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U.S. tops 500,000 COVID-19 cases in children
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
States have reported 513,415 cases of COVID-19 in children since the beginning of the pandemic, with almost 37,000 coming in the last week, the AAP and the CHA said Sept. 8 in the weekly report. That figure includes New York City – the rest of New York State is not reporting ages for COVID-19 patients – as well as Puerto Rico, the District of Columbia, and Guam.
“These numbers are a chilling reminder of why we need to take this virus seriously,” AAP President Sara Goza, MD, said in a written statement.
Children now represent 9.8% of the almost 5.3 million cases that have been reported in Americans of all ages. The proportion of child cases has continued to increase as the pandemic has progressed – it was 8.0% as of mid-July and 5.2% in early June, the data show.
“Throughout the summer, surges in the virus have occurred in Southern, Western, and Midwestern states,” the AAP statement said.
The latest AAP/CHA report shows that, from Aug. 27 to Sept. 3, the total number of child cases jumped by 33.7% in South Dakota, more than any other state. North Dakota was next at 22.7%, followed by Hawaii (18.1%), Missouri (16.8%), and Kentucky (16.4%).
“This rapid rise in positive cases occurred over the summer, and as the weather cools, we know people will spend more time indoors,” said Sean O’Leary, MD, MPH, vice chair of the AAP Committee on Infectious Diseases. “The goal is to get children back into schools for in-person learning, but in many communities, this is not possible as the virus spreads unchecked.”
The smallest increase over the last week, just 0.9%, came in Rhode Island, with Massachusetts just a bit higher at 1.0%. Also at the low end of the increase scale are Arizona (3.3%) and Louisiana (4.0%), two states that have very high rates of cumulative cases: 1,380 per 100,000 children for Arizona and 1,234 per 100,000 for Louisiana, the report said.
To give those figures some context, Tennessee has the highest cumulative count of any state at 1,553 cases per 100,000 children and Vermont has the lowest at 151, based on the data gathered by the AAP and CHA.
“While much remains unknown about COVID-19, we do know that the spread among children reflects what is happening in the broader communities. A disproportionate number of cases are reported in Black and Hispanic children and in places where there is high poverty. We must work harder to address societal inequities that contribute to these disparities,” Dr. Goza said.
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
States have reported 513,415 cases of COVID-19 in children since the beginning of the pandemic, with almost 37,000 coming in the last week, the AAP and the CHA said Sept. 8 in the weekly report. That figure includes New York City – the rest of New York State is not reporting ages for COVID-19 patients – as well as Puerto Rico, the District of Columbia, and Guam.
“These numbers are a chilling reminder of why we need to take this virus seriously,” AAP President Sara Goza, MD, said in a written statement.
Children now represent 9.8% of the almost 5.3 million cases that have been reported in Americans of all ages. The proportion of child cases has continued to increase as the pandemic has progressed – it was 8.0% as of mid-July and 5.2% in early June, the data show.
“Throughout the summer, surges in the virus have occurred in Southern, Western, and Midwestern states,” the AAP statement said.
The latest AAP/CHA report shows that, from Aug. 27 to Sept. 3, the total number of child cases jumped by 33.7% in South Dakota, more than any other state. North Dakota was next at 22.7%, followed by Hawaii (18.1%), Missouri (16.8%), and Kentucky (16.4%).
“This rapid rise in positive cases occurred over the summer, and as the weather cools, we know people will spend more time indoors,” said Sean O’Leary, MD, MPH, vice chair of the AAP Committee on Infectious Diseases. “The goal is to get children back into schools for in-person learning, but in many communities, this is not possible as the virus spreads unchecked.”
The smallest increase over the last week, just 0.9%, came in Rhode Island, with Massachusetts just a bit higher at 1.0%. Also at the low end of the increase scale are Arizona (3.3%) and Louisiana (4.0%), two states that have very high rates of cumulative cases: 1,380 per 100,000 children for Arizona and 1,234 per 100,000 for Louisiana, the report said.
To give those figures some context, Tennessee has the highest cumulative count of any state at 1,553 cases per 100,000 children and Vermont has the lowest at 151, based on the data gathered by the AAP and CHA.
“While much remains unknown about COVID-19, we do know that the spread among children reflects what is happening in the broader communities. A disproportionate number of cases are reported in Black and Hispanic children and in places where there is high poverty. We must work harder to address societal inequities that contribute to these disparities,” Dr. Goza said.
according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
States have reported 513,415 cases of COVID-19 in children since the beginning of the pandemic, with almost 37,000 coming in the last week, the AAP and the CHA said Sept. 8 in the weekly report. That figure includes New York City – the rest of New York State is not reporting ages for COVID-19 patients – as well as Puerto Rico, the District of Columbia, and Guam.
“These numbers are a chilling reminder of why we need to take this virus seriously,” AAP President Sara Goza, MD, said in a written statement.
Children now represent 9.8% of the almost 5.3 million cases that have been reported in Americans of all ages. The proportion of child cases has continued to increase as the pandemic has progressed – it was 8.0% as of mid-July and 5.2% in early June, the data show.
“Throughout the summer, surges in the virus have occurred in Southern, Western, and Midwestern states,” the AAP statement said.
The latest AAP/CHA report shows that, from Aug. 27 to Sept. 3, the total number of child cases jumped by 33.7% in South Dakota, more than any other state. North Dakota was next at 22.7%, followed by Hawaii (18.1%), Missouri (16.8%), and Kentucky (16.4%).
“This rapid rise in positive cases occurred over the summer, and as the weather cools, we know people will spend more time indoors,” said Sean O’Leary, MD, MPH, vice chair of the AAP Committee on Infectious Diseases. “The goal is to get children back into schools for in-person learning, but in many communities, this is not possible as the virus spreads unchecked.”
The smallest increase over the last week, just 0.9%, came in Rhode Island, with Massachusetts just a bit higher at 1.0%. Also at the low end of the increase scale are Arizona (3.3%) and Louisiana (4.0%), two states that have very high rates of cumulative cases: 1,380 per 100,000 children for Arizona and 1,234 per 100,000 for Louisiana, the report said.
To give those figures some context, Tennessee has the highest cumulative count of any state at 1,553 cases per 100,000 children and Vermont has the lowest at 151, based on the data gathered by the AAP and CHA.
“While much remains unknown about COVID-19, we do know that the spread among children reflects what is happening in the broader communities. A disproportionate number of cases are reported in Black and Hispanic children and in places where there is high poverty. We must work harder to address societal inequities that contribute to these disparities,” Dr. Goza said.
Mounting data support COVID-19 acute pancreatitis
Mounting data support acute pancreatitis as one possible GI manifestation of COVID-19, according to investigators.
While previous case reports suggested that infection with SARS-CoV2 may lead to pancreatitis, this retrospective analysis, which is the largest to date, is the first to offer substantial evidence for this claim, reported lead author Sumant Inamdar, MBBS, of the University of Arkansas, Little Rock, and colleagues.
“It has become increasingly clear that COVID-19 has systemic effects that also includes the gastrointestinal and pancreaticobiliary systems,” the investigators wrote in Gastroenterology. “As islet cells of the pancreas contain ACE2 receptor proteins, SARS-CoV2 can bind to these receptors and cause pancreatic injury.”
For the present analysis, Dr. Inamdar and colleagues reviewed charts from 48,012 patients who were hospitalized in New York between March and June of this year. While pancreatitis is usually diagnosed based on two out of three criteria, disease classification in the study required all three: characteristic upper abdominal pain upon admission, lipase greater than three times the upper limit of normal, and evidence of pancreatitis on cross-sectional imaging.
“[B]y including all three criteria for pancreatitis in our definition, we may be underestimating the rate of pancreatitis,” the investigators wrote. “However, we felt including diagnostic lipase levels and imaging was important for the accuracy of the diagnosis.”
Primary outcomes included mechanical ventilation, length of stay, development of pancreatic necrosis, and mortality. Outcomes were compared between patients with and without COVID-19.
Out of 48,012 hospitalized patients, 11,883 (24.75%) tested positive for SARS-CoV2. Across the entire population, 189 patients had pancreatitis (0.39%), and of these, 32 (17%) also had COVID-19. This translates to a point prevalence for pancreatitis of 0.27% for patients hospitalized with COVID-19.
Among patients with pancreatitis who did not have COVID-19, the most common etiologies for pancreatitis were gallstones (34%) and alcohol (37%), compared with just 16% and 6% of SARS-CoV2-positive cases of pancreatitis, respectively. Idiopathic pancreatitis was significantly more common among patients with COVID-19 than those without (69% vs 21%; P less than .0001).
Black or Hispanic patients with pancreatitis were 4-5 times more likely to have COVID-19 than patients with pancreatitis who were white. Across all races/ethnicities, patients with pancreatitis and COVID-19 more often required mechanical ventilation (odds ratio [OR], 5.65) and longer hospital stays (OR, 3.22), compared with those who had pancreatitis alone. While rates of mortality and pancreatic necrosis showed similar trends, associations with COVID-19 were not statistically significant.
“These findings support the notion that pancreatitis should be included in the list of GI manifestations of COVID-19,” the investigators wrote.
When caring for patients with COVID-19, Dr. Inamdar and colleagues recommended that clinicians pay close attention to any history of abdominal pain, and consider testing serum lipase levels.
“Further large studies are needed to confirm our findings,” they concluded.
Gyanprakash Avinash Ketwaroo, MD, of Baylor College of Medicine in Houston, agreed that more work is needed; in the meantime, he suggested that evidence is now strong enough for clinicians to take notice.
“Overall, this study adds further weight to COVID-19 acute pancreatitis,” he said. “Larger studies, and convincing pathophysiologic data, will be needed to confirm COVID-19 as a cause of acute pancreatitis. However, there appears to be enough circumstantial evidence to consider a COVID-19 diagnosis in patients presenting with acute pancreatitis.”
He noted that the new clinical evidence also stands on a solid theoretical foundation.
“Viruses, especially mumps and measles, have long been known to cause acute pancreatitis,” he said. “Additionally, the ACE2 receptor is present on pancreatic beta-cells and may mediate COVID-19 induced pancreatitis.”
Along with larger observational studies, Dr. Ketwaroo suggested that a number of interventional questions remain unanswered.
“While most acute pancreatitis is treated with supportive care, could proven therapies for COVID-19, such as steroids, also mitigate COVID-19 acute pancreatitis?” he asked. “Is COVID-19 a cofactor for acute pancreatitis caused by alcohol or endoscopic retrograde cholangiopancreatography? We await further information from an active area of research.”
The investigators disclosed relationships with Boston Scientific, Olympus, Fujifilm, and others.
SOURCE: Inamdar S et al. Gastroenterology. 2020 Aug 26. doi: 10.1053/j.gastro.2020.08.044.
Mounting data support acute pancreatitis as one possible GI manifestation of COVID-19, according to investigators.
While previous case reports suggested that infection with SARS-CoV2 may lead to pancreatitis, this retrospective analysis, which is the largest to date, is the first to offer substantial evidence for this claim, reported lead author Sumant Inamdar, MBBS, of the University of Arkansas, Little Rock, and colleagues.
“It has become increasingly clear that COVID-19 has systemic effects that also includes the gastrointestinal and pancreaticobiliary systems,” the investigators wrote in Gastroenterology. “As islet cells of the pancreas contain ACE2 receptor proteins, SARS-CoV2 can bind to these receptors and cause pancreatic injury.”
For the present analysis, Dr. Inamdar and colleagues reviewed charts from 48,012 patients who were hospitalized in New York between March and June of this year. While pancreatitis is usually diagnosed based on two out of three criteria, disease classification in the study required all three: characteristic upper abdominal pain upon admission, lipase greater than three times the upper limit of normal, and evidence of pancreatitis on cross-sectional imaging.
“[B]y including all three criteria for pancreatitis in our definition, we may be underestimating the rate of pancreatitis,” the investigators wrote. “However, we felt including diagnostic lipase levels and imaging was important for the accuracy of the diagnosis.”
Primary outcomes included mechanical ventilation, length of stay, development of pancreatic necrosis, and mortality. Outcomes were compared between patients with and without COVID-19.
Out of 48,012 hospitalized patients, 11,883 (24.75%) tested positive for SARS-CoV2. Across the entire population, 189 patients had pancreatitis (0.39%), and of these, 32 (17%) also had COVID-19. This translates to a point prevalence for pancreatitis of 0.27% for patients hospitalized with COVID-19.
Among patients with pancreatitis who did not have COVID-19, the most common etiologies for pancreatitis were gallstones (34%) and alcohol (37%), compared with just 16% and 6% of SARS-CoV2-positive cases of pancreatitis, respectively. Idiopathic pancreatitis was significantly more common among patients with COVID-19 than those without (69% vs 21%; P less than .0001).
Black or Hispanic patients with pancreatitis were 4-5 times more likely to have COVID-19 than patients with pancreatitis who were white. Across all races/ethnicities, patients with pancreatitis and COVID-19 more often required mechanical ventilation (odds ratio [OR], 5.65) and longer hospital stays (OR, 3.22), compared with those who had pancreatitis alone. While rates of mortality and pancreatic necrosis showed similar trends, associations with COVID-19 were not statistically significant.
“These findings support the notion that pancreatitis should be included in the list of GI manifestations of COVID-19,” the investigators wrote.
When caring for patients with COVID-19, Dr. Inamdar and colleagues recommended that clinicians pay close attention to any history of abdominal pain, and consider testing serum lipase levels.
“Further large studies are needed to confirm our findings,” they concluded.
Gyanprakash Avinash Ketwaroo, MD, of Baylor College of Medicine in Houston, agreed that more work is needed; in the meantime, he suggested that evidence is now strong enough for clinicians to take notice.
“Overall, this study adds further weight to COVID-19 acute pancreatitis,” he said. “Larger studies, and convincing pathophysiologic data, will be needed to confirm COVID-19 as a cause of acute pancreatitis. However, there appears to be enough circumstantial evidence to consider a COVID-19 diagnosis in patients presenting with acute pancreatitis.”
He noted that the new clinical evidence also stands on a solid theoretical foundation.
“Viruses, especially mumps and measles, have long been known to cause acute pancreatitis,” he said. “Additionally, the ACE2 receptor is present on pancreatic beta-cells and may mediate COVID-19 induced pancreatitis.”
Along with larger observational studies, Dr. Ketwaroo suggested that a number of interventional questions remain unanswered.
“While most acute pancreatitis is treated with supportive care, could proven therapies for COVID-19, such as steroids, also mitigate COVID-19 acute pancreatitis?” he asked. “Is COVID-19 a cofactor for acute pancreatitis caused by alcohol or endoscopic retrograde cholangiopancreatography? We await further information from an active area of research.”
The investigators disclosed relationships with Boston Scientific, Olympus, Fujifilm, and others.
SOURCE: Inamdar S et al. Gastroenterology. 2020 Aug 26. doi: 10.1053/j.gastro.2020.08.044.
Mounting data support acute pancreatitis as one possible GI manifestation of COVID-19, according to investigators.
While previous case reports suggested that infection with SARS-CoV2 may lead to pancreatitis, this retrospective analysis, which is the largest to date, is the first to offer substantial evidence for this claim, reported lead author Sumant Inamdar, MBBS, of the University of Arkansas, Little Rock, and colleagues.
“It has become increasingly clear that COVID-19 has systemic effects that also includes the gastrointestinal and pancreaticobiliary systems,” the investigators wrote in Gastroenterology. “As islet cells of the pancreas contain ACE2 receptor proteins, SARS-CoV2 can bind to these receptors and cause pancreatic injury.”
For the present analysis, Dr. Inamdar and colleagues reviewed charts from 48,012 patients who were hospitalized in New York between March and June of this year. While pancreatitis is usually diagnosed based on two out of three criteria, disease classification in the study required all three: characteristic upper abdominal pain upon admission, lipase greater than three times the upper limit of normal, and evidence of pancreatitis on cross-sectional imaging.
“[B]y including all three criteria for pancreatitis in our definition, we may be underestimating the rate of pancreatitis,” the investigators wrote. “However, we felt including diagnostic lipase levels and imaging was important for the accuracy of the diagnosis.”
Primary outcomes included mechanical ventilation, length of stay, development of pancreatic necrosis, and mortality. Outcomes were compared between patients with and without COVID-19.
Out of 48,012 hospitalized patients, 11,883 (24.75%) tested positive for SARS-CoV2. Across the entire population, 189 patients had pancreatitis (0.39%), and of these, 32 (17%) also had COVID-19. This translates to a point prevalence for pancreatitis of 0.27% for patients hospitalized with COVID-19.
Among patients with pancreatitis who did not have COVID-19, the most common etiologies for pancreatitis were gallstones (34%) and alcohol (37%), compared with just 16% and 6% of SARS-CoV2-positive cases of pancreatitis, respectively. Idiopathic pancreatitis was significantly more common among patients with COVID-19 than those without (69% vs 21%; P less than .0001).
Black or Hispanic patients with pancreatitis were 4-5 times more likely to have COVID-19 than patients with pancreatitis who were white. Across all races/ethnicities, patients with pancreatitis and COVID-19 more often required mechanical ventilation (odds ratio [OR], 5.65) and longer hospital stays (OR, 3.22), compared with those who had pancreatitis alone. While rates of mortality and pancreatic necrosis showed similar trends, associations with COVID-19 were not statistically significant.
“These findings support the notion that pancreatitis should be included in the list of GI manifestations of COVID-19,” the investigators wrote.
When caring for patients with COVID-19, Dr. Inamdar and colleagues recommended that clinicians pay close attention to any history of abdominal pain, and consider testing serum lipase levels.
“Further large studies are needed to confirm our findings,” they concluded.
Gyanprakash Avinash Ketwaroo, MD, of Baylor College of Medicine in Houston, agreed that more work is needed; in the meantime, he suggested that evidence is now strong enough for clinicians to take notice.
“Overall, this study adds further weight to COVID-19 acute pancreatitis,” he said. “Larger studies, and convincing pathophysiologic data, will be needed to confirm COVID-19 as a cause of acute pancreatitis. However, there appears to be enough circumstantial evidence to consider a COVID-19 diagnosis in patients presenting with acute pancreatitis.”
He noted that the new clinical evidence also stands on a solid theoretical foundation.
“Viruses, especially mumps and measles, have long been known to cause acute pancreatitis,” he said. “Additionally, the ACE2 receptor is present on pancreatic beta-cells and may mediate COVID-19 induced pancreatitis.”
Along with larger observational studies, Dr. Ketwaroo suggested that a number of interventional questions remain unanswered.
“While most acute pancreatitis is treated with supportive care, could proven therapies for COVID-19, such as steroids, also mitigate COVID-19 acute pancreatitis?” he asked. “Is COVID-19 a cofactor for acute pancreatitis caused by alcohol or endoscopic retrograde cholangiopancreatography? We await further information from an active area of research.”
The investigators disclosed relationships with Boston Scientific, Olympus, Fujifilm, and others.
SOURCE: Inamdar S et al. Gastroenterology. 2020 Aug 26. doi: 10.1053/j.gastro.2020.08.044.
FROM GASTROENTEROLOGY
Five reasons why medical meetings will never be the same
In the wake of the COVID-19 pandemic, the virtual medical meeting is now the norm. And while it’s admirable that key data are being disseminated (often for free), there is no escaping the fact that it is a fundamentally different and lesser experience.
Watching from home, most of us split our attention between live streams of the meeting and work and family obligations. There is far less urgency when early live presentations are recorded and can be viewed later.
In terms of discussing the data, Twitter may offer broader participation than a live meeting, yet only a small number of attendees actively engage online.
And the exhibit halls for these online meetings? With neither free coffee nor company-branded tchotchkes, I expect that they have virtual tumbleweeds blowing through and crickets chirping.
Even still, the virtual meeting experience, while inferior to the live one, is a tremendous advance. It should never be banished as a historical footnote but rather should remain an option. It’s analogous to watching the Super Bowl at home: Obviously, it’s not the same as being there, but it’s a terrific alternative. Like telemedicine, this pandemic has provided a critical proof of concept that there is a better model.
Reshaping the medical meeting
Let’s consider five reasons why medical meetings should be permanently reshaped by this pandemic.
This pandemic isn’t going away in 2020. While nearly every country has done a far better job than the United States of containing COVID-19 thus far, outbreaks remain a problem wherever crowds assemble. You’d be hard-pressed to devise a setting more conducive to mass spread than a conference of 20,000 attendees from all over the world sitting alongside each other cheek to jowl for 5 days. Worse yet is the thought of them returning home and infecting their patients, families, and friends. What medical society wants to be remembered for creating a COVID-19 superspreader event? Professional medical societies will need to offer this option as the safest alternative moving forward.
Virtual learning still conveys the most important content. Despite the many social benefits of a live meeting, its core purpose is to disseminate new research and current and emerging treatment options. Virtual meetings have proven that this format can effectively deliver the content, and not as a secondary offering but as the sole platform in real time.
Virtual learning levels the playing field. Traveling to attend conferences typically costs thousands of dollars, accounting for the registration fees, inflated hotel rates, ground transportation, and meals out for days on end. Most meetings also demand several days away from our work and families, forcing many of us to work extra in the days before we leave and upon our return. Parents and those with commitments at home also face special challenges. For international participants, the financial and time costs are even greater. A virtual meeting helps overcome these hurdles and erases barriers that have long precluded many from attending a conference.
Virtual learning is efficient and comfortable. Virtual meetings over the past 6 months have given us a glimpse of an astonishingly more efficient form. If the content seems of a lower magnitude without the fanfare of a live conference, it is in part because so much of a live meeting is spent walking a mile between session rooms, waiting in concession or taxi lines, sitting in traffic between venues, or simply waiting for a session to begin. All of that has been replaced with time that you can use productively in between video sessions viewed either live or on demand. And with a virtual meeting, you can comfortably watch the sessions. There’s no need to stand along the back wall of an overcrowded room or step over 10 people to squeeze into an open middle seat. You can be focused, rather than having an end-of-day presentation wash over you as your eyes cross because you’ve been running around for the past 12 hours.
Virtual learning and social media will only improve. While virtual meetings unquestionably have limitations, it’s important to acknowledge that the successes thus far still represent only the earliest forays into this endeavor. In-person meetings evolved to their present form over centuries. In contrast, virtual meetings are being cobbled together within a few weeks or months. They can only be expected to improve as presenters adapt their skills to the online audience and new tools improve virtual discussions.
I am not implying that live meetings will or should be replaced by virtual ones. We still need that experience of trainees and experts presenting to a live audience and discussing the results together, all while sharing the energy of the moment. But there should be room for both a live conference and a virtual version.
Practically speaking, it is unclear whether professional societies could forgo the revenue they receive from registration fees, meeting sponsorships, and corporate exhibits. Yet, there are certainly ways to obtain sponsorship revenue for a virtual program. Even if the virtual version of a conference costs far less than attending in person, there is plenty of room between that number and free. It costs remarkably little for a professional society to share its content, and virtual offerings further the mission of distributing this content broadly.
We should not rush to return to the previous status quo. Despite their limitations, virtual meetings have brought a new, higher standard of access and efficiency for sharing important new data and treatment options in medicine.
H. Jack West, MD, associate clinical professor and executive director of employer services at City of Hope Comprehensive Cancer Center in Duarte, Calif., regularly comments on lung cancer for Medscape. West serves as web editor for JAMA Oncology, edits and writes several sections on lung cancer for UpToDate, and leads a wide range of continuing education programs and other educational programs, including hosting the audio podcast West Wind.
This article first appeared on Medscape.com.
In the wake of the COVID-19 pandemic, the virtual medical meeting is now the norm. And while it’s admirable that key data are being disseminated (often for free), there is no escaping the fact that it is a fundamentally different and lesser experience.
Watching from home, most of us split our attention between live streams of the meeting and work and family obligations. There is far less urgency when early live presentations are recorded and can be viewed later.
In terms of discussing the data, Twitter may offer broader participation than a live meeting, yet only a small number of attendees actively engage online.
And the exhibit halls for these online meetings? With neither free coffee nor company-branded tchotchkes, I expect that they have virtual tumbleweeds blowing through and crickets chirping.
Even still, the virtual meeting experience, while inferior to the live one, is a tremendous advance. It should never be banished as a historical footnote but rather should remain an option. It’s analogous to watching the Super Bowl at home: Obviously, it’s not the same as being there, but it’s a terrific alternative. Like telemedicine, this pandemic has provided a critical proof of concept that there is a better model.
Reshaping the medical meeting
Let’s consider five reasons why medical meetings should be permanently reshaped by this pandemic.
This pandemic isn’t going away in 2020. While nearly every country has done a far better job than the United States of containing COVID-19 thus far, outbreaks remain a problem wherever crowds assemble. You’d be hard-pressed to devise a setting more conducive to mass spread than a conference of 20,000 attendees from all over the world sitting alongside each other cheek to jowl for 5 days. Worse yet is the thought of them returning home and infecting their patients, families, and friends. What medical society wants to be remembered for creating a COVID-19 superspreader event? Professional medical societies will need to offer this option as the safest alternative moving forward.
Virtual learning still conveys the most important content. Despite the many social benefits of a live meeting, its core purpose is to disseminate new research and current and emerging treatment options. Virtual meetings have proven that this format can effectively deliver the content, and not as a secondary offering but as the sole platform in real time.
Virtual learning levels the playing field. Traveling to attend conferences typically costs thousands of dollars, accounting for the registration fees, inflated hotel rates, ground transportation, and meals out for days on end. Most meetings also demand several days away from our work and families, forcing many of us to work extra in the days before we leave and upon our return. Parents and those with commitments at home also face special challenges. For international participants, the financial and time costs are even greater. A virtual meeting helps overcome these hurdles and erases barriers that have long precluded many from attending a conference.
Virtual learning is efficient and comfortable. Virtual meetings over the past 6 months have given us a glimpse of an astonishingly more efficient form. If the content seems of a lower magnitude without the fanfare of a live conference, it is in part because so much of a live meeting is spent walking a mile between session rooms, waiting in concession or taxi lines, sitting in traffic between venues, or simply waiting for a session to begin. All of that has been replaced with time that you can use productively in between video sessions viewed either live or on demand. And with a virtual meeting, you can comfortably watch the sessions. There’s no need to stand along the back wall of an overcrowded room or step over 10 people to squeeze into an open middle seat. You can be focused, rather than having an end-of-day presentation wash over you as your eyes cross because you’ve been running around for the past 12 hours.
Virtual learning and social media will only improve. While virtual meetings unquestionably have limitations, it’s important to acknowledge that the successes thus far still represent only the earliest forays into this endeavor. In-person meetings evolved to their present form over centuries. In contrast, virtual meetings are being cobbled together within a few weeks or months. They can only be expected to improve as presenters adapt their skills to the online audience and new tools improve virtual discussions.
I am not implying that live meetings will or should be replaced by virtual ones. We still need that experience of trainees and experts presenting to a live audience and discussing the results together, all while sharing the energy of the moment. But there should be room for both a live conference and a virtual version.
Practically speaking, it is unclear whether professional societies could forgo the revenue they receive from registration fees, meeting sponsorships, and corporate exhibits. Yet, there are certainly ways to obtain sponsorship revenue for a virtual program. Even if the virtual version of a conference costs far less than attending in person, there is plenty of room between that number and free. It costs remarkably little for a professional society to share its content, and virtual offerings further the mission of distributing this content broadly.
We should not rush to return to the previous status quo. Despite their limitations, virtual meetings have brought a new, higher standard of access and efficiency for sharing important new data and treatment options in medicine.
H. Jack West, MD, associate clinical professor and executive director of employer services at City of Hope Comprehensive Cancer Center in Duarte, Calif., regularly comments on lung cancer for Medscape. West serves as web editor for JAMA Oncology, edits and writes several sections on lung cancer for UpToDate, and leads a wide range of continuing education programs and other educational programs, including hosting the audio podcast West Wind.
This article first appeared on Medscape.com.
In the wake of the COVID-19 pandemic, the virtual medical meeting is now the norm. And while it’s admirable that key data are being disseminated (often for free), there is no escaping the fact that it is a fundamentally different and lesser experience.
Watching from home, most of us split our attention between live streams of the meeting and work and family obligations. There is far less urgency when early live presentations are recorded and can be viewed later.
In terms of discussing the data, Twitter may offer broader participation than a live meeting, yet only a small number of attendees actively engage online.
And the exhibit halls for these online meetings? With neither free coffee nor company-branded tchotchkes, I expect that they have virtual tumbleweeds blowing through and crickets chirping.
Even still, the virtual meeting experience, while inferior to the live one, is a tremendous advance. It should never be banished as a historical footnote but rather should remain an option. It’s analogous to watching the Super Bowl at home: Obviously, it’s not the same as being there, but it’s a terrific alternative. Like telemedicine, this pandemic has provided a critical proof of concept that there is a better model.
Reshaping the medical meeting
Let’s consider five reasons why medical meetings should be permanently reshaped by this pandemic.
This pandemic isn’t going away in 2020. While nearly every country has done a far better job than the United States of containing COVID-19 thus far, outbreaks remain a problem wherever crowds assemble. You’d be hard-pressed to devise a setting more conducive to mass spread than a conference of 20,000 attendees from all over the world sitting alongside each other cheek to jowl for 5 days. Worse yet is the thought of them returning home and infecting their patients, families, and friends. What medical society wants to be remembered for creating a COVID-19 superspreader event? Professional medical societies will need to offer this option as the safest alternative moving forward.
Virtual learning still conveys the most important content. Despite the many social benefits of a live meeting, its core purpose is to disseminate new research and current and emerging treatment options. Virtual meetings have proven that this format can effectively deliver the content, and not as a secondary offering but as the sole platform in real time.
Virtual learning levels the playing field. Traveling to attend conferences typically costs thousands of dollars, accounting for the registration fees, inflated hotel rates, ground transportation, and meals out for days on end. Most meetings also demand several days away from our work and families, forcing many of us to work extra in the days before we leave and upon our return. Parents and those with commitments at home also face special challenges. For international participants, the financial and time costs are even greater. A virtual meeting helps overcome these hurdles and erases barriers that have long precluded many from attending a conference.
Virtual learning is efficient and comfortable. Virtual meetings over the past 6 months have given us a glimpse of an astonishingly more efficient form. If the content seems of a lower magnitude without the fanfare of a live conference, it is in part because so much of a live meeting is spent walking a mile between session rooms, waiting in concession or taxi lines, sitting in traffic between venues, or simply waiting for a session to begin. All of that has been replaced with time that you can use productively in between video sessions viewed either live or on demand. And with a virtual meeting, you can comfortably watch the sessions. There’s no need to stand along the back wall of an overcrowded room or step over 10 people to squeeze into an open middle seat. You can be focused, rather than having an end-of-day presentation wash over you as your eyes cross because you’ve been running around for the past 12 hours.
Virtual learning and social media will only improve. While virtual meetings unquestionably have limitations, it’s important to acknowledge that the successes thus far still represent only the earliest forays into this endeavor. In-person meetings evolved to their present form over centuries. In contrast, virtual meetings are being cobbled together within a few weeks or months. They can only be expected to improve as presenters adapt their skills to the online audience and new tools improve virtual discussions.
I am not implying that live meetings will or should be replaced by virtual ones. We still need that experience of trainees and experts presenting to a live audience and discussing the results together, all while sharing the energy of the moment. But there should be room for both a live conference and a virtual version.
Practically speaking, it is unclear whether professional societies could forgo the revenue they receive from registration fees, meeting sponsorships, and corporate exhibits. Yet, there are certainly ways to obtain sponsorship revenue for a virtual program. Even if the virtual version of a conference costs far less than attending in person, there is plenty of room between that number and free. It costs remarkably little for a professional society to share its content, and virtual offerings further the mission of distributing this content broadly.
We should not rush to return to the previous status quo. Despite their limitations, virtual meetings have brought a new, higher standard of access and efficiency for sharing important new data and treatment options in medicine.
H. Jack West, MD, associate clinical professor and executive director of employer services at City of Hope Comprehensive Cancer Center in Duarte, Calif., regularly comments on lung cancer for Medscape. West serves as web editor for JAMA Oncology, edits and writes several sections on lung cancer for UpToDate, and leads a wide range of continuing education programs and other educational programs, including hosting the audio podcast West Wind.
This article first appeared on Medscape.com.
Lowering rituximab dose in patients with MS proves safe and effective
“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.
To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.
All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
Study results
All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).
During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).
A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
Validating clinical experience
“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”
Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.
“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”
The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”
The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.
SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.
“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.
To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.
All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
Study results
All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).
During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).
A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
Validating clinical experience
“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”
Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.
“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”
The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”
The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.
SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.
“Given its favorable cost-effectiveness profile, [rituximab] remains a valuable treatment option in the current landscape of MS treatments, even at the reduced dose,” wrote Giulio Disanto, MD, PhD, of the Neurocenter of Southern Switzerland in Lugano, and coauthors. The study was published in Multiple Sclerosis Journal.
To determine the clinical and radiologic effectiveness of deescalating rituximab dosage – along with assessing any adverse outcomes – this observational, single-center study examined 59 patients with MS who had been treated with rituximab at 1,000 mg for at least 1 year before the study began. Roughly 63% (n = 37) of the patients had relapsing remitting MS (RRMS), while the rest (n = 22) had secondary progressive disease (SPD). Their median age was 51, and nearly 75% were women.
All patients underwent neurologic examinations at baseline and then every 3 months for 1 year, with new symptoms, infections, or adverse events being assessed via the Expanded Disability Status Scale (EDSS). They also underwent brain and spinal MRI at baseline and at 12 months while blood samples were taken at baseline and then every 3 months for 1 year, with previous data for both collected when available.
Study results
All 59 patients completed 12-month follow-up, and no relapses occurred in the year after lowering rituximab dosage to 500 mg. No significant differences were observed when comparing EDSS scores at the start of the 1,000-mg dose with the start of the 500-mg dose (Wilcoxon P = .131) as well as from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .284). Analyzing RRMS and SPD patients separately also led to no differences in EDSS scores from the start of the 500-mg dose to the end of follow-up (Wilcoxon P = .531; Wilcoxon P = .408).
During the 1,000-mg treatment period the number of patients who developed at least one new T2 lesion on their brain or spine was 9 and 4, respectively. During the 500-mg period, just one patient developed a new T2 brain lesion and two patients developed new T2 spine lesions. IgG and IgM levels did not change from the start of 500-mg treatment, although total dose of rituximab was inversely associated with IgG concentrations when previous treatment with 1,000 mg was factored in (coefficient, −0.439; P = 0.041).
A total of 33 patients reported at least one adverse event during the 500-mg treatment period, with only three events being classified as serious: one pancreatitis, one coronary stenting, and one neutropenia.
Validating clinical experience
“This randomized trial is an important step,” said Timothy Vollmer, MD, of the Rocky Mountain MS Center in Westminster, Colo., in an interview. “It clearly supports that you can lessen the dose, which will allow us to use this revolutionary drug for a longer period of time in patients.”
Dr. Vollmer noted that, at his center, they have been using 500 mg of rituximab over a 6-month period since 2010 without a formal clinical trial and with no notable difference in adverse outcomes on MRIs or disability scales. “This validates what we’ve been doing, which we appreciate,” he said.
“The next thing you have to do is determine whether you really have to give it every 6 months,” he added, “because the treatment effect in most patients will last, in terms of B-cell depletion, about a year or more. What we should be testing next is giving the 500 mg and waiting until patients begin to recover B cells before we give them the next cycle, to see if that helps decrease the major side effect, which is a drop in IgG levels.”
The authors acknowledged their study’s limitations, including a moderate sample size, a short follow-up period after 500-mg dosage, and an inability to confirm consistency among 1,000-mg dose administration among all patients, which “may well influence efficacy and safety measures.”
The study was supported by the Neurocenter of Southern Switzerland. One author declared numerous potential conflicts of interest, including receiving speaker fees, research fees, and travel support, and serving on advisory boards for various foundations, universities, and pharmaceutical companies.
SOURCE: Disanto G et al. Mult Scler J. 2020 Aug 25. doi: 10.1177/1352458520952036.
FROM MULTIPLE SCLEROSIS JOURNAL
Tools emerging to predict liver failure in cirrhosis
Systemic inflammation and portal hypertension are key predictors of acute-on-chronic liver failure (ACLF) in the 3 months after a hospital stay for acute decompensated cirrhosis and also of death after 12 months, a preliminary analysis of data from the PREDICT study shows.
“Before this, we never had any patient signatures to identify ACLF,” said Jonel Trebicka, MD, PhD, from the JW Goethe University Hospital in Frankfurt, Germany.
Now, Dr. Trebicka’s team has “characterized the phenotypes in pre-ACLF that will progress within 3 months,” he said in an interview. “Those with high levels of inflammatory proteins, white blood cell count, are more likely to develop ACLF.”
ACLF is a highly complex disorder that can lead liver, cardiovascular, renal, cerebral, pulmonary, intestinal, adrenal, and immune systems to fail, Dr. Trebicka explained when he discussed the analysis – published online in the Journal of Hepatology – during the virtual International Liver Congress (ILC) 2020.
The chance of survival after the onset of ACLF is low – the 28-day survival rate is 30% – and “the only treatment we have is liver transplant,” he said.
For their prospective observational study, Dr. Trebicka and his colleagues assessed 1071 participants from 48 European hospitals in 14 countries who were admitted for an episode of acute decompensation, defined as the development of ascites, hepatic encephalopathy, gastrointestinal hemorrhage, infection, or a combination thereof.
The researchers identified three distinct clinical courses for a patient hospitalized with acute decompensated cirrhosis that will help clinicians predict the development of ACLF.
At study enrollment, more than half of the patients at highest risk for ACLF had pre-ACLF and high-grade systemic inflammation. The patients at intermediate risk had unstable decompensated cirrhosis with low-grade systemic inflammation and complications related to severe portal hypertension. And those at lowest risk for ACLF had stable decompensated cirrhosis and no severe systemic inflammation or portal hypertension complications, and did not develop ACLF or another episode of acute decompensation in the subsequent 3 months.
“There have been hints of possible phenotypes before – for stable and unstable ACLF – but we never had anything specific to diagnose,” Trebicka reported.
“We found that there are two main mechanisms in the development of ACLF that are most important,” he said. The first is systemic inflammation with high levels of proteins, which “leads to organ failure. This is the most striking acute mechanism.”
The second is the development of portal hypertension. “This is slower, but also very important, causing increased pressure in the portal vein, and leading to bleeding if the pressure is too great,” he said.
More tools emerging to help predict ACLF
The Albumin-functionality-test (AFT), which uses serum albumin levels to evaluate liver and kidney function, might also be useful in the prediction of ACLF and 12-month survival, according to a separate study an Italian group presented at the virtual ILC.
“Our main results are that parameters from albumin predict the development of ACLF in acute decompensated patients with the same diagnostic performance as the CLIF-AD score,” said Katja Waterstradt, PhD, from the University of Bologna in Italy.
And when the two tests are combined, diagnostic performance is increased, she added.
Dr. Trebicka has disclosed no relevant financial relationships. Dr. Waterstrand is a researcher for MedInnovation GmbH.
This article first appeared on Medscape.com.
Systemic inflammation and portal hypertension are key predictors of acute-on-chronic liver failure (ACLF) in the 3 months after a hospital stay for acute decompensated cirrhosis and also of death after 12 months, a preliminary analysis of data from the PREDICT study shows.
“Before this, we never had any patient signatures to identify ACLF,” said Jonel Trebicka, MD, PhD, from the JW Goethe University Hospital in Frankfurt, Germany.
Now, Dr. Trebicka’s team has “characterized the phenotypes in pre-ACLF that will progress within 3 months,” he said in an interview. “Those with high levels of inflammatory proteins, white blood cell count, are more likely to develop ACLF.”
ACLF is a highly complex disorder that can lead liver, cardiovascular, renal, cerebral, pulmonary, intestinal, adrenal, and immune systems to fail, Dr. Trebicka explained when he discussed the analysis – published online in the Journal of Hepatology – during the virtual International Liver Congress (ILC) 2020.
The chance of survival after the onset of ACLF is low – the 28-day survival rate is 30% – and “the only treatment we have is liver transplant,” he said.
For their prospective observational study, Dr. Trebicka and his colleagues assessed 1071 participants from 48 European hospitals in 14 countries who were admitted for an episode of acute decompensation, defined as the development of ascites, hepatic encephalopathy, gastrointestinal hemorrhage, infection, or a combination thereof.
The researchers identified three distinct clinical courses for a patient hospitalized with acute decompensated cirrhosis that will help clinicians predict the development of ACLF.
At study enrollment, more than half of the patients at highest risk for ACLF had pre-ACLF and high-grade systemic inflammation. The patients at intermediate risk had unstable decompensated cirrhosis with low-grade systemic inflammation and complications related to severe portal hypertension. And those at lowest risk for ACLF had stable decompensated cirrhosis and no severe systemic inflammation or portal hypertension complications, and did not develop ACLF or another episode of acute decompensation in the subsequent 3 months.
“There have been hints of possible phenotypes before – for stable and unstable ACLF – but we never had anything specific to diagnose,” Trebicka reported.
“We found that there are two main mechanisms in the development of ACLF that are most important,” he said. The first is systemic inflammation with high levels of proteins, which “leads to organ failure. This is the most striking acute mechanism.”
The second is the development of portal hypertension. “This is slower, but also very important, causing increased pressure in the portal vein, and leading to bleeding if the pressure is too great,” he said.
More tools emerging to help predict ACLF
The Albumin-functionality-test (AFT), which uses serum albumin levels to evaluate liver and kidney function, might also be useful in the prediction of ACLF and 12-month survival, according to a separate study an Italian group presented at the virtual ILC.
“Our main results are that parameters from albumin predict the development of ACLF in acute decompensated patients with the same diagnostic performance as the CLIF-AD score,” said Katja Waterstradt, PhD, from the University of Bologna in Italy.
And when the two tests are combined, diagnostic performance is increased, she added.
Dr. Trebicka has disclosed no relevant financial relationships. Dr. Waterstrand is a researcher for MedInnovation GmbH.
This article first appeared on Medscape.com.
Systemic inflammation and portal hypertension are key predictors of acute-on-chronic liver failure (ACLF) in the 3 months after a hospital stay for acute decompensated cirrhosis and also of death after 12 months, a preliminary analysis of data from the PREDICT study shows.
“Before this, we never had any patient signatures to identify ACLF,” said Jonel Trebicka, MD, PhD, from the JW Goethe University Hospital in Frankfurt, Germany.
Now, Dr. Trebicka’s team has “characterized the phenotypes in pre-ACLF that will progress within 3 months,” he said in an interview. “Those with high levels of inflammatory proteins, white blood cell count, are more likely to develop ACLF.”
ACLF is a highly complex disorder that can lead liver, cardiovascular, renal, cerebral, pulmonary, intestinal, adrenal, and immune systems to fail, Dr. Trebicka explained when he discussed the analysis – published online in the Journal of Hepatology – during the virtual International Liver Congress (ILC) 2020.
The chance of survival after the onset of ACLF is low – the 28-day survival rate is 30% – and “the only treatment we have is liver transplant,” he said.
For their prospective observational study, Dr. Trebicka and his colleagues assessed 1071 participants from 48 European hospitals in 14 countries who were admitted for an episode of acute decompensation, defined as the development of ascites, hepatic encephalopathy, gastrointestinal hemorrhage, infection, or a combination thereof.
The researchers identified three distinct clinical courses for a patient hospitalized with acute decompensated cirrhosis that will help clinicians predict the development of ACLF.
At study enrollment, more than half of the patients at highest risk for ACLF had pre-ACLF and high-grade systemic inflammation. The patients at intermediate risk had unstable decompensated cirrhosis with low-grade systemic inflammation and complications related to severe portal hypertension. And those at lowest risk for ACLF had stable decompensated cirrhosis and no severe systemic inflammation or portal hypertension complications, and did not develop ACLF or another episode of acute decompensation in the subsequent 3 months.
“There have been hints of possible phenotypes before – for stable and unstable ACLF – but we never had anything specific to diagnose,” Trebicka reported.
“We found that there are two main mechanisms in the development of ACLF that are most important,” he said. The first is systemic inflammation with high levels of proteins, which “leads to organ failure. This is the most striking acute mechanism.”
The second is the development of portal hypertension. “This is slower, but also very important, causing increased pressure in the portal vein, and leading to bleeding if the pressure is too great,” he said.
More tools emerging to help predict ACLF
The Albumin-functionality-test (AFT), which uses serum albumin levels to evaluate liver and kidney function, might also be useful in the prediction of ACLF and 12-month survival, according to a separate study an Italian group presented at the virtual ILC.
“Our main results are that parameters from albumin predict the development of ACLF in acute decompensated patients with the same diagnostic performance as the CLIF-AD score,” said Katja Waterstradt, PhD, from the University of Bologna in Italy.
And when the two tests are combined, diagnostic performance is increased, she added.
Dr. Trebicka has disclosed no relevant financial relationships. Dr. Waterstrand is a researcher for MedInnovation GmbH.
This article first appeared on Medscape.com.
Vascepa maker loses patent appeal, plans ‘vigorous’ fight
Amarin’s hopes of fending off generic competition for its blockbuster high-strength eicosapentaenoic acid product, icosapent ethyl (Vascepa), have dimmed following a decision by the U.S. Court of Appeals for the Federal Circuit in the company’s ongoing patent litigation.
The court upheld the March ruling by the District Court for the District of Nevada in favor of two generic companies in connection with their abbreviated new drug applications (ANDAs) for the product.
Amarin said it is currently reviewing its legal options and within 30 days expects to file a petition for an en banc review of the current decision by the full panel of 12 active judges at the Court of Appeals for the Federal Circuit.
“We are extremely disappointed with [the] ruling and plan to vigorously pursue available remedies,” John Thero, Amarin president and chief executive officer, said in a statement.
In 2012, Vascepa became the first and only prescription treatment approved by the Food and Drug Administration made up solely of the active ingredient icosapent ethyl, a unique form of eicosapentaenoic acid. It was initially approved for the reduction of very high triglyceride levels (≥500 mg/dL).
In late 2019, the FDA extended the indication to reduce the risk for cardiovascular events in people with elevated triglyceride levels and either established CV disease or diabetes with other CV risk factors.
The extended indication was based on results of the landmark REDUCE-IT trial, which showed a 25% relative risk reduction in major adverse CV events with icosapent ethyl, compared with placebo, in patients with triglyceride levels above 135 mg/dL and who had CV disease (70% of the study population), or who were high-risk primary-prevention patients with diabetes and one additional risk factor (30% of the study population).
According to Amarin, since its launch, Vascepa has been prescribed more than 8 million times.
The company said demand for the product in the United States remains “strong” and indicated that, despite the legal setback, it would continue promotional efforts. The company is also seeking additional regulatory approvals in China, Europe, and additional countries in the Middle East.
“We are particularly excited about the anticipated commercialization opportunities for Vascepa in Europe as we prepare for expected approval and launch in early 2021,” Mr. Thero said.
The company anticipates 10 years of market protection because of regulatory exclusivity in the European Union once approved, and said patent protection could extend into 2039.
Only Vascepa sold in the United States is subject to this litigation and judgment. No generic litigation is pending outside the United States, Amarin said.
A version of this article originally appeared on Medscape.com.
Amarin’s hopes of fending off generic competition for its blockbuster high-strength eicosapentaenoic acid product, icosapent ethyl (Vascepa), have dimmed following a decision by the U.S. Court of Appeals for the Federal Circuit in the company’s ongoing patent litigation.
The court upheld the March ruling by the District Court for the District of Nevada in favor of two generic companies in connection with their abbreviated new drug applications (ANDAs) for the product.
Amarin said it is currently reviewing its legal options and within 30 days expects to file a petition for an en banc review of the current decision by the full panel of 12 active judges at the Court of Appeals for the Federal Circuit.
“We are extremely disappointed with [the] ruling and plan to vigorously pursue available remedies,” John Thero, Amarin president and chief executive officer, said in a statement.
In 2012, Vascepa became the first and only prescription treatment approved by the Food and Drug Administration made up solely of the active ingredient icosapent ethyl, a unique form of eicosapentaenoic acid. It was initially approved for the reduction of very high triglyceride levels (≥500 mg/dL).
In late 2019, the FDA extended the indication to reduce the risk for cardiovascular events in people with elevated triglyceride levels and either established CV disease or diabetes with other CV risk factors.
The extended indication was based on results of the landmark REDUCE-IT trial, which showed a 25% relative risk reduction in major adverse CV events with icosapent ethyl, compared with placebo, in patients with triglyceride levels above 135 mg/dL and who had CV disease (70% of the study population), or who were high-risk primary-prevention patients with diabetes and one additional risk factor (30% of the study population).
According to Amarin, since its launch, Vascepa has been prescribed more than 8 million times.
The company said demand for the product in the United States remains “strong” and indicated that, despite the legal setback, it would continue promotional efforts. The company is also seeking additional regulatory approvals in China, Europe, and additional countries in the Middle East.
“We are particularly excited about the anticipated commercialization opportunities for Vascepa in Europe as we prepare for expected approval and launch in early 2021,” Mr. Thero said.
The company anticipates 10 years of market protection because of regulatory exclusivity in the European Union once approved, and said patent protection could extend into 2039.
Only Vascepa sold in the United States is subject to this litigation and judgment. No generic litigation is pending outside the United States, Amarin said.
A version of this article originally appeared on Medscape.com.
Amarin’s hopes of fending off generic competition for its blockbuster high-strength eicosapentaenoic acid product, icosapent ethyl (Vascepa), have dimmed following a decision by the U.S. Court of Appeals for the Federal Circuit in the company’s ongoing patent litigation.
The court upheld the March ruling by the District Court for the District of Nevada in favor of two generic companies in connection with their abbreviated new drug applications (ANDAs) for the product.
Amarin said it is currently reviewing its legal options and within 30 days expects to file a petition for an en banc review of the current decision by the full panel of 12 active judges at the Court of Appeals for the Federal Circuit.
“We are extremely disappointed with [the] ruling and plan to vigorously pursue available remedies,” John Thero, Amarin president and chief executive officer, said in a statement.
In 2012, Vascepa became the first and only prescription treatment approved by the Food and Drug Administration made up solely of the active ingredient icosapent ethyl, a unique form of eicosapentaenoic acid. It was initially approved for the reduction of very high triglyceride levels (≥500 mg/dL).
In late 2019, the FDA extended the indication to reduce the risk for cardiovascular events in people with elevated triglyceride levels and either established CV disease or diabetes with other CV risk factors.
The extended indication was based on results of the landmark REDUCE-IT trial, which showed a 25% relative risk reduction in major adverse CV events with icosapent ethyl, compared with placebo, in patients with triglyceride levels above 135 mg/dL and who had CV disease (70% of the study population), or who were high-risk primary-prevention patients with diabetes and one additional risk factor (30% of the study population).
According to Amarin, since its launch, Vascepa has been prescribed more than 8 million times.
The company said demand for the product in the United States remains “strong” and indicated that, despite the legal setback, it would continue promotional efforts. The company is also seeking additional regulatory approvals in China, Europe, and additional countries in the Middle East.
“We are particularly excited about the anticipated commercialization opportunities for Vascepa in Europe as we prepare for expected approval and launch in early 2021,” Mr. Thero said.
The company anticipates 10 years of market protection because of regulatory exclusivity in the European Union once approved, and said patent protection could extend into 2039.
Only Vascepa sold in the United States is subject to this litigation and judgment. No generic litigation is pending outside the United States, Amarin said.
A version of this article originally appeared on Medscape.com.
First U.S. trial to test aerosolized chemotherapy in advanced cancers
A team of U.S. researchers is investigating whether pressurized intraperitoneal aerosolized chemotherapy (PIPAC) can benefit patients with advanced cancer and peritoneal carcinomatosis.
The team’s phase 1 trial is the first in the United States to test PIPAC, and it will enroll patients with ovarian, uterine, colorectal, or gastric cancer who have peritoneal carcinomatosis.
Data from studies outside the United States suggest PIPAC can induce regression of peritoneal carcinomatosis, even in end-stage, therapy-resistant gastric, ovarian, and colorectal cancers (Lancet Oncol. 2019 Jul;20[7]:e368-e377).
The current study (NCT04329494) formally introduces PIPAC to the United States and serves as a launching pad for further investigation into how the treatment should be administered and which types of chemotherapies can be used.
About PIPAC
“PIPAC is a novel therapeutic approach that is minimally invasive, does not require cytoreduction, and can be repeated frequently,” said Thanh Dellinger, MD, a gynecologic oncology surgeon at City of Hope in Duarte, Calif., and co–principal investigator of the phase 1 trial.
“[PIPAC] entails accessing the abdominal cavity using standard laparoscopic techniques and relies on the increased intra-abdominal pressure (15 mm Hg) achieved with laparoscopic surgery, which generates a convective flux that forces aerosolized chemotherapy drugs from the peritoneal cavity into the subperitoneal tissue and overcomes the tumor’s interstitial pressure,” Dr. Dellinger explained in an interview.
“The surgical procedure to deliver PIPAC does not typically cause adhesive disease and allows for repeated delivery of intraperitoneal chemotherapy, objective tumor staging, and response assessment,” she noted.
Dr. Dellinger said the advantages of PIPAC include a minimally invasive approach; no debulking surgery required; deeper uptake of drugs in tumor tissues; wider, more effective drug distribution; fewer toxicities caused by lower drug dosage; repeatable administration; and palliation of peritoneal carcinomatosis symptoms, including abdominal bloating and ascites.
PIPAC achieves a deeper peritoneal nodule penetration of several millimeters with cisplatin, compared to less than 1 mm with heated intraoperative peritoneal chemotherapy (HIPEC) and other intraperitoneal methods, according to Amit Merchea, MD, an assistant professor of surgery at the Mayo Clinic in Jacksonville, Fla.
Dr. Merchea performed the first PIPAC procedure in the United States in December 2019.
Innovative therapies needed
Peritoneal carcinomatosis is often a late-stage manifestation of abdominal cancers and is usually lethal, Dr. Dellinger said. She noted that systemic chemotherapy in the palliative setting is relatively ineffective in patients with peritoneal carcinomatosis because of pharmacokinetic limitations, poor peritoneal drug uptake, and impaired local drug distribution.
“Innovative, effective therapies are urgently needed for people who have ovarian, uterine, gastric, or colorectal cancer with peritoneal carcinomatosis,” Dr. Dellinger said.
“PIPAC is a novel treatment option that has had very favorable and exciting results,” Dr. Merchea said. “It is a potential option for patients when no other treatment options exist, and it is an avenue to provide hope to patients when often they have none.”
Potential candidates for PIPAC include patients who have peritoneal carcinomatosis, have failed other standard therapies, have more than 6 months’ life expectancy, and are not candidates for cytoreduction with HIPEC. There remains very limited data on the use of PIPAC as a neoadjuvant approach to convert patients who were previously unresectable to resectable disease, Dr. Merchea noted.
“To deliver chemotherapy directly to the tumor under pressure allows PIPAC to better penetrate the peritoneal surface and tumor nodules than traditional approaches, such as HIPEC,” Dr. Merchea said. “And the drug distribution at the tissue level is better than what is often achieved by systemic chemotherapy, but without the systemic effects of chemotherapy, such as hair loss. The treatment gives essentially a real-time, quantitative assessment of response by being able to directly assess the tumor via laparoscopic visualization and repeat biopsy.”
“Importantly, patients who undergo PIPAC don’t notice a decrease in their quality of life, and some patients note improvement, particularly with respect to nausea, vomiting, appetite, fatigue, and constipation,” Dr. Merchea said.
Trial details
The phase 1 trial of PIPAC will include a maximum of 24 patients. They will receive treatment every 6 weeks for up to three cycles and be followed for up to 3 years.
Patients with ovarian, uterine, or gastric cancer will undergo PIPAC with cisplatin, followed by doxorubicin. Patients with colorectal cancer will undergo PIPAC with oxaliplatin preceded by leucovorin and fluorouracil for cycles 2 and 3.
The researchers also plan to profile patients’ tumors.
“Tumor samples will be chronologically evaluated with genomics, spatial transcriptomics, pharmacodynamics, and single-cell sequencing throughout a patient’s treatment course, thus elucidating the treatment effects and natural history of peritoneal cancers,” Dr. Dellinger said.
The trial sites include City of Hope, Mayo Clinic in Florida, Northwell Health in New York, and the National Cancer Institute in Maryland.
The trial is sponsored by City of Hope in collaboration with the National Cancer Institute. Dr. Merchea and Dr. Dellinger reported having no conflicts of interest.
A team of U.S. researchers is investigating whether pressurized intraperitoneal aerosolized chemotherapy (PIPAC) can benefit patients with advanced cancer and peritoneal carcinomatosis.
The team’s phase 1 trial is the first in the United States to test PIPAC, and it will enroll patients with ovarian, uterine, colorectal, or gastric cancer who have peritoneal carcinomatosis.
Data from studies outside the United States suggest PIPAC can induce regression of peritoneal carcinomatosis, even in end-stage, therapy-resistant gastric, ovarian, and colorectal cancers (Lancet Oncol. 2019 Jul;20[7]:e368-e377).
The current study (NCT04329494) formally introduces PIPAC to the United States and serves as a launching pad for further investigation into how the treatment should be administered and which types of chemotherapies can be used.
About PIPAC
“PIPAC is a novel therapeutic approach that is minimally invasive, does not require cytoreduction, and can be repeated frequently,” said Thanh Dellinger, MD, a gynecologic oncology surgeon at City of Hope in Duarte, Calif., and co–principal investigator of the phase 1 trial.
“[PIPAC] entails accessing the abdominal cavity using standard laparoscopic techniques and relies on the increased intra-abdominal pressure (15 mm Hg) achieved with laparoscopic surgery, which generates a convective flux that forces aerosolized chemotherapy drugs from the peritoneal cavity into the subperitoneal tissue and overcomes the tumor’s interstitial pressure,” Dr. Dellinger explained in an interview.
“The surgical procedure to deliver PIPAC does not typically cause adhesive disease and allows for repeated delivery of intraperitoneal chemotherapy, objective tumor staging, and response assessment,” she noted.
Dr. Dellinger said the advantages of PIPAC include a minimally invasive approach; no debulking surgery required; deeper uptake of drugs in tumor tissues; wider, more effective drug distribution; fewer toxicities caused by lower drug dosage; repeatable administration; and palliation of peritoneal carcinomatosis symptoms, including abdominal bloating and ascites.
PIPAC achieves a deeper peritoneal nodule penetration of several millimeters with cisplatin, compared to less than 1 mm with heated intraoperative peritoneal chemotherapy (HIPEC) and other intraperitoneal methods, according to Amit Merchea, MD, an assistant professor of surgery at the Mayo Clinic in Jacksonville, Fla.
Dr. Merchea performed the first PIPAC procedure in the United States in December 2019.
Innovative therapies needed
Peritoneal carcinomatosis is often a late-stage manifestation of abdominal cancers and is usually lethal, Dr. Dellinger said. She noted that systemic chemotherapy in the palliative setting is relatively ineffective in patients with peritoneal carcinomatosis because of pharmacokinetic limitations, poor peritoneal drug uptake, and impaired local drug distribution.
“Innovative, effective therapies are urgently needed for people who have ovarian, uterine, gastric, or colorectal cancer with peritoneal carcinomatosis,” Dr. Dellinger said.
“PIPAC is a novel treatment option that has had very favorable and exciting results,” Dr. Merchea said. “It is a potential option for patients when no other treatment options exist, and it is an avenue to provide hope to patients when often they have none.”
Potential candidates for PIPAC include patients who have peritoneal carcinomatosis, have failed other standard therapies, have more than 6 months’ life expectancy, and are not candidates for cytoreduction with HIPEC. There remains very limited data on the use of PIPAC as a neoadjuvant approach to convert patients who were previously unresectable to resectable disease, Dr. Merchea noted.
“To deliver chemotherapy directly to the tumor under pressure allows PIPAC to better penetrate the peritoneal surface and tumor nodules than traditional approaches, such as HIPEC,” Dr. Merchea said. “And the drug distribution at the tissue level is better than what is often achieved by systemic chemotherapy, but without the systemic effects of chemotherapy, such as hair loss. The treatment gives essentially a real-time, quantitative assessment of response by being able to directly assess the tumor via laparoscopic visualization and repeat biopsy.”
“Importantly, patients who undergo PIPAC don’t notice a decrease in their quality of life, and some patients note improvement, particularly with respect to nausea, vomiting, appetite, fatigue, and constipation,” Dr. Merchea said.
Trial details
The phase 1 trial of PIPAC will include a maximum of 24 patients. They will receive treatment every 6 weeks for up to three cycles and be followed for up to 3 years.
Patients with ovarian, uterine, or gastric cancer will undergo PIPAC with cisplatin, followed by doxorubicin. Patients with colorectal cancer will undergo PIPAC with oxaliplatin preceded by leucovorin and fluorouracil for cycles 2 and 3.
The researchers also plan to profile patients’ tumors.
“Tumor samples will be chronologically evaluated with genomics, spatial transcriptomics, pharmacodynamics, and single-cell sequencing throughout a patient’s treatment course, thus elucidating the treatment effects and natural history of peritoneal cancers,” Dr. Dellinger said.
The trial sites include City of Hope, Mayo Clinic in Florida, Northwell Health in New York, and the National Cancer Institute in Maryland.
The trial is sponsored by City of Hope in collaboration with the National Cancer Institute. Dr. Merchea and Dr. Dellinger reported having no conflicts of interest.
A team of U.S. researchers is investigating whether pressurized intraperitoneal aerosolized chemotherapy (PIPAC) can benefit patients with advanced cancer and peritoneal carcinomatosis.
The team’s phase 1 trial is the first in the United States to test PIPAC, and it will enroll patients with ovarian, uterine, colorectal, or gastric cancer who have peritoneal carcinomatosis.
Data from studies outside the United States suggest PIPAC can induce regression of peritoneal carcinomatosis, even in end-stage, therapy-resistant gastric, ovarian, and colorectal cancers (Lancet Oncol. 2019 Jul;20[7]:e368-e377).
The current study (NCT04329494) formally introduces PIPAC to the United States and serves as a launching pad for further investigation into how the treatment should be administered and which types of chemotherapies can be used.
About PIPAC
“PIPAC is a novel therapeutic approach that is minimally invasive, does not require cytoreduction, and can be repeated frequently,” said Thanh Dellinger, MD, a gynecologic oncology surgeon at City of Hope in Duarte, Calif., and co–principal investigator of the phase 1 trial.
“[PIPAC] entails accessing the abdominal cavity using standard laparoscopic techniques and relies on the increased intra-abdominal pressure (15 mm Hg) achieved with laparoscopic surgery, which generates a convective flux that forces aerosolized chemotherapy drugs from the peritoneal cavity into the subperitoneal tissue and overcomes the tumor’s interstitial pressure,” Dr. Dellinger explained in an interview.
“The surgical procedure to deliver PIPAC does not typically cause adhesive disease and allows for repeated delivery of intraperitoneal chemotherapy, objective tumor staging, and response assessment,” she noted.
Dr. Dellinger said the advantages of PIPAC include a minimally invasive approach; no debulking surgery required; deeper uptake of drugs in tumor tissues; wider, more effective drug distribution; fewer toxicities caused by lower drug dosage; repeatable administration; and palliation of peritoneal carcinomatosis symptoms, including abdominal bloating and ascites.
PIPAC achieves a deeper peritoneal nodule penetration of several millimeters with cisplatin, compared to less than 1 mm with heated intraoperative peritoneal chemotherapy (HIPEC) and other intraperitoneal methods, according to Amit Merchea, MD, an assistant professor of surgery at the Mayo Clinic in Jacksonville, Fla.
Dr. Merchea performed the first PIPAC procedure in the United States in December 2019.
Innovative therapies needed
Peritoneal carcinomatosis is often a late-stage manifestation of abdominal cancers and is usually lethal, Dr. Dellinger said. She noted that systemic chemotherapy in the palliative setting is relatively ineffective in patients with peritoneal carcinomatosis because of pharmacokinetic limitations, poor peritoneal drug uptake, and impaired local drug distribution.
“Innovative, effective therapies are urgently needed for people who have ovarian, uterine, gastric, or colorectal cancer with peritoneal carcinomatosis,” Dr. Dellinger said.
“PIPAC is a novel treatment option that has had very favorable and exciting results,” Dr. Merchea said. “It is a potential option for patients when no other treatment options exist, and it is an avenue to provide hope to patients when often they have none.”
Potential candidates for PIPAC include patients who have peritoneal carcinomatosis, have failed other standard therapies, have more than 6 months’ life expectancy, and are not candidates for cytoreduction with HIPEC. There remains very limited data on the use of PIPAC as a neoadjuvant approach to convert patients who were previously unresectable to resectable disease, Dr. Merchea noted.
“To deliver chemotherapy directly to the tumor under pressure allows PIPAC to better penetrate the peritoneal surface and tumor nodules than traditional approaches, such as HIPEC,” Dr. Merchea said. “And the drug distribution at the tissue level is better than what is often achieved by systemic chemotherapy, but without the systemic effects of chemotherapy, such as hair loss. The treatment gives essentially a real-time, quantitative assessment of response by being able to directly assess the tumor via laparoscopic visualization and repeat biopsy.”
“Importantly, patients who undergo PIPAC don’t notice a decrease in their quality of life, and some patients note improvement, particularly with respect to nausea, vomiting, appetite, fatigue, and constipation,” Dr. Merchea said.
Trial details
The phase 1 trial of PIPAC will include a maximum of 24 patients. They will receive treatment every 6 weeks for up to three cycles and be followed for up to 3 years.
Patients with ovarian, uterine, or gastric cancer will undergo PIPAC with cisplatin, followed by doxorubicin. Patients with colorectal cancer will undergo PIPAC with oxaliplatin preceded by leucovorin and fluorouracil for cycles 2 and 3.
The researchers also plan to profile patients’ tumors.
“Tumor samples will be chronologically evaluated with genomics, spatial transcriptomics, pharmacodynamics, and single-cell sequencing throughout a patient’s treatment course, thus elucidating the treatment effects and natural history of peritoneal cancers,” Dr. Dellinger said.
The trial sites include City of Hope, Mayo Clinic in Florida, Northwell Health in New York, and the National Cancer Institute in Maryland.
The trial is sponsored by City of Hope in collaboration with the National Cancer Institute. Dr. Merchea and Dr. Dellinger reported having no conflicts of interest.
Oxidative stress linked to cytogenetic abnormalities in CLL
Oxidative stress may play a role in pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL), according to the results of a biochemical and cytogenetic study of patients published online in Experimental and Molecular Pathology.
The study evaluated the serum levels of oxidative stress biomarkers [conjugated dienes (CD), malondialdehyde (MDA), and nitrite levels] and the levels of antioxidant biomarkers [ceruloplasmin (CP) and glutathione peroxidase (GPx)] in 64 B-CLL patients. The relationship between these biomarkers and the presence of cytogenetic abnormalities was examined, according to Tatiana Zhevak, MD, of Sechenov First Moscow (Russia) State Medical University, and colleagues.
Cytogenetic abnormalities have previously been determined to be linked to a poorer prognosis in CLL patients, and factors that increase the frequency of CA have been shown to increase the risk of rapid tumor progression, Dr. Zhevak and her colleagues stated.
Oxidative stress connection
Enhanced oxidative stress was detected in B-CLL patients as shown by their increased levels of serum CD, MDA, and nitrite, as well as a demonstrated imbalance in the antioxidant defense system as shown by an increased serum CP level and decreased serum GPx activity, according to the researchers.
In addition, these metabolic changes were found to be greater in those patients whose lymphocytes harbored specific cytogenetic abnormalities, and could be predicted by the serum levels of CD. Specifically, the odds of harboring a cytogenetic abnormality increased by a factor of 1.88 (P = .004) for every one-unit increase in serum CD level (mcmol/L), according to the authors.
“Collectively, the results support our hypothesis that oxidative stress and resulting lipid peroxidation play a role in pathogenesis of B-CLL and provide a rational basis for the use of agents regulating the pro-oxidant and antioxidant activity in the treatment of B-CLL patients,” the researchers concluded.
The research was unsponsored and the authors reported having no conflicts.
SOURCE: Zhevak T et al. Exp Mol Patholo. 2020 Oct;16:104524 doi: 10.1016/j.yexmp.2020.104524.
Oxidative stress may play a role in pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL), according to the results of a biochemical and cytogenetic study of patients published online in Experimental and Molecular Pathology.
The study evaluated the serum levels of oxidative stress biomarkers [conjugated dienes (CD), malondialdehyde (MDA), and nitrite levels] and the levels of antioxidant biomarkers [ceruloplasmin (CP) and glutathione peroxidase (GPx)] in 64 B-CLL patients. The relationship between these biomarkers and the presence of cytogenetic abnormalities was examined, according to Tatiana Zhevak, MD, of Sechenov First Moscow (Russia) State Medical University, and colleagues.
Cytogenetic abnormalities have previously been determined to be linked to a poorer prognosis in CLL patients, and factors that increase the frequency of CA have been shown to increase the risk of rapid tumor progression, Dr. Zhevak and her colleagues stated.
Oxidative stress connection
Enhanced oxidative stress was detected in B-CLL patients as shown by their increased levels of serum CD, MDA, and nitrite, as well as a demonstrated imbalance in the antioxidant defense system as shown by an increased serum CP level and decreased serum GPx activity, according to the researchers.
In addition, these metabolic changes were found to be greater in those patients whose lymphocytes harbored specific cytogenetic abnormalities, and could be predicted by the serum levels of CD. Specifically, the odds of harboring a cytogenetic abnormality increased by a factor of 1.88 (P = .004) for every one-unit increase in serum CD level (mcmol/L), according to the authors.
“Collectively, the results support our hypothesis that oxidative stress and resulting lipid peroxidation play a role in pathogenesis of B-CLL and provide a rational basis for the use of agents regulating the pro-oxidant and antioxidant activity in the treatment of B-CLL patients,” the researchers concluded.
The research was unsponsored and the authors reported having no conflicts.
SOURCE: Zhevak T et al. Exp Mol Patholo. 2020 Oct;16:104524 doi: 10.1016/j.yexmp.2020.104524.
Oxidative stress may play a role in pathogenesis of B-cell chronic lymphocytic leukemia (B-CLL), according to the results of a biochemical and cytogenetic study of patients published online in Experimental and Molecular Pathology.
The study evaluated the serum levels of oxidative stress biomarkers [conjugated dienes (CD), malondialdehyde (MDA), and nitrite levels] and the levels of antioxidant biomarkers [ceruloplasmin (CP) and glutathione peroxidase (GPx)] in 64 B-CLL patients. The relationship between these biomarkers and the presence of cytogenetic abnormalities was examined, according to Tatiana Zhevak, MD, of Sechenov First Moscow (Russia) State Medical University, and colleagues.
Cytogenetic abnormalities have previously been determined to be linked to a poorer prognosis in CLL patients, and factors that increase the frequency of CA have been shown to increase the risk of rapid tumor progression, Dr. Zhevak and her colleagues stated.
Oxidative stress connection
Enhanced oxidative stress was detected in B-CLL patients as shown by their increased levels of serum CD, MDA, and nitrite, as well as a demonstrated imbalance in the antioxidant defense system as shown by an increased serum CP level and decreased serum GPx activity, according to the researchers.
In addition, these metabolic changes were found to be greater in those patients whose lymphocytes harbored specific cytogenetic abnormalities, and could be predicted by the serum levels of CD. Specifically, the odds of harboring a cytogenetic abnormality increased by a factor of 1.88 (P = .004) for every one-unit increase in serum CD level (mcmol/L), according to the authors.
“Collectively, the results support our hypothesis that oxidative stress and resulting lipid peroxidation play a role in pathogenesis of B-CLL and provide a rational basis for the use of agents regulating the pro-oxidant and antioxidant activity in the treatment of B-CLL patients,” the researchers concluded.
The research was unsponsored and the authors reported having no conflicts.
SOURCE: Zhevak T et al. Exp Mol Patholo. 2020 Oct;16:104524 doi: 10.1016/j.yexmp.2020.104524.
FROM Experimental and Molecular Pathology
Deaths sky high in hospitalized COVID patients with kidney injury
More evidence indicates that the development of acute kidney injury
“This ... is the first study in the United States to report the persistence of kidney dysfunction (lack of recovery) in survivors of COVID-19–associated AKI [and] this is in marked contrast to other forms of AKI where over 80% of patients recover their renal function by 10 days,” Lili Chan, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues observed.
The research is a retrospective, observational cohort study published online Sept. 3 in the Journal of the American Society of Nephrology
“We may be facing an epidemic of post–COVID-19 kidney disease and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants,” said senior author Girish Nadkarni, MD, a nephrologist, in a statement from Mount Sinai.
Nephrologists will need to prepare for a significant uptick in patients with chronic kidney disease as a result of exposure to the SARS-CoV-2 virus that causes COVID-19, the researchers warned.
“These findings may help centers with resource planning and preparing for the increased load resulting from survivors of COVID-19–associated AKI who do not experience recovery of kidney function,” they added.
Analysis of patients from February to end of May 2020
“AKI among hospitalized patients with COVID-19 in the United States is not well described,” they noted in their article.
And so they analyzed data from five major hospitals in the Mount Sinai Health System between Feb. 27 and May 30 of this year, during which 3,993 patients were hospitalized within the system for COVID-19. The MSHS has a patient population of racially and ethnically diverse citizens from New York.
AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. AKI occurred in 46% of the overall cohort of patients, 19% of whom required dialysis.
However, among those patients who required admission to the ICU, over three-quarters (76%) developed AKI and almost one-third of ICU patients required dialysis, the investigators said.
“The median time from hospital admission until AKI diagnoses was 1 day and the median time from AKI diagnosis to dialysis was 3 days,” they explain.
The proportion of patients with stages 1, 2, or 3 AKI among those admitted to hospital were 39%, 19%, and 42%, respectively. In patients requiring admission to ICU, 28% had stage 1 AKI, 17% had stage 2, and 56% had stage 3.
And among those who required dialysis for AKI, the median peak serum creatinine was 8.2 mg/dL, compared with 2.2 mg/dL for those who did not require dialysis.
Predictors of AKI: male sex, potassium levels, and preexisting CKD
Almost two thirds of patients (65%) had recovered from their kidney injury by the time they left hospital but 35% had acute kidney disease. Of this latter group, on follow-up, 36% had recovered from it, the investigators noted.
Conversely, of those patients who had recovered from AKI by hospital discharge, 14% went on to develop acute kidney disease at the time of follow-up.
And 30% of patients who had required dialysis at some point during their hospital care required dialysis again within 72 hours of being discharged, the investigators noted.
Predictors of severe AKI included male sex (adjusted odds ratio, 1.46), potassium levels on admission (aOR, 1.7), and preexisting chronic kidney disease (CKD) (aOR, 2.8).
Most compellingly, “in-hospital mortality in patients who experienced AKI was 50% [versus] 8% in patients without AKI (P < .001),” Dr. Nadkarni and colleagues reported.
Among those who required ICU care, 42% of patients with AKI died, compared with 7% of those in ICU who did not develop AKI, while in patients cared for outside of ICU, 62% with AKI died compared with only 13% of those who did not develop AKI.
And after adjusting for demographics, comorbidities, and laboratory values, the aOR for death was 11.4 times higher for ICU patients with AKI, compared with ICU patients without AKI, the authors emphasize.
In all patients who developed AKI, the aOR for mortality was 9.2, compared with patients who did not develop AKI, they added.
Perhaps predictably, the risk of death rose with increasing stage of AKI, and patients with stage 3 AKI who required dialysis were at highest risk of death, the authors observe.
Sheer number of AKI cases, need for dialysis unprecedented
“The sheer number of AKI cases and the overwhelming need for dialysis that we are seeing in the context of COVID-19 is unprecedented,” Dr. Nadkarni said.
“These findings bring clinical evidence to the hypothesis of lingering organ dysfunction among patients recovering from COVID-19 and serve as a reminder to hospitals around the country to be very strategic in the allocation of resources to care for patients who experience AKI,” he cautioned.
“We are grappling with a great deal of uncertainty as to how the virus will impact the kidneys in the long haul,” Dr. Nadkarni added. “We may be facing an epidemic of post–COVID-19 kidney disease, and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants.”
Dr. Nadkarni reported serving as a consultant and advisory board member for RenalytixAI and owns equity in the company.
This article first appeared on Medscape.com.
More evidence indicates that the development of acute kidney injury
“This ... is the first study in the United States to report the persistence of kidney dysfunction (lack of recovery) in survivors of COVID-19–associated AKI [and] this is in marked contrast to other forms of AKI where over 80% of patients recover their renal function by 10 days,” Lili Chan, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues observed.
The research is a retrospective, observational cohort study published online Sept. 3 in the Journal of the American Society of Nephrology
“We may be facing an epidemic of post–COVID-19 kidney disease and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants,” said senior author Girish Nadkarni, MD, a nephrologist, in a statement from Mount Sinai.
Nephrologists will need to prepare for a significant uptick in patients with chronic kidney disease as a result of exposure to the SARS-CoV-2 virus that causes COVID-19, the researchers warned.
“These findings may help centers with resource planning and preparing for the increased load resulting from survivors of COVID-19–associated AKI who do not experience recovery of kidney function,” they added.
Analysis of patients from February to end of May 2020
“AKI among hospitalized patients with COVID-19 in the United States is not well described,” they noted in their article.
And so they analyzed data from five major hospitals in the Mount Sinai Health System between Feb. 27 and May 30 of this year, during which 3,993 patients were hospitalized within the system for COVID-19. The MSHS has a patient population of racially and ethnically diverse citizens from New York.
AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. AKI occurred in 46% of the overall cohort of patients, 19% of whom required dialysis.
However, among those patients who required admission to the ICU, over three-quarters (76%) developed AKI and almost one-third of ICU patients required dialysis, the investigators said.
“The median time from hospital admission until AKI diagnoses was 1 day and the median time from AKI diagnosis to dialysis was 3 days,” they explain.
The proportion of patients with stages 1, 2, or 3 AKI among those admitted to hospital were 39%, 19%, and 42%, respectively. In patients requiring admission to ICU, 28% had stage 1 AKI, 17% had stage 2, and 56% had stage 3.
And among those who required dialysis for AKI, the median peak serum creatinine was 8.2 mg/dL, compared with 2.2 mg/dL for those who did not require dialysis.
Predictors of AKI: male sex, potassium levels, and preexisting CKD
Almost two thirds of patients (65%) had recovered from their kidney injury by the time they left hospital but 35% had acute kidney disease. Of this latter group, on follow-up, 36% had recovered from it, the investigators noted.
Conversely, of those patients who had recovered from AKI by hospital discharge, 14% went on to develop acute kidney disease at the time of follow-up.
And 30% of patients who had required dialysis at some point during their hospital care required dialysis again within 72 hours of being discharged, the investigators noted.
Predictors of severe AKI included male sex (adjusted odds ratio, 1.46), potassium levels on admission (aOR, 1.7), and preexisting chronic kidney disease (CKD) (aOR, 2.8).
Most compellingly, “in-hospital mortality in patients who experienced AKI was 50% [versus] 8% in patients without AKI (P < .001),” Dr. Nadkarni and colleagues reported.
Among those who required ICU care, 42% of patients with AKI died, compared with 7% of those in ICU who did not develop AKI, while in patients cared for outside of ICU, 62% with AKI died compared with only 13% of those who did not develop AKI.
And after adjusting for demographics, comorbidities, and laboratory values, the aOR for death was 11.4 times higher for ICU patients with AKI, compared with ICU patients without AKI, the authors emphasize.
In all patients who developed AKI, the aOR for mortality was 9.2, compared with patients who did not develop AKI, they added.
Perhaps predictably, the risk of death rose with increasing stage of AKI, and patients with stage 3 AKI who required dialysis were at highest risk of death, the authors observe.
Sheer number of AKI cases, need for dialysis unprecedented
“The sheer number of AKI cases and the overwhelming need for dialysis that we are seeing in the context of COVID-19 is unprecedented,” Dr. Nadkarni said.
“These findings bring clinical evidence to the hypothesis of lingering organ dysfunction among patients recovering from COVID-19 and serve as a reminder to hospitals around the country to be very strategic in the allocation of resources to care for patients who experience AKI,” he cautioned.
“We are grappling with a great deal of uncertainty as to how the virus will impact the kidneys in the long haul,” Dr. Nadkarni added. “We may be facing an epidemic of post–COVID-19 kidney disease, and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants.”
Dr. Nadkarni reported serving as a consultant and advisory board member for RenalytixAI and owns equity in the company.
This article first appeared on Medscape.com.
More evidence indicates that the development of acute kidney injury
“This ... is the first study in the United States to report the persistence of kidney dysfunction (lack of recovery) in survivors of COVID-19–associated AKI [and] this is in marked contrast to other forms of AKI where over 80% of patients recover their renal function by 10 days,” Lili Chan, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues observed.
The research is a retrospective, observational cohort study published online Sept. 3 in the Journal of the American Society of Nephrology
“We may be facing an epidemic of post–COVID-19 kidney disease and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants,” said senior author Girish Nadkarni, MD, a nephrologist, in a statement from Mount Sinai.
Nephrologists will need to prepare for a significant uptick in patients with chronic kidney disease as a result of exposure to the SARS-CoV-2 virus that causes COVID-19, the researchers warned.
“These findings may help centers with resource planning and preparing for the increased load resulting from survivors of COVID-19–associated AKI who do not experience recovery of kidney function,” they added.
Analysis of patients from February to end of May 2020
“AKI among hospitalized patients with COVID-19 in the United States is not well described,” they noted in their article.
And so they analyzed data from five major hospitals in the Mount Sinai Health System between Feb. 27 and May 30 of this year, during which 3,993 patients were hospitalized within the system for COVID-19. The MSHS has a patient population of racially and ethnically diverse citizens from New York.
AKI was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. AKI occurred in 46% of the overall cohort of patients, 19% of whom required dialysis.
However, among those patients who required admission to the ICU, over three-quarters (76%) developed AKI and almost one-third of ICU patients required dialysis, the investigators said.
“The median time from hospital admission until AKI diagnoses was 1 day and the median time from AKI diagnosis to dialysis was 3 days,” they explain.
The proportion of patients with stages 1, 2, or 3 AKI among those admitted to hospital were 39%, 19%, and 42%, respectively. In patients requiring admission to ICU, 28% had stage 1 AKI, 17% had stage 2, and 56% had stage 3.
And among those who required dialysis for AKI, the median peak serum creatinine was 8.2 mg/dL, compared with 2.2 mg/dL for those who did not require dialysis.
Predictors of AKI: male sex, potassium levels, and preexisting CKD
Almost two thirds of patients (65%) had recovered from their kidney injury by the time they left hospital but 35% had acute kidney disease. Of this latter group, on follow-up, 36% had recovered from it, the investigators noted.
Conversely, of those patients who had recovered from AKI by hospital discharge, 14% went on to develop acute kidney disease at the time of follow-up.
And 30% of patients who had required dialysis at some point during their hospital care required dialysis again within 72 hours of being discharged, the investigators noted.
Predictors of severe AKI included male sex (adjusted odds ratio, 1.46), potassium levels on admission (aOR, 1.7), and preexisting chronic kidney disease (CKD) (aOR, 2.8).
Most compellingly, “in-hospital mortality in patients who experienced AKI was 50% [versus] 8% in patients without AKI (P < .001),” Dr. Nadkarni and colleagues reported.
Among those who required ICU care, 42% of patients with AKI died, compared with 7% of those in ICU who did not develop AKI, while in patients cared for outside of ICU, 62% with AKI died compared with only 13% of those who did not develop AKI.
And after adjusting for demographics, comorbidities, and laboratory values, the aOR for death was 11.4 times higher for ICU patients with AKI, compared with ICU patients without AKI, the authors emphasize.
In all patients who developed AKI, the aOR for mortality was 9.2, compared with patients who did not develop AKI, they added.
Perhaps predictably, the risk of death rose with increasing stage of AKI, and patients with stage 3 AKI who required dialysis were at highest risk of death, the authors observe.
Sheer number of AKI cases, need for dialysis unprecedented
“The sheer number of AKI cases and the overwhelming need for dialysis that we are seeing in the context of COVID-19 is unprecedented,” Dr. Nadkarni said.
“These findings bring clinical evidence to the hypothesis of lingering organ dysfunction among patients recovering from COVID-19 and serve as a reminder to hospitals around the country to be very strategic in the allocation of resources to care for patients who experience AKI,” he cautioned.
“We are grappling with a great deal of uncertainty as to how the virus will impact the kidneys in the long haul,” Dr. Nadkarni added. “We may be facing an epidemic of post–COVID-19 kidney disease, and that, in turn, could mean much greater numbers of patients who require kidney dialysis and even transplants.”
Dr. Nadkarni reported serving as a consultant and advisory board member for RenalytixAI and owns equity in the company.
This article first appeared on Medscape.com.
Could these old drugs help fight COVID-19 and save lives?
Early in the COVID-19 pandemic, entrepreneur and philanthropist Steve Kirsch realized that until we have a vaccine against SARS-CoV-2, we would be at the mercy of this virus. He realized that the fastest and most effective way to reduce COVID-19 fatalities would be to leverage existing drugs to treat patients at the onset of infection — before they become sick.
Medscape spoke with CETF’s chief medical advisor, Lisa Danzig, MD, about the organization’s aim to fund promising research on repurposed drugs to treat COVID-19.
What is CETF trying to do?
Two things: save lives, and get control of this pandemic.
We are facing perhaps the greatest crisis of our lifetime. Doctors who have taken care of patients with COVID are really frustrated about not having anything to offer; they just watch patients die. We want to change that. CETF was founded to find treatments that, when given early, could improve outcomes and avoid catastrophic complications in patients suffering from COVID-19. That means reducing hospitalizations, which can reduce mortality, but it also can mean reducing viral load, and that can have a profound impact on transmission within communities. We are a funding organization — a Band-Aid. We shouldn’t exist, but we do, aiming to close gaps until a coordinated response can get set up.
Tell us about drug repurposing and why you think existing drugs might have a role in mitigating COVID-19 or slowing its transmission.
This disease has two components — the viral infection, and the immunopathology. So the two promising categories of drugs are classical antivirals (or repurposed drugs with antiviral activity), and the immunomodulators. We are mechanism-agnostic. It doesn’t matter what kind of drug it is if it keeps people out of the hospital and prevents chronic morbidity and mortality.
Repurposed drugs are sort of the low-hanging fruit of clinical drugs. The QBI Coronavirus Research Group identified 69 compounds that have theoretical activity against SARS-CoV-2, 29 of which are already FDA-approved drugs. We thought, why don’t we start testing them?
Some people might call this a long shot. Does drug repurposing really work?
Drugmakers don’t test their drugs on every disease they might be effective for. Drug repurposing can work, but if we don’t look, we definitely won’t find anything. The classic repurposed drug is Viagra, a failed hypertension drug. When the studies ended because it didn’t work, the drug company asked patients to send back the unused drugs. The women all returned the drugs, but the men didn’t. And the rest is history.
There’s a long list of potential drugs that can be repurposed, but few are being tested. The famous poster child of a repurposed drug — hydroxychloroquine — has been the subject of more than 250 clinical trials, but the others weren’t getting much attention.
The beauty of a repurposed drug is that if you can get funding and start enrolling patients, you could potentially find out fairly quickly, as early as a few months, if that drug has an antiviral effect or not. These data would help prioritize drugs to be tested in larger confirmatory studies.
Your focus is on early treatment. What’s the rationale for that?
We are focusing on early treatment because it has been overlooked. The attention has been on vaccines and therapeutics for hospitalized patients. But if you are spending $20 billion on potential vaccines and billions more on diagnostics, we need to give proportional resources toward drugs that might actually work, when given early, in preventing severe disease and death.
Early treatment, if successful, would allow us to avoid the severe complications that we are seeing now. If we can find an early treatment with an existing drug, it would be the fastest, most clinically- and cost-effective way to mitigate the impact of COVID-19 and get us on the road to recovery.
How do you get from a potential repurposed drug for COVID-19 to having a therapeutic agent that will save lives?
Most of the studies we are funding are smaller outpatient studies with virologic endpoints. We are looking for a signal that the drug has antiviral activity. We want to know whether a drug works before we spend the money on questions that take a much larger sample size to answer, for example, a big postexposure prophylaxis study. We’d like to see a meaningful signal in proof-of-concept studies, so we can look at a small group of patients with positive tests and see whether their viral load dropped by more than half if they got the drug compared with those who took the placebo. If the drug had an impact on the viral load and shortened the period of infectivity and was safe, these findings would provide justification to spend a lot of money on a large clinical trial. That would probably encourage the NIH and ACTIV [Accelerating COVID-19 Therapeutic Interventions and Vaccines] collaboration to prioritize the drug for one of their big platform trials. That›s what we are aiming for.
CETF isn’t a drug developer — we are a funder for a good proposal to study a repurposed drug. We want to help move the dial — can we get an early yes or an early no? In drug development, we say, “fail fast and fail early.” It’s a numbers game. Only 10% of early candidates will become approved drugs. The value is in the data, whether they are positive or negative — it doesn’t matter. If the study is a definitive “no,” that is just as helpful as a definitive “yes.” Of course, we all want the definitive “yes,” but there are so many things to look at, the “no’s” will help us redirect resources toward what may really help.
You first announced these funding opportunities in April. How is it going so far?
As soon as the website went up, we got 40 applications. Our scientific advisory board, which has expertise from medicinal chemistry and coronavirology to translational and clinical trial expertise, reviewed the applications and prioritized 11 fundable proposals. We are using milestone-based funding; in other words, funding those who are ready to go.
Which drugs are being tested in the funded studies?
One of the earliest grants we supported was Dr David Boulaware’s randomized controlled trial of hydroxychloroquine (NCT 04308668) in 821 asymptomatic patients within 4 days after a high-risk or moderate-risk exposure. That trial did not show any benefit of hydroxychloroquine as postexposure prophylaxis against COVID-19. This trial was important for another reason. It proved the feasibility of a no-contact trial design in the setting of COVID-19, and participants enrolled themselves through a secure Internet-based survey using the Research Electronic Data Capture (REDCap) system.
Camostat, a transmembrane serine protease (TMPRSS2) inhibitor licensed for use in Japan to treat pancreatitis and esophagitis, combined with the antiandrogen bicalutamide, is being explored for early COVID-19 treatment. TMPRSS2 primes the SARS-CoV-2 spike protein to bind to the ACE2 receptor and gain entry to the cell, and has been shown to have antiviral activity. CETF has provided funding support to ongoing trials of Camostat at Yale University and Aarhus University in Denmark.
Another outpatient trial for fluvoxamine, a drug approved in the United States and routinely prescribed for depression, was also partially funded by a CETF grant to Washington University in St. Louis. Fluvoxamine is a serotonin regulator but also activates the sigma-1 receptor, which reduces the body’s immune response to prevent an overactive immune response or cytokine storm, a major cause of clinical deterioration, serious organ damage, and even death from COVID. This trial was recently completed, and the results have been submitted for publication.
Other promising drugs include niclosamide, doxazosin, favipiravir, leronlimab, interferon beta, interferon lambda, and other monoclonal antibodies. New compounds considered to have potential against COVID include a flu drug (MK-4482/EIDD-2801) and GS-441524, a metabolite of the antiviral drug, remdesivir.
Why not just put all of our resources into vaccine development?
We absolutely need a vaccine to control the outbreak and stop the pandemic. However, it’s a long road to finding an effective vaccine, and in the meantime, we need tools to keep people alive. If we can find an antiviral drug that acts early, we can reduce transmission and contribute to outbreak control. All these tools help us get back to normal while we are waiting for a vaccine. The vaccine is only good if we can give it to every susceptible person in the world — which will take longer than 3 years. And there are no guarantees. Remember, we are still waiting for an HIV vaccine.
You are calling on Americans to help. What do you want them to do?
Everyone must participate in the behavioral changes designed to control the outbreak — physical distancing, face-covering, and paying attention to case counts in local areas to enable them to take appropriate precautions. I know people are bored of that message, but we are going to repeat it until we have a vaccine or herd immunity.
This organism is ripping like wildfire through our unimmunized population. Personal behaviors might slow it down, but finding a drug that can be given to people after they’ve been exposed and test positive will have a meaningful impact on helping us get back to normal.
There’s a great spirit of volunteerism — people are constantly asking how they can help. Through us at CETF, we offer three ways that people can help. They can participate as subjects in clinical trials, many of which are ongoing, including clinical trials, surveillance studies, and follow-up studies. They can donate to our fund and help support the research needed to find an effective early treatment. We have a link on our website, TreatEarly.org. And finally, researchers can apply for funding. We think everybody can help in one of these ways by participating in trials, donating, or applying for funding. It’s an all-hands-on-deck moment for our country.
Danzig is the chief medical advisor of the COVID-19 Early Treatment Fund. She has spent more than 20 years in the pharmaceutical industry developing vaccines, diagnostics, and drugs and is currently advising companies and investors.
This article first appeared on Medscape.com.
Early in the COVID-19 pandemic, entrepreneur and philanthropist Steve Kirsch realized that until we have a vaccine against SARS-CoV-2, we would be at the mercy of this virus. He realized that the fastest and most effective way to reduce COVID-19 fatalities would be to leverage existing drugs to treat patients at the onset of infection — before they become sick.
Medscape spoke with CETF’s chief medical advisor, Lisa Danzig, MD, about the organization’s aim to fund promising research on repurposed drugs to treat COVID-19.
What is CETF trying to do?
Two things: save lives, and get control of this pandemic.
We are facing perhaps the greatest crisis of our lifetime. Doctors who have taken care of patients with COVID are really frustrated about not having anything to offer; they just watch patients die. We want to change that. CETF was founded to find treatments that, when given early, could improve outcomes and avoid catastrophic complications in patients suffering from COVID-19. That means reducing hospitalizations, which can reduce mortality, but it also can mean reducing viral load, and that can have a profound impact on transmission within communities. We are a funding organization — a Band-Aid. We shouldn’t exist, but we do, aiming to close gaps until a coordinated response can get set up.
Tell us about drug repurposing and why you think existing drugs might have a role in mitigating COVID-19 or slowing its transmission.
This disease has two components — the viral infection, and the immunopathology. So the two promising categories of drugs are classical antivirals (or repurposed drugs with antiviral activity), and the immunomodulators. We are mechanism-agnostic. It doesn’t matter what kind of drug it is if it keeps people out of the hospital and prevents chronic morbidity and mortality.
Repurposed drugs are sort of the low-hanging fruit of clinical drugs. The QBI Coronavirus Research Group identified 69 compounds that have theoretical activity against SARS-CoV-2, 29 of which are already FDA-approved drugs. We thought, why don’t we start testing them?
Some people might call this a long shot. Does drug repurposing really work?
Drugmakers don’t test their drugs on every disease they might be effective for. Drug repurposing can work, but if we don’t look, we definitely won’t find anything. The classic repurposed drug is Viagra, a failed hypertension drug. When the studies ended because it didn’t work, the drug company asked patients to send back the unused drugs. The women all returned the drugs, but the men didn’t. And the rest is history.
There’s a long list of potential drugs that can be repurposed, but few are being tested. The famous poster child of a repurposed drug — hydroxychloroquine — has been the subject of more than 250 clinical trials, but the others weren’t getting much attention.
The beauty of a repurposed drug is that if you can get funding and start enrolling patients, you could potentially find out fairly quickly, as early as a few months, if that drug has an antiviral effect or not. These data would help prioritize drugs to be tested in larger confirmatory studies.
Your focus is on early treatment. What’s the rationale for that?
We are focusing on early treatment because it has been overlooked. The attention has been on vaccines and therapeutics for hospitalized patients. But if you are spending $20 billion on potential vaccines and billions more on diagnostics, we need to give proportional resources toward drugs that might actually work, when given early, in preventing severe disease and death.
Early treatment, if successful, would allow us to avoid the severe complications that we are seeing now. If we can find an early treatment with an existing drug, it would be the fastest, most clinically- and cost-effective way to mitigate the impact of COVID-19 and get us on the road to recovery.
How do you get from a potential repurposed drug for COVID-19 to having a therapeutic agent that will save lives?
Most of the studies we are funding are smaller outpatient studies with virologic endpoints. We are looking for a signal that the drug has antiviral activity. We want to know whether a drug works before we spend the money on questions that take a much larger sample size to answer, for example, a big postexposure prophylaxis study. We’d like to see a meaningful signal in proof-of-concept studies, so we can look at a small group of patients with positive tests and see whether their viral load dropped by more than half if they got the drug compared with those who took the placebo. If the drug had an impact on the viral load and shortened the period of infectivity and was safe, these findings would provide justification to spend a lot of money on a large clinical trial. That would probably encourage the NIH and ACTIV [Accelerating COVID-19 Therapeutic Interventions and Vaccines] collaboration to prioritize the drug for one of their big platform trials. That›s what we are aiming for.
CETF isn’t a drug developer — we are a funder for a good proposal to study a repurposed drug. We want to help move the dial — can we get an early yes or an early no? In drug development, we say, “fail fast and fail early.” It’s a numbers game. Only 10% of early candidates will become approved drugs. The value is in the data, whether they are positive or negative — it doesn’t matter. If the study is a definitive “no,” that is just as helpful as a definitive “yes.” Of course, we all want the definitive “yes,” but there are so many things to look at, the “no’s” will help us redirect resources toward what may really help.
You first announced these funding opportunities in April. How is it going so far?
As soon as the website went up, we got 40 applications. Our scientific advisory board, which has expertise from medicinal chemistry and coronavirology to translational and clinical trial expertise, reviewed the applications and prioritized 11 fundable proposals. We are using milestone-based funding; in other words, funding those who are ready to go.
Which drugs are being tested in the funded studies?
One of the earliest grants we supported was Dr David Boulaware’s randomized controlled trial of hydroxychloroquine (NCT 04308668) in 821 asymptomatic patients within 4 days after a high-risk or moderate-risk exposure. That trial did not show any benefit of hydroxychloroquine as postexposure prophylaxis against COVID-19. This trial was important for another reason. It proved the feasibility of a no-contact trial design in the setting of COVID-19, and participants enrolled themselves through a secure Internet-based survey using the Research Electronic Data Capture (REDCap) system.
Camostat, a transmembrane serine protease (TMPRSS2) inhibitor licensed for use in Japan to treat pancreatitis and esophagitis, combined with the antiandrogen bicalutamide, is being explored for early COVID-19 treatment. TMPRSS2 primes the SARS-CoV-2 spike protein to bind to the ACE2 receptor and gain entry to the cell, and has been shown to have antiviral activity. CETF has provided funding support to ongoing trials of Camostat at Yale University and Aarhus University in Denmark.
Another outpatient trial for fluvoxamine, a drug approved in the United States and routinely prescribed for depression, was also partially funded by a CETF grant to Washington University in St. Louis. Fluvoxamine is a serotonin regulator but also activates the sigma-1 receptor, which reduces the body’s immune response to prevent an overactive immune response or cytokine storm, a major cause of clinical deterioration, serious organ damage, and even death from COVID. This trial was recently completed, and the results have been submitted for publication.
Other promising drugs include niclosamide, doxazosin, favipiravir, leronlimab, interferon beta, interferon lambda, and other monoclonal antibodies. New compounds considered to have potential against COVID include a flu drug (MK-4482/EIDD-2801) and GS-441524, a metabolite of the antiviral drug, remdesivir.
Why not just put all of our resources into vaccine development?
We absolutely need a vaccine to control the outbreak and stop the pandemic. However, it’s a long road to finding an effective vaccine, and in the meantime, we need tools to keep people alive. If we can find an antiviral drug that acts early, we can reduce transmission and contribute to outbreak control. All these tools help us get back to normal while we are waiting for a vaccine. The vaccine is only good if we can give it to every susceptible person in the world — which will take longer than 3 years. And there are no guarantees. Remember, we are still waiting for an HIV vaccine.
You are calling on Americans to help. What do you want them to do?
Everyone must participate in the behavioral changes designed to control the outbreak — physical distancing, face-covering, and paying attention to case counts in local areas to enable them to take appropriate precautions. I know people are bored of that message, but we are going to repeat it until we have a vaccine or herd immunity.
This organism is ripping like wildfire through our unimmunized population. Personal behaviors might slow it down, but finding a drug that can be given to people after they’ve been exposed and test positive will have a meaningful impact on helping us get back to normal.
There’s a great spirit of volunteerism — people are constantly asking how they can help. Through us at CETF, we offer three ways that people can help. They can participate as subjects in clinical trials, many of which are ongoing, including clinical trials, surveillance studies, and follow-up studies. They can donate to our fund and help support the research needed to find an effective early treatment. We have a link on our website, TreatEarly.org. And finally, researchers can apply for funding. We think everybody can help in one of these ways by participating in trials, donating, or applying for funding. It’s an all-hands-on-deck moment for our country.
Danzig is the chief medical advisor of the COVID-19 Early Treatment Fund. She has spent more than 20 years in the pharmaceutical industry developing vaccines, diagnostics, and drugs and is currently advising companies and investors.
This article first appeared on Medscape.com.
Early in the COVID-19 pandemic, entrepreneur and philanthropist Steve Kirsch realized that until we have a vaccine against SARS-CoV-2, we would be at the mercy of this virus. He realized that the fastest and most effective way to reduce COVID-19 fatalities would be to leverage existing drugs to treat patients at the onset of infection — before they become sick.
Medscape spoke with CETF’s chief medical advisor, Lisa Danzig, MD, about the organization’s aim to fund promising research on repurposed drugs to treat COVID-19.
What is CETF trying to do?
Two things: save lives, and get control of this pandemic.
We are facing perhaps the greatest crisis of our lifetime. Doctors who have taken care of patients with COVID are really frustrated about not having anything to offer; they just watch patients die. We want to change that. CETF was founded to find treatments that, when given early, could improve outcomes and avoid catastrophic complications in patients suffering from COVID-19. That means reducing hospitalizations, which can reduce mortality, but it also can mean reducing viral load, and that can have a profound impact on transmission within communities. We are a funding organization — a Band-Aid. We shouldn’t exist, but we do, aiming to close gaps until a coordinated response can get set up.
Tell us about drug repurposing and why you think existing drugs might have a role in mitigating COVID-19 or slowing its transmission.
This disease has two components — the viral infection, and the immunopathology. So the two promising categories of drugs are classical antivirals (or repurposed drugs with antiviral activity), and the immunomodulators. We are mechanism-agnostic. It doesn’t matter what kind of drug it is if it keeps people out of the hospital and prevents chronic morbidity and mortality.
Repurposed drugs are sort of the low-hanging fruit of clinical drugs. The QBI Coronavirus Research Group identified 69 compounds that have theoretical activity against SARS-CoV-2, 29 of which are already FDA-approved drugs. We thought, why don’t we start testing them?
Some people might call this a long shot. Does drug repurposing really work?
Drugmakers don’t test their drugs on every disease they might be effective for. Drug repurposing can work, but if we don’t look, we definitely won’t find anything. The classic repurposed drug is Viagra, a failed hypertension drug. When the studies ended because it didn’t work, the drug company asked patients to send back the unused drugs. The women all returned the drugs, but the men didn’t. And the rest is history.
There’s a long list of potential drugs that can be repurposed, but few are being tested. The famous poster child of a repurposed drug — hydroxychloroquine — has been the subject of more than 250 clinical trials, but the others weren’t getting much attention.
The beauty of a repurposed drug is that if you can get funding and start enrolling patients, you could potentially find out fairly quickly, as early as a few months, if that drug has an antiviral effect or not. These data would help prioritize drugs to be tested in larger confirmatory studies.
Your focus is on early treatment. What’s the rationale for that?
We are focusing on early treatment because it has been overlooked. The attention has been on vaccines and therapeutics for hospitalized patients. But if you are spending $20 billion on potential vaccines and billions more on diagnostics, we need to give proportional resources toward drugs that might actually work, when given early, in preventing severe disease and death.
Early treatment, if successful, would allow us to avoid the severe complications that we are seeing now. If we can find an early treatment with an existing drug, it would be the fastest, most clinically- and cost-effective way to mitigate the impact of COVID-19 and get us on the road to recovery.
How do you get from a potential repurposed drug for COVID-19 to having a therapeutic agent that will save lives?
Most of the studies we are funding are smaller outpatient studies with virologic endpoints. We are looking for a signal that the drug has antiviral activity. We want to know whether a drug works before we spend the money on questions that take a much larger sample size to answer, for example, a big postexposure prophylaxis study. We’d like to see a meaningful signal in proof-of-concept studies, so we can look at a small group of patients with positive tests and see whether their viral load dropped by more than half if they got the drug compared with those who took the placebo. If the drug had an impact on the viral load and shortened the period of infectivity and was safe, these findings would provide justification to spend a lot of money on a large clinical trial. That would probably encourage the NIH and ACTIV [Accelerating COVID-19 Therapeutic Interventions and Vaccines] collaboration to prioritize the drug for one of their big platform trials. That›s what we are aiming for.
CETF isn’t a drug developer — we are a funder for a good proposal to study a repurposed drug. We want to help move the dial — can we get an early yes or an early no? In drug development, we say, “fail fast and fail early.” It’s a numbers game. Only 10% of early candidates will become approved drugs. The value is in the data, whether they are positive or negative — it doesn’t matter. If the study is a definitive “no,” that is just as helpful as a definitive “yes.” Of course, we all want the definitive “yes,” but there are so many things to look at, the “no’s” will help us redirect resources toward what may really help.
You first announced these funding opportunities in April. How is it going so far?
As soon as the website went up, we got 40 applications. Our scientific advisory board, which has expertise from medicinal chemistry and coronavirology to translational and clinical trial expertise, reviewed the applications and prioritized 11 fundable proposals. We are using milestone-based funding; in other words, funding those who are ready to go.
Which drugs are being tested in the funded studies?
One of the earliest grants we supported was Dr David Boulaware’s randomized controlled trial of hydroxychloroquine (NCT 04308668) in 821 asymptomatic patients within 4 days after a high-risk or moderate-risk exposure. That trial did not show any benefit of hydroxychloroquine as postexposure prophylaxis against COVID-19. This trial was important for another reason. It proved the feasibility of a no-contact trial design in the setting of COVID-19, and participants enrolled themselves through a secure Internet-based survey using the Research Electronic Data Capture (REDCap) system.
Camostat, a transmembrane serine protease (TMPRSS2) inhibitor licensed for use in Japan to treat pancreatitis and esophagitis, combined with the antiandrogen bicalutamide, is being explored for early COVID-19 treatment. TMPRSS2 primes the SARS-CoV-2 spike protein to bind to the ACE2 receptor and gain entry to the cell, and has been shown to have antiviral activity. CETF has provided funding support to ongoing trials of Camostat at Yale University and Aarhus University in Denmark.
Another outpatient trial for fluvoxamine, a drug approved in the United States and routinely prescribed for depression, was also partially funded by a CETF grant to Washington University in St. Louis. Fluvoxamine is a serotonin regulator but also activates the sigma-1 receptor, which reduces the body’s immune response to prevent an overactive immune response or cytokine storm, a major cause of clinical deterioration, serious organ damage, and even death from COVID. This trial was recently completed, and the results have been submitted for publication.
Other promising drugs include niclosamide, doxazosin, favipiravir, leronlimab, interferon beta, interferon lambda, and other monoclonal antibodies. New compounds considered to have potential against COVID include a flu drug (MK-4482/EIDD-2801) and GS-441524, a metabolite of the antiviral drug, remdesivir.
Why not just put all of our resources into vaccine development?
We absolutely need a vaccine to control the outbreak and stop the pandemic. However, it’s a long road to finding an effective vaccine, and in the meantime, we need tools to keep people alive. If we can find an antiviral drug that acts early, we can reduce transmission and contribute to outbreak control. All these tools help us get back to normal while we are waiting for a vaccine. The vaccine is only good if we can give it to every susceptible person in the world — which will take longer than 3 years. And there are no guarantees. Remember, we are still waiting for an HIV vaccine.
You are calling on Americans to help. What do you want them to do?
Everyone must participate in the behavioral changes designed to control the outbreak — physical distancing, face-covering, and paying attention to case counts in local areas to enable them to take appropriate precautions. I know people are bored of that message, but we are going to repeat it until we have a vaccine or herd immunity.
This organism is ripping like wildfire through our unimmunized population. Personal behaviors might slow it down, but finding a drug that can be given to people after they’ve been exposed and test positive will have a meaningful impact on helping us get back to normal.
There’s a great spirit of volunteerism — people are constantly asking how they can help. Through us at CETF, we offer three ways that people can help. They can participate as subjects in clinical trials, many of which are ongoing, including clinical trials, surveillance studies, and follow-up studies. They can donate to our fund and help support the research needed to find an effective early treatment. We have a link on our website, TreatEarly.org. And finally, researchers can apply for funding. We think everybody can help in one of these ways by participating in trials, donating, or applying for funding. It’s an all-hands-on-deck moment for our country.
Danzig is the chief medical advisor of the COVID-19 Early Treatment Fund. She has spent more than 20 years in the pharmaceutical industry developing vaccines, diagnostics, and drugs and is currently advising companies and investors.
This article first appeared on Medscape.com.