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Better continence rate gives robotic prostatectomy the edge
At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).
“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.
Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.
The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.
“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
Providing higher quality evidence
Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.
The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.
In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).
That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.
A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).
The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
Multicenter experience
The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.
Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”
Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.
“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.
“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.
“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.
“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.
Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.
“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.
This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.
SOURCE: Stolzenburg J-E. EAU20, Abstract.
At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).
“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.
Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.
The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.
“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
Providing higher quality evidence
Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.
The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.
In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).
That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.
A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).
The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
Multicenter experience
The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.
Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”
Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.
“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.
“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.
“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.
“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.
Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.
“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.
This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.
SOURCE: Stolzenburg J-E. EAU20, Abstract.
At 3 months, 54.3% of prostate cancer patients who underwent RARP and 45.6% of those who had LRP were continent after catheter removal (P = .027).
“We did use a very strong definition for continence, meaning no pad or safety pad; patients wearing one pad per day we’re not classified as continent,” said study investigator Jens-Uwe Stolzenburg, MD, PhD, professor and head of urology at the University of Leipzig Hospital in Germany.
Dr. Stolzenburg presented these findings at the European Association of Urology virtual annual congress.
The findings fit with previous research showing higher continence rates with RARP (69%-80%) than with LRP (62%-63%), although those studies did not always find the difference to be statistically significant, and higher quality evidence was needed (J Sex Med. 2011 May;8[5]:1503-12; Eur Urol. 2013 Apr;63[4]:606-14). “Up to now, there are only two randomized studies published in the literature comparing robotic and classical laparoscopic prostatectomy, and my point of view is that there are strong limitations of both studies,” Dr. Stolzenburg said.
“First of all, both studies are based on the single experience of surgeons, so only one surgeon has performed surgery. The second limitation is the limited numbers of patients included,” he observed. One study had 64 patients in each arm, and the other had 60 patients in each arm.
Providing higher quality evidence
Dr. Stolzenburg presented results of the LAP-01 study, which was designed to close the knowledge gap and determine if there really was an advantage for RARP over LRP for preserving continence.
The trial was conducted at three academic centers and one public hospital in Germany. The final analysis included 718 patients with prostate cancer referred for prostate surgery. They were randomized, in a ratio of three to one, to undergo RARP (n = 530) or LRP (n = 188), being unaware themselves of which surgery they would be having until the 3-month primary endpoint.
In addition to improved continence over LRP, RARP was associated with significantly better erectile function at 3 months (P = .016), as measured by the International Index of Erectile Function (IIEF).
That said, erectile function was still severely affected by both surgical procedures. Total IIEF scores were 6.0 with RARP and 4.7 with LRP, compared with 15.9 and 16.2, respectively, at baseline.
A higher percentage of men who had nerve-sparing procedures reported having an erection suitable for sexual intercourse at 2 months in the RARP group than in the LRP group (17.7% vs. 6.7%, P = .007).
The complication rate was “a little bit higher” in the LRP group than in the RARP group, “but the difference was not statistically significant,” Dr. Stolzenburg said. He added that “the most frequent complication was anastomotic leakage, and most complications overall were low-grade complications in both groups.”
Multicenter experience
The potential for prostatectomy to have effects on urinary continence and sexual function are important issues that need to be discussed upfront with patients, observed Alexandre de la Taille, MD, PhD, who was invited to discuss the study.
Current European guidance says “there is no surgical approach – open, laparoscopic, or robotic radical prostatectomy – that has proven superiority in terms of functional or oncological results,” he said. However, the LAP-01 study “found that the continence rate was better when we use a robotic approach compared to a laparoscopic approach.”
Dr. de la Taille, who is professor and chair of the urology service at CHU Mondor in Cretéil, France, also highlighted that this result was achieved with no increase in the morbidity profile or compromise of cancer control.
“My very first impression is that we are missing a little bit, some granularity of the data in terms of one key question, which is volume of surgery,” said the chair of the session Alberto Briganti, MD, PhD, associate professor of urology at Università Vita-Salute San Raffaele, and deputy director of the Urological Research Institute of IRCCS Ospedale San Raffaele, both in Milan.
“We know that recovery of outcomes is volume-dependent, both in the laparoscopic and robotic setting,” Dr. Briganti added.
“This is really a multicenter study including a lot of surgeons,” Dr. de la Taille countered, agreeing that the volume of surgeries might be something the LAP-01 study investigators could look at in a sub-analysis.
“Of course, some of them have a huge experience in the robotic approach and some of them a lower experience of the robotic approach, but when you put all together, there is a better continence recovery at 3 months when compared to the laparoscopic approach,” Dr. de la Taille said.
Calling the study a “real-life practice study,” he noted that urinary continence at 12 months might be a stronger endpoint, and the difference between the two surgical approaches may become less with time.
“But for the patient, again, daily practice, it’s better to have early urinary continence recovery compared to a late recovery,” Dr. de la Taille said.
This study was funded by the University of Leipzig via a German Cancer Aid grant. All speakers declared no conflicts of interest.
SOURCE: Stolzenburg J-E. EAU20, Abstract.
FROM EAU20
Heart damage even after COVID-19 ‘recovery’ evokes specter of later heart failure
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/m2.
- A greater LV mass index: 51 g/m2 vs. 47 g/m2 and 53 g/m2.
- 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/m2.
- A greater LV mass index: 51 g/m2 vs. 47 g/m2 and 53 g/m2.
- 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/m2.
- A greater LV mass index: 51 g/m2 vs. 47 g/m2 and 53 g/m2.
- 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.
AAP report aims to educate providers on female genital mutilation/cutting
Although female genital mutilation or cutting (FGM/C) is outlawed in much of the world, it still occurs for cultural reasons despite having no medical benefit, according to a clinical report from the American Academy of Pediatrics.
FGM/C is mainly performed on children and adolescents, but most of the research and teaching to date has addressed the impact of FGM/C on women of childbearing age and management during pregnancy and post partum, wrote Janine Young, MD, of the University of Colorado Denver in Aurora and colleagues. They are members of the AAP section on global health, committee on medical liability and risk management, or the committee on bioethics.
Published in Pediatrics, the report provides “the first comprehensive summary of FGM/C in children and includes education regarding a standard-of-care approach for examination of external female genitalia at all health supervision examinations, diagnosis, complications, management, treatment, culturally sensitive discussion and counseling approaches, and legal and ethical considerations,” they wrote.
The World Health Organization categorizes FGM/C into four subtypes. “Type I includes cutting of the glans or part of the body of the clitoris and/or prepuce; type II includes excision of the clitoris and labia minora, with or without excision of the labia majora; type III, infibulation, includes cutting and apposing the labia minora and/or majora over the urethral meatus and vaginal opening to significantly narrow it and may include clitoral excision; and type IV includes piercing, scraping, nicking, stretching, or otherwise injuring the external female genitalia without removing any genital tissue and includes practices that do not fall into the other three categories,” the authors wrote. Of these, type III is associated with the greatest long-term morbidity.
Data suggest that the prevalence and type of FGM/C varies by region, with the highest prevalence of type III in East Africa, where 82%-99% of girls reported FGM/C and 34%-79% of these cases involved type III, the authors reported.
Generally, pediatric health care providers in the United States have limited knowledge of FGM/C in the absence of any required courses on diagnosis or treatment for most primary care specialties. However, clinicians should be aware of possible risk factors, including a mother or sibling with a history of FGM/C, or patients with a country of origin, birth country, or travel history to a country where FGM/C is practiced, Dr. Young and associates noted.
They recommend that but acknowledged the challenges in raising the topic and addressing it in a culturally sensitive way. “Experts suggest that health care providers ask the patient or parent the term they use to name female genital cutting” and avoid the term mutilation, which may be offensive or misunderstood.
Many girls who have undergone FGM/C were too young to remember, the authors note. “Instead, it is advisable that the FGM/C clinical history taking include both the girl and parent or guardian once rapport has been established.”
Review potential medical complications if FGM/C is identified, and plans should be made for follow-up visits to monitor development of complications, the authors said. In addition, engage in a culturally sensitive discussion with teenagers, who may or may not have known about their FGM/C. In some cases, parents and caregivers may not have known about the FGM/C, which may be a community practice in some cultures with decisions made by other family members or authority figures.
“It is important for health care providers to assess each patient individually and make no assumptions about her and her parents’ beliefs regarding FGM/C,” Dr. Young and associates emphasized. “Mothers and fathers may or may not hold discordant views about FGM/C, and some clinical experts suggest that mothers who have themselves undergone FGM/C may nonetheless oppose subjecting their daughters to this practice. Instead, treating patients and caregivers with respect, sensitivity, and professionalism will encourage them to return and supports health-seeking behavior.”
The report presents 11 specific recommendations, including that health care providers should not perform any type of FGM/C and actively counsel families against such practices. In addition, children should have external genitalia checked at all health supervision examinations (with the consent of the guardian and/or child), and an assessment for FGM/C should be documented in the health records of patients with risk factors.
Notably, “[i]f genital examination findings are equivocal for the presence of FGM/C and risk factors for FGM/ C are present, a specialist trained in identification of FGM/C should be consulted,” Dr. Young and associates recommended. They also recommended defibulation for all girls and teenagers with type III FGM/C, especially for those with complications, and the procedure should be performed by an experienced pediatric gynecologist, gynecologist, urologist, or urogynecologist.
Finally, “[i]f FGM/C is suspected to have occurred in the United States, or as vacation cutting after immigration to the United States, the child should be evaluated for potential abuse. ... Expressed intention to engage in FGM/C, either in the United States or abroad, should also prompt a report to CPS [child protective services] if the child’s parent or caregiver cannot be dissuaded,” the authors wrote.
The report also includes case examples and expert analyses from legal and medical ethics experts to provide additional guidance for clinicians.
“This work seeks to educate pediatric health care providers on the occurrence of FGM/C, and the broader applications to the patients/population it impacts as well as the intersecting issues of diagnosis, complications, treatment, counseling needs, and the ethical and legal implications,” M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview.
However, challenges in implementing the recommendations “relate to the complexity of the issue and also the need for greater education of primary providers,” Dr. Jay said. “The overall message for providers, I believe, is a greater understanding of the practice [of FGM/C] as most providers have limited knowledge of this practice in the United States.”
“I believe the case-based presentations allow for a better understanding of how best to approach patients and families,” she added.
Kelly Curran, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, said, “I think one of largest barriers to implementing the strategies [from] this report is the limited knowledge of FGM/C by most clinicians.”
“In general, many pediatricians are uncomfortable with genital examinations,” she said in an interview. “I suspect most feel uncomfortable with identifying FGM/C versus other genital pathology and may not have ready access to FGM/C experts. Additionally, having these difficult conversations with families about this sensitive topic may be challenging,” said Dr. Curran. “Fortunately, this report is incredibly comprehensive, providing extensive background into FGM/C, effectively using diagrams and pictures, and explaining the legal and ethical issues that arise in the care of these patients.”
“Ultimately, I think there will need to be more education within medical training and further research into FGM/C,” Dr. Curran added. “Clinicians should be knowledgeable about FGM/C, including prevalence, identification, health complications, and treatment, as well as legal and ethical implications.” However, “in addition to knowledge, clinicians must be able to navigate counseling patients and their families around this culturally sensitive topic.”
The report is thorough and well written, yet “there still remains significant gaps in knowledge about FGM/C in children and adolescents,” she said. “I think future research into prevalence, along with the health effects of FGM/C, including its impact on mental and sexual health, in the pediatric population will be essential.”
The study received no outside funding. Coauthor Christa Johnson-Agbakwu, MD, disclosed a grant relationship with Arizona State University from the 2018 copyright of “Female Genital Mutilation/Cutting (FGM/C): A Visual Reference and Learning Tool for Health Care Professionals.” The other researchers had no financial conflicts to disclose. Dr. Jay and Dr. Curran had no relevant financial conflicts to disclose. They are members of the Pediatric News editorial advisory board.
SOURCE: Young J et al. Pediatrics. 2020 Jul 27. doi: 10.1542/peds.2020-1012.
Although female genital mutilation or cutting (FGM/C) is outlawed in much of the world, it still occurs for cultural reasons despite having no medical benefit, according to a clinical report from the American Academy of Pediatrics.
FGM/C is mainly performed on children and adolescents, but most of the research and teaching to date has addressed the impact of FGM/C on women of childbearing age and management during pregnancy and post partum, wrote Janine Young, MD, of the University of Colorado Denver in Aurora and colleagues. They are members of the AAP section on global health, committee on medical liability and risk management, or the committee on bioethics.
Published in Pediatrics, the report provides “the first comprehensive summary of FGM/C in children and includes education regarding a standard-of-care approach for examination of external female genitalia at all health supervision examinations, diagnosis, complications, management, treatment, culturally sensitive discussion and counseling approaches, and legal and ethical considerations,” they wrote.
The World Health Organization categorizes FGM/C into four subtypes. “Type I includes cutting of the glans or part of the body of the clitoris and/or prepuce; type II includes excision of the clitoris and labia minora, with or without excision of the labia majora; type III, infibulation, includes cutting and apposing the labia minora and/or majora over the urethral meatus and vaginal opening to significantly narrow it and may include clitoral excision; and type IV includes piercing, scraping, nicking, stretching, or otherwise injuring the external female genitalia without removing any genital tissue and includes practices that do not fall into the other three categories,” the authors wrote. Of these, type III is associated with the greatest long-term morbidity.
Data suggest that the prevalence and type of FGM/C varies by region, with the highest prevalence of type III in East Africa, where 82%-99% of girls reported FGM/C and 34%-79% of these cases involved type III, the authors reported.
Generally, pediatric health care providers in the United States have limited knowledge of FGM/C in the absence of any required courses on diagnosis or treatment for most primary care specialties. However, clinicians should be aware of possible risk factors, including a mother or sibling with a history of FGM/C, or patients with a country of origin, birth country, or travel history to a country where FGM/C is practiced, Dr. Young and associates noted.
They recommend that but acknowledged the challenges in raising the topic and addressing it in a culturally sensitive way. “Experts suggest that health care providers ask the patient or parent the term they use to name female genital cutting” and avoid the term mutilation, which may be offensive or misunderstood.
Many girls who have undergone FGM/C were too young to remember, the authors note. “Instead, it is advisable that the FGM/C clinical history taking include both the girl and parent or guardian once rapport has been established.”
Review potential medical complications if FGM/C is identified, and plans should be made for follow-up visits to monitor development of complications, the authors said. In addition, engage in a culturally sensitive discussion with teenagers, who may or may not have known about their FGM/C. In some cases, parents and caregivers may not have known about the FGM/C, which may be a community practice in some cultures with decisions made by other family members or authority figures.
“It is important for health care providers to assess each patient individually and make no assumptions about her and her parents’ beliefs regarding FGM/C,” Dr. Young and associates emphasized. “Mothers and fathers may or may not hold discordant views about FGM/C, and some clinical experts suggest that mothers who have themselves undergone FGM/C may nonetheless oppose subjecting their daughters to this practice. Instead, treating patients and caregivers with respect, sensitivity, and professionalism will encourage them to return and supports health-seeking behavior.”
The report presents 11 specific recommendations, including that health care providers should not perform any type of FGM/C and actively counsel families against such practices. In addition, children should have external genitalia checked at all health supervision examinations (with the consent of the guardian and/or child), and an assessment for FGM/C should be documented in the health records of patients with risk factors.
Notably, “[i]f genital examination findings are equivocal for the presence of FGM/C and risk factors for FGM/ C are present, a specialist trained in identification of FGM/C should be consulted,” Dr. Young and associates recommended. They also recommended defibulation for all girls and teenagers with type III FGM/C, especially for those with complications, and the procedure should be performed by an experienced pediatric gynecologist, gynecologist, urologist, or urogynecologist.
Finally, “[i]f FGM/C is suspected to have occurred in the United States, or as vacation cutting after immigration to the United States, the child should be evaluated for potential abuse. ... Expressed intention to engage in FGM/C, either in the United States or abroad, should also prompt a report to CPS [child protective services] if the child’s parent or caregiver cannot be dissuaded,” the authors wrote.
The report also includes case examples and expert analyses from legal and medical ethics experts to provide additional guidance for clinicians.
“This work seeks to educate pediatric health care providers on the occurrence of FGM/C, and the broader applications to the patients/population it impacts as well as the intersecting issues of diagnosis, complications, treatment, counseling needs, and the ethical and legal implications,” M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview.
However, challenges in implementing the recommendations “relate to the complexity of the issue and also the need for greater education of primary providers,” Dr. Jay said. “The overall message for providers, I believe, is a greater understanding of the practice [of FGM/C] as most providers have limited knowledge of this practice in the United States.”
“I believe the case-based presentations allow for a better understanding of how best to approach patients and families,” she added.
Kelly Curran, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, said, “I think one of largest barriers to implementing the strategies [from] this report is the limited knowledge of FGM/C by most clinicians.”
“In general, many pediatricians are uncomfortable with genital examinations,” she said in an interview. “I suspect most feel uncomfortable with identifying FGM/C versus other genital pathology and may not have ready access to FGM/C experts. Additionally, having these difficult conversations with families about this sensitive topic may be challenging,” said Dr. Curran. “Fortunately, this report is incredibly comprehensive, providing extensive background into FGM/C, effectively using diagrams and pictures, and explaining the legal and ethical issues that arise in the care of these patients.”
“Ultimately, I think there will need to be more education within medical training and further research into FGM/C,” Dr. Curran added. “Clinicians should be knowledgeable about FGM/C, including prevalence, identification, health complications, and treatment, as well as legal and ethical implications.” However, “in addition to knowledge, clinicians must be able to navigate counseling patients and their families around this culturally sensitive topic.”
The report is thorough and well written, yet “there still remains significant gaps in knowledge about FGM/C in children and adolescents,” she said. “I think future research into prevalence, along with the health effects of FGM/C, including its impact on mental and sexual health, in the pediatric population will be essential.”
The study received no outside funding. Coauthor Christa Johnson-Agbakwu, MD, disclosed a grant relationship with Arizona State University from the 2018 copyright of “Female Genital Mutilation/Cutting (FGM/C): A Visual Reference and Learning Tool for Health Care Professionals.” The other researchers had no financial conflicts to disclose. Dr. Jay and Dr. Curran had no relevant financial conflicts to disclose. They are members of the Pediatric News editorial advisory board.
SOURCE: Young J et al. Pediatrics. 2020 Jul 27. doi: 10.1542/peds.2020-1012.
Although female genital mutilation or cutting (FGM/C) is outlawed in much of the world, it still occurs for cultural reasons despite having no medical benefit, according to a clinical report from the American Academy of Pediatrics.
FGM/C is mainly performed on children and adolescents, but most of the research and teaching to date has addressed the impact of FGM/C on women of childbearing age and management during pregnancy and post partum, wrote Janine Young, MD, of the University of Colorado Denver in Aurora and colleagues. They are members of the AAP section on global health, committee on medical liability and risk management, or the committee on bioethics.
Published in Pediatrics, the report provides “the first comprehensive summary of FGM/C in children and includes education regarding a standard-of-care approach for examination of external female genitalia at all health supervision examinations, diagnosis, complications, management, treatment, culturally sensitive discussion and counseling approaches, and legal and ethical considerations,” they wrote.
The World Health Organization categorizes FGM/C into four subtypes. “Type I includes cutting of the glans or part of the body of the clitoris and/or prepuce; type II includes excision of the clitoris and labia minora, with or without excision of the labia majora; type III, infibulation, includes cutting and apposing the labia minora and/or majora over the urethral meatus and vaginal opening to significantly narrow it and may include clitoral excision; and type IV includes piercing, scraping, nicking, stretching, or otherwise injuring the external female genitalia without removing any genital tissue and includes practices that do not fall into the other three categories,” the authors wrote. Of these, type III is associated with the greatest long-term morbidity.
Data suggest that the prevalence and type of FGM/C varies by region, with the highest prevalence of type III in East Africa, where 82%-99% of girls reported FGM/C and 34%-79% of these cases involved type III, the authors reported.
Generally, pediatric health care providers in the United States have limited knowledge of FGM/C in the absence of any required courses on diagnosis or treatment for most primary care specialties. However, clinicians should be aware of possible risk factors, including a mother or sibling with a history of FGM/C, or patients with a country of origin, birth country, or travel history to a country where FGM/C is practiced, Dr. Young and associates noted.
They recommend that but acknowledged the challenges in raising the topic and addressing it in a culturally sensitive way. “Experts suggest that health care providers ask the patient or parent the term they use to name female genital cutting” and avoid the term mutilation, which may be offensive or misunderstood.
Many girls who have undergone FGM/C were too young to remember, the authors note. “Instead, it is advisable that the FGM/C clinical history taking include both the girl and parent or guardian once rapport has been established.”
Review potential medical complications if FGM/C is identified, and plans should be made for follow-up visits to monitor development of complications, the authors said. In addition, engage in a culturally sensitive discussion with teenagers, who may or may not have known about their FGM/C. In some cases, parents and caregivers may not have known about the FGM/C, which may be a community practice in some cultures with decisions made by other family members or authority figures.
“It is important for health care providers to assess each patient individually and make no assumptions about her and her parents’ beliefs regarding FGM/C,” Dr. Young and associates emphasized. “Mothers and fathers may or may not hold discordant views about FGM/C, and some clinical experts suggest that mothers who have themselves undergone FGM/C may nonetheless oppose subjecting their daughters to this practice. Instead, treating patients and caregivers with respect, sensitivity, and professionalism will encourage them to return and supports health-seeking behavior.”
The report presents 11 specific recommendations, including that health care providers should not perform any type of FGM/C and actively counsel families against such practices. In addition, children should have external genitalia checked at all health supervision examinations (with the consent of the guardian and/or child), and an assessment for FGM/C should be documented in the health records of patients with risk factors.
Notably, “[i]f genital examination findings are equivocal for the presence of FGM/C and risk factors for FGM/ C are present, a specialist trained in identification of FGM/C should be consulted,” Dr. Young and associates recommended. They also recommended defibulation for all girls and teenagers with type III FGM/C, especially for those with complications, and the procedure should be performed by an experienced pediatric gynecologist, gynecologist, urologist, or urogynecologist.
Finally, “[i]f FGM/C is suspected to have occurred in the United States, or as vacation cutting after immigration to the United States, the child should be evaluated for potential abuse. ... Expressed intention to engage in FGM/C, either in the United States or abroad, should also prompt a report to CPS [child protective services] if the child’s parent or caregiver cannot be dissuaded,” the authors wrote.
The report also includes case examples and expert analyses from legal and medical ethics experts to provide additional guidance for clinicians.
“This work seeks to educate pediatric health care providers on the occurrence of FGM/C, and the broader applications to the patients/population it impacts as well as the intersecting issues of diagnosis, complications, treatment, counseling needs, and the ethical and legal implications,” M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview.
However, challenges in implementing the recommendations “relate to the complexity of the issue and also the need for greater education of primary providers,” Dr. Jay said. “The overall message for providers, I believe, is a greater understanding of the practice [of FGM/C] as most providers have limited knowledge of this practice in the United States.”
“I believe the case-based presentations allow for a better understanding of how best to approach patients and families,” she added.
Kelly Curran, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, said, “I think one of largest barriers to implementing the strategies [from] this report is the limited knowledge of FGM/C by most clinicians.”
“In general, many pediatricians are uncomfortable with genital examinations,” she said in an interview. “I suspect most feel uncomfortable with identifying FGM/C versus other genital pathology and may not have ready access to FGM/C experts. Additionally, having these difficult conversations with families about this sensitive topic may be challenging,” said Dr. Curran. “Fortunately, this report is incredibly comprehensive, providing extensive background into FGM/C, effectively using diagrams and pictures, and explaining the legal and ethical issues that arise in the care of these patients.”
“Ultimately, I think there will need to be more education within medical training and further research into FGM/C,” Dr. Curran added. “Clinicians should be knowledgeable about FGM/C, including prevalence, identification, health complications, and treatment, as well as legal and ethical implications.” However, “in addition to knowledge, clinicians must be able to navigate counseling patients and their families around this culturally sensitive topic.”
The report is thorough and well written, yet “there still remains significant gaps in knowledge about FGM/C in children and adolescents,” she said. “I think future research into prevalence, along with the health effects of FGM/C, including its impact on mental and sexual health, in the pediatric population will be essential.”
The study received no outside funding. Coauthor Christa Johnson-Agbakwu, MD, disclosed a grant relationship with Arizona State University from the 2018 copyright of “Female Genital Mutilation/Cutting (FGM/C): A Visual Reference and Learning Tool for Health Care Professionals.” The other researchers had no financial conflicts to disclose. Dr. Jay and Dr. Curran had no relevant financial conflicts to disclose. They are members of the Pediatric News editorial advisory board.
SOURCE: Young J et al. Pediatrics. 2020 Jul 27. doi: 10.1542/peds.2020-1012.
FROM PEDIATRICS
Patients with COPD plus sleep problems should be screened for mood disorders
A study has shown a strong link between sleeping disturbances and depression in patients with chronic obstructive pulmonary disease.
Adults with clinically stable COPD who reported sleep problems were significantly more likely to report depression or anxiety, poor self-efficacy, and poor health-related quality of life, compared with those not reporting sleep problems, according to the findings from a study of 245 patients.
Sleep problems are common in patients with COPD and have been associated with poor COPD-related outcomes, wrote Sang Hee Lee, MD, of Wonkwang University Sanbon Hospital, Gunpo-si, South Korea, and colleagues.
“However, there is a lack of research on factors associated with sleep disturbance in patients with COPD,” they wrote.
In a prospective, multicenter, cross-sectional study published in the Clinical Respiratory Journal, the researchers enrolled 245 adults with COPD who completed the COPD and Asthma Impact Scale (CASIS) to determine sleep impairment. The CASIS was developed to measure sleep-related problems associated with respiratory disease, and scored on a scale of 1-100, with higher scores indicating greater sleep impairment. The average CASIS score was 40.9. The average age of the patients was 67 years, and 92% were men.
Patients’ health-related quality of life, anxiety/depression, and self-efficacy were assessed using the St. George’s Respiratory Questionnaire (SGRQ), the 36-item Short-Form Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS), and the COPD Self-Efficacy Scale (CSES). The average scores on these measures were 36.0 for the SGRQ; 48.1 and 50.6, respectively, for the physical and mental components of the SF-36; 3.8 and 6.4, respectively, for the HADS-A and HADS-D measures of anxiety and depression; and 3.3 on the CSES.
Worse sleep in these patients was associated with worse scores on measures of mood. In a multivariate analysis, higher scores on all four measures of health-related quality of life were significantly associated with higher CASIS scores (P = .006 for SGRQ; P = .037 for SF-36, P < .001 for HADS, and P = .010 for CSES).
Although the CASIS did not allow for measurement of symptom severity and did not include many items related to breathing problems, the test “shows good internal consistency, test-retest reproducibility, and construct validity according to previous studies,” the researchers wrote. “The CASIS may be a good tool for evaluating sleep disturbances in COPD patients, and further study is needed,” they added.
The study findings were limited by several factors including the cross-sectional study design, lack of data on obstructive sleep apnea, and lack of information on specific treatments such as at-home oxygen use or high-dose steroid use, the researchers noted. However, the results were strengthened by the use of a disease-specific sleep measure, and the study is the first known to include self-efficacy in relation to sleep quality in COPD patients, they reported.
The results highlight the association between depression, poor quality of life, and self-efficacy in relation to poor sleep, and suggest that “Sleep quality could be improved by enhancing HRQL and self-efficacy,” the researchers said. “Screening for mood disorder in patients with COPD is also needed,” they concluded.
The study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology. The researchers had no financial conflicts to disclose.
SOURCE: Lee SH et al. Clin Respir J. 2020 Jul 24. doi: 10.1111/crj.13235.
A study has shown a strong link between sleeping disturbances and depression in patients with chronic obstructive pulmonary disease.
Adults with clinically stable COPD who reported sleep problems were significantly more likely to report depression or anxiety, poor self-efficacy, and poor health-related quality of life, compared with those not reporting sleep problems, according to the findings from a study of 245 patients.
Sleep problems are common in patients with COPD and have been associated with poor COPD-related outcomes, wrote Sang Hee Lee, MD, of Wonkwang University Sanbon Hospital, Gunpo-si, South Korea, and colleagues.
“However, there is a lack of research on factors associated with sleep disturbance in patients with COPD,” they wrote.
In a prospective, multicenter, cross-sectional study published in the Clinical Respiratory Journal, the researchers enrolled 245 adults with COPD who completed the COPD and Asthma Impact Scale (CASIS) to determine sleep impairment. The CASIS was developed to measure sleep-related problems associated with respiratory disease, and scored on a scale of 1-100, with higher scores indicating greater sleep impairment. The average CASIS score was 40.9. The average age of the patients was 67 years, and 92% were men.
Patients’ health-related quality of life, anxiety/depression, and self-efficacy were assessed using the St. George’s Respiratory Questionnaire (SGRQ), the 36-item Short-Form Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS), and the COPD Self-Efficacy Scale (CSES). The average scores on these measures were 36.0 for the SGRQ; 48.1 and 50.6, respectively, for the physical and mental components of the SF-36; 3.8 and 6.4, respectively, for the HADS-A and HADS-D measures of anxiety and depression; and 3.3 on the CSES.
Worse sleep in these patients was associated with worse scores on measures of mood. In a multivariate analysis, higher scores on all four measures of health-related quality of life were significantly associated with higher CASIS scores (P = .006 for SGRQ; P = .037 for SF-36, P < .001 for HADS, and P = .010 for CSES).
Although the CASIS did not allow for measurement of symptom severity and did not include many items related to breathing problems, the test “shows good internal consistency, test-retest reproducibility, and construct validity according to previous studies,” the researchers wrote. “The CASIS may be a good tool for evaluating sleep disturbances in COPD patients, and further study is needed,” they added.
The study findings were limited by several factors including the cross-sectional study design, lack of data on obstructive sleep apnea, and lack of information on specific treatments such as at-home oxygen use or high-dose steroid use, the researchers noted. However, the results were strengthened by the use of a disease-specific sleep measure, and the study is the first known to include self-efficacy in relation to sleep quality in COPD patients, they reported.
The results highlight the association between depression, poor quality of life, and self-efficacy in relation to poor sleep, and suggest that “Sleep quality could be improved by enhancing HRQL and self-efficacy,” the researchers said. “Screening for mood disorder in patients with COPD is also needed,” they concluded.
The study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology. The researchers had no financial conflicts to disclose.
SOURCE: Lee SH et al. Clin Respir J. 2020 Jul 24. doi: 10.1111/crj.13235.
A study has shown a strong link between sleeping disturbances and depression in patients with chronic obstructive pulmonary disease.
Adults with clinically stable COPD who reported sleep problems were significantly more likely to report depression or anxiety, poor self-efficacy, and poor health-related quality of life, compared with those not reporting sleep problems, according to the findings from a study of 245 patients.
Sleep problems are common in patients with COPD and have been associated with poor COPD-related outcomes, wrote Sang Hee Lee, MD, of Wonkwang University Sanbon Hospital, Gunpo-si, South Korea, and colleagues.
“However, there is a lack of research on factors associated with sleep disturbance in patients with COPD,” they wrote.
In a prospective, multicenter, cross-sectional study published in the Clinical Respiratory Journal, the researchers enrolled 245 adults with COPD who completed the COPD and Asthma Impact Scale (CASIS) to determine sleep impairment. The CASIS was developed to measure sleep-related problems associated with respiratory disease, and scored on a scale of 1-100, with higher scores indicating greater sleep impairment. The average CASIS score was 40.9. The average age of the patients was 67 years, and 92% were men.
Patients’ health-related quality of life, anxiety/depression, and self-efficacy were assessed using the St. George’s Respiratory Questionnaire (SGRQ), the 36-item Short-Form Health Survey (SF-36), Hospital Anxiety and Depression Scale (HADS), and the COPD Self-Efficacy Scale (CSES). The average scores on these measures were 36.0 for the SGRQ; 48.1 and 50.6, respectively, for the physical and mental components of the SF-36; 3.8 and 6.4, respectively, for the HADS-A and HADS-D measures of anxiety and depression; and 3.3 on the CSES.
Worse sleep in these patients was associated with worse scores on measures of mood. In a multivariate analysis, higher scores on all four measures of health-related quality of life were significantly associated with higher CASIS scores (P = .006 for SGRQ; P = .037 for SF-36, P < .001 for HADS, and P = .010 for CSES).
Although the CASIS did not allow for measurement of symptom severity and did not include many items related to breathing problems, the test “shows good internal consistency, test-retest reproducibility, and construct validity according to previous studies,” the researchers wrote. “The CASIS may be a good tool for evaluating sleep disturbances in COPD patients, and further study is needed,” they added.
The study findings were limited by several factors including the cross-sectional study design, lack of data on obstructive sleep apnea, and lack of information on specific treatments such as at-home oxygen use or high-dose steroid use, the researchers noted. However, the results were strengthened by the use of a disease-specific sleep measure, and the study is the first known to include self-efficacy in relation to sleep quality in COPD patients, they reported.
The results highlight the association between depression, poor quality of life, and self-efficacy in relation to poor sleep, and suggest that “Sleep quality could be improved by enhancing HRQL and self-efficacy,” the researchers said. “Screening for mood disorder in patients with COPD is also needed,” they concluded.
The study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology. The researchers had no financial conflicts to disclose.
SOURCE: Lee SH et al. Clin Respir J. 2020 Jul 24. doi: 10.1111/crj.13235.
FROM THE CLINICAL RESPIRATORY JOURNAL
So, you’ve been sued. What now?
By the time physicians turn 65 years old, more than 75% of those in low-risk specialties such as pediatric dermatology have been named in a lawsuit, compared with 99% of those in high-risk specialties such as obstetrics and gynecology, according to Ilona J. Frieden, MD.
“We all know there’s a possibility that we could get named in a lawsuit,” she said during the virtual annual meeting of the Society for Pediatric Dermatology. “It could happen to any of us. Lawsuits are not uncommon, but few of us have received any kind of training for how to handle them.”
Based on her experience being named in a malpractice/wrongful death lawsuit, Dr. Frieden, who has had a nearly 4-decade career as a pediatric dermatologist at the University of California, San Francisco, offered the following tips for clinicians facing practice-related litigation:
First, immediately inform the risk management representatives at your institution or your malpractice insurance carrier. “Tell them about the situation and arrange to talk to a lawyer,” she advised.
Second, prepare to confront a range of emotions. “Depending on the circumstances, [that could be] fear, anger, dread, and defensiveness,” said Dr. Frieden, professor of dermatology and pediatrics, at UCSF. “What surprised me was this sort of physical sensation. I felt like I had been kicked in the stomach. In retrospect, this is not such a surprising finding. It really is an assault on your professional identity, so it made sense to me as I thought about this.”
Third, slow yourself down. The litigation process typically takes 2-5 years, “so this is a marathon; this is not a sprint,” she said. “While you are waiting you will be told, ‘Don’t discuss this case with anyone.’ While this may be true for the specific details of the case, it isn’t true about what you are feeling and how this affects you. You can and you should talk to a trusted friend, to a spouse, or even to a therapist so that you can process what you’re going through and not feel alone.”
Fourth, try to focus on the patients that you help. Having a patient in your pediatric dermatology practice die “is a rare event,” she said. “Try to not let such an event define you in terms of your professional identity. Meanwhile [remember that] you’re helping lots and lots of people.”
Fifth, be humble, both for yourself and the experts you might turn to for advice when you’re facing a complex case. “Though I have decades of experience, I find myself feeling more willing rather than less willing to ask for help,” Dr. Frieden said. “Also, the culture has changed. We email colleagues all the time to say, ‘This doesn’t make sense. Can you please tell me what your thoughts are?’ ”
She closed her remarks by noting that physicians “put ourselves in harm’s way in the process of trying to do the best we can for patients. That is something we have to accept.” She reported having no financial disclosures.
By the time physicians turn 65 years old, more than 75% of those in low-risk specialties such as pediatric dermatology have been named in a lawsuit, compared with 99% of those in high-risk specialties such as obstetrics and gynecology, according to Ilona J. Frieden, MD.
“We all know there’s a possibility that we could get named in a lawsuit,” she said during the virtual annual meeting of the Society for Pediatric Dermatology. “It could happen to any of us. Lawsuits are not uncommon, but few of us have received any kind of training for how to handle them.”
Based on her experience being named in a malpractice/wrongful death lawsuit, Dr. Frieden, who has had a nearly 4-decade career as a pediatric dermatologist at the University of California, San Francisco, offered the following tips for clinicians facing practice-related litigation:
First, immediately inform the risk management representatives at your institution or your malpractice insurance carrier. “Tell them about the situation and arrange to talk to a lawyer,” she advised.
Second, prepare to confront a range of emotions. “Depending on the circumstances, [that could be] fear, anger, dread, and defensiveness,” said Dr. Frieden, professor of dermatology and pediatrics, at UCSF. “What surprised me was this sort of physical sensation. I felt like I had been kicked in the stomach. In retrospect, this is not such a surprising finding. It really is an assault on your professional identity, so it made sense to me as I thought about this.”
Third, slow yourself down. The litigation process typically takes 2-5 years, “so this is a marathon; this is not a sprint,” she said. “While you are waiting you will be told, ‘Don’t discuss this case with anyone.’ While this may be true for the specific details of the case, it isn’t true about what you are feeling and how this affects you. You can and you should talk to a trusted friend, to a spouse, or even to a therapist so that you can process what you’re going through and not feel alone.”
Fourth, try to focus on the patients that you help. Having a patient in your pediatric dermatology practice die “is a rare event,” she said. “Try to not let such an event define you in terms of your professional identity. Meanwhile [remember that] you’re helping lots and lots of people.”
Fifth, be humble, both for yourself and the experts you might turn to for advice when you’re facing a complex case. “Though I have decades of experience, I find myself feeling more willing rather than less willing to ask for help,” Dr. Frieden said. “Also, the culture has changed. We email colleagues all the time to say, ‘This doesn’t make sense. Can you please tell me what your thoughts are?’ ”
She closed her remarks by noting that physicians “put ourselves in harm’s way in the process of trying to do the best we can for patients. That is something we have to accept.” She reported having no financial disclosures.
By the time physicians turn 65 years old, more than 75% of those in low-risk specialties such as pediatric dermatology have been named in a lawsuit, compared with 99% of those in high-risk specialties such as obstetrics and gynecology, according to Ilona J. Frieden, MD.
“We all know there’s a possibility that we could get named in a lawsuit,” she said during the virtual annual meeting of the Society for Pediatric Dermatology. “It could happen to any of us. Lawsuits are not uncommon, but few of us have received any kind of training for how to handle them.”
Based on her experience being named in a malpractice/wrongful death lawsuit, Dr. Frieden, who has had a nearly 4-decade career as a pediatric dermatologist at the University of California, San Francisco, offered the following tips for clinicians facing practice-related litigation:
First, immediately inform the risk management representatives at your institution or your malpractice insurance carrier. “Tell them about the situation and arrange to talk to a lawyer,” she advised.
Second, prepare to confront a range of emotions. “Depending on the circumstances, [that could be] fear, anger, dread, and defensiveness,” said Dr. Frieden, professor of dermatology and pediatrics, at UCSF. “What surprised me was this sort of physical sensation. I felt like I had been kicked in the stomach. In retrospect, this is not such a surprising finding. It really is an assault on your professional identity, so it made sense to me as I thought about this.”
Third, slow yourself down. The litigation process typically takes 2-5 years, “so this is a marathon; this is not a sprint,” she said. “While you are waiting you will be told, ‘Don’t discuss this case with anyone.’ While this may be true for the specific details of the case, it isn’t true about what you are feeling and how this affects you. You can and you should talk to a trusted friend, to a spouse, or even to a therapist so that you can process what you’re going through and not feel alone.”
Fourth, try to focus on the patients that you help. Having a patient in your pediatric dermatology practice die “is a rare event,” she said. “Try to not let such an event define you in terms of your professional identity. Meanwhile [remember that] you’re helping lots and lots of people.”
Fifth, be humble, both for yourself and the experts you might turn to for advice when you’re facing a complex case. “Though I have decades of experience, I find myself feeling more willing rather than less willing to ask for help,” Dr. Frieden said. “Also, the culture has changed. We email colleagues all the time to say, ‘This doesn’t make sense. Can you please tell me what your thoughts are?’ ”
She closed her remarks by noting that physicians “put ourselves in harm’s way in the process of trying to do the best we can for patients. That is something we have to accept.” She reported having no financial disclosures.
FROM SPD 2020
SCD-HeFT 10-year results: Primary-prevention ICD insights in nonischemic heart failure
A 10-year follow-up analysis based on one of cardiology’s most influential trials has shed further light on one of its key issues: how to sharpen selection of patients most likely to benefit from a primary prevention implantable cardioverter-defibrillator (ICD).
In a new report from SCD-HeFT, the survival advantage in patients with heart failure seen 5 years after receiving ICDs, compared with a non-ICD control group, narrowed a bit but remained significant after an additional 5 years. But not all patients with devices shared in that long-term ICD benefit. Patients with either ischemic disease or nonischemic cardiomyopathy (NICM) with devices showed a similar mortality risk reduction in the trial’s previously reported 5-year outcomes. That advantage, compared with non-ICD control patients, persisted throughout the subsequent 5 years for ischemic patients but tapered to nil for those with NICM.
The NICM patients “had what appears to be some accrual of benefit maybe out to about 6 years, and then the curves appear to come together where there’s no apparent further benefit after 6 years,” Jeanne E. Poole, MD, of the University of Washington, Seattle, said in an interview.
In both the 10-year analysis and the earlier results, ICD survival gains went preferentially to patients who enrolled with New York Heart Association (NYHA) functional class II symptoms. Patients who entered in NYHA class III “didn’t appear to have any benefit whatsoever” in either period, Dr. Poole said.
“The simple message is that the same groups of patients that benefited strongly from the ICD in the original SCD-HeFT – the NYHA class 2 patients and those with ischemic cardiomyopathy – were really the ones who benefited the greatest over the long term,” she said.
Dr. Poole is lead author on the SCD-HeFT 10-year analysis, which was published in the July 28 issue of the Journal of the American College of Cardiology.
Why the ICD survival effect disappeared midway in patients with NICM “is hard to sort out,” she said. Many in the control group were offered such devices after the trial concluded. Among those, it’s possible that disproportionately more control patients with NICM, compared with patients with ischemic disease, were fitted with ICDs that were also cardiac resynchronization therapy (CRT) devices, Dr. Poole and her colleagues speculated. That could have shifted their late outcomes to be more in line with patients who had received ICDs when the trial started.
Or “it is possible that the intermediate-term benefit of ICD therapy in NICM is overwhelmed by nonarrhythmic death in extended follow-up” given that ICDs prolong survival only by preventing arrhythmic death, noted an editorial accompanying the new SCD-HeFT publication.
Another possibility: Because NICM is a heterogeneous disorder with many potential causes, perhaps “the absence of long-term mortality benefit among SCD-HeFT participants with NICM was due to an unintended but preferential enrollment of subtypes at relatively lower risk for arrhythmic death in the longer term,” proposed Eric C. Stecker, MD, MPH, Oregon Health & Science University, Portland, and coauthors in their editorial.
“What are the take-away messages from the current analysis by Poole et al?” they asked. “These findings strongly support the clinical efficacy and cost-effectiveness of ICD therapy for the majority of patients with severe but mildly symptomatic ischemic cardiomyopathy who do not have an excessive comorbidity burden.”
But “the implications for patients with NICM are less clear,” they wrote. “Given evidence for intermediate-term benefit and the limitations inherent to assessing longer-term benefit, we do not believe it is appropriate to walk back guideline recommendations regarding ICD implantation for NICM patients.”
The findings in nonischemic patients invite comparison with the randomized DANISH trial, which entered only patients with NICM and, over more than 5 years, saw no primary-prevention ICD advantage for the end point of all-cause mortality.
But patients who received ICDs showed a reduction in arrhythmic death, a secondary end point. And mortality in the trial showed a significant interaction with patient age; survival went up sharply with ICDs for those younger than 60 years.
Also in DANISH, “the ICD treatment effect appears to vary over time, with an earlier phase showing possible survival benefit and a later phase showing attenuation of that benefit,” similar to what was seen long-term in SCD-HeFT, in which the interaction between mortality and time since implantation was significant at P = .0015, observe Dr. Poole and colleagues.
However, Dr. Poole cautioned when interviewed, patient management in DANISH, conducted exclusively in Denmark, may not have been representative of the rest of the world, complicating comparisons with other studies. For example, nearly 60% of all patients in DANISH had defibrillating CRT devices. Virtually everyone was on ACE inhibitors or angiotensin-receptor blockers, and almost 60% were taking aldosterone inhibitors.
“DANISH is an unusually high bar and probably does not reflect all patients with heart failure, and certainly does not reflect patients in the United States in terms of those high levels of guideline-directed medical therapy,” Dr. Poole said. The message from DANISH, she said, seems to be that patients with NICM who are definitely on goal-directed heart failure medications with CRT devices “probably don’t have a meaningful benefit from an ICD, on total mortality, because their sudden death rates are simply so low.”
SCD-HeFT had originally assigned 2,521 patients with heart failure of NYHA class II or III and an left ventricular ejection fraction of less than 35% to receive an ICD, amiodarone without an ICD, or an amiodarone placebo and no ICD; patients in the latter cohorts made up the non-ICD control group.
Those who received an ICD, compared with the non-ICD control patients, showed a 23% drop in all-cause mortality over a median of 45.5 months ending on October 31, 2003, Dr. Poole and colleagues noted in their current report. The trial’s primary results were unveiled 2005.
The current analysis, based on data collected in 2010 and 2011, followed the 1,855 patients alive at the trial’s official conclusion and combined outcomes before and after that time for a median follow-up of 11 years, Dr. Poole and colleagues reported.
In the ICD group, the overall hazard ratio for mortality by intention-to-treat was 0.87 (95% confidence interval, 0.76-0.98; P = .028), compared with the non-ICD control group.
In their report, Poole and associates clarified one of the foremost potential confounders in the current analysis: device implantations after the trial in patients who had been in the non-ICD groups. From partial clinical data collected after the trial, they wrote, the estimated rate of subsequent ICD implantation in non-ICD control patients was about 55%. Such a low number is consistent with clinical practice in the United States, where “a surprisingly low number of patients who are eligible actually end up getting devices,” Dr. Poole said.
Subsequent ICD use in the former non-ICD control patients presumably boosted their survival over the long term, narrowing the gap between their all-cause mortality and that of the original ICD patients, Dr. Poole observed. Despite that, the ICD-group’s late survival advantage remained significant.
SCD-HeFT was sponsored by Medtronic, Wyeth Pharmaceuticals, and the National Heart, Lung, and Blood Institute. The current analysis was partially supported by a grant from St. Jude Medical. Dr. Poole disclosed receiving research support from Medtronic, Biotronik, AtriCure, and Kestra; serving as a speaker for Boston Scientific, Medtronic, and MediaSphere Medical and on an advisory board for Boston Scientific; serving on a committee for Medtronic and on a data and safety monitoring board for EBR Systems; and receiving royalties from Elsevier and compensation from the Heart Rhythm Society for serving as editor in chief for the Heart Rhythm O2 journal. Disclosures for the other authors are in the report. Dr. Stecker and coauthors disclosed that they have no relevant relationships.
A version of this article originally appeared on Medscape.com.
A 10-year follow-up analysis based on one of cardiology’s most influential trials has shed further light on one of its key issues: how to sharpen selection of patients most likely to benefit from a primary prevention implantable cardioverter-defibrillator (ICD).
In a new report from SCD-HeFT, the survival advantage in patients with heart failure seen 5 years after receiving ICDs, compared with a non-ICD control group, narrowed a bit but remained significant after an additional 5 years. But not all patients with devices shared in that long-term ICD benefit. Patients with either ischemic disease or nonischemic cardiomyopathy (NICM) with devices showed a similar mortality risk reduction in the trial’s previously reported 5-year outcomes. That advantage, compared with non-ICD control patients, persisted throughout the subsequent 5 years for ischemic patients but tapered to nil for those with NICM.
The NICM patients “had what appears to be some accrual of benefit maybe out to about 6 years, and then the curves appear to come together where there’s no apparent further benefit after 6 years,” Jeanne E. Poole, MD, of the University of Washington, Seattle, said in an interview.
In both the 10-year analysis and the earlier results, ICD survival gains went preferentially to patients who enrolled with New York Heart Association (NYHA) functional class II symptoms. Patients who entered in NYHA class III “didn’t appear to have any benefit whatsoever” in either period, Dr. Poole said.
“The simple message is that the same groups of patients that benefited strongly from the ICD in the original SCD-HeFT – the NYHA class 2 patients and those with ischemic cardiomyopathy – were really the ones who benefited the greatest over the long term,” she said.
Dr. Poole is lead author on the SCD-HeFT 10-year analysis, which was published in the July 28 issue of the Journal of the American College of Cardiology.
Why the ICD survival effect disappeared midway in patients with NICM “is hard to sort out,” she said. Many in the control group were offered such devices after the trial concluded. Among those, it’s possible that disproportionately more control patients with NICM, compared with patients with ischemic disease, were fitted with ICDs that were also cardiac resynchronization therapy (CRT) devices, Dr. Poole and her colleagues speculated. That could have shifted their late outcomes to be more in line with patients who had received ICDs when the trial started.
Or “it is possible that the intermediate-term benefit of ICD therapy in NICM is overwhelmed by nonarrhythmic death in extended follow-up” given that ICDs prolong survival only by preventing arrhythmic death, noted an editorial accompanying the new SCD-HeFT publication.
Another possibility: Because NICM is a heterogeneous disorder with many potential causes, perhaps “the absence of long-term mortality benefit among SCD-HeFT participants with NICM was due to an unintended but preferential enrollment of subtypes at relatively lower risk for arrhythmic death in the longer term,” proposed Eric C. Stecker, MD, MPH, Oregon Health & Science University, Portland, and coauthors in their editorial.
“What are the take-away messages from the current analysis by Poole et al?” they asked. “These findings strongly support the clinical efficacy and cost-effectiveness of ICD therapy for the majority of patients with severe but mildly symptomatic ischemic cardiomyopathy who do not have an excessive comorbidity burden.”
But “the implications for patients with NICM are less clear,” they wrote. “Given evidence for intermediate-term benefit and the limitations inherent to assessing longer-term benefit, we do not believe it is appropriate to walk back guideline recommendations regarding ICD implantation for NICM patients.”
The findings in nonischemic patients invite comparison with the randomized DANISH trial, which entered only patients with NICM and, over more than 5 years, saw no primary-prevention ICD advantage for the end point of all-cause mortality.
But patients who received ICDs showed a reduction in arrhythmic death, a secondary end point. And mortality in the trial showed a significant interaction with patient age; survival went up sharply with ICDs for those younger than 60 years.
Also in DANISH, “the ICD treatment effect appears to vary over time, with an earlier phase showing possible survival benefit and a later phase showing attenuation of that benefit,” similar to what was seen long-term in SCD-HeFT, in which the interaction between mortality and time since implantation was significant at P = .0015, observe Dr. Poole and colleagues.
However, Dr. Poole cautioned when interviewed, patient management in DANISH, conducted exclusively in Denmark, may not have been representative of the rest of the world, complicating comparisons with other studies. For example, nearly 60% of all patients in DANISH had defibrillating CRT devices. Virtually everyone was on ACE inhibitors or angiotensin-receptor blockers, and almost 60% were taking aldosterone inhibitors.
“DANISH is an unusually high bar and probably does not reflect all patients with heart failure, and certainly does not reflect patients in the United States in terms of those high levels of guideline-directed medical therapy,” Dr. Poole said. The message from DANISH, she said, seems to be that patients with NICM who are definitely on goal-directed heart failure medications with CRT devices “probably don’t have a meaningful benefit from an ICD, on total mortality, because their sudden death rates are simply so low.”
SCD-HeFT had originally assigned 2,521 patients with heart failure of NYHA class II or III and an left ventricular ejection fraction of less than 35% to receive an ICD, amiodarone without an ICD, or an amiodarone placebo and no ICD; patients in the latter cohorts made up the non-ICD control group.
Those who received an ICD, compared with the non-ICD control patients, showed a 23% drop in all-cause mortality over a median of 45.5 months ending on October 31, 2003, Dr. Poole and colleagues noted in their current report. The trial’s primary results were unveiled 2005.
The current analysis, based on data collected in 2010 and 2011, followed the 1,855 patients alive at the trial’s official conclusion and combined outcomes before and after that time for a median follow-up of 11 years, Dr. Poole and colleagues reported.
In the ICD group, the overall hazard ratio for mortality by intention-to-treat was 0.87 (95% confidence interval, 0.76-0.98; P = .028), compared with the non-ICD control group.
In their report, Poole and associates clarified one of the foremost potential confounders in the current analysis: device implantations after the trial in patients who had been in the non-ICD groups. From partial clinical data collected after the trial, they wrote, the estimated rate of subsequent ICD implantation in non-ICD control patients was about 55%. Such a low number is consistent with clinical practice in the United States, where “a surprisingly low number of patients who are eligible actually end up getting devices,” Dr. Poole said.
Subsequent ICD use in the former non-ICD control patients presumably boosted their survival over the long term, narrowing the gap between their all-cause mortality and that of the original ICD patients, Dr. Poole observed. Despite that, the ICD-group’s late survival advantage remained significant.
SCD-HeFT was sponsored by Medtronic, Wyeth Pharmaceuticals, and the National Heart, Lung, and Blood Institute. The current analysis was partially supported by a grant from St. Jude Medical. Dr. Poole disclosed receiving research support from Medtronic, Biotronik, AtriCure, and Kestra; serving as a speaker for Boston Scientific, Medtronic, and MediaSphere Medical and on an advisory board for Boston Scientific; serving on a committee for Medtronic and on a data and safety monitoring board for EBR Systems; and receiving royalties from Elsevier and compensation from the Heart Rhythm Society for serving as editor in chief for the Heart Rhythm O2 journal. Disclosures for the other authors are in the report. Dr. Stecker and coauthors disclosed that they have no relevant relationships.
A version of this article originally appeared on Medscape.com.
A 10-year follow-up analysis based on one of cardiology’s most influential trials has shed further light on one of its key issues: how to sharpen selection of patients most likely to benefit from a primary prevention implantable cardioverter-defibrillator (ICD).
In a new report from SCD-HeFT, the survival advantage in patients with heart failure seen 5 years after receiving ICDs, compared with a non-ICD control group, narrowed a bit but remained significant after an additional 5 years. But not all patients with devices shared in that long-term ICD benefit. Patients with either ischemic disease or nonischemic cardiomyopathy (NICM) with devices showed a similar mortality risk reduction in the trial’s previously reported 5-year outcomes. That advantage, compared with non-ICD control patients, persisted throughout the subsequent 5 years for ischemic patients but tapered to nil for those with NICM.
The NICM patients “had what appears to be some accrual of benefit maybe out to about 6 years, and then the curves appear to come together where there’s no apparent further benefit after 6 years,” Jeanne E. Poole, MD, of the University of Washington, Seattle, said in an interview.
In both the 10-year analysis and the earlier results, ICD survival gains went preferentially to patients who enrolled with New York Heart Association (NYHA) functional class II symptoms. Patients who entered in NYHA class III “didn’t appear to have any benefit whatsoever” in either period, Dr. Poole said.
“The simple message is that the same groups of patients that benefited strongly from the ICD in the original SCD-HeFT – the NYHA class 2 patients and those with ischemic cardiomyopathy – were really the ones who benefited the greatest over the long term,” she said.
Dr. Poole is lead author on the SCD-HeFT 10-year analysis, which was published in the July 28 issue of the Journal of the American College of Cardiology.
Why the ICD survival effect disappeared midway in patients with NICM “is hard to sort out,” she said. Many in the control group were offered such devices after the trial concluded. Among those, it’s possible that disproportionately more control patients with NICM, compared with patients with ischemic disease, were fitted with ICDs that were also cardiac resynchronization therapy (CRT) devices, Dr. Poole and her colleagues speculated. That could have shifted their late outcomes to be more in line with patients who had received ICDs when the trial started.
Or “it is possible that the intermediate-term benefit of ICD therapy in NICM is overwhelmed by nonarrhythmic death in extended follow-up” given that ICDs prolong survival only by preventing arrhythmic death, noted an editorial accompanying the new SCD-HeFT publication.
Another possibility: Because NICM is a heterogeneous disorder with many potential causes, perhaps “the absence of long-term mortality benefit among SCD-HeFT participants with NICM was due to an unintended but preferential enrollment of subtypes at relatively lower risk for arrhythmic death in the longer term,” proposed Eric C. Stecker, MD, MPH, Oregon Health & Science University, Portland, and coauthors in their editorial.
“What are the take-away messages from the current analysis by Poole et al?” they asked. “These findings strongly support the clinical efficacy and cost-effectiveness of ICD therapy for the majority of patients with severe but mildly symptomatic ischemic cardiomyopathy who do not have an excessive comorbidity burden.”
But “the implications for patients with NICM are less clear,” they wrote. “Given evidence for intermediate-term benefit and the limitations inherent to assessing longer-term benefit, we do not believe it is appropriate to walk back guideline recommendations regarding ICD implantation for NICM patients.”
The findings in nonischemic patients invite comparison with the randomized DANISH trial, which entered only patients with NICM and, over more than 5 years, saw no primary-prevention ICD advantage for the end point of all-cause mortality.
But patients who received ICDs showed a reduction in arrhythmic death, a secondary end point. And mortality in the trial showed a significant interaction with patient age; survival went up sharply with ICDs for those younger than 60 years.
Also in DANISH, “the ICD treatment effect appears to vary over time, with an earlier phase showing possible survival benefit and a later phase showing attenuation of that benefit,” similar to what was seen long-term in SCD-HeFT, in which the interaction between mortality and time since implantation was significant at P = .0015, observe Dr. Poole and colleagues.
However, Dr. Poole cautioned when interviewed, patient management in DANISH, conducted exclusively in Denmark, may not have been representative of the rest of the world, complicating comparisons with other studies. For example, nearly 60% of all patients in DANISH had defibrillating CRT devices. Virtually everyone was on ACE inhibitors or angiotensin-receptor blockers, and almost 60% were taking aldosterone inhibitors.
“DANISH is an unusually high bar and probably does not reflect all patients with heart failure, and certainly does not reflect patients in the United States in terms of those high levels of guideline-directed medical therapy,” Dr. Poole said. The message from DANISH, she said, seems to be that patients with NICM who are definitely on goal-directed heart failure medications with CRT devices “probably don’t have a meaningful benefit from an ICD, on total mortality, because their sudden death rates are simply so low.”
SCD-HeFT had originally assigned 2,521 patients with heart failure of NYHA class II or III and an left ventricular ejection fraction of less than 35% to receive an ICD, amiodarone without an ICD, or an amiodarone placebo and no ICD; patients in the latter cohorts made up the non-ICD control group.
Those who received an ICD, compared with the non-ICD control patients, showed a 23% drop in all-cause mortality over a median of 45.5 months ending on October 31, 2003, Dr. Poole and colleagues noted in their current report. The trial’s primary results were unveiled 2005.
The current analysis, based on data collected in 2010 and 2011, followed the 1,855 patients alive at the trial’s official conclusion and combined outcomes before and after that time for a median follow-up of 11 years, Dr. Poole and colleagues reported.
In the ICD group, the overall hazard ratio for mortality by intention-to-treat was 0.87 (95% confidence interval, 0.76-0.98; P = .028), compared with the non-ICD control group.
In their report, Poole and associates clarified one of the foremost potential confounders in the current analysis: device implantations after the trial in patients who had been in the non-ICD groups. From partial clinical data collected after the trial, they wrote, the estimated rate of subsequent ICD implantation in non-ICD control patients was about 55%. Such a low number is consistent with clinical practice in the United States, where “a surprisingly low number of patients who are eligible actually end up getting devices,” Dr. Poole said.
Subsequent ICD use in the former non-ICD control patients presumably boosted their survival over the long term, narrowing the gap between their all-cause mortality and that of the original ICD patients, Dr. Poole observed. Despite that, the ICD-group’s late survival advantage remained significant.
SCD-HeFT was sponsored by Medtronic, Wyeth Pharmaceuticals, and the National Heart, Lung, and Blood Institute. The current analysis was partially supported by a grant from St. Jude Medical. Dr. Poole disclosed receiving research support from Medtronic, Biotronik, AtriCure, and Kestra; serving as a speaker for Boston Scientific, Medtronic, and MediaSphere Medical and on an advisory board for Boston Scientific; serving on a committee for Medtronic and on a data and safety monitoring board for EBR Systems; and receiving royalties from Elsevier and compensation from the Heart Rhythm Society for serving as editor in chief for the Heart Rhythm O2 journal. Disclosures for the other authors are in the report. Dr. Stecker and coauthors disclosed that they have no relevant relationships.
A version of this article originally appeared on Medscape.com.
FDA approves triple drug combo for melanoma
The US Food and Drug Administration (FDA) has approved the triple-therapy combination of atezolizumab (Tecentriq) plus cobimetinib (Cotellic) and vemurafenib (Zelboraf) for the treatment of BRAF V600 mutation-positive advanced melanoma, according to a press statement from Genentech, which owns all three drugs.
This is the first melanoma indication for the PD-L1 inhibitor atezolizumab; the other two drugs, cobimetinib and vemurafenib, are a MEK- plus BRAF-inhibitor combination previously approved for BRAF-mutated melanoma.
The new approval is based on safety and efficacy results from the randomized, phase 3 IMspire150 study from patients with previously untreated BRAF V600 mutation-positive metastatic or unresectable locally advanced melanoma.
Progression-free survival (PFS), the primary endpoint, was improved by 4.5 months with the triple therapy compared to the doublet.
The addition of atezolizumab to cobimetinib and vemurafenib led to a longer median PFS of 15.1 months, compared to 10.6 months with placebo plus cobimetinib and vemurafenib (hazard ratio, 0.78; 95% CI, 0.63 – 0.97; P = .025).
The most common adverse reactions (rate ≥ 20%) in patients who received the triple combination were rash (75%), musculoskeletal pain (62%), fatigue (51%), hepatotoxicity (50%), pyrexia (49%), nausea (30%), pruritus (26%), edema (26%), stomatitis (23%), hypothyroidism (22%), and photosensitivity reaction (21%).
The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that facilitates concurrent submission and review of oncology products among international partners.
This article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved the triple-therapy combination of atezolizumab (Tecentriq) plus cobimetinib (Cotellic) and vemurafenib (Zelboraf) for the treatment of BRAF V600 mutation-positive advanced melanoma, according to a press statement from Genentech, which owns all three drugs.
This is the first melanoma indication for the PD-L1 inhibitor atezolizumab; the other two drugs, cobimetinib and vemurafenib, are a MEK- plus BRAF-inhibitor combination previously approved for BRAF-mutated melanoma.
The new approval is based on safety and efficacy results from the randomized, phase 3 IMspire150 study from patients with previously untreated BRAF V600 mutation-positive metastatic or unresectable locally advanced melanoma.
Progression-free survival (PFS), the primary endpoint, was improved by 4.5 months with the triple therapy compared to the doublet.
The addition of atezolizumab to cobimetinib and vemurafenib led to a longer median PFS of 15.1 months, compared to 10.6 months with placebo plus cobimetinib and vemurafenib (hazard ratio, 0.78; 95% CI, 0.63 – 0.97; P = .025).
The most common adverse reactions (rate ≥ 20%) in patients who received the triple combination were rash (75%), musculoskeletal pain (62%), fatigue (51%), hepatotoxicity (50%), pyrexia (49%), nausea (30%), pruritus (26%), edema (26%), stomatitis (23%), hypothyroidism (22%), and photosensitivity reaction (21%).
The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that facilitates concurrent submission and review of oncology products among international partners.
This article first appeared on Medscape.com.
The US Food and Drug Administration (FDA) has approved the triple-therapy combination of atezolizumab (Tecentriq) plus cobimetinib (Cotellic) and vemurafenib (Zelboraf) for the treatment of BRAF V600 mutation-positive advanced melanoma, according to a press statement from Genentech, which owns all three drugs.
This is the first melanoma indication for the PD-L1 inhibitor atezolizumab; the other two drugs, cobimetinib and vemurafenib, are a MEK- plus BRAF-inhibitor combination previously approved for BRAF-mutated melanoma.
The new approval is based on safety and efficacy results from the randomized, phase 3 IMspire150 study from patients with previously untreated BRAF V600 mutation-positive metastatic or unresectable locally advanced melanoma.
Progression-free survival (PFS), the primary endpoint, was improved by 4.5 months with the triple therapy compared to the doublet.
The addition of atezolizumab to cobimetinib and vemurafenib led to a longer median PFS of 15.1 months, compared to 10.6 months with placebo plus cobimetinib and vemurafenib (hazard ratio, 0.78; 95% CI, 0.63 – 0.97; P = .025).
The most common adverse reactions (rate ≥ 20%) in patients who received the triple combination were rash (75%), musculoskeletal pain (62%), fatigue (51%), hepatotoxicity (50%), pyrexia (49%), nausea (30%), pruritus (26%), edema (26%), stomatitis (23%), hypothyroidism (22%), and photosensitivity reaction (21%).
The review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence that facilitates concurrent submission and review of oncology products among international partners.
This article first appeared on Medscape.com.
Range of interventions reduces likelihood of infection after hysterectomy
Improving hand hygiene, optimizing antibiotic order sets, and removing catheters sooner were among the interventions associated with a decreased risk of infections after hysterectomy, according to research presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons.
“Implementation of said study author Shitanshu Uppal, MBBS, an ob.gyn. specializing in gynecologic oncology at the University of Michigan in Ann Arbor.
To assess the impact of quality improvement efforts on infectious morbidity after hysterectomy, Dr. Uppal and colleagues analyzed data from 1,867 hysterectomies performed between Oct. 8, 2015, and Oct. 7, 2018. Patients were at least 18 years old, younger than 90 years old, and underwent hysterectomy via any route at the University of Michigan Medical Center Hospital.
Interventions to reduce infections included the use of cefazolin as a preferred antibiotic, the addition of metronidazole to first-generation cephalosporins for antibiotic prophylaxis, subcuticular closure of open incisions, and earlier removal of Foley catheters. In addition, the institution evaluated and shared information about doctors’ hand hygiene, implemented enhanced recovery after surgery (ERAS) protocols, and held periodic meetings with doctors to discuss efforts to reduce infections. Most interventions were implemented by November 2017.
The primary outcome was overall infection rate in the 30 days after surgery for each of the 3 years included the study. Infections included superficial surgical site infections, deep infections, Clostridium difficile infections, and urinary tract infections, among others.
Patients’ baseline clinical characteristics did not differ during the 3 years studied. Length of stay decreased, which may be attributed to increased use of ERAS protocols and institution of same-day discharge in laparoscopic cases, Dr. Uppal said. The rate of malignancy on final pathology decreased from 29% in year 1 to 23% in year 3. The rate of laparoscopic surgery increased from 55% to 64%.
Infectious morbidity rates decreased from 7% in year 1 (47 infections per 644 cases) to 4% in year 3 (22 infections per 616 cases).
“We saw a reduction in infection rate in all categories,” said Dr. Uppal. “However, the reduction in urinary tract infection as well as superficial surgical site infection was most pronounced.”
After adjustment for the route of surgery, body mass index, age, malignancy on final pathology, modality of surgery, and comorbidities, performance of hysterectomy in year 3 was independently predictive of lower rates of infectious morbidity by 56%.
In addition, the standardized incidence ratio for surgical site infection as reported by the Centers for Medicare & Medicaid Services decreased. In December 2016, Michigan Medicine’s ratio was 1.057. At the end of 2018, the projected ratio was 0.243.
The interventions started on different dates, and “we are unable to conclude, from all the implemented interventions, which one worked,” Dr. Uppal noted.
“I hope the elements from this quality improvement initiative will become the standard of care in order to benefit our patients,” said Amy Park, MD, section head of female pelvic medicine and reconstructive surgery at Cleveland Clinic.
In addition, the study “pertains to one of CMS’s major programs to reduce and prevent health care-associated infections,” Dr. Park said at the virtual meeting. Several CMS quality indicators in 2020 relate to gynecologic surgery, including postoperative wound dehiscence rate, catheter-related UTI rate, and surgical site infection related to hysterectomy. The CMS will reduce hospital payments to institutions in the worst performing quartile for hospital-acquired infection scores by 1%.
Dr. Uppal advised that hospitals need four things to achieve similar results: a commitment from the team and leadership to reduce infections; patience; making it easy for doctors to implement the new interventions; and periodic feedback.
The process may be tedious but worth it in the end, he said.
Dr. Uppal disclosed salary support from Blue Cross Blue Shield of Michigan. A coauthor disclosed salary support from the company plus royalties from UpToDate. Dr. Park disclosed speaking for Allergan and royalties from UpToDate.
SOURCE: Uppal S et al. SGS 2020, Abstract 16.
Improving hand hygiene, optimizing antibiotic order sets, and removing catheters sooner were among the interventions associated with a decreased risk of infections after hysterectomy, according to research presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons.
“Implementation of said study author Shitanshu Uppal, MBBS, an ob.gyn. specializing in gynecologic oncology at the University of Michigan in Ann Arbor.
To assess the impact of quality improvement efforts on infectious morbidity after hysterectomy, Dr. Uppal and colleagues analyzed data from 1,867 hysterectomies performed between Oct. 8, 2015, and Oct. 7, 2018. Patients were at least 18 years old, younger than 90 years old, and underwent hysterectomy via any route at the University of Michigan Medical Center Hospital.
Interventions to reduce infections included the use of cefazolin as a preferred antibiotic, the addition of metronidazole to first-generation cephalosporins for antibiotic prophylaxis, subcuticular closure of open incisions, and earlier removal of Foley catheters. In addition, the institution evaluated and shared information about doctors’ hand hygiene, implemented enhanced recovery after surgery (ERAS) protocols, and held periodic meetings with doctors to discuss efforts to reduce infections. Most interventions were implemented by November 2017.
The primary outcome was overall infection rate in the 30 days after surgery for each of the 3 years included the study. Infections included superficial surgical site infections, deep infections, Clostridium difficile infections, and urinary tract infections, among others.
Patients’ baseline clinical characteristics did not differ during the 3 years studied. Length of stay decreased, which may be attributed to increased use of ERAS protocols and institution of same-day discharge in laparoscopic cases, Dr. Uppal said. The rate of malignancy on final pathology decreased from 29% in year 1 to 23% in year 3. The rate of laparoscopic surgery increased from 55% to 64%.
Infectious morbidity rates decreased from 7% in year 1 (47 infections per 644 cases) to 4% in year 3 (22 infections per 616 cases).
“We saw a reduction in infection rate in all categories,” said Dr. Uppal. “However, the reduction in urinary tract infection as well as superficial surgical site infection was most pronounced.”
After adjustment for the route of surgery, body mass index, age, malignancy on final pathology, modality of surgery, and comorbidities, performance of hysterectomy in year 3 was independently predictive of lower rates of infectious morbidity by 56%.
In addition, the standardized incidence ratio for surgical site infection as reported by the Centers for Medicare & Medicaid Services decreased. In December 2016, Michigan Medicine’s ratio was 1.057. At the end of 2018, the projected ratio was 0.243.
The interventions started on different dates, and “we are unable to conclude, from all the implemented interventions, which one worked,” Dr. Uppal noted.
“I hope the elements from this quality improvement initiative will become the standard of care in order to benefit our patients,” said Amy Park, MD, section head of female pelvic medicine and reconstructive surgery at Cleveland Clinic.
In addition, the study “pertains to one of CMS’s major programs to reduce and prevent health care-associated infections,” Dr. Park said at the virtual meeting. Several CMS quality indicators in 2020 relate to gynecologic surgery, including postoperative wound dehiscence rate, catheter-related UTI rate, and surgical site infection related to hysterectomy. The CMS will reduce hospital payments to institutions in the worst performing quartile for hospital-acquired infection scores by 1%.
Dr. Uppal advised that hospitals need four things to achieve similar results: a commitment from the team and leadership to reduce infections; patience; making it easy for doctors to implement the new interventions; and periodic feedback.
The process may be tedious but worth it in the end, he said.
Dr. Uppal disclosed salary support from Blue Cross Blue Shield of Michigan. A coauthor disclosed salary support from the company plus royalties from UpToDate. Dr. Park disclosed speaking for Allergan and royalties from UpToDate.
SOURCE: Uppal S et al. SGS 2020, Abstract 16.
Improving hand hygiene, optimizing antibiotic order sets, and removing catheters sooner were among the interventions associated with a decreased risk of infections after hysterectomy, according to research presented at the virtual annual scientific meeting of the Society of Gynecologic Surgeons.
“Implementation of said study author Shitanshu Uppal, MBBS, an ob.gyn. specializing in gynecologic oncology at the University of Michigan in Ann Arbor.
To assess the impact of quality improvement efforts on infectious morbidity after hysterectomy, Dr. Uppal and colleagues analyzed data from 1,867 hysterectomies performed between Oct. 8, 2015, and Oct. 7, 2018. Patients were at least 18 years old, younger than 90 years old, and underwent hysterectomy via any route at the University of Michigan Medical Center Hospital.
Interventions to reduce infections included the use of cefazolin as a preferred antibiotic, the addition of metronidazole to first-generation cephalosporins for antibiotic prophylaxis, subcuticular closure of open incisions, and earlier removal of Foley catheters. In addition, the institution evaluated and shared information about doctors’ hand hygiene, implemented enhanced recovery after surgery (ERAS) protocols, and held periodic meetings with doctors to discuss efforts to reduce infections. Most interventions were implemented by November 2017.
The primary outcome was overall infection rate in the 30 days after surgery for each of the 3 years included the study. Infections included superficial surgical site infections, deep infections, Clostridium difficile infections, and urinary tract infections, among others.
Patients’ baseline clinical characteristics did not differ during the 3 years studied. Length of stay decreased, which may be attributed to increased use of ERAS protocols and institution of same-day discharge in laparoscopic cases, Dr. Uppal said. The rate of malignancy on final pathology decreased from 29% in year 1 to 23% in year 3. The rate of laparoscopic surgery increased from 55% to 64%.
Infectious morbidity rates decreased from 7% in year 1 (47 infections per 644 cases) to 4% in year 3 (22 infections per 616 cases).
“We saw a reduction in infection rate in all categories,” said Dr. Uppal. “However, the reduction in urinary tract infection as well as superficial surgical site infection was most pronounced.”
After adjustment for the route of surgery, body mass index, age, malignancy on final pathology, modality of surgery, and comorbidities, performance of hysterectomy in year 3 was independently predictive of lower rates of infectious morbidity by 56%.
In addition, the standardized incidence ratio for surgical site infection as reported by the Centers for Medicare & Medicaid Services decreased. In December 2016, Michigan Medicine’s ratio was 1.057. At the end of 2018, the projected ratio was 0.243.
The interventions started on different dates, and “we are unable to conclude, from all the implemented interventions, which one worked,” Dr. Uppal noted.
“I hope the elements from this quality improvement initiative will become the standard of care in order to benefit our patients,” said Amy Park, MD, section head of female pelvic medicine and reconstructive surgery at Cleveland Clinic.
In addition, the study “pertains to one of CMS’s major programs to reduce and prevent health care-associated infections,” Dr. Park said at the virtual meeting. Several CMS quality indicators in 2020 relate to gynecologic surgery, including postoperative wound dehiscence rate, catheter-related UTI rate, and surgical site infection related to hysterectomy. The CMS will reduce hospital payments to institutions in the worst performing quartile for hospital-acquired infection scores by 1%.
Dr. Uppal advised that hospitals need four things to achieve similar results: a commitment from the team and leadership to reduce infections; patience; making it easy for doctors to implement the new interventions; and periodic feedback.
The process may be tedious but worth it in the end, he said.
Dr. Uppal disclosed salary support from Blue Cross Blue Shield of Michigan. A coauthor disclosed salary support from the company plus royalties from UpToDate. Dr. Park disclosed speaking for Allergan and royalties from UpToDate.
SOURCE: Uppal S et al. SGS 2020, Abstract 16.
FROM SGS 2020
Poll: Institutions should implement mandatory implicit bias training and policies for inclusion and diversity to address inequities in health care
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[polldaddy:10586792]
[polldaddy:10586792]
More data needed to better understand COVID-19 skin manifestations
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.
In an interview, Alisa N. Femia, MD, director of inpatient dermatology in the department of dermatology at New York University, said that the cutaneous signs described in the review align well with what she has seen in patients with COVID-19.
At this point, it is unclear whether cutaneous manifestations of COVID-19 are a result of SARS-CoV-2 invading the skin or an immune response related to SARS-CoV-2, noted Dr. Femia, who was not involved in the research. One method of entry could be through transmitting virus present on the skin to another part of the body where infection is more likely.
While it is possible COVID-19 could be contracted through the skin, she noted, it is much more likely an individual would be infected by SARS-CoV-2 through more traditionally understood means of transmission, such as through respiratory droplets in person-to-person contact. “I think we are far away from drawing that conclusion, that one could touch a surface or a person who has COVID and contract it through their skin,” Dr. Femia said. “The skin has a lot of other ways to protect against that from occurring,” she added.
“SAR-CoV-2 obviously enters through the ACE2 receptor, which is fairly ubiquitous, and it has been seen in keratinocytes,” she said. “But the skin is one of our biggest barriers ... and further, studies to date have shown that that receptor is expressed in relatively low levels of the keratinocytes.”
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.
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.
In an interview, Alisa N. Femia, MD, director of inpatient dermatology in the department of dermatology at New York University, said that the cutaneous signs described in the review align well with what she has seen in patients with COVID-19.
At this point, it is unclear whether cutaneous manifestations of COVID-19 are a result of SARS-CoV-2 invading the skin or an immune response related to SARS-CoV-2, noted Dr. Femia, who was not involved in the research. One method of entry could be through transmitting virus present on the skin to another part of the body where infection is more likely.
While it is possible COVID-19 could be contracted through the skin, she noted, it is much more likely an individual would be infected by SARS-CoV-2 through more traditionally understood means of transmission, such as through respiratory droplets in person-to-person contact. “I think we are far away from drawing that conclusion, that one could touch a surface or a person who has COVID and contract it through their skin,” Dr. Femia said. “The skin has a lot of other ways to protect against that from occurring,” she added.
“SAR-CoV-2 obviously enters through the ACE2 receptor, which is fairly ubiquitous, and it has been seen in keratinocytes,” she said. “But the skin is one of our biggest barriers ... and further, studies to date have shown that that receptor is expressed in relatively low levels of the keratinocytes.”
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.
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.
In an interview, Alisa N. Femia, MD, director of inpatient dermatology in the department of dermatology at New York University, said that the cutaneous signs described in the review align well with what she has seen in patients with COVID-19.
At this point, it is unclear whether cutaneous manifestations of COVID-19 are a result of SARS-CoV-2 invading the skin or an immune response related to SARS-CoV-2, noted Dr. Femia, who was not involved in the research. One method of entry could be through transmitting virus present on the skin to another part of the body where infection is more likely.
While it is possible COVID-19 could be contracted through the skin, she noted, it is much more likely an individual would be infected by SARS-CoV-2 through more traditionally understood means of transmission, such as through respiratory droplets in person-to-person contact. “I think we are far away from drawing that conclusion, that one could touch a surface or a person who has COVID and contract it through their skin,” Dr. Femia said. “The skin has a lot of other ways to protect against that from occurring,” she added.
“SAR-CoV-2 obviously enters through the ACE2 receptor, which is fairly ubiquitous, and it has been seen in keratinocytes,” she said. “But the skin is one of our biggest barriers ... and further, studies to date have shown that that receptor is expressed in relatively low levels of the keratinocytes.”
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.
FROM THE JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY