MDedge Endocrinology

A 76-year-old woman presented recently to a Toronto-area hospital with acute onset muscle pain, limb weakness, difficulty walking, and rhabdomyolysis associated with a sharp spike in her plasma level of rosuvastatin – a drug she had been on uneventfully for more than 5 years, within days of starting for the first time treatment with the SGLT2 inhibitor canagliflozin (Invokana).

The patient’s Canadian clinicians stopped her treatment with both rosuvastatin and canagliflozin, administered intravenous crystalloid fluids, and within days her pain subsided and her limb weakness gradually improved, allowing her discharge 10 days later while she was ambulating with a walker.

“To our knowledge this is the first published report of a drug interaction between rosuvastatin and canagliflozin,” wrote the authors of the case report (Ann Intern Med. 2020 Aug 3. doi: 10.7326/L20-0549). They cited the importance of the observation given the widespread use today of rosuvastatin for lowering low density lipoprotein cholesterol and exerting pleiotropic effects; and canagliflozin for its modest effects for reducing hyperglycemia, as well as its important role in reducing adverse cardiovascular outcomes, slowing progression of chronic kidney disease, and having a mild but important diuretic effect. “We encourage clinicians to remain vigilant for features of myotoxicity when canagliflozin and rosuvastatin are coprescribed,” they wrote, avoiding discussion of whether this may represent class or drug-specific effects.

“It’s reasonable to be mindful of this risk, but this is not a reason to not use rosuvastatin and canagliflozin in a patient,” nor for the time being to avoid any other combination of a statin and SGLT2 (sodium-glucose cotransporter 2) inhibitor, said David Juurlink, MD, head of the division of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre in Toronto and lead author of the report. “Few drug interactions have absolute contraindications. The admonition is just to be careful. It’s premature to say they shouldn’t be used together,” he said in an interview.

“We don’t know how much of an outlier this patient is. But it would be important to tell patients” on this or a similar combination to alert their clinicians if they start to have muscle aches, which should be a “red flag” to stop the statin, the SGLT2 inhibitor, or both until the situation can be fully assessed, Dr. Juurlink advised.
 

Sky high rosuvastatin levels

The linchpin of the observed adverse effects appeared to be a startlingly high elevation of the patient’s plasma rosuvastatin level when she was hospitalized 15 days after starting canagliflozin and 12 days after the onset of her thigh pain and weakness. Testing showed a plasma rosuvastatin concentration of 176 ng/mL, “more than 15-fold higher than the mean value expected” in patients taking 40 mg rosuvastatin daily, the maximum labeled dosage for the drug and what the affected patient had been taking without prior incident for more than 5 years. The patient’s canagliflozin dosage was 100 mg/day, the standard starting dosage according to the drug’s label.

The report’s authors noted that genetic assessment of the patient, a woman originally from the Philippines who was “high functioning,” and diagnosed with type 2 diabetes, showed she was heterozygous for a polymorphism, c.421C>A, which is linked with increased rosuvastatin plasma levels in the plasma. They also cited a report that canagliflozin can interact with proteins involved in hepatic drug uptake.

“We speculate that, in our patient, the addition of canagliflozin enhanced intestinal rosuvastatin absorption, inhibited its hepatocellular uptake, and impaired its excretion into bile canaliculi and the proximal tubule, resulting in rosuvastatin accumulation and leading to hepatotoxicity and myotoxicity,” the clinicians wrote in their report.

“There is little doubt this was a drug interaction, but it does not apply uniformly to everyone.” The severity of the interaction would depend on the dosages, the comorbidities a patient has, and their genetic profile, Dr. Juurlink said.
 

Concern and skepticism

Other clinicians who regularly prescribe these drugs expressed concern about the observation as well as skepticism about the prevalence of patients who could potentially experience similar effects.

Catherine Hackett/MDedge News

“We don’t know how common are these genetic abnormalities. If this is extremely rare, then it doesn’t have many clinical implications, but if a large portion of the population has this [genetic] abnormality, it’s something we’d need to pay attention to,” Steven E. Nissen, MD, chair of cardiovascular medicine at the Cleveland Clinic Foundation, said in an interview. “It will be important to know the prevalence” of the genetic polymorphism carried by the reported patient, said Dr. Nissen, who has done research on lipid-lowering medications and drug safety.

“This could be important, or a very rare one-off. I can’t say which,” based on what’s currently known, he said. “There are many unanswered questions that make it hard to know how important this will be. It requires further investigation. There is a lot of uncertainty.”

Dr. Nissen particularly endorsed studies that approach this issue by looking at the prevalence rates of the implicated genetic polymorphism rather than pharmacovigilance studies that make epidemiologic assessments of adverse-effect prevalence. Studies that look for adverse-effect associations in large patient populations are “sloppy, and unless the interaction is incredibly intense they are not very sensitive,” he said.

But Dr. Juurlink, a pharmacoepidemiologist whose specialty includes studies of this sort, said that they could be useful if carefully designed. He suggested, for example, comparing in large patient databases the observed incidence of rhabdomyolysis among patients on an SGLT2 inhibitor and also on rosuvastatin with those on pravastatin, a statin with a different metabolic profile. Another approach to further examining the observation would be dosage studies with rosuvastatin and canagliflozin in healthy volunteers, he said.

Dr. Nissen noted that rosuvastatin is a key agent from the statin class because it’s the “most effective” for lowering low density lipoprotein cholesterol. “Rosuvastatin is a go-to drug,” he declared. On the other hand, canagliflozin is “a little less used” than other drugs in the SGLT2 inhibitor class, specifically dapagliflozin (Farxiga) and empagliflozin (Jardiance), he said.

One in a million?

“This was a freak accident. I don’t find it at all concerning. It was definitely one in a million,” Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of America in Tarzana, Calif., said in an interview. “None of us have seen it” in either the several cardiovascular outcome trials now run on multiple drugs in the SGLT2 inhibitor class that included many patients also taking a statin, or in routine practice, he said. Dr. Handelsman noted that in his practice he had never seen a similar case despite treating “hundreds if not thousands of patients” with type 2 diabetes, virtually all of whom were on a statin and were also treated with an SGLT2 inhibitor, including many with canagliflozin.

Dr. Handelsman cited the notably low estimated glomerular filtration rate in the reported patient, who was described as having a serum creatinine level of 150 mcmol/L (1.7 mg/dL) prior to canagliflozin treatment that then rose to 194 mcmol/L (2.19 mg/dL) at the time of hospitalization, which corresponds to estimated glomerular filtration rates of 29-31 and 21-23 mL/min per 1.73 m², respectively, depending on the calculator used, rates that were possibly below the labeled minimum rate of 30 mL/min per 1.73 m² for patients starting canagliflozin treatment. The case report cited the patient as having stage 3B chronic kidney disease, which corresponds to a eGFR of 30-44* mL/min per 1.73 m².

“I think the patient had acute kidney injury” on starting canagliflozin “that may have affected the [rosuvastatin] metabolism,” Dr. Handelsman suggested. “She had severe kidney dysfunction to start with that fell further with SGLT2 inhibitor treatment,” a well described and usually transient effect of starting drugs in this class because of changes the SGLT2 inhibitors cause in renal blood flow. He noted that the patient had not been receiving an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, which may have contributed to her acute problems with fluid balance. Most similar patients with type 2 diabetes, cardiovascular disease risk, and chronic kidney disease would be on stable treatment with a drug that inhibits the renin-angiotensin system before starting an SGLT2 inhibitor, and not already having a RAS inhibitor on board before starting canagliflozin may have somehow contributed to the observed adverse effects, Dr. Handelsman said.

Dr. Juurlink was skeptical that the kidneys played a major role. “An abrupt change in renal function can influence statin clearance, but this was a 15-fold increase. You can’t explain such a dramatic increase by a transient reduction in renal function,” he said.

Dr. Juurlink and coauthors had no disclosures. Dr. Nissen had no relevant disclosures. Dr. Handelsman has been a consultant to companies that market drugs in the SGLT2 inhibitor class.

mzoler@mdedge.com

SOURCE: Brailovski E et al. Ann Intern Med. 2020 Aug 3. doi: 10.7326/L20-0549.

*Correction: This value was missing from the original article.

A 76-year-old woman presented recently to a Toronto-area hospital with acute onset muscle pain, limb weakness, difficulty walking, and rhabdomyolysis associated with a sharp spike in her plasma level of rosuvastatin – a drug she had been on uneventfully for more than 5 years, within days of starting for the first time treatment with the SGLT2 inhibitor canagliflozin (Invokana).

The patient’s Canadian clinicians stopped her treatment with both rosuvastatin and canagliflozin, administered intravenous crystalloid fluids, and within days her pain subsided and her limb weakness gradually improved, allowing her discharge 10 days later while she was ambulating with a walker.

“To our knowledge this is the first published report of a drug interaction between rosuvastatin and canagliflozin,” wrote the authors of the case report (Ann Intern Med. 2020 Aug 3. doi: 10.7326/L20-0549). They cited the importance of the observation given the widespread use today of rosuvastatin for lowering low density lipoprotein cholesterol and exerting pleiotropic effects; and canagliflozin for its modest effects for reducing hyperglycemia, as well as its important role in reducing adverse cardiovascular outcomes, slowing progression of chronic kidney disease, and having a mild but important diuretic effect. “We encourage clinicians to remain vigilant for features of myotoxicity when canagliflozin and rosuvastatin are coprescribed,” they wrote, avoiding discussion of whether this may represent class or drug-specific effects.

“It’s reasonable to be mindful of this risk, but this is not a reason to not use rosuvastatin and canagliflozin in a patient,” nor for the time being to avoid any other combination of a statin and SGLT2 (sodium-glucose cotransporter 2) inhibitor, said David Juurlink, MD, head of the division of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre in Toronto and lead author of the report. “Few drug interactions have absolute contraindications. The admonition is just to be careful. It’s premature to say they shouldn’t be used together,” he said in an interview.

“We don’t know how much of an outlier this patient is. But it would be important to tell patients” on this or a similar combination to alert their clinicians if they start to have muscle aches, which should be a “red flag” to stop the statin, the SGLT2 inhibitor, or both until the situation can be fully assessed, Dr. Juurlink advised.
 

Sky high rosuvastatin levels

The linchpin of the observed adverse effects appeared to be a startlingly high elevation of the patient’s plasma rosuvastatin level when she was hospitalized 15 days after starting canagliflozin and 12 days after the onset of her thigh pain and weakness. Testing showed a plasma rosuvastatin concentration of 176 ng/mL, “more than 15-fold higher than the mean value expected” in patients taking 40 mg rosuvastatin daily, the maximum labeled dosage for the drug and what the affected patient had been taking without prior incident for more than 5 years. The patient’s canagliflozin dosage was 100 mg/day, the standard starting dosage according to the drug’s label.

The report’s authors noted that genetic assessment of the patient, a woman originally from the Philippines who was “high functioning,” and diagnosed with type 2 diabetes, showed she was heterozygous for a polymorphism, c.421C>A, which is linked with increased rosuvastatin plasma levels in the plasma. They also cited a report that canagliflozin can interact with proteins involved in hepatic drug uptake.

“We speculate that, in our patient, the addition of canagliflozin enhanced intestinal rosuvastatin absorption, inhibited its hepatocellular uptake, and impaired its excretion into bile canaliculi and the proximal tubule, resulting in rosuvastatin accumulation and leading to hepatotoxicity and myotoxicity,” the clinicians wrote in their report.

“There is little doubt this was a drug interaction, but it does not apply uniformly to everyone.” The severity of the interaction would depend on the dosages, the comorbidities a patient has, and their genetic profile, Dr. Juurlink said.
 

Concern and skepticism

Other clinicians who regularly prescribe these drugs expressed concern about the observation as well as skepticism about the prevalence of patients who could potentially experience similar effects.

Catherine Hackett/MDedge News

“We don’t know how common are these genetic abnormalities. If this is extremely rare, then it doesn’t have many clinical implications, but if a large portion of the population has this [genetic] abnormality, it’s something we’d need to pay attention to,” Steven E. Nissen, MD, chair of cardiovascular medicine at the Cleveland Clinic Foundation, said in an interview. “It will be important to know the prevalence” of the genetic polymorphism carried by the reported patient, said Dr. Nissen, who has done research on lipid-lowering medications and drug safety.

“This could be important, or a very rare one-off. I can’t say which,” based on what’s currently known, he said. “There are many unanswered questions that make it hard to know how important this will be. It requires further investigation. There is a lot of uncertainty.”

Dr. Nissen particularly endorsed studies that approach this issue by looking at the prevalence rates of the implicated genetic polymorphism rather than pharmacovigilance studies that make epidemiologic assessments of adverse-effect prevalence. Studies that look for adverse-effect associations in large patient populations are “sloppy, and unless the interaction is incredibly intense they are not very sensitive,” he said.

But Dr. Juurlink, a pharmacoepidemiologist whose specialty includes studies of this sort, said that they could be useful if carefully designed. He suggested, for example, comparing in large patient databases the observed incidence of rhabdomyolysis among patients on an SGLT2 inhibitor and also on rosuvastatin with those on pravastatin, a statin with a different metabolic profile. Another approach to further examining the observation would be dosage studies with rosuvastatin and canagliflozin in healthy volunteers, he said.

Dr. Nissen noted that rosuvastatin is a key agent from the statin class because it’s the “most effective” for lowering low density lipoprotein cholesterol. “Rosuvastatin is a go-to drug,” he declared. On the other hand, canagliflozin is “a little less used” than other drugs in the SGLT2 inhibitor class, specifically dapagliflozin (Farxiga) and empagliflozin (Jardiance), he said.

One in a million?

“This was a freak accident. I don’t find it at all concerning. It was definitely one in a million,” Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of America in Tarzana, Calif., said in an interview. “None of us have seen it” in either the several cardiovascular outcome trials now run on multiple drugs in the SGLT2 inhibitor class that included many patients also taking a statin, or in routine practice, he said. Dr. Handelsman noted that in his practice he had never seen a similar case despite treating “hundreds if not thousands of patients” with type 2 diabetes, virtually all of whom were on a statin and were also treated with an SGLT2 inhibitor, including many with canagliflozin.

Dr. Handelsman cited the notably low estimated glomerular filtration rate in the reported patient, who was described as having a serum creatinine level of 150 mcmol/L (1.7 mg/dL) prior to canagliflozin treatment that then rose to 194 mcmol/L (2.19 mg/dL) at the time of hospitalization, which corresponds to estimated glomerular filtration rates of 29-31 and 21-23 mL/min per 1.73 m², respectively, depending on the calculator used, rates that were possibly below the labeled minimum rate of 30 mL/min per 1.73 m² for patients starting canagliflozin treatment. The case report cited the patient as having stage 3B chronic kidney disease, which corresponds to a eGFR of 30-44* mL/min per 1.73 m².

“I think the patient had acute kidney injury” on starting canagliflozin “that may have affected the [rosuvastatin] metabolism,” Dr. Handelsman suggested. “She had severe kidney dysfunction to start with that fell further with SGLT2 inhibitor treatment,” a well described and usually transient effect of starting drugs in this class because of changes the SGLT2 inhibitors cause in renal blood flow. He noted that the patient had not been receiving an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, which may have contributed to her acute problems with fluid balance. Most similar patients with type 2 diabetes, cardiovascular disease risk, and chronic kidney disease would be on stable treatment with a drug that inhibits the renin-angiotensin system before starting an SGLT2 inhibitor, and not already having a RAS inhibitor on board before starting canagliflozin may have somehow contributed to the observed adverse effects, Dr. Handelsman said.

Dr. Juurlink was skeptical that the kidneys played a major role. “An abrupt change in renal function can influence statin clearance, but this was a 15-fold increase. You can’t explain such a dramatic increase by a transient reduction in renal function,” he said.

Dr. Juurlink and coauthors had no disclosures. Dr. Nissen had no relevant disclosures. Dr. Handelsman has been a consultant to companies that market drugs in the SGLT2 inhibitor class.

mzoler@mdedge.com

SOURCE: Brailovski E et al. Ann Intern Med. 2020 Aug 3. doi: 10.7326/L20-0549.

*Correction: This value was missing from the original article.

A 76-year-old woman presented recently to a Toronto-area hospital with acute onset muscle pain, limb weakness, difficulty walking, and rhabdomyolysis associated with a sharp spike in her plasma level of rosuvastatin – a drug she had been on uneventfully for more than 5 years, within days of starting for the first time treatment with the SGLT2 inhibitor canagliflozin (Invokana).

The patient’s Canadian clinicians stopped her treatment with both rosuvastatin and canagliflozin, administered intravenous crystalloid fluids, and within days her pain subsided and her limb weakness gradually improved, allowing her discharge 10 days later while she was ambulating with a walker.

“To our knowledge this is the first published report of a drug interaction between rosuvastatin and canagliflozin,” wrote the authors of the case report (Ann Intern Med. 2020 Aug 3. doi: 10.7326/L20-0549). They cited the importance of the observation given the widespread use today of rosuvastatin for lowering low density lipoprotein cholesterol and exerting pleiotropic effects; and canagliflozin for its modest effects for reducing hyperglycemia, as well as its important role in reducing adverse cardiovascular outcomes, slowing progression of chronic kidney disease, and having a mild but important diuretic effect. “We encourage clinicians to remain vigilant for features of myotoxicity when canagliflozin and rosuvastatin are coprescribed,” they wrote, avoiding discussion of whether this may represent class or drug-specific effects.

“It’s reasonable to be mindful of this risk, but this is not a reason to not use rosuvastatin and canagliflozin in a patient,” nor for the time being to avoid any other combination of a statin and SGLT2 (sodium-glucose cotransporter 2) inhibitor, said David Juurlink, MD, head of the division of clinical pharmacology and toxicology at Sunnybrook Health Sciences Centre in Toronto and lead author of the report. “Few drug interactions have absolute contraindications. The admonition is just to be careful. It’s premature to say they shouldn’t be used together,” he said in an interview.

“We don’t know how much of an outlier this patient is. But it would be important to tell patients” on this or a similar combination to alert their clinicians if they start to have muscle aches, which should be a “red flag” to stop the statin, the SGLT2 inhibitor, or both until the situation can be fully assessed, Dr. Juurlink advised.
 

Sky high rosuvastatin levels

The linchpin of the observed adverse effects appeared to be a startlingly high elevation of the patient’s plasma rosuvastatin level when she was hospitalized 15 days after starting canagliflozin and 12 days after the onset of her thigh pain and weakness. Testing showed a plasma rosuvastatin concentration of 176 ng/mL, “more than 15-fold higher than the mean value expected” in patients taking 40 mg rosuvastatin daily, the maximum labeled dosage for the drug and what the affected patient had been taking without prior incident for more than 5 years. The patient’s canagliflozin dosage was 100 mg/day, the standard starting dosage according to the drug’s label.

The report’s authors noted that genetic assessment of the patient, a woman originally from the Philippines who was “high functioning,” and diagnosed with type 2 diabetes, showed she was heterozygous for a polymorphism, c.421C>A, which is linked with increased rosuvastatin plasma levels in the plasma. They also cited a report that canagliflozin can interact with proteins involved in hepatic drug uptake.

“We speculate that, in our patient, the addition of canagliflozin enhanced intestinal rosuvastatin absorption, inhibited its hepatocellular uptake, and impaired its excretion into bile canaliculi and the proximal tubule, resulting in rosuvastatin accumulation and leading to hepatotoxicity and myotoxicity,” the clinicians wrote in their report.

“There is little doubt this was a drug interaction, but it does not apply uniformly to everyone.” The severity of the interaction would depend on the dosages, the comorbidities a patient has, and their genetic profile, Dr. Juurlink said.
 

Concern and skepticism

Other clinicians who regularly prescribe these drugs expressed concern about the observation as well as skepticism about the prevalence of patients who could potentially experience similar effects.

Catherine Hackett/MDedge News

“We don’t know how common are these genetic abnormalities. If this is extremely rare, then it doesn’t have many clinical implications, but if a large portion of the population has this [genetic] abnormality, it’s something we’d need to pay attention to,” Steven E. Nissen, MD, chair of cardiovascular medicine at the Cleveland Clinic Foundation, said in an interview. “It will be important to know the prevalence” of the genetic polymorphism carried by the reported patient, said Dr. Nissen, who has done research on lipid-lowering medications and drug safety.

“This could be important, or a very rare one-off. I can’t say which,” based on what’s currently known, he said. “There are many unanswered questions that make it hard to know how important this will be. It requires further investigation. There is a lot of uncertainty.”

Dr. Nissen particularly endorsed studies that approach this issue by looking at the prevalence rates of the implicated genetic polymorphism rather than pharmacovigilance studies that make epidemiologic assessments of adverse-effect prevalence. Studies that look for adverse-effect associations in large patient populations are “sloppy, and unless the interaction is incredibly intense they are not very sensitive,” he said.

But Dr. Juurlink, a pharmacoepidemiologist whose specialty includes studies of this sort, said that they could be useful if carefully designed. He suggested, for example, comparing in large patient databases the observed incidence of rhabdomyolysis among patients on an SGLT2 inhibitor and also on rosuvastatin with those on pravastatin, a statin with a different metabolic profile. Another approach to further examining the observation would be dosage studies with rosuvastatin and canagliflozin in healthy volunteers, he said.

Dr. Nissen noted that rosuvastatin is a key agent from the statin class because it’s the “most effective” for lowering low density lipoprotein cholesterol. “Rosuvastatin is a go-to drug,” he declared. On the other hand, canagliflozin is “a little less used” than other drugs in the SGLT2 inhibitor class, specifically dapagliflozin (Farxiga) and empagliflozin (Jardiance), he said.

One in a million?

“This was a freak accident. I don’t find it at all concerning. It was definitely one in a million,” Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of America in Tarzana, Calif., said in an interview. “None of us have seen it” in either the several cardiovascular outcome trials now run on multiple drugs in the SGLT2 inhibitor class that included many patients also taking a statin, or in routine practice, he said. Dr. Handelsman noted that in his practice he had never seen a similar case despite treating “hundreds if not thousands of patients” with type 2 diabetes, virtually all of whom were on a statin and were also treated with an SGLT2 inhibitor, including many with canagliflozin.

Dr. Handelsman cited the notably low estimated glomerular filtration rate in the reported patient, who was described as having a serum creatinine level of 150 mcmol/L (1.7 mg/dL) prior to canagliflozin treatment that then rose to 194 mcmol/L (2.19 mg/dL) at the time of hospitalization, which corresponds to estimated glomerular filtration rates of 29-31 and 21-23 mL/min per 1.73 m², respectively, depending on the calculator used, rates that were possibly below the labeled minimum rate of 30 mL/min per 1.73 m² for patients starting canagliflozin treatment. The case report cited the patient as having stage 3B chronic kidney disease, which corresponds to a eGFR of 30-44* mL/min per 1.73 m².

“I think the patient had acute kidney injury” on starting canagliflozin “that may have affected the [rosuvastatin] metabolism,” Dr. Handelsman suggested. “She had severe kidney dysfunction to start with that fell further with SGLT2 inhibitor treatment,” a well described and usually transient effect of starting drugs in this class because of changes the SGLT2 inhibitors cause in renal blood flow. He noted that the patient had not been receiving an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, which may have contributed to her acute problems with fluid balance. Most similar patients with type 2 diabetes, cardiovascular disease risk, and chronic kidney disease would be on stable treatment with a drug that inhibits the renin-angiotensin system before starting an SGLT2 inhibitor, and not already having a RAS inhibitor on board before starting canagliflozin may have somehow contributed to the observed adverse effects, Dr. Handelsman said.

Dr. Juurlink was skeptical that the kidneys played a major role. “An abrupt change in renal function can influence statin clearance, but this was a 15-fold increase. You can’t explain such a dramatic increase by a transient reduction in renal function,” he said.

Dr. Juurlink and coauthors had no disclosures. Dr. Nissen had no relevant disclosures. Dr. Handelsman has been a consultant to companies that market drugs in the SGLT2 inhibitor class.

mzoler@mdedge.com

SOURCE: Brailovski E et al. Ann Intern Med. 2020 Aug 3. doi: 10.7326/L20-0549.

*Correction: This value was missing from the original article.

Clinical guidelines for cholesterol management may have two blind spots when it comes to heart attack prevention: Most younger adults with premature coronary artery disease who’ve had a myocardial infarction don’t meet guideline criteria for preventative statin therapy, and survivors under age 55 don’t meet the criteria for continuing nonstatin lipid-lowering treatments, a large single-center retrospective study has shown.

“The classic approach we’ve taken to identifying young adults for prevention is inadequate in younger adults,” corresponding author Ann Marie Navar, MD, PhD, of Duke University, Durham, N.C., said in an interview. “While awaiting more definitive research we should at minimum be using all the tools at our disposal, including broader use of coronary artery calcium [CAC] scoring, to identify young people who may benefit from statin therapy.”

The retrospective observational study analyzed records of 6,639 adults who had cardiac catheterization at Duke University Medical Center from 1995 to 2012 for a first myocardial infarction with obstructive coronary artery disease. The study considered those under age 55 years as “younger” patients, comprising 41% of the study group (2,733); 35% were “middle-aged” at 55-65 years (2,324) and 24% were “older,” at 66-75 years (1,582).

The report, published online Aug. 3 in the Journal of the American College of Cardiology, noted that most of the adults with premature CAD did not meet criteria for preventative statin therapy before their first MI based on ACC/American Heart Association clinical guidelines from 2013 and 2018. It also noted that younger MI survivors are also less frequently eligible for secondary prevention with intensive nonstatin lipid-lowering therapies than are older adults despite a much longer potential life span – and opportunity for another MI – for the former.

The researchers sought to evaluate the real-world implications of changes made in the 2018 guideline for adults who develop premature ischemic heart disease, and found that fewer younger patients qualify for preventative statin therapy under the 2018 guidelines.

“Younger individuals with very high-risk criteria are at higher risk of major adverse cardiovascular events, a finding supporting the appropriate implementation of intensive lipid-lowering therapies in these patients,” wrote lead author Michel Zeitouni, MD, MSc, and colleagues.
 

Key findings

The investigators reported that younger adults were significantly less likely to meet a class I recommendation for statins under the 2013 guideline (42.9%), compared with their middle-aged (70%) and older (82.5%) counterparts; and under the 2018 guideline, at 39.4%, 59.5%, and 77.4%, respectively (both P < .001).

Similarly, when both class I and class IIa recommendations were accounted for, younger patients were significantly less likely than were middle-aged and older patients to be eligible for statins before their index MI under both the 2013 (56.7%, 79.5%, and 85.2%, respectively and 2018 guidelines (46.4%, 73.5%, and 88.2%, respectively (both P < .01).

After their first MI, one in four younger patients (28.3%) met the very high-risk criteria compared with 40% of middle-aged and 81.4% of older patients (P trend < .001). In 8 years of follow-up, patients with very high-risk criteria based on the 2018 guideline had twice the rate of death, nonfatal MI, or stroke (hazard ratio [HR]: 2.15; 95% confidence interval, 1.98-2.33; P < .001).

The researchers acknowledged that the 2018 guideline took the important step of implementing risk enhancers – patient characteristics such as obesity and metabolic syndrome – along with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to better identify high-risk young individuals who need statins. However, they also noted that the ability of the guidelines to identify young adults before their first MI “remains suboptimal.”

How to protect younger patients

“The 2018 guidelines will be most effective if we as providers do our best to identify risk enhancers and if we can use CAC scoring more broadly,” Dr. Navar said, noting that although CAC scoring has been shown to improve risk prediction, insurance coverage can be problematic.

“We also need to be careful to screen for the presence of the risk enhancers, such as inflammatory disease, family history, and women-specific risk factors, to make sure we aren’t missing an important high-risk group,” she added.

Other solutions to better identify at-risk younger adults include considering upgrades to the guidelines’ class IIb recommendation to class IIa to emphasize the importance of recognizing lower-risk younger adults, and recommending statins for patients at higher lifetime risk than age- and sex-matched peers, the researchers noted. “In our cohort, young individuals admitted for a first MI had a higher lifetime ASCVD risk score than did patients in the older age categories,” Dr. Zeitouni and colleagues wrote.

Dr. Navar said that these findings are a reminder that guidelines aren’t mandates. “Guidelines are meant to be a starting point for patients and physicians,” she said. “The absence of a recommendation doesn’t mean something isn’t recommended, but that there is not enough data to say one way or another.” 

The study “provides important evidence” that the 2018 guidelines exempted about half of the younger adults who had a first MI from preventative statin therapy, Ron Blankstein, MD, and Avinainder Singh, MD, MMSc, noted in an editorial (J Am Coll Cardiol. 2020;76:665-8).

Brigham and Women&#039;s Hospital

“Data from both the Duke and Young-MI registries should force us to reexamine how we allocate statin use among young individuals,” they noted. Dr. Blankstein is with Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Singh is with Yale University, New Haven, Conn.

Dr. Zeitouni reported receiving lecture fees from Bristol-Myers Squibb/Pfizer. Dr. Navar reported financial relationships with Amarin, Janssen, Amgen, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Esperion, Novo Nordisk, Novartis, The Medicine Company, New Amsterdam, Cerner and Pfizer. Dr. Blankstein reported receiving research support from Amgen. Dr. Singh has no relevant financial relationships to report.

SOURCE: M. Zeitouni et al. J Am Coll Cardiol 2020 Aug 3;76:653-64.

Clinical guidelines for cholesterol management may have two blind spots when it comes to heart attack prevention: Most younger adults with premature coronary artery disease who’ve had a myocardial infarction don’t meet guideline criteria for preventative statin therapy, and survivors under age 55 don’t meet the criteria for continuing nonstatin lipid-lowering treatments, a large single-center retrospective study has shown.

“The classic approach we’ve taken to identifying young adults for prevention is inadequate in younger adults,” corresponding author Ann Marie Navar, MD, PhD, of Duke University, Durham, N.C., said in an interview. “While awaiting more definitive research we should at minimum be using all the tools at our disposal, including broader use of coronary artery calcium [CAC] scoring, to identify young people who may benefit from statin therapy.”

The retrospective observational study analyzed records of 6,639 adults who had cardiac catheterization at Duke University Medical Center from 1995 to 2012 for a first myocardial infarction with obstructive coronary artery disease. The study considered those under age 55 years as “younger” patients, comprising 41% of the study group (2,733); 35% were “middle-aged” at 55-65 years (2,324) and 24% were “older,” at 66-75 years (1,582).

The report, published online Aug. 3 in the Journal of the American College of Cardiology, noted that most of the adults with premature CAD did not meet criteria for preventative statin therapy before their first MI based on ACC/American Heart Association clinical guidelines from 2013 and 2018. It also noted that younger MI survivors are also less frequently eligible for secondary prevention with intensive nonstatin lipid-lowering therapies than are older adults despite a much longer potential life span – and opportunity for another MI – for the former.

The researchers sought to evaluate the real-world implications of changes made in the 2018 guideline for adults who develop premature ischemic heart disease, and found that fewer younger patients qualify for preventative statin therapy under the 2018 guidelines.

“Younger individuals with very high-risk criteria are at higher risk of major adverse cardiovascular events, a finding supporting the appropriate implementation of intensive lipid-lowering therapies in these patients,” wrote lead author Michel Zeitouni, MD, MSc, and colleagues.
 

Key findings

The investigators reported that younger adults were significantly less likely to meet a class I recommendation for statins under the 2013 guideline (42.9%), compared with their middle-aged (70%) and older (82.5%) counterparts; and under the 2018 guideline, at 39.4%, 59.5%, and 77.4%, respectively (both P < .001).

Similarly, when both class I and class IIa recommendations were accounted for, younger patients were significantly less likely than were middle-aged and older patients to be eligible for statins before their index MI under both the 2013 (56.7%, 79.5%, and 85.2%, respectively and 2018 guidelines (46.4%, 73.5%, and 88.2%, respectively (both P < .01).

After their first MI, one in four younger patients (28.3%) met the very high-risk criteria compared with 40% of middle-aged and 81.4% of older patients (P trend < .001). In 8 years of follow-up, patients with very high-risk criteria based on the 2018 guideline had twice the rate of death, nonfatal MI, or stroke (hazard ratio [HR]: 2.15; 95% confidence interval, 1.98-2.33; P < .001).

The researchers acknowledged that the 2018 guideline took the important step of implementing risk enhancers – patient characteristics such as obesity and metabolic syndrome – along with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to better identify high-risk young individuals who need statins. However, they also noted that the ability of the guidelines to identify young adults before their first MI “remains suboptimal.”

How to protect younger patients

“The 2018 guidelines will be most effective if we as providers do our best to identify risk enhancers and if we can use CAC scoring more broadly,” Dr. Navar said, noting that although CAC scoring has been shown to improve risk prediction, insurance coverage can be problematic.

“We also need to be careful to screen for the presence of the risk enhancers, such as inflammatory disease, family history, and women-specific risk factors, to make sure we aren’t missing an important high-risk group,” she added.

Other solutions to better identify at-risk younger adults include considering upgrades to the guidelines’ class IIb recommendation to class IIa to emphasize the importance of recognizing lower-risk younger adults, and recommending statins for patients at higher lifetime risk than age- and sex-matched peers, the researchers noted. “In our cohort, young individuals admitted for a first MI had a higher lifetime ASCVD risk score than did patients in the older age categories,” Dr. Zeitouni and colleagues wrote.

Dr. Navar said that these findings are a reminder that guidelines aren’t mandates. “Guidelines are meant to be a starting point for patients and physicians,” she said. “The absence of a recommendation doesn’t mean something isn’t recommended, but that there is not enough data to say one way or another.” 

The study “provides important evidence” that the 2018 guidelines exempted about half of the younger adults who had a first MI from preventative statin therapy, Ron Blankstein, MD, and Avinainder Singh, MD, MMSc, noted in an editorial (J Am Coll Cardiol. 2020;76:665-8).

Brigham and Women&#039;s Hospital

“Data from both the Duke and Young-MI registries should force us to reexamine how we allocate statin use among young individuals,” they noted. Dr. Blankstein is with Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Singh is with Yale University, New Haven, Conn.

Dr. Zeitouni reported receiving lecture fees from Bristol-Myers Squibb/Pfizer. Dr. Navar reported financial relationships with Amarin, Janssen, Amgen, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Esperion, Novo Nordisk, Novartis, The Medicine Company, New Amsterdam, Cerner and Pfizer. Dr. Blankstein reported receiving research support from Amgen. Dr. Singh has no relevant financial relationships to report.

SOURCE: M. Zeitouni et al. J Am Coll Cardiol 2020 Aug 3;76:653-64.

Clinical guidelines for cholesterol management may have two blind spots when it comes to heart attack prevention: Most younger adults with premature coronary artery disease who’ve had a myocardial infarction don’t meet guideline criteria for preventative statin therapy, and survivors under age 55 don’t meet the criteria for continuing nonstatin lipid-lowering treatments, a large single-center retrospective study has shown.

“The classic approach we’ve taken to identifying young adults for prevention is inadequate in younger adults,” corresponding author Ann Marie Navar, MD, PhD, of Duke University, Durham, N.C., said in an interview. “While awaiting more definitive research we should at minimum be using all the tools at our disposal, including broader use of coronary artery calcium [CAC] scoring, to identify young people who may benefit from statin therapy.”

The retrospective observational study analyzed records of 6,639 adults who had cardiac catheterization at Duke University Medical Center from 1995 to 2012 for a first myocardial infarction with obstructive coronary artery disease. The study considered those under age 55 years as “younger” patients, comprising 41% of the study group (2,733); 35% were “middle-aged” at 55-65 years (2,324) and 24% were “older,” at 66-75 years (1,582).

The report, published online Aug. 3 in the Journal of the American College of Cardiology, noted that most of the adults with premature CAD did not meet criteria for preventative statin therapy before their first MI based on ACC/American Heart Association clinical guidelines from 2013 and 2018. It also noted that younger MI survivors are also less frequently eligible for secondary prevention with intensive nonstatin lipid-lowering therapies than are older adults despite a much longer potential life span – and opportunity for another MI – for the former.

The researchers sought to evaluate the real-world implications of changes made in the 2018 guideline for adults who develop premature ischemic heart disease, and found that fewer younger patients qualify for preventative statin therapy under the 2018 guidelines.

“Younger individuals with very high-risk criteria are at higher risk of major adverse cardiovascular events, a finding supporting the appropriate implementation of intensive lipid-lowering therapies in these patients,” wrote lead author Michel Zeitouni, MD, MSc, and colleagues.
 

Key findings

The investigators reported that younger adults were significantly less likely to meet a class I recommendation for statins under the 2013 guideline (42.9%), compared with their middle-aged (70%) and older (82.5%) counterparts; and under the 2018 guideline, at 39.4%, 59.5%, and 77.4%, respectively (both P < .001).

Similarly, when both class I and class IIa recommendations were accounted for, younger patients were significantly less likely than were middle-aged and older patients to be eligible for statins before their index MI under both the 2013 (56.7%, 79.5%, and 85.2%, respectively and 2018 guidelines (46.4%, 73.5%, and 88.2%, respectively (both P < .01).

After their first MI, one in four younger patients (28.3%) met the very high-risk criteria compared with 40% of middle-aged and 81.4% of older patients (P trend < .001). In 8 years of follow-up, patients with very high-risk criteria based on the 2018 guideline had twice the rate of death, nonfatal MI, or stroke (hazard ratio [HR]: 2.15; 95% confidence interval, 1.98-2.33; P < .001).

The researchers acknowledged that the 2018 guideline took the important step of implementing risk enhancers – patient characteristics such as obesity and metabolic syndrome – along with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to better identify high-risk young individuals who need statins. However, they also noted that the ability of the guidelines to identify young adults before their first MI “remains suboptimal.”

How to protect younger patients

“The 2018 guidelines will be most effective if we as providers do our best to identify risk enhancers and if we can use CAC scoring more broadly,” Dr. Navar said, noting that although CAC scoring has been shown to improve risk prediction, insurance coverage can be problematic.

“We also need to be careful to screen for the presence of the risk enhancers, such as inflammatory disease, family history, and women-specific risk factors, to make sure we aren’t missing an important high-risk group,” she added.

Other solutions to better identify at-risk younger adults include considering upgrades to the guidelines’ class IIb recommendation to class IIa to emphasize the importance of recognizing lower-risk younger adults, and recommending statins for patients at higher lifetime risk than age- and sex-matched peers, the researchers noted. “In our cohort, young individuals admitted for a first MI had a higher lifetime ASCVD risk score than did patients in the older age categories,” Dr. Zeitouni and colleagues wrote.

Dr. Navar said that these findings are a reminder that guidelines aren’t mandates. “Guidelines are meant to be a starting point for patients and physicians,” she said. “The absence of a recommendation doesn’t mean something isn’t recommended, but that there is not enough data to say one way or another.” 

The study “provides important evidence” that the 2018 guidelines exempted about half of the younger adults who had a first MI from preventative statin therapy, Ron Blankstein, MD, and Avinainder Singh, MD, MMSc, noted in an editorial (J Am Coll Cardiol. 2020;76:665-8).

Brigham and Women&#039;s Hospital

“Data from both the Duke and Young-MI registries should force us to reexamine how we allocate statin use among young individuals,” they noted. Dr. Blankstein is with Brigham and Women’s Hospital, Harvard Medical School, Boston. Dr. Singh is with Yale University, New Haven, Conn.

Dr. Zeitouni reported receiving lecture fees from Bristol-Myers Squibb/Pfizer. Dr. Navar reported financial relationships with Amarin, Janssen, Amgen, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Esperion, Novo Nordisk, Novartis, The Medicine Company, New Amsterdam, Cerner and Pfizer. Dr. Blankstein reported receiving research support from Amgen. Dr. Singh has no relevant financial relationships to report.

SOURCE: M. Zeitouni et al. J Am Coll Cardiol 2020 Aug 3;76:653-64.

At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.

The research will track and evaluate the short- and long-term impact of the novel coronavirus on the brain, including cognition, behavior, and function. The target sample size is 20,000-40,000 total participants.

Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.

“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
 

‘Frightening’ headlines

As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.

Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.

The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.

She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
 

New recommendations

Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:

• Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
• Having a single portal that is easy and efficient for reporting cases
• Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
• Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)

“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”

Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”

Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.

With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.

Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.

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

At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.

The research will track and evaluate the short- and long-term impact of the novel coronavirus on the brain, including cognition, behavior, and function. The target sample size is 20,000-40,000 total participants.

Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.

“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
 

‘Frightening’ headlines

As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.

Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.

The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.

She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
 

New recommendations

Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:

• Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
• Having a single portal that is easy and efficient for reporting cases
• Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
• Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)

“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”

Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”

Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.

With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.

Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.

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

At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.

The research will track and evaluate the short- and long-term impact of the novel coronavirus on the brain, including cognition, behavior, and function. The target sample size is 20,000-40,000 total participants.

Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.

“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
 

‘Frightening’ headlines

As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.

Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.

The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.

She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
 

New recommendations

Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:

• Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
• Having a single portal that is easy and efficient for reporting cases
• Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
• Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)

“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”

Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”

Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.

With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.

Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.

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

The COVID-19 pandemic is taking a particularly severe financial toll on people with diabetes, new research from the United States suggests.

Results from a national online survey of 5,000 people with diabetes conducted between June 26 and July 1, 2020, were posted July 29 on the American Diabetes Association website.

The survey, conducted by the diabetes research company dQ&A in association with the ADA, revealed that Americans with diabetes are experiencing extreme financial pressures, leading to medication and supply rationing.

A high proportion of respondents had either lost income or are working in jobs that place them at risk for catching the novel coronavirus.

“These new numbers show the urgency needed to adopt measures to protect and assist the millions of people with diabetes who are suffering through this pandemic,” Tracey D. Brown, CEO of the ADA, said in a statement.

She called for states to extend health care coverage to people who have lost their jobs, for the eradication of insulin copays during the pandemic, and for increased COVID-19 testing capacity in high-risk communities.

“If these actions aren’t taken immediately, we will continue to see devastating impacts and outcomes for millions of vulnerable Americans,” Ms. Brown stressed.
 

COVID-19 has worsened financial pressures for people with diabetes

In the survey, 24% of respondents reported having used savings, loans, or stimulus check money to pay for diabetes care in the past 3 months. Among those who have lost income, half are using savings or stimulus money.

A quarter of respondents said they have been self-rationing supplies to cut costs.

Extrapolating to the entire U.S. population with diabetes, dQ&A estimated that roughly 650,000 are skipping insulin doses or taking less than prescribed, and 3 million are skipping blood glucose tests.

In June, the unemployment rate for people with diabetes was 18%, higher than the national rate of 12%.

Also higher is the proportion of those working prior to the pandemic who have since lost income: 33%, compared with 29% for the general population.

Among those who are self-employed, 7 in 10 of those with diabetes have lost some or all of their income.
 

Many with diabetes who are employed are vulnerable to exposure

Of those who remain employed, half said they can’t work from home.

Of those, 60% work in essential industries, with 22% in health care. A large majority, 90%, reported lack of social distancing at work and nearly a third work in places that don’t require masks.

“People with diabetes are helping to provide the services we all depend on during this pandemic, even as it puts their own well-being at risk,” the report said.

It concluded that “these numbers represent a conservative estimate of the pandemic’s impact. They are generated from an ongoing online study of the diabetes population amongst people who have opted in to participate.”

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

The COVID-19 pandemic is taking a particularly severe financial toll on people with diabetes, new research from the United States suggests.

Results from a national online survey of 5,000 people with diabetes conducted between June 26 and July 1, 2020, were posted July 29 on the American Diabetes Association website.

The survey, conducted by the diabetes research company dQ&A in association with the ADA, revealed that Americans with diabetes are experiencing extreme financial pressures, leading to medication and supply rationing.

A high proportion of respondents had either lost income or are working in jobs that place them at risk for catching the novel coronavirus.

“These new numbers show the urgency needed to adopt measures to protect and assist the millions of people with diabetes who are suffering through this pandemic,” Tracey D. Brown, CEO of the ADA, said in a statement.

She called for states to extend health care coverage to people who have lost their jobs, for the eradication of insulin copays during the pandemic, and for increased COVID-19 testing capacity in high-risk communities.

“If these actions aren’t taken immediately, we will continue to see devastating impacts and outcomes for millions of vulnerable Americans,” Ms. Brown stressed.
 

COVID-19 has worsened financial pressures for people with diabetes

In the survey, 24% of respondents reported having used savings, loans, or stimulus check money to pay for diabetes care in the past 3 months. Among those who have lost income, half are using savings or stimulus money.

A quarter of respondents said they have been self-rationing supplies to cut costs.

Extrapolating to the entire U.S. population with diabetes, dQ&A estimated that roughly 650,000 are skipping insulin doses or taking less than prescribed, and 3 million are skipping blood glucose tests.

In June, the unemployment rate for people with diabetes was 18%, higher than the national rate of 12%.

Also higher is the proportion of those working prior to the pandemic who have since lost income: 33%, compared with 29% for the general population.

Among those who are self-employed, 7 in 10 of those with diabetes have lost some or all of their income.
 

Many with diabetes who are employed are vulnerable to exposure

Of those who remain employed, half said they can’t work from home.

Of those, 60% work in essential industries, with 22% in health care. A large majority, 90%, reported lack of social distancing at work and nearly a third work in places that don’t require masks.

“People with diabetes are helping to provide the services we all depend on during this pandemic, even as it puts their own well-being at risk,” the report said.

It concluded that “these numbers represent a conservative estimate of the pandemic’s impact. They are generated from an ongoing online study of the diabetes population amongst people who have opted in to participate.”

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

The COVID-19 pandemic is taking a particularly severe financial toll on people with diabetes, new research from the United States suggests.

Results from a national online survey of 5,000 people with diabetes conducted between June 26 and July 1, 2020, were posted July 29 on the American Diabetes Association website.

The survey, conducted by the diabetes research company dQ&A in association with the ADA, revealed that Americans with diabetes are experiencing extreme financial pressures, leading to medication and supply rationing.

A high proportion of respondents had either lost income or are working in jobs that place them at risk for catching the novel coronavirus.

“These new numbers show the urgency needed to adopt measures to protect and assist the millions of people with diabetes who are suffering through this pandemic,” Tracey D. Brown, CEO of the ADA, said in a statement.

She called for states to extend health care coverage to people who have lost their jobs, for the eradication of insulin copays during the pandemic, and for increased COVID-19 testing capacity in high-risk communities.

“If these actions aren’t taken immediately, we will continue to see devastating impacts and outcomes for millions of vulnerable Americans,” Ms. Brown stressed.
 

COVID-19 has worsened financial pressures for people with diabetes

In the survey, 24% of respondents reported having used savings, loans, or stimulus check money to pay for diabetes care in the past 3 months. Among those who have lost income, half are using savings or stimulus money.

A quarter of respondents said they have been self-rationing supplies to cut costs.

Extrapolating to the entire U.S. population with diabetes, dQ&A estimated that roughly 650,000 are skipping insulin doses or taking less than prescribed, and 3 million are skipping blood glucose tests.

In June, the unemployment rate for people with diabetes was 18%, higher than the national rate of 12%.

Also higher is the proportion of those working prior to the pandemic who have since lost income: 33%, compared with 29% for the general population.

Among those who are self-employed, 7 in 10 of those with diabetes have lost some or all of their income.
 

Many with diabetes who are employed are vulnerable to exposure

Of those who remain employed, half said they can’t work from home.

Of those, 60% work in essential industries, with 22% in health care. A large majority, 90%, reported lack of social distancing at work and nearly a third work in places that don’t require masks.

“People with diabetes are helping to provide the services we all depend on during this pandemic, even as it puts their own well-being at risk,” the report said.

It concluded that “these numbers represent a conservative estimate of the pandemic’s impact. They are generated from an ongoing online study of the diabetes population amongst people who have opted in to participate.”

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

A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.

“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.

The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.

“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.

More imaging has led to detection of more adrenal tumors

Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.

Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.

Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.

All three tests together give best predictive value: EURINE-ACT

To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.

The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.

Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.

Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.

Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).

Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.

A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.

Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.

“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.

Limit urine test to patients with larger tumors

They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.

“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.

And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.

In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.

However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.

“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.

The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.

Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.

The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
 

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

A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.

“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.

The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.

“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.

More imaging has led to detection of more adrenal tumors

Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.

Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.

Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.

All three tests together give best predictive value: EURINE-ACT

To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.

The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.

Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.

Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.

Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).

Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.

A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.

Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.

“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.

Limit urine test to patients with larger tumors

They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.

“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.

And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.

In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.

However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.

“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.

The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.

Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.

The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
 

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

A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.

“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.

The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.

“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.

More imaging has led to detection of more adrenal tumors

Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.

Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.

Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.

All three tests together give best predictive value: EURINE-ACT

To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.

The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.

Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.

Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.

Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).

Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.

A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.

Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.

“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.

Limit urine test to patients with larger tumors

They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.

“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.

And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.

In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.

However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.

“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.

The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.

Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.

The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
 

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

Belatedly, the disproportionate impact of COVID-19 on patients of color is getting attention. By now, we’ve read the headlines. Black people in the United States make up about 13% of the population but account for almost three times (34%) as many deaths. This story repeats – in other countries and in other minority communities.

Early detection is critical both to initiate supportive care and to isolate affected individuals and limit spread. Skin manifestations of COVID-19, especially those that occur early in the disease (eg, vesicular eruptions) or have prognostic significance (livedo, retiform purpura, necrosis), are critical to this goal of early recognition.

In this context, a recent systematic literature review looked at all articles describing skin manifestations associated with COVID-19. The investigators identified 46 articles published between March and May 2020 which included a total of 130 clinical images.

The following findings from this study are striking:

• 92% of the published images of COVID-associated skin manifestations were in I-III.
• Only 6% of COVID skin lesions included in the articles were in patients with skin type IV.
• None showed COVID skin lesions in skin types V or VI.
• Only six of the articles reported race and ethnicity demographics. In those, 91% of the patients were White and 9% were Hispanic.

These results reveal a critical lack of representative clinical images of COVID-associated skin manifestations in patients of color. This deficiency is made all the more egregious given the fact that patients of color, including those who are Black, Latinx, and Native American, have been especially hard hit by the COVID-19 pandemic and suffer disproportionate disease-related morbidity and mortality.
 

As the study authors point out, skin manifestations in people of color often differ significantly from findings in White skin (for example, look at the figure depicting the rash typical of Kawasaki disease in a dark-skinned child compared with a light-skinned child). It is not a stretch to suggest that skin manifestations associated with COVID-19 may look very different in darker skin.

These investigators have identified a damning lack of images of COVID-19–associated skin manifestations in patients with darker skin. This isn’t a new phenomenon. Almost half of dermatologists feel that they’ve had insufficient exposure to skin disease in darker skin types. Skin of color remains underrepresented in medical journals.

Like other forms of passive, institutional racism, this deficiency will only be improved if dermatologists and dermatology publications actively seek out COVID-associated skin manifestations in patients of color and prioritize sharing these images. A medical student in the United Kingdom has gotten the ball rolling, compiling a handbook of clinical signs in darker skin types as part of a student-staff partnership at St. George’s Hospital and the University of London. At this time, Mind the Gap is looking for a publisher.

Dr. Lipper is an assistant clinical professor at the University of Vermont, Burlington, and a staff physician in the department of dermatology at Danbury (Conn.) Hospital. He has disclosed no relevant financial relationships.
 

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

Belatedly, the disproportionate impact of COVID-19 on patients of color is getting attention. By now, we’ve read the headlines. Black people in the United States make up about 13% of the population but account for almost three times (34%) as many deaths. This story repeats – in other countries and in other minority communities.

Early detection is critical both to initiate supportive care and to isolate affected individuals and limit spread. Skin manifestations of COVID-19, especially those that occur early in the disease (eg, vesicular eruptions) or have prognostic significance (livedo, retiform purpura, necrosis), are critical to this goal of early recognition.

In this context, a recent systematic literature review looked at all articles describing skin manifestations associated with COVID-19. The investigators identified 46 articles published between March and May 2020 which included a total of 130 clinical images.

The following findings from this study are striking:

• 92% of the published images of COVID-associated skin manifestations were in I-III.
• Only 6% of COVID skin lesions included in the articles were in patients with skin type IV.
• None showed COVID skin lesions in skin types V or VI.
• Only six of the articles reported race and ethnicity demographics. In those, 91% of the patients were White and 9% were Hispanic.

These results reveal a critical lack of representative clinical images of COVID-associated skin manifestations in patients of color. This deficiency is made all the more egregious given the fact that patients of color, including those who are Black, Latinx, and Native American, have been especially hard hit by the COVID-19 pandemic and suffer disproportionate disease-related morbidity and mortality.
 

As the study authors point out, skin manifestations in people of color often differ significantly from findings in White skin (for example, look at the figure depicting the rash typical of Kawasaki disease in a dark-skinned child compared with a light-skinned child). It is not a stretch to suggest that skin manifestations associated with COVID-19 may look very different in darker skin.

These investigators have identified a damning lack of images of COVID-19–associated skin manifestations in patients with darker skin. This isn’t a new phenomenon. Almost half of dermatologists feel that they’ve had insufficient exposure to skin disease in darker skin types. Skin of color remains underrepresented in medical journals.

Like other forms of passive, institutional racism, this deficiency will only be improved if dermatologists and dermatology publications actively seek out COVID-associated skin manifestations in patients of color and prioritize sharing these images. A medical student in the United Kingdom has gotten the ball rolling, compiling a handbook of clinical signs in darker skin types as part of a student-staff partnership at St. George’s Hospital and the University of London. At this time, Mind the Gap is looking for a publisher.

Dr. Lipper is an assistant clinical professor at the University of Vermont, Burlington, and a staff physician in the department of dermatology at Danbury (Conn.) Hospital. He has disclosed no relevant financial relationships.
 

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

Belatedly, the disproportionate impact of COVID-19 on patients of color is getting attention. By now, we’ve read the headlines. Black people in the United States make up about 13% of the population but account for almost three times (34%) as many deaths. This story repeats – in other countries and in other minority communities.

Early detection is critical both to initiate supportive care and to isolate affected individuals and limit spread. Skin manifestations of COVID-19, especially those that occur early in the disease (eg, vesicular eruptions) or have prognostic significance (livedo, retiform purpura, necrosis), are critical to this goal of early recognition.

In this context, a recent systematic literature review looked at all articles describing skin manifestations associated with COVID-19. The investigators identified 46 articles published between March and May 2020 which included a total of 130 clinical images.

The following findings from this study are striking:

• 92% of the published images of COVID-associated skin manifestations were in I-III.
• Only 6% of COVID skin lesions included in the articles were in patients with skin type IV.
• None showed COVID skin lesions in skin types V or VI.
• Only six of the articles reported race and ethnicity demographics. In those, 91% of the patients were White and 9% were Hispanic.

These results reveal a critical lack of representative clinical images of COVID-associated skin manifestations in patients of color. This deficiency is made all the more egregious given the fact that patients of color, including those who are Black, Latinx, and Native American, have been especially hard hit by the COVID-19 pandemic and suffer disproportionate disease-related morbidity and mortality.
 

As the study authors point out, skin manifestations in people of color often differ significantly from findings in White skin (for example, look at the figure depicting the rash typical of Kawasaki disease in a dark-skinned child compared with a light-skinned child). It is not a stretch to suggest that skin manifestations associated with COVID-19 may look very different in darker skin.

These investigators have identified a damning lack of images of COVID-19–associated skin manifestations in patients with darker skin. This isn’t a new phenomenon. Almost half of dermatologists feel that they’ve had insufficient exposure to skin disease in darker skin types. Skin of color remains underrepresented in medical journals.

Like other forms of passive, institutional racism, this deficiency will only be improved if dermatologists and dermatology publications actively seek out COVID-associated skin manifestations in patients of color and prioritize sharing these images. A medical student in the United Kingdom has gotten the ball rolling, compiling a handbook of clinical signs in darker skin types as part of a student-staff partnership at St. George’s Hospital and the University of London. At this time, Mind the Gap is looking for a publisher.

Dr. Lipper is an assistant clinical professor at the University of Vermont, Burlington, and a staff physician in the department of dermatology at Danbury (Conn.) Hospital. He has disclosed no relevant financial relationships.
 

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

Evidence that the heart can take a major hit in patients hospitalized with COVID-19, especially those already with cardiovascular disease (CV) or its risk factors, has been sadly apparent from the pandemic’s earliest days.

Less clear from case studies and small series to date has been whether SARS-CoV-2 directly attacks the heart and whether acute cardiac effects of the illness may lead to some kind of lingering cardiomyopathy.

The field’s grasp of those issues advanced a bit in two new reports published July 27 in JAMA Cardiology that seem to validate concerns the virus can infect the myocardium, without necessarily causing myocarditis and the possibility that some “recovered” patients may be left with persisting myocardial injury and inflammation that potentially could later manifest as heart failure.

Persisting inflammation by cardiac magnetic resonance

A prospective cohort study with 100 patients recovered from a recent bout of the disease showed evidence of ventricular dysfunction, greater ventricular mass, and in 78% of the cohort, signs of myocardial inflammation by cardiac magnetic resonance (CMR) imaging. The CMR findings correlated with elevations in troponin T by high-sensitivity assay (hs-TnT).

Two-thirds of the cohort, whose acute COVID-19 severity had “ranged from asymptomatic to minor-to-moderate symptoms,” had recovered at home, whereas the remaining “severely unwell patients” had been hospitalized, wrote the authors, led by Valentina O. Püntmann, MD, PhD, University Hospital Frankfurt (Germany).

None of the patients had a history of heart failure or cardiomyopathy, although some had hypertension, diabetes, or evidence of coronary disease.

“Our findings demonstrate that participants with a relative paucity of preexisting cardiovascular condition and with mostly home-based recovery had frequent cardiac inflammatory involvement, which was similar to the hospitalized subgroup with regards to severity and extent,” the group noted.

“There is a considerable ongoing myocardial inflammation in the heart muscle weeks after recovery from COVID-19 illness. This finding is important because it may herald a considerable burden of heart failure in a few years down the line,” Dr. Püntmann said in an interview.

Early diagnosis would offer “a good chance that early treatment could reduce the relentless course of inflammatory damage or even halt it,” she said.

“The relatively clear onset of COVID-19 illness provides an opportunity, which we often do not have with other conditions, to take a proactive action and to look for heart involvement early, within a few weeks of recovery.”

The study’s CMR evidence of inflammation edema, scarring, and pericardial effusion are among “the major diagnostic criteria for inflammatory and viral myocarditis,” observed Biykem Bozkurt, MD, PhD, from Baylor College of Medicine, Houston, who wasn’t part of either new study.

The findings suggest – consistent with previous evidence – that some patients with recent COVID-19 may be left with ongoing myocardial inflammation, and this study further adds that it could potentially become subacute or even chronic and in some may not be totally reversible, she said in an interview. How long the effects are likely to persist “remains to be determined. We need longer-term outcomes data.”

Viral presence without myocarditis

The accompanying report featured a postmortem analysis of hearts from 39 patients with mostly severe COVID-19 that pointed to a significant SARS-CoV-2 presence and signs that the virus vigorously replicated in the myocardium.

But there was no evidence that the infection led to fulminant myocarditis. Rather, the virus had apparently infiltrated the heart by localizing in interstitial cells or in macrophages that took up in the myocardium without actually entering myocytes, concluded the report’s authors, led by Diana Lindner, PhD, from the University Heart and Vascular Centre, Hamburg (Germany).

The findings suggest “that the presence of SARS-CoV-2 in cardiac tissue does not necessarily cause an inflammatory reaction consistent with clinical myocarditis,” the group wrote.

Previously in the literature, in “cases in which myocardial inflammation was present, there was also evidence of clinical myocarditis, and therefore the current cases underlie a different pathophysiology,” they concluded.

No evidence of the virus was seen in 15 cases, about 61% of the group. In 16 of the remaining 24 hearts, the viral load exceeded 1,000 copies per mcg of RNA, a substantial presence. Those 16 showed increased expression of inflammatory cytokines but no inflammatory cell infiltrates or changes in leukocyte counts, the researchers noted.

“Findings of suggested viral replication in the cases with a very high viral load are showing that we need to do more studies to find out long-term consequences, which we do not know right now,” senior author Dirk Westermann, MD, also from the University Heart and Vascular Centre, Hamburg, said.

Implications for heart failure

The postmortem findings from Dr. Lindner and associates “provide intriguing evidence that COVID-19 is associated with at least some component of myocardial injury, perhaps as the result of direct viral infection of the heart,” wrote Clyde W. Yancy, MD, MSc, from Northwestern University, Chicago, and Gregg C. Fonarow, MD, from the University of California, Los Angeles, in an editorial accompanying both reports.

The CMR study from Dr. Püntmann and colleagues – on the backdrop of earlier COVID-19 observations – suggests the potential for “residual left ventricular dysfunction and ongoing inflammation” in the months following a COVID-19 diagnosis. Both developments may be “of sufficient concern to represent a nidus for new-onset heart failure and other cardiovascular complications,” contend Dr. Yancy and Dr. Fonarow.

“When added to the postmortem pathological findings from Lindner et al, we see the plot thickening and we are inclined to raise a new and very evident concern that cardiomyopathy and heart failure related to COVID-19 may potentially evolve as the natural history of this infection becomes clearer,” they wrote.

Some patients, having recovered from the acute illness, may be left with a chronic inflammatory state that probably puts them at increased risk for future heart failure, agreed Dr. Bozkurt when interviewed. “They could show further decline in cardiac function, and their recovery might take longer than with the usual viral illnesses that we see,” she said.

“There could also be a risk of sudden death. Inflammation sometimes gives rise to sudden death and ventricular arrhythmia, which I would be very worried about, especially if the myocardium is stressed,” Dr. Bozkurt said. “So competitive sports in those patients potentially could be risky.”

COVID-19 cohort vs. matched control subjects

The CMR study from Dr. Püntmann and colleagues prospectively entered 100 patients recently recovered from an acute bout of COVID-19, either at home or at a hospital, who were followed in a registry based at University Hospital Frankfurt. Their median age was 49 years; 47% were female. They were compared with 50 age- and sex-matched control patients and 50 apparently healthy volunteers matched for risk factors, the group noted.

On the same day as the CMR assessment, the recently recovered patients, compared with the healthy control subjects and risk-factor matched control subjects, respectively, showed (P ≤ .001 in each case):

• A reduced left ventricular (LV) ejection fraction: 56% vs. 60% and 61%.
• A higher LV end-diastolic volume index: 86 mL/m² vs. 80 mL/m² and 75 mL/m^2.
• A greater LV mass index: 51 g/m² vs. 47 g/m² and 53 g/m^2.
• A higher hs-TnT level: 5.6 pg/mL vs. 3.2 pg/mL and 3.9 pg/mL.
• A greater prevalence of hs-TnT levels 3 pg/mL or more: 71% vs. 11% and 31%.

At CMR, 78% of the recovered COVID-19 patients showed abnormalities that included raised myocardial native T1 and T2 mapping, which is suggestive of fibrosis and edema from inflammation, compared with the two control groups (P < .001 for all differences), “independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis,” the group wrote. Native T1 and T2 mapping correlated significantly with hs-TnT.

“We now have the diagnostic means to detect cardiac inflammation early, and we need make every effort to apply them in every day practice,”Dr. Püntmann said in the interview.

“Using cardiac MRI will allow us to raise our game against COVID-19 and proactively develop efficient cardioprotective treatments,” she said. “Until we have effective means of protecting from the infection, that is vaccination, we must act swiftly and within the means at hand.”

The analysis evokes several other ways patients with COVID-19 might be screened for significant myocardial involvement.

“Strategies could include checking troponins, not only at admission but maybe at discharge and perhaps even those individuals who are at home and are not necessarily requiring care,” Dr. Bozkurt said.

“Biomarker profiling and screening for ongoing inflammation probably are going to be important components of COVID-19, especially for those with subclinical risk and disease.”

Dr. Westermann proposed that troponin elevations at discharge “might be a good starting point” for selecting COVID-19 patients for functional testing or imaging to screen for cardiac sequelae. Performing such tests routinely now “would be overwhelming given the massive increase in patients we still see today.”

Dr. Püntmann had no disclosures; statements of potential conflict for the other authors are in the report. Dr. Bozkurt has previously disclosed receiving consultant fees or honoraria from Bayer Healthcare, Bristol-Myers Squibb, Lantheus Medical Imaging, and Respicardia; serving on a data safety monitoring board for LivaNova USA ; and having unspecified relationships with Abbott Laboratories. Dr. Lindner had no disclosures; Dr. Westermann reported receiving personal fees from AstraZeneca, Bayer, Novartis, and Medtronic. Dr. Yancy is a deputy editor and Dr. Fonarow a section editor for JAMA Cardiology. Dr. Yancy had no other disclosures. Dr. Fonarow reported receiving personal fees from Abbott Laboratories, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards Lifesciences, Janssen, Medtronic, Merck, and Novartis.

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

Evidence that the heart can take a major hit in patients hospitalized with COVID-19, especially those already with cardiovascular disease (CV) or its risk factors, has been sadly apparent from the pandemic’s earliest days.

Less clear from case studies and small series to date has been whether SARS-CoV-2 directly attacks the heart and whether acute cardiac effects of the illness may lead to some kind of lingering cardiomyopathy.

The field’s grasp of those issues advanced a bit in two new reports published July 27 in JAMA Cardiology that seem to validate concerns the virus can infect the myocardium, without necessarily causing myocarditis and the possibility that some “recovered” patients may be left with persisting myocardial injury and inflammation that potentially could later manifest as heart failure.

Persisting inflammation by cardiac magnetic resonance

A prospective cohort study with 100 patients recovered from a recent bout of the disease showed evidence of ventricular dysfunction, greater ventricular mass, and in 78% of the cohort, signs of myocardial inflammation by cardiac magnetic resonance (CMR) imaging. The CMR findings correlated with elevations in troponin T by high-sensitivity assay (hs-TnT).

Two-thirds of the cohort, whose acute COVID-19 severity had “ranged from asymptomatic to minor-to-moderate symptoms,” had recovered at home, whereas the remaining “severely unwell patients” had been hospitalized, wrote the authors, led by Valentina O. Püntmann, MD, PhD, University Hospital Frankfurt (Germany).

None of the patients had a history of heart failure or cardiomyopathy, although some had hypertension, diabetes, or evidence of coronary disease.

“Our findings demonstrate that participants with a relative paucity of preexisting cardiovascular condition and with mostly home-based recovery had frequent cardiac inflammatory involvement, which was similar to the hospitalized subgroup with regards to severity and extent,” the group noted.

“There is a considerable ongoing myocardial inflammation in the heart muscle weeks after recovery from COVID-19 illness. This finding is important because it may herald a considerable burden of heart failure in a few years down the line,” Dr. Püntmann said in an interview.

Early diagnosis would offer “a good chance that early treatment could reduce the relentless course of inflammatory damage or even halt it,” she said.

“The relatively clear onset of COVID-19 illness provides an opportunity, which we often do not have with other conditions, to take a proactive action and to look for heart involvement early, within a few weeks of recovery.”

The study’s CMR evidence of inflammation edema, scarring, and pericardial effusion are among “the major diagnostic criteria for inflammatory and viral myocarditis,” observed Biykem Bozkurt, MD, PhD, from Baylor College of Medicine, Houston, who wasn’t part of either new study.

The findings suggest – consistent with previous evidence – that some patients with recent COVID-19 may be left with ongoing myocardial inflammation, and this study further adds that it could potentially become subacute or even chronic and in some may not be totally reversible, she said in an interview. How long the effects are likely to persist “remains to be determined. We need longer-term outcomes data.”

Viral presence without myocarditis

The accompanying report featured a postmortem analysis of hearts from 39 patients with mostly severe COVID-19 that pointed to a significant SARS-CoV-2 presence and signs that the virus vigorously replicated in the myocardium.

But there was no evidence that the infection led to fulminant myocarditis. Rather, the virus had apparently infiltrated the heart by localizing in interstitial cells or in macrophages that took up in the myocardium without actually entering myocytes, concluded the report’s authors, led by Diana Lindner, PhD, from the University Heart and Vascular Centre, Hamburg (Germany).

The findings suggest “that the presence of SARS-CoV-2 in cardiac tissue does not necessarily cause an inflammatory reaction consistent with clinical myocarditis,” the group wrote.

Previously in the literature, in “cases in which myocardial inflammation was present, there was also evidence of clinical myocarditis, and therefore the current cases underlie a different pathophysiology,” they concluded.

No evidence of the virus was seen in 15 cases, about 61% of the group. In 16 of the remaining 24 hearts, the viral load exceeded 1,000 copies per mcg of RNA, a substantial presence. Those 16 showed increased expression of inflammatory cytokines but no inflammatory cell infiltrates or changes in leukocyte counts, the researchers noted.

“Findings of suggested viral replication in the cases with a very high viral load are showing that we need to do more studies to find out long-term consequences, which we do not know right now,” senior author Dirk Westermann, MD, also from the University Heart and Vascular Centre, Hamburg, said.

Implications for heart failure

The postmortem findings from Dr. Lindner and associates “provide intriguing evidence that COVID-19 is associated with at least some component of myocardial injury, perhaps as the result of direct viral infection of the heart,” wrote Clyde W. Yancy, MD, MSc, from Northwestern University, Chicago, and Gregg C. Fonarow, MD, from the University of California, Los Angeles, in an editorial accompanying both reports.

The CMR study from Dr. Püntmann and colleagues – on the backdrop of earlier COVID-19 observations – suggests the potential for “residual left ventricular dysfunction and ongoing inflammation” in the months following a COVID-19 diagnosis. Both developments may be “of sufficient concern to represent a nidus for new-onset heart failure and other cardiovascular complications,” contend Dr. Yancy and Dr. Fonarow.

“When added to the postmortem pathological findings from Lindner et al, we see the plot thickening and we are inclined to raise a new and very evident concern that cardiomyopathy and heart failure related to COVID-19 may potentially evolve as the natural history of this infection becomes clearer,” they wrote.

Some patients, having recovered from the acute illness, may be left with a chronic inflammatory state that probably puts them at increased risk for future heart failure, agreed Dr. Bozkurt when interviewed. “They could show further decline in cardiac function, and their recovery might take longer than with the usual viral illnesses that we see,” she said.

“There could also be a risk of sudden death. Inflammation sometimes gives rise to sudden death and ventricular arrhythmia, which I would be very worried about, especially if the myocardium is stressed,” Dr. Bozkurt said. “So competitive sports in those patients potentially could be risky.”

COVID-19 cohort vs. matched control subjects

The CMR study from Dr. Püntmann and colleagues prospectively entered 100 patients recently recovered from an acute bout of COVID-19, either at home or at a hospital, who were followed in a registry based at University Hospital Frankfurt. Their median age was 49 years; 47% were female. They were compared with 50 age- and sex-matched control patients and 50 apparently healthy volunteers matched for risk factors, the group noted.

On the same day as the CMR assessment, the recently recovered patients, compared with the healthy control subjects and risk-factor matched control subjects, respectively, showed (P ≤ .001 in each case):

• A reduced left ventricular (LV) ejection fraction: 56% vs. 60% and 61%.
• A higher LV end-diastolic volume index: 86 mL/m² vs. 80 mL/m² and 75 mL/m^2.
• A greater LV mass index: 51 g/m² vs. 47 g/m² and 53 g/m^2.
• A higher hs-TnT level: 5.6 pg/mL vs. 3.2 pg/mL and 3.9 pg/mL.
• A greater prevalence of hs-TnT levels 3 pg/mL or more: 71% vs. 11% and 31%.

At CMR, 78% of the recovered COVID-19 patients showed abnormalities that included raised myocardial native T1 and T2 mapping, which is suggestive of fibrosis and edema from inflammation, compared with the two control groups (P < .001 for all differences), “independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis,” the group wrote. Native T1 and T2 mapping correlated significantly with hs-TnT.

“We now have the diagnostic means to detect cardiac inflammation early, and we need make every effort to apply them in every day practice,”Dr. Püntmann said in the interview.

“Using cardiac MRI will allow us to raise our game against COVID-19 and proactively develop efficient cardioprotective treatments,” she said. “Until we have effective means of protecting from the infection, that is vaccination, we must act swiftly and within the means at hand.”

The analysis evokes several other ways patients with COVID-19 might be screened for significant myocardial involvement.

“Strategies could include checking troponins, not only at admission but maybe at discharge and perhaps even those individuals who are at home and are not necessarily requiring care,” Dr. Bozkurt said.

“Biomarker profiling and screening for ongoing inflammation probably are going to be important components of COVID-19, especially for those with subclinical risk and disease.”

Dr. Westermann proposed that troponin elevations at discharge “might be a good starting point” for selecting COVID-19 patients for functional testing or imaging to screen for cardiac sequelae. Performing such tests routinely now “would be overwhelming given the massive increase in patients we still see today.”

Dr. Püntmann had no disclosures; statements of potential conflict for the other authors are in the report. Dr. Bozkurt has previously disclosed receiving consultant fees or honoraria from Bayer Healthcare, Bristol-Myers Squibb, Lantheus Medical Imaging, and Respicardia; serving on a data safety monitoring board for LivaNova USA ; and having unspecified relationships with Abbott Laboratories. Dr. Lindner had no disclosures; Dr. Westermann reported receiving personal fees from AstraZeneca, Bayer, Novartis, and Medtronic. Dr. Yancy is a deputy editor and Dr. Fonarow a section editor for JAMA Cardiology. Dr. Yancy had no other disclosures. Dr. Fonarow reported receiving personal fees from Abbott Laboratories, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards Lifesciences, Janssen, Medtronic, Merck, and Novartis.

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

Evidence that the heart can take a major hit in patients hospitalized with COVID-19, especially those already with cardiovascular disease (CV) or its risk factors, has been sadly apparent from the pandemic’s earliest days.

Less clear from case studies and small series to date has been whether SARS-CoV-2 directly attacks the heart and whether acute cardiac effects of the illness may lead to some kind of lingering cardiomyopathy.

The field’s grasp of those issues advanced a bit in two new reports published July 27 in JAMA Cardiology that seem to validate concerns the virus can infect the myocardium, without necessarily causing myocarditis and the possibility that some “recovered” patients may be left with persisting myocardial injury and inflammation that potentially could later manifest as heart failure.

Persisting inflammation by cardiac magnetic resonance

A prospective cohort study with 100 patients recovered from a recent bout of the disease showed evidence of ventricular dysfunction, greater ventricular mass, and in 78% of the cohort, signs of myocardial inflammation by cardiac magnetic resonance (CMR) imaging. The CMR findings correlated with elevations in troponin T by high-sensitivity assay (hs-TnT).

Two-thirds of the cohort, whose acute COVID-19 severity had “ranged from asymptomatic to minor-to-moderate symptoms,” had recovered at home, whereas the remaining “severely unwell patients” had been hospitalized, wrote the authors, led by Valentina O. Püntmann, MD, PhD, University Hospital Frankfurt (Germany).

None of the patients had a history of heart failure or cardiomyopathy, although some had hypertension, diabetes, or evidence of coronary disease.

“Our findings demonstrate that participants with a relative paucity of preexisting cardiovascular condition and with mostly home-based recovery had frequent cardiac inflammatory involvement, which was similar to the hospitalized subgroup with regards to severity and extent,” the group noted.

“There is a considerable ongoing myocardial inflammation in the heart muscle weeks after recovery from COVID-19 illness. This finding is important because it may herald a considerable burden of heart failure in a few years down the line,” Dr. Püntmann said in an interview.

Early diagnosis would offer “a good chance that early treatment could reduce the relentless course of inflammatory damage or even halt it,” she said.

“The relatively clear onset of COVID-19 illness provides an opportunity, which we often do not have with other conditions, to take a proactive action and to look for heart involvement early, within a few weeks of recovery.”

The study’s CMR evidence of inflammation edema, scarring, and pericardial effusion are among “the major diagnostic criteria for inflammatory and viral myocarditis,” observed Biykem Bozkurt, MD, PhD, from Baylor College of Medicine, Houston, who wasn’t part of either new study.

The findings suggest – consistent with previous evidence – that some patients with recent COVID-19 may be left with ongoing myocardial inflammation, and this study further adds that it could potentially become subacute or even chronic and in some may not be totally reversible, she said in an interview. How long the effects are likely to persist “remains to be determined. We need longer-term outcomes data.”

Viral presence without myocarditis

The accompanying report featured a postmortem analysis of hearts from 39 patients with mostly severe COVID-19 that pointed to a significant SARS-CoV-2 presence and signs that the virus vigorously replicated in the myocardium.

But there was no evidence that the infection led to fulminant myocarditis. Rather, the virus had apparently infiltrated the heart by localizing in interstitial cells or in macrophages that took up in the myocardium without actually entering myocytes, concluded the report’s authors, led by Diana Lindner, PhD, from the University Heart and Vascular Centre, Hamburg (Germany).

The findings suggest “that the presence of SARS-CoV-2 in cardiac tissue does not necessarily cause an inflammatory reaction consistent with clinical myocarditis,” the group wrote.

Previously in the literature, in “cases in which myocardial inflammation was present, there was also evidence of clinical myocarditis, and therefore the current cases underlie a different pathophysiology,” they concluded.

No evidence of the virus was seen in 15 cases, about 61% of the group. In 16 of the remaining 24 hearts, the viral load exceeded 1,000 copies per mcg of RNA, a substantial presence. Those 16 showed increased expression of inflammatory cytokines but no inflammatory cell infiltrates or changes in leukocyte counts, the researchers noted.

“Findings of suggested viral replication in the cases with a very high viral load are showing that we need to do more studies to find out long-term consequences, which we do not know right now,” senior author Dirk Westermann, MD, also from the University Heart and Vascular Centre, Hamburg, said.

Implications for heart failure

The postmortem findings from Dr. Lindner and associates “provide intriguing evidence that COVID-19 is associated with at least some component of myocardial injury, perhaps as the result of direct viral infection of the heart,” wrote Clyde W. Yancy, MD, MSc, from Northwestern University, Chicago, and Gregg C. Fonarow, MD, from the University of California, Los Angeles, in an editorial accompanying both reports.

The CMR study from Dr. Püntmann and colleagues – on the backdrop of earlier COVID-19 observations – suggests the potential for “residual left ventricular dysfunction and ongoing inflammation” in the months following a COVID-19 diagnosis. Both developments may be “of sufficient concern to represent a nidus for new-onset heart failure and other cardiovascular complications,” contend Dr. Yancy and Dr. Fonarow.

“When added to the postmortem pathological findings from Lindner et al, we see the plot thickening and we are inclined to raise a new and very evident concern that cardiomyopathy and heart failure related to COVID-19 may potentially evolve as the natural history of this infection becomes clearer,” they wrote.

Some patients, having recovered from the acute illness, may be left with a chronic inflammatory state that probably puts them at increased risk for future heart failure, agreed Dr. Bozkurt when interviewed. “They could show further decline in cardiac function, and their recovery might take longer than with the usual viral illnesses that we see,” she said.

“There could also be a risk of sudden death. Inflammation sometimes gives rise to sudden death and ventricular arrhythmia, which I would be very worried about, especially if the myocardium is stressed,” Dr. Bozkurt said. “So competitive sports in those patients potentially could be risky.”

COVID-19 cohort vs. matched control subjects

The CMR study from Dr. Püntmann and colleagues prospectively entered 100 patients recently recovered from an acute bout of COVID-19, either at home or at a hospital, who were followed in a registry based at University Hospital Frankfurt. Their median age was 49 years; 47% were female. They were compared with 50 age- and sex-matched control patients and 50 apparently healthy volunteers matched for risk factors, the group noted.

On the same day as the CMR assessment, the recently recovered patients, compared with the healthy control subjects and risk-factor matched control subjects, respectively, showed (P ≤ .001 in each case):

• A reduced left ventricular (LV) ejection fraction: 56% vs. 60% and 61%.
• A higher LV end-diastolic volume index: 86 mL/m² vs. 80 mL/m² and 75 mL/m^2.
• A greater LV mass index: 51 g/m² vs. 47 g/m² and 53 g/m^2.
• A higher hs-TnT level: 5.6 pg/mL vs. 3.2 pg/mL and 3.9 pg/mL.
• A greater prevalence of hs-TnT levels 3 pg/mL or more: 71% vs. 11% and 31%.

At CMR, 78% of the recovered COVID-19 patients showed abnormalities that included raised myocardial native T1 and T2 mapping, which is suggestive of fibrosis and edema from inflammation, compared with the two control groups (P < .001 for all differences), “independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis,” the group wrote. Native T1 and T2 mapping correlated significantly with hs-TnT.

“We now have the diagnostic means to detect cardiac inflammation early, and we need make every effort to apply them in every day practice,”Dr. Püntmann said in the interview.

“Using cardiac MRI will allow us to raise our game against COVID-19 and proactively develop efficient cardioprotective treatments,” she said. “Until we have effective means of protecting from the infection, that is vaccination, we must act swiftly and within the means at hand.”

The analysis evokes several other ways patients with COVID-19 might be screened for significant myocardial involvement.

“Strategies could include checking troponins, not only at admission but maybe at discharge and perhaps even those individuals who are at home and are not necessarily requiring care,” Dr. Bozkurt said.

“Biomarker profiling and screening for ongoing inflammation probably are going to be important components of COVID-19, especially for those with subclinical risk and disease.”

Dr. Westermann proposed that troponin elevations at discharge “might be a good starting point” for selecting COVID-19 patients for functional testing or imaging to screen for cardiac sequelae. Performing such tests routinely now “would be overwhelming given the massive increase in patients we still see today.”

Dr. Püntmann had no disclosures; statements of potential conflict for the other authors are in the report. Dr. Bozkurt has previously disclosed receiving consultant fees or honoraria from Bayer Healthcare, Bristol-Myers Squibb, Lantheus Medical Imaging, and Respicardia; serving on a data safety monitoring board for LivaNova USA ; and having unspecified relationships with Abbott Laboratories. Dr. Lindner had no disclosures; Dr. Westermann reported receiving personal fees from AstraZeneca, Bayer, Novartis, and Medtronic. Dr. Yancy is a deputy editor and Dr. Fonarow a section editor for JAMA Cardiology. Dr. Yancy had no other disclosures. Dr. Fonarow reported receiving personal fees from Abbott Laboratories, Amgen, AstraZeneca, Bayer, CHF Solutions, Edwards Lifesciences, Janssen, Medtronic, Merck, and Novartis.

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

An erythematous rash was the most common cutaneous manifestation in patients with COVID-19, followed by chilblain-like lesions and urticaria-like lesions in a systematic review of mostly European studies.

Qing Zhao, MD, Xiaokai Fang, MD, and their colleagues at the Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, in Jinan, China, reported the results of a literature review of 44 articles published through May 2020 that included 507 patients with cutaneous manifestations of COVID-19. The review was published in the Journal of The European Academy of Dermatology and Venereology.

Nearly all of the patients (96%) were from Europe, and more than half were women (60%), with an average age of 49 years. Most patients had multiple skin symptoms, with the most common being erythema (44%), chilblain-like lesions (20%), urticaria-like lesions (16%), vesicular manifestations (13%), livedo/necrosis (6%), and petechiae (almost 2%). The authors described erythema as being present in specific sites, such as the trunk, extremities, flexural regions, face, and mucous membranes. Slightly less than half of all patients had significant pruritus.

Data on systemic COVID-19 symptoms were available for 431 patients and included fever in about two-thirds of patients and cough in almost 70%, with dyspnea in almost half of patients. Almost 60% had fatigue, and almost 60% had asthenia. Information about the onset of skin symptoms was available in 88 patients; of these patients, lesions were seen an average of almost 10 days after systemic symptoms appeared and, in almost 15%, were the first symptoms noted.

Histopathologic exams were done for only 23 patients and, in all cases, showed “inflammatory features without specific pathological changes, such as lymphocyte infiltration.” In one study, reverse transcription polymerase chain reaction testing of skin biopsy specimens tested negative for SARS-CoV-2.

Expression of ACE2, the receptor of SARS-CoV-2, in the skin was evaluated in six of the studies. “Higher ACE2 expression was identified in keratinocytes, mainly in differentiating keratinocytes and basal cells compared to the other cells of skin tissues,” the authors wrote. These results were confirmed with immunohistochemistry, which, they said, found “ACE2-positive keratinocytes in the stratum basal, the stratum spinosum, and the stratum granulosum of epiderma.” They added that this provides evidence “for percutaneous infection or the entry of virus into patients through skin tissues,” but cautioned that more research is needed.

The authors acknowledged that there are still many unanswered questions about COVID-19, and that more clinical data and research are needed, to improve the understanding of the cutaneous manifestations associated with COVID-19.

Pathogenesis of different cutaneous manifestations may be different, Dr. Femia said. For example, urticaria and morbilliform eruption were described by the authors of the review as more benign eruptions, but pathogenesis may differ from that of so-called COVID toes and from the pathogenesis of purpura and ulcerations seen in patients with more severe disease, she noted. It is plausible, she added, that purpura and ulcerations may be a “direct invasion of SARS-CoV-2 into endothelial cells,” which creates secondary processes “that ultimately destroy the skin.”

Urticaria and morbilliform eruptions, on the other hand, “are more simply that the immune system is recognizing COVID, and in doing so, is also recognizing some antigens in the skin and creating a hypersensitive response to the skin” and has “nothing to do with the SARS-CoV-2 virus actually being in that location,” she said.

It is important to differentiate between patients who have skin manifestations attributed to COVID-19 and those with manifestations independent of COVID-19, which is difficult, Dr. Femia noted. A patient with COVID-19 and a cutaneous manifestation may be having a reaction to a medication. “It’s important to have a critical eye and to remember that, when we see these manifestations, we should always be investigating whether there was an alternative cause so that we can better learn what exactly we should be attributing to this infection,” she said

Adam Friedman, MD, professor and interim chair of dermatology at George Washington University, Washington, said the authors of the review had presented interesting work, but made some “assumptions that need to be proven.” Dr. Friedman also was not involved in the research, but agreed in an interview with the assessment that it is unlikely SARS-CoV-2 would penetrate the skin. While some viruses – such as the poxvirus that causes molluscum contagiosum and the herpes simplex virus – invade keratinocytes specifically, there is a particular clinical phenotype that results that is associated with changes in the epidermis. However, “the skin manifestations of COVID-19 do not fit with direct skin invasion, [but] rather the immune response to systemic disease,” he said.

“[I]n terms of systemic invasion through the skin, it is possible, but this study certainly doesn’t show that. The presence/expression of ACE2 in the epidermis doesn’t translate to route of infection,” Dr. Friedman said..

The study received financial support from Shandong First Medical University, the Innovation Project of Shandong Academy of Medical Sciences and the Shandong Province Taishan Scholar Project. The authors report no relevant financial disclosures. Dr. Femia and Dr. Friedman had no relevant financial disclosures.

SOURCE: Zhao Q et al. J Eur Acad Dermatol Venereol. 2020 Jun 28. doi: 10.1111/jdv.16778.

An erythematous rash was the most common cutaneous manifestation in patients with COVID-19, followed by chilblain-like lesions and urticaria-like lesions in a systematic review of mostly European studies.

Qing Zhao, MD, Xiaokai Fang, MD, and their colleagues at the Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, in Jinan, China, reported the results of a literature review of 44 articles published through May 2020 that included 507 patients with cutaneous manifestations of COVID-19. The review was published in the Journal of The European Academy of Dermatology and Venereology.

Nearly all of the patients (96%) were from Europe, and more than half were women (60%), with an average age of 49 years. Most patients had multiple skin symptoms, with the most common being erythema (44%), chilblain-like lesions (20%), urticaria-like lesions (16%), vesicular manifestations (13%), livedo/necrosis (6%), and petechiae (almost 2%). The authors described erythema as being present in specific sites, such as the trunk, extremities, flexural regions, face, and mucous membranes. Slightly less than half of all patients had significant pruritus.

Data on systemic COVID-19 symptoms were available for 431 patients and included fever in about two-thirds of patients and cough in almost 70%, with dyspnea in almost half of patients. Almost 60% had fatigue, and almost 60% had asthenia. Information about the onset of skin symptoms was available in 88 patients; of these patients, lesions were seen an average of almost 10 days after systemic symptoms appeared and, in almost 15%, were the first symptoms noted.

Histopathologic exams were done for only 23 patients and, in all cases, showed “inflammatory features without specific pathological changes, such as lymphocyte infiltration.” In one study, reverse transcription polymerase chain reaction testing of skin biopsy specimens tested negative for SARS-CoV-2.

Expression of ACE2, the receptor of SARS-CoV-2, in the skin was evaluated in six of the studies. “Higher ACE2 expression was identified in keratinocytes, mainly in differentiating keratinocytes and basal cells compared to the other cells of skin tissues,” the authors wrote. These results were confirmed with immunohistochemistry, which, they said, found “ACE2-positive keratinocytes in the stratum basal, the stratum spinosum, and the stratum granulosum of epiderma.” They added that this provides evidence “for percutaneous infection or the entry of virus into patients through skin tissues,” but cautioned that more research is needed.

The authors acknowledged that there are still many unanswered questions about COVID-19, and that more clinical data and research are needed, to improve the understanding of the cutaneous manifestations associated with COVID-19.

Pathogenesis of different cutaneous manifestations may be different, Dr. Femia said. For example, urticaria and morbilliform eruption were described by the authors of the review as more benign eruptions, but pathogenesis may differ from that of so-called COVID toes and from the pathogenesis of purpura and ulcerations seen in patients with more severe disease, she noted. It is plausible, she added, that purpura and ulcerations may be a “direct invasion of SARS-CoV-2 into endothelial cells,” which creates secondary processes “that ultimately destroy the skin.”

Urticaria and morbilliform eruptions, on the other hand, “are more simply that the immune system is recognizing COVID, and in doing so, is also recognizing some antigens in the skin and creating a hypersensitive response to the skin” and has “nothing to do with the SARS-CoV-2 virus actually being in that location,” she said.

It is important to differentiate between patients who have skin manifestations attributed to COVID-19 and those with manifestations independent of COVID-19, which is difficult, Dr. Femia noted. A patient with COVID-19 and a cutaneous manifestation may be having a reaction to a medication. “It’s important to have a critical eye and to remember that, when we see these manifestations, we should always be investigating whether there was an alternative cause so that we can better learn what exactly we should be attributing to this infection,” she said

Adam Friedman, MD, professor and interim chair of dermatology at George Washington University, Washington, said the authors of the review had presented interesting work, but made some “assumptions that need to be proven.” Dr. Friedman also was not involved in the research, but agreed in an interview with the assessment that it is unlikely SARS-CoV-2 would penetrate the skin. While some viruses – such as the poxvirus that causes molluscum contagiosum and the herpes simplex virus – invade keratinocytes specifically, there is a particular clinical phenotype that results that is associated with changes in the epidermis. However, “the skin manifestations of COVID-19 do not fit with direct skin invasion, [but] rather the immune response to systemic disease,” he said.

“[I]n terms of systemic invasion through the skin, it is possible, but this study certainly doesn’t show that. The presence/expression of ACE2 in the epidermis doesn’t translate to route of infection,” Dr. Friedman said..

The study received financial support from Shandong First Medical University, the Innovation Project of Shandong Academy of Medical Sciences and the Shandong Province Taishan Scholar Project. The authors report no relevant financial disclosures. Dr. Femia and Dr. Friedman had no relevant financial disclosures.

SOURCE: Zhao Q et al. J Eur Acad Dermatol Venereol. 2020 Jun 28. doi: 10.1111/jdv.16778.

An erythematous rash was the most common cutaneous manifestation in patients with COVID-19, followed by chilblain-like lesions and urticaria-like lesions in a systematic review of mostly European studies.

Qing Zhao, MD, Xiaokai Fang, MD, and their colleagues at the Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, in Jinan, China, reported the results of a literature review of 44 articles published through May 2020 that included 507 patients with cutaneous manifestations of COVID-19. The review was published in the Journal of The European Academy of Dermatology and Venereology.

Nearly all of the patients (96%) were from Europe, and more than half were women (60%), with an average age of 49 years. Most patients had multiple skin symptoms, with the most common being erythema (44%), chilblain-like lesions (20%), urticaria-like lesions (16%), vesicular manifestations (13%), livedo/necrosis (6%), and petechiae (almost 2%). The authors described erythema as being present in specific sites, such as the trunk, extremities, flexural regions, face, and mucous membranes. Slightly less than half of all patients had significant pruritus.

Data on systemic COVID-19 symptoms were available for 431 patients and included fever in about two-thirds of patients and cough in almost 70%, with dyspnea in almost half of patients. Almost 60% had fatigue, and almost 60% had asthenia. Information about the onset of skin symptoms was available in 88 patients; of these patients, lesions were seen an average of almost 10 days after systemic symptoms appeared and, in almost 15%, were the first symptoms noted.

Histopathologic exams were done for only 23 patients and, in all cases, showed “inflammatory features without specific pathological changes, such as lymphocyte infiltration.” In one study, reverse transcription polymerase chain reaction testing of skin biopsy specimens tested negative for SARS-CoV-2.

Expression of ACE2, the receptor of SARS-CoV-2, in the skin was evaluated in six of the studies. “Higher ACE2 expression was identified in keratinocytes, mainly in differentiating keratinocytes and basal cells compared to the other cells of skin tissues,” the authors wrote. These results were confirmed with immunohistochemistry, which, they said, found “ACE2-positive keratinocytes in the stratum basal, the stratum spinosum, and the stratum granulosum of epiderma.” They added that this provides evidence “for percutaneous infection or the entry of virus into patients through skin tissues,” but cautioned that more research is needed.

The authors acknowledged that there are still many unanswered questions about COVID-19, and that more clinical data and research are needed, to improve the understanding of the cutaneous manifestations associated with COVID-19.

Pathogenesis of different cutaneous manifestations may be different, Dr. Femia said. For example, urticaria and morbilliform eruption were described by the authors of the review as more benign eruptions, but pathogenesis may differ from that of so-called COVID toes and from the pathogenesis of purpura and ulcerations seen in patients with more severe disease, she noted. It is plausible, she added, that purpura and ulcerations may be a “direct invasion of SARS-CoV-2 into endothelial cells,” which creates secondary processes “that ultimately destroy the skin.”

Urticaria and morbilliform eruptions, on the other hand, “are more simply that the immune system is recognizing COVID, and in doing so, is also recognizing some antigens in the skin and creating a hypersensitive response to the skin” and has “nothing to do with the SARS-CoV-2 virus actually being in that location,” she said.

It is important to differentiate between patients who have skin manifestations attributed to COVID-19 and those with manifestations independent of COVID-19, which is difficult, Dr. Femia noted. A patient with COVID-19 and a cutaneous manifestation may be having a reaction to a medication. “It’s important to have a critical eye and to remember that, when we see these manifestations, we should always be investigating whether there was an alternative cause so that we can better learn what exactly we should be attributing to this infection,” she said

Adam Friedman, MD, professor and interim chair of dermatology at George Washington University, Washington, said the authors of the review had presented interesting work, but made some “assumptions that need to be proven.” Dr. Friedman also was not involved in the research, but agreed in an interview with the assessment that it is unlikely SARS-CoV-2 would penetrate the skin. While some viruses – such as the poxvirus that causes molluscum contagiosum and the herpes simplex virus – invade keratinocytes specifically, there is a particular clinical phenotype that results that is associated with changes in the epidermis. However, “the skin manifestations of COVID-19 do not fit with direct skin invasion, [but] rather the immune response to systemic disease,” he said.

“[I]n terms of systemic invasion through the skin, it is possible, but this study certainly doesn’t show that. The presence/expression of ACE2 in the epidermis doesn’t translate to route of infection,” Dr. Friedman said..

The study received financial support from Shandong First Medical University, the Innovation Project of Shandong Academy of Medical Sciences and the Shandong Province Taishan Scholar Project. The authors report no relevant financial disclosures. Dr. Femia and Dr. Friedman had no relevant financial disclosures.

SOURCE: Zhao Q et al. J Eur Acad Dermatol Venereol. 2020 Jun 28. doi: 10.1111/jdv.16778.

When the pandemic was just emerging from its infancy and we were just beginning to think about social distancing, I was sitting around enjoying an adult beverage and some gluten free (not my choice) snacks with some friends. A retired nurse who had just celebrated her 80th birthday said, “I can’t wait until they’ve developed a vaccine.” A former electrical engineer sitting just short of 2 meters to her left responded, “Don’t save me a place near the front of the line for something that is being developed in a program called Warp Speed.”

Micah Young/istockphoto.com

How do you feel about the potential SARS-CoV-2 vaccine? Are you going to roll up your sleeve as soon as the vaccine becomes available in your community? What are you going to suggest to your patients, your children? I suspect many of you will answer, “It depends.” What factors will you be considering when you try to decide between what is likely to be several competing SARS-CoV-2 vaccines?

Will it make any difference to you which biochemical-immune-bending strategy is being used to make the vaccine? All of them will probably be the result of a clever sounding but novel technique, all of them with a track record that is measured in months and not years. Will you be swayed by how large the trials were? Or how long the follow-up lasted? How effective must the vaccine be to convince you that it is worth receiving or recommending? Do you have the tools and experience to make a decision like that? I know I don’t. And should you and I even be put in a position to make that decision?

In the past, you and I may have relied on the Centers for Disease Control and Prevention for advice. But given the somewhat murky and stormy relationship between the CDC and the president, the vaccine recommendation may be issued by the White House and not the CDC.

For those of us who were practicing medicine during the Swine Flu fiasco of 1976, the pace and the politics surrounding the development of a SARS-CoV-2 vaccine has a discomforting déjà vu quality about it. The fact that like this year 1976 was an election year that infused the development process with a sense of urgency above and beyond any of the concerns about the pandemic that never happened. Although causality was never proven, there was a surge in Guillain-Barré syndrome cases that had been linked temporally to the vaccine.

Of course, our pandemic is real, and it would be imprudent to wait a year or more to watch for long-term vaccine sequelae. However, I am more than a little concerned that fast tracking the development process may result in unfortunate consequences in the short term that could have been avoided with a more measured approach to trialing the vaccines.

The sad reality is that as a nation we tend to be impatient. We are drawn to quick fixes that come in a vial or a capsule. We are learning that simple measures like mask wearing and social distancing can make a difference in slowing the spread of the virus. It would be tragic to rush a vaccine into production that at best turns out to simply be an expensive alternative to the measures that we know work or at worst injures more of us than it saves.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

When the pandemic was just emerging from its infancy and we were just beginning to think about social distancing, I was sitting around enjoying an adult beverage and some gluten free (not my choice) snacks with some friends. A retired nurse who had just celebrated her 80th birthday said, “I can’t wait until they’ve developed a vaccine.” A former electrical engineer sitting just short of 2 meters to her left responded, “Don’t save me a place near the front of the line for something that is being developed in a program called Warp Speed.”

Micah Young/istockphoto.com

How do you feel about the potential SARS-CoV-2 vaccine? Are you going to roll up your sleeve as soon as the vaccine becomes available in your community? What are you going to suggest to your patients, your children? I suspect many of you will answer, “It depends.” What factors will you be considering when you try to decide between what is likely to be several competing SARS-CoV-2 vaccines?

Will it make any difference to you which biochemical-immune-bending strategy is being used to make the vaccine? All of them will probably be the result of a clever sounding but novel technique, all of them with a track record that is measured in months and not years. Will you be swayed by how large the trials were? Or how long the follow-up lasted? How effective must the vaccine be to convince you that it is worth receiving or recommending? Do you have the tools and experience to make a decision like that? I know I don’t. And should you and I even be put in a position to make that decision?

In the past, you and I may have relied on the Centers for Disease Control and Prevention for advice. But given the somewhat murky and stormy relationship between the CDC and the president, the vaccine recommendation may be issued by the White House and not the CDC.

For those of us who were practicing medicine during the Swine Flu fiasco of 1976, the pace and the politics surrounding the development of a SARS-CoV-2 vaccine has a discomforting déjà vu quality about it. The fact that like this year 1976 was an election year that infused the development process with a sense of urgency above and beyond any of the concerns about the pandemic that never happened. Although causality was never proven, there was a surge in Guillain-Barré syndrome cases that had been linked temporally to the vaccine.

Of course, our pandemic is real, and it would be imprudent to wait a year or more to watch for long-term vaccine sequelae. However, I am more than a little concerned that fast tracking the development process may result in unfortunate consequences in the short term that could have been avoided with a more measured approach to trialing the vaccines.

The sad reality is that as a nation we tend to be impatient. We are drawn to quick fixes that come in a vial or a capsule. We are learning that simple measures like mask wearing and social distancing can make a difference in slowing the spread of the virus. It would be tragic to rush a vaccine into production that at best turns out to simply be an expensive alternative to the measures that we know work or at worst injures more of us than it saves.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

When the pandemic was just emerging from its infancy and we were just beginning to think about social distancing, I was sitting around enjoying an adult beverage and some gluten free (not my choice) snacks with some friends. A retired nurse who had just celebrated her 80th birthday said, “I can’t wait until they’ve developed a vaccine.” A former electrical engineer sitting just short of 2 meters to her left responded, “Don’t save me a place near the front of the line for something that is being developed in a program called Warp Speed.”

Micah Young/istockphoto.com

How do you feel about the potential SARS-CoV-2 vaccine? Are you going to roll up your sleeve as soon as the vaccine becomes available in your community? What are you going to suggest to your patients, your children? I suspect many of you will answer, “It depends.” What factors will you be considering when you try to decide between what is likely to be several competing SARS-CoV-2 vaccines?

Will it make any difference to you which biochemical-immune-bending strategy is being used to make the vaccine? All of them will probably be the result of a clever sounding but novel technique, all of them with a track record that is measured in months and not years. Will you be swayed by how large the trials were? Or how long the follow-up lasted? How effective must the vaccine be to convince you that it is worth receiving or recommending? Do you have the tools and experience to make a decision like that? I know I don’t. And should you and I even be put in a position to make that decision?

In the past, you and I may have relied on the Centers for Disease Control and Prevention for advice. But given the somewhat murky and stormy relationship between the CDC and the president, the vaccine recommendation may be issued by the White House and not the CDC.

For those of us who were practicing medicine during the Swine Flu fiasco of 1976, the pace and the politics surrounding the development of a SARS-CoV-2 vaccine has a discomforting déjà vu quality about it. The fact that like this year 1976 was an election year that infused the development process with a sense of urgency above and beyond any of the concerns about the pandemic that never happened. Although causality was never proven, there was a surge in Guillain-Barré syndrome cases that had been linked temporally to the vaccine.

Of course, our pandemic is real, and it would be imprudent to wait a year or more to watch for long-term vaccine sequelae. However, I am more than a little concerned that fast tracking the development process may result in unfortunate consequences in the short term that could have been avoided with a more measured approach to trialing the vaccines.

The sad reality is that as a nation we tend to be impatient. We are drawn to quick fixes that come in a vial or a capsule. We are learning that simple measures like mask wearing and social distancing can make a difference in slowing the spread of the virus. It would be tragic to rush a vaccine into production that at best turns out to simply be an expensive alternative to the measures that we know work or at worst injures more of us than it saves.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

It turns out that a pandemic, at least this COVID-19 version, can be a challenge for folks like me who are seldom at a loss for words. The pandemic has so overwhelmed every corner of our lives that it is hard to think of another topic on which to pontificate and still not tromp on someone’s political toes. One can always write about the pandemic itself, and I’ve tried that, but as the curtain is gradually being pulled back on this crafty little germ one runs the risk of making an observation today that will be disproved in a week or 2. However, I can’t suppress my urge to write, and so I have decided to share a few brief random observations. Of course they are related to the pandemic. And of course I realize that there is a better than fifty percent chance that they will be proved wrong by the time you read my next Letters from Maine.

Under the radar

Phynart Studio/Getty Images

Two of the many mysteries about SARS-CoV-2 involve young children who as a group appear to be less easily infected than adults and even when infected seem to be less likely to spread the disease to other people, particularly adults. One explanation posited by some researchers in France is that young children are less likely to have symptoms such as cough and are less powerful speakers and so might be less likely to spew out a significant number of infected aerosolized droplets (“How to Reopen Schools: What Science and Other Countries Teach Us.” By Pam Belluck, Apoorva Mandavill, and Benedict Carey. New York Times, July 11, 2020). While there are probably several factors to explain this observation, one may be that young children are short, seldom taller than an adult waistline. I suspect the majority of aerosols they emit fall and inactivate harmlessly to the floor several feet below an adult’s nose and mouth. Regardless of the explanation, it appears to be good news for the opening of schools, at least for the early grades.

Forget the deep cleaning

There has been a glut of news stories about reopening schools, and many of these stories are accompanied by images of school custodians with buckets, mops, spray bottles, and sponges scouring desks and walls. The most recent image in our local newspaper was of someone scrubbing the underside of a desk. I know it’s taking the World Health Organization an unconscionable period of time to acknowledge that SARS-CoV-2 is airborne, but the rest of us should have gotten the message long ago and been directing our attention to air handling and ventilation. The urge to scrub and deep clean is a hard habit to break, but this nasty bug is not like influenza or a flesh eating bacteria in which deep cleaning might help. A better image to attach to a story on school reopening would be one of a custodian with a screwdriver struggling to pry open a classroom window that had been painted shut a decade ago.

Managing the inevitable

Middlebury College in Vermont and Bowdoin College here in Brunswick, Maine, are similar in many respects because they are small and situated in relatively isolated small New England towns with good track records for pandemic management. Middlebury has elected to invite all its 2,750 students back to campus, whereas Bowdoin has decided to allow only incoming first years and transfer students (for a total of about 600) to return. Both schools will institute similar testing and social distancing protocols and restrict students from access to their respective towns (“A Tale of 2 Colleges.” By Bill Burger. Inside Higher Ed, June 29,2020). It will be an interesting experiment. I’m voting for Middlebury and not because my son and daughter-in-law are alums, but because I think Middlebury seems to have acknowledged that no matter how diligent one is in creating a SARS-CoV-2–free environment at the outset, these are college kids and there will be some cases on both campuses. It is on how those inevitable realities are managed and contained that an institution should be judged.

Patience

Unfortunately, the pandemic has exposed some of our weaknesses as a nation. We always have been a restless and impatient population eager to get moving and it has driven us to greatness. Hopefully, patience will be a lesson that we will learn, along with many others.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

It turns out that a pandemic, at least this COVID-19 version, can be a challenge for folks like me who are seldom at a loss for words. The pandemic has so overwhelmed every corner of our lives that it is hard to think of another topic on which to pontificate and still not tromp on someone’s political toes. One can always write about the pandemic itself, and I’ve tried that, but as the curtain is gradually being pulled back on this crafty little germ one runs the risk of making an observation today that will be disproved in a week or 2. However, I can’t suppress my urge to write, and so I have decided to share a few brief random observations. Of course they are related to the pandemic. And of course I realize that there is a better than fifty percent chance that they will be proved wrong by the time you read my next Letters from Maine.

Under the radar

Phynart Studio/Getty Images

Two of the many mysteries about SARS-CoV-2 involve young children who as a group appear to be less easily infected than adults and even when infected seem to be less likely to spread the disease to other people, particularly adults. One explanation posited by some researchers in France is that young children are less likely to have symptoms such as cough and are less powerful speakers and so might be less likely to spew out a significant number of infected aerosolized droplets (“How to Reopen Schools: What Science and Other Countries Teach Us.” By Pam Belluck, Apoorva Mandavill, and Benedict Carey. New York Times, July 11, 2020). While there are probably several factors to explain this observation, one may be that young children are short, seldom taller than an adult waistline. I suspect the majority of aerosols they emit fall and inactivate harmlessly to the floor several feet below an adult’s nose and mouth. Regardless of the explanation, it appears to be good news for the opening of schools, at least for the early grades.

Forget the deep cleaning

There has been a glut of news stories about reopening schools, and many of these stories are accompanied by images of school custodians with buckets, mops, spray bottles, and sponges scouring desks and walls. The most recent image in our local newspaper was of someone scrubbing the underside of a desk. I know it’s taking the World Health Organization an unconscionable period of time to acknowledge that SARS-CoV-2 is airborne, but the rest of us should have gotten the message long ago and been directing our attention to air handling and ventilation. The urge to scrub and deep clean is a hard habit to break, but this nasty bug is not like influenza or a flesh eating bacteria in which deep cleaning might help. A better image to attach to a story on school reopening would be one of a custodian with a screwdriver struggling to pry open a classroom window that had been painted shut a decade ago.

Managing the inevitable

Middlebury College in Vermont and Bowdoin College here in Brunswick, Maine, are similar in many respects because they are small and situated in relatively isolated small New England towns with good track records for pandemic management. Middlebury has elected to invite all its 2,750 students back to campus, whereas Bowdoin has decided to allow only incoming first years and transfer students (for a total of about 600) to return. Both schools will institute similar testing and social distancing protocols and restrict students from access to their respective towns (“A Tale of 2 Colleges.” By Bill Burger. Inside Higher Ed, June 29,2020). It will be an interesting experiment. I’m voting for Middlebury and not because my son and daughter-in-law are alums, but because I think Middlebury seems to have acknowledged that no matter how diligent one is in creating a SARS-CoV-2–free environment at the outset, these are college kids and there will be some cases on both campuses. It is on how those inevitable realities are managed and contained that an institution should be judged.

Patience

Unfortunately, the pandemic has exposed some of our weaknesses as a nation. We always have been a restless and impatient population eager to get moving and it has driven us to greatness. Hopefully, patience will be a lesson that we will learn, along with many others.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

It turns out that a pandemic, at least this COVID-19 version, can be a challenge for folks like me who are seldom at a loss for words. The pandemic has so overwhelmed every corner of our lives that it is hard to think of another topic on which to pontificate and still not tromp on someone’s political toes. One can always write about the pandemic itself, and I’ve tried that, but as the curtain is gradually being pulled back on this crafty little germ one runs the risk of making an observation today that will be disproved in a week or 2. However, I can’t suppress my urge to write, and so I have decided to share a few brief random observations. Of course they are related to the pandemic. And of course I realize that there is a better than fifty percent chance that they will be proved wrong by the time you read my next Letters from Maine.

Under the radar

Phynart Studio/Getty Images

Two of the many mysteries about SARS-CoV-2 involve young children who as a group appear to be less easily infected than adults and even when infected seem to be less likely to spread the disease to other people, particularly adults. One explanation posited by some researchers in France is that young children are less likely to have symptoms such as cough and are less powerful speakers and so might be less likely to spew out a significant number of infected aerosolized droplets (“How to Reopen Schools: What Science and Other Countries Teach Us.” By Pam Belluck, Apoorva Mandavill, and Benedict Carey. New York Times, July 11, 2020). While there are probably several factors to explain this observation, one may be that young children are short, seldom taller than an adult waistline. I suspect the majority of aerosols they emit fall and inactivate harmlessly to the floor several feet below an adult’s nose and mouth. Regardless of the explanation, it appears to be good news for the opening of schools, at least for the early grades.

Forget the deep cleaning

There has been a glut of news stories about reopening schools, and many of these stories are accompanied by images of school custodians with buckets, mops, spray bottles, and sponges scouring desks and walls. The most recent image in our local newspaper was of someone scrubbing the underside of a desk. I know it’s taking the World Health Organization an unconscionable period of time to acknowledge that SARS-CoV-2 is airborne, but the rest of us should have gotten the message long ago and been directing our attention to air handling and ventilation. The urge to scrub and deep clean is a hard habit to break, but this nasty bug is not like influenza or a flesh eating bacteria in which deep cleaning might help. A better image to attach to a story on school reopening would be one of a custodian with a screwdriver struggling to pry open a classroom window that had been painted shut a decade ago.

Managing the inevitable

Middlebury College in Vermont and Bowdoin College here in Brunswick, Maine, are similar in many respects because they are small and situated in relatively isolated small New England towns with good track records for pandemic management. Middlebury has elected to invite all its 2,750 students back to campus, whereas Bowdoin has decided to allow only incoming first years and transfer students (for a total of about 600) to return. Both schools will institute similar testing and social distancing protocols and restrict students from access to their respective towns (“A Tale of 2 Colleges.” By Bill Burger. Inside Higher Ed, June 29,2020). It will be an interesting experiment. I’m voting for Middlebury and not because my son and daughter-in-law are alums, but because I think Middlebury seems to have acknowledged that no matter how diligent one is in creating a SARS-CoV-2–free environment at the outset, these are college kids and there will be some cases on both campuses. It is on how those inevitable realities are managed and contained that an institution should be judged.

Patience

Unfortunately, the pandemic has exposed some of our weaknesses as a nation. We always have been a restless and impatient population eager to get moving and it has driven us to greatness. Hopefully, patience will be a lesson that we will learn, along with many others.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.