MDedge Infectious Disease

TOPLINE:

The COVID-19 booster vaccine typically causes transient, clinically insignificant elevations in glucose levels in people with type 1 diabetes, but some individuals may develop more pronounced hyperglycemia.

METHODOLOGY:

• In a single-center prospective cohort study of 21 adults with type 1 diabetes, patients were given a blinded Dexcom G6 Pro continuous glucose monitor (CGM) at the first research clinic visit.
• After 3-4 days, participants received a COVID-19 booster vaccine.
• They returned to the clinic 10 days after the initial visit (5-6 days after booster vaccination) to have the CGM removed and glycemia assessed.

TAKEAWAY:

• Compared with baseline, the mean daily glucose level was significantly increased at day 2 (162.9 mg/dL vs. 172.8 mg/dL; P = .04) and day 3 (173.1 mg/dL; P = .02) post vaccination.
• Glucose excursions at day 0 (173.2 mg/dL; P = .058) and day 1 (173.1 mg/dL; P = .078) didn’t quite reach statistical significance.
• One participant experienced increases in glucose of 36%, 69%, 35%, 26%, 22%, and 19% on days 0-5, respectively, compared with baseline.
• Glucose excursions of at least 25% above baseline occurred in four participants on day 0 and day 1 and in three participants on days 2 and 5.
• Insulin resistance, as measured by Total Daily Insulin Resistance (a metric that integrates daily mean glucose concentration with total daily insulin dose), was also significantly increased from baseline to day 2 post vaccination (7,171 mg/dL vs. 8,070 mg/dL units; P = .03).
• No other measures of glycemia differed significantly, compared with baseline.
• Outcomes didn’t differ significantly by sex, age, or vaccine manufacturer.

IN PRACTICE:

• “To our knowledge this is the first study investigating the effect of the COVID-19 booster vaccine on glycemia specifically in people with type 1 diabetes,” say the authors.
• “Clinicians, pharmacists, and other health care providers may need to counsel people with T1D to be more vigilant with glucose testing and insulin dosing for the first 5 days after vaccination. Most importantly, insulin, required to control glycemia, may need to be transiently increased.”
• “Further studies are warranted to investigate whether other vaccines have similar glycemic effects, and which individuals are at highest risk for profound glucose perturbations post vaccination.”

SOURCE:

The study was conducted by Mihail Zilbermint, MD, of the division of hospital medicine, Johns Hopkins Medicine, Bethesda, Md., and colleagues. It was published in Diabetes Research and Clinical Practice.

LIMITATIONS:

• The sample size was small.
• There were no measurements of inflammatory markers, dietary intake, physical activity, or survey patient symptomatology to adjust for variables that may have influenced glycemic control.
• In the study cohort, glycemia was moderately well controlled at baseline.

DISCLOSURES:

The study was supported by an investigator-initiated study grant from DexCom Inc. Dr. Zilbermint has consulted for EMD Serono.

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

TOPLINE:

The COVID-19 booster vaccine typically causes transient, clinically insignificant elevations in glucose levels in people with type 1 diabetes, but some individuals may develop more pronounced hyperglycemia.

METHODOLOGY:

• In a single-center prospective cohort study of 21 adults with type 1 diabetes, patients were given a blinded Dexcom G6 Pro continuous glucose monitor (CGM) at the first research clinic visit.
• After 3-4 days, participants received a COVID-19 booster vaccine.
• They returned to the clinic 10 days after the initial visit (5-6 days after booster vaccination) to have the CGM removed and glycemia assessed.

TAKEAWAY:

• Compared with baseline, the mean daily glucose level was significantly increased at day 2 (162.9 mg/dL vs. 172.8 mg/dL; P = .04) and day 3 (173.1 mg/dL; P = .02) post vaccination.
• Glucose excursions at day 0 (173.2 mg/dL; P = .058) and day 1 (173.1 mg/dL; P = .078) didn’t quite reach statistical significance.
• One participant experienced increases in glucose of 36%, 69%, 35%, 26%, 22%, and 19% on days 0-5, respectively, compared with baseline.
• Glucose excursions of at least 25% above baseline occurred in four participants on day 0 and day 1 and in three participants on days 2 and 5.
• Insulin resistance, as measured by Total Daily Insulin Resistance (a metric that integrates daily mean glucose concentration with total daily insulin dose), was also significantly increased from baseline to day 2 post vaccination (7,171 mg/dL vs. 8,070 mg/dL units; P = .03).
• No other measures of glycemia differed significantly, compared with baseline.
• Outcomes didn’t differ significantly by sex, age, or vaccine manufacturer.

IN PRACTICE:

• “To our knowledge this is the first study investigating the effect of the COVID-19 booster vaccine on glycemia specifically in people with type 1 diabetes,” say the authors.
• “Clinicians, pharmacists, and other health care providers may need to counsel people with T1D to be more vigilant with glucose testing and insulin dosing for the first 5 days after vaccination. Most importantly, insulin, required to control glycemia, may need to be transiently increased.”
• “Further studies are warranted to investigate whether other vaccines have similar glycemic effects, and which individuals are at highest risk for profound glucose perturbations post vaccination.”

SOURCE:

The study was conducted by Mihail Zilbermint, MD, of the division of hospital medicine, Johns Hopkins Medicine, Bethesda, Md., and colleagues. It was published in Diabetes Research and Clinical Practice.

LIMITATIONS:

• The sample size was small.
• There were no measurements of inflammatory markers, dietary intake, physical activity, or survey patient symptomatology to adjust for variables that may have influenced glycemic control.
• In the study cohort, glycemia was moderately well controlled at baseline.

DISCLOSURES:

The study was supported by an investigator-initiated study grant from DexCom Inc. Dr. Zilbermint has consulted for EMD Serono.

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

TOPLINE:

The COVID-19 booster vaccine typically causes transient, clinically insignificant elevations in glucose levels in people with type 1 diabetes, but some individuals may develop more pronounced hyperglycemia.

METHODOLOGY:

• In a single-center prospective cohort study of 21 adults with type 1 diabetes, patients were given a blinded Dexcom G6 Pro continuous glucose monitor (CGM) at the first research clinic visit.
• After 3-4 days, participants received a COVID-19 booster vaccine.
• They returned to the clinic 10 days after the initial visit (5-6 days after booster vaccination) to have the CGM removed and glycemia assessed.

TAKEAWAY:

• Compared with baseline, the mean daily glucose level was significantly increased at day 2 (162.9 mg/dL vs. 172.8 mg/dL; P = .04) and day 3 (173.1 mg/dL; P = .02) post vaccination.
• Glucose excursions at day 0 (173.2 mg/dL; P = .058) and day 1 (173.1 mg/dL; P = .078) didn’t quite reach statistical significance.
• One participant experienced increases in glucose of 36%, 69%, 35%, 26%, 22%, and 19% on days 0-5, respectively, compared with baseline.
• Glucose excursions of at least 25% above baseline occurred in four participants on day 0 and day 1 and in three participants on days 2 and 5.
• Insulin resistance, as measured by Total Daily Insulin Resistance (a metric that integrates daily mean glucose concentration with total daily insulin dose), was also significantly increased from baseline to day 2 post vaccination (7,171 mg/dL vs. 8,070 mg/dL units; P = .03).
• No other measures of glycemia differed significantly, compared with baseline.
• Outcomes didn’t differ significantly by sex, age, or vaccine manufacturer.

IN PRACTICE:

• “To our knowledge this is the first study investigating the effect of the COVID-19 booster vaccine on glycemia specifically in people with type 1 diabetes,” say the authors.
• “Clinicians, pharmacists, and other health care providers may need to counsel people with T1D to be more vigilant with glucose testing and insulin dosing for the first 5 days after vaccination. Most importantly, insulin, required to control glycemia, may need to be transiently increased.”
• “Further studies are warranted to investigate whether other vaccines have similar glycemic effects, and which individuals are at highest risk for profound glucose perturbations post vaccination.”

SOURCE:

The study was conducted by Mihail Zilbermint, MD, of the division of hospital medicine, Johns Hopkins Medicine, Bethesda, Md., and colleagues. It was published in Diabetes Research and Clinical Practice.

LIMITATIONS:

• The sample size was small.
• There were no measurements of inflammatory markers, dietary intake, physical activity, or survey patient symptomatology to adjust for variables that may have influenced glycemic control.
• In the study cohort, glycemia was moderately well controlled at baseline.

DISCLOSURES:

The study was supported by an investigator-initiated study grant from DexCom Inc. Dr. Zilbermint has consulted for EMD Serono.

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

A new meta-analysis has shown that SGLT2 inhibitors do not lead to lower 28-day all-cause mortality, compared with usual care or placebo, in patients hospitalized with COVID-19.

However, no major safety issues were identified with the use of SGLT2 inhibitors in these acutely ill patients, the researchers report.

“While these findings do not support the use of SGLT2-inhibitors as standard of care for patients hospitalized with COVID-19, I think the most important take home message here is that the use of these medications appears to be safe even in really acutely ill hospitalized patients,” lead investigator of the meta-analysis, Mikhail Kosiborod, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., concluded.

He said this was important because the list of indications for SGLT2 inhibitors is rapidly growing.

“These medications are being used in more and more patients. And we know that when we discontinue medications in the hospital they frequently don’t get restarted, which can lead to real risks if SGLT2 inhibitors are stopped in patients with heart failure, chronic kidney disease, or diabetes. So, the bottom line is that there is no compelling reason to stop these medications in the hospital,” he added.

The new meta-analysis was presented at the recent annual congress of the European Society of Cardiology, held in Amsterdam.

Discussant of the presentation at the ESC Hotline session, Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital, Boston, agreed with Dr. Kosiborod’s interpretation.

“Until today we have had very limited information on the safety of SGLT2-inhibitors in acute illness, as the pivotal trials which established the use of these drugs in diabetes and chronic kidney disease largely excluded patients who were hospitalized,” Dr. Vaduganathan said.

“While the overall results of this meta-analysis are neutral and SGLT2 inhibitors will not be added as drugs to be used in the primary care of patients with COVID-19, it certainly sends a strong message of safety in acutely ill patients,” he added.

Dr. Vaduganathan explained that from the beginning of the COVID-19 pandemic, there was great interest in repurposing established therapies for alternative indications for their use in the management of COVID-19.

“Conditions that strongly predispose to adverse COVID outcomes strongly overlap with established indications for SGLT2-inhibitors. So many wondered whether these drugs may be an ideal treatment candidate for the management of COVID-19. However, there have been many safety concerns about the use of SGLT2-inhibitors in this acute setting, with worries that they may induce hemodynamic changes such an excessive lowering of blood pressure, or metabolic changes such as ketoacidosis in acutely ill patients,” he noted.

The initial DARE-19 study investigating SGLT2-inhibitors in COVID-19, with 1,250 participants, found a 20% reduction in the primary outcome of organ dysfunction or death, but this did not reach statistical significance, and no safety issues were seen. This “intriguing” result led to two further larger trials – the ACTIV-4a and RECOVERY trials, Dr. Vaduganathan reported.

“Those early signals of benefit seen in DARE-19 were largely not substantiated in the ACTIV-4A and RECOVERY trials, or in this new meta-analysis, and now we have this much larger body of evidence and more stable estimates about the efficacy of these drugs in acutely ill COVID-19 patients,” he said.

“But the story that we will all take forward is one of safety. This set of trials was arguably conducted in some of the sickest patients we’ve seen who have been exposed to SGLT2-inhibitors, and they strongly affirm that these agents can be safely continued in the setting of acute illness, with very low rates of ketoacidosis and kidney injury, and there was no prolongation of hospital stay,” he commented.

In his presentation, Dr. Kosiborod explained that treatments targeting COVID-19 pathobiology such as dysregulated immune responses, endothelial damage, microvascular thrombosis, and inflammation have been shown to improve the key outcomes in this patient group.

SGLT2 inhibitors, which modulate similar pathobiology, provide cardiovascular protection and prevent the progression of kidney disease in patients at risk for these events, including those with type 2 diabetes, heart failure, and kidney disease, and may also lead to organ protection in a setting of acute illness such as COVID-19, he noted. However, the role of SGLT2 inhibitors in patients hospitalized with COVID-19 remains uncertain.

To address the need for more definitive efficacy data, the World Health Organization Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group conducted a prospective meta-analysis using data from the three randomized controlled trials, DARE-19, RECOVERY, and ACTIV-4a, evaluating SGLT2 inhibitors in patients hospitalized with COVID-19.

Overall, these trials randomized 6,096 participants: 3,025 to SGLT2 inhibitors and 3,071 to usual care or placebo. The average age of participants ranged between 62 and 73 years across the trials, 39% were women, and 25% had type 2 diabetes.

By 28 days after randomization, all-cause mortality, the primary endpoint, had occurred in 11.6% of the SGLT2-inhibitor patients, compared with 12.4% of those randomized to usual care or placebo, giving an odds ratio of 0.93 (95% confidence interval, 0.79-1.08; P = .33) for SGLT2 inhibitors, with consistency across trials.

Data on in-hospital and 90-day all-cause mortality were only available for two out of three trials (DARE-19 and ACTIV-4a), but the results were similar to the primary endpoint showing nonsignificant trends toward a possible benefit in the SGLT2-inhibitor group.

The results were also similar for the secondary outcomes of progression to acute kidney injury or requirement for dialysis or death, and progression to invasive mechanical ventilation, extracorporeal membrane oxygenation, or death, both assessed at 28 days.

The primary safety outcome of ketoacidosis by 28 days was observed in seven and two patients allocated to SGLT2 inhibitors and usual care or placebo, respectively, and overall, the incidence of reported serious adverse events was balanced between treatment groups.

The RECOVERY trial was supported by grants to the University of Oxford from UK Research and Innovation, the National Institute for Health and Care Research, and Wellcome. The ACTIV-4a platform was sponsored by the National Heart, Lung, and Blood Institute. DARE-19 was an investigator-initiated collaborative trial supported by AstraZeneca. Dr. Kosiborod reported numerous conflicts of interest.

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

A new meta-analysis has shown that SGLT2 inhibitors do not lead to lower 28-day all-cause mortality, compared with usual care or placebo, in patients hospitalized with COVID-19.

However, no major safety issues were identified with the use of SGLT2 inhibitors in these acutely ill patients, the researchers report.

“While these findings do not support the use of SGLT2-inhibitors as standard of care for patients hospitalized with COVID-19, I think the most important take home message here is that the use of these medications appears to be safe even in really acutely ill hospitalized patients,” lead investigator of the meta-analysis, Mikhail Kosiborod, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., concluded.

He said this was important because the list of indications for SGLT2 inhibitors is rapidly growing.

“These medications are being used in more and more patients. And we know that when we discontinue medications in the hospital they frequently don’t get restarted, which can lead to real risks if SGLT2 inhibitors are stopped in patients with heart failure, chronic kidney disease, or diabetes. So, the bottom line is that there is no compelling reason to stop these medications in the hospital,” he added.

The new meta-analysis was presented at the recent annual congress of the European Society of Cardiology, held in Amsterdam.

Discussant of the presentation at the ESC Hotline session, Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital, Boston, agreed with Dr. Kosiborod’s interpretation.

“Until today we have had very limited information on the safety of SGLT2-inhibitors in acute illness, as the pivotal trials which established the use of these drugs in diabetes and chronic kidney disease largely excluded patients who were hospitalized,” Dr. Vaduganathan said.

“While the overall results of this meta-analysis are neutral and SGLT2 inhibitors will not be added as drugs to be used in the primary care of patients with COVID-19, it certainly sends a strong message of safety in acutely ill patients,” he added.

Dr. Vaduganathan explained that from the beginning of the COVID-19 pandemic, there was great interest in repurposing established therapies for alternative indications for their use in the management of COVID-19.

“Conditions that strongly predispose to adverse COVID outcomes strongly overlap with established indications for SGLT2-inhibitors. So many wondered whether these drugs may be an ideal treatment candidate for the management of COVID-19. However, there have been many safety concerns about the use of SGLT2-inhibitors in this acute setting, with worries that they may induce hemodynamic changes such an excessive lowering of blood pressure, or metabolic changes such as ketoacidosis in acutely ill patients,” he noted.

The initial DARE-19 study investigating SGLT2-inhibitors in COVID-19, with 1,250 participants, found a 20% reduction in the primary outcome of organ dysfunction or death, but this did not reach statistical significance, and no safety issues were seen. This “intriguing” result led to two further larger trials – the ACTIV-4a and RECOVERY trials, Dr. Vaduganathan reported.

“Those early signals of benefit seen in DARE-19 were largely not substantiated in the ACTIV-4A and RECOVERY trials, or in this new meta-analysis, and now we have this much larger body of evidence and more stable estimates about the efficacy of these drugs in acutely ill COVID-19 patients,” he said.

“But the story that we will all take forward is one of safety. This set of trials was arguably conducted in some of the sickest patients we’ve seen who have been exposed to SGLT2-inhibitors, and they strongly affirm that these agents can be safely continued in the setting of acute illness, with very low rates of ketoacidosis and kidney injury, and there was no prolongation of hospital stay,” he commented.

In his presentation, Dr. Kosiborod explained that treatments targeting COVID-19 pathobiology such as dysregulated immune responses, endothelial damage, microvascular thrombosis, and inflammation have been shown to improve the key outcomes in this patient group.

SGLT2 inhibitors, which modulate similar pathobiology, provide cardiovascular protection and prevent the progression of kidney disease in patients at risk for these events, including those with type 2 diabetes, heart failure, and kidney disease, and may also lead to organ protection in a setting of acute illness such as COVID-19, he noted. However, the role of SGLT2 inhibitors in patients hospitalized with COVID-19 remains uncertain.

To address the need for more definitive efficacy data, the World Health Organization Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group conducted a prospective meta-analysis using data from the three randomized controlled trials, DARE-19, RECOVERY, and ACTIV-4a, evaluating SGLT2 inhibitors in patients hospitalized with COVID-19.

Overall, these trials randomized 6,096 participants: 3,025 to SGLT2 inhibitors and 3,071 to usual care or placebo. The average age of participants ranged between 62 and 73 years across the trials, 39% were women, and 25% had type 2 diabetes.

By 28 days after randomization, all-cause mortality, the primary endpoint, had occurred in 11.6% of the SGLT2-inhibitor patients, compared with 12.4% of those randomized to usual care or placebo, giving an odds ratio of 0.93 (95% confidence interval, 0.79-1.08; P = .33) for SGLT2 inhibitors, with consistency across trials.

Data on in-hospital and 90-day all-cause mortality were only available for two out of three trials (DARE-19 and ACTIV-4a), but the results were similar to the primary endpoint showing nonsignificant trends toward a possible benefit in the SGLT2-inhibitor group.

The results were also similar for the secondary outcomes of progression to acute kidney injury or requirement for dialysis or death, and progression to invasive mechanical ventilation, extracorporeal membrane oxygenation, or death, both assessed at 28 days.

The primary safety outcome of ketoacidosis by 28 days was observed in seven and two patients allocated to SGLT2 inhibitors and usual care or placebo, respectively, and overall, the incidence of reported serious adverse events was balanced between treatment groups.

The RECOVERY trial was supported by grants to the University of Oxford from UK Research and Innovation, the National Institute for Health and Care Research, and Wellcome. The ACTIV-4a platform was sponsored by the National Heart, Lung, and Blood Institute. DARE-19 was an investigator-initiated collaborative trial supported by AstraZeneca. Dr. Kosiborod reported numerous conflicts of interest.

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

A new meta-analysis has shown that SGLT2 inhibitors do not lead to lower 28-day all-cause mortality, compared with usual care or placebo, in patients hospitalized with COVID-19.

However, no major safety issues were identified with the use of SGLT2 inhibitors in these acutely ill patients, the researchers report.

“While these findings do not support the use of SGLT2-inhibitors as standard of care for patients hospitalized with COVID-19, I think the most important take home message here is that the use of these medications appears to be safe even in really acutely ill hospitalized patients,” lead investigator of the meta-analysis, Mikhail Kosiborod, MD, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., concluded.

He said this was important because the list of indications for SGLT2 inhibitors is rapidly growing.

“These medications are being used in more and more patients. And we know that when we discontinue medications in the hospital they frequently don’t get restarted, which can lead to real risks if SGLT2 inhibitors are stopped in patients with heart failure, chronic kidney disease, or diabetes. So, the bottom line is that there is no compelling reason to stop these medications in the hospital,” he added.

The new meta-analysis was presented at the recent annual congress of the European Society of Cardiology, held in Amsterdam.

Discussant of the presentation at the ESC Hotline session, Muthiah Vaduganathan, MD, MPH, Brigham and Women’s Hospital, Boston, agreed with Dr. Kosiborod’s interpretation.

“Until today we have had very limited information on the safety of SGLT2-inhibitors in acute illness, as the pivotal trials which established the use of these drugs in diabetes and chronic kidney disease largely excluded patients who were hospitalized,” Dr. Vaduganathan said.

“While the overall results of this meta-analysis are neutral and SGLT2 inhibitors will not be added as drugs to be used in the primary care of patients with COVID-19, it certainly sends a strong message of safety in acutely ill patients,” he added.

Dr. Vaduganathan explained that from the beginning of the COVID-19 pandemic, there was great interest in repurposing established therapies for alternative indications for their use in the management of COVID-19.

“Conditions that strongly predispose to adverse COVID outcomes strongly overlap with established indications for SGLT2-inhibitors. So many wondered whether these drugs may be an ideal treatment candidate for the management of COVID-19. However, there have been many safety concerns about the use of SGLT2-inhibitors in this acute setting, with worries that they may induce hemodynamic changes such an excessive lowering of blood pressure, or metabolic changes such as ketoacidosis in acutely ill patients,” he noted.

The initial DARE-19 study investigating SGLT2-inhibitors in COVID-19, with 1,250 participants, found a 20% reduction in the primary outcome of organ dysfunction or death, but this did not reach statistical significance, and no safety issues were seen. This “intriguing” result led to two further larger trials – the ACTIV-4a and RECOVERY trials, Dr. Vaduganathan reported.

“Those early signals of benefit seen in DARE-19 were largely not substantiated in the ACTIV-4A and RECOVERY trials, or in this new meta-analysis, and now we have this much larger body of evidence and more stable estimates about the efficacy of these drugs in acutely ill COVID-19 patients,” he said.

“But the story that we will all take forward is one of safety. This set of trials was arguably conducted in some of the sickest patients we’ve seen who have been exposed to SGLT2-inhibitors, and they strongly affirm that these agents can be safely continued in the setting of acute illness, with very low rates of ketoacidosis and kidney injury, and there was no prolongation of hospital stay,” he commented.

In his presentation, Dr. Kosiborod explained that treatments targeting COVID-19 pathobiology such as dysregulated immune responses, endothelial damage, microvascular thrombosis, and inflammation have been shown to improve the key outcomes in this patient group.

SGLT2 inhibitors, which modulate similar pathobiology, provide cardiovascular protection and prevent the progression of kidney disease in patients at risk for these events, including those with type 2 diabetes, heart failure, and kidney disease, and may also lead to organ protection in a setting of acute illness such as COVID-19, he noted. However, the role of SGLT2 inhibitors in patients hospitalized with COVID-19 remains uncertain.

To address the need for more definitive efficacy data, the World Health Organization Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group conducted a prospective meta-analysis using data from the three randomized controlled trials, DARE-19, RECOVERY, and ACTIV-4a, evaluating SGLT2 inhibitors in patients hospitalized with COVID-19.

Overall, these trials randomized 6,096 participants: 3,025 to SGLT2 inhibitors and 3,071 to usual care or placebo. The average age of participants ranged between 62 and 73 years across the trials, 39% were women, and 25% had type 2 diabetes.

By 28 days after randomization, all-cause mortality, the primary endpoint, had occurred in 11.6% of the SGLT2-inhibitor patients, compared with 12.4% of those randomized to usual care or placebo, giving an odds ratio of 0.93 (95% confidence interval, 0.79-1.08; P = .33) for SGLT2 inhibitors, with consistency across trials.

Data on in-hospital and 90-day all-cause mortality were only available for two out of three trials (DARE-19 and ACTIV-4a), but the results were similar to the primary endpoint showing nonsignificant trends toward a possible benefit in the SGLT2-inhibitor group.

The results were also similar for the secondary outcomes of progression to acute kidney injury or requirement for dialysis or death, and progression to invasive mechanical ventilation, extracorporeal membrane oxygenation, or death, both assessed at 28 days.

The primary safety outcome of ketoacidosis by 28 days was observed in seven and two patients allocated to SGLT2 inhibitors and usual care or placebo, respectively, and overall, the incidence of reported serious adverse events was balanced between treatment groups.

The RECOVERY trial was supported by grants to the University of Oxford from UK Research and Innovation, the National Institute for Health and Care Research, and Wellcome. The ACTIV-4a platform was sponsored by the National Heart, Lung, and Blood Institute. DARE-19 was an investigator-initiated collaborative trial supported by AstraZeneca. Dr. Kosiborod reported numerous conflicts of interest.

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

A physician in your office is hot-tempered, critical, and upsets both the physicians and staff. Two of your partners are arguing over a software vendor and refuse to compromise. One doctor’s spouse is the office manager and snipes at everyone; the lead partner micromanages and second-guesses other doctors’ treatment plans, and no one will stand up to her.

If your practice has similar scenarios, you’re likely dealing with your own anger, irritation, and dread at work. You’re struggling with a toxic practice atmosphere, and you must make changes – fast.

However, this isn’t easy, given that what goes on in a doctor’s office is “high consequence,” says Leonard J. Marcus, PhD, founding director of the program for health care negotiation and conflict resolution at the Harvard School of Public Health in Boston.

The two things that tend to plague medical practices most: A culture of fear and someone who is letting ego run the day-to-day, he says.

“Fear overwhelms any chance for good morale among colleagues,” says Dr. Marcus, who is also the coauthor of “Renegotiating Health Care: Resolving Conflict to Build Collaboration.” “In a work environment where the fear is overwhelming, the ego can take over, and someone at the practice becomes overly concerned about getting credit, taking control, ordering other people around, and deciding who is on top and who is on the bottom.”

Tension, stress, back-biting, and rudeness are also symptoms of a more significant problem, says Jes Montgomery, MD, a psychiatrist and medical director of APN Dallas, a mental health–focused practice.

“If you don’t get toxicity under control, it will blow the office apart,” Dr. Montgomery says.

Here are five tips to turn around a toxic practice culture.
 

1. Recognize the signs

Part of the problem with a toxic medical practice is that, culturally, we don’t treat mental health and burnout as real illnesses. “A physician who is depressed is not going to be melancholy or bursting into tears with patients,” Dr. Montgomery says. “They’ll get behind on paperwork, skip meals, or find that it’s difficult to sleep at night. Next, they’ll yell at the partners and staff, always be in a foul mood, and gripe about inconsequential things. Their behavior affects everyone.”

Dr. Montgomery says that physicians aren’t taught to ask for help, making it difficult to see what’s really going on when someone displays toxic behavior in the practice. If it’s a partner, take time to ask what’s going on. If it’s yourself, step back and see if you can ask someone for the help you need.
 

2. Have difficult conversations

This is tough for most of us, says Jeremy Pollack, PhD, CEO and founder of Pollack Peacebuilding Systems, a conflict resolution consulting firm. If a team member is hot-tempered, disrespectful, or talking to patients in an unproductive manner, see if you can have an effective conversation with that person. The tricky part is critiquing in a way that doesn’t make them feel defensive – and wanting to push back.

For a micromanaging office manager, for example, you could say something like,”You’re doing a great job with the inventory, but I need you to let the staff have some autonomy and not hover over every supply they use in the break room, so that people won’t feel resentful toward us.” Make it clear you’re a team, and this is a team challenge. “However, if a doctor feels like they’ve tried to communicate to that colleague and are still walking on eggshells, it’s time to try to get help from someone – perhaps a practice management organization,” says Dr. Pollack.
 

3. Open lines of communication

It’s critical to create a comfortable space to speak with your colleagues, says Marisa Garshick, MD, a dermatologist in private practice in New York. “Creating an environment where there is an open line of communication, whether it’s directly to somebody in charge or having a system where you can give feedback more privately or anonymously, is important so that tension doesn’t build.”

“Being a doctor is a social enterprise,” Dr. Marcus says. “The science of medicine is critically important, but patients and the other health care workers on your team are also critically important. In the long run, the most successful physicians pay attention to both. It’s a full package.”
 

4. Emphasize the positive

Instead of discussing things only when they go wrong, try optimism, Dr. Garshick said. When positive things happen, whether it’s an excellent patient encounter or the office did something really well together, highlight it so everyone has a sense of accomplishment. If a patient compliments a medical assistant or raves about a nurse, share those compliments with the employees so that not every encounter you have calls out problems and staff missteps.

Suppose partners have a conflict with one another or are arguing over something. In that case, you may need to mediate or invest in a meaningful intervention so people can reflect on the narrative they’re contributing to the culture.
 

5. Practice self-care

Finally, the work of a physician is exhausting, so it’s crucial to practice personal TLC. That may mean taking micro breaks, getting adequate sleep, maintaining a healthy diet, and exercising well and managing stress to maintain energy levels and patience.

“Sometimes, when I’m fed up with the office, I need to get away,” Dr. Montgomery says. “I’ll take a day to go fishing, golfing, and not think about the office.” Just a small break can shift the lens that you see through when you return to the office and put problems in perspective.

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

A physician in your office is hot-tempered, critical, and upsets both the physicians and staff. Two of your partners are arguing over a software vendor and refuse to compromise. One doctor’s spouse is the office manager and snipes at everyone; the lead partner micromanages and second-guesses other doctors’ treatment plans, and no one will stand up to her.

If your practice has similar scenarios, you’re likely dealing with your own anger, irritation, and dread at work. You’re struggling with a toxic practice atmosphere, and you must make changes – fast.

However, this isn’t easy, given that what goes on in a doctor’s office is “high consequence,” says Leonard J. Marcus, PhD, founding director of the program for health care negotiation and conflict resolution at the Harvard School of Public Health in Boston.

The two things that tend to plague medical practices most: A culture of fear and someone who is letting ego run the day-to-day, he says.

“Fear overwhelms any chance for good morale among colleagues,” says Dr. Marcus, who is also the coauthor of “Renegotiating Health Care: Resolving Conflict to Build Collaboration.” “In a work environment where the fear is overwhelming, the ego can take over, and someone at the practice becomes overly concerned about getting credit, taking control, ordering other people around, and deciding who is on top and who is on the bottom.”

Tension, stress, back-biting, and rudeness are also symptoms of a more significant problem, says Jes Montgomery, MD, a psychiatrist and medical director of APN Dallas, a mental health–focused practice.

“If you don’t get toxicity under control, it will blow the office apart,” Dr. Montgomery says.

Here are five tips to turn around a toxic practice culture.
 

1. Recognize the signs

Part of the problem with a toxic medical practice is that, culturally, we don’t treat mental health and burnout as real illnesses. “A physician who is depressed is not going to be melancholy or bursting into tears with patients,” Dr. Montgomery says. “They’ll get behind on paperwork, skip meals, or find that it’s difficult to sleep at night. Next, they’ll yell at the partners and staff, always be in a foul mood, and gripe about inconsequential things. Their behavior affects everyone.”

Dr. Montgomery says that physicians aren’t taught to ask for help, making it difficult to see what’s really going on when someone displays toxic behavior in the practice. If it’s a partner, take time to ask what’s going on. If it’s yourself, step back and see if you can ask someone for the help you need.
 

2. Have difficult conversations

This is tough for most of us, says Jeremy Pollack, PhD, CEO and founder of Pollack Peacebuilding Systems, a conflict resolution consulting firm. If a team member is hot-tempered, disrespectful, or talking to patients in an unproductive manner, see if you can have an effective conversation with that person. The tricky part is critiquing in a way that doesn’t make them feel defensive – and wanting to push back.

For a micromanaging office manager, for example, you could say something like,”You’re doing a great job with the inventory, but I need you to let the staff have some autonomy and not hover over every supply they use in the break room, so that people won’t feel resentful toward us.” Make it clear you’re a team, and this is a team challenge. “However, if a doctor feels like they’ve tried to communicate to that colleague and are still walking on eggshells, it’s time to try to get help from someone – perhaps a practice management organization,” says Dr. Pollack.
 

3. Open lines of communication

It’s critical to create a comfortable space to speak with your colleagues, says Marisa Garshick, MD, a dermatologist in private practice in New York. “Creating an environment where there is an open line of communication, whether it’s directly to somebody in charge or having a system where you can give feedback more privately or anonymously, is important so that tension doesn’t build.”

“Being a doctor is a social enterprise,” Dr. Marcus says. “The science of medicine is critically important, but patients and the other health care workers on your team are also critically important. In the long run, the most successful physicians pay attention to both. It’s a full package.”
 

4. Emphasize the positive

Instead of discussing things only when they go wrong, try optimism, Dr. Garshick said. When positive things happen, whether it’s an excellent patient encounter or the office did something really well together, highlight it so everyone has a sense of accomplishment. If a patient compliments a medical assistant or raves about a nurse, share those compliments with the employees so that not every encounter you have calls out problems and staff missteps.

Suppose partners have a conflict with one another or are arguing over something. In that case, you may need to mediate or invest in a meaningful intervention so people can reflect on the narrative they’re contributing to the culture.
 

5. Practice self-care

Finally, the work of a physician is exhausting, so it’s crucial to practice personal TLC. That may mean taking micro breaks, getting adequate sleep, maintaining a healthy diet, and exercising well and managing stress to maintain energy levels and patience.

“Sometimes, when I’m fed up with the office, I need to get away,” Dr. Montgomery says. “I’ll take a day to go fishing, golfing, and not think about the office.” Just a small break can shift the lens that you see through when you return to the office and put problems in perspective.

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

A physician in your office is hot-tempered, critical, and upsets both the physicians and staff. Two of your partners are arguing over a software vendor and refuse to compromise. One doctor’s spouse is the office manager and snipes at everyone; the lead partner micromanages and second-guesses other doctors’ treatment plans, and no one will stand up to her.

If your practice has similar scenarios, you’re likely dealing with your own anger, irritation, and dread at work. You’re struggling with a toxic practice atmosphere, and you must make changes – fast.

However, this isn’t easy, given that what goes on in a doctor’s office is “high consequence,” says Leonard J. Marcus, PhD, founding director of the program for health care negotiation and conflict resolution at the Harvard School of Public Health in Boston.

The two things that tend to plague medical practices most: A culture of fear and someone who is letting ego run the day-to-day, he says.

“Fear overwhelms any chance for good morale among colleagues,” says Dr. Marcus, who is also the coauthor of “Renegotiating Health Care: Resolving Conflict to Build Collaboration.” “In a work environment where the fear is overwhelming, the ego can take over, and someone at the practice becomes overly concerned about getting credit, taking control, ordering other people around, and deciding who is on top and who is on the bottom.”

Tension, stress, back-biting, and rudeness are also symptoms of a more significant problem, says Jes Montgomery, MD, a psychiatrist and medical director of APN Dallas, a mental health–focused practice.

“If you don’t get toxicity under control, it will blow the office apart,” Dr. Montgomery says.

Here are five tips to turn around a toxic practice culture.
 

1. Recognize the signs

Part of the problem with a toxic medical practice is that, culturally, we don’t treat mental health and burnout as real illnesses. “A physician who is depressed is not going to be melancholy or bursting into tears with patients,” Dr. Montgomery says. “They’ll get behind on paperwork, skip meals, or find that it’s difficult to sleep at night. Next, they’ll yell at the partners and staff, always be in a foul mood, and gripe about inconsequential things. Their behavior affects everyone.”

Dr. Montgomery says that physicians aren’t taught to ask for help, making it difficult to see what’s really going on when someone displays toxic behavior in the practice. If it’s a partner, take time to ask what’s going on. If it’s yourself, step back and see if you can ask someone for the help you need.
 

2. Have difficult conversations

This is tough for most of us, says Jeremy Pollack, PhD, CEO and founder of Pollack Peacebuilding Systems, a conflict resolution consulting firm. If a team member is hot-tempered, disrespectful, or talking to patients in an unproductive manner, see if you can have an effective conversation with that person. The tricky part is critiquing in a way that doesn’t make them feel defensive – and wanting to push back.

For a micromanaging office manager, for example, you could say something like,”You’re doing a great job with the inventory, but I need you to let the staff have some autonomy and not hover over every supply they use in the break room, so that people won’t feel resentful toward us.” Make it clear you’re a team, and this is a team challenge. “However, if a doctor feels like they’ve tried to communicate to that colleague and are still walking on eggshells, it’s time to try to get help from someone – perhaps a practice management organization,” says Dr. Pollack.
 

3. Open lines of communication

It’s critical to create a comfortable space to speak with your colleagues, says Marisa Garshick, MD, a dermatologist in private practice in New York. “Creating an environment where there is an open line of communication, whether it’s directly to somebody in charge or having a system where you can give feedback more privately or anonymously, is important so that tension doesn’t build.”

“Being a doctor is a social enterprise,” Dr. Marcus says. “The science of medicine is critically important, but patients and the other health care workers on your team are also critically important. In the long run, the most successful physicians pay attention to both. It’s a full package.”
 

4. Emphasize the positive

Instead of discussing things only when they go wrong, try optimism, Dr. Garshick said. When positive things happen, whether it’s an excellent patient encounter or the office did something really well together, highlight it so everyone has a sense of accomplishment. If a patient compliments a medical assistant or raves about a nurse, share those compliments with the employees so that not every encounter you have calls out problems and staff missteps.

Suppose partners have a conflict with one another or are arguing over something. In that case, you may need to mediate or invest in a meaningful intervention so people can reflect on the narrative they’re contributing to the culture.
 

5. Practice self-care

Finally, the work of a physician is exhausting, so it’s crucial to practice personal TLC. That may mean taking micro breaks, getting adequate sleep, maintaining a healthy diet, and exercising well and managing stress to maintain energy levels and patience.

“Sometimes, when I’m fed up with the office, I need to get away,” Dr. Montgomery says. “I’ll take a day to go fishing, golfing, and not think about the office.” Just a small break can shift the lens that you see through when you return to the office and put problems in perspective.

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

This transcript has been edited for clarity.

How do you tell if a condition is caused by an infection?

It seems like an obvious question, right? In the post–van Leeuwenhoek era we can look at whatever part of the body is diseased under a microscope and see microbes – you know, the usual suspects.

Except when we can’t. And there are plenty of cases where we can’t: where the microbe is too small to be seen without more advanced imaging techniques, like with viruses; or when the pathogen is sparsely populated or hard to culture, like Mycobacterium.

Finding out that a condition is the result of an infection is not only an exercise for 19th century physicians. After all, it was 2008 when Barry Marshall and Robin Warren won their Nobel Prize for proving that stomach ulcers, long thought to be due to “stress,” were actually caused by a tiny microbe called Helicobacter pylori.

And this week, we are looking at a study which, once again, begins to suggest that a condition thought to be more or less random – cerebral amyloid angiopathy – may actually be the result of an infectious disease.

We’re talking about this paper, appearing in JAMA, which is just a great example of old-fashioned shoe-leather epidemiology. But let’s get up to speed on cerebral amyloid angiopathy (CAA) first.

CAA is characterized by the deposition of amyloid protein in the brain. While there are some genetic causes, they are quite rare, and most cases are thought to be idiopathic. Recent analyses suggest that somewhere between 5% and 7% of cognitively normal older adults have CAA, but the rate is much higher among those with intracerebral hemorrhage – brain bleeds. In fact, CAA is the second-most common cause of bleeding in the brain, second only to severe hypertension.

Most of the textbooks continue to describe CAA as a sporadic condition, but there have been some intriguing studies that suggest it may be transmissible. An article in Nature highlights cases that seemed to develop after the administration of cadaveric pituitary hormone.

Other studies have shown potential transmission via dura mater grafts and neurosurgical instruments. But despite those clues, no infectious organism has been identified. Some have suggested that the long latent period and difficulty of finding a responsible microbe points to a prion-like disease not yet known. But these studies are more or less case series. The new JAMA paper gives us, if not a smoking gun, a pretty decent set of fingerprints.

Here’s the idea: If CAA is caused by some infectious agent, it may be transmitted in the blood. We know that a decent percentage of people who have spontaneous brain bleeds have CAA. If those people donated blood in the past, maybe the people who received that blood would be at risk for brain bleeds too.

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy JAMA Internal Medicine

Dr. F. Perry Wilson is an associate professor of medicine and public health and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.
 

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

This transcript has been edited for clarity.

How do you tell if a condition is caused by an infection?

It seems like an obvious question, right? In the post–van Leeuwenhoek era we can look at whatever part of the body is diseased under a microscope and see microbes – you know, the usual suspects.

Except when we can’t. And there are plenty of cases where we can’t: where the microbe is too small to be seen without more advanced imaging techniques, like with viruses; or when the pathogen is sparsely populated or hard to culture, like Mycobacterium.

Finding out that a condition is the result of an infection is not only an exercise for 19th century physicians. After all, it was 2008 when Barry Marshall and Robin Warren won their Nobel Prize for proving that stomach ulcers, long thought to be due to “stress,” were actually caused by a tiny microbe called Helicobacter pylori.

And this week, we are looking at a study which, once again, begins to suggest that a condition thought to be more or less random – cerebral amyloid angiopathy – may actually be the result of an infectious disease.

We’re talking about this paper, appearing in JAMA, which is just a great example of old-fashioned shoe-leather epidemiology. But let’s get up to speed on cerebral amyloid angiopathy (CAA) first.

CAA is characterized by the deposition of amyloid protein in the brain. While there are some genetic causes, they are quite rare, and most cases are thought to be idiopathic. Recent analyses suggest that somewhere between 5% and 7% of cognitively normal older adults have CAA, but the rate is much higher among those with intracerebral hemorrhage – brain bleeds. In fact, CAA is the second-most common cause of bleeding in the brain, second only to severe hypertension.

Most of the textbooks continue to describe CAA as a sporadic condition, but there have been some intriguing studies that suggest it may be transmissible. An article in Nature highlights cases that seemed to develop after the administration of cadaveric pituitary hormone.

Other studies have shown potential transmission via dura mater grafts and neurosurgical instruments. But despite those clues, no infectious organism has been identified. Some have suggested that the long latent period and difficulty of finding a responsible microbe points to a prion-like disease not yet known. But these studies are more or less case series. The new JAMA paper gives us, if not a smoking gun, a pretty decent set of fingerprints.

Here’s the idea: If CAA is caused by some infectious agent, it may be transmitted in the blood. We know that a decent percentage of people who have spontaneous brain bleeds have CAA. If those people donated blood in the past, maybe the people who received that blood would be at risk for brain bleeds too.

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy JAMA Internal Medicine

Dr. F. Perry Wilson is an associate professor of medicine and public health and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.
 

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

This transcript has been edited for clarity.

How do you tell if a condition is caused by an infection?

It seems like an obvious question, right? In the post–van Leeuwenhoek era we can look at whatever part of the body is diseased under a microscope and see microbes – you know, the usual suspects.

Except when we can’t. And there are plenty of cases where we can’t: where the microbe is too small to be seen without more advanced imaging techniques, like with viruses; or when the pathogen is sparsely populated or hard to culture, like Mycobacterium.

Finding out that a condition is the result of an infection is not only an exercise for 19th century physicians. After all, it was 2008 when Barry Marshall and Robin Warren won their Nobel Prize for proving that stomach ulcers, long thought to be due to “stress,” were actually caused by a tiny microbe called Helicobacter pylori.

And this week, we are looking at a study which, once again, begins to suggest that a condition thought to be more or less random – cerebral amyloid angiopathy – may actually be the result of an infectious disease.

We’re talking about this paper, appearing in JAMA, which is just a great example of old-fashioned shoe-leather epidemiology. But let’s get up to speed on cerebral amyloid angiopathy (CAA) first.

CAA is characterized by the deposition of amyloid protein in the brain. While there are some genetic causes, they are quite rare, and most cases are thought to be idiopathic. Recent analyses suggest that somewhere between 5% and 7% of cognitively normal older adults have CAA, but the rate is much higher among those with intracerebral hemorrhage – brain bleeds. In fact, CAA is the second-most common cause of bleeding in the brain, second only to severe hypertension.

Most of the textbooks continue to describe CAA as a sporadic condition, but there have been some intriguing studies that suggest it may be transmissible. An article in Nature highlights cases that seemed to develop after the administration of cadaveric pituitary hormone.

Other studies have shown potential transmission via dura mater grafts and neurosurgical instruments. But despite those clues, no infectious organism has been identified. Some have suggested that the long latent period and difficulty of finding a responsible microbe points to a prion-like disease not yet known. But these studies are more or less case series. The new JAMA paper gives us, if not a smoking gun, a pretty decent set of fingerprints.

Here’s the idea: If CAA is caused by some infectious agent, it may be transmitted in the blood. We know that a decent percentage of people who have spontaneous brain bleeds have CAA. If those people donated blood in the past, maybe the people who received that blood would be at risk for brain bleeds too.

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy Dr. F. Perry Wilson

courtesy JAMA Internal Medicine

Dr. F. Perry Wilson is an associate professor of medicine and public health and director of Yale University’s Clinical and Translational Research Accelerator in New Haven, Conn. He reported no conflicts of interest.
 

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

COVID vaccines will have a new formulation in 2023, according to a decision announced by the U.S. Food and Drug Administration, that will focus efforts on circulating variants. The move pushes last year’s bivalent vaccines out of circulation because they will no longer be authorized for use in the United States.

The updated mRNA vaccines for 2023-2024 are being revised to include a single component that corresponds to the Omicron variant XBB.1.5. Like the bivalents offered before, the new monovalents are being manufactured by Moderna and Pfizer.

The new vaccines are authorized for use in individuals age 6 months and older.  And the new options are being developed using a similar process as previous formulations, according to the FDA.
 

Targeting circulating variants

In recent studies, regulators point out the extent of neutralization observed by the updated vaccines against currently circulating viral variants causing COVID-19, including EG.5, BA.2.86, appears to be of a similar magnitude to the extent of neutralization observed with previous versions of the vaccines against corresponding prior variants.

“This suggests that the vaccines are a good match for protecting against the currently circulating COVID-19 variants,” according to the report.

Hundreds of millions of people in the United States have already received previously approved mRNA COVID vaccines, according to regulators who say the benefit-to-risk profile is well understood as they move forward with new formulations.

“Vaccination remains critical to public health and continued protection against serious consequences of COVID-19, including hospitalization and death,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement. “The public can be assured that these updated vaccines have met the agency’s rigorous scientific standards for safety, effectiveness, and manufacturing quality. We very much encourage those who are eligible to consider getting vaccinated.”
 

Timing the effort

On Sept. 12 the U.S. Centers for Disease Control and Prevention recommended that everyone 6 months and older get an updated COVID-19 vaccine. Updated vaccines from Pfizer-BioNTech and Moderna will be available later this week, according to the agency.

This article was updated 9/14/23.

A version of this article appeared on Medscape.com.

COVID vaccines will have a new formulation in 2023, according to a decision announced by the U.S. Food and Drug Administration, that will focus efforts on circulating variants. The move pushes last year’s bivalent vaccines out of circulation because they will no longer be authorized for use in the United States.

The updated mRNA vaccines for 2023-2024 are being revised to include a single component that corresponds to the Omicron variant XBB.1.5. Like the bivalents offered before, the new monovalents are being manufactured by Moderna and Pfizer.

The new vaccines are authorized for use in individuals age 6 months and older.  And the new options are being developed using a similar process as previous formulations, according to the FDA.
 

Targeting circulating variants

In recent studies, regulators point out the extent of neutralization observed by the updated vaccines against currently circulating viral variants causing COVID-19, including EG.5, BA.2.86, appears to be of a similar magnitude to the extent of neutralization observed with previous versions of the vaccines against corresponding prior variants.

“This suggests that the vaccines are a good match for protecting against the currently circulating COVID-19 variants,” according to the report.

Hundreds of millions of people in the United States have already received previously approved mRNA COVID vaccines, according to regulators who say the benefit-to-risk profile is well understood as they move forward with new formulations.

“Vaccination remains critical to public health and continued protection against serious consequences of COVID-19, including hospitalization and death,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement. “The public can be assured that these updated vaccines have met the agency’s rigorous scientific standards for safety, effectiveness, and manufacturing quality. We very much encourage those who are eligible to consider getting vaccinated.”
 

Timing the effort

On Sept. 12 the U.S. Centers for Disease Control and Prevention recommended that everyone 6 months and older get an updated COVID-19 vaccine. Updated vaccines from Pfizer-BioNTech and Moderna will be available later this week, according to the agency.

This article was updated 9/14/23.

A version of this article appeared on Medscape.com.

COVID vaccines will have a new formulation in 2023, according to a decision announced by the U.S. Food and Drug Administration, that will focus efforts on circulating variants. The move pushes last year’s bivalent vaccines out of circulation because they will no longer be authorized for use in the United States.

The updated mRNA vaccines for 2023-2024 are being revised to include a single component that corresponds to the Omicron variant XBB.1.5. Like the bivalents offered before, the new monovalents are being manufactured by Moderna and Pfizer.

The new vaccines are authorized for use in individuals age 6 months and older.  And the new options are being developed using a similar process as previous formulations, according to the FDA.
 

Targeting circulating variants

In recent studies, regulators point out the extent of neutralization observed by the updated vaccines against currently circulating viral variants causing COVID-19, including EG.5, BA.2.86, appears to be of a similar magnitude to the extent of neutralization observed with previous versions of the vaccines against corresponding prior variants.

“This suggests that the vaccines are a good match for protecting against the currently circulating COVID-19 variants,” according to the report.

Hundreds of millions of people in the United States have already received previously approved mRNA COVID vaccines, according to regulators who say the benefit-to-risk profile is well understood as they move forward with new formulations.

“Vaccination remains critical to public health and continued protection against serious consequences of COVID-19, including hospitalization and death,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement. “The public can be assured that these updated vaccines have met the agency’s rigorous scientific standards for safety, effectiveness, and manufacturing quality. We very much encourage those who are eligible to consider getting vaccinated.”
 

Timing the effort

On Sept. 12 the U.S. Centers for Disease Control and Prevention recommended that everyone 6 months and older get an updated COVID-19 vaccine. Updated vaccines from Pfizer-BioNTech and Moderna will be available later this week, according to the agency.

This article was updated 9/14/23.

A version of this article appeared on Medscape.com.

An increase in cases of respiratory syncytial virus (RSV) in Florida and Georgia signals that RSV season has begun. 

The Centers for Disease Control and Prevention issued a national alert to health officials Sept. 5, urging them to offer new medicines that can prevent severe cases of the respiratory virus in very young children and in older people. Those two groups are at the highest risk of potentially deadly complications from RSV.

Typically, the CDC considers the start of RSV season to occur when the rate of positive tests for the virus goes above 3% for 2 consecutive weeks. In Florida, the rate has been around 5% in recent weeks, and in Georgia, there has been an increase in RSV-related hospitalizations. Most of the hospitalizations in Georgia have been among infants less than a year old.

“Historically, such regional increases have predicted the beginning of RSV season nationally, with increased RSV activity spreading north and west over the following 2-3 months,” the CDC said.

Most children have been infected with RSV by the time they are 2 years old. Historically, up to 80,000 children under 5 years old are hospitalized annually because of the virus, and between 100 and 300 die from complications each year. 

Those figures could be drastically different this year because new preventive treatments are available.

The CDC recommends that all children under 8 months old receive the newly approved monoclonal antibody treatment nirsevimab (Beyfortus). Children up to 19 months old at high risk of severe complications from RSV are also eligible for the single-dose shot. In clinical trials, the treatment was 80% effective at preventing RSV infections from becoming so severe that children had to be hospitalized. The protection lasted about 5 months.

Older people are also at a heightened risk of severe illness from RSV, and two new vaccines are available this season. The vaccines are called Arexvy and Abrysvo, and the single-dose shots are approved for people ages 60 years and older. They are more than 80% effective at making severe lower respiratory complications less likely.

Last year’s RSV season started during the summer and peaked in October and November, which was earlier than usual. There’s no indication yet of when RSV season may peak this year. Last year and throughout the pandemic, RSV held its historical pattern of starting in Florida.

A version of this article appeared on WebMD.com.

An increase in cases of respiratory syncytial virus (RSV) in Florida and Georgia signals that RSV season has begun. 

The Centers for Disease Control and Prevention issued a national alert to health officials Sept. 5, urging them to offer new medicines that can prevent severe cases of the respiratory virus in very young children and in older people. Those two groups are at the highest risk of potentially deadly complications from RSV.

Typically, the CDC considers the start of RSV season to occur when the rate of positive tests for the virus goes above 3% for 2 consecutive weeks. In Florida, the rate has been around 5% in recent weeks, and in Georgia, there has been an increase in RSV-related hospitalizations. Most of the hospitalizations in Georgia have been among infants less than a year old.

“Historically, such regional increases have predicted the beginning of RSV season nationally, with increased RSV activity spreading north and west over the following 2-3 months,” the CDC said.

Most children have been infected with RSV by the time they are 2 years old. Historically, up to 80,000 children under 5 years old are hospitalized annually because of the virus, and between 100 and 300 die from complications each year. 

Those figures could be drastically different this year because new preventive treatments are available.

The CDC recommends that all children under 8 months old receive the newly approved monoclonal antibody treatment nirsevimab (Beyfortus). Children up to 19 months old at high risk of severe complications from RSV are also eligible for the single-dose shot. In clinical trials, the treatment was 80% effective at preventing RSV infections from becoming so severe that children had to be hospitalized. The protection lasted about 5 months.

Older people are also at a heightened risk of severe illness from RSV, and two new vaccines are available this season. The vaccines are called Arexvy and Abrysvo, and the single-dose shots are approved for people ages 60 years and older. They are more than 80% effective at making severe lower respiratory complications less likely.

Last year’s RSV season started during the summer and peaked in October and November, which was earlier than usual. There’s no indication yet of when RSV season may peak this year. Last year and throughout the pandemic, RSV held its historical pattern of starting in Florida.

A version of this article appeared on WebMD.com.

An increase in cases of respiratory syncytial virus (RSV) in Florida and Georgia signals that RSV season has begun. 

The Centers for Disease Control and Prevention issued a national alert to health officials Sept. 5, urging them to offer new medicines that can prevent severe cases of the respiratory virus in very young children and in older people. Those two groups are at the highest risk of potentially deadly complications from RSV.

Typically, the CDC considers the start of RSV season to occur when the rate of positive tests for the virus goes above 3% for 2 consecutive weeks. In Florida, the rate has been around 5% in recent weeks, and in Georgia, there has been an increase in RSV-related hospitalizations. Most of the hospitalizations in Georgia have been among infants less than a year old.

“Historically, such regional increases have predicted the beginning of RSV season nationally, with increased RSV activity spreading north and west over the following 2-3 months,” the CDC said.

Most children have been infected with RSV by the time they are 2 years old. Historically, up to 80,000 children under 5 years old are hospitalized annually because of the virus, and between 100 and 300 die from complications each year. 

Those figures could be drastically different this year because new preventive treatments are available.

The CDC recommends that all children under 8 months old receive the newly approved monoclonal antibody treatment nirsevimab (Beyfortus). Children up to 19 months old at high risk of severe complications from RSV are also eligible for the single-dose shot. In clinical trials, the treatment was 80% effective at preventing RSV infections from becoming so severe that children had to be hospitalized. The protection lasted about 5 months.

Older people are also at a heightened risk of severe illness from RSV, and two new vaccines are available this season. The vaccines are called Arexvy and Abrysvo, and the single-dose shots are approved for people ages 60 years and older. They are more than 80% effective at making severe lower respiratory complications less likely.

Last year’s RSV season started during the summer and peaked in October and November, which was earlier than usual. There’s no indication yet of when RSV season may peak this year. Last year and throughout the pandemic, RSV held its historical pattern of starting in Florida.

A version of this article appeared on WebMD.com.

Moderna says its upcoming COVID-19 vaccine should work against the BA.2.86 variant that has caused worry about a possible surge in cases.

“The company said its shot generated an 8.7-fold increase in neutralizing antibodies in humans against BA.2.86, which is being tracked by the World Health Organization and the U.S. Centers for Disease Control and Prevention,” Reuters reported.

“We think this is news people will want to hear as they prepare to go out and get their fall boosters,” Jacqueline Miller, Moderna head of infectious diseases, told the news agency.

The CDC said that the BA.2.86 variant might be more likely to infect people who have already had COVID or previous vaccinations. BA.2.86 is an Omicron variant. It has undergone more mutations than XBB.1.5, which has dominated most of this year and was the intended target of the updated shots.

BA.2.86 does not have a strong presence in the United States yet. However, officials are concerned about its high number of mutations, NBC News reported.

The FDA is expected to approve the new Moderna shot by early October.

Pfizer told NBC that its updated booster also generated a strong antibody response against Omicron variants, including BA.2.86.

COVID-19 cases and hospitalizations have been increasing in the U.S. because of the rise of several variants. 

Experts told Reuters that BA.2.86 probably won’t cause a wave of severe disease and death because immunity has been built up around the world through previous infections and mass vaccinations.

A version of this article appeared on WebMD.com.

Moderna says its upcoming COVID-19 vaccine should work against the BA.2.86 variant that has caused worry about a possible surge in cases.

“The company said its shot generated an 8.7-fold increase in neutralizing antibodies in humans against BA.2.86, which is being tracked by the World Health Organization and the U.S. Centers for Disease Control and Prevention,” Reuters reported.

“We think this is news people will want to hear as they prepare to go out and get their fall boosters,” Jacqueline Miller, Moderna head of infectious diseases, told the news agency.

The CDC said that the BA.2.86 variant might be more likely to infect people who have already had COVID or previous vaccinations. BA.2.86 is an Omicron variant. It has undergone more mutations than XBB.1.5, which has dominated most of this year and was the intended target of the updated shots.

BA.2.86 does not have a strong presence in the United States yet. However, officials are concerned about its high number of mutations, NBC News reported.

The FDA is expected to approve the new Moderna shot by early October.

Pfizer told NBC that its updated booster also generated a strong antibody response against Omicron variants, including BA.2.86.

COVID-19 cases and hospitalizations have been increasing in the U.S. because of the rise of several variants. 

Experts told Reuters that BA.2.86 probably won’t cause a wave of severe disease and death because immunity has been built up around the world through previous infections and mass vaccinations.

A version of this article appeared on WebMD.com.

Moderna says its upcoming COVID-19 vaccine should work against the BA.2.86 variant that has caused worry about a possible surge in cases.

“The company said its shot generated an 8.7-fold increase in neutralizing antibodies in humans against BA.2.86, which is being tracked by the World Health Organization and the U.S. Centers for Disease Control and Prevention,” Reuters reported.

“We think this is news people will want to hear as they prepare to go out and get their fall boosters,” Jacqueline Miller, Moderna head of infectious diseases, told the news agency.

The CDC said that the BA.2.86 variant might be more likely to infect people who have already had COVID or previous vaccinations. BA.2.86 is an Omicron variant. It has undergone more mutations than XBB.1.5, which has dominated most of this year and was the intended target of the updated shots.

BA.2.86 does not have a strong presence in the United States yet. However, officials are concerned about its high number of mutations, NBC News reported.

The FDA is expected to approve the new Moderna shot by early October.

Pfizer told NBC that its updated booster also generated a strong antibody response against Omicron variants, including BA.2.86.

COVID-19 cases and hospitalizations have been increasing in the U.S. because of the rise of several variants. 

Experts told Reuters that BA.2.86 probably won’t cause a wave of severe disease and death because immunity has been built up around the world through previous infections and mass vaccinations.

A version of this article appeared on WebMD.com.

AMSTERDAM – A short course of the interleukin-1 receptor antagonist, anakinra, appeared safe but did not reduce complications of acute myocarditis in the ARAMIS trial.

The trial was presented at the annual congress of the European Society of Cardiology.

Lead investigator, Mathieu Kerneis, MD, Pitie Salpetriere APHP University Hospital, Paris, said this was the largest randomized controlled trial of patients with acute myocarditis and probably the first ever study in the acute setting of myocarditis patients diagnosed with cardiac magnetic resonance (CMR) imaging, not on biopsy, who are mostly at low risk for events.

He suggested that one of the reasons for the neutral result could have been the low-risk population involved and the low complication rate. “We enrolled an all-comer acute myocarditis population diagnosed with CMR, who were mostly at a low risk of complications,” he noted.

“I don’t think the story of anti-inflammatory drugs in acute myocarditis is over. This is just the beginning. This was the first trial, and it was just a phase 2 trial. We need further randomized trials to explore the potential benefit of an anti-inflammatory strategy in acute myocarditis patients at higher risk of complications. In addition, larger studies are needed to evaluate prolonged anti-inflammatory strategies in acute myocarditis patients at low-to-moderate risk of complications,” Dr. Kerneis concluded.

“It is very challenging to do a trial in high-risk patients with myocarditis as these patients are quite rare,” he added.
 

Inflammation of the myocardium

Dr. Kerneis explained that acute myocarditis is an inflammation of the myocardium that can cause permanent damage to the heart muscle and lead to myocardial infarction, stroke, heart failure, arrhythmias, and death. The condition can occur in individuals of all ages but is most frequent in young people. There is no specific treatment, but patients are generally treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and sometimes steroids.

Anakinra is an interleukin-1 receptor antagonist that works by targeting the interleukin-1β innate immune pathway. Anakinra is used for the treatment of rheumatoid arthritis and has shown efficacy in pericarditis. Dr. Kerneis noted that there have been several case reports of successful treatment with anakinra in acute myocarditis.

The ARAMIS trial – conducted at six academic centers in France – was the first randomized study to evaluate inhibition of the interleukin-1β innate immune pathway in myocarditis patients. The trial enrolled 120 hospitalized, symptomatic patients with chest pain, increased cardiac troponin, and acute myocarditis diagnosed using CMR. More than half had had a recent bacterial or viral infection.

Patients were randomized within 72 hours of hospital admission to a daily subcutaneous dose of anakinra 100 mg or placebo until hospital discharge. Patients in both groups received standard-of-care treatments, including an ACE inhibitor, for at least 1 month. Consistent with prior data, the median age of participants was 28 years and 90% were men.

The primary endpoint was the number of days free of myocarditis complications (heart failure requiring hospitalization, chest pain requiring medication, left ventricular ejection fraction less than 50%, and ventricular arrhythmias) within 28 days postdischarge.

There was no significant difference in this endpoint between the two arms, with a median of 30 days for anakinra versus 31 days for placebo.

Overall, the rate of the composite endpoint of myocarditis complications occurred in 13.7% of patients, and there was a numerical reduction in the number of patients with these myocarditis complications with anakinra – 6 patients (10.5%) in the anakinra group versus 10 patients (16.5%) in the placebo group (odds ratio, 0.59; 95% confidence interval, 0.19-1.78). This was driven by fewer patients with chest pain requiring new medication (two patients versus six patients).

The safety endpoint was the number of serious adverse events within 28 days postdischarge. This endpoint occurred in seven patients (12.1%) in the anakinra arm and six patients (10.2%) in the placebo arm, with no significant difference between groups. Cases of severe infection within 28 days postdischarge were reported in both arms.
 

Low-risk population

Designated discussant of the study at the ESC Hotline session, Enrico Ammirati, MD, PhD, University of Milano-Bicocca, Monza, Italy, said that patients involved in ARAMIS fit the profile of acute myocarditis and that the CMR diagnosis was positive in all the patients enrolled.

Dr. Ammirati agreed with Dr. Kerneis that the neutral results of the study were probably caused by the low-risk population. “If we look at retrospective registries, at 30 days there are zero cardiac deaths or heart transplants at 30 days in patients with a low-risk presentation.

“The ARAMIS trial has shown the feasibility of conducting studies in the setting of acute myocarditis, and even if the primary endpoint was neutral, some important data are still missing, such as change in ejection fraction and troponin levels,” he noted.

“In terms of future perspective, we are moving to assessing efficacy of anakinra or other immunosuppressive drugs from acute low risk patients to higher risk patients with heart failure and severe dysfunction,” he said.  

Dr. Ammirati is the lead investigator of another ongoing study in such a higher-risk population; the MYTHS trial is investigating the use of intravenous steroids in patients with suspected acute myocarditis complicated by acute heart failure or cardiogenic shock, and an ejection fraction below 41%.

“So, we will have more results on the best treatment in this higher risk group of patients,” he concluded.

The ARAMIS trial was an academic study funded by the French Health Ministry and coordinated by the ACTION Group. Dr. Kerneis reports having received consulting fees from Kiniksa, Sanofi, and Bayer, and holds a patent for use of abatacept in immune checkpoint inhibitor (ICI)–induced myocarditis.

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

AMSTERDAM – A short course of the interleukin-1 receptor antagonist, anakinra, appeared safe but did not reduce complications of acute myocarditis in the ARAMIS trial.

The trial was presented at the annual congress of the European Society of Cardiology.

Lead investigator, Mathieu Kerneis, MD, Pitie Salpetriere APHP University Hospital, Paris, said this was the largest randomized controlled trial of patients with acute myocarditis and probably the first ever study in the acute setting of myocarditis patients diagnosed with cardiac magnetic resonance (CMR) imaging, not on biopsy, who are mostly at low risk for events.

He suggested that one of the reasons for the neutral result could have been the low-risk population involved and the low complication rate. “We enrolled an all-comer acute myocarditis population diagnosed with CMR, who were mostly at a low risk of complications,” he noted.

“I don’t think the story of anti-inflammatory drugs in acute myocarditis is over. This is just the beginning. This was the first trial, and it was just a phase 2 trial. We need further randomized trials to explore the potential benefit of an anti-inflammatory strategy in acute myocarditis patients at higher risk of complications. In addition, larger studies are needed to evaluate prolonged anti-inflammatory strategies in acute myocarditis patients at low-to-moderate risk of complications,” Dr. Kerneis concluded.

“It is very challenging to do a trial in high-risk patients with myocarditis as these patients are quite rare,” he added.
 

Inflammation of the myocardium

Dr. Kerneis explained that acute myocarditis is an inflammation of the myocardium that can cause permanent damage to the heart muscle and lead to myocardial infarction, stroke, heart failure, arrhythmias, and death. The condition can occur in individuals of all ages but is most frequent in young people. There is no specific treatment, but patients are generally treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and sometimes steroids.

Anakinra is an interleukin-1 receptor antagonist that works by targeting the interleukin-1β innate immune pathway. Anakinra is used for the treatment of rheumatoid arthritis and has shown efficacy in pericarditis. Dr. Kerneis noted that there have been several case reports of successful treatment with anakinra in acute myocarditis.

The ARAMIS trial – conducted at six academic centers in France – was the first randomized study to evaluate inhibition of the interleukin-1β innate immune pathway in myocarditis patients. The trial enrolled 120 hospitalized, symptomatic patients with chest pain, increased cardiac troponin, and acute myocarditis diagnosed using CMR. More than half had had a recent bacterial or viral infection.

Patients were randomized within 72 hours of hospital admission to a daily subcutaneous dose of anakinra 100 mg or placebo until hospital discharge. Patients in both groups received standard-of-care treatments, including an ACE inhibitor, for at least 1 month. Consistent with prior data, the median age of participants was 28 years and 90% were men.

The primary endpoint was the number of days free of myocarditis complications (heart failure requiring hospitalization, chest pain requiring medication, left ventricular ejection fraction less than 50%, and ventricular arrhythmias) within 28 days postdischarge.

There was no significant difference in this endpoint between the two arms, with a median of 30 days for anakinra versus 31 days for placebo.

Overall, the rate of the composite endpoint of myocarditis complications occurred in 13.7% of patients, and there was a numerical reduction in the number of patients with these myocarditis complications with anakinra – 6 patients (10.5%) in the anakinra group versus 10 patients (16.5%) in the placebo group (odds ratio, 0.59; 95% confidence interval, 0.19-1.78). This was driven by fewer patients with chest pain requiring new medication (two patients versus six patients).

The safety endpoint was the number of serious adverse events within 28 days postdischarge. This endpoint occurred in seven patients (12.1%) in the anakinra arm and six patients (10.2%) in the placebo arm, with no significant difference between groups. Cases of severe infection within 28 days postdischarge were reported in both arms.
 

Low-risk population

Designated discussant of the study at the ESC Hotline session, Enrico Ammirati, MD, PhD, University of Milano-Bicocca, Monza, Italy, said that patients involved in ARAMIS fit the profile of acute myocarditis and that the CMR diagnosis was positive in all the patients enrolled.

Dr. Ammirati agreed with Dr. Kerneis that the neutral results of the study were probably caused by the low-risk population. “If we look at retrospective registries, at 30 days there are zero cardiac deaths or heart transplants at 30 days in patients with a low-risk presentation.

“The ARAMIS trial has shown the feasibility of conducting studies in the setting of acute myocarditis, and even if the primary endpoint was neutral, some important data are still missing, such as change in ejection fraction and troponin levels,” he noted.

“In terms of future perspective, we are moving to assessing efficacy of anakinra or other immunosuppressive drugs from acute low risk patients to higher risk patients with heart failure and severe dysfunction,” he said.  

Dr. Ammirati is the lead investigator of another ongoing study in such a higher-risk population; the MYTHS trial is investigating the use of intravenous steroids in patients with suspected acute myocarditis complicated by acute heart failure or cardiogenic shock, and an ejection fraction below 41%.

“So, we will have more results on the best treatment in this higher risk group of patients,” he concluded.

The ARAMIS trial was an academic study funded by the French Health Ministry and coordinated by the ACTION Group. Dr. Kerneis reports having received consulting fees from Kiniksa, Sanofi, and Bayer, and holds a patent for use of abatacept in immune checkpoint inhibitor (ICI)–induced myocarditis.

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

AMSTERDAM – A short course of the interleukin-1 receptor antagonist, anakinra, appeared safe but did not reduce complications of acute myocarditis in the ARAMIS trial.

The trial was presented at the annual congress of the European Society of Cardiology.

Lead investigator, Mathieu Kerneis, MD, Pitie Salpetriere APHP University Hospital, Paris, said this was the largest randomized controlled trial of patients with acute myocarditis and probably the first ever study in the acute setting of myocarditis patients diagnosed with cardiac magnetic resonance (CMR) imaging, not on biopsy, who are mostly at low risk for events.

He suggested that one of the reasons for the neutral result could have been the low-risk population involved and the low complication rate. “We enrolled an all-comer acute myocarditis population diagnosed with CMR, who were mostly at a low risk of complications,” he noted.

“I don’t think the story of anti-inflammatory drugs in acute myocarditis is over. This is just the beginning. This was the first trial, and it was just a phase 2 trial. We need further randomized trials to explore the potential benefit of an anti-inflammatory strategy in acute myocarditis patients at higher risk of complications. In addition, larger studies are needed to evaluate prolonged anti-inflammatory strategies in acute myocarditis patients at low-to-moderate risk of complications,” Dr. Kerneis concluded.

“It is very challenging to do a trial in high-risk patients with myocarditis as these patients are quite rare,” he added.
 

Inflammation of the myocardium

Dr. Kerneis explained that acute myocarditis is an inflammation of the myocardium that can cause permanent damage to the heart muscle and lead to myocardial infarction, stroke, heart failure, arrhythmias, and death. The condition can occur in individuals of all ages but is most frequent in young people. There is no specific treatment, but patients are generally treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and sometimes steroids.

Anakinra is an interleukin-1 receptor antagonist that works by targeting the interleukin-1β innate immune pathway. Anakinra is used for the treatment of rheumatoid arthritis and has shown efficacy in pericarditis. Dr. Kerneis noted that there have been several case reports of successful treatment with anakinra in acute myocarditis.

The ARAMIS trial – conducted at six academic centers in France – was the first randomized study to evaluate inhibition of the interleukin-1β innate immune pathway in myocarditis patients. The trial enrolled 120 hospitalized, symptomatic patients with chest pain, increased cardiac troponin, and acute myocarditis diagnosed using CMR. More than half had had a recent bacterial or viral infection.

Patients were randomized within 72 hours of hospital admission to a daily subcutaneous dose of anakinra 100 mg or placebo until hospital discharge. Patients in both groups received standard-of-care treatments, including an ACE inhibitor, for at least 1 month. Consistent with prior data, the median age of participants was 28 years and 90% were men.

The primary endpoint was the number of days free of myocarditis complications (heart failure requiring hospitalization, chest pain requiring medication, left ventricular ejection fraction less than 50%, and ventricular arrhythmias) within 28 days postdischarge.

There was no significant difference in this endpoint between the two arms, with a median of 30 days for anakinra versus 31 days for placebo.

Overall, the rate of the composite endpoint of myocarditis complications occurred in 13.7% of patients, and there was a numerical reduction in the number of patients with these myocarditis complications with anakinra – 6 patients (10.5%) in the anakinra group versus 10 patients (16.5%) in the placebo group (odds ratio, 0.59; 95% confidence interval, 0.19-1.78). This was driven by fewer patients with chest pain requiring new medication (two patients versus six patients).

The safety endpoint was the number of serious adverse events within 28 days postdischarge. This endpoint occurred in seven patients (12.1%) in the anakinra arm and six patients (10.2%) in the placebo arm, with no significant difference between groups. Cases of severe infection within 28 days postdischarge were reported in both arms.
 

Low-risk population

Designated discussant of the study at the ESC Hotline session, Enrico Ammirati, MD, PhD, University of Milano-Bicocca, Monza, Italy, said that patients involved in ARAMIS fit the profile of acute myocarditis and that the CMR diagnosis was positive in all the patients enrolled.

Dr. Ammirati agreed with Dr. Kerneis that the neutral results of the study were probably caused by the low-risk population. “If we look at retrospective registries, at 30 days there are zero cardiac deaths or heart transplants at 30 days in patients with a low-risk presentation.

“The ARAMIS trial has shown the feasibility of conducting studies in the setting of acute myocarditis, and even if the primary endpoint was neutral, some important data are still missing, such as change in ejection fraction and troponin levels,” he noted.

“In terms of future perspective, we are moving to assessing efficacy of anakinra or other immunosuppressive drugs from acute low risk patients to higher risk patients with heart failure and severe dysfunction,” he said.  

Dr. Ammirati is the lead investigator of another ongoing study in such a higher-risk population; the MYTHS trial is investigating the use of intravenous steroids in patients with suspected acute myocarditis complicated by acute heart failure or cardiogenic shock, and an ejection fraction below 41%.

“So, we will have more results on the best treatment in this higher risk group of patients,” he concluded.

The ARAMIS trial was an academic study funded by the French Health Ministry and coordinated by the ACTION Group. Dr. Kerneis reports having received consulting fees from Kiniksa, Sanofi, and Bayer, and holds a patent for use of abatacept in immune checkpoint inhibitor (ICI)–induced myocarditis.

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

This transcript has been edited for clarity.

Every branch of science has its constants. Physics has the speed of light, the gravitational constant, the Planck constant. Chemistry gives us Avogadro’s number, Faraday’s constant, the charge of an electron. Medicine isn’t quite as reliable as physics when it comes to these things, but insofar as there are any constants in medicine, might I suggest normal body temperature: 37° Celsius, 98.6° Fahrenheit.

Sure, serum sodium may be less variable and lactate concentration more clinically relevant, but even my 7-year-old knows that normal body temperature is 98.6°.

Except, as it turns out, 98.6° isn’t normal at all.

How did we arrive at 37.0° C for normal body temperature? We got it from this guy – German physician Carl Reinhold August Wunderlich, who, in addition to looking eerily like Luciano Pavarotti, was the first to realize that fever was not itself a disease but a symptom of one.

In 1851, Dr. Wunderlich released his measurements of more than 1 million body temperatures taken from 25,000 Germans – a painstaking process at the time, which employed a foot-long thermometer and took 20 minutes to obtain a measurement.

The average temperature measured, of course, was 37° C.

We’re more than 150 years post-Wunderlich right now, and the average person in the United States might be quite a bit different from the average German in 1850. Moreover, we can do a lot better than just measuring a ton of people and taking the average, because we have statistics. The problem with measuring a bunch of people and taking the average temperature as normal is that you can’t be sure that the people you are measuring are normal. There are obvious causes of elevated temperature that you could exclude. Let’s not take people with a respiratory infection or who are taking Tylenol, for example. But as highlighted in this paper in JAMA Internal Medicine, we can do a lot better than that.

The study leverages the fact that body temperature is typically measured during all medical office visits and recorded in the ever-present electronic medical record.

Researchers from Stanford identified 724,199 patient encounters with outpatient temperature data. They excluded extreme temperatures – less than 34° C or greater than 40° C – excluded patients under 20 or above 80 years, and excluded those with extremes of height, weight, or body mass index.

You end up with a distribution like this. Note that the peak is clearly lower than 37° C.

JAMA Internal Medicine

JAMA Internal Medicine

Dr. Wilson

JAMA Internal Medicine

JAMA Internal Medicine

JAMA Internal Medicine

Dr. Wilson is associate professor of medicine and public health at Yale University, New Haven, Conn., and director of Yale’s Clinical and Translational Research Accelerator. He has no disclosures.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Every branch of science has its constants. Physics has the speed of light, the gravitational constant, the Planck constant. Chemistry gives us Avogadro’s number, Faraday’s constant, the charge of an electron. Medicine isn’t quite as reliable as physics when it comes to these things, but insofar as there are any constants in medicine, might I suggest normal body temperature: 37° Celsius, 98.6° Fahrenheit.

Sure, serum sodium may be less variable and lactate concentration more clinically relevant, but even my 7-year-old knows that normal body temperature is 98.6°.

Except, as it turns out, 98.6° isn’t normal at all.

How did we arrive at 37.0° C for normal body temperature? We got it from this guy – German physician Carl Reinhold August Wunderlich, who, in addition to looking eerily like Luciano Pavarotti, was the first to realize that fever was not itself a disease but a symptom of one.

In 1851, Dr. Wunderlich released his measurements of more than 1 million body temperatures taken from 25,000 Germans – a painstaking process at the time, which employed a foot-long thermometer and took 20 minutes to obtain a measurement.

The average temperature measured, of course, was 37° C.

We’re more than 150 years post-Wunderlich right now, and the average person in the United States might be quite a bit different from the average German in 1850. Moreover, we can do a lot better than just measuring a ton of people and taking the average, because we have statistics. The problem with measuring a bunch of people and taking the average temperature as normal is that you can’t be sure that the people you are measuring are normal. There are obvious causes of elevated temperature that you could exclude. Let’s not take people with a respiratory infection or who are taking Tylenol, for example. But as highlighted in this paper in JAMA Internal Medicine, we can do a lot better than that.

The study leverages the fact that body temperature is typically measured during all medical office visits and recorded in the ever-present electronic medical record.

Researchers from Stanford identified 724,199 patient encounters with outpatient temperature data. They excluded extreme temperatures – less than 34° C or greater than 40° C – excluded patients under 20 or above 80 years, and excluded those with extremes of height, weight, or body mass index.

You end up with a distribution like this. Note that the peak is clearly lower than 37° C.

JAMA Internal Medicine

JAMA Internal Medicine

Dr. Wilson

JAMA Internal Medicine

JAMA Internal Medicine

JAMA Internal Medicine

Dr. Wilson is associate professor of medicine and public health at Yale University, New Haven, Conn., and director of Yale’s Clinical and Translational Research Accelerator. He has no disclosures.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Every branch of science has its constants. Physics has the speed of light, the gravitational constant, the Planck constant. Chemistry gives us Avogadro’s number, Faraday’s constant, the charge of an electron. Medicine isn’t quite as reliable as physics when it comes to these things, but insofar as there are any constants in medicine, might I suggest normal body temperature: 37° Celsius, 98.6° Fahrenheit.

Sure, serum sodium may be less variable and lactate concentration more clinically relevant, but even my 7-year-old knows that normal body temperature is 98.6°.

Except, as it turns out, 98.6° isn’t normal at all.

How did we arrive at 37.0° C for normal body temperature? We got it from this guy – German physician Carl Reinhold August Wunderlich, who, in addition to looking eerily like Luciano Pavarotti, was the first to realize that fever was not itself a disease but a symptom of one.

In 1851, Dr. Wunderlich released his measurements of more than 1 million body temperatures taken from 25,000 Germans – a painstaking process at the time, which employed a foot-long thermometer and took 20 minutes to obtain a measurement.

The average temperature measured, of course, was 37° C.

We’re more than 150 years post-Wunderlich right now, and the average person in the United States might be quite a bit different from the average German in 1850. Moreover, we can do a lot better than just measuring a ton of people and taking the average, because we have statistics. The problem with measuring a bunch of people and taking the average temperature as normal is that you can’t be sure that the people you are measuring are normal. There are obvious causes of elevated temperature that you could exclude. Let’s not take people with a respiratory infection or who are taking Tylenol, for example. But as highlighted in this paper in JAMA Internal Medicine, we can do a lot better than that.

The study leverages the fact that body temperature is typically measured during all medical office visits and recorded in the ever-present electronic medical record.

Researchers from Stanford identified 724,199 patient encounters with outpatient temperature data. They excluded extreme temperatures – less than 34° C or greater than 40° C – excluded patients under 20 or above 80 years, and excluded those with extremes of height, weight, or body mass index.

You end up with a distribution like this. Note that the peak is clearly lower than 37° C.

JAMA Internal Medicine

JAMA Internal Medicine

Dr. Wilson

JAMA Internal Medicine

JAMA Internal Medicine

JAMA Internal Medicine

Dr. Wilson is associate professor of medicine and public health at Yale University, New Haven, Conn., and director of Yale’s Clinical and Translational Research Accelerator. He has no disclosures.

A version of this article appeared on Medscape.com.

You cut yourself. You put on a bandage. In a week or so, your wound heals.

Most people take this routine for granted. But for the more than 8.2 million Americans who have chronic wounds, it’s not so simple.

Traumatic injuries, post-surgical complications, advanced age, and chronic illnesses like diabetes and vascular disease can all disrupt the delicate healing process, leading to wounds that last months or years. 

Left untreated, about 30% led to amputation. And recent studies show the risk of dying from a chronic wound complication within 5 years rivals that of most cancers.

Yet until recently, medical technology had not kept up with what experts say is a snowballing threat to public health.

“Wound care – even with all of the billions of products that are sold – still exists on kind of a medieval level,” said Geoffrey Gurtner, MD, chair of the department of surgery and professor of biomedical engineering at the University of Arizona College of Medicine. “We’re still putting on poultices and salves ... and when it comes to diagnosing infection, it’s really an art. I think we can do better.” 
 

Old-school bandage meets AI

Dr. Gurtner is among dozens of clinicians and researchers reimagining the humble bandage, combining cutting-edge materials science with artificial intelligence and patient data to develop “smart bandages” that do far more than shield a wound.

Someday soon, these paper-thin bandages embedded with miniaturized electronics could monitor the healing process in real time, alerting the patient – or a doctor – when things go wrong. With the press of a smartphone button, that bandage could deliver medicine to fight an infection or an electrical pulse to stimulate healing.

Some “closed-loop” designs need no prompting, instead monitoring the wound and automatically giving it what it needs.

Others in development could halt a battlefield wound from hemorrhaging or kick-start healing in a blast wound, preventing longer-term disability. 

The same technologies could – if the price is right – speed up healing and reduce scarring in minor cuts and scrapes, too, said Dr. Gurtner. 

And unlike many cutting-edge medical innovations, these next-generation bandages could be made relatively cheaply and benefit some of the most vulnerable populations, including older adults, people with low incomes, and those in developing countries.

They could also save the health care system money, as the U.S. spends more than $28 billion annually treating chronic wounds.

“This is a condition that many patients find shameful and embarrassing, so there hasn’t been a lot of advocacy,” said Dr. Gurtner, outgoing board president of the Wound Healing Society. “It’s a relatively ignored problem afflicting an underserved population that has a huge cost. It’s a perfect storm.”
 

How wounds heal, or don’t

Wound healing is one of the most complex processes of the human body.

First platelets rush to the injury, prompting blood to clot. Then immune cells emit compounds called inflammatory cytokines, helping to fight off pathogens and keep infection at bay. Other compounds, including nitric oxide, spark the growth of new blood vessels and collagen to rebuild skin and connective tissue. As inflammation slows and stops, the flesh continues to reform.

But some conditions can stall the process, often in the inflammatory stage. 

In people with diabetes, high glucose levels and poor circulation tend to sabotage the process. And people with nerve damage from spinal cord injuries, diabetes, or other ailments may not be able to feel it when a wound is getting worse or reinjured.

“We end up with patients going months with open wounds that are festering and infected,” said Roslyn Rivkah Isseroff, MD, professor of dermatology at the University of California Davis and head of the VA Northern California Health Care System’s wound healing clinic. “The patients are upset with the smell. These open ulcers put the patient at risk for systemic infection, like sepsis.” It can impact mental health, draining the patient’s ability to care for their wound.

“We see them once a week and send them home and say change your dressing every day, and they say, ‘I can barely move. I can’t do this,’ ” said Dr. Isseroff.

Checking for infection means removing bandages and culturing the wound. That can be painful, and results take time. 

A lot can happen to a wound in a week.

“Sometimes, they come back and it’s a disaster, and they have to be admitted to the ER or even get an amputation,” Dr. Gurtner said. 

People who are housing insecure or lack access to health care are even more vulnerable to complications. 

“If you had the ability to say ‘there is something bad happening,’ you could do a lot to prevent this cascade and downward spiral.” 
 

Bandages 2.0

In 2019, the Defense Advanced Research Projects Agency, the research arm of the Department of Defense, launched the Bioelectronics for Tissue Regeneration program to encourage scientists to develop a “closed-loop” bandage capable of both monitoring and hastening healing.

Tens of millions in funding has kick-started a flood of innovation since.

“It’s kind of a race to the finish,” said Marco Rolandi, PhD, associate professor of electrical and computer engineering at the University of California Santa Cruz and the principal investigator for a team including engineers, medical doctors, and computer scientists from UC Santa Cruz, UC Davis, and Tufts. “I’ve been amazed and impressed at all the work coming out.”

His team’s goal is to cut healing time in half by using (a) real-time monitoring of how a wound is healing – using indicators like temperature, pH level, oxygen, moisture, glucose, electrical activity, and certain proteins, and (b) appropriate stimulation.

“Every wound is different, so there is no one solution,” said Dr. Isseroff, the team’s clinical lead. “The idea is that it will be able to sense different parameters unique to the wound, use AI to figure out what stage it is in, and provide the right stimulus to kick it out of that stalled stage.”

The team has developed a proof-of-concept prototype: a bandage embedded with a tiny camera that takes pictures and transmits them to a computer algorithm to assess the wound’s progress. Miniaturized battery-powered actuators, or motors, automatically deliver medication.

Phase I trials in rodents went well, Dr. Rolandi said. The team is now testing the bandage on pigs.

Across the globe, other promising developments are underway.

In a scientific paper published in May, researchers at the University of Glasgow described a new “low-cost, environmentally friendly” bandage embedded with light-emitting diodes that use ultraviolet light to kill bacteria – no antibiotics needed. The fabric is stitched with a slim, flexible coil that powers the lights without a battery using wireless power transfer. In lab studies, it eradicated gram-negative bacteria (some of the nastiest bugs) in 6 hours.

Also in May, in the journal Bioactive Materials, a Penn State team detailed a bandage with medicine-injecting microneedles that can halt bleeding immediately after injury. In lab and animal tests, it reduced clotting time from 11.5 minutes to 1.3 minutes and bleeding by 90%.

“With hemorrhaging injuries, it is often the loss of blood – not the injury itself – that causes death,” said study author Amir Sheikhi, PhD, assistant professor of chemical and biomedical engineering at Penn State. “Those 10 minutes could be the difference between life and death.” 

Another smart bandage, developed at Northwestern University, Chicago, harmlessly dissolves – electrodes and all – into the body after it is no longer needed, eliminating what can be a painful removal.

Guillermo Ameer, DSc, a study author reporting on the technology in Science Advances, hopes it could be made cheaply and used in developing countries.

“We’d like to create something that you could use in your home, even in a very remote village,” said Dr. Ameer, professor of biomedical engineering at Northwestern.
 

Timeline for clinical use

These are early days for the smart bandage, scientists say. Most studies have been in rodents and more work is needed to develop human-scale bandages, reduce cost, solve long-term data storage, and ensure material adheres well without irritating the skin.

But Dr. Gurtner is hopeful that some iteration could be used in clinical practice within a few years.

In May, he and colleagues at Stanford (Calif.) University published a paper in Nature Biotechnology describing their smart bandage. It includes a microcontroller unit, a radio antenna, biosensors, and an electrical stimulator all affixed to a rubbery, skin-like polymer (or hydrogel) about the thickness of a single coat of latex paint.

The bandage senses changes in temperature and electrical conductivity as the wound heals, and it gives electrical stimulation to accelerate that healing.

Animals treated with the bandage healed 25% faster, with 50% less scarring.

Electrical currents are already used for wound healing in clinical practice, Dr. Gurtner said. Because the stimulus is already approved and the cost to make the bandage could be low (as little as $10 to $50), he believes it could be ushered through the approval processes relatively quickly.

“Is this the ultimate embodiment of all the bells and whistles that are possible in a smart bandage? No. Not yet,” he said. “But we think it will help people. And right now, that’s good enough.”

A version of this article appeared on WebMD.com.

You cut yourself. You put on a bandage. In a week or so, your wound heals.

Most people take this routine for granted. But for the more than 8.2 million Americans who have chronic wounds, it’s not so simple.

Traumatic injuries, post-surgical complications, advanced age, and chronic illnesses like diabetes and vascular disease can all disrupt the delicate healing process, leading to wounds that last months or years. 

Left untreated, about 30% led to amputation. And recent studies show the risk of dying from a chronic wound complication within 5 years rivals that of most cancers.

Yet until recently, medical technology had not kept up with what experts say is a snowballing threat to public health.

“Wound care – even with all of the billions of products that are sold – still exists on kind of a medieval level,” said Geoffrey Gurtner, MD, chair of the department of surgery and professor of biomedical engineering at the University of Arizona College of Medicine. “We’re still putting on poultices and salves ... and when it comes to diagnosing infection, it’s really an art. I think we can do better.” 
 

Old-school bandage meets AI

Dr. Gurtner is among dozens of clinicians and researchers reimagining the humble bandage, combining cutting-edge materials science with artificial intelligence and patient data to develop “smart bandages” that do far more than shield a wound.

Someday soon, these paper-thin bandages embedded with miniaturized electronics could monitor the healing process in real time, alerting the patient – or a doctor – when things go wrong. With the press of a smartphone button, that bandage could deliver medicine to fight an infection or an electrical pulse to stimulate healing.

Some “closed-loop” designs need no prompting, instead monitoring the wound and automatically giving it what it needs.

Others in development could halt a battlefield wound from hemorrhaging or kick-start healing in a blast wound, preventing longer-term disability. 

The same technologies could – if the price is right – speed up healing and reduce scarring in minor cuts and scrapes, too, said Dr. Gurtner. 

And unlike many cutting-edge medical innovations, these next-generation bandages could be made relatively cheaply and benefit some of the most vulnerable populations, including older adults, people with low incomes, and those in developing countries.

They could also save the health care system money, as the U.S. spends more than $28 billion annually treating chronic wounds.

“This is a condition that many patients find shameful and embarrassing, so there hasn’t been a lot of advocacy,” said Dr. Gurtner, outgoing board president of the Wound Healing Society. “It’s a relatively ignored problem afflicting an underserved population that has a huge cost. It’s a perfect storm.”
 

How wounds heal, or don’t

Wound healing is one of the most complex processes of the human body.

First platelets rush to the injury, prompting blood to clot. Then immune cells emit compounds called inflammatory cytokines, helping to fight off pathogens and keep infection at bay. Other compounds, including nitric oxide, spark the growth of new blood vessels and collagen to rebuild skin and connective tissue. As inflammation slows and stops, the flesh continues to reform.

But some conditions can stall the process, often in the inflammatory stage. 

In people with diabetes, high glucose levels and poor circulation tend to sabotage the process. And people with nerve damage from spinal cord injuries, diabetes, or other ailments may not be able to feel it when a wound is getting worse or reinjured.

“We end up with patients going months with open wounds that are festering and infected,” said Roslyn Rivkah Isseroff, MD, professor of dermatology at the University of California Davis and head of the VA Northern California Health Care System’s wound healing clinic. “The patients are upset with the smell. These open ulcers put the patient at risk for systemic infection, like sepsis.” It can impact mental health, draining the patient’s ability to care for their wound.

“We see them once a week and send them home and say change your dressing every day, and they say, ‘I can barely move. I can’t do this,’ ” said Dr. Isseroff.

Checking for infection means removing bandages and culturing the wound. That can be painful, and results take time. 

A lot can happen to a wound in a week.

“Sometimes, they come back and it’s a disaster, and they have to be admitted to the ER or even get an amputation,” Dr. Gurtner said. 

People who are housing insecure or lack access to health care are even more vulnerable to complications. 

“If you had the ability to say ‘there is something bad happening,’ you could do a lot to prevent this cascade and downward spiral.” 
 

Bandages 2.0

In 2019, the Defense Advanced Research Projects Agency, the research arm of the Department of Defense, launched the Bioelectronics for Tissue Regeneration program to encourage scientists to develop a “closed-loop” bandage capable of both monitoring and hastening healing.

Tens of millions in funding has kick-started a flood of innovation since.

“It’s kind of a race to the finish,” said Marco Rolandi, PhD, associate professor of electrical and computer engineering at the University of California Santa Cruz and the principal investigator for a team including engineers, medical doctors, and computer scientists from UC Santa Cruz, UC Davis, and Tufts. “I’ve been amazed and impressed at all the work coming out.”

His team’s goal is to cut healing time in half by using (a) real-time monitoring of how a wound is healing – using indicators like temperature, pH level, oxygen, moisture, glucose, electrical activity, and certain proteins, and (b) appropriate stimulation.

“Every wound is different, so there is no one solution,” said Dr. Isseroff, the team’s clinical lead. “The idea is that it will be able to sense different parameters unique to the wound, use AI to figure out what stage it is in, and provide the right stimulus to kick it out of that stalled stage.”

The team has developed a proof-of-concept prototype: a bandage embedded with a tiny camera that takes pictures and transmits them to a computer algorithm to assess the wound’s progress. Miniaturized battery-powered actuators, or motors, automatically deliver medication.

Phase I trials in rodents went well, Dr. Rolandi said. The team is now testing the bandage on pigs.

Across the globe, other promising developments are underway.

In a scientific paper published in May, researchers at the University of Glasgow described a new “low-cost, environmentally friendly” bandage embedded with light-emitting diodes that use ultraviolet light to kill bacteria – no antibiotics needed. The fabric is stitched with a slim, flexible coil that powers the lights without a battery using wireless power transfer. In lab studies, it eradicated gram-negative bacteria (some of the nastiest bugs) in 6 hours.

Also in May, in the journal Bioactive Materials, a Penn State team detailed a bandage with medicine-injecting microneedles that can halt bleeding immediately after injury. In lab and animal tests, it reduced clotting time from 11.5 minutes to 1.3 minutes and bleeding by 90%.

“With hemorrhaging injuries, it is often the loss of blood – not the injury itself – that causes death,” said study author Amir Sheikhi, PhD, assistant professor of chemical and biomedical engineering at Penn State. “Those 10 minutes could be the difference between life and death.” 

Another smart bandage, developed at Northwestern University, Chicago, harmlessly dissolves – electrodes and all – into the body after it is no longer needed, eliminating what can be a painful removal.

Guillermo Ameer, DSc, a study author reporting on the technology in Science Advances, hopes it could be made cheaply and used in developing countries.

“We’d like to create something that you could use in your home, even in a very remote village,” said Dr. Ameer, professor of biomedical engineering at Northwestern.
 

Timeline for clinical use

These are early days for the smart bandage, scientists say. Most studies have been in rodents and more work is needed to develop human-scale bandages, reduce cost, solve long-term data storage, and ensure material adheres well without irritating the skin.

But Dr. Gurtner is hopeful that some iteration could be used in clinical practice within a few years.

In May, he and colleagues at Stanford (Calif.) University published a paper in Nature Biotechnology describing their smart bandage. It includes a microcontroller unit, a radio antenna, biosensors, and an electrical stimulator all affixed to a rubbery, skin-like polymer (or hydrogel) about the thickness of a single coat of latex paint.

The bandage senses changes in temperature and electrical conductivity as the wound heals, and it gives electrical stimulation to accelerate that healing.

Animals treated with the bandage healed 25% faster, with 50% less scarring.

Electrical currents are already used for wound healing in clinical practice, Dr. Gurtner said. Because the stimulus is already approved and the cost to make the bandage could be low (as little as $10 to $50), he believes it could be ushered through the approval processes relatively quickly.

“Is this the ultimate embodiment of all the bells and whistles that are possible in a smart bandage? No. Not yet,” he said. “But we think it will help people. And right now, that’s good enough.”

A version of this article appeared on WebMD.com.

You cut yourself. You put on a bandage. In a week or so, your wound heals.

Most people take this routine for granted. But for the more than 8.2 million Americans who have chronic wounds, it’s not so simple.

Traumatic injuries, post-surgical complications, advanced age, and chronic illnesses like diabetes and vascular disease can all disrupt the delicate healing process, leading to wounds that last months or years. 

Left untreated, about 30% led to amputation. And recent studies show the risk of dying from a chronic wound complication within 5 years rivals that of most cancers.

Yet until recently, medical technology had not kept up with what experts say is a snowballing threat to public health.

“Wound care – even with all of the billions of products that are sold – still exists on kind of a medieval level,” said Geoffrey Gurtner, MD, chair of the department of surgery and professor of biomedical engineering at the University of Arizona College of Medicine. “We’re still putting on poultices and salves ... and when it comes to diagnosing infection, it’s really an art. I think we can do better.” 
 

Old-school bandage meets AI

Dr. Gurtner is among dozens of clinicians and researchers reimagining the humble bandage, combining cutting-edge materials science with artificial intelligence and patient data to develop “smart bandages” that do far more than shield a wound.

Someday soon, these paper-thin bandages embedded with miniaturized electronics could monitor the healing process in real time, alerting the patient – or a doctor – when things go wrong. With the press of a smartphone button, that bandage could deliver medicine to fight an infection or an electrical pulse to stimulate healing.

Some “closed-loop” designs need no prompting, instead monitoring the wound and automatically giving it what it needs.

Others in development could halt a battlefield wound from hemorrhaging or kick-start healing in a blast wound, preventing longer-term disability. 

The same technologies could – if the price is right – speed up healing and reduce scarring in minor cuts and scrapes, too, said Dr. Gurtner. 

And unlike many cutting-edge medical innovations, these next-generation bandages could be made relatively cheaply and benefit some of the most vulnerable populations, including older adults, people with low incomes, and those in developing countries.

They could also save the health care system money, as the U.S. spends more than $28 billion annually treating chronic wounds.

“This is a condition that many patients find shameful and embarrassing, so there hasn’t been a lot of advocacy,” said Dr. Gurtner, outgoing board president of the Wound Healing Society. “It’s a relatively ignored problem afflicting an underserved population that has a huge cost. It’s a perfect storm.”
 

How wounds heal, or don’t

Wound healing is one of the most complex processes of the human body.

First platelets rush to the injury, prompting blood to clot. Then immune cells emit compounds called inflammatory cytokines, helping to fight off pathogens and keep infection at bay. Other compounds, including nitric oxide, spark the growth of new blood vessels and collagen to rebuild skin and connective tissue. As inflammation slows and stops, the flesh continues to reform.

But some conditions can stall the process, often in the inflammatory stage. 

In people with diabetes, high glucose levels and poor circulation tend to sabotage the process. And people with nerve damage from spinal cord injuries, diabetes, or other ailments may not be able to feel it when a wound is getting worse or reinjured.

“We end up with patients going months with open wounds that are festering and infected,” said Roslyn Rivkah Isseroff, MD, professor of dermatology at the University of California Davis and head of the VA Northern California Health Care System’s wound healing clinic. “The patients are upset with the smell. These open ulcers put the patient at risk for systemic infection, like sepsis.” It can impact mental health, draining the patient’s ability to care for their wound.

“We see them once a week and send them home and say change your dressing every day, and they say, ‘I can barely move. I can’t do this,’ ” said Dr. Isseroff.

Checking for infection means removing bandages and culturing the wound. That can be painful, and results take time. 

A lot can happen to a wound in a week.

“Sometimes, they come back and it’s a disaster, and they have to be admitted to the ER or even get an amputation,” Dr. Gurtner said. 

People who are housing insecure or lack access to health care are even more vulnerable to complications. 

“If you had the ability to say ‘there is something bad happening,’ you could do a lot to prevent this cascade and downward spiral.” 
 

Bandages 2.0

In 2019, the Defense Advanced Research Projects Agency, the research arm of the Department of Defense, launched the Bioelectronics for Tissue Regeneration program to encourage scientists to develop a “closed-loop” bandage capable of both monitoring and hastening healing.

Tens of millions in funding has kick-started a flood of innovation since.

“It’s kind of a race to the finish,” said Marco Rolandi, PhD, associate professor of electrical and computer engineering at the University of California Santa Cruz and the principal investigator for a team including engineers, medical doctors, and computer scientists from UC Santa Cruz, UC Davis, and Tufts. “I’ve been amazed and impressed at all the work coming out.”

His team’s goal is to cut healing time in half by using (a) real-time monitoring of how a wound is healing – using indicators like temperature, pH level, oxygen, moisture, glucose, electrical activity, and certain proteins, and (b) appropriate stimulation.

“Every wound is different, so there is no one solution,” said Dr. Isseroff, the team’s clinical lead. “The idea is that it will be able to sense different parameters unique to the wound, use AI to figure out what stage it is in, and provide the right stimulus to kick it out of that stalled stage.”

The team has developed a proof-of-concept prototype: a bandage embedded with a tiny camera that takes pictures and transmits them to a computer algorithm to assess the wound’s progress. Miniaturized battery-powered actuators, or motors, automatically deliver medication.

Phase I trials in rodents went well, Dr. Rolandi said. The team is now testing the bandage on pigs.

Across the globe, other promising developments are underway.

In a scientific paper published in May, researchers at the University of Glasgow described a new “low-cost, environmentally friendly” bandage embedded with light-emitting diodes that use ultraviolet light to kill bacteria – no antibiotics needed. The fabric is stitched with a slim, flexible coil that powers the lights without a battery using wireless power transfer. In lab studies, it eradicated gram-negative bacteria (some of the nastiest bugs) in 6 hours.

Also in May, in the journal Bioactive Materials, a Penn State team detailed a bandage with medicine-injecting microneedles that can halt bleeding immediately after injury. In lab and animal tests, it reduced clotting time from 11.5 minutes to 1.3 minutes and bleeding by 90%.

“With hemorrhaging injuries, it is often the loss of blood – not the injury itself – that causes death,” said study author Amir Sheikhi, PhD, assistant professor of chemical and biomedical engineering at Penn State. “Those 10 minutes could be the difference between life and death.” 

Another smart bandage, developed at Northwestern University, Chicago, harmlessly dissolves – electrodes and all – into the body after it is no longer needed, eliminating what can be a painful removal.

Guillermo Ameer, DSc, a study author reporting on the technology in Science Advances, hopes it could be made cheaply and used in developing countries.

“We’d like to create something that you could use in your home, even in a very remote village,” said Dr. Ameer, professor of biomedical engineering at Northwestern.
 

Timeline for clinical use

These are early days for the smart bandage, scientists say. Most studies have been in rodents and more work is needed to develop human-scale bandages, reduce cost, solve long-term data storage, and ensure material adheres well without irritating the skin.

But Dr. Gurtner is hopeful that some iteration could be used in clinical practice within a few years.

In May, he and colleagues at Stanford (Calif.) University published a paper in Nature Biotechnology describing their smart bandage. It includes a microcontroller unit, a radio antenna, biosensors, and an electrical stimulator all affixed to a rubbery, skin-like polymer (or hydrogel) about the thickness of a single coat of latex paint.

The bandage senses changes in temperature and electrical conductivity as the wound heals, and it gives electrical stimulation to accelerate that healing.

Animals treated with the bandage healed 25% faster, with 50% less scarring.

Electrical currents are already used for wound healing in clinical practice, Dr. Gurtner said. Because the stimulus is already approved and the cost to make the bandage could be low (as little as $10 to $50), he believes it could be ushered through the approval processes relatively quickly.

“Is this the ultimate embodiment of all the bells and whistles that are possible in a smart bandage? No. Not yet,” he said. “But we think it will help people. And right now, that’s good enough.”

A version of this article appeared on WebMD.com.