The U.S. Food and Drug Administration (FDA) has approved the first vaccine for respiratory syncytial virus (RSV) in the United States, the agency announced May 3. Arexvy, manufactured by GSK, is the world’s first RSV vaccine for adults aged 60 years and older,the company said in an announcement.

Every year, RSV is responsible for 60,000–120,000 hospitalizations and 6,000–10,000 deaths among U.S. adults older than age, according to the FDA. Older adults with underlying health conditions — such as diabetes, a weakened immune system, or lung or heart disease — are at high risk for severe disease. "Today’s approval of the first RSV vaccine is an important public health achievement to prevent a disease which can be life-threatening and reflects the FDA’s continued commitment to facilitating the development of safe and effective vaccines for use in the United States," said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement.

The FDA approval of Arexvy was based on a clinical study of approximately 25,000 patients. Half of these patients received Arexvy, while the other half received a placebo. Researchers found that the RSV vaccine reduced RSV-associated lower respiratory tract disease (LRTD) by nearly 83% and reduced the risk of developing severe RSV-associated LRTD by 94%. The most commonly reported side effects were injection site pain, fatigue, muscle pain, headache, and joint stiffness/pain. Ten patients who received Arexvy and four patients who received placebo experienced atrial fibrillation within 30 days of vaccination. The company is planning to assess risk for atrial fibrillation in postmarking studies, the FDA said. The European Medicine Agency’s Committee for Medicinal Products for Human Use recommended approval of Arexvy on April 25, 2023, on the basis of data from the same clinical trial.

GSK said that the U.S. launch of Arexvy will occur sometime in the fall before the 2023/2024 RSV season, but the company did not provide exact dates. "Today marks a turning point in our effort to reduce the significant burden of RSV," said GSK’s chief scientific officer, Tony Wood, PhD, in a company statement. "Our focus now is to ensure eligible older adults in the U.S. can access the vaccine as quickly as possible and to progress regulatory review in other countries."

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

The U.S. Food and Drug Administration (FDA) has approved the first vaccine for respiratory syncytial virus (RSV) in the United States, the agency announced May 3. Arexvy, manufactured by GSK, is the world’s first RSV vaccine for adults aged 60 years and older,the company said in an announcement.

Every year, RSV is responsible for 60,000–120,000 hospitalizations and 6,000–10,000 deaths among U.S. adults older than age, according to the FDA. Older adults with underlying health conditions — such as diabetes, a weakened immune system, or lung or heart disease — are at high risk for severe disease. "Today’s approval of the first RSV vaccine is an important public health achievement to prevent a disease which can be life-threatening and reflects the FDA’s continued commitment to facilitating the development of safe and effective vaccines for use in the United States," said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement.

The FDA approval of Arexvy was based on a clinical study of approximately 25,000 patients. Half of these patients received Arexvy, while the other half received a placebo. Researchers found that the RSV vaccine reduced RSV-associated lower respiratory tract disease (LRTD) by nearly 83% and reduced the risk of developing severe RSV-associated LRTD by 94%. The most commonly reported side effects were injection site pain, fatigue, muscle pain, headache, and joint stiffness/pain. Ten patients who received Arexvy and four patients who received placebo experienced atrial fibrillation within 30 days of vaccination. The company is planning to assess risk for atrial fibrillation in postmarking studies, the FDA said. The European Medicine Agency’s Committee for Medicinal Products for Human Use recommended approval of Arexvy on April 25, 2023, on the basis of data from the same clinical trial.

GSK said that the U.S. launch of Arexvy will occur sometime in the fall before the 2023/2024 RSV season, but the company did not provide exact dates. "Today marks a turning point in our effort to reduce the significant burden of RSV," said GSK’s chief scientific officer, Tony Wood, PhD, in a company statement. "Our focus now is to ensure eligible older adults in the U.S. can access the vaccine as quickly as possible and to progress regulatory review in other countries."

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

The U.S. Food and Drug Administration (FDA) has approved the first vaccine for respiratory syncytial virus (RSV) in the United States, the agency announced May 3. Arexvy, manufactured by GSK, is the world’s first RSV vaccine for adults aged 60 years and older,the company said in an announcement.

Every year, RSV is responsible for 60,000–120,000 hospitalizations and 6,000–10,000 deaths among U.S. adults older than age, according to the FDA. Older adults with underlying health conditions — such as diabetes, a weakened immune system, or lung or heart disease — are at high risk for severe disease. "Today’s approval of the first RSV vaccine is an important public health achievement to prevent a disease which can be life-threatening and reflects the FDA’s continued commitment to facilitating the development of safe and effective vaccines for use in the United States," said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement.

The FDA approval of Arexvy was based on a clinical study of approximately 25,000 patients. Half of these patients received Arexvy, while the other half received a placebo. Researchers found that the RSV vaccine reduced RSV-associated lower respiratory tract disease (LRTD) by nearly 83% and reduced the risk of developing severe RSV-associated LRTD by 94%. The most commonly reported side effects were injection site pain, fatigue, muscle pain, headache, and joint stiffness/pain. Ten patients who received Arexvy and four patients who received placebo experienced atrial fibrillation within 30 days of vaccination. The company is planning to assess risk for atrial fibrillation in postmarking studies, the FDA said. The European Medicine Agency’s Committee for Medicinal Products for Human Use recommended approval of Arexvy on April 25, 2023, on the basis of data from the same clinical trial.

GSK said that the U.S. launch of Arexvy will occur sometime in the fall before the 2023/2024 RSV season, but the company did not provide exact dates. "Today marks a turning point in our effort to reduce the significant burden of RSV," said GSK’s chief scientific officer, Tony Wood, PhD, in a company statement. "Our focus now is to ensure eligible older adults in the U.S. can access the vaccine as quickly as possible and to progress regulatory review in other countries."

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

Gastroenterology

January 2023

Yardeni D et al. Current Best Practice in Hepatitis B Management and Understanding Long-term Prospects for Cure. Gastroenterology. 2023 Jan;164(1):42-60.e6. doi: 10.1053/j.gastro.2022.10.008. Epub 2022 Oct 12. PMID: 36243037; PMCID: PMC9772068.

Laine L et al. Vonoprazan Versus Lansoprazole for Healing and Maintenance of Healing of Erosive Esophagitis: A Randomized Trial. Gastroenterology. 2023 Jan;164(1):61-71. doi: 10.1053/j.gastro.2022.09.041. Epub 2022 Oct 10. PMID: 36228734.

February 2023

Ufere NN et al. Promoting Prognostic Understanding and Health Equity for Patients With Advanced Liver Disease: Using “Best Case/Worst Case.” Gastroenterology. 2023 Feb;164(2):171-6. doi: 10.1053/j.gastro.2022.12.005. PMID: 36702571.

March 2023

Heath JK et al. Training Generations of Clinician Educators: Applying the Novel Clinician Educator Milestones to Faculty Development. Gastroenterology. 2023 Mar;164(3):325-8.e1. doi: 10.1053/j.gastro.2022.12.003. Epub 2022 Dec 9. PMID: 36509156.
 

Singh S et al. AGA Clinical Guidelines Committee. Electronic address: [email protected]. AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis. Gastroenterology. 2023 Mar;164(3):344-72. doi: 10.1053/j.gastro.2022.12.007. PMID: 36822736.

Clinical Gastroenterology and Hepatology

January 2023

Speicher LL and Francis D. Improving Employee Experience: Reducing Burnout, Decreasing Turnover and Building Well-being. Clin Gastroenterol Hepatol. 2023 Jan;21(1):11-4. doi: 10.1016/j.cgh.2022.09.020. Epub 2022 Sep 22. PMID: 36155248; PMCID: PMC9547273.

Penagini R et al. Rapid Drink Challenge During High-resolution Manometry for Evaluation of Esophageal Emptying in Treated Achalasia. Clin Gastroenterol Hepatol. 2023 Jan;21(1):55-63. doi: 10.1016/j.cgh.2022.02.047. Epub 2022 Feb 28. PMID: 35240328.

February 2023

Zaki TA et al. Racial and Ethnic Disparities in Early-Onset Colorectal Cancer Survival. Clin Gastroenterol Hepatol. 2023 Feb;21(2):497-506.e3. doi: 10.1016/j.cgh.2022.05.035. Epub 2022 Jun 16. PMID: 35716905; PMCID: PMC9835097.

Brenner DM et al. Rare, Overlooked, or Underappreciated Causes of Recurrent Abdominal Pain: A Primer for Gastroenterologists. Clin Gastroenterol Hepatol. 2023 Feb;21(2):264-79. doi: 10.1016/j.cgh.2022.09.022. Epub 2022 Sep 27. PMID: 36180010.

March 2023

Hanna M et al. Emerging Tests for Noninvasive Colorectal Cancer Screening. Clin Gastroenterol Hepatol. 2023 Mar;21(3):604-16. doi: 10.1016/j.cgh.2022.12.008. Epub 2022 Dec 17. PMID: 36539002; PMCID: PMC9974876.

Ormsby EL et al. Association of Standardized Radiology Reporting and Management of Abdominal CT and MRI With Diagnosis of Pancreatic Cancer. Clin Gastroenterol Hepatol. 2023 Mar;21(3):644-52.e2. doi: 10.1016/j.cgh.2022.03.047. Epub 2022 Apr 15. PMID: 35436626.

Techniques and Innovations in Gastrointestinal Endoscopy

Mohapatra S et al. (Accepted/In press). Outcomes of Endoscopic Resection for Colorectal Polyps with High-Grade Dysplasia or Intramucosal Cancer. Tech Innov Gastrointest Endosc. 2023 Jan 22. doi: 10.1016/j.tige.2023.01.003.

Holzwanger EA et al. Improving Dysplasia Detection in Barrett’s Esophagus. Techniques and Innovations in Gastrointestinal Endoscopy. Tech Innov Gastrointest Endosc. 2023;25(2):157-66. doi: 10.1016/j.tige.2023.01.002.

Gastroenterology

January 2023

Yardeni D et al. Current Best Practice in Hepatitis B Management and Understanding Long-term Prospects for Cure. Gastroenterology. 2023 Jan;164(1):42-60.e6. doi: 10.1053/j.gastro.2022.10.008. Epub 2022 Oct 12. PMID: 36243037; PMCID: PMC9772068.

Laine L et al. Vonoprazan Versus Lansoprazole for Healing and Maintenance of Healing of Erosive Esophagitis: A Randomized Trial. Gastroenterology. 2023 Jan;164(1):61-71. doi: 10.1053/j.gastro.2022.09.041. Epub 2022 Oct 10. PMID: 36228734.

February 2023

Ufere NN et al. Promoting Prognostic Understanding and Health Equity for Patients With Advanced Liver Disease: Using “Best Case/Worst Case.” Gastroenterology. 2023 Feb;164(2):171-6. doi: 10.1053/j.gastro.2022.12.005. PMID: 36702571.

March 2023

Heath JK et al. Training Generations of Clinician Educators: Applying the Novel Clinician Educator Milestones to Faculty Development. Gastroenterology. 2023 Mar;164(3):325-8.e1. doi: 10.1053/j.gastro.2022.12.003. Epub 2022 Dec 9. PMID: 36509156.
 

Singh S et al. AGA Clinical Guidelines Committee. Electronic address: [email protected]. AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis. Gastroenterology. 2023 Mar;164(3):344-72. doi: 10.1053/j.gastro.2022.12.007. PMID: 36822736.

Clinical Gastroenterology and Hepatology

January 2023

Speicher LL and Francis D. Improving Employee Experience: Reducing Burnout, Decreasing Turnover and Building Well-being. Clin Gastroenterol Hepatol. 2023 Jan;21(1):11-4. doi: 10.1016/j.cgh.2022.09.020. Epub 2022 Sep 22. PMID: 36155248; PMCID: PMC9547273.

Penagini R et al. Rapid Drink Challenge During High-resolution Manometry for Evaluation of Esophageal Emptying in Treated Achalasia. Clin Gastroenterol Hepatol. 2023 Jan;21(1):55-63. doi: 10.1016/j.cgh.2022.02.047. Epub 2022 Feb 28. PMID: 35240328.

February 2023

Zaki TA et al. Racial and Ethnic Disparities in Early-Onset Colorectal Cancer Survival. Clin Gastroenterol Hepatol. 2023 Feb;21(2):497-506.e3. doi: 10.1016/j.cgh.2022.05.035. Epub 2022 Jun 16. PMID: 35716905; PMCID: PMC9835097.

Brenner DM et al. Rare, Overlooked, or Underappreciated Causes of Recurrent Abdominal Pain: A Primer for Gastroenterologists. Clin Gastroenterol Hepatol. 2023 Feb;21(2):264-79. doi: 10.1016/j.cgh.2022.09.022. Epub 2022 Sep 27. PMID: 36180010.

March 2023

Hanna M et al. Emerging Tests for Noninvasive Colorectal Cancer Screening. Clin Gastroenterol Hepatol. 2023 Mar;21(3):604-16. doi: 10.1016/j.cgh.2022.12.008. Epub 2022 Dec 17. PMID: 36539002; PMCID: PMC9974876.

Ormsby EL et al. Association of Standardized Radiology Reporting and Management of Abdominal CT and MRI With Diagnosis of Pancreatic Cancer. Clin Gastroenterol Hepatol. 2023 Mar;21(3):644-52.e2. doi: 10.1016/j.cgh.2022.03.047. Epub 2022 Apr 15. PMID: 35436626.

Techniques and Innovations in Gastrointestinal Endoscopy

Mohapatra S et al. (Accepted/In press). Outcomes of Endoscopic Resection for Colorectal Polyps with High-Grade Dysplasia or Intramucosal Cancer. Tech Innov Gastrointest Endosc. 2023 Jan 22. doi: 10.1016/j.tige.2023.01.003.

Holzwanger EA et al. Improving Dysplasia Detection in Barrett’s Esophagus. Techniques and Innovations in Gastrointestinal Endoscopy. Tech Innov Gastrointest Endosc. 2023;25(2):157-66. doi: 10.1016/j.tige.2023.01.002.

Gastroenterology

January 2023

Yardeni D et al. Current Best Practice in Hepatitis B Management and Understanding Long-term Prospects for Cure. Gastroenterology. 2023 Jan;164(1):42-60.e6. doi: 10.1053/j.gastro.2022.10.008. Epub 2022 Oct 12. PMID: 36243037; PMCID: PMC9772068.

Laine L et al. Vonoprazan Versus Lansoprazole for Healing and Maintenance of Healing of Erosive Esophagitis: A Randomized Trial. Gastroenterology. 2023 Jan;164(1):61-71. doi: 10.1053/j.gastro.2022.09.041. Epub 2022 Oct 10. PMID: 36228734.

February 2023

Ufere NN et al. Promoting Prognostic Understanding and Health Equity for Patients With Advanced Liver Disease: Using “Best Case/Worst Case.” Gastroenterology. 2023 Feb;164(2):171-6. doi: 10.1053/j.gastro.2022.12.005. PMID: 36702571.

March 2023

Heath JK et al. Training Generations of Clinician Educators: Applying the Novel Clinician Educator Milestones to Faculty Development. Gastroenterology. 2023 Mar;164(3):325-8.e1. doi: 10.1053/j.gastro.2022.12.003. Epub 2022 Dec 9. PMID: 36509156.
 

Singh S et al. AGA Clinical Guidelines Committee. Electronic address: [email protected]. AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis. Gastroenterology. 2023 Mar;164(3):344-72. doi: 10.1053/j.gastro.2022.12.007. PMID: 36822736.

Clinical Gastroenterology and Hepatology

January 2023

Speicher LL and Francis D. Improving Employee Experience: Reducing Burnout, Decreasing Turnover and Building Well-being. Clin Gastroenterol Hepatol. 2023 Jan;21(1):11-4. doi: 10.1016/j.cgh.2022.09.020. Epub 2022 Sep 22. PMID: 36155248; PMCID: PMC9547273.

Penagini R et al. Rapid Drink Challenge During High-resolution Manometry for Evaluation of Esophageal Emptying in Treated Achalasia. Clin Gastroenterol Hepatol. 2023 Jan;21(1):55-63. doi: 10.1016/j.cgh.2022.02.047. Epub 2022 Feb 28. PMID: 35240328.

February 2023

Zaki TA et al. Racial and Ethnic Disparities in Early-Onset Colorectal Cancer Survival. Clin Gastroenterol Hepatol. 2023 Feb;21(2):497-506.e3. doi: 10.1016/j.cgh.2022.05.035. Epub 2022 Jun 16. PMID: 35716905; PMCID: PMC9835097.

Brenner DM et al. Rare, Overlooked, or Underappreciated Causes of Recurrent Abdominal Pain: A Primer for Gastroenterologists. Clin Gastroenterol Hepatol. 2023 Feb;21(2):264-79. doi: 10.1016/j.cgh.2022.09.022. Epub 2022 Sep 27. PMID: 36180010.

March 2023

Hanna M et al. Emerging Tests for Noninvasive Colorectal Cancer Screening. Clin Gastroenterol Hepatol. 2023 Mar;21(3):604-16. doi: 10.1016/j.cgh.2022.12.008. Epub 2022 Dec 17. PMID: 36539002; PMCID: PMC9974876.

Ormsby EL et al. Association of Standardized Radiology Reporting and Management of Abdominal CT and MRI With Diagnosis of Pancreatic Cancer. Clin Gastroenterol Hepatol. 2023 Mar;21(3):644-52.e2. doi: 10.1016/j.cgh.2022.03.047. Epub 2022 Apr 15. PMID: 35436626.

Techniques and Innovations in Gastrointestinal Endoscopy

Mohapatra S et al. (Accepted/In press). Outcomes of Endoscopic Resection for Colorectal Polyps with High-Grade Dysplasia or Intramucosal Cancer. Tech Innov Gastrointest Endosc. 2023 Jan 22. doi: 10.1016/j.tige.2023.01.003.

Holzwanger EA et al. Improving Dysplasia Detection in Barrett’s Esophagus. Techniques and Innovations in Gastrointestinal Endoscopy. Tech Innov Gastrointest Endosc. 2023;25(2):157-66. doi: 10.1016/j.tige.2023.01.002.

PHOENIX – While the use of lasers and energy-based devices for genitourinary indications dates back more than 50 years, a large body of scientific evidence has since accumulated for conditions ranging from genitourinary syndrome of menopause (GSM), lichen sclerosus, urinary incontinence, and vulvovaginal laxity.

“Even a cursory review of PubMed today yields over 100,000 results” on this topic, Macrene R. Alexiades, MD, PhD, associate clinical professor of dermatology at Yale University, New Haven, Conn., said at the annual conference of the American Society for Laser Medicine and Surgery. “Add to that radiofrequency and various diagnoses, the number of publications has skyrocketed, particularly over the last 10 years.”

What has been missing from this hot research topic all these years, she continued, is that no one has distilled this pile of data into a practical guide for office-based clinicians who use lasers and energy-based devices for genitourinary conditions – until now. Working with experts in gynecology and urogynecology, Dr. Alexiades spearheaded a 2-year-long effort to assemble a document on optimal protocols and best practices for genitourinary application of lasers and energy-based devices. The document, published soon after the ASLMS meeting in Lasers in Medicine and Surgery, includes a table that lists the current Food and Drug Administration approval status of devices in genitourinary applications, as well as individual sections dedicated to fractional lasers, radiofrequency (RF) devices, and high-intensity focused electromagnetic technology. It concludes with a section on the current status of clearances and future pathways.

“The work we did was exhaustive,” said Dr. Alexiades, who is also founder and director of Dermatology & Laser Surgery Center of New York. “We went through all the clinical trial data and compiled the parameters that, as a consensus, we agree are best practices for each technology for which we had rigorous published data.”

The document contains a brief background on the history of the devices used for genitourinary issues and it addresses core topics for each technology, such as conditions treated, contraindications, preoperative physical assessment and preparation, perioperative protocols, and postoperative care.

Contraindications to the genitourinary use of lasers and energy-based devices are numerous and include use of an intrauterine device, active urinary tract or genital infection, vaginal bleeding, current pregnancy, active or recent malignancy, having an electrical implant anywhere in the body, significant concurrent illness, and an anticoagulative or thromboembolic condition or taking anticoagulant medications 1 week prior to the procedure. Another condition to screen for is advanced prolapse, which was considered a contraindication in all clinical trials, she added. “It’s important that you’re able to do the speculum exam and stage the prolapse” so that a patient with this contraindication is not treated.

Dr. Alexiades shared the following highlights from the document’s section related to the use of fractional CO₂ lasers:

Preoperative management. Schedule the treatment one week after the patient’s menstrual period. Patients should avoid blood thinners for 7 days and avoid intercourse the night before the procedure. Reschedule in the case of fever, chills, or vaginal bleeding or discharge.

Preoperative physical exam and testing. A normal speculum exam and a recent negative PAP smear are required. For those of child-bearing potential, a pregnancy test is warranted. Obtain written and verbal consent, including discussion of all treatment options, risks, and benefits. No topical or local anesthesia is necessary internally. “Externally, we sometimes apply topical lidocaine gel, but I have found that’s not necessary in most cases,” Dr. Alexiades said. “The treatment is so quick.”

Peri-operative management. In general, device settings are provided by the manufacturer. “For most of the studies that had successful outcomes and no adverse events, researchers adhered to the mild or moderate settings on the technology,” she said. Energy settings were between 15 and 30 watts, delivered at a laser fluence of about 250-300 mJ/cm² with a spacing of microbeams 1 mm apart. Typically, three treatments are done at 1-month intervals and maintenance treatments are recommended at 6 and 12 months based on duration of the outcomes.

Vulvovaginal postoperative management. A 3-day recovery time is recommended with avoidance of intercourse during this period, because “re-epithelialization is usually complete in 3 days, so we want to give the opportunity for the lining to heal prior to introducing any friction, Dr. Alexiades said.” Rarely, spotting or discharge may occur and there should be no discomfort. “Any severe discomfort or burning may potentially signify infection and should prompt evaluation and possibly vaginal cultures. The patient can shower, but we recommend avoiding seated baths to decrease any introduction of infectious agents.”

Patients should be followed up monthly until three treatments are completed, and a maintenance treatment is considered appropriate between 6 and 12 months. “I do recommend doing a 1-month follow-up following the final treatment, unless it’s a patient who has already had a series of three treatments and is coming in for maintenance,” she said.

In a study from her own practice, Dr. Alexiades evaluated a series of three fractional CO₂ laser treatments to the vulva and vagina with a 1-year follow-up in postmenopausal patients. She used the Vaginal Health Index (VHI) to assess changes in vaginal elasticity, fluid volume, vaginal pH, epithelial integrity, and moisture. She and her colleagues discovered that there was improvement in every VHI category after treatment and during the follow-up interval up to 6 months.

“Between 6 and 12 months, we started to see a return a bit toward baseline on all of these parameters,” she said. “The serendipitous discovery that I made during the course of that study was that early intervention improves outcomes. I observed that the younger, most recently postmenopausal cohort seemed to attain normal or near normal VHI quicker than the more extended postmenopausal cohorts.”

In an editorial published in 2020, Dr. Alexiades reviewed the effects of fractional CO₂ laser treatment of vulvar skin on vaginal pH and referred to a study she conducted that found that the mean baseline pH pretreatment was 6.32 in the cohort of postmenopausal patients, and was reduced after 3 treatments. “Postmenopausally, the normal acidic pH becomes alkaline,” she said. But she did not expect to see an additional reduction in pH following the treatment out to 6 months. “This indicates that, whatever the wound healing and other restorative effects of these devices are, they seem to continue out to 6 months, at which point it turns around and moves toward baseline [levels].”

Dr. Alexiades highlighted two published meta-analyses of studies related to the genitourinary use of lasers and energy-based devices. One included 59 studies of 3,609 women treated for vaginal rejuvenation using either radiofrequency or fractional ablative laser therapy. The studies reported improvements in symptoms of GSM/VVA and sexual function, high patient satisfaction, with minor adverse events, including treatment-associated vaginal swelling or vaginal discharge.

“Further research needs to be completed to determine which specific pathologies can be treated, if maintenance treatment is necessary, and long-term safety concerns,” the authors concluded.

In another review, researchers analyzed 64 studies related to vaginal laser therapy for GSM. Of these, 47 were before and after studies without a control group, 10 were controlled intervention studies, and 7 were observational cohort and cross-sectional studies.

Vaginal laser treatment “seems to improve scores on the visual analogue scale, Female Sexual Function Index, and the Vaginal Health Index over the short term,” the authors wrote. “Safety outcomes are underreported and short term. Further well-designed clinical trials with sham-laser control groups and evaluating objective variables are needed to provide the best evidence on efficacy.”

“Lasers and energy-based devices are now considered alternative therapeutic modalities for genitourinary conditions,” Dr. Alexiades concluded. “The shortcomings in the literature with respect to lasers and device treatments demonstrate the need for the consensus on best practices and protocols.”

During a separate presentation at the meeting, Michael Gold, MD, highlighted data from Grand View Research, a market research database, which estimated that the global women’s health and wellness market is valued at more than $31 billion globally and is expected to grow at a compound annual growth rate of 4.8% from 2022 to 2030.

“Sales of women’s health energy-based devices continue to grow as new technologies are developed,” said Dr. Gold, a Nashville, Tenn.–based dermatologist and cosmetic surgeon who is also editor-in-chief of the Journal of Cosmetic Dermatology. “Evolving societal norms have made discussions about feminine health issues acceptable. Suffering in silence is no longer necessary or advocated.”

Dr. Alexiades disclosed that she has conducted research for Candela Lasers, Lumenis, Allergan/AbbVie, InMode, and Endymed. She is also the founder and CEO of Macrene Actives. Dr. Gold disclosed that he is a consultant to and/or an investigator and a speaker for Joylux, InMode, and Alma Lasers.
 

PHOENIX – While the use of lasers and energy-based devices for genitourinary indications dates back more than 50 years, a large body of scientific evidence has since accumulated for conditions ranging from genitourinary syndrome of menopause (GSM), lichen sclerosus, urinary incontinence, and vulvovaginal laxity.

“Even a cursory review of PubMed today yields over 100,000 results” on this topic, Macrene R. Alexiades, MD, PhD, associate clinical professor of dermatology at Yale University, New Haven, Conn., said at the annual conference of the American Society for Laser Medicine and Surgery. “Add to that radiofrequency and various diagnoses, the number of publications has skyrocketed, particularly over the last 10 years.”

What has been missing from this hot research topic all these years, she continued, is that no one has distilled this pile of data into a practical guide for office-based clinicians who use lasers and energy-based devices for genitourinary conditions – until now. Working with experts in gynecology and urogynecology, Dr. Alexiades spearheaded a 2-year-long effort to assemble a document on optimal protocols and best practices for genitourinary application of lasers and energy-based devices. The document, published soon after the ASLMS meeting in Lasers in Medicine and Surgery, includes a table that lists the current Food and Drug Administration approval status of devices in genitourinary applications, as well as individual sections dedicated to fractional lasers, radiofrequency (RF) devices, and high-intensity focused electromagnetic technology. It concludes with a section on the current status of clearances and future pathways.

“The work we did was exhaustive,” said Dr. Alexiades, who is also founder and director of Dermatology & Laser Surgery Center of New York. “We went through all the clinical trial data and compiled the parameters that, as a consensus, we agree are best practices for each technology for which we had rigorous published data.”

The document contains a brief background on the history of the devices used for genitourinary issues and it addresses core topics for each technology, such as conditions treated, contraindications, preoperative physical assessment and preparation, perioperative protocols, and postoperative care.

Contraindications to the genitourinary use of lasers and energy-based devices are numerous and include use of an intrauterine device, active urinary tract or genital infection, vaginal bleeding, current pregnancy, active or recent malignancy, having an electrical implant anywhere in the body, significant concurrent illness, and an anticoagulative or thromboembolic condition or taking anticoagulant medications 1 week prior to the procedure. Another condition to screen for is advanced prolapse, which was considered a contraindication in all clinical trials, she added. “It’s important that you’re able to do the speculum exam and stage the prolapse” so that a patient with this contraindication is not treated.

Dr. Alexiades shared the following highlights from the document’s section related to the use of fractional CO₂ lasers:

Preoperative management. Schedule the treatment one week after the patient’s menstrual period. Patients should avoid blood thinners for 7 days and avoid intercourse the night before the procedure. Reschedule in the case of fever, chills, or vaginal bleeding or discharge.

Preoperative physical exam and testing. A normal speculum exam and a recent negative PAP smear are required. For those of child-bearing potential, a pregnancy test is warranted. Obtain written and verbal consent, including discussion of all treatment options, risks, and benefits. No topical or local anesthesia is necessary internally. “Externally, we sometimes apply topical lidocaine gel, but I have found that’s not necessary in most cases,” Dr. Alexiades said. “The treatment is so quick.”

Peri-operative management. In general, device settings are provided by the manufacturer. “For most of the studies that had successful outcomes and no adverse events, researchers adhered to the mild or moderate settings on the technology,” she said. Energy settings were between 15 and 30 watts, delivered at a laser fluence of about 250-300 mJ/cm² with a spacing of microbeams 1 mm apart. Typically, three treatments are done at 1-month intervals and maintenance treatments are recommended at 6 and 12 months based on duration of the outcomes.

Vulvovaginal postoperative management. A 3-day recovery time is recommended with avoidance of intercourse during this period, because “re-epithelialization is usually complete in 3 days, so we want to give the opportunity for the lining to heal prior to introducing any friction, Dr. Alexiades said.” Rarely, spotting or discharge may occur and there should be no discomfort. “Any severe discomfort or burning may potentially signify infection and should prompt evaluation and possibly vaginal cultures. The patient can shower, but we recommend avoiding seated baths to decrease any introduction of infectious agents.”

Patients should be followed up monthly until three treatments are completed, and a maintenance treatment is considered appropriate between 6 and 12 months. “I do recommend doing a 1-month follow-up following the final treatment, unless it’s a patient who has already had a series of three treatments and is coming in for maintenance,” she said.

In a study from her own practice, Dr. Alexiades evaluated a series of three fractional CO₂ laser treatments to the vulva and vagina with a 1-year follow-up in postmenopausal patients. She used the Vaginal Health Index (VHI) to assess changes in vaginal elasticity, fluid volume, vaginal pH, epithelial integrity, and moisture. She and her colleagues discovered that there was improvement in every VHI category after treatment and during the follow-up interval up to 6 months.

“Between 6 and 12 months, we started to see a return a bit toward baseline on all of these parameters,” she said. “The serendipitous discovery that I made during the course of that study was that early intervention improves outcomes. I observed that the younger, most recently postmenopausal cohort seemed to attain normal or near normal VHI quicker than the more extended postmenopausal cohorts.”

In an editorial published in 2020, Dr. Alexiades reviewed the effects of fractional CO₂ laser treatment of vulvar skin on vaginal pH and referred to a study she conducted that found that the mean baseline pH pretreatment was 6.32 in the cohort of postmenopausal patients, and was reduced after 3 treatments. “Postmenopausally, the normal acidic pH becomes alkaline,” she said. But she did not expect to see an additional reduction in pH following the treatment out to 6 months. “This indicates that, whatever the wound healing and other restorative effects of these devices are, they seem to continue out to 6 months, at which point it turns around and moves toward baseline [levels].”

Dr. Alexiades highlighted two published meta-analyses of studies related to the genitourinary use of lasers and energy-based devices. One included 59 studies of 3,609 women treated for vaginal rejuvenation using either radiofrequency or fractional ablative laser therapy. The studies reported improvements in symptoms of GSM/VVA and sexual function, high patient satisfaction, with minor adverse events, including treatment-associated vaginal swelling or vaginal discharge.

“Further research needs to be completed to determine which specific pathologies can be treated, if maintenance treatment is necessary, and long-term safety concerns,” the authors concluded.

In another review, researchers analyzed 64 studies related to vaginal laser therapy for GSM. Of these, 47 were before and after studies without a control group, 10 were controlled intervention studies, and 7 were observational cohort and cross-sectional studies.

Vaginal laser treatment “seems to improve scores on the visual analogue scale, Female Sexual Function Index, and the Vaginal Health Index over the short term,” the authors wrote. “Safety outcomes are underreported and short term. Further well-designed clinical trials with sham-laser control groups and evaluating objective variables are needed to provide the best evidence on efficacy.”

“Lasers and energy-based devices are now considered alternative therapeutic modalities for genitourinary conditions,” Dr. Alexiades concluded. “The shortcomings in the literature with respect to lasers and device treatments demonstrate the need for the consensus on best practices and protocols.”

During a separate presentation at the meeting, Michael Gold, MD, highlighted data from Grand View Research, a market research database, which estimated that the global women’s health and wellness market is valued at more than $31 billion globally and is expected to grow at a compound annual growth rate of 4.8% from 2022 to 2030.

“Sales of women’s health energy-based devices continue to grow as new technologies are developed,” said Dr. Gold, a Nashville, Tenn.–based dermatologist and cosmetic surgeon who is also editor-in-chief of the Journal of Cosmetic Dermatology. “Evolving societal norms have made discussions about feminine health issues acceptable. Suffering in silence is no longer necessary or advocated.”

Dr. Alexiades disclosed that she has conducted research for Candela Lasers, Lumenis, Allergan/AbbVie, InMode, and Endymed. She is also the founder and CEO of Macrene Actives. Dr. Gold disclosed that he is a consultant to and/or an investigator and a speaker for Joylux, InMode, and Alma Lasers.
 

PHOENIX – While the use of lasers and energy-based devices for genitourinary indications dates back more than 50 years, a large body of scientific evidence has since accumulated for conditions ranging from genitourinary syndrome of menopause (GSM), lichen sclerosus, urinary incontinence, and vulvovaginal laxity.

“Even a cursory review of PubMed today yields over 100,000 results” on this topic, Macrene R. Alexiades, MD, PhD, associate clinical professor of dermatology at Yale University, New Haven, Conn., said at the annual conference of the American Society for Laser Medicine and Surgery. “Add to that radiofrequency and various diagnoses, the number of publications has skyrocketed, particularly over the last 10 years.”

What has been missing from this hot research topic all these years, she continued, is that no one has distilled this pile of data into a practical guide for office-based clinicians who use lasers and energy-based devices for genitourinary conditions – until now. Working with experts in gynecology and urogynecology, Dr. Alexiades spearheaded a 2-year-long effort to assemble a document on optimal protocols and best practices for genitourinary application of lasers and energy-based devices. The document, published soon after the ASLMS meeting in Lasers in Medicine and Surgery, includes a table that lists the current Food and Drug Administration approval status of devices in genitourinary applications, as well as individual sections dedicated to fractional lasers, radiofrequency (RF) devices, and high-intensity focused electromagnetic technology. It concludes with a section on the current status of clearances and future pathways.

“The work we did was exhaustive,” said Dr. Alexiades, who is also founder and director of Dermatology & Laser Surgery Center of New York. “We went through all the clinical trial data and compiled the parameters that, as a consensus, we agree are best practices for each technology for which we had rigorous published data.”

The document contains a brief background on the history of the devices used for genitourinary issues and it addresses core topics for each technology, such as conditions treated, contraindications, preoperative physical assessment and preparation, perioperative protocols, and postoperative care.

Contraindications to the genitourinary use of lasers and energy-based devices are numerous and include use of an intrauterine device, active urinary tract or genital infection, vaginal bleeding, current pregnancy, active or recent malignancy, having an electrical implant anywhere in the body, significant concurrent illness, and an anticoagulative or thromboembolic condition or taking anticoagulant medications 1 week prior to the procedure. Another condition to screen for is advanced prolapse, which was considered a contraindication in all clinical trials, she added. “It’s important that you’re able to do the speculum exam and stage the prolapse” so that a patient with this contraindication is not treated.

Dr. Alexiades shared the following highlights from the document’s section related to the use of fractional CO₂ lasers:

Preoperative management. Schedule the treatment one week after the patient’s menstrual period. Patients should avoid blood thinners for 7 days and avoid intercourse the night before the procedure. Reschedule in the case of fever, chills, or vaginal bleeding or discharge.

Preoperative physical exam and testing. A normal speculum exam and a recent negative PAP smear are required. For those of child-bearing potential, a pregnancy test is warranted. Obtain written and verbal consent, including discussion of all treatment options, risks, and benefits. No topical or local anesthesia is necessary internally. “Externally, we sometimes apply topical lidocaine gel, but I have found that’s not necessary in most cases,” Dr. Alexiades said. “The treatment is so quick.”

Peri-operative management. In general, device settings are provided by the manufacturer. “For most of the studies that had successful outcomes and no adverse events, researchers adhered to the mild or moderate settings on the technology,” she said. Energy settings were between 15 and 30 watts, delivered at a laser fluence of about 250-300 mJ/cm² with a spacing of microbeams 1 mm apart. Typically, three treatments are done at 1-month intervals and maintenance treatments are recommended at 6 and 12 months based on duration of the outcomes.

Vulvovaginal postoperative management. A 3-day recovery time is recommended with avoidance of intercourse during this period, because “re-epithelialization is usually complete in 3 days, so we want to give the opportunity for the lining to heal prior to introducing any friction, Dr. Alexiades said.” Rarely, spotting or discharge may occur and there should be no discomfort. “Any severe discomfort or burning may potentially signify infection and should prompt evaluation and possibly vaginal cultures. The patient can shower, but we recommend avoiding seated baths to decrease any introduction of infectious agents.”

Patients should be followed up monthly until three treatments are completed, and a maintenance treatment is considered appropriate between 6 and 12 months. “I do recommend doing a 1-month follow-up following the final treatment, unless it’s a patient who has already had a series of three treatments and is coming in for maintenance,” she said.

In a study from her own practice, Dr. Alexiades evaluated a series of three fractional CO₂ laser treatments to the vulva and vagina with a 1-year follow-up in postmenopausal patients. She used the Vaginal Health Index (VHI) to assess changes in vaginal elasticity, fluid volume, vaginal pH, epithelial integrity, and moisture. She and her colleagues discovered that there was improvement in every VHI category after treatment and during the follow-up interval up to 6 months.

“Between 6 and 12 months, we started to see a return a bit toward baseline on all of these parameters,” she said. “The serendipitous discovery that I made during the course of that study was that early intervention improves outcomes. I observed that the younger, most recently postmenopausal cohort seemed to attain normal or near normal VHI quicker than the more extended postmenopausal cohorts.”

In an editorial published in 2020, Dr. Alexiades reviewed the effects of fractional CO₂ laser treatment of vulvar skin on vaginal pH and referred to a study she conducted that found that the mean baseline pH pretreatment was 6.32 in the cohort of postmenopausal patients, and was reduced after 3 treatments. “Postmenopausally, the normal acidic pH becomes alkaline,” she said. But she did not expect to see an additional reduction in pH following the treatment out to 6 months. “This indicates that, whatever the wound healing and other restorative effects of these devices are, they seem to continue out to 6 months, at which point it turns around and moves toward baseline [levels].”

Dr. Alexiades highlighted two published meta-analyses of studies related to the genitourinary use of lasers and energy-based devices. One included 59 studies of 3,609 women treated for vaginal rejuvenation using either radiofrequency or fractional ablative laser therapy. The studies reported improvements in symptoms of GSM/VVA and sexual function, high patient satisfaction, with minor adverse events, including treatment-associated vaginal swelling or vaginal discharge.

“Further research needs to be completed to determine which specific pathologies can be treated, if maintenance treatment is necessary, and long-term safety concerns,” the authors concluded.

In another review, researchers analyzed 64 studies related to vaginal laser therapy for GSM. Of these, 47 were before and after studies without a control group, 10 were controlled intervention studies, and 7 were observational cohort and cross-sectional studies.

Vaginal laser treatment “seems to improve scores on the visual analogue scale, Female Sexual Function Index, and the Vaginal Health Index over the short term,” the authors wrote. “Safety outcomes are underreported and short term. Further well-designed clinical trials with sham-laser control groups and evaluating objective variables are needed to provide the best evidence on efficacy.”

“Lasers and energy-based devices are now considered alternative therapeutic modalities for genitourinary conditions,” Dr. Alexiades concluded. “The shortcomings in the literature with respect to lasers and device treatments demonstrate the need for the consensus on best practices and protocols.”

During a separate presentation at the meeting, Michael Gold, MD, highlighted data from Grand View Research, a market research database, which estimated that the global women’s health and wellness market is valued at more than $31 billion globally and is expected to grow at a compound annual growth rate of 4.8% from 2022 to 2030.

“Sales of women’s health energy-based devices continue to grow as new technologies are developed,” said Dr. Gold, a Nashville, Tenn.–based dermatologist and cosmetic surgeon who is also editor-in-chief of the Journal of Cosmetic Dermatology. “Evolving societal norms have made discussions about feminine health issues acceptable. Suffering in silence is no longer necessary or advocated.”

Dr. Alexiades disclosed that she has conducted research for Candela Lasers, Lumenis, Allergan/AbbVie, InMode, and Endymed. She is also the founder and CEO of Macrene Actives. Dr. Gold disclosed that he is a consultant to and/or an investigator and a speaker for Joylux, InMode, and Alma Lasers.
 

The theme of this month's round-up is women's health, specifically as it relates to migraine. Three recent studies have highlighted the connection between estrogen and migraine, in terms of the potential increase in risk for certain conditions, such as gestational hypertension and endometriosis, and the use of potential therapies, such as calcitonin gene-related peptide (CGRP) antagonist medications to treat menstrual migraine.

Although most practitioners know that there is a deep connection between vascular risk and migraine, most are unfamiliar with the specific interplay between these two conditions. Antihypertensive medications are common preventive treatments for migraine, and migraine itself has been associated with an increased risk for specific vascular issues in pregnancy, most notably venous sinus thrombosis. Crowe and colleagues specifically looked at whether women with migraine experience a higher risk for hypertensive disorders of pregnancy.

This was a UK-based prospective cohort study using a large longitudinal database called the Clinical Practice Research Datalink. Over 1 million live-born or stillborn deliveries were analyzed from 1993 through 2020. The data were linked to diagnosis and prescription codes for migraine that were filled or documented before 20 weeks of gestation and compared with diagnosis codes for hypertensive disorders that occurred from week 20 through the pregnancy and delivery. Regression models were then used to estimate risk ratios and CI. Only single pregnancies were counted because multiple pregnancies already are associated with a higher risk for most other vascular conditions.

Any history of migraine prior to pregnancy was associated with an increased risk for gestational hypertension, eclampsia, and preeclampsia (relative risk 1.17). The greatest risk was higher frequency. Migraine that persisted into the first trimester led to a relative risk of 1.84. The use of migraine medications, especially vasoconstrictive-type medications, was also associated with a higher risk compared with women without migraine.

Women with migraine frequently present before family planning to discuss the potential risks and options of migraine treatment during pregnancy. In addition to discussing the most appropriate preventive and acute medications, it would be appropriate also to discuss any potential red flag symptoms that may occur during pregnancy. This discussion should include hypertensive disorders of pregnancy as per this study.

Since the advent of CGRP antagonist treatments for migraine, many practitioners and patients have been curious to know whether specific features of migraine are better treated with this class of medication. There are now both acute and preventive CGRP antagonists, both as small molecule agents and monoclonal antibodies (mAb). Menstrual migraines specifically can be a more difficult-to-treat subtype, and often when other triggers are negated, hormonal fluctuation can still be a significant problem for many patients. Verhagen and colleagues set out to determine whether CGRP mAb are more or less effective for menstrually associated migraine.

This analysis was post hoc, using data from a single-arm study investigating the efficacy of two of the CGRP mAb medications: erenumab and fremanezumab. Patients were included if they had a history of migraine with > 8 monthly migraine days and at least one antihypertensive or antiepileptic preventive treatment for migraine had previously failed. Any other prophylactic medications were tapered before starting this trial; patients were given a validated electronic diary, and adherence to this diary had to be > 80%. Women were also excluded if they did not have regular menses (for instance, if they were on continuous hormonal contraception) or they were postmenopausal. Logistic regression was used to compare the preventive effect of these medications on perimenstrual and non-perimenstrual migraine attacks.

A total of 45 women were included in this observation. The relative reduction in total monthly migraine days was 31.4%; 28% were noted during and around menses, 32% were during other times of the menstrual cycle. Sensitivity analysis showed no significant difference between these two periods of time, and the ratio remained statistically similar as well.

It appears that the relative reduction in monthly migraine days did not fluctuate when the patient was treated with a CGRP antagonist mAb. Although other classes of preventive medication, specifically onabotulinumtoxinA (Botox), may affect menstrually associated migraine less potently, it appears that the CGRP antagonist class may be just as effective regardless of the underlying migraine trigger. It would definitely be worth considering a CGRP antagonist trial, or the addition of a CGRP mAb, if menstrual migraine remains significant despite otherwise effective preventive treatment.

Migraine is strongly affected by fluctuations in estrogen, and women with endometriosis often experience headaches associated with their severe attacks. Pasquini and colleagues specifically looked to see if the headache associated with endometriosis could be better diagnosed. Specifically, were these women experiencing migraine or another headache disorder?

This was a consecutive case-control series of 131 women admitted to a specialty endometriosis clinic. They were given a validated headache questionnaire that was reviewed by a neurologist to determine a diagnosis of migraine vs a diagnosis of another headache disorder. The case group included women with a history of endometriosis who were previously diagnosed with migraine, while the control group consisted of women with endometriosis only who did not have a history of headache.

Diagnosis of migraine was made in 53.4% of all patients: 18.6% of those experienced pure menstrual migraine (defined as migraine only occurring perimenstrually), 46% had some menstrually associated migraine symptoms, and 36% had purely non-menstrual migraine. Painful periods and dysuria were more frequent in patients with endometriosis and migraine compared with those without migraine. Other menstrually related conditions, including the duration of endometriosis, the phenotype of endometriosis, the presence of other systemic comorbidities, or heavy menstrual bleeding did not seem to differ significantly between the migraine and non-migraine groups.

Women of reproductive age consistently are seen most often for migraine and other headache conditions. Much of this is related to menstrual migraine and the effect that hormonal fluctuation has on migraine frequency and severity. Most practitioners work closely with their patient's gynecologist to determine which hormonal treatments and migraine treatments are most appropriate and safe for each individual situation. This study in particular sheds light on the particular phenotypes of headache pain and the specific headache diagnosis that most women with endometriosis experience.

The theme of this month's round-up is women's health, specifically as it relates to migraine. Three recent studies have highlighted the connection between estrogen and migraine, in terms of the potential increase in risk for certain conditions, such as gestational hypertension and endometriosis, and the use of potential therapies, such as calcitonin gene-related peptide (CGRP) antagonist medications to treat menstrual migraine.

Although most practitioners know that there is a deep connection between vascular risk and migraine, most are unfamiliar with the specific interplay between these two conditions. Antihypertensive medications are common preventive treatments for migraine, and migraine itself has been associated with an increased risk for specific vascular issues in pregnancy, most notably venous sinus thrombosis. Crowe and colleagues specifically looked at whether women with migraine experience a higher risk for hypertensive disorders of pregnancy.

This was a UK-based prospective cohort study using a large longitudinal database called the Clinical Practice Research Datalink. Over 1 million live-born or stillborn deliveries were analyzed from 1993 through 2020. The data were linked to diagnosis and prescription codes for migraine that were filled or documented before 20 weeks of gestation and compared with diagnosis codes for hypertensive disorders that occurred from week 20 through the pregnancy and delivery. Regression models were then used to estimate risk ratios and CI. Only single pregnancies were counted because multiple pregnancies already are associated with a higher risk for most other vascular conditions.

Any history of migraine prior to pregnancy was associated with an increased risk for gestational hypertension, eclampsia, and preeclampsia (relative risk 1.17). The greatest risk was higher frequency. Migraine that persisted into the first trimester led to a relative risk of 1.84. The use of migraine medications, especially vasoconstrictive-type medications, was also associated with a higher risk compared with women without migraine.

Women with migraine frequently present before family planning to discuss the potential risks and options of migraine treatment during pregnancy. In addition to discussing the most appropriate preventive and acute medications, it would be appropriate also to discuss any potential red flag symptoms that may occur during pregnancy. This discussion should include hypertensive disorders of pregnancy as per this study.

Since the advent of CGRP antagonist treatments for migraine, many practitioners and patients have been curious to know whether specific features of migraine are better treated with this class of medication. There are now both acute and preventive CGRP antagonists, both as small molecule agents and monoclonal antibodies (mAb). Menstrual migraines specifically can be a more difficult-to-treat subtype, and often when other triggers are negated, hormonal fluctuation can still be a significant problem for many patients. Verhagen and colleagues set out to determine whether CGRP mAb are more or less effective for menstrually associated migraine.

This analysis was post hoc, using data from a single-arm study investigating the efficacy of two of the CGRP mAb medications: erenumab and fremanezumab. Patients were included if they had a history of migraine with > 8 monthly migraine days and at least one antihypertensive or antiepileptic preventive treatment for migraine had previously failed. Any other prophylactic medications were tapered before starting this trial; patients were given a validated electronic diary, and adherence to this diary had to be > 80%. Women were also excluded if they did not have regular menses (for instance, if they were on continuous hormonal contraception) or they were postmenopausal. Logistic regression was used to compare the preventive effect of these medications on perimenstrual and non-perimenstrual migraine attacks.

A total of 45 women were included in this observation. The relative reduction in total monthly migraine days was 31.4%; 28% were noted during and around menses, 32% were during other times of the menstrual cycle. Sensitivity analysis showed no significant difference between these two periods of time, and the ratio remained statistically similar as well.

It appears that the relative reduction in monthly migraine days did not fluctuate when the patient was treated with a CGRP antagonist mAb. Although other classes of preventive medication, specifically onabotulinumtoxinA (Botox), may affect menstrually associated migraine less potently, it appears that the CGRP antagonist class may be just as effective regardless of the underlying migraine trigger. It would definitely be worth considering a CGRP antagonist trial, or the addition of a CGRP mAb, if menstrual migraine remains significant despite otherwise effective preventive treatment.

Migraine is strongly affected by fluctuations in estrogen, and women with endometriosis often experience headaches associated with their severe attacks. Pasquini and colleagues specifically looked to see if the headache associated with endometriosis could be better diagnosed. Specifically, were these women experiencing migraine or another headache disorder?

This was a consecutive case-control series of 131 women admitted to a specialty endometriosis clinic. They were given a validated headache questionnaire that was reviewed by a neurologist to determine a diagnosis of migraine vs a diagnosis of another headache disorder. The case group included women with a history of endometriosis who were previously diagnosed with migraine, while the control group consisted of women with endometriosis only who did not have a history of headache.

Diagnosis of migraine was made in 53.4% of all patients: 18.6% of those experienced pure menstrual migraine (defined as migraine only occurring perimenstrually), 46% had some menstrually associated migraine symptoms, and 36% had purely non-menstrual migraine. Painful periods and dysuria were more frequent in patients with endometriosis and migraine compared with those without migraine. Other menstrually related conditions, including the duration of endometriosis, the phenotype of endometriosis, the presence of other systemic comorbidities, or heavy menstrual bleeding did not seem to differ significantly between the migraine and non-migraine groups.

Women of reproductive age consistently are seen most often for migraine and other headache conditions. Much of this is related to menstrual migraine and the effect that hormonal fluctuation has on migraine frequency and severity. Most practitioners work closely with their patient's gynecologist to determine which hormonal treatments and migraine treatments are most appropriate and safe for each individual situation. This study in particular sheds light on the particular phenotypes of headache pain and the specific headache diagnosis that most women with endometriosis experience.

The theme of this month's round-up is women's health, specifically as it relates to migraine. Three recent studies have highlighted the connection between estrogen and migraine, in terms of the potential increase in risk for certain conditions, such as gestational hypertension and endometriosis, and the use of potential therapies, such as calcitonin gene-related peptide (CGRP) antagonist medications to treat menstrual migraine.

Although most practitioners know that there is a deep connection between vascular risk and migraine, most are unfamiliar with the specific interplay between these two conditions. Antihypertensive medications are common preventive treatments for migraine, and migraine itself has been associated with an increased risk for specific vascular issues in pregnancy, most notably venous sinus thrombosis. Crowe and colleagues specifically looked at whether women with migraine experience a higher risk for hypertensive disorders of pregnancy.

This was a UK-based prospective cohort study using a large longitudinal database called the Clinical Practice Research Datalink. Over 1 million live-born or stillborn deliveries were analyzed from 1993 through 2020. The data were linked to diagnosis and prescription codes for migraine that were filled or documented before 20 weeks of gestation and compared with diagnosis codes for hypertensive disorders that occurred from week 20 through the pregnancy and delivery. Regression models were then used to estimate risk ratios and CI. Only single pregnancies were counted because multiple pregnancies already are associated with a higher risk for most other vascular conditions.

Any history of migraine prior to pregnancy was associated with an increased risk for gestational hypertension, eclampsia, and preeclampsia (relative risk 1.17). The greatest risk was higher frequency. Migraine that persisted into the first trimester led to a relative risk of 1.84. The use of migraine medications, especially vasoconstrictive-type medications, was also associated with a higher risk compared with women without migraine.

Women with migraine frequently present before family planning to discuss the potential risks and options of migraine treatment during pregnancy. In addition to discussing the most appropriate preventive and acute medications, it would be appropriate also to discuss any potential red flag symptoms that may occur during pregnancy. This discussion should include hypertensive disorders of pregnancy as per this study.

Since the advent of CGRP antagonist treatments for migraine, many practitioners and patients have been curious to know whether specific features of migraine are better treated with this class of medication. There are now both acute and preventive CGRP antagonists, both as small molecule agents and monoclonal antibodies (mAb). Menstrual migraines specifically can be a more difficult-to-treat subtype, and often when other triggers are negated, hormonal fluctuation can still be a significant problem for many patients. Verhagen and colleagues set out to determine whether CGRP mAb are more or less effective for menstrually associated migraine.

This analysis was post hoc, using data from a single-arm study investigating the efficacy of two of the CGRP mAb medications: erenumab and fremanezumab. Patients were included if they had a history of migraine with > 8 monthly migraine days and at least one antihypertensive or antiepileptic preventive treatment for migraine had previously failed. Any other prophylactic medications were tapered before starting this trial; patients were given a validated electronic diary, and adherence to this diary had to be > 80%. Women were also excluded if they did not have regular menses (for instance, if they were on continuous hormonal contraception) or they were postmenopausal. Logistic regression was used to compare the preventive effect of these medications on perimenstrual and non-perimenstrual migraine attacks.

A total of 45 women were included in this observation. The relative reduction in total monthly migraine days was 31.4%; 28% were noted during and around menses, 32% were during other times of the menstrual cycle. Sensitivity analysis showed no significant difference between these two periods of time, and the ratio remained statistically similar as well.

It appears that the relative reduction in monthly migraine days did not fluctuate when the patient was treated with a CGRP antagonist mAb. Although other classes of preventive medication, specifically onabotulinumtoxinA (Botox), may affect menstrually associated migraine less potently, it appears that the CGRP antagonist class may be just as effective regardless of the underlying migraine trigger. It would definitely be worth considering a CGRP antagonist trial, or the addition of a CGRP mAb, if menstrual migraine remains significant despite otherwise effective preventive treatment.

Migraine is strongly affected by fluctuations in estrogen, and women with endometriosis often experience headaches associated with their severe attacks. Pasquini and colleagues specifically looked to see if the headache associated with endometriosis could be better diagnosed. Specifically, were these women experiencing migraine or another headache disorder?

This was a consecutive case-control series of 131 women admitted to a specialty endometriosis clinic. They were given a validated headache questionnaire that was reviewed by a neurologist to determine a diagnosis of migraine vs a diagnosis of another headache disorder. The case group included women with a history of endometriosis who were previously diagnosed with migraine, while the control group consisted of women with endometriosis only who did not have a history of headache.

Diagnosis of migraine was made in 53.4% of all patients: 18.6% of those experienced pure menstrual migraine (defined as migraine only occurring perimenstrually), 46% had some menstrually associated migraine symptoms, and 36% had purely non-menstrual migraine. Painful periods and dysuria were more frequent in patients with endometriosis and migraine compared with those without migraine. Other menstrually related conditions, including the duration of endometriosis, the phenotype of endometriosis, the presence of other systemic comorbidities, or heavy menstrual bleeding did not seem to differ significantly between the migraine and non-migraine groups.

Women of reproductive age consistently are seen most often for migraine and other headache conditions. Much of this is related to menstrual migraine and the effect that hormonal fluctuation has on migraine frequency and severity. Most practitioners work closely with their patient's gynecologist to determine which hormonal treatments and migraine treatments are most appropriate and safe for each individual situation. This study in particular sheds light on the particular phenotypes of headache pain and the specific headache diagnosis that most women with endometriosis experience.

Diffuse large B-cell lymphoma (DLBCL) is both a clinically and molecularly heterogenous disease. The International Prognostic Index (IPI), which is based on clinical and laboratory variables, is still currently used to delineate risk at the time of diagnosis. Diffuse large B-cell lymphoma can also further be classified into either germinal center B-cell (GCB) or activated B-cell (ABC) subtype, also known as the cell-of-origin classification (COO), which has been prognostic in prior studies.¹ COO is based on gene expression profiling (GEP), though it can be estimated by immunohistochemistry.

Although these classifications are available, treatment of DLBCL has largely remained uniform over the past few decades. Despite encouraging preclinical data and early trials, large randomized studies had not demonstrated an advantage of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) plus X over R-CHOP alone.^2,3 The REMoDL-B trial, which included 801 adult patients with DLBCL, including patients with ABC, GCB, or molecular high grade (MHG) classification by GEP. Patients received one cycle of R-CHOP and were randomly assigned to R-CHOP (n = 407) alone or bortezomib–R-CHOP (n = 394) for cycles 2-6. Initial reports did not demonstrate any clear benefit of the addition of bortezomib.⁴ More recently, however, 5-year follow-up data demonstrate that the addition of bortezomib confers an advantage over R-CHOP in patients with ABC and MHG DLBCL (Davies et al). Bortezomib–R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P = .041) and MHG (aHR 0.46; P = .011) groups and overall survival (OS) in the ABC group (aHR 0.58; P = .032). The GCB group showed no significant difference in PFS or OS.

Despite the results of REMoDL-B, it is unlikely that this study will change practice. GEP is not readily available and with the approval of polatuzumab (pola)–R-CHP, based on the results of POLARIX trial, there is new option available for patients with newly diagnosed DLBCL with a high IPI. A recent meta-analysis of 12 randomized controlled trials (Sheng et al) involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received pola–R-CHP or other regimens was also recently performed. This study showed that pola–R-CHP prolonged PFS in patients with ABC-type DLBCL compared with bortezomib–R-CHOP (hazard ratio [HR] 0.52; P = .02); ibrutinib–R-CHOP (HR 0.43; P = .001); lenalidomide–R-CHOP (HR 0.51; P = .009); Obinutuzumab–CHOP (HR 0.46; P = .008); R-CHOP (HR 0.40; P < .001); and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P = .07). Pola–R-CHP had no PFS benefit in patients with GCB-type DLBCL. Although it is difficult to directly compare trials, these data suggest that pola–R-CHP is active in ABC subtype DLBCL.

Together, these trials suggest that there still may be a role for more personalized therapy in DLBCL, though there may be room for improvement. Recent studies have suggested more complex genomic underpinnings in DLBCL beyond COO, which will hopefully be studied in the context of DLBCL trials.⁵

In the second line, patients with primary refractory or early relapse of DLBCL now have the option of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, based on the results of the ZUMA-7 and TRANSFORM studies.^6,7 Lisocabtagene maraleucel (liso-cel) was also found to have a manageable safety profile in older patients with large B-cell lymphoma who were not transplant candidates in the PILOT study, leading to approval in this setting.⁸ More recently, axicabtagene ciloleucel (axi-cel) was found to be an effective second-line therapy with a manageable safety profile for patients aged ≥ 65 years as well (Westin et al). These findings are from a preplanned analysis of 109 patients aged ≥ 65 years from ZUMA-7 who were randomly assigned to receive second-line axi-cel (n = 51) or standard of care (SOC) (n = 58; two or three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation). At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs SOC; 21.5 vs 2.5 months; HR, 0.276; descriptive P < .0001). Rates of grade 3 or higher treatment-emergent adverse events were 94% and 82% with axi-cel and SOC, respectively. Although these patients were considered transplant eligible, this study demonstrates that axi-cel can be safely administered to older patients.

Additional References

1.         Rosenwald A, Wright G, Chan WC, et al; Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:1937-1947. doi: 10.1056/NEJMoa012914

2.         Younes A, Sehn LH, Johnson P, et al; PHOENIX investigators. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019;37:1285-1295. doi: 10.1200/JCO.18.02403

3.         Nowakowski GS, Chiappella A, Gascoyne RD, et al; ROBUST Trial Investigators. ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021;39:1317-1328. doi: 10.1200/JCO.20.01366

4.         Davies A, Cummin TE, Barrans S, et al. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20:649-662. doi: 10.1016/S1470-2045(18)30935-5

5.         Crombie JL, Armand P. Diffuse large B-cell lymphoma's new genomics: the bridge and the chasm. J Clin Oncol. 2020;38:3565-3574. doi: 10.1200/JCO.20.01501

6.         Locke FL, Miklos DB, Jacobson CA, et al for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133

7.         Abramson JS, Solomon SR, Arnason JE, et al; TRANSFORM Investigators. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of phase 3 TRANSFORM study. Blood. 2023:141:1675-1684. doi: 10.1182/blood.2022018730

8.         Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022;23:1066-1077. doi: 10.1016/S1470-2045(22)00339-4

Diffuse large B-cell lymphoma (DLBCL) is both a clinically and molecularly heterogenous disease. The International Prognostic Index (IPI), which is based on clinical and laboratory variables, is still currently used to delineate risk at the time of diagnosis. Diffuse large B-cell lymphoma can also further be classified into either germinal center B-cell (GCB) or activated B-cell (ABC) subtype, also known as the cell-of-origin classification (COO), which has been prognostic in prior studies.¹ COO is based on gene expression profiling (GEP), though it can be estimated by immunohistochemistry.

Although these classifications are available, treatment of DLBCL has largely remained uniform over the past few decades. Despite encouraging preclinical data and early trials, large randomized studies had not demonstrated an advantage of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) plus X over R-CHOP alone.^2,3 The REMoDL-B trial, which included 801 adult patients with DLBCL, including patients with ABC, GCB, or molecular high grade (MHG) classification by GEP. Patients received one cycle of R-CHOP and were randomly assigned to R-CHOP (n = 407) alone or bortezomib–R-CHOP (n = 394) for cycles 2-6. Initial reports did not demonstrate any clear benefit of the addition of bortezomib.⁴ More recently, however, 5-year follow-up data demonstrate that the addition of bortezomib confers an advantage over R-CHOP in patients with ABC and MHG DLBCL (Davies et al). Bortezomib–R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P = .041) and MHG (aHR 0.46; P = .011) groups and overall survival (OS) in the ABC group (aHR 0.58; P = .032). The GCB group showed no significant difference in PFS or OS.

Despite the results of REMoDL-B, it is unlikely that this study will change practice. GEP is not readily available and with the approval of polatuzumab (pola)–R-CHP, based on the results of POLARIX trial, there is new option available for patients with newly diagnosed DLBCL with a high IPI. A recent meta-analysis of 12 randomized controlled trials (Sheng et al) involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received pola–R-CHP or other regimens was also recently performed. This study showed that pola–R-CHP prolonged PFS in patients with ABC-type DLBCL compared with bortezomib–R-CHOP (hazard ratio [HR] 0.52; P = .02); ibrutinib–R-CHOP (HR 0.43; P = .001); lenalidomide–R-CHOP (HR 0.51; P = .009); Obinutuzumab–CHOP (HR 0.46; P = .008); R-CHOP (HR 0.40; P < .001); and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P = .07). Pola–R-CHP had no PFS benefit in patients with GCB-type DLBCL. Although it is difficult to directly compare trials, these data suggest that pola–R-CHP is active in ABC subtype DLBCL.

Together, these trials suggest that there still may be a role for more personalized therapy in DLBCL, though there may be room for improvement. Recent studies have suggested more complex genomic underpinnings in DLBCL beyond COO, which will hopefully be studied in the context of DLBCL trials.⁵

In the second line, patients with primary refractory or early relapse of DLBCL now have the option of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, based on the results of the ZUMA-7 and TRANSFORM studies.^6,7 Lisocabtagene maraleucel (liso-cel) was also found to have a manageable safety profile in older patients with large B-cell lymphoma who were not transplant candidates in the PILOT study, leading to approval in this setting.⁸ More recently, axicabtagene ciloleucel (axi-cel) was found to be an effective second-line therapy with a manageable safety profile for patients aged ≥ 65 years as well (Westin et al). These findings are from a preplanned analysis of 109 patients aged ≥ 65 years from ZUMA-7 who were randomly assigned to receive second-line axi-cel (n = 51) or standard of care (SOC) (n = 58; two or three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation). At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs SOC; 21.5 vs 2.5 months; HR, 0.276; descriptive P < .0001). Rates of grade 3 or higher treatment-emergent adverse events were 94% and 82% with axi-cel and SOC, respectively. Although these patients were considered transplant eligible, this study demonstrates that axi-cel can be safely administered to older patients.

Additional References

1.         Rosenwald A, Wright G, Chan WC, et al; Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:1937-1947. doi: 10.1056/NEJMoa012914

2.         Younes A, Sehn LH, Johnson P, et al; PHOENIX investigators. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019;37:1285-1295. doi: 10.1200/JCO.18.02403

3.         Nowakowski GS, Chiappella A, Gascoyne RD, et al; ROBUST Trial Investigators. ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021;39:1317-1328. doi: 10.1200/JCO.20.01366

4.         Davies A, Cummin TE, Barrans S, et al. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20:649-662. doi: 10.1016/S1470-2045(18)30935-5

5.         Crombie JL, Armand P. Diffuse large B-cell lymphoma's new genomics: the bridge and the chasm. J Clin Oncol. 2020;38:3565-3574. doi: 10.1200/JCO.20.01501

6.         Locke FL, Miklos DB, Jacobson CA, et al for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133

7.         Abramson JS, Solomon SR, Arnason JE, et al; TRANSFORM Investigators. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of phase 3 TRANSFORM study. Blood. 2023:141:1675-1684. doi: 10.1182/blood.2022018730

8.         Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022;23:1066-1077. doi: 10.1016/S1470-2045(22)00339-4

Diffuse large B-cell lymphoma (DLBCL) is both a clinically and molecularly heterogenous disease. The International Prognostic Index (IPI), which is based on clinical and laboratory variables, is still currently used to delineate risk at the time of diagnosis. Diffuse large B-cell lymphoma can also further be classified into either germinal center B-cell (GCB) or activated B-cell (ABC) subtype, also known as the cell-of-origin classification (COO), which has been prognostic in prior studies.¹ COO is based on gene expression profiling (GEP), though it can be estimated by immunohistochemistry.

Although these classifications are available, treatment of DLBCL has largely remained uniform over the past few decades. Despite encouraging preclinical data and early trials, large randomized studies had not demonstrated an advantage of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (R-CHOP) plus X over R-CHOP alone.^2,3 The REMoDL-B trial, which included 801 adult patients with DLBCL, including patients with ABC, GCB, or molecular high grade (MHG) classification by GEP. Patients received one cycle of R-CHOP and were randomly assigned to R-CHOP (n = 407) alone or bortezomib–R-CHOP (n = 394) for cycles 2-6. Initial reports did not demonstrate any clear benefit of the addition of bortezomib.⁴ More recently, however, 5-year follow-up data demonstrate that the addition of bortezomib confers an advantage over R-CHOP in patients with ABC and MHG DLBCL (Davies et al). Bortezomib–R-CHOP vs R-CHOP significantly improved 60-month progression-free survival (PFS) in the ABC (adjusted hazard ratio [aHR] 0.65; P = .041) and MHG (aHR 0.46; P = .011) groups and overall survival (OS) in the ABC group (aHR 0.58; P = .032). The GCB group showed no significant difference in PFS or OS.

Despite the results of REMoDL-B, it is unlikely that this study will change practice. GEP is not readily available and with the approval of polatuzumab (pola)–R-CHP, based on the results of POLARIX trial, there is new option available for patients with newly diagnosed DLBCL with a high IPI. A recent meta-analysis of 12 randomized controlled trials (Sheng et al) involving 8376 patients with previously untreated ABC- or GCB-type DLBCL who received pola–R-CHP or other regimens was also recently performed. This study showed that pola–R-CHP prolonged PFS in patients with ABC-type DLBCL compared with bortezomib–R-CHOP (hazard ratio [HR] 0.52; P = .02); ibrutinib–R-CHOP (HR 0.43; P = .001); lenalidomide–R-CHOP (HR 0.51; P = .009); Obinutuzumab–CHOP (HR 0.46; P = .008); R-CHOP (HR 0.40; P < .001); and bortezomib, rituximab, and cyclophosphamide (HR 0.44; P = .07). Pola–R-CHP had no PFS benefit in patients with GCB-type DLBCL. Although it is difficult to directly compare trials, these data suggest that pola–R-CHP is active in ABC subtype DLBCL.

Together, these trials suggest that there still may be a role for more personalized therapy in DLBCL, though there may be room for improvement. Recent studies have suggested more complex genomic underpinnings in DLBCL beyond COO, which will hopefully be studied in the context of DLBCL trials.⁵

In the second line, patients with primary refractory or early relapse of DLBCL now have the option of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, based on the results of the ZUMA-7 and TRANSFORM studies.^6,7 Lisocabtagene maraleucel (liso-cel) was also found to have a manageable safety profile in older patients with large B-cell lymphoma who were not transplant candidates in the PILOT study, leading to approval in this setting.⁸ More recently, axicabtagene ciloleucel (axi-cel) was found to be an effective second-line therapy with a manageable safety profile for patients aged ≥ 65 years as well (Westin et al). These findings are from a preplanned analysis of 109 patients aged ≥ 65 years from ZUMA-7 who were randomly assigned to receive second-line axi-cel (n = 51) or standard of care (SOC) (n = 58; two or three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation). At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs SOC; 21.5 vs 2.5 months; HR, 0.276; descriptive P < .0001). Rates of grade 3 or higher treatment-emergent adverse events were 94% and 82% with axi-cel and SOC, respectively. Although these patients were considered transplant eligible, this study demonstrates that axi-cel can be safely administered to older patients.

Additional References

1.         Rosenwald A, Wright G, Chan WC, et al; Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:1937-1947. doi: 10.1056/NEJMoa012914

2.         Younes A, Sehn LH, Johnson P, et al; PHOENIX investigators. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019;37:1285-1295. doi: 10.1200/JCO.18.02403

3.         Nowakowski GS, Chiappella A, Gascoyne RD, et al; ROBUST Trial Investigators. ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021;39:1317-1328. doi: 10.1200/JCO.20.01366

4.         Davies A, Cummin TE, Barrans S, et al. Gene-expression profiling of bortezomib added to standard chemoimmunotherapy for diffuse large B-cell lymphoma (REMoDL-B): an open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20:649-662. doi: 10.1016/S1470-2045(18)30935-5

5.         Crombie JL, Armand P. Diffuse large B-cell lymphoma's new genomics: the bridge and the chasm. J Clin Oncol. 2020;38:3565-3574. doi: 10.1200/JCO.20.01501

6.         Locke FL, Miklos DB, Jacobson CA, et al for All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133

7.         Abramson JS, Solomon SR, Arnason JE, et al; TRANSFORM Investigators. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of phase 3 TRANSFORM study. Blood. 2023:141:1675-1684. doi: 10.1182/blood.2022018730

8.         Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022;23:1066-1077. doi: 10.1016/S1470-2045(22)00339-4

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.

All the participants in the study I am going to tell you about this week died. And three of them died twice. But their deaths provide us with a fascinating window into the complex electrochemistry of the dying brain. What we might be looking at, indeed, is the physiologic correlate of the near-death experience.

The concept of the near-death experience is culturally ubiquitous. And though the content seems to track along culture lines – Western Christians are more likely to report seeing guardian angels, while Hindus are more likely to report seeing messengers of the god of death – certain factors seem to transcend culture: an out-of-body experience; a feeling of peace; and, of course, the light at the end of the tunnel.

As a materialist, I won’t discuss the possibility that these commonalities reflect some metaphysical structure to the afterlife. More likely, it seems to me, is that the commonalities result from the fact that the experience is mediated by our brains, and our brains, when dying, may be more alike than different.

We are talking about this study, appearing in the Proceedings of the National Academy of Sciences, by Jimo Borjigin and her team.

Dr. Borjigin studies the neural correlates of consciousness, perhaps one of the biggest questions in all of science today. To wit, if consciousness is derived from processes in the brain, what set of processes are minimally necessary for consciousness?

The study in question follows four unconscious patients –comatose patients, really – as life-sustaining support was withdrawn, up until the moment of death. Three had suffered severe anoxic brain injury in the setting of prolonged cardiac arrest. Though the heart was restarted, the brain damage was severe. The fourth had a large brain hemorrhage. All four patients were thus comatose and, though not brain-dead, unresponsive – with the lowest possible Glasgow Coma Scale score. No response to outside stimuli.

The families had made the decision to withdraw life support – to remove the breathing tube – but agreed to enroll their loved one in the study.

The team applied EEG leads to the head, EKG leads to the chest, and other monitoring equipment to observe the physiologic changes that occurred as the comatose and unresponsive patient died.

As the heart rhythm evolved from this:

PNAS

PNAS

PNAS/F. Perry Wilson, MD, MSCE

PNAS/F. Perry Wilson, MD, MSCE

PNAS/F. Perry Wilson, MD, MSCE

PNAS/F. Perry Wilson, MD, MSCE

PNAS

Dr. Wilson is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator, Yale University, New Haven, Conn. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and his new book, How Medicine Works and When It Doesn’t, is available now. Dr. Wilson has disclosed no relevant financial relationships.
 

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.

All the participants in the study I am going to tell you about this week died. And three of them died twice. But their deaths provide us with a fascinating window into the complex electrochemistry of the dying brain. What we might be looking at, indeed, is the physiologic correlate of the near-death experience.

The concept of the near-death experience is culturally ubiquitous. And though the content seems to track along culture lines – Western Christians are more likely to report seeing guardian angels, while Hindus are more likely to report seeing messengers of the god of death – certain factors seem to transcend culture: an out-of-body experience; a feeling of peace; and, of course, the light at the end of the tunnel.

As a materialist, I won’t discuss the possibility that these commonalities reflect some metaphysical structure to the afterlife. More likely, it seems to me, is that the commonalities result from the fact that the experience is mediated by our brains, and our brains, when dying, may be more alike than different.

We are talking about this study, appearing in the Proceedings of the National Academy of Sciences, by Jimo Borjigin and her team.

Dr. Borjigin studies the neural correlates of consciousness, perhaps one of the biggest questions in all of science today. To wit, if consciousness is derived from processes in the brain, what set of processes are minimally necessary for consciousness?

The study in question follows four unconscious patients –comatose patients, really – as life-sustaining support was withdrawn, up until the moment of death. Three had suffered severe anoxic brain injury in the setting of prolonged cardiac arrest. Though the heart was restarted, the brain damage was severe. The fourth had a large brain hemorrhage. All four patients were thus comatose and, though not brain-dead, unresponsive – with the lowest possible Glasgow Coma Scale score. No response to outside stimuli.

The families had made the decision to withdraw life support – to remove the breathing tube – but agreed to enroll their loved one in the study.

The team applied EEG leads to the head, EKG leads to the chest, and other monitoring equipment to observe the physiologic changes that occurred as the comatose and unresponsive patient died.

As the heart rhythm evolved from this:

PNAS

PNAS

PNAS/F. Perry Wilson, MD, MSCE

PNAS/F. Perry Wilson, MD, MSCE

PNAS/F. Perry Wilson, MD, MSCE

PNAS/F. Perry Wilson, MD, MSCE

PNAS

Dr. Wilson is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator, Yale University, New Haven, Conn. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and his new book, How Medicine Works and When It Doesn’t, is available now. Dr. Wilson has disclosed no relevant financial relationships.
 

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.

All the participants in the study I am going to tell you about this week died. And three of them died twice. But their deaths provide us with a fascinating window into the complex electrochemistry of the dying brain. What we might be looking at, indeed, is the physiologic correlate of the near-death experience.

The concept of the near-death experience is culturally ubiquitous. And though the content seems to track along culture lines – Western Christians are more likely to report seeing guardian angels, while Hindus are more likely to report seeing messengers of the god of death – certain factors seem to transcend culture: an out-of-body experience; a feeling of peace; and, of course, the light at the end of the tunnel.

As a materialist, I won’t discuss the possibility that these commonalities reflect some metaphysical structure to the afterlife. More likely, it seems to me, is that the commonalities result from the fact that the experience is mediated by our brains, and our brains, when dying, may be more alike than different.

We are talking about this study, appearing in the Proceedings of the National Academy of Sciences, by Jimo Borjigin and her team.

Dr. Borjigin studies the neural correlates of consciousness, perhaps one of the biggest questions in all of science today. To wit, if consciousness is derived from processes in the brain, what set of processes are minimally necessary for consciousness?

The study in question follows four unconscious patients –comatose patients, really – as life-sustaining support was withdrawn, up until the moment of death. Three had suffered severe anoxic brain injury in the setting of prolonged cardiac arrest. Though the heart was restarted, the brain damage was severe. The fourth had a large brain hemorrhage. All four patients were thus comatose and, though not brain-dead, unresponsive – with the lowest possible Glasgow Coma Scale score. No response to outside stimuli.

The families had made the decision to withdraw life support – to remove the breathing tube – but agreed to enroll their loved one in the study.

The team applied EEG leads to the head, EKG leads to the chest, and other monitoring equipment to observe the physiologic changes that occurred as the comatose and unresponsive patient died.

As the heart rhythm evolved from this:

PNAS

PNAS

PNAS/F. Perry Wilson, MD, MSCE

PNAS/F. Perry Wilson, MD, MSCE

PNAS/F. Perry Wilson, MD, MSCE

PNAS/F. Perry Wilson, MD, MSCE

PNAS

Dr. Wilson is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator, Yale University, New Haven, Conn. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and his new book, How Medicine Works and When It Doesn’t, is available now. Dr. Wilson has disclosed no relevant financial relationships.
 

Adults with cancer experienced significant reductions in pain after taking medicinal cannabis, in a study.

Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.

However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.

In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.

The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.

Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.

Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).

Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).

“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.

In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.

Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.

Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.

The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.

The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.

The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.

Adults with cancer experienced significant reductions in pain after taking medicinal cannabis, in a study.

Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.

However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.

In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.

The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.

Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.

Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).

Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).

“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.

In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.

Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.

Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.

The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.

The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.

The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.

Adults with cancer experienced significant reductions in pain after taking medicinal cannabis, in a study.

Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.

However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.

In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.

The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.

Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.

Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).

Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).

“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.

In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.

Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.

Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.

The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.

The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.

The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.

What do green monkeys, fruit bats, and python caves all have in common? All have been implicated in outbreaks as transmission sources of the rare but deadly Marburg virus. Marburg virus is in the same Filoviridae family of highly pathogenic RNA viruses as Ebola virus, and similarly can cause a rapidly progressive and fatal viral hemorrhagic fever.

In the first reported Marburg outbreak in 1967, laboratory workers in Marburg and Frankfurt, Germany, and in Belgrade, Yugoslavia, developed severe febrile illnesses with massive hemorrhage and multiorgan system dysfunction after contact with infected African green monkeys imported from Uganda. Since the first discovery of Marburg virus, there have been over 14 Marburg virus disease (MVD) outbreaks worldwide with nearly 600 cases and case fatality rates of 23%-90%.

The majority of MVD outbreaks have occurred in sub-Saharan Africa, and primarily in three African countries: Angola, the Democratic Republic of Congo, and Uganda. In sub-Saharan Africa, these sporadic outbreaks have had high case fatality rates (up to 80%-90%) and been linked to human exposure to the oral secretions or urinary/fecal droppings of Egyptian fruit bats (Rousettus aegyptiacus), the animal reservoir for Marburg virus. These exposures have primarily occurred among miners or tourists frequenting bat-infested mines or caves, including Uganda’s python cave, where Centers for Disease Control and Prevention investigators have conducted ecological studies on Marburg-infected bats. Person-to-person transmission occurs from direct contact with the blood or bodily fluids of an infected person or contact with a contaminated object (for example, unsterilized needles and syringes in a large nosocomial outbreak in Angola).

On April 6, 2023, the CDC issued a Health Advisory for U.S. clinicians and public health departments regarding two separate MVD outbreaks in Equatorial Guinea and Tanzania. These first-ever MVD outbreaks in both West and East African countries appear to be epidemiologically unrelated. As of March 24, 2023, in Equatorial Guinea, a total of 15 confirmed cases, including 11 deaths, and 23 probable cases, all deceased, have been identified in multiple districts since the outbreak declaration in February 2023. In Tanzania, a total of eight cases, including five deaths, have been reported among villagers in a northwest region since the outbreak declaration in March 2023. While so far cases in the Tanzania MVD outbreak have been epidemiologically linked, in Equatorial Guinea some cases have no identified epidemiological links, raising concern for ongoing community spread.

To date, no cases in these outbreaks have been reported in the United States or outside the affected countries. Overall, the risk of MVD in nonendemic countries, like the United States, is low but there is still a risk of importation. As of May 2, 2023, CDC has issued a Level 2 travel alert (practice enhanced precautions) for Marburg in Equatorial Guinea and a Level 1 travel watch (practice usual precautions) for Marburg in Tanzania. Travelers to these countries are advised to avoid nonessential travel to areas with active outbreaks and practice preventative measures, including avoiding contact with sick people, blood and bodily fluids, dead bodies, fruit bats, and nonhuman primates. International travelers returning to the United States from these countries are advised to self-monitor for Marburg symptoms during travel and for 21 days after country departure. Travelers who develop signs or symptoms of MVD should immediately self-isolate and contact their local health department or clinician.

So, how should clinicians manage such return travelers? In the setting of these new MVD outbreaks in sub-Saharan Africa, what do U.S. clinicians need to know? Clinicians should consider MVD in the differential diagnosis of ill patients with a compatible exposure history and clinical presentation. A detailed exposure history should be obtained to determine if patients have been to an area with an active MVD outbreak during their incubation period (in the past 21 days), had concerning epidemiologic risk factors (for example, presence at funerals, health care facilities, in mines/caves) while in the affected area, and/or had contact with a suspected or confirmed MVD case.

Clinical diagnosis of MVD is challenging as the initial dry symptoms of infection are nonspecific (fever, influenza-like illness, malaise, anorexia, etc.) and can resemble other febrile infectious illnesses. Similarly, presenting alternative or concurrent infections, particularly in febrile return travelers, include malaria, Lassa fever, typhoid, and measles. From these nonspecific symptoms, patients with MVD can then progress to the more severe wet symptoms (for example, vomiting, diarrhea, and bleeding). Common clinical features of MVD have been described based on the clinical presentation and course of cases in MVD outbreaks. Notably, in the original Marburg outbreak, maculopapular rash and conjunctival injection were early patient symptoms and most patient deaths occurred during the second week of illness progression.

Supportive care, including aggressive fluid replacement, is the mainstay of therapy for MVD. Currently, there are no Food and Drug Administration–approved antiviral treatments or vaccines for Marburg virus. Despite their viral similarities, vaccines against Ebola virus have not been shown to be protective against Marburg virus. Marburg virus vaccine development is ongoing, with a few promising candidate vaccines in early phase 1 and 2 clinical trials. In 2022, in response to MVD outbreaks in Ghana and Guinea, the World Health Organization convened an international Marburg virus vaccine consortium which is working to promote global research collaboration for more rapid vaccine development.

In the absence of definitive therapies, early identification of patients with suspected MVD is critical for preventing the spread of infection to close contacts. Like Ebola virus–infected patients, only symptomatic MVD patients are infectious and all patients with suspected MVD should be isolated in a private room and cared for in accordance with infection control procedures. As MVD is a nationally notifiable disease, suspected cases should be reported to local or state health departments as per jurisdictional requirements. Clinicians should also consult with their local or state health department and CDC for guidance on testing patients with suspected MVD and consider prompt evaluation for other infectious etiologies in the patient’s differential diagnosis. Comprehensive guidance for clinicians on screening and diagnosing patients with MVD is available on the CDC website at https://www.cdc.gov/vhf/marburg/index.html.

Dr. Appiah (she/her) is a medical epidemiologist in the division of global migration and quarantine at the CDC. Dr. Appiah holds adjunct faculty appointment in the division of infectious diseases at Emory University, Atlanta. She also holds a commission in the U.S. Public Health Service and is a resident advisor, Uganda, U.S. President’s Malaria Initiative, at the CDC.

What do green monkeys, fruit bats, and python caves all have in common? All have been implicated in outbreaks as transmission sources of the rare but deadly Marburg virus. Marburg virus is in the same Filoviridae family of highly pathogenic RNA viruses as Ebola virus, and similarly can cause a rapidly progressive and fatal viral hemorrhagic fever.

In the first reported Marburg outbreak in 1967, laboratory workers in Marburg and Frankfurt, Germany, and in Belgrade, Yugoslavia, developed severe febrile illnesses with massive hemorrhage and multiorgan system dysfunction after contact with infected African green monkeys imported from Uganda. Since the first discovery of Marburg virus, there have been over 14 Marburg virus disease (MVD) outbreaks worldwide with nearly 600 cases and case fatality rates of 23%-90%.

The majority of MVD outbreaks have occurred in sub-Saharan Africa, and primarily in three African countries: Angola, the Democratic Republic of Congo, and Uganda. In sub-Saharan Africa, these sporadic outbreaks have had high case fatality rates (up to 80%-90%) and been linked to human exposure to the oral secretions or urinary/fecal droppings of Egyptian fruit bats (Rousettus aegyptiacus), the animal reservoir for Marburg virus. These exposures have primarily occurred among miners or tourists frequenting bat-infested mines or caves, including Uganda’s python cave, where Centers for Disease Control and Prevention investigators have conducted ecological studies on Marburg-infected bats. Person-to-person transmission occurs from direct contact with the blood or bodily fluids of an infected person or contact with a contaminated object (for example, unsterilized needles and syringes in a large nosocomial outbreak in Angola).

On April 6, 2023, the CDC issued a Health Advisory for U.S. clinicians and public health departments regarding two separate MVD outbreaks in Equatorial Guinea and Tanzania. These first-ever MVD outbreaks in both West and East African countries appear to be epidemiologically unrelated. As of March 24, 2023, in Equatorial Guinea, a total of 15 confirmed cases, including 11 deaths, and 23 probable cases, all deceased, have been identified in multiple districts since the outbreak declaration in February 2023. In Tanzania, a total of eight cases, including five deaths, have been reported among villagers in a northwest region since the outbreak declaration in March 2023. While so far cases in the Tanzania MVD outbreak have been epidemiologically linked, in Equatorial Guinea some cases have no identified epidemiological links, raising concern for ongoing community spread.

To date, no cases in these outbreaks have been reported in the United States or outside the affected countries. Overall, the risk of MVD in nonendemic countries, like the United States, is low but there is still a risk of importation. As of May 2, 2023, CDC has issued a Level 2 travel alert (practice enhanced precautions) for Marburg in Equatorial Guinea and a Level 1 travel watch (practice usual precautions) for Marburg in Tanzania. Travelers to these countries are advised to avoid nonessential travel to areas with active outbreaks and practice preventative measures, including avoiding contact with sick people, blood and bodily fluids, dead bodies, fruit bats, and nonhuman primates. International travelers returning to the United States from these countries are advised to self-monitor for Marburg symptoms during travel and for 21 days after country departure. Travelers who develop signs or symptoms of MVD should immediately self-isolate and contact their local health department or clinician.

So, how should clinicians manage such return travelers? In the setting of these new MVD outbreaks in sub-Saharan Africa, what do U.S. clinicians need to know? Clinicians should consider MVD in the differential diagnosis of ill patients with a compatible exposure history and clinical presentation. A detailed exposure history should be obtained to determine if patients have been to an area with an active MVD outbreak during their incubation period (in the past 21 days), had concerning epidemiologic risk factors (for example, presence at funerals, health care facilities, in mines/caves) while in the affected area, and/or had contact with a suspected or confirmed MVD case.

Clinical diagnosis of MVD is challenging as the initial dry symptoms of infection are nonspecific (fever, influenza-like illness, malaise, anorexia, etc.) and can resemble other febrile infectious illnesses. Similarly, presenting alternative or concurrent infections, particularly in febrile return travelers, include malaria, Lassa fever, typhoid, and measles. From these nonspecific symptoms, patients with MVD can then progress to the more severe wet symptoms (for example, vomiting, diarrhea, and bleeding). Common clinical features of MVD have been described based on the clinical presentation and course of cases in MVD outbreaks. Notably, in the original Marburg outbreak, maculopapular rash and conjunctival injection were early patient symptoms and most patient deaths occurred during the second week of illness progression.

Supportive care, including aggressive fluid replacement, is the mainstay of therapy for MVD. Currently, there are no Food and Drug Administration–approved antiviral treatments or vaccines for Marburg virus. Despite their viral similarities, vaccines against Ebola virus have not been shown to be protective against Marburg virus. Marburg virus vaccine development is ongoing, with a few promising candidate vaccines in early phase 1 and 2 clinical trials. In 2022, in response to MVD outbreaks in Ghana and Guinea, the World Health Organization convened an international Marburg virus vaccine consortium which is working to promote global research collaboration for more rapid vaccine development.

In the absence of definitive therapies, early identification of patients with suspected MVD is critical for preventing the spread of infection to close contacts. Like Ebola virus–infected patients, only symptomatic MVD patients are infectious and all patients with suspected MVD should be isolated in a private room and cared for in accordance with infection control procedures. As MVD is a nationally notifiable disease, suspected cases should be reported to local or state health departments as per jurisdictional requirements. Clinicians should also consult with their local or state health department and CDC for guidance on testing patients with suspected MVD and consider prompt evaluation for other infectious etiologies in the patient’s differential diagnosis. Comprehensive guidance for clinicians on screening and diagnosing patients with MVD is available on the CDC website at https://www.cdc.gov/vhf/marburg/index.html.

Dr. Appiah (she/her) is a medical epidemiologist in the division of global migration and quarantine at the CDC. Dr. Appiah holds adjunct faculty appointment in the division of infectious diseases at Emory University, Atlanta. She also holds a commission in the U.S. Public Health Service and is a resident advisor, Uganda, U.S. President’s Malaria Initiative, at the CDC.

What do green monkeys, fruit bats, and python caves all have in common? All have been implicated in outbreaks as transmission sources of the rare but deadly Marburg virus. Marburg virus is in the same Filoviridae family of highly pathogenic RNA viruses as Ebola virus, and similarly can cause a rapidly progressive and fatal viral hemorrhagic fever.

In the first reported Marburg outbreak in 1967, laboratory workers in Marburg and Frankfurt, Germany, and in Belgrade, Yugoslavia, developed severe febrile illnesses with massive hemorrhage and multiorgan system dysfunction after contact with infected African green monkeys imported from Uganda. Since the first discovery of Marburg virus, there have been over 14 Marburg virus disease (MVD) outbreaks worldwide with nearly 600 cases and case fatality rates of 23%-90%.

The majority of MVD outbreaks have occurred in sub-Saharan Africa, and primarily in three African countries: Angola, the Democratic Republic of Congo, and Uganda. In sub-Saharan Africa, these sporadic outbreaks have had high case fatality rates (up to 80%-90%) and been linked to human exposure to the oral secretions or urinary/fecal droppings of Egyptian fruit bats (Rousettus aegyptiacus), the animal reservoir for Marburg virus. These exposures have primarily occurred among miners or tourists frequenting bat-infested mines or caves, including Uganda’s python cave, where Centers for Disease Control and Prevention investigators have conducted ecological studies on Marburg-infected bats. Person-to-person transmission occurs from direct contact with the blood or bodily fluids of an infected person or contact with a contaminated object (for example, unsterilized needles and syringes in a large nosocomial outbreak in Angola).

On April 6, 2023, the CDC issued a Health Advisory for U.S. clinicians and public health departments regarding two separate MVD outbreaks in Equatorial Guinea and Tanzania. These first-ever MVD outbreaks in both West and East African countries appear to be epidemiologically unrelated. As of March 24, 2023, in Equatorial Guinea, a total of 15 confirmed cases, including 11 deaths, and 23 probable cases, all deceased, have been identified in multiple districts since the outbreak declaration in February 2023. In Tanzania, a total of eight cases, including five deaths, have been reported among villagers in a northwest region since the outbreak declaration in March 2023. While so far cases in the Tanzania MVD outbreak have been epidemiologically linked, in Equatorial Guinea some cases have no identified epidemiological links, raising concern for ongoing community spread.

To date, no cases in these outbreaks have been reported in the United States or outside the affected countries. Overall, the risk of MVD in nonendemic countries, like the United States, is low but there is still a risk of importation. As of May 2, 2023, CDC has issued a Level 2 travel alert (practice enhanced precautions) for Marburg in Equatorial Guinea and a Level 1 travel watch (practice usual precautions) for Marburg in Tanzania. Travelers to these countries are advised to avoid nonessential travel to areas with active outbreaks and practice preventative measures, including avoiding contact with sick people, blood and bodily fluids, dead bodies, fruit bats, and nonhuman primates. International travelers returning to the United States from these countries are advised to self-monitor for Marburg symptoms during travel and for 21 days after country departure. Travelers who develop signs or symptoms of MVD should immediately self-isolate and contact their local health department or clinician.

So, how should clinicians manage such return travelers? In the setting of these new MVD outbreaks in sub-Saharan Africa, what do U.S. clinicians need to know? Clinicians should consider MVD in the differential diagnosis of ill patients with a compatible exposure history and clinical presentation. A detailed exposure history should be obtained to determine if patients have been to an area with an active MVD outbreak during their incubation period (in the past 21 days), had concerning epidemiologic risk factors (for example, presence at funerals, health care facilities, in mines/caves) while in the affected area, and/or had contact with a suspected or confirmed MVD case.

Clinical diagnosis of MVD is challenging as the initial dry symptoms of infection are nonspecific (fever, influenza-like illness, malaise, anorexia, etc.) and can resemble other febrile infectious illnesses. Similarly, presenting alternative or concurrent infections, particularly in febrile return travelers, include malaria, Lassa fever, typhoid, and measles. From these nonspecific symptoms, patients with MVD can then progress to the more severe wet symptoms (for example, vomiting, diarrhea, and bleeding). Common clinical features of MVD have been described based on the clinical presentation and course of cases in MVD outbreaks. Notably, in the original Marburg outbreak, maculopapular rash and conjunctival injection were early patient symptoms and most patient deaths occurred during the second week of illness progression.

Supportive care, including aggressive fluid replacement, is the mainstay of therapy for MVD. Currently, there are no Food and Drug Administration–approved antiviral treatments or vaccines for Marburg virus. Despite their viral similarities, vaccines against Ebola virus have not been shown to be protective against Marburg virus. Marburg virus vaccine development is ongoing, with a few promising candidate vaccines in early phase 1 and 2 clinical trials. In 2022, in response to MVD outbreaks in Ghana and Guinea, the World Health Organization convened an international Marburg virus vaccine consortium which is working to promote global research collaboration for more rapid vaccine development.

In the absence of definitive therapies, early identification of patients with suspected MVD is critical for preventing the spread of infection to close contacts. Like Ebola virus–infected patients, only symptomatic MVD patients are infectious and all patients with suspected MVD should be isolated in a private room and cared for in accordance with infection control procedures. As MVD is a nationally notifiable disease, suspected cases should be reported to local or state health departments as per jurisdictional requirements. Clinicians should also consult with their local or state health department and CDC for guidance on testing patients with suspected MVD and consider prompt evaluation for other infectious etiologies in the patient’s differential diagnosis. Comprehensive guidance for clinicians on screening and diagnosing patients with MVD is available on the CDC website at https://www.cdc.gov/vhf/marburg/index.html.

Dr. Appiah (she/her) is a medical epidemiologist in the division of global migration and quarantine at the CDC. Dr. Appiah holds adjunct faculty appointment in the division of infectious diseases at Emory University, Atlanta. She also holds a commission in the U.S. Public Health Service and is a resident advisor, Uganda, U.S. President’s Malaria Initiative, at the CDC.

An evidence-based analysis of 10 popular dietary patterns shows that some promote heart health better than others.

A new American Heart Association scientific statement concludes that the Mediterranean, Dietary Approach to Stop Hypertension (DASH), pescatarian, and vegetarian eating patterns most strongly align with heart-healthy eating guidelines issued by the AHA in 2021, whereas the popular paleolithic (paleo) and ketogenic (keto) diets fall short.

“The good news for the public and their clinicians is that there are several dietary patterns that allow for substantial flexibility for following a heart healthy diet – DASH, Mediterranean, vegetarian,” writing-group chair Christopher Gardner, PhD, with Stanford (Calif.) University, told this news organization.

Lisovskaya/iStock/Getty Images

A tool for clinicians

“The number of different, popular dietary patterns has proliferated in recent years, and the amount of misinformation about them on social media has reached critical levels,” Dr. Gardner said in a news release.

“The public – and even many health care professionals – may rightfully be confused about heart-healthy eating, and they may feel that they don’t have the time or the training to evaluate the different diets. We hope this statement serves as a tool for clinicians and the public to understand which diets promote good cardiometabolic health,” he noted.

The writing group rated on a scale of 1-100 how well 10 popular diets or eating patterns align with AHA dietary advice for heart-healthy eating.

That advice includes consuming a wide variety of fruits and vegetables; choosing mostly whole grains instead of refined grains; using liquid plant oils rather than tropical oils; eating healthy sources of protein, such as from plants, seafood, or lean meats; minimizing added sugars and salt; limiting alcohol; choosing minimally processed foods instead of ultraprocessed foods; and following this guidance wherever food is prepared or consumed.

The 10 diets/dietary patterns were DASH, Mediterranean-style, pescatarian, ovo-lacto vegetarian, vegan, low-fat, very low–fat, low-carbohydrate, paleo, and very low–carbohydrate/keto patterns.

The diets were divided into four tiers on the basis of their scores, which ranged from a low of 31 to a high of 100.

Only the DASH eating plan got a perfect score of 100. This eating pattern is low in salt, added sugar, tropical oil, alcohol, and processed foods and high in nonstarchy vegetables, fruits, whole grains, and legumes. Proteins are mostly plant-based, such as legumes, beans, or nuts, along with fish or seafood, lean poultry and meats, and low-fat or fat-free dairy products.

The Mediterranean eating pattern achieved a slightly lower score of 89 because unlike DASH, it allows for moderate alcohol consumption and does not address added salt.

The other two top tier eating patterns were pescatarian, with a score of 92, and vegetarian, with a score of 86.

“If implemented as intended, the top-tier dietary patterns align best with the American Heart Association’s guidance and may be adapted to respect cultural practices, food preferences and budgets to enable people to always eat this way, for the long term,” Dr. Gardner said in the release.

Vegan and low-fat diets (each with a score of 78) fell into the second tier.

Though these diets emphasize fruits, vegetables, whole grains, legumes, and nuts while limiting alcohol and added sugars, the vegan diet is so restrictive that it could be challenging to follow long-term or when eating out and may increase the risk for vitamin B12 deficiency, which can lead to anemia, the writing group notes.

There also are concerns that low-fat diets treat all fats equally, whereas the AHA guidance calls for replacing saturated fats with healthier fats, they point out.

The third tier includes the very low–fat diet (score 72) and low-carb diet (score 64), whereas the paleo and very low–carb/keto diets fall into the fourth tier, with the lowest scores of 53 and 31, respectively.

Dr. Gardner said that it’s important to note that all 10 diet patterns “share four positive characteristics: more veggies, more whole foods, less added sugars, less refined grains.”

“These are all areas for which Americans have substantial room for improvement, and these are all things that we could work on together. Progress across these aspects would make a large difference in the heart-healthiness of the U.S. diet,” he told this news organization.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health, the Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, and the Council on Peripheral Vascular Disease.

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

An evidence-based analysis of 10 popular dietary patterns shows that some promote heart health better than others.

A new American Heart Association scientific statement concludes that the Mediterranean, Dietary Approach to Stop Hypertension (DASH), pescatarian, and vegetarian eating patterns most strongly align with heart-healthy eating guidelines issued by the AHA in 2021, whereas the popular paleolithic (paleo) and ketogenic (keto) diets fall short.

“The good news for the public and their clinicians is that there are several dietary patterns that allow for substantial flexibility for following a heart healthy diet – DASH, Mediterranean, vegetarian,” writing-group chair Christopher Gardner, PhD, with Stanford (Calif.) University, told this news organization.

Lisovskaya/iStock/Getty Images

A tool for clinicians

“The number of different, popular dietary patterns has proliferated in recent years, and the amount of misinformation about them on social media has reached critical levels,” Dr. Gardner said in a news release.

“The public – and even many health care professionals – may rightfully be confused about heart-healthy eating, and they may feel that they don’t have the time or the training to evaluate the different diets. We hope this statement serves as a tool for clinicians and the public to understand which diets promote good cardiometabolic health,” he noted.

The writing group rated on a scale of 1-100 how well 10 popular diets or eating patterns align with AHA dietary advice for heart-healthy eating.

That advice includes consuming a wide variety of fruits and vegetables; choosing mostly whole grains instead of refined grains; using liquid plant oils rather than tropical oils; eating healthy sources of protein, such as from plants, seafood, or lean meats; minimizing added sugars and salt; limiting alcohol; choosing minimally processed foods instead of ultraprocessed foods; and following this guidance wherever food is prepared or consumed.

The 10 diets/dietary patterns were DASH, Mediterranean-style, pescatarian, ovo-lacto vegetarian, vegan, low-fat, very low–fat, low-carbohydrate, paleo, and very low–carbohydrate/keto patterns.

The diets were divided into four tiers on the basis of their scores, which ranged from a low of 31 to a high of 100.

Only the DASH eating plan got a perfect score of 100. This eating pattern is low in salt, added sugar, tropical oil, alcohol, and processed foods and high in nonstarchy vegetables, fruits, whole grains, and legumes. Proteins are mostly plant-based, such as legumes, beans, or nuts, along with fish or seafood, lean poultry and meats, and low-fat or fat-free dairy products.

The Mediterranean eating pattern achieved a slightly lower score of 89 because unlike DASH, it allows for moderate alcohol consumption and does not address added salt.

The other two top tier eating patterns were pescatarian, with a score of 92, and vegetarian, with a score of 86.

“If implemented as intended, the top-tier dietary patterns align best with the American Heart Association’s guidance and may be adapted to respect cultural practices, food preferences and budgets to enable people to always eat this way, for the long term,” Dr. Gardner said in the release.

Vegan and low-fat diets (each with a score of 78) fell into the second tier.

Though these diets emphasize fruits, vegetables, whole grains, legumes, and nuts while limiting alcohol and added sugars, the vegan diet is so restrictive that it could be challenging to follow long-term or when eating out and may increase the risk for vitamin B12 deficiency, which can lead to anemia, the writing group notes.

There also are concerns that low-fat diets treat all fats equally, whereas the AHA guidance calls for replacing saturated fats with healthier fats, they point out.

The third tier includes the very low–fat diet (score 72) and low-carb diet (score 64), whereas the paleo and very low–carb/keto diets fall into the fourth tier, with the lowest scores of 53 and 31, respectively.

Dr. Gardner said that it’s important to note that all 10 diet patterns “share four positive characteristics: more veggies, more whole foods, less added sugars, less refined grains.”

“These are all areas for which Americans have substantial room for improvement, and these are all things that we could work on together. Progress across these aspects would make a large difference in the heart-healthiness of the U.S. diet,” he told this news organization.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health, the Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, and the Council on Peripheral Vascular Disease.

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

An evidence-based analysis of 10 popular dietary patterns shows that some promote heart health better than others.

A new American Heart Association scientific statement concludes that the Mediterranean, Dietary Approach to Stop Hypertension (DASH), pescatarian, and vegetarian eating patterns most strongly align with heart-healthy eating guidelines issued by the AHA in 2021, whereas the popular paleolithic (paleo) and ketogenic (keto) diets fall short.

“The good news for the public and their clinicians is that there are several dietary patterns that allow for substantial flexibility for following a heart healthy diet – DASH, Mediterranean, vegetarian,” writing-group chair Christopher Gardner, PhD, with Stanford (Calif.) University, told this news organization.

Lisovskaya/iStock/Getty Images

A tool for clinicians

“The number of different, popular dietary patterns has proliferated in recent years, and the amount of misinformation about them on social media has reached critical levels,” Dr. Gardner said in a news release.

“The public – and even many health care professionals – may rightfully be confused about heart-healthy eating, and they may feel that they don’t have the time or the training to evaluate the different diets. We hope this statement serves as a tool for clinicians and the public to understand which diets promote good cardiometabolic health,” he noted.

The writing group rated on a scale of 1-100 how well 10 popular diets or eating patterns align with AHA dietary advice for heart-healthy eating.

That advice includes consuming a wide variety of fruits and vegetables; choosing mostly whole grains instead of refined grains; using liquid plant oils rather than tropical oils; eating healthy sources of protein, such as from plants, seafood, or lean meats; minimizing added sugars and salt; limiting alcohol; choosing minimally processed foods instead of ultraprocessed foods; and following this guidance wherever food is prepared or consumed.

The 10 diets/dietary patterns were DASH, Mediterranean-style, pescatarian, ovo-lacto vegetarian, vegan, low-fat, very low–fat, low-carbohydrate, paleo, and very low–carbohydrate/keto patterns.

The diets were divided into four tiers on the basis of their scores, which ranged from a low of 31 to a high of 100.

Only the DASH eating plan got a perfect score of 100. This eating pattern is low in salt, added sugar, tropical oil, alcohol, and processed foods and high in nonstarchy vegetables, fruits, whole grains, and legumes. Proteins are mostly plant-based, such as legumes, beans, or nuts, along with fish or seafood, lean poultry and meats, and low-fat or fat-free dairy products.

The Mediterranean eating pattern achieved a slightly lower score of 89 because unlike DASH, it allows for moderate alcohol consumption and does not address added salt.

The other two top tier eating patterns were pescatarian, with a score of 92, and vegetarian, with a score of 86.

“If implemented as intended, the top-tier dietary patterns align best with the American Heart Association’s guidance and may be adapted to respect cultural practices, food preferences and budgets to enable people to always eat this way, for the long term,” Dr. Gardner said in the release.

Vegan and low-fat diets (each with a score of 78) fell into the second tier.

Though these diets emphasize fruits, vegetables, whole grains, legumes, and nuts while limiting alcohol and added sugars, the vegan diet is so restrictive that it could be challenging to follow long-term or when eating out and may increase the risk for vitamin B12 deficiency, which can lead to anemia, the writing group notes.

There also are concerns that low-fat diets treat all fats equally, whereas the AHA guidance calls for replacing saturated fats with healthier fats, they point out.

The third tier includes the very low–fat diet (score 72) and low-carb diet (score 64), whereas the paleo and very low–carb/keto diets fall into the fourth tier, with the lowest scores of 53 and 31, respectively.

Dr. Gardner said that it’s important to note that all 10 diet patterns “share four positive characteristics: more veggies, more whole foods, less added sugars, less refined grains.”

“These are all areas for which Americans have substantial room for improvement, and these are all things that we could work on together. Progress across these aspects would make a large difference in the heart-healthiness of the U.S. diet,” he told this news organization.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Lifestyle and Cardiometabolic Health, the Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, and the Council on Peripheral Vascular Disease.

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

SAN DIEGO – For patients with obesity, surgery, lifestyle changes, and pharmacologic interventions are all treatment options, but antiobesity medications provide a better risk-to-benefit ratio, according to a presenter at the annual meeting of the American College of Physicians.

Lifestyle changes result in the least weight loss and may be safest, while surgery provides the most weight loss and has the greatest risk. Antiobesity medications, especially the newer ones used in combination with lifestyle changes, can provide significant and sustained weight loss with manageable side effects, said Daniel Bessesen, MD, a professor in the endocrinology, diabetes, and metabolism at University of Colorado at Denver, Aurora.

New and more effective antiobesity medications have given internists more potential options to discuss with their patients, Dr. Bessesen said. He reviewed the pros and cons of the different options.

Medications are indicated for patients with a body mass index greater than 30, including those with a weight-related comorbidity, Dr. Bessesen said. The average weight loss is 5%-15% over 3-6 months but may vary greatly. Insurance often does not cover the medication costs.
 

Older FDA-approved antiobesity medications

Phentermine is the most widely prescribed antiobesity medication, partly because it is the only option most people can afford out of pocket. Dr. Bessesen presented recent data showing that long-term use of phentermine was associated with greater weight loss and that patients continuously taking phentermine for 24 months lost 7.5% of their weight.

Phentermine suppresses appetite by increasing norepinephrine production. Dr. Bessesen warned that internists should be careful when prescribing it to patients with mental conditions, because it acts as a stimulant. Early studies raised concerns about the risk of cardiovascular disease (CVD) in patients taking phentermine. However, analysis of data from over 13,000 individuals showed no evidence of a relationship between phentermine exposure and CVD events.

“These data provide some reassurance that it could be used in patients with CVD risk,” he noted. Phentermine can also be combined with topiramate extended release, a combination that provides greater efficacy (up to 10% weight loss) with fewer side effects. However, this combination is less effective in patients with diabetes than in those without.

Additional treatment options included orlistat and naltrexone sustained release/bupropion SR. Orlistat is a good treatment alternative for patients with constipation and is the safest option among older anti-obesity medications, whereas naltrexone SR/bupropion SR may be useful in patients with food cravings. However, there is more variability in the individual-level benefit from these agents compared to phentermine and phentermine/topiramate ER, Dr. Bessesen said.
 

Newer anti‐obesity medications

Liraglutide, an agent used for the management of type 2 diabetes, has recently been approved for weight loss. Liraglutide causes moderate weight loss, and it may reduce the risk of CVD. However, there are tolerability issues, such as nausea and other risks, and Dr. Bessesen advises internists to “start at low doses and increase slowly.”

Semaglutide is the newest and most effective antiobesity drug approved by the Food and Drug Administration, providing sustained weight loss of 8% for up to 48 weeks after starting treatment. Although its efficacy is lower in patients with diabetes, Dr. Bessesen noted that “this is common for antiobesity agents, and clinicians should not refrain from prescribing it in this population.”

Setmelanotide is another new medication approved for chronic weight management in patients with monogenic obesity. This medication can be considered for patients with early-onset severe obesity with abnormal feeding behavior.

Commenting on barriers to access to new antiobesity medications, Dr. Bessesen said that “the high cost of these medications is a substantial problem, but as more companies become involved and products are on the market for a longer period of time, I am hopeful that prices will come down.”
 

Emerging antiobesity medications

Dr. Bessesen presented recent phase 3 data showing that treatment with tirzepatide provided sustained chronic loss and improved cardiometabolic measures with no diet. Tirzepatide, which targets receptors for glucagonlike peptide–1 and glucose-dependent insulinotropic polypeptide, is used for the management of type 2 diabetes and is expected to be reviewed soon by the FDA for its use in weight management.

A semaglutide/cagrilintide combination may also provide a new treatment option for patients with obesity. In a phase 1b trial, semaglutide/cagrilintide treatment resulted in up to 17% weight loss in patients with obesity who were otherwise healthy; however, phase 2 and 3 data are needed to confirm its efficacy.
 

A ‘holistic approach’

When deciding whether to prescribe antiobesity medications, Dr. Bessesen noted that medications are better than exercise alone. Factors to consider when deciding whether to prescribe drugs, as well as which ones, include costs, local regulatory guidelines, requirement for long-term use, and patient comorbidities.

He also stated that lifestyle changes, such as adopting healthy nutrition and exercising regularly, are also important and can enhance weight loss when combined with medications.

Richele Corrado, DO, MPH, agreed that lifestyle management in combination with medications may provide greater weight loss than each of these interventions alone.

“If you look at the data, exercise doesn’t help you lose much weight,” said Dr. Corrado, a staff internist and obesity medicine specialist at Walter Reed National Military Medical Center in Bethesda, Md., who spoke at the same session. She added that she has many patients who struggle to lose weight despite having a healthy lifestyle. “It’s important to discuss with these patients about medications and surgery.”

Dr. Bessesen noted that management of mental health and emotional well-being should also be an integral part of obesity management. “Treatment for obesity may be more successful when underlying psychological conditions such as depression, childhood sexual trauma, or anxiety are addressed and treated,” he said.

Dr. Bessesen was involved in the study of the efficacy of semaglutide/cagrilintide. He does not have any financial conflicts with the companies that make other mentioned medications. He has received research grants or contracts from Novo Nordisk, honoraria from Novo Nordisk, and consultantship from Eli Lilly. Dr. Corrado reported no relevant financial conflicts.

SAN DIEGO – For patients with obesity, surgery, lifestyle changes, and pharmacologic interventions are all treatment options, but antiobesity medications provide a better risk-to-benefit ratio, according to a presenter at the annual meeting of the American College of Physicians.

Lifestyle changes result in the least weight loss and may be safest, while surgery provides the most weight loss and has the greatest risk. Antiobesity medications, especially the newer ones used in combination with lifestyle changes, can provide significant and sustained weight loss with manageable side effects, said Daniel Bessesen, MD, a professor in the endocrinology, diabetes, and metabolism at University of Colorado at Denver, Aurora.

New and more effective antiobesity medications have given internists more potential options to discuss with their patients, Dr. Bessesen said. He reviewed the pros and cons of the different options.

Medications are indicated for patients with a body mass index greater than 30, including those with a weight-related comorbidity, Dr. Bessesen said. The average weight loss is 5%-15% over 3-6 months but may vary greatly. Insurance often does not cover the medication costs.
 

Older FDA-approved antiobesity medications

Phentermine is the most widely prescribed antiobesity medication, partly because it is the only option most people can afford out of pocket. Dr. Bessesen presented recent data showing that long-term use of phentermine was associated with greater weight loss and that patients continuously taking phentermine for 24 months lost 7.5% of their weight.

Phentermine suppresses appetite by increasing norepinephrine production. Dr. Bessesen warned that internists should be careful when prescribing it to patients with mental conditions, because it acts as a stimulant. Early studies raised concerns about the risk of cardiovascular disease (CVD) in patients taking phentermine. However, analysis of data from over 13,000 individuals showed no evidence of a relationship between phentermine exposure and CVD events.

“These data provide some reassurance that it could be used in patients with CVD risk,” he noted. Phentermine can also be combined with topiramate extended release, a combination that provides greater efficacy (up to 10% weight loss) with fewer side effects. However, this combination is less effective in patients with diabetes than in those without.

Additional treatment options included orlistat and naltrexone sustained release/bupropion SR. Orlistat is a good treatment alternative for patients with constipation and is the safest option among older anti-obesity medications, whereas naltrexone SR/bupropion SR may be useful in patients with food cravings. However, there is more variability in the individual-level benefit from these agents compared to phentermine and phentermine/topiramate ER, Dr. Bessesen said.
 

Newer anti‐obesity medications

Liraglutide, an agent used for the management of type 2 diabetes, has recently been approved for weight loss. Liraglutide causes moderate weight loss, and it may reduce the risk of CVD. However, there are tolerability issues, such as nausea and other risks, and Dr. Bessesen advises internists to “start at low doses and increase slowly.”

Semaglutide is the newest and most effective antiobesity drug approved by the Food and Drug Administration, providing sustained weight loss of 8% for up to 48 weeks after starting treatment. Although its efficacy is lower in patients with diabetes, Dr. Bessesen noted that “this is common for antiobesity agents, and clinicians should not refrain from prescribing it in this population.”

Setmelanotide is another new medication approved for chronic weight management in patients with monogenic obesity. This medication can be considered for patients with early-onset severe obesity with abnormal feeding behavior.

Commenting on barriers to access to new antiobesity medications, Dr. Bessesen said that “the high cost of these medications is a substantial problem, but as more companies become involved and products are on the market for a longer period of time, I am hopeful that prices will come down.”
 

Emerging antiobesity medications

Dr. Bessesen presented recent phase 3 data showing that treatment with tirzepatide provided sustained chronic loss and improved cardiometabolic measures with no diet. Tirzepatide, which targets receptors for glucagonlike peptide–1 and glucose-dependent insulinotropic polypeptide, is used for the management of type 2 diabetes and is expected to be reviewed soon by the FDA for its use in weight management.

A semaglutide/cagrilintide combination may also provide a new treatment option for patients with obesity. In a phase 1b trial, semaglutide/cagrilintide treatment resulted in up to 17% weight loss in patients with obesity who were otherwise healthy; however, phase 2 and 3 data are needed to confirm its efficacy.
 

A ‘holistic approach’

When deciding whether to prescribe antiobesity medications, Dr. Bessesen noted that medications are better than exercise alone. Factors to consider when deciding whether to prescribe drugs, as well as which ones, include costs, local regulatory guidelines, requirement for long-term use, and patient comorbidities.

He also stated that lifestyle changes, such as adopting healthy nutrition and exercising regularly, are also important and can enhance weight loss when combined with medications.

Richele Corrado, DO, MPH, agreed that lifestyle management in combination with medications may provide greater weight loss than each of these interventions alone.

“If you look at the data, exercise doesn’t help you lose much weight,” said Dr. Corrado, a staff internist and obesity medicine specialist at Walter Reed National Military Medical Center in Bethesda, Md., who spoke at the same session. She added that she has many patients who struggle to lose weight despite having a healthy lifestyle. “It’s important to discuss with these patients about medications and surgery.”

Dr. Bessesen noted that management of mental health and emotional well-being should also be an integral part of obesity management. “Treatment for obesity may be more successful when underlying psychological conditions such as depression, childhood sexual trauma, or anxiety are addressed and treated,” he said.

Dr. Bessesen was involved in the study of the efficacy of semaglutide/cagrilintide. He does not have any financial conflicts with the companies that make other mentioned medications. He has received research grants or contracts from Novo Nordisk, honoraria from Novo Nordisk, and consultantship from Eli Lilly. Dr. Corrado reported no relevant financial conflicts.

SAN DIEGO – For patients with obesity, surgery, lifestyle changes, and pharmacologic interventions are all treatment options, but antiobesity medications provide a better risk-to-benefit ratio, according to a presenter at the annual meeting of the American College of Physicians.

Lifestyle changes result in the least weight loss and may be safest, while surgery provides the most weight loss and has the greatest risk. Antiobesity medications, especially the newer ones used in combination with lifestyle changes, can provide significant and sustained weight loss with manageable side effects, said Daniel Bessesen, MD, a professor in the endocrinology, diabetes, and metabolism at University of Colorado at Denver, Aurora.

New and more effective antiobesity medications have given internists more potential options to discuss with their patients, Dr. Bessesen said. He reviewed the pros and cons of the different options.

Medications are indicated for patients with a body mass index greater than 30, including those with a weight-related comorbidity, Dr. Bessesen said. The average weight loss is 5%-15% over 3-6 months but may vary greatly. Insurance often does not cover the medication costs.
 

Older FDA-approved antiobesity medications

Phentermine is the most widely prescribed antiobesity medication, partly because it is the only option most people can afford out of pocket. Dr. Bessesen presented recent data showing that long-term use of phentermine was associated with greater weight loss and that patients continuously taking phentermine for 24 months lost 7.5% of their weight.

Phentermine suppresses appetite by increasing norepinephrine production. Dr. Bessesen warned that internists should be careful when prescribing it to patients with mental conditions, because it acts as a stimulant. Early studies raised concerns about the risk of cardiovascular disease (CVD) in patients taking phentermine. However, analysis of data from over 13,000 individuals showed no evidence of a relationship between phentermine exposure and CVD events.

“These data provide some reassurance that it could be used in patients with CVD risk,” he noted. Phentermine can also be combined with topiramate extended release, a combination that provides greater efficacy (up to 10% weight loss) with fewer side effects. However, this combination is less effective in patients with diabetes than in those without.

Additional treatment options included orlistat and naltrexone sustained release/bupropion SR. Orlistat is a good treatment alternative for patients with constipation and is the safest option among older anti-obesity medications, whereas naltrexone SR/bupropion SR may be useful in patients with food cravings. However, there is more variability in the individual-level benefit from these agents compared to phentermine and phentermine/topiramate ER, Dr. Bessesen said.
 

Newer anti‐obesity medications

Liraglutide, an agent used for the management of type 2 diabetes, has recently been approved for weight loss. Liraglutide causes moderate weight loss, and it may reduce the risk of CVD. However, there are tolerability issues, such as nausea and other risks, and Dr. Bessesen advises internists to “start at low doses and increase slowly.”

Semaglutide is the newest and most effective antiobesity drug approved by the Food and Drug Administration, providing sustained weight loss of 8% for up to 48 weeks after starting treatment. Although its efficacy is lower in patients with diabetes, Dr. Bessesen noted that “this is common for antiobesity agents, and clinicians should not refrain from prescribing it in this population.”

Setmelanotide is another new medication approved for chronic weight management in patients with monogenic obesity. This medication can be considered for patients with early-onset severe obesity with abnormal feeding behavior.

Commenting on barriers to access to new antiobesity medications, Dr. Bessesen said that “the high cost of these medications is a substantial problem, but as more companies become involved and products are on the market for a longer period of time, I am hopeful that prices will come down.”
 

Emerging antiobesity medications

Dr. Bessesen presented recent phase 3 data showing that treatment with tirzepatide provided sustained chronic loss and improved cardiometabolic measures with no diet. Tirzepatide, which targets receptors for glucagonlike peptide–1 and glucose-dependent insulinotropic polypeptide, is used for the management of type 2 diabetes and is expected to be reviewed soon by the FDA for its use in weight management.

A semaglutide/cagrilintide combination may also provide a new treatment option for patients with obesity. In a phase 1b trial, semaglutide/cagrilintide treatment resulted in up to 17% weight loss in patients with obesity who were otherwise healthy; however, phase 2 and 3 data are needed to confirm its efficacy.
 

A ‘holistic approach’

When deciding whether to prescribe antiobesity medications, Dr. Bessesen noted that medications are better than exercise alone. Factors to consider when deciding whether to prescribe drugs, as well as which ones, include costs, local regulatory guidelines, requirement for long-term use, and patient comorbidities.

He also stated that lifestyle changes, such as adopting healthy nutrition and exercising regularly, are also important and can enhance weight loss when combined with medications.

Richele Corrado, DO, MPH, agreed that lifestyle management in combination with medications may provide greater weight loss than each of these interventions alone.

“If you look at the data, exercise doesn’t help you lose much weight,” said Dr. Corrado, a staff internist and obesity medicine specialist at Walter Reed National Military Medical Center in Bethesda, Md., who spoke at the same session. She added that she has many patients who struggle to lose weight despite having a healthy lifestyle. “It’s important to discuss with these patients about medications and surgery.”

Dr. Bessesen noted that management of mental health and emotional well-being should also be an integral part of obesity management. “Treatment for obesity may be more successful when underlying psychological conditions such as depression, childhood sexual trauma, or anxiety are addressed and treated,” he said.

Dr. Bessesen was involved in the study of the efficacy of semaglutide/cagrilintide. He does not have any financial conflicts with the companies that make other mentioned medications. He has received research grants or contracts from Novo Nordisk, honoraria from Novo Nordisk, and consultantship from Eli Lilly. Dr. Corrado reported no relevant financial conflicts.