pharma. Dr. Cleland declares grant support, support for travel, and personal honoraria from Pharmacosmos and Vifor. Disclosures for other authors are in the published report and editorial.

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

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A cohort study of patients with pulmonary hypertension (PH) has questioned the guideline definition of iron deficiency and the criteria used to identify and potentially treat it, with implications that may extend to cardiovascular disease in general.

In the study involving more than 900 patients with PH, investigators at seven U.S. centers determined the prevalence of iron deficiency by two separate definitions and assessed its associations with functional measures and quality of life (QoL) scores.

An iron deficiency definition used conventionally in heart failure (HF) – ferritin less than 100 g/mL or 100-299 ng/mL with transferrin saturation (TSAT) less than 20% – failed to discriminate patients with reduced peak oxygen consumption (peakVO2), 6-minute walk test (6MWT) results, and QoL scores on the 36-item Short Form Survey (SF-36).

But an alternative definition for iron deficiency, simply a TSAT less than 21%, did predict such patients with reduced peakVO2, 6MWT, and QoL. It was also associated with an increased mortality risk. The study was published in the European Heart Journal.

“A low TSAT, less than 21%, is key in the pathophysiology of iron deficiency in pulmonary hypertension” and is associated with those important clinical and functional characteristics, lead author Pieter Martens MD, PhD, said in an interview. The study “underscores the importance of these criteria in future intervention studies in the field of pulmonary hypertension testing iron therapies.”

A broader implication is that “we should revise how we define iron deficiency in heart failure and cardiovascular disease in general and how we select patients for iron therapies,” said Dr. Martens, of the Heart, Vascular & Thoracic Institute of the Cleveland Clinic.
 

Iron’s role in pulmonary vascular disease

“Iron deficiency is associated with an energetic deficit, especially in high energy–demanding tissue, leading to early skeletal muscle acidification and diminished left and right ventricular (RV) contractile reserve during exercise,” the published report states. It can lead to “maladaptive RV remodeling,” which is a “hallmark feature” predictive of morbidity and mortality in patients with pulmonary vascular disease (PVD).

Some studies have suggested that iron deficiency is a common comorbidity in patients with PVD, their estimates of its prevalence ranging widely due in part to the “absence of a uniform definition,” write the authors.

Dr. Martens said the current study was conducted partly in response to the increasingly common observation that the HF-associated definition of iron deficiency “has limitations.” Yet, “without validation in the field of pulmonary hypertension, the 2022 pulmonary hypertension guidelines endorse this definition.”

As iron deficiency is a causal risk factor for HF progression, Dr. Martens added, the HF field has “taught us the importance of using validated definitions for iron deficiency when selecting patients for iron treatment in randomized controlled trials.”

Moreover, some evidence suggests that iron deficiency by some definitions may be associated with diminished exercise capacity and QoL in patients with PVD, which are associations that have not been confirmed in large studies, the report notes.

Therefore, it continues, the study sought to “determine and validate” the optimal definition of iron deficiency in patients with PVD; document its prevalence; and explore associations between iron deficiency and exercise capacity, QoL, and cardiac and pulmonary vascular remodeling.
 

 

 

Evaluating definitions of iron deficiency

The prospective study, called PVDOMICS, entered 1,195 subjects with available iron levels. After exclusion of 38 patients with sarcoidosis, myeloproliferative disease, or hemoglobinopathy, there remained 693 patients with “overt” PH, 225 with a milder form of PH who served as PVD comparators, and 90 age-, sex-, race/ethnicity- matched “healthy” adults who served as controls.

According to the conventional HF definition of iron deficiency – that is, ferritin 100-299 ng/mL and TSAT less than 20% – the prevalences were 74% in patients with overt PH and 72% of those “across the PVD spectrum.”

But by that definition, iron deficient and non-iron deficient patients didn’t differ significantly in peakVO2, 6MWT distance, or SF-36 physical component scores.

In contrast, patients meeting the alternative definition of iron deficiency of TSAT less than 21% showed significantly reduced functional and QoL measures, compared with those with TSAT greater than or equal to 21%.



The group with TSAT less than 21% also showed significantly more RV remodeling at cardiac MRI, compared with those who had TSAT greater than or equal to 21%, but their invasively measured pulmonary vascular resistance was comparable.

Of note, those with TSAT less than 21% also showed significantly increased all-cause mortality (hazard ratio, 1.63; 95% confidence interval, 1.13-2.34; P = .009) after adjustment for age, sex, hemoglobin, and natriuretic peptide levels.

“Proper validation of the definition of iron deficiency is important for prognostication,” the published report states, “but also for providing a working definition that can be used to identify suitable patients for inclusion in randomized controlled trials” of drugs for iron deficiency.

Additionally, the finding that TSAT less than 21% points to patients with diminished functional and exercise capacity is “consistent with more recent studies in the field of heart failure” that suggest “functional abnormalities and adverse cardiac remodeling are worse in patients with a low TSAT.” Indeed, the report states, such treatment effects have been “the most convincing” in HF trials.
 

Broader implications

An accompanying editorial agrees that the study’s implications apply well beyond PH. It highlights that iron deficiency is common in PH, while such PH is “not substantially different from the problem in patients with heart failure, chronic kidney disease, and cardiovascular disease in general,” lead editorialist John G.F. Cleland, MD, PhD, University of Glasgow, said in an interview. “It’s also common as people get older, even in those without these diseases.”

Dr. Cleland said the anemia definition currently used in cardiovascular research and practice is based on a hemoglobin concentration below the 5th percentile of age and sex in primarily young, healthy people, and not on its association with clinical outcomes.

“We recently analyzed data on a large population in the United Kingdom with a broad range of cardiovascular diseases and found that unless anemia is severe, [other] markers of iron deficiency are usually not measured,” he said. A low hemoglobin and TSAT, but not low ferritin levels, are associated with worse prognosis.

Dr. Cleland agreed that the HF-oriented definition is “poor,” with profound implications for the conduct of clinical trials. “If the definition of iron deficiency lacks specificity, then clinical trials will include many patients without iron deficiency who are unlikely to benefit from and might be harmed by IV iron.” Inclusion of such patients may also “dilute” any benefit that might emerge and render the outcome inaccurate.

But if the definition of iron deficiency lacks sensitivity, “then in clinical practice, many patients with iron deficiency may be denied a simple and effective treatment.”

Measuring serum iron could potentially be useful, but it’s usually not done in randomized trials “especially since taking an iron tablet can give a temporary ‘blip’ in serum iron,” Dr. Cleland said. “So TSAT is a reasonable compromise.” He said he “looks forward” to any further data on serum iron as a way of assessing iron deficiency and anemia.
 

 

 

Half full vs. half empty

Dr. Cleland likened the question of whom to treat with iron supplementation as a “glass half full versus half empty” clinical dilemma. “One approach is to give iron to everyone unless there’s evidence that they’re overloaded,” he said, “while the other is to withhold iron from everyone unless there’s evidence that they’re iron depleted.”

Recent evidence from the IRONMAN trial suggested that its patients with HF who received intravenous iron were less likely to be hospitalized for infections, particularly COVID-19, than a usual-care group. The treatment may also help reduce frailty.

“So should we be offering IV iron specifically to people considered iron deficient, or should we be ensuring that everyone over age 70 get iron supplements?” Dr. Cleland mused rhetorically. On a cautionary note, he added, perhaps iron supplementation will be harmful if it’s not necessary.

Dr. Cleland proposed “focusing for the moment on people who are iron deficient but investigating the possibility that we are being overly restrictive and should be giving iron to a much broader population.” That course, however, would require large population-based studies.

“We need more experience,” Dr. Cleland said, “to make sure that the benefits outweigh any risks before we can just give iron to everyone.”

Dr. Martens has received consultancy fees from AstraZeneca, Abbott, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Novartis, Novo Nordisk, and Vifor Pharma. Dr. Cleland declares grant support, support for travel, and personal honoraria from Pharmacosmos and Vifor. Disclosures for other authors are in the published report and editorial.

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

A cohort study of patients with pulmonary hypertension (PH) has questioned the guideline definition of iron deficiency and the criteria used to identify and potentially treat it, with implications that may extend to cardiovascular disease in general.

In the study involving more than 900 patients with PH, investigators at seven U.S. centers determined the prevalence of iron deficiency by two separate definitions and assessed its associations with functional measures and quality of life (QoL) scores.

An iron deficiency definition used conventionally in heart failure (HF) – ferritin less than 100 g/mL or 100-299 ng/mL with transferrin saturation (TSAT) less than 20% – failed to discriminate patients with reduced peak oxygen consumption (peakVO2), 6-minute walk test (6MWT) results, and QoL scores on the 36-item Short Form Survey (SF-36).

But an alternative definition for iron deficiency, simply a TSAT less than 21%, did predict such patients with reduced peakVO2, 6MWT, and QoL. It was also associated with an increased mortality risk. The study was published in the European Heart Journal.

“A low TSAT, less than 21%, is key in the pathophysiology of iron deficiency in pulmonary hypertension” and is associated with those important clinical and functional characteristics, lead author Pieter Martens MD, PhD, said in an interview. The study “underscores the importance of these criteria in future intervention studies in the field of pulmonary hypertension testing iron therapies.”

A broader implication is that “we should revise how we define iron deficiency in heart failure and cardiovascular disease in general and how we select patients for iron therapies,” said Dr. Martens, of the Heart, Vascular & Thoracic Institute of the Cleveland Clinic.
 

Iron’s role in pulmonary vascular disease

“Iron deficiency is associated with an energetic deficit, especially in high energy–demanding tissue, leading to early skeletal muscle acidification and diminished left and right ventricular (RV) contractile reserve during exercise,” the published report states. It can lead to “maladaptive RV remodeling,” which is a “hallmark feature” predictive of morbidity and mortality in patients with pulmonary vascular disease (PVD).

Some studies have suggested that iron deficiency is a common comorbidity in patients with PVD, their estimates of its prevalence ranging widely due in part to the “absence of a uniform definition,” write the authors.

Dr. Martens said the current study was conducted partly in response to the increasingly common observation that the HF-associated definition of iron deficiency “has limitations.” Yet, “without validation in the field of pulmonary hypertension, the 2022 pulmonary hypertension guidelines endorse this definition.”

As iron deficiency is a causal risk factor for HF progression, Dr. Martens added, the HF field has “taught us the importance of using validated definitions for iron deficiency when selecting patients for iron treatment in randomized controlled trials.”

Moreover, some evidence suggests that iron deficiency by some definitions may be associated with diminished exercise capacity and QoL in patients with PVD, which are associations that have not been confirmed in large studies, the report notes.

Therefore, it continues, the study sought to “determine and validate” the optimal definition of iron deficiency in patients with PVD; document its prevalence; and explore associations between iron deficiency and exercise capacity, QoL, and cardiac and pulmonary vascular remodeling.
 

 

 

Evaluating definitions of iron deficiency

The prospective study, called PVDOMICS, entered 1,195 subjects with available iron levels. After exclusion of 38 patients with sarcoidosis, myeloproliferative disease, or hemoglobinopathy, there remained 693 patients with “overt” PH, 225 with a milder form of PH who served as PVD comparators, and 90 age-, sex-, race/ethnicity- matched “healthy” adults who served as controls.

According to the conventional HF definition of iron deficiency – that is, ferritin 100-299 ng/mL and TSAT less than 20% – the prevalences were 74% in patients with overt PH and 72% of those “across the PVD spectrum.”

But by that definition, iron deficient and non-iron deficient patients didn’t differ significantly in peakVO2, 6MWT distance, or SF-36 physical component scores.

In contrast, patients meeting the alternative definition of iron deficiency of TSAT less than 21% showed significantly reduced functional and QoL measures, compared with those with TSAT greater than or equal to 21%.



The group with TSAT less than 21% also showed significantly more RV remodeling at cardiac MRI, compared with those who had TSAT greater than or equal to 21%, but their invasively measured pulmonary vascular resistance was comparable.

Of note, those with TSAT less than 21% also showed significantly increased all-cause mortality (hazard ratio, 1.63; 95% confidence interval, 1.13-2.34; P = .009) after adjustment for age, sex, hemoglobin, and natriuretic peptide levels.

“Proper validation of the definition of iron deficiency is important for prognostication,” the published report states, “but also for providing a working definition that can be used to identify suitable patients for inclusion in randomized controlled trials” of drugs for iron deficiency.

Additionally, the finding that TSAT less than 21% points to patients with diminished functional and exercise capacity is “consistent with more recent studies in the field of heart failure” that suggest “functional abnormalities and adverse cardiac remodeling are worse in patients with a low TSAT.” Indeed, the report states, such treatment effects have been “the most convincing” in HF trials.
 

Broader implications

An accompanying editorial agrees that the study’s implications apply well beyond PH. It highlights that iron deficiency is common in PH, while such PH is “not substantially different from the problem in patients with heart failure, chronic kidney disease, and cardiovascular disease in general,” lead editorialist John G.F. Cleland, MD, PhD, University of Glasgow, said in an interview. “It’s also common as people get older, even in those without these diseases.”

Dr. Cleland said the anemia definition currently used in cardiovascular research and practice is based on a hemoglobin concentration below the 5th percentile of age and sex in primarily young, healthy people, and not on its association with clinical outcomes.

“We recently analyzed data on a large population in the United Kingdom with a broad range of cardiovascular diseases and found that unless anemia is severe, [other] markers of iron deficiency are usually not measured,” he said. A low hemoglobin and TSAT, but not low ferritin levels, are associated with worse prognosis.

Dr. Cleland agreed that the HF-oriented definition is “poor,” with profound implications for the conduct of clinical trials. “If the definition of iron deficiency lacks specificity, then clinical trials will include many patients without iron deficiency who are unlikely to benefit from and might be harmed by IV iron.” Inclusion of such patients may also “dilute” any benefit that might emerge and render the outcome inaccurate.

But if the definition of iron deficiency lacks sensitivity, “then in clinical practice, many patients with iron deficiency may be denied a simple and effective treatment.”

Measuring serum iron could potentially be useful, but it’s usually not done in randomized trials “especially since taking an iron tablet can give a temporary ‘blip’ in serum iron,” Dr. Cleland said. “So TSAT is a reasonable compromise.” He said he “looks forward” to any further data on serum iron as a way of assessing iron deficiency and anemia.
 

 

 

Half full vs. half empty

Dr. Cleland likened the question of whom to treat with iron supplementation as a “glass half full versus half empty” clinical dilemma. “One approach is to give iron to everyone unless there’s evidence that they’re overloaded,” he said, “while the other is to withhold iron from everyone unless there’s evidence that they’re iron depleted.”

Recent evidence from the IRONMAN trial suggested that its patients with HF who received intravenous iron were less likely to be hospitalized for infections, particularly COVID-19, than a usual-care group. The treatment may also help reduce frailty.

“So should we be offering IV iron specifically to people considered iron deficient, or should we be ensuring that everyone over age 70 get iron supplements?” Dr. Cleland mused rhetorically. On a cautionary note, he added, perhaps iron supplementation will be harmful if it’s not necessary.

Dr. Cleland proposed “focusing for the moment on people who are iron deficient but investigating the possibility that we are being overly restrictive and should be giving iron to a much broader population.” That course, however, would require large population-based studies.

“We need more experience,” Dr. Cleland said, “to make sure that the benefits outweigh any risks before we can just give iron to everyone.”

Dr. Martens has received consultancy fees from AstraZeneca, Abbott, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Novartis, Novo Nordisk, and Vifor Pharma. Dr. Cleland declares grant support, support for travel, and personal honoraria from Pharmacosmos and Vifor. Disclosures for other authors are in the published report and editorial.

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

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New Classifications and Emerging Treatments in Brain Cancer

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Display Headline
New Classifications and Emerging Treatments in Brain Cancer
References
  1. Sokolov AV et al. Pharmacol Rev. 2021;73(4):1-32. doi:10.1124/pharmrev.121.000317
  2. Louis DN et al. Neuro Oncol. 2021;23(8):1231-1251. doi:10.1093/neuonc/noab106
  3. Mellinghoff IK et al. Clin Cancer Res. 2021;27(16):4491-4499. doi:10.1158/1078-0432.CCR-21-0611
  4. Woo C et al. JCO Clin Cancer Inform. 2021;5:985-994. doi:10.1200/CCI.21.00052
  5. Study of vorasidenib (AG-881) in participants with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation (INDIGO). ClinicalTrials.gov. Updated May 17, 2022. Accessed December 8, 2022. https://clinicaltrials.gov/ct2/show/NCT04164901
  6. Servier's pivotal phase 3 indigo trial investigating vorasidenib in IDH-mutant low-grade glioma meets primary endpoint of progression-free survival (PFS) and key secondary endpoint of time to next intervention (TTNI) (no date) Servier US. March 14, 2023. Accessed March 20, 2023. https://www.servier.us/serviers-pivotal-phase-3-indigo-trial-meets-primary-endpoint
  7. Nehra M et al. J Control Release. 2021;338:224-243. doi:10.1016/j.jconrel.2021.08.027
  8. Hersh AM et al. Cancers (Basel). 2022;14(19):4920. doi:10.3390/cancers14194920
  9. Shoaf ML, Desjardins A. Neurotherapeutics. 2022;19(6):1818-1831. doi:10.1007/s13311-022-01256-1
  10. Bagley SJ, O’Rourke DM. Pharmacol Ther. 2020;205:107419. doi:10.1016/j.pharmthera.2019.107419
  11. Batich KA et al. Clin Cancer Res. 2020;26(20):5297-5303. doi:10.1158/1078-0432.CCR-20-1082
  12. Lin J et al. Cancer. 2020;126(13):3053-3060. doi:10.1002/cncr.32884
  13. Barth SK et al. Cancer Epidemiol. 2017;50(pt A):22-29. doi:10.1016/j.canep.2017.07.012
  14. VA and partners hope APOLLO program will be leap forward for precision oncology. US Department of Veteran Affairs. May 1, 2019. Accessed December 8, 2022. https://www.research.va.gov/currents/0519-VA-and-partners-hope-APOLLO-program-will-be-leap-forward-for-precision-oncology.cfm
  15. Konteatis Z et al. ACS Med Chem Lett. 2020;11(2):101-107. doi:10.1021/acsmedchemlett.9b00509
Author and Disclosure Information

Margaret O. Johnson, MD, MPH
Neuro-oncologist, National TeleOncology and National Precision Oncology Program
Veterans Health Administration
Assistant Professor of Neurosurgery,
Preston Robert Tisch Brain Tumor Center,
Duke University School of Medicine
Durham, NC

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Margaret O. Johnson, MD, MPH
Neuro-oncologist, National TeleOncology and National Precision Oncology Program
Veterans Health Administration
Assistant Professor of Neurosurgery,
Preston Robert Tisch Brain Tumor Center,
Duke University School of Medicine
Durham, NC

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Margaret O. Johnson, MD, MPH
Neuro-oncologist, National TeleOncology and National Precision Oncology Program
Veterans Health Administration
Assistant Professor of Neurosurgery,
Preston Robert Tisch Brain Tumor Center,
Duke University School of Medicine
Durham, NC

References
  1. Sokolov AV et al. Pharmacol Rev. 2021;73(4):1-32. doi:10.1124/pharmrev.121.000317
  2. Louis DN et al. Neuro Oncol. 2021;23(8):1231-1251. doi:10.1093/neuonc/noab106
  3. Mellinghoff IK et al. Clin Cancer Res. 2021;27(16):4491-4499. doi:10.1158/1078-0432.CCR-21-0611
  4. Woo C et al. JCO Clin Cancer Inform. 2021;5:985-994. doi:10.1200/CCI.21.00052
  5. Study of vorasidenib (AG-881) in participants with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation (INDIGO). ClinicalTrials.gov. Updated May 17, 2022. Accessed December 8, 2022. https://clinicaltrials.gov/ct2/show/NCT04164901
  6. Servier's pivotal phase 3 indigo trial investigating vorasidenib in IDH-mutant low-grade glioma meets primary endpoint of progression-free survival (PFS) and key secondary endpoint of time to next intervention (TTNI) (no date) Servier US. March 14, 2023. Accessed March 20, 2023. https://www.servier.us/serviers-pivotal-phase-3-indigo-trial-meets-primary-endpoint
  7. Nehra M et al. J Control Release. 2021;338:224-243. doi:10.1016/j.jconrel.2021.08.027
  8. Hersh AM et al. Cancers (Basel). 2022;14(19):4920. doi:10.3390/cancers14194920
  9. Shoaf ML, Desjardins A. Neurotherapeutics. 2022;19(6):1818-1831. doi:10.1007/s13311-022-01256-1
  10. Bagley SJ, O’Rourke DM. Pharmacol Ther. 2020;205:107419. doi:10.1016/j.pharmthera.2019.107419
  11. Batich KA et al. Clin Cancer Res. 2020;26(20):5297-5303. doi:10.1158/1078-0432.CCR-20-1082
  12. Lin J et al. Cancer. 2020;126(13):3053-3060. doi:10.1002/cncr.32884
  13. Barth SK et al. Cancer Epidemiol. 2017;50(pt A):22-29. doi:10.1016/j.canep.2017.07.012
  14. VA and partners hope APOLLO program will be leap forward for precision oncology. US Department of Veteran Affairs. May 1, 2019. Accessed December 8, 2022. https://www.research.va.gov/currents/0519-VA-and-partners-hope-APOLLO-program-will-be-leap-forward-for-precision-oncology.cfm
  15. Konteatis Z et al. ACS Med Chem Lett. 2020;11(2):101-107. doi:10.1021/acsmedchemlett.9b00509
References
  1. Sokolov AV et al. Pharmacol Rev. 2021;73(4):1-32. doi:10.1124/pharmrev.121.000317
  2. Louis DN et al. Neuro Oncol. 2021;23(8):1231-1251. doi:10.1093/neuonc/noab106
  3. Mellinghoff IK et al. Clin Cancer Res. 2021;27(16):4491-4499. doi:10.1158/1078-0432.CCR-21-0611
  4. Woo C et al. JCO Clin Cancer Inform. 2021;5:985-994. doi:10.1200/CCI.21.00052
  5. Study of vorasidenib (AG-881) in participants with residual or recurrent grade 2 glioma with an IDH1 or IDH2 mutation (INDIGO). ClinicalTrials.gov. Updated May 17, 2022. Accessed December 8, 2022. https://clinicaltrials.gov/ct2/show/NCT04164901
  6. Servier's pivotal phase 3 indigo trial investigating vorasidenib in IDH-mutant low-grade glioma meets primary endpoint of progression-free survival (PFS) and key secondary endpoint of time to next intervention (TTNI) (no date) Servier US. March 14, 2023. Accessed March 20, 2023. https://www.servier.us/serviers-pivotal-phase-3-indigo-trial-meets-primary-endpoint
  7. Nehra M et al. J Control Release. 2021;338:224-243. doi:10.1016/j.jconrel.2021.08.027
  8. Hersh AM et al. Cancers (Basel). 2022;14(19):4920. doi:10.3390/cancers14194920
  9. Shoaf ML, Desjardins A. Neurotherapeutics. 2022;19(6):1818-1831. doi:10.1007/s13311-022-01256-1
  10. Bagley SJ, O’Rourke DM. Pharmacol Ther. 2020;205:107419. doi:10.1016/j.pharmthera.2019.107419
  11. Batich KA et al. Clin Cancer Res. 2020;26(20):5297-5303. doi:10.1158/1078-0432.CCR-20-1082
  12. Lin J et al. Cancer. 2020;126(13):3053-3060. doi:10.1002/cncr.32884
  13. Barth SK et al. Cancer Epidemiol. 2017;50(pt A):22-29. doi:10.1016/j.canep.2017.07.012
  14. VA and partners hope APOLLO program will be leap forward for precision oncology. US Department of Veteran Affairs. May 1, 2019. Accessed December 8, 2022. https://www.research.va.gov/currents/0519-VA-and-partners-hope-APOLLO-program-will-be-leap-forward-for-precision-oncology.cfm
  15. Konteatis Z et al. ACS Med Chem Lett. 2020;11(2):101-107. doi:10.1021/acsmedchemlett.9b00509
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New Classifications and Emerging Treatments in Brain Cancer
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New Classifications and Emerging Treatments in Brain Cancer
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Brain cancer remains a tremendous challenge in oncology, often with the worst prognosis and fewest approved treatment options.1 Classifying, treating, and identifying the causes in both the general population and in veterans have been challenging; but recently, there has been progress.2-4 In 2021, the World Health Organization (WHO) updated the classification system for primary brain and spinal cord tumors.2 Most importantly, the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5) updates included the importance of molecular diagnostic techniques to ensure appropriate diagnoses.

Along with the progress in tumor classification, treatment advances are also showing promise with the use of new targeted therapies.3 A multi-site phase 3 clinical trial investigating an isocitrate dehydrogenase (IDH) inhibitor, vorasidenib, in patients with residual or recurrent IDH mutant low-grade glioma met its primary endpoint of PFS in March 2023.5,6 In addition to brain-penetrant targeted therapies, advances in drug administration and delivery have also emerged to circumvent the blood-brain barrier using nanotechnology, focused ultrasound, oncolytic viruses, vaccines, and CAR T-cell therapies.7-11

Many unanswered questions remain regarding the rates and outcomes for veterans with brain cancer. However, investigations and initiatives are ongoing to better understand the role of military service and exposures that may be associated with an increased risk of developing brain tumors.4,12,13 In addition, efforts are in place to improve molecular characterization and personalized treatments for brain cancer through the Applied Proteogenomics Organizational Learning and Outcomes (APOLLO) and NPOP.14 Despite the complexity of brain cancer, with its numerous challenges and unknowns, there have been recent advances in classification and potential treatments. Understanding the causes and improving treatments for brain cancer in the veteran population is paramount.

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COVID-19 Outcomes in Veterans With Hematologic Malignancies

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COVID-19 Outcomes in Veterans with Hematologic Malignancies
References
  1. Parker S. Lancet Oncol. 2022;23(1):2 doi:10.1016/S1470-2045(21)00713-0
  2. Englum BR et al. Cancer. 2022;128(5):1048-1056. doi:10.1002/cncr.34011
  3. Leuva H et al. Semin Oncol. 2022:49(5):363-370. doi:10.1053/j.seminoncol.2022.07.005
  4. Wu JTY et al. JAMA Oncol. 2022;8(2):281-286. doi:10.1001/jamaoncol.2021.5771
  5. Fillmore NR et al. J Natl Cancer Inst. 2021;113(6):691-698. doi:10.1093/jnci/djaa159
  6. Morawska M. Eur J Haematol. 2022;108(2):91-98. doi:10.1111/ejh.13722
  7. Passamonti F et al. Hematol Oncol. 2023;41(1):3-15. doi:10.1002/hon.3086
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Durham VA Medical Center
Duke University School of Medicine
Durham, NC

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Duke University School of Medicine
Durham, NC

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Durham VA Medical Center
Duke University School of Medicine
Durham, NC

References
  1. Parker S. Lancet Oncol. 2022;23(1):2 doi:10.1016/S1470-2045(21)00713-0
  2. Englum BR et al. Cancer. 2022;128(5):1048-1056. doi:10.1002/cncr.34011
  3. Leuva H et al. Semin Oncol. 2022:49(5):363-370. doi:10.1053/j.seminoncol.2022.07.005
  4. Wu JTY et al. JAMA Oncol. 2022;8(2):281-286. doi:10.1001/jamaoncol.2021.5771
  5. Fillmore NR et al. J Natl Cancer Inst. 2021;113(6):691-698. doi:10.1093/jnci/djaa159
  6. Morawska M. Eur J Haematol. 2022;108(2):91-98. doi:10.1111/ejh.13722
  7. Passamonti F et al. Hematol Oncol. 2023;41(1):3-15. doi:10.1002/hon.3086
References
  1. Parker S. Lancet Oncol. 2022;23(1):2 doi:10.1016/S1470-2045(21)00713-0
  2. Englum BR et al. Cancer. 2022;128(5):1048-1056. doi:10.1002/cncr.34011
  3. Leuva H et al. Semin Oncol. 2022:49(5):363-370. doi:10.1053/j.seminoncol.2022.07.005
  4. Wu JTY et al. JAMA Oncol. 2022;8(2):281-286. doi:10.1001/jamaoncol.2021.5771
  5. Fillmore NR et al. J Natl Cancer Inst. 2021;113(6):691-698. doi:10.1093/jnci/djaa159
  6. Morawska M. Eur J Haematol. 2022;108(2):91-98. doi:10.1111/ejh.13722
  7. Passamonti F et al. Hematol Oncol. 2023;41(1):3-15. doi:10.1002/hon.3086
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The COVID–19 pandemic has forever changed the world, but the true extent of its lasting impact remains unclear. There were immediate diagnostic and treatment ramifications at the start of the pandemic. Stay-at-home ordinances, fear of infection, and decreased staffing availability made in-person health care appointments more challenging. A stark decline in diagnostic screening procedures and imaging was observed early during the pandemic.1,2 There was a paucity of information to help guide health care practitioners as they designed treatment strategies in anticipation of potential COVID–19 infections in their patients with cancer. The unknown relationship between cancer therapy and COVID–19 infection introduced uncertainty and confusion for patients and hindered ongoing surveillance efforts.

Several studies performed within the VA have highlighted the concern that although vaccination is effective in reducing infection and mortality rates in patients with cancer, such benefits are distributed unequally. Despite vaccination status, patients with hematologic malignancies appear more likely to contract COVID–19 and have worse COVID–19–related outcomes. Nevertheless, vaccinated patients fare better than their unvaccinated counterparts, demonstrating the ongoing importance of immunization.3-5 We now know that cancer treatment history also affects vaccine efficacy, which is critical to consider when deciding on potential chemotherapy and targeted agents for cancer treatment.6,7

We now have more robust data to help guide decision-making along with an expanding armamentarium of vaccines and therapeutics to lower the risk of COVID–19 infection. Vaccines, while less effective in patients with hematologic malignancies, continue to reduce severity of COVID–19. This knowledge has led to increased risk mitigation strategies for our patients with hematologic malignancies, particularly those receiving cancer therapy, such as recommendations for increased masking in social situations and administration of antiviral and monoclonal antibody therapy. Practitioners remain uniquely positioned to help guide their vulnerable patients through these turbulent times. This relationship undoubtedly saves lives.

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Association Between Psoriasis and Obesity Among US Adults in the 2009-2014 National Health and Nutrition Examination Survey

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Association Between Psoriasis and Obesity Among US Adults in the 2009-2014 National Health and Nutrition Examination Survey

To the Editor:

Psoriasis is an immune-mediated dermatologic condition that is associated with various comorbidities, including obesity.1 The underlying pathophysiology of psoriasis has been extensively studied, and recent research has discussed the role of obesity in IL-17 secretion.2 The relationship between being overweight/obese and having psoriasis has been documented in the literature.1,2 However, this association in a recent population is lacking. We sought to investigate the association between psoriasis and obesity utilizing a representative US population of adults—the 2009-2014 National Health and Nutrition Examination Survey (NHANES) data,3 which contains the most recent psoriasis data.

We conducted a population-based, cross-sectional study focused on patients 20 years and older with psoriasis from the 2009-2014 NHANES database. Three 2-year cycles of NHANES data were combined to create our 2009 to 2014 dataset. In the Table, numerous variables including age, sex, household income, race/ethnicity, education, diabetes status, tobacco use, body mass index (BMI), waist circumference, and being called overweight by a health care provider were analyzed using χ2 or t test analyses to evaluate for differences among those with and without psoriasis. Diabetes status was assessed by the question “Other than during pregnancy, have you ever been told by a doctor or health professional that you have diabetes or sugar diabetes?” Tobacco use was assessed by the question “Have you smoked at least 100 cigarettes in your entire life?” Psoriasis status was assessed by a self-reported response to the question “Have you ever been told by a doctor or other health care professional that you had psoriasis?” Three different outcome variables were used to determine if patients were overweight or obese: BMI, waist circumference, and response to the question “Has a doctor or other health professional ever told you that you were overweight?” Obesity was defined as having a BMI of 30 or higher or waist circumference of 102 cm or more in males and 88 cm or more in females.4 Being overweight was defined as having a BMI of 25 to 29.99 or response of Yes to “Has a doctor or other health professional ever told you that you were overweight?”

Characteristics of US Adults With and Without Psoriasisa  in NHANES 2009-2014 (N=15,893)

Initially, there were 17,547 participants 20 years and older from 2009 to 2014, but 1654 participants were excluded because of missing data for obesity or psoriasis; therefore, 15,893 patients were included in our analysis. Multivariable logistic regressions were utilized to examine the association between psoriasis and being overweight/obese (eTable). Additionally, the models were adjusted based on age, sex, household income, race/ethnicity, diabetes status, and tobacco use. All data processing and analysis were performed in Stata/MP 17 (StataCorp LLC). P<.05 was considered statistically significant.

Association Between Psoriasis and Being Overweight/Obese in Adults in NHANES 2009-2014 Utilizing Multivariable Logistic Regression

The Table shows characteristics of US adults with and without psoriasis in NHANES 2009-2014. We found that the variables of interest evaluating body weight that were significantly different on analysis between patients with and without psoriasis included waist circumference—patients with psoriasis had a significantly higher waist circumference (P=.009)—and being told by a health care provider that they are overweight (P<.0001), which supports the findings by Love et al,5 who reported abdominal obesity was the most common feature of metabolic syndrome exhibited among patients with psoriasis.

Multivariable logistic regression analysis (eTable) revealed that there was a significant association between psoriasis and BMI of 25 to 29.99 (adjusted odds ratio [AOR], 1.34; 95% CI, 1.02-1.76; P=.04) and being told by a health care provider that they are overweight (AOR, 1.91; 95% CI, 1.44-2.52; P<.001). After adjusting for confounding variables, there was no significant association between psoriasis and a BMI of 30 or higher (AOR, 1.00; 95% CI, 0.73-1.38; P=.99) or a waist circumference of 102 cm or more in males and 88 cm or more in females (AOR, 1.15; 95% CI, 0.86-1.53; P=.3).

Our findings suggest that a few variables indicative of being overweight or obese are associated with psoriasis. This relationship most likely is due to increased adipokine, including resistin, levels in overweight individuals, resulting in a proinflammatory state.6 It has been suggested that BMI alone is not a definitive marker for measuring fat storage levels in individuals. People can have a normal or slightly elevated BMI but possess excessive adiposity, resulting in chronic inflammation.6 Therefore, our findings of a significant association between psoriasis and being told by a health care provider that they are overweight might be a stronger measurement for possessing excessive fat, as this is likely due to clinical judgment rather than BMI measurement.

Moreover, it should be noted that the potential reason for the lack of association between BMI of 30 or higher and psoriasis in our analysis may be a result of BMI serving as a poor measurement for adiposity. Additionally, Armstrong and colleagues7 discussed that the association between BMI and psoriasis was stronger for patients with moderate to severe psoriasis. Our study consisted of NHANES data for self-reported psoriasis diagnoses without a psoriasis severity index, making it difficult to extrapolate which individuals had mild or moderate to severe psoriasis, which may have contributed to our finding of no association between BMI of 30 or higher and psoriasis.

The self-reported nature of the survey questions and lack of questions regarding psoriasis severity serve as limitations to the study. Both obesity and psoriasis can have various systemic consequences, such as cardiovascular disease, due to the development of an inflammatory state.8 Future studies may explore other body measurements that indicate being overweight or obese and the potential synergistic relationship of obesity and psoriasis severity, optimizing the development of effective treatment plans.

References
  1. Jensen P, Skov L. Psoriasis and obesity. Dermatology. 2016;232:633-639.
  2. Xu C, Ji J, Su T, et al. The association of psoriasis and obesity: focusing on IL-17A-related immunological mechanisms. Int J Dermatol Venereol. 2021;4:116-121.
  3. National Center for Health Statistics. NHANES questionnaires, datasets, and related documentation. Centers for Disease Control and Prevention website. Accessed June 22, 2023. https://wwwn.cdc.govnchs/nhanes/Default.aspx
  4. Ross R, Neeland IJ, Yamashita S, et al. Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol. 2020;16:177-189.
  5. Love TJ, Qureshi AA, Karlson EW, et al. Prevalence of the metabolic syndrome in psoriasis: results from the National Health and Nutrition Examination Survey, 2003-2006. Arch Dermatol. 2011;147:419-424.
  6. Paroutoglou K, Papadavid E, Christodoulatos GS, et al. Deciphering the association between psoriasis and obesity: current evidence and treatment considerations. Curr Obes Rep. 2020;9:165-178.
  7. Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and obesity: a systematic review and meta-analysis of observational studies. Nutr Diabetes. 2012;2:E54.
  8. Hamminga EA, van der Lely AJ, Neumann HAM, et al. Chronic inflammation in psoriasis and obesity: implications for therapy. Med Hypotheses. 2006;67:768-773.
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Brandon Smith is from the Drexel University College of Medicine, Philadelphia, Pennsylvania. Shivali Devjani is from the SUNY Downstate College of Medicine, Brooklyn, New York. Michael R. Collier is from the University of South Florida Health Morsani College of Medicine, Tampa. Dr. Maul is from the Department of Dermatology and Venereology, University Hospital of Zurich, Switzerland. Dr. Wu is from the University of Miami Leonard M. Miller School of Medicine, Florida.

Brandon Smith, Shivali Devjani, Michael R. Collier, and Dr. Maul report no conflict of interest. Dr. Wu is or has been a consultant, investigator, or speaker for AbbVie; Almirall; Amgen; Arcutis Biotherapeutics; Aristea Therapeutics, Inc; Bausch Health; Boehringer Ingelheim; Bristol-Myers Squibb Company; Dermavant Sciences, Inc; DermTech; Dr. Reddy’s Laboratories; Eli Lilly and Company; EPI Health; Galderma; Janssen Pharmaceuticals; LEO Pharma; Mindera; Novartis; Pfizer; Regeneron Pharmaceuticals; Samsung Bioepis; Sanofi Genzyme; Solius; Sun Pharmaceutical Industries Ltd; UCB; and Zerigo Health.

The eTable is available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Jashin J. Wu, MD, University of Miami Leonard M. Miller School of Medicine, 1600 NW 10th Ave, RMSB, Room 2023-A, Miami, FL 33136 ([email protected]).

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Brandon Smith is from the Drexel University College of Medicine, Philadelphia, Pennsylvania. Shivali Devjani is from the SUNY Downstate College of Medicine, Brooklyn, New York. Michael R. Collier is from the University of South Florida Health Morsani College of Medicine, Tampa. Dr. Maul is from the Department of Dermatology and Venereology, University Hospital of Zurich, Switzerland. Dr. Wu is from the University of Miami Leonard M. Miller School of Medicine, Florida.

Brandon Smith, Shivali Devjani, Michael R. Collier, and Dr. Maul report no conflict of interest. Dr. Wu is or has been a consultant, investigator, or speaker for AbbVie; Almirall; Amgen; Arcutis Biotherapeutics; Aristea Therapeutics, Inc; Bausch Health; Boehringer Ingelheim; Bristol-Myers Squibb Company; Dermavant Sciences, Inc; DermTech; Dr. Reddy’s Laboratories; Eli Lilly and Company; EPI Health; Galderma; Janssen Pharmaceuticals; LEO Pharma; Mindera; Novartis; Pfizer; Regeneron Pharmaceuticals; Samsung Bioepis; Sanofi Genzyme; Solius; Sun Pharmaceutical Industries Ltd; UCB; and Zerigo Health.

The eTable is available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Jashin J. Wu, MD, University of Miami Leonard M. Miller School of Medicine, 1600 NW 10th Ave, RMSB, Room 2023-A, Miami, FL 33136 ([email protected]).

Author and Disclosure Information

Brandon Smith is from the Drexel University College of Medicine, Philadelphia, Pennsylvania. Shivali Devjani is from the SUNY Downstate College of Medicine, Brooklyn, New York. Michael R. Collier is from the University of South Florida Health Morsani College of Medicine, Tampa. Dr. Maul is from the Department of Dermatology and Venereology, University Hospital of Zurich, Switzerland. Dr. Wu is from the University of Miami Leonard M. Miller School of Medicine, Florida.

Brandon Smith, Shivali Devjani, Michael R. Collier, and Dr. Maul report no conflict of interest. Dr. Wu is or has been a consultant, investigator, or speaker for AbbVie; Almirall; Amgen; Arcutis Biotherapeutics; Aristea Therapeutics, Inc; Bausch Health; Boehringer Ingelheim; Bristol-Myers Squibb Company; Dermavant Sciences, Inc; DermTech; Dr. Reddy’s Laboratories; Eli Lilly and Company; EPI Health; Galderma; Janssen Pharmaceuticals; LEO Pharma; Mindera; Novartis; Pfizer; Regeneron Pharmaceuticals; Samsung Bioepis; Sanofi Genzyme; Solius; Sun Pharmaceutical Industries Ltd; UCB; and Zerigo Health.

The eTable is available in the Appendix online at www.mdedge.com/dermatology.

Correspondence: Jashin J. Wu, MD, University of Miami Leonard M. Miller School of Medicine, 1600 NW 10th Ave, RMSB, Room 2023-A, Miami, FL 33136 ([email protected]).

Article PDF
Article PDF

To the Editor:

Psoriasis is an immune-mediated dermatologic condition that is associated with various comorbidities, including obesity.1 The underlying pathophysiology of psoriasis has been extensively studied, and recent research has discussed the role of obesity in IL-17 secretion.2 The relationship between being overweight/obese and having psoriasis has been documented in the literature.1,2 However, this association in a recent population is lacking. We sought to investigate the association between psoriasis and obesity utilizing a representative US population of adults—the 2009-2014 National Health and Nutrition Examination Survey (NHANES) data,3 which contains the most recent psoriasis data.

We conducted a population-based, cross-sectional study focused on patients 20 years and older with psoriasis from the 2009-2014 NHANES database. Three 2-year cycles of NHANES data were combined to create our 2009 to 2014 dataset. In the Table, numerous variables including age, sex, household income, race/ethnicity, education, diabetes status, tobacco use, body mass index (BMI), waist circumference, and being called overweight by a health care provider were analyzed using χ2 or t test analyses to evaluate for differences among those with and without psoriasis. Diabetes status was assessed by the question “Other than during pregnancy, have you ever been told by a doctor or health professional that you have diabetes or sugar diabetes?” Tobacco use was assessed by the question “Have you smoked at least 100 cigarettes in your entire life?” Psoriasis status was assessed by a self-reported response to the question “Have you ever been told by a doctor or other health care professional that you had psoriasis?” Three different outcome variables were used to determine if patients were overweight or obese: BMI, waist circumference, and response to the question “Has a doctor or other health professional ever told you that you were overweight?” Obesity was defined as having a BMI of 30 or higher or waist circumference of 102 cm or more in males and 88 cm or more in females.4 Being overweight was defined as having a BMI of 25 to 29.99 or response of Yes to “Has a doctor or other health professional ever told you that you were overweight?”

Characteristics of US Adults With and Without Psoriasisa  in NHANES 2009-2014 (N=15,893)

Initially, there were 17,547 participants 20 years and older from 2009 to 2014, but 1654 participants were excluded because of missing data for obesity or psoriasis; therefore, 15,893 patients were included in our analysis. Multivariable logistic regressions were utilized to examine the association between psoriasis and being overweight/obese (eTable). Additionally, the models were adjusted based on age, sex, household income, race/ethnicity, diabetes status, and tobacco use. All data processing and analysis were performed in Stata/MP 17 (StataCorp LLC). P<.05 was considered statistically significant.

Association Between Psoriasis and Being Overweight/Obese in Adults in NHANES 2009-2014 Utilizing Multivariable Logistic Regression

The Table shows characteristics of US adults with and without psoriasis in NHANES 2009-2014. We found that the variables of interest evaluating body weight that were significantly different on analysis between patients with and without psoriasis included waist circumference—patients with psoriasis had a significantly higher waist circumference (P=.009)—and being told by a health care provider that they are overweight (P<.0001), which supports the findings by Love et al,5 who reported abdominal obesity was the most common feature of metabolic syndrome exhibited among patients with psoriasis.

Multivariable logistic regression analysis (eTable) revealed that there was a significant association between psoriasis and BMI of 25 to 29.99 (adjusted odds ratio [AOR], 1.34; 95% CI, 1.02-1.76; P=.04) and being told by a health care provider that they are overweight (AOR, 1.91; 95% CI, 1.44-2.52; P<.001). After adjusting for confounding variables, there was no significant association between psoriasis and a BMI of 30 or higher (AOR, 1.00; 95% CI, 0.73-1.38; P=.99) or a waist circumference of 102 cm or more in males and 88 cm or more in females (AOR, 1.15; 95% CI, 0.86-1.53; P=.3).

Our findings suggest that a few variables indicative of being overweight or obese are associated with psoriasis. This relationship most likely is due to increased adipokine, including resistin, levels in overweight individuals, resulting in a proinflammatory state.6 It has been suggested that BMI alone is not a definitive marker for measuring fat storage levels in individuals. People can have a normal or slightly elevated BMI but possess excessive adiposity, resulting in chronic inflammation.6 Therefore, our findings of a significant association between psoriasis and being told by a health care provider that they are overweight might be a stronger measurement for possessing excessive fat, as this is likely due to clinical judgment rather than BMI measurement.

Moreover, it should be noted that the potential reason for the lack of association between BMI of 30 or higher and psoriasis in our analysis may be a result of BMI serving as a poor measurement for adiposity. Additionally, Armstrong and colleagues7 discussed that the association between BMI and psoriasis was stronger for patients with moderate to severe psoriasis. Our study consisted of NHANES data for self-reported psoriasis diagnoses without a psoriasis severity index, making it difficult to extrapolate which individuals had mild or moderate to severe psoriasis, which may have contributed to our finding of no association between BMI of 30 or higher and psoriasis.

The self-reported nature of the survey questions and lack of questions regarding psoriasis severity serve as limitations to the study. Both obesity and psoriasis can have various systemic consequences, such as cardiovascular disease, due to the development of an inflammatory state.8 Future studies may explore other body measurements that indicate being overweight or obese and the potential synergistic relationship of obesity and psoriasis severity, optimizing the development of effective treatment plans.

To the Editor:

Psoriasis is an immune-mediated dermatologic condition that is associated with various comorbidities, including obesity.1 The underlying pathophysiology of psoriasis has been extensively studied, and recent research has discussed the role of obesity in IL-17 secretion.2 The relationship between being overweight/obese and having psoriasis has been documented in the literature.1,2 However, this association in a recent population is lacking. We sought to investigate the association between psoriasis and obesity utilizing a representative US population of adults—the 2009-2014 National Health and Nutrition Examination Survey (NHANES) data,3 which contains the most recent psoriasis data.

We conducted a population-based, cross-sectional study focused on patients 20 years and older with psoriasis from the 2009-2014 NHANES database. Three 2-year cycles of NHANES data were combined to create our 2009 to 2014 dataset. In the Table, numerous variables including age, sex, household income, race/ethnicity, education, diabetes status, tobacco use, body mass index (BMI), waist circumference, and being called overweight by a health care provider were analyzed using χ2 or t test analyses to evaluate for differences among those with and without psoriasis. Diabetes status was assessed by the question “Other than during pregnancy, have you ever been told by a doctor or health professional that you have diabetes or sugar diabetes?” Tobacco use was assessed by the question “Have you smoked at least 100 cigarettes in your entire life?” Psoriasis status was assessed by a self-reported response to the question “Have you ever been told by a doctor or other health care professional that you had psoriasis?” Three different outcome variables were used to determine if patients were overweight or obese: BMI, waist circumference, and response to the question “Has a doctor or other health professional ever told you that you were overweight?” Obesity was defined as having a BMI of 30 or higher or waist circumference of 102 cm or more in males and 88 cm or more in females.4 Being overweight was defined as having a BMI of 25 to 29.99 or response of Yes to “Has a doctor or other health professional ever told you that you were overweight?”

Characteristics of US Adults With and Without Psoriasisa  in NHANES 2009-2014 (N=15,893)

Initially, there were 17,547 participants 20 years and older from 2009 to 2014, but 1654 participants were excluded because of missing data for obesity or psoriasis; therefore, 15,893 patients were included in our analysis. Multivariable logistic regressions were utilized to examine the association between psoriasis and being overweight/obese (eTable). Additionally, the models were adjusted based on age, sex, household income, race/ethnicity, diabetes status, and tobacco use. All data processing and analysis were performed in Stata/MP 17 (StataCorp LLC). P<.05 was considered statistically significant.

Association Between Psoriasis and Being Overweight/Obese in Adults in NHANES 2009-2014 Utilizing Multivariable Logistic Regression

The Table shows characteristics of US adults with and without psoriasis in NHANES 2009-2014. We found that the variables of interest evaluating body weight that were significantly different on analysis between patients with and without psoriasis included waist circumference—patients with psoriasis had a significantly higher waist circumference (P=.009)—and being told by a health care provider that they are overweight (P<.0001), which supports the findings by Love et al,5 who reported abdominal obesity was the most common feature of metabolic syndrome exhibited among patients with psoriasis.

Multivariable logistic regression analysis (eTable) revealed that there was a significant association between psoriasis and BMI of 25 to 29.99 (adjusted odds ratio [AOR], 1.34; 95% CI, 1.02-1.76; P=.04) and being told by a health care provider that they are overweight (AOR, 1.91; 95% CI, 1.44-2.52; P<.001). After adjusting for confounding variables, there was no significant association between psoriasis and a BMI of 30 or higher (AOR, 1.00; 95% CI, 0.73-1.38; P=.99) or a waist circumference of 102 cm or more in males and 88 cm or more in females (AOR, 1.15; 95% CI, 0.86-1.53; P=.3).

Our findings suggest that a few variables indicative of being overweight or obese are associated with psoriasis. This relationship most likely is due to increased adipokine, including resistin, levels in overweight individuals, resulting in a proinflammatory state.6 It has been suggested that BMI alone is not a definitive marker for measuring fat storage levels in individuals. People can have a normal or slightly elevated BMI but possess excessive adiposity, resulting in chronic inflammation.6 Therefore, our findings of a significant association between psoriasis and being told by a health care provider that they are overweight might be a stronger measurement for possessing excessive fat, as this is likely due to clinical judgment rather than BMI measurement.

Moreover, it should be noted that the potential reason for the lack of association between BMI of 30 or higher and psoriasis in our analysis may be a result of BMI serving as a poor measurement for adiposity. Additionally, Armstrong and colleagues7 discussed that the association between BMI and psoriasis was stronger for patients with moderate to severe psoriasis. Our study consisted of NHANES data for self-reported psoriasis diagnoses without a psoriasis severity index, making it difficult to extrapolate which individuals had mild or moderate to severe psoriasis, which may have contributed to our finding of no association between BMI of 30 or higher and psoriasis.

The self-reported nature of the survey questions and lack of questions regarding psoriasis severity serve as limitations to the study. Both obesity and psoriasis can have various systemic consequences, such as cardiovascular disease, due to the development of an inflammatory state.8 Future studies may explore other body measurements that indicate being overweight or obese and the potential synergistic relationship of obesity and psoriasis severity, optimizing the development of effective treatment plans.

References
  1. Jensen P, Skov L. Psoriasis and obesity. Dermatology. 2016;232:633-639.
  2. Xu C, Ji J, Su T, et al. The association of psoriasis and obesity: focusing on IL-17A-related immunological mechanisms. Int J Dermatol Venereol. 2021;4:116-121.
  3. National Center for Health Statistics. NHANES questionnaires, datasets, and related documentation. Centers for Disease Control and Prevention website. Accessed June 22, 2023. https://wwwn.cdc.govnchs/nhanes/Default.aspx
  4. Ross R, Neeland IJ, Yamashita S, et al. Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol. 2020;16:177-189.
  5. Love TJ, Qureshi AA, Karlson EW, et al. Prevalence of the metabolic syndrome in psoriasis: results from the National Health and Nutrition Examination Survey, 2003-2006. Arch Dermatol. 2011;147:419-424.
  6. Paroutoglou K, Papadavid E, Christodoulatos GS, et al. Deciphering the association between psoriasis and obesity: current evidence and treatment considerations. Curr Obes Rep. 2020;9:165-178.
  7. Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and obesity: a systematic review and meta-analysis of observational studies. Nutr Diabetes. 2012;2:E54.
  8. Hamminga EA, van der Lely AJ, Neumann HAM, et al. Chronic inflammation in psoriasis and obesity: implications for therapy. Med Hypotheses. 2006;67:768-773.
References
  1. Jensen P, Skov L. Psoriasis and obesity. Dermatology. 2016;232:633-639.
  2. Xu C, Ji J, Su T, et al. The association of psoriasis and obesity: focusing on IL-17A-related immunological mechanisms. Int J Dermatol Venereol. 2021;4:116-121.
  3. National Center for Health Statistics. NHANES questionnaires, datasets, and related documentation. Centers for Disease Control and Prevention website. Accessed June 22, 2023. https://wwwn.cdc.govnchs/nhanes/Default.aspx
  4. Ross R, Neeland IJ, Yamashita S, et al. Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol. 2020;16:177-189.
  5. Love TJ, Qureshi AA, Karlson EW, et al. Prevalence of the metabolic syndrome in psoriasis: results from the National Health and Nutrition Examination Survey, 2003-2006. Arch Dermatol. 2011;147:419-424.
  6. Paroutoglou K, Papadavid E, Christodoulatos GS, et al. Deciphering the association between psoriasis and obesity: current evidence and treatment considerations. Curr Obes Rep. 2020;9:165-178.
  7. Armstrong AW, Harskamp CT, Armstrong EJ. The association between psoriasis and obesity: a systematic review and meta-analysis of observational studies. Nutr Diabetes. 2012;2:E54.
  8. Hamminga EA, van der Lely AJ, Neumann HAM, et al. Chronic inflammation in psoriasis and obesity: implications for therapy. Med Hypotheses. 2006;67:768-773.
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  • There are many comorbidities that are associated with psoriasis, making it crucial to evaluate for these diseases in patients with psoriasis.
  • Obesity may be a contributing factor to psoriasis development due to the role of IL-17 secretion.
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Nebulized amphotericin B does not affect aspergillosis exacerbation-free status at 1 year

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Topline

Nebulized amphotericin B does not improve exacerbation-free status at 1 year for patients with bronchopulmonary aspergillosis, though it may delay onset and incidence.

Methodology

Investigators searched PubMed and Embase databases for studies that included at least five patients with allergic bronchopulmonary aspergillosis who were managed with nebulized amphotericin B.

They included five studies, two of which were randomized controlled trials (RCTs), and three were observational studies; there was a total of 188 patients.

The primary objective of this systematic review and meta-analysis was to determine the frequency of patients remaining exacerbation free 1 year after initiating treatment with nebulized amphotericin B.
 

Takeaway

From the studies (one observational, two RCTs; n = 84) with exacerbation data at 1 or 2 years, the pooled proportion of patients who remained exacerbation free with nebulized amphotericin B at 1 year was 76% (I2 = 64.6%).

The pooled difference in risk with the two RCTs that assessed exacerbation-free status at 1 year was 0.33 and was not significantly different between the nebulized amphotericin B and control arms, which received nebulized saline.

Two RCTs provided the time to first exacerbation, which was significantly longer with nebulized amphotericin B than with nebulized saline (337 vs. 177 days; P = .004; I2 = 82%).

The proportion of patients who experienced two or more exacerbations was significantly lower with nebulized amphotericin B than with nebulized saline (9/33 [27.3%] vs 20/38 [52.6%]; P = .03).
 

In practice

“The time to first exacerbation was prolonged with [nebulized amphotericin B] therapy and is an important indicator of effectiveness. Also, the proportion of subjects experiencing ≥ 2 exacerbations was also lesser with NAB than in the control,” concluded Valliappan Muthu, MD, and colleagues. However, “the ideal duration and optimal dose of LAMB for nebulization are unclear.”

Study details

“Nebulized amphotericin B for preventing exacerbations in allergic bronchopulmonary aspergillosis: A systematic review and meta-analysis” was published online in Pulmonary Pharmacology and Therapeutics.

Limitations

The current review is limited by the small number of included trials and may have a high risk of bias. Therefore, more evidence is required for the use of nebulized amphotericin B in routine care. The authors have disclosed no conflicts of interest.

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

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Topline

Nebulized amphotericin B does not improve exacerbation-free status at 1 year for patients with bronchopulmonary aspergillosis, though it may delay onset and incidence.

Methodology

Investigators searched PubMed and Embase databases for studies that included at least five patients with allergic bronchopulmonary aspergillosis who were managed with nebulized amphotericin B.

They included five studies, two of which were randomized controlled trials (RCTs), and three were observational studies; there was a total of 188 patients.

The primary objective of this systematic review and meta-analysis was to determine the frequency of patients remaining exacerbation free 1 year after initiating treatment with nebulized amphotericin B.
 

Takeaway

From the studies (one observational, two RCTs; n = 84) with exacerbation data at 1 or 2 years, the pooled proportion of patients who remained exacerbation free with nebulized amphotericin B at 1 year was 76% (I2 = 64.6%).

The pooled difference in risk with the two RCTs that assessed exacerbation-free status at 1 year was 0.33 and was not significantly different between the nebulized amphotericin B and control arms, which received nebulized saline.

Two RCTs provided the time to first exacerbation, which was significantly longer with nebulized amphotericin B than with nebulized saline (337 vs. 177 days; P = .004; I2 = 82%).

The proportion of patients who experienced two or more exacerbations was significantly lower with nebulized amphotericin B than with nebulized saline (9/33 [27.3%] vs 20/38 [52.6%]; P = .03).
 

In practice

“The time to first exacerbation was prolonged with [nebulized amphotericin B] therapy and is an important indicator of effectiveness. Also, the proportion of subjects experiencing ≥ 2 exacerbations was also lesser with NAB than in the control,” concluded Valliappan Muthu, MD, and colleagues. However, “the ideal duration and optimal dose of LAMB for nebulization are unclear.”

Study details

“Nebulized amphotericin B for preventing exacerbations in allergic bronchopulmonary aspergillosis: A systematic review and meta-analysis” was published online in Pulmonary Pharmacology and Therapeutics.

Limitations

The current review is limited by the small number of included trials and may have a high risk of bias. Therefore, more evidence is required for the use of nebulized amphotericin B in routine care. The authors have disclosed no conflicts of interest.

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

 

Topline

Nebulized amphotericin B does not improve exacerbation-free status at 1 year for patients with bronchopulmonary aspergillosis, though it may delay onset and incidence.

Methodology

Investigators searched PubMed and Embase databases for studies that included at least five patients with allergic bronchopulmonary aspergillosis who were managed with nebulized amphotericin B.

They included five studies, two of which were randomized controlled trials (RCTs), and three were observational studies; there was a total of 188 patients.

The primary objective of this systematic review and meta-analysis was to determine the frequency of patients remaining exacerbation free 1 year after initiating treatment with nebulized amphotericin B.
 

Takeaway

From the studies (one observational, two RCTs; n = 84) with exacerbation data at 1 or 2 years, the pooled proportion of patients who remained exacerbation free with nebulized amphotericin B at 1 year was 76% (I2 = 64.6%).

The pooled difference in risk with the two RCTs that assessed exacerbation-free status at 1 year was 0.33 and was not significantly different between the nebulized amphotericin B and control arms, which received nebulized saline.

Two RCTs provided the time to first exacerbation, which was significantly longer with nebulized amphotericin B than with nebulized saline (337 vs. 177 days; P = .004; I2 = 82%).

The proportion of patients who experienced two or more exacerbations was significantly lower with nebulized amphotericin B than with nebulized saline (9/33 [27.3%] vs 20/38 [52.6%]; P = .03).
 

In practice

“The time to first exacerbation was prolonged with [nebulized amphotericin B] therapy and is an important indicator of effectiveness. Also, the proportion of subjects experiencing ≥ 2 exacerbations was also lesser with NAB than in the control,” concluded Valliappan Muthu, MD, and colleagues. However, “the ideal duration and optimal dose of LAMB for nebulization are unclear.”

Study details

“Nebulized amphotericin B for preventing exacerbations in allergic bronchopulmonary aspergillosis: A systematic review and meta-analysis” was published online in Pulmonary Pharmacology and Therapeutics.

Limitations

The current review is limited by the small number of included trials and may have a high risk of bias. Therefore, more evidence is required for the use of nebulized amphotericin B in routine care. The authors have disclosed no conflicts of interest.

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

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Palliative Care: Utilization Patterns in Inpatient Dermatology

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Palliative Care: Utilization Patterns in Inpatient Dermatology
IN PARTNERSHIP WITH THE SOCIETY OF DERMATOLOGY HOSPITALISTS

Palliative care (PC) is a field of medicine that focuses on improving quality of life by managing physical symptoms as well as mental and spiritual well-being in patients with severe illnesses.1,2 Despite cases of severe dermatologic disease, the use of PC in the field of dermatology is limited, often leaving patients with a range of unmet needs.2,3 In one study that explored PC in patients with melanoma, only one-third of patients with advanced melanoma had a PC consultation.4 Reasons behind the lack of utilization of PC in dermatology include time constraints and limited training in addressing the complex psychosocial needs of patients with severe dermatologic illnesses.1 We conducted a retrospective, cross-sectional, single-institution study of specific inpatient dermatology consultations over a 5-year period to describe PC utilization among patients who were hospitalized with select severe dermatologic diseases.

Methods

A retrospective, cross-sectional study of inpatient dermatology consultations over a 5-year period (October 2016 to October 2021) was performed at Atrium Health Wake Forest Baptist Medical Center (Winston-Salem, North Carolina). Patients’ medical records were reviewed if they had one of the following diseases: bullous pemphigoid, calciphylaxis, cutaneous T-cell lymphoma (CTCL), drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, erythrodermic psoriasis, graft-vs-host disease, pemphigus vulgaris (PV), purpura fulminans, pyoderma gangrenosum, and Stevens-Johnson syndrome/toxic epidermal necrolysis. These diseases were selected for inclusion because they have been associated with a documented increase in inpatient mortality and have been described in the published literature on PC in dermatology.2 This study was reviewed and approved by the Wake Forest University institutional review board.

Use of PC consultative services along with other associated consultative care (ie, recreation therapy [RT], acute pain management, pastoral care) was assessed for each patient. Recreation therapy included specific interventions such as music therapy, arts/craft therapy, pet therapy, and other services with the goal of improving patient cognitive, emotional, and social function. For patients with a completed PC consultation, goals for PC intervention were recorded.

Results

The total study sample included 193 inpatient dermatology consultations. The mean age of the patients was 58.9 years (range, 2–100 years); 66.8% (129/193) were White and 28.5% (55/193) were Black (Table). Palliative care was consulted in 5.7% of cases, with consultations being requested by the primary care team. Reasons for PC consultation included assessment of the patient’s goals of care (4.1% [8/193]), pain management (3.6% [7/193]), non–pain symptom management (2.6% [5/193]), psychosocial support (1.6% [3/193]), and transitions of care (1.0% [2/193]). The average length of patients’ hospital stay prior to PC consultation was 11.5 days(range, 1–32 days). Acute pain management was the reason for consultation in 15.0% of cases (29/193), RT in 21.8% (42/193), and pastoral care in 13.5% (26/193) of cases. Patients with calciphylaxis received the most PC and pain consultations, but fewer than half received these services. Patients with calciphylaxis, PV, purpura fulminans, and CTCL received a higher percentage of PC consultations than the overall cohort, while patients with calciphylaxis, DRESS syndrome, PV, and pyoderma gangrenosum received relatively more pain consultations than the overall cohort (Figure).

Patient Demographics and Dermatologic Diagnosis

Comment

Clinical practice guidelines for quality PC stress the importance of specialists being familiar with these services and the ability to involve PC as part of the treatment plan to achieve better care for patients with serious illnesses.5 Our results demonstrated low rates of PC consultation services for dermatology patients, which supports the existing literature and suggests that PC may be highly underutilized in inpatient settings for patients with serious skin diseases. Use of PC was infrequent and was initiated relatively late in the course of hospital admission, which can negatively impact a patient’s well-being and care experience and can increase the care burden on their caregivers and families.2

Percentage of patients within each disease entity who received palliative care (PC), acute pain management, recreation therapy (RT), or pastoral care consultations during hospitalization.
Percentage of patients within each disease entity who received palliative care (PC), acute pain management, recreation therapy (RT), or pastoral care consultations during hospitalization. BP indicates bullous pemphigoid; CTCL, cutaneous T-cell lymphoma; DRESS, drug reaction with eosinophilia and systemic symptoms; GVHD, graft-vs-host disease; PG, pyoderma gangrenosum; PV, pemphigus vulgaris; SJS/TEN, StevensJohnson syndrome/toxic epidermal necrolysis.

Our results suggest a discrepancy in the frequency of formal PC and other palliative consultative services used for dermatologic diseases, with non-PC services including RT, acute pain management, and pastoral care more likely to be utilized. Impacting this finding may be that RT, pastoral care, and acute pain management are provided by nonphysician providers at our institution, not attending faculty staffing PC services. Patients with calciphylaxis were more likely to have PC consultations, potentially due to medicine providers’ familiarity with its morbidity and mortality, as it is commonly associated with end-stage renal disease. Similarly, internal medicine providers may be more familiar with pain classically associated with PG and PV and may be more likely to engage pain experts. Some diseases with notable morbidity and potential mortality were underrepresented including SJS/TEN, erythrodermic psoriasis, CTCL, and GVHD.

Limitations of our study included examination of data from a single institution, as well as the small sample sizes in specific subgroups, which prevented us from making comparisons between diseases. The cross-sectional design also limited our ability to control for confounding variables.

Conclusion

We urge dermatology consultation services to advocate for patients with serious skin diseases andinclude PC consultation as part of their recommendations to primary care teams. Further research should characterize the specific needs of patients that may be addressed by PC services and explore ways dermatologists and others can identify and provide specialty care to hospitalized patients.

References
  1. Kelley AS, Morrison RS. Palliative care for the seriously ill. N Engl J Med. 2015;373:747-755.
  2. Thompson LL, Chen ST, Lawton A, et al. Palliative care in dermatology: a clinical primer, review of the literature, and needs assessment. J Am Acad Dermatol. 2021;85:708-717. doi:10.1016/j.jaad.2020.08.029
  3. Yang CS, Quan VL, Charrow A. The power of a palliative perspective in dermatology. JAMA Dermatol. 2022;158:609-610. doi:10.1001/jamadermatol.2022.1298
  4. Osagiede O, Colibaseanu DT, Spaulding AC, et al. Palliative care use among patients with solid cancer tumors. J Palliat Care. 2018;33:149-158.
  5. Clinical Practice Guidelines for Quality Palliative Care. 4th ed. National Coalition for Hospice and Palliative Care; 2018. Accessed June 21, 2023. https://www.nationalcoalitionhpc.org/wp-content/uploads/2018/10/NCHPC-NCPGuidelines_4thED_web_FINAL.pdf
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From the Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

The authors no conflict of interest.

Correspondence: Lindsay C. Strowd, MD, Wake Forest University School of Medicine, Department of Dermatology, Medical Center Blvd, Winston-Salem, NC 27157 ([email protected]).

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From the Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

The authors no conflict of interest.

Correspondence: Lindsay C. Strowd, MD, Wake Forest University School of Medicine, Department of Dermatology, Medical Center Blvd, Winston-Salem, NC 27157 ([email protected]).

Author and Disclosure Information

From the Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

The authors no conflict of interest.

Correspondence: Lindsay C. Strowd, MD, Wake Forest University School of Medicine, Department of Dermatology, Medical Center Blvd, Winston-Salem, NC 27157 ([email protected]).

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IN PARTNERSHIP WITH THE SOCIETY OF DERMATOLOGY HOSPITALISTS
IN PARTNERSHIP WITH THE SOCIETY OF DERMATOLOGY HOSPITALISTS

Palliative care (PC) is a field of medicine that focuses on improving quality of life by managing physical symptoms as well as mental and spiritual well-being in patients with severe illnesses.1,2 Despite cases of severe dermatologic disease, the use of PC in the field of dermatology is limited, often leaving patients with a range of unmet needs.2,3 In one study that explored PC in patients with melanoma, only one-third of patients with advanced melanoma had a PC consultation.4 Reasons behind the lack of utilization of PC in dermatology include time constraints and limited training in addressing the complex psychosocial needs of patients with severe dermatologic illnesses.1 We conducted a retrospective, cross-sectional, single-institution study of specific inpatient dermatology consultations over a 5-year period to describe PC utilization among patients who were hospitalized with select severe dermatologic diseases.

Methods

A retrospective, cross-sectional study of inpatient dermatology consultations over a 5-year period (October 2016 to October 2021) was performed at Atrium Health Wake Forest Baptist Medical Center (Winston-Salem, North Carolina). Patients’ medical records were reviewed if they had one of the following diseases: bullous pemphigoid, calciphylaxis, cutaneous T-cell lymphoma (CTCL), drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, erythrodermic psoriasis, graft-vs-host disease, pemphigus vulgaris (PV), purpura fulminans, pyoderma gangrenosum, and Stevens-Johnson syndrome/toxic epidermal necrolysis. These diseases were selected for inclusion because they have been associated with a documented increase in inpatient mortality and have been described in the published literature on PC in dermatology.2 This study was reviewed and approved by the Wake Forest University institutional review board.

Use of PC consultative services along with other associated consultative care (ie, recreation therapy [RT], acute pain management, pastoral care) was assessed for each patient. Recreation therapy included specific interventions such as music therapy, arts/craft therapy, pet therapy, and other services with the goal of improving patient cognitive, emotional, and social function. For patients with a completed PC consultation, goals for PC intervention were recorded.

Results

The total study sample included 193 inpatient dermatology consultations. The mean age of the patients was 58.9 years (range, 2–100 years); 66.8% (129/193) were White and 28.5% (55/193) were Black (Table). Palliative care was consulted in 5.7% of cases, with consultations being requested by the primary care team. Reasons for PC consultation included assessment of the patient’s goals of care (4.1% [8/193]), pain management (3.6% [7/193]), non–pain symptom management (2.6% [5/193]), psychosocial support (1.6% [3/193]), and transitions of care (1.0% [2/193]). The average length of patients’ hospital stay prior to PC consultation was 11.5 days(range, 1–32 days). Acute pain management was the reason for consultation in 15.0% of cases (29/193), RT in 21.8% (42/193), and pastoral care in 13.5% (26/193) of cases. Patients with calciphylaxis received the most PC and pain consultations, but fewer than half received these services. Patients with calciphylaxis, PV, purpura fulminans, and CTCL received a higher percentage of PC consultations than the overall cohort, while patients with calciphylaxis, DRESS syndrome, PV, and pyoderma gangrenosum received relatively more pain consultations than the overall cohort (Figure).

Patient Demographics and Dermatologic Diagnosis

Comment

Clinical practice guidelines for quality PC stress the importance of specialists being familiar with these services and the ability to involve PC as part of the treatment plan to achieve better care for patients with serious illnesses.5 Our results demonstrated low rates of PC consultation services for dermatology patients, which supports the existing literature and suggests that PC may be highly underutilized in inpatient settings for patients with serious skin diseases. Use of PC was infrequent and was initiated relatively late in the course of hospital admission, which can negatively impact a patient’s well-being and care experience and can increase the care burden on their caregivers and families.2

Percentage of patients within each disease entity who received palliative care (PC), acute pain management, recreation therapy (RT), or pastoral care consultations during hospitalization.
Percentage of patients within each disease entity who received palliative care (PC), acute pain management, recreation therapy (RT), or pastoral care consultations during hospitalization. BP indicates bullous pemphigoid; CTCL, cutaneous T-cell lymphoma; DRESS, drug reaction with eosinophilia and systemic symptoms; GVHD, graft-vs-host disease; PG, pyoderma gangrenosum; PV, pemphigus vulgaris; SJS/TEN, StevensJohnson syndrome/toxic epidermal necrolysis.

Our results suggest a discrepancy in the frequency of formal PC and other palliative consultative services used for dermatologic diseases, with non-PC services including RT, acute pain management, and pastoral care more likely to be utilized. Impacting this finding may be that RT, pastoral care, and acute pain management are provided by nonphysician providers at our institution, not attending faculty staffing PC services. Patients with calciphylaxis were more likely to have PC consultations, potentially due to medicine providers’ familiarity with its morbidity and mortality, as it is commonly associated with end-stage renal disease. Similarly, internal medicine providers may be more familiar with pain classically associated with PG and PV and may be more likely to engage pain experts. Some diseases with notable morbidity and potential mortality were underrepresented including SJS/TEN, erythrodermic psoriasis, CTCL, and GVHD.

Limitations of our study included examination of data from a single institution, as well as the small sample sizes in specific subgroups, which prevented us from making comparisons between diseases. The cross-sectional design also limited our ability to control for confounding variables.

Conclusion

We urge dermatology consultation services to advocate for patients with serious skin diseases andinclude PC consultation as part of their recommendations to primary care teams. Further research should characterize the specific needs of patients that may be addressed by PC services and explore ways dermatologists and others can identify and provide specialty care to hospitalized patients.

Palliative care (PC) is a field of medicine that focuses on improving quality of life by managing physical symptoms as well as mental and spiritual well-being in patients with severe illnesses.1,2 Despite cases of severe dermatologic disease, the use of PC in the field of dermatology is limited, often leaving patients with a range of unmet needs.2,3 In one study that explored PC in patients with melanoma, only one-third of patients with advanced melanoma had a PC consultation.4 Reasons behind the lack of utilization of PC in dermatology include time constraints and limited training in addressing the complex psychosocial needs of patients with severe dermatologic illnesses.1 We conducted a retrospective, cross-sectional, single-institution study of specific inpatient dermatology consultations over a 5-year period to describe PC utilization among patients who were hospitalized with select severe dermatologic diseases.

Methods

A retrospective, cross-sectional study of inpatient dermatology consultations over a 5-year period (October 2016 to October 2021) was performed at Atrium Health Wake Forest Baptist Medical Center (Winston-Salem, North Carolina). Patients’ medical records were reviewed if they had one of the following diseases: bullous pemphigoid, calciphylaxis, cutaneous T-cell lymphoma (CTCL), drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, erythrodermic psoriasis, graft-vs-host disease, pemphigus vulgaris (PV), purpura fulminans, pyoderma gangrenosum, and Stevens-Johnson syndrome/toxic epidermal necrolysis. These diseases were selected for inclusion because they have been associated with a documented increase in inpatient mortality and have been described in the published literature on PC in dermatology.2 This study was reviewed and approved by the Wake Forest University institutional review board.

Use of PC consultative services along with other associated consultative care (ie, recreation therapy [RT], acute pain management, pastoral care) was assessed for each patient. Recreation therapy included specific interventions such as music therapy, arts/craft therapy, pet therapy, and other services with the goal of improving patient cognitive, emotional, and social function. For patients with a completed PC consultation, goals for PC intervention were recorded.

Results

The total study sample included 193 inpatient dermatology consultations. The mean age of the patients was 58.9 years (range, 2–100 years); 66.8% (129/193) were White and 28.5% (55/193) were Black (Table). Palliative care was consulted in 5.7% of cases, with consultations being requested by the primary care team. Reasons for PC consultation included assessment of the patient’s goals of care (4.1% [8/193]), pain management (3.6% [7/193]), non–pain symptom management (2.6% [5/193]), psychosocial support (1.6% [3/193]), and transitions of care (1.0% [2/193]). The average length of patients’ hospital stay prior to PC consultation was 11.5 days(range, 1–32 days). Acute pain management was the reason for consultation in 15.0% of cases (29/193), RT in 21.8% (42/193), and pastoral care in 13.5% (26/193) of cases. Patients with calciphylaxis received the most PC and pain consultations, but fewer than half received these services. Patients with calciphylaxis, PV, purpura fulminans, and CTCL received a higher percentage of PC consultations than the overall cohort, while patients with calciphylaxis, DRESS syndrome, PV, and pyoderma gangrenosum received relatively more pain consultations than the overall cohort (Figure).

Patient Demographics and Dermatologic Diagnosis

Comment

Clinical practice guidelines for quality PC stress the importance of specialists being familiar with these services and the ability to involve PC as part of the treatment plan to achieve better care for patients with serious illnesses.5 Our results demonstrated low rates of PC consultation services for dermatology patients, which supports the existing literature and suggests that PC may be highly underutilized in inpatient settings for patients with serious skin diseases. Use of PC was infrequent and was initiated relatively late in the course of hospital admission, which can negatively impact a patient’s well-being and care experience and can increase the care burden on their caregivers and families.2

Percentage of patients within each disease entity who received palliative care (PC), acute pain management, recreation therapy (RT), or pastoral care consultations during hospitalization.
Percentage of patients within each disease entity who received palliative care (PC), acute pain management, recreation therapy (RT), or pastoral care consultations during hospitalization. BP indicates bullous pemphigoid; CTCL, cutaneous T-cell lymphoma; DRESS, drug reaction with eosinophilia and systemic symptoms; GVHD, graft-vs-host disease; PG, pyoderma gangrenosum; PV, pemphigus vulgaris; SJS/TEN, StevensJohnson syndrome/toxic epidermal necrolysis.

Our results suggest a discrepancy in the frequency of formal PC and other palliative consultative services used for dermatologic diseases, with non-PC services including RT, acute pain management, and pastoral care more likely to be utilized. Impacting this finding may be that RT, pastoral care, and acute pain management are provided by nonphysician providers at our institution, not attending faculty staffing PC services. Patients with calciphylaxis were more likely to have PC consultations, potentially due to medicine providers’ familiarity with its morbidity and mortality, as it is commonly associated with end-stage renal disease. Similarly, internal medicine providers may be more familiar with pain classically associated with PG and PV and may be more likely to engage pain experts. Some diseases with notable morbidity and potential mortality were underrepresented including SJS/TEN, erythrodermic psoriasis, CTCL, and GVHD.

Limitations of our study included examination of data from a single institution, as well as the small sample sizes in specific subgroups, which prevented us from making comparisons between diseases. The cross-sectional design also limited our ability to control for confounding variables.

Conclusion

We urge dermatology consultation services to advocate for patients with serious skin diseases andinclude PC consultation as part of their recommendations to primary care teams. Further research should characterize the specific needs of patients that may be addressed by PC services and explore ways dermatologists and others can identify and provide specialty care to hospitalized patients.

References
  1. Kelley AS, Morrison RS. Palliative care for the seriously ill. N Engl J Med. 2015;373:747-755.
  2. Thompson LL, Chen ST, Lawton A, et al. Palliative care in dermatology: a clinical primer, review of the literature, and needs assessment. J Am Acad Dermatol. 2021;85:708-717. doi:10.1016/j.jaad.2020.08.029
  3. Yang CS, Quan VL, Charrow A. The power of a palliative perspective in dermatology. JAMA Dermatol. 2022;158:609-610. doi:10.1001/jamadermatol.2022.1298
  4. Osagiede O, Colibaseanu DT, Spaulding AC, et al. Palliative care use among patients with solid cancer tumors. J Palliat Care. 2018;33:149-158.
  5. Clinical Practice Guidelines for Quality Palliative Care. 4th ed. National Coalition for Hospice and Palliative Care; 2018. Accessed June 21, 2023. https://www.nationalcoalitionhpc.org/wp-content/uploads/2018/10/NCHPC-NCPGuidelines_4thED_web_FINAL.pdf
References
  1. Kelley AS, Morrison RS. Palliative care for the seriously ill. N Engl J Med. 2015;373:747-755.
  2. Thompson LL, Chen ST, Lawton A, et al. Palliative care in dermatology: a clinical primer, review of the literature, and needs assessment. J Am Acad Dermatol. 2021;85:708-717. doi:10.1016/j.jaad.2020.08.029
  3. Yang CS, Quan VL, Charrow A. The power of a palliative perspective in dermatology. JAMA Dermatol. 2022;158:609-610. doi:10.1001/jamadermatol.2022.1298
  4. Osagiede O, Colibaseanu DT, Spaulding AC, et al. Palliative care use among patients with solid cancer tumors. J Palliat Care. 2018;33:149-158.
  5. Clinical Practice Guidelines for Quality Palliative Care. 4th ed. National Coalition for Hospice and Palliative Care; 2018. Accessed June 21, 2023. https://www.nationalcoalitionhpc.org/wp-content/uploads/2018/10/NCHPC-NCPGuidelines_4thED_web_FINAL.pdf
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  • Although severe dermatologic disease negatively impacts patients’ quality of life, palliative care may be underutilized in this population.
  • Palliative care should be an integral part of caring for patients who are admitted to the hospital with serious dermatologic illnesses.
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