Federal Practitioner

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

New guidelines recommend against retreatment with poly (ADP-ribose) polymerase (PARP) inhibitors in women with epithelial ovarian, tubal, or primary peritoneal cancer (EOC). However, trials investigating retreatment are underway, so this recommendation may change.

The guidelines, from the American Society of Clinical Oncology (ASCO), do not recommend PARP inhibitors for the initial treatment of stage I-II EOC.

However, PARP inhibitor maintenance should be offered to women with newly diagnosed stage III-IV EOC who achieved a complete or partial response with first-line platinum-based chemotherapy, according to the guidelines. Niraparib can be offered to all women meeting those criteria, while olaparib can be considered for patients with mutations in BRCA1/2.

The guidelines, published in the Journal of Clinical Oncology, are based on a systematic review of recent randomized PARP inhibitor trials, including PRIMA and SOLO1, among others.

What’s not available now is overall survival results from key clinical trials, the guideline authors noted. They added that further research is needed to address the issue of conserving platinum sensitivity in patients with disease progression on or after PARP inhibitor maintenance.

“Given the expectation that early treatment may confer the best outcome, maintenance therapy with PARP inhibitors should be offered, with these caveats,” the authors wrote.

Olaparib can also be added to bevacizumab maintenance therapy following response to first-line chemotherapy plus bevacizumab, according to the guidelines, which also address PARP inhibitor use for women with recurrent EOC, as well as management of adverse events.

The guidelines recommend against pairing PARP inhibitors with chemotherapy, targeted therapy, or immunotherapy outside a clinical trial.
 

Which drug, which setting, which dose?

This new ASCO guidelines may help cut through the complexity of treatment decision-making for women with EOC, according to Roisin E. O’Cearbhaill, MD, of Memorial Sloan Kettering Cancer Center in New York.

“Today as clinicians, we have a whole range of opportunities to give our patients PARP inhibitors in the upfront and recurrent setting,” Dr. O’Cearbhaill said in an interview. “It is quite complicated to know which PARP inhibitor should be used in which setting and which patients.”

“We want to make sure that patients who would derive the most benefit from PARP inhibitors are offered these agents but also that we’re careful not to use PARP inhibitors in settings where there is little or no data,” added Dr. O’Cearbhaill, who was not involved in the drafting of the guidelines.

The ASCO guidelines provide a detailed review of 17 clinical trials to address key issues, including the histologic types of EOC and biomarker subsets for which PARP inhibitors are recommended in the newly diagnosed setting, as well as the settings, dose, and duration of treatment that are recommended for patients with recurrent EOC who have not yet received a PARP inhibitor.

While PARP inhibitors are generally well tolerated, some characteristic toxicities – such as anemia, neutropenia, thrombocytopenia, persistent cytopenias, and nausea – may warrant dose reductions, the guidelines state.

Special attention must be paid to low-grade adverse events since PARP inhibitors are administered continuously on a daily basis, according to the guidelines. If a dose is held because of a grade 2 adverse event, the subsequent dose should be reduced to avoid a second dose hold.

“Reescalation or resumption of the initial dose is never recommended,” the guidelines state.
 

Retreatment

Dr. O’Cearbhaill said she is eager to see future guidelines addressing PARP inhibitor retreatment following disease progression, especially since more and more patients will receive these agents in the upfront setting.

Right now, there is little data available to address PARP inhibitor retreatment. However, the ASCO guidelines do mention the ongoing OReO/ENGOT OV-38 phase 3 trial of maintenance retreatment with olaparib in women with EOC.

This study, which includes patients who previously received a PARP inhibitor and who are responding to additional platinum-based chemotherapy, has an estimated completion date in May 2021, according to details on ClinicalTrials.gov.

That’s one of several trials designed to determine how best to incorporate PARP inhibitor retreatment into the treatment paradigm, according to Dr. O’Cearbhaill.

“Even if a high proportion of patients aren’t ultimately cured by this approach, if we can delay progression of disease by the order of months or even years, whilst proactively managing side effects, it would make such a big difference for patients,” she said. “It allows them to have a better quality of life and go about their daily activities without symptomatic ovarian cancer.”

Cochairs of the ASCO expert panel for the guidelines were William P. Tew, MD, of Memorial Sloan Kettering Cancer Center in New York, and Elise C. Kohn, MD, of the National Cancer Institute in Bethesda, Md. Dr. Tew and Dr. Kohn provided no disclosures, while their coauthors reported disclosures related to Roche, AstraZeneca, Tesaro, Clovis Oncology, Merck, Seattle Genetics, and other companies. Dr. O’Cearbhaill disclosed that she is a coauthor on the PRIMA/ENGOT-OV26/GOG-3012 phase 3 clinical trial (NCT02655016) and serves on the steering committee for DUO-O (NCT0373643). She reported personal fees from Clovis, Tesaro, Regeneron, and GlaxoSmithKline.

SOURCE: Tew WP et al. J Clin Oncol. 2020 Aug 13. doi: 10.1200/JCO.20.01924.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Novel therapies are poised to dramatically change frontline therapy for acute myeloid leukemia (AML), and they have the potential to replace chemotherapy, a hematologist/oncologist told colleagues at the virtual Acute Leukemia Forum of Hemedicus.

But more work needs to be done, noted Alexander Perl, MD, MS, associate professor at the University of Pennsylvania, Philadelphia. While advances have transformed AML treatment in the relapsed/refractory setting, “we’re just not seeing that substantive improvement” for newly diagnosed patients, he said. “We need to find the disease-modifying drugs that work in the relapsed/refractory setting and move those frontline. That’s where we’re going to see the transformations.”

Research suggests that low-intensity therapy holds tremendous promise, he said, “with the idea that we could make therapy much more tolerable for the vast majority of patients affected by AML, who, as we know, are older patients.”

Dr. Perl highlighted the 2020 VIALE-A study – venetoclax/azacitidine versus azacitidine/placebo – which reported that “in previously untreated patients who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.”

Venetoclax promotes apoptosis in leukemia cells, Dr. Perl said. “To a certain extent, you can think of it as putting the rubber to the road in terms of what actually chemotherapy is designed to do, which is to make leukemic blasts apoptose. It does so without DNA damage and with much less toxicity to the patient. Therefore it can be added to any number of regimens – granted, with mild suppression, but with relatively little extramedullary toxicity.”

Dr. Perl noted that the venetoclax arm “showed a higher response rate than azacitidine in pretty much every subgroup that was looked at, whether patients had de novo leukemia, secondary leukemia, multiple mutational complements, various different karyotypes. The response rates on this study are as high as what we often will see with intensive chemotherapy.” He added that “the winning arm on this trial seems to hold up against any low-intensity therapy, and I would argue against many high-intensity therapies in older patients.”

As for other targeted agents, isocitrate dehydrogenase (IDH) inhibitors “are very promising drugs in the relapsed/refractory setting, which is primarily where these drugs are given. In regard to frontline treatment, “data are coming from a very small study, but they’re very encouraging. It’s hard to entirely say that we’re ready to change practice based on this. But it’s very encouraging – the idea that earlier use of a drug-targeting IDH mutation might lead to substantially better outcomes.”

Moving forward, he said, “we could put all of our eggs in one basket and use many active drugs [at] front line. Or we can perhaps be smart about sequencing these drugs one after another, or using more intensive approaches followed by maintenance approaches followed by more intensive approaches.”

This approach is similar to strategies in myeloma patients “who less and less are relying on an autologous transplant for durable control of their disease, and more and more are using low-intensity biologically targeted drugs,” he said.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Dr. Perl reported numerous disclosures, including relationships with Daiichi Sankyo, Abbvie, and Astellas.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Vertebral fractures appear to be common in people with severe COVID-19, and also raise the mortality risk, findings from a retrospective cohort suggest.

Among 114 patients with COVID-19 who underwent lateral chest x-rays at the San Raffaele Hospital ED in Milan, more than a third were found to have thoracic vertebral fractures. And, those individuals were more than twice as likely to die as were those without vertebral fractures.

“Morphometric vertebral fractures are one of the most common comorbidities among adults hospitalized with COVID-19, and the presence of such fractures may predict the severity of disease outcomes,” lead investigator Andrea Giustina, MD, said in an interview.

This is the first study to examine vertebral fracture prevalence in any coronavirus disease, but such fractures have been linked to an increased risk of pneumonia and impaired respiratory function, including restrictive pulmonary dysfunction. One possible mechanism may be that they cause anatomical changes, such as kyphosis, which negatively impact respiratory function by decreasing vital capacity, forced expiratory volume in 1 second, and inspiratory time, explained Dr. Giustina, professor of endocrinology, San Raffaele Vita Salute University, Milan, and president of the European Society of Endocrinology. The results were published in the Journal of Clinical Endocrinology and Metabolism.

Clinically, the findings suggest that all patients with COVID-19 who are undergoing chest x-rays should have morphometric vertebral x-ray evaluation, said Dr. Giustina.

“One interesting aspect of the study is that without morphometry, approximatively two thirds of vertebral fractures [would have been] missed. Therefore, they are largely underestimated in clinical practice,” he noted.
 

Thoracic vertebral fractures assessed via lateral chest x-rays

The 114 study subjects included were those whose lateral chest x-rays allowed for a high-quality assessment and in which all the thoracic tract of T4-T12 were viewable and assessable. None had been using glucocorticoids and only 3% had a prior diagnosis of osteoporosis.

The majority (75%) were male, and median age was 57 years. Most (79%) were hospitalized after evaluation in the ED. Of those, 12% (13) were admitted to the ICU and 15% (16) died.

Thoracic vertebral fractures were detected on the lateral chest x-rays in 36% (41) of the patients. In contrast, in studies of women aged 50 years and older from the general European population, morphometric vertebral fracture prevalence ranged from 18% to 26%, the investigators noted.

Of the total 65 vertebral fractures detected, 60% were classified as mild (height ratio decrease <25%), 33.3% as moderate (25%-40% decrease) and 7.7% as severe (>40%). Patients with more than one vertebral fracture were classified by their most severe one.

Those with versus without vertebral fractures didn’t differ by sex, body mass index, or clinical or biological parameters evaluated in the ED. But, compared with those without vertebral fractures, those with them were significantly older (68 vs. 54 years) and were more likely to have arterial hypertension (56% vs. 30%) and coronary artery disease (22% vs. 7%).

In multivariate analysis, age was the only statistically significant predictor of vertebral fractures (odds ratio, 1.04; P < .001).

Mortality doubled, though not significantly

Those with vertebral fractures were more likely to be hospitalized, although not significantly (88% vs. 74%). There was no significant difference in ICU admission (11% vs. 12.5%).

However, those with vertebral fractures required noninvasive mechanical ventilation significantly more often (48.8% vs. 27.4%; P = .02), and were more than twice as likely to die (22% vs. 10%; P = .07). While the difference in overall mortality wasn’t quite statistically significant, those with severe vertebral fractures were significantly more likely to die, compared with those with mild or moderate fractures (60%, 7%, 24%, respectively, for severe, moderate, and mild; P = .04), despite no significant differences in clinical or laboratory parameters.

“Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID pandemic with at least those patients already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D, which have also been suggested very recently to have no relevant predisposing effect on COVID-19,” Dr. Giustina and colleagues wrote.

Moreover, they added, “continuity of care should also include bone density monitoring despite very restricted access to clinical facilities, during the COVID-19 pandemic. Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay.”

The authors reported having no disclosures.

SOURCE: Giustina A et al. J Clin Endocrinol Metab. 2020 Oct 21. doi: 10.1210/clinem/dgaa738.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

Screening for colorectal cancer (CRC) should begin at age 45 years instead of 50 years, as recommended in the current guideline, the US Preventive Services Task Force (USPSTF) said in a draft recommendation that is open for public comment.

“This is the only change that was made,” said task force member Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston.

The recommendation is that all adults aged 45-75 years be screened for CRC.

This is an “A” recommendation for adults aged 50-75 and a “B” recommendation for adults aged 45-49. Dr. Barry explained that the reason for this difference is that the benefit is smaller for the 45- to 49-years age group. “But there’s not much difference between A and B from a practical standpoint,” he explained.

For adults aged 76-85, the benefits and harms of screening need to be weighed against the individual’s overall health and personal circumstances. This is a “C” recommendation.

Barry emphasized that the USPSTF document is not final. The draft recommendation and supporting evidence is posted on the task force website and will be available for public comments until Nov. 23.
 

Mounting pressure

The move comes after mounting evidence of an increase in CRC among younger adults and mounting pressure to lower the starting age.

Two years ago, the American Cancer Society (ACS) revised its own screening guidelines and lowered the starting age to 45 years. Soon afterward, a coalition of 22 public health and patient advocacy groups joined the ACS in submitting a letter to the USPSTF asking that the task force reconsider its 2016 guidance (which recommends starting at age 50 years).

The starting age for screening is an important issue, commented Judy Yee, MD, chair of radiology at the Albert Einstein College of Medicine and the Montefiore Health System in New York and chair of the Colon Cancer Committee of the American College of Radiology.

“Right now it is very confusing to physicians and to the public,” Dr. Yee said in an interview at that time. “The USPSTF and the ACS differ as far as the age to begin screening, and insurers may not cover the cost of colorectal cancer screening before age 50.”

Dr. Barry said that the Task Force took notice of recent data showing an increase in the incidence of CRC among younger adults. “The risk now for age 45 to 49 is pretty similar to the risk for people in their early 50s. So in some ways, today’s late 40-year-olds are like yesterday’s 50-year-olds,” he commented.

The task force used simulation models that confirmed what the epidemiologic data suggested and “that we could prevent some additional colorectal cancer deaths by starting screening at age 45,” he said.

The rest of the new draft recommendation is similar to the 2016 guidelines, in which the task force says there is convincing evidence that CRC screening substantially reduces disease-related mortality. However, it does not recommend any one screening approach over another. It recommends both direct visualization, such as colonoscopy, as well as noninvasive stool-based tests. It does not recommend serum tests, urine tests, or capsule endoscopy because there is not yet enough evidence about the benefits and harms of these tests.

“The right test is the one a patient will do,” Dr. Barry commented.

Defining populations

CRC in young adults made the news in August 2020 when Chadwick Boseman, known for his role as King T’Challa in Marvel’s “Black Panther,” died of colon cancer. Diagnosed in 2016, he was only 43 years old.

“The recent passing of Chadwick Boseman is tragic, and our thoughts are with his loved ones during this difficult time,” said Dr. Barry. “As a Black man, the data show that Chadwick was at higher risk for developing colorectal cancer.”

Unfortunately, there is currently not enough evidence that screening Black men younger than 45 could help prevent tragic deaths such as Chadwick’s, he commented. “The task force is calling for more research on colorectal cancer screening in Black adults,” he added.
 

Limit screening to those at higher risk

In contrast to the USPSTF and ACS guidelines, which recommend screening for CRC for everyone over a certain age, a set of recommendations developed by an international panel of experts suggests screening only for individuals who are at higher risk for CRC.

As previously reported, these guidelines suggest restricting screening to adults whose cumulative cancer risk is 3% or more in the next 15 years, the point at which the balance between benefits and harms favors screening.

The authors, led by Lise Helsingen, MD, Clinical Effectiveness Research Group, University of Oslo, said “the optimal choice for each person requires shared decision-making.”

Such a risk-based approach is “increasingly regarded as the most appropriate way to discuss cancer screening.” That approach is already used in prostate and lung cancer screening, they noted.
 

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

Screening for colorectal cancer (CRC) should begin at age 45 years instead of 50 years, as recommended in the current guideline, the US Preventive Services Task Force (USPSTF) said in a draft recommendation that is open for public comment.

“This is the only change that was made,” said task force member Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston.

The recommendation is that all adults aged 45-75 years be screened for CRC.

This is an “A” recommendation for adults aged 50-75 and a “B” recommendation for adults aged 45-49. Dr. Barry explained that the reason for this difference is that the benefit is smaller for the 45- to 49-years age group. “But there’s not much difference between A and B from a practical standpoint,” he explained.

For adults aged 76-85, the benefits and harms of screening need to be weighed against the individual’s overall health and personal circumstances. This is a “C” recommendation.

Barry emphasized that the USPSTF document is not final. The draft recommendation and supporting evidence is posted on the task force website and will be available for public comments until Nov. 23.
 

Mounting pressure

The move comes after mounting evidence of an increase in CRC among younger adults and mounting pressure to lower the starting age.

Two years ago, the American Cancer Society (ACS) revised its own screening guidelines and lowered the starting age to 45 years. Soon afterward, a coalition of 22 public health and patient advocacy groups joined the ACS in submitting a letter to the USPSTF asking that the task force reconsider its 2016 guidance (which recommends starting at age 50 years).

The starting age for screening is an important issue, commented Judy Yee, MD, chair of radiology at the Albert Einstein College of Medicine and the Montefiore Health System in New York and chair of the Colon Cancer Committee of the American College of Radiology.

“Right now it is very confusing to physicians and to the public,” Dr. Yee said in an interview at that time. “The USPSTF and the ACS differ as far as the age to begin screening, and insurers may not cover the cost of colorectal cancer screening before age 50.”

Dr. Barry said that the Task Force took notice of recent data showing an increase in the incidence of CRC among younger adults. “The risk now for age 45 to 49 is pretty similar to the risk for people in their early 50s. So in some ways, today’s late 40-year-olds are like yesterday’s 50-year-olds,” he commented.

The task force used simulation models that confirmed what the epidemiologic data suggested and “that we could prevent some additional colorectal cancer deaths by starting screening at age 45,” he said.

The rest of the new draft recommendation is similar to the 2016 guidelines, in which the task force says there is convincing evidence that CRC screening substantially reduces disease-related mortality. However, it does not recommend any one screening approach over another. It recommends both direct visualization, such as colonoscopy, as well as noninvasive stool-based tests. It does not recommend serum tests, urine tests, or capsule endoscopy because there is not yet enough evidence about the benefits and harms of these tests.

“The right test is the one a patient will do,” Dr. Barry commented.

Defining populations

CRC in young adults made the news in August 2020 when Chadwick Boseman, known for his role as King T’Challa in Marvel’s “Black Panther,” died of colon cancer. Diagnosed in 2016, he was only 43 years old.

“The recent passing of Chadwick Boseman is tragic, and our thoughts are with his loved ones during this difficult time,” said Dr. Barry. “As a Black man, the data show that Chadwick was at higher risk for developing colorectal cancer.”

Unfortunately, there is currently not enough evidence that screening Black men younger than 45 could help prevent tragic deaths such as Chadwick’s, he commented. “The task force is calling for more research on colorectal cancer screening in Black adults,” he added.
 

Limit screening to those at higher risk

In contrast to the USPSTF and ACS guidelines, which recommend screening for CRC for everyone over a certain age, a set of recommendations developed by an international panel of experts suggests screening only for individuals who are at higher risk for CRC.

As previously reported, these guidelines suggest restricting screening to adults whose cumulative cancer risk is 3% or more in the next 15 years, the point at which the balance between benefits and harms favors screening.

The authors, led by Lise Helsingen, MD, Clinical Effectiveness Research Group, University of Oslo, said “the optimal choice for each person requires shared decision-making.”

Such a risk-based approach is “increasingly regarded as the most appropriate way to discuss cancer screening.” That approach is already used in prostate and lung cancer screening, they noted.
 

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

Screening for colorectal cancer (CRC) should begin at age 45 years instead of 50 years, as recommended in the current guideline, the US Preventive Services Task Force (USPSTF) said in a draft recommendation that is open for public comment.

“This is the only change that was made,” said task force member Michael Barry, MD, director of the Informed Medical Decisions Program in the Health Decision Sciences Center at Massachusetts General Hospital, Boston.

The recommendation is that all adults aged 45-75 years be screened for CRC.

This is an “A” recommendation for adults aged 50-75 and a “B” recommendation for adults aged 45-49. Dr. Barry explained that the reason for this difference is that the benefit is smaller for the 45- to 49-years age group. “But there’s not much difference between A and B from a practical standpoint,” he explained.

For adults aged 76-85, the benefits and harms of screening need to be weighed against the individual’s overall health and personal circumstances. This is a “C” recommendation.

Barry emphasized that the USPSTF document is not final. The draft recommendation and supporting evidence is posted on the task force website and will be available for public comments until Nov. 23.
 

Mounting pressure

The move comes after mounting evidence of an increase in CRC among younger adults and mounting pressure to lower the starting age.

Two years ago, the American Cancer Society (ACS) revised its own screening guidelines and lowered the starting age to 45 years. Soon afterward, a coalition of 22 public health and patient advocacy groups joined the ACS in submitting a letter to the USPSTF asking that the task force reconsider its 2016 guidance (which recommends starting at age 50 years).

The starting age for screening is an important issue, commented Judy Yee, MD, chair of radiology at the Albert Einstein College of Medicine and the Montefiore Health System in New York and chair of the Colon Cancer Committee of the American College of Radiology.

“Right now it is very confusing to physicians and to the public,” Dr. Yee said in an interview at that time. “The USPSTF and the ACS differ as far as the age to begin screening, and insurers may not cover the cost of colorectal cancer screening before age 50.”

Dr. Barry said that the Task Force took notice of recent data showing an increase in the incidence of CRC among younger adults. “The risk now for age 45 to 49 is pretty similar to the risk for people in their early 50s. So in some ways, today’s late 40-year-olds are like yesterday’s 50-year-olds,” he commented.

The task force used simulation models that confirmed what the epidemiologic data suggested and “that we could prevent some additional colorectal cancer deaths by starting screening at age 45,” he said.

The rest of the new draft recommendation is similar to the 2016 guidelines, in which the task force says there is convincing evidence that CRC screening substantially reduces disease-related mortality. However, it does not recommend any one screening approach over another. It recommends both direct visualization, such as colonoscopy, as well as noninvasive stool-based tests. It does not recommend serum tests, urine tests, or capsule endoscopy because there is not yet enough evidence about the benefits and harms of these tests.

“The right test is the one a patient will do,” Dr. Barry commented.

Defining populations

CRC in young adults made the news in August 2020 when Chadwick Boseman, known for his role as King T’Challa in Marvel’s “Black Panther,” died of colon cancer. Diagnosed in 2016, he was only 43 years old.

“The recent passing of Chadwick Boseman is tragic, and our thoughts are with his loved ones during this difficult time,” said Dr. Barry. “As a Black man, the data show that Chadwick was at higher risk for developing colorectal cancer.”

Unfortunately, there is currently not enough evidence that screening Black men younger than 45 could help prevent tragic deaths such as Chadwick’s, he commented. “The task force is calling for more research on colorectal cancer screening in Black adults,” he added.
 

Limit screening to those at higher risk

In contrast to the USPSTF and ACS guidelines, which recommend screening for CRC for everyone over a certain age, a set of recommendations developed by an international panel of experts suggests screening only for individuals who are at higher risk for CRC.

As previously reported, these guidelines suggest restricting screening to adults whose cumulative cancer risk is 3% or more in the next 15 years, the point at which the balance between benefits and harms favors screening.

The authors, led by Lise Helsingen, MD, Clinical Effectiveness Research Group, University of Oslo, said “the optimal choice for each person requires shared decision-making.”

Such a risk-based approach is “increasingly regarded as the most appropriate way to discuss cancer screening.” That approach is already used in prostate and lung cancer screening, they noted.
 

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

Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.

This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.

Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.

“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”

Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.

To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.

The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).

After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.

These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.

More studies are needed to explore this relation, said Dr. Achebe.
 

The challenge of self-reported use

The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.

It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”

And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”

This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.

Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.

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

Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.

This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.

Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.

“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”

Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.

To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.

The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).

After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.

These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.

More studies are needed to explore this relation, said Dr. Achebe.
 

The challenge of self-reported use

The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.

It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”

And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”

This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.

Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.

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

Cannabis use is associated with a decrease in the prevalence of steatohepatitis and a slowing of its progression in patients with obesity, results from a retrospective cohort study show.

This suggests “that the anti-inflammatory effects of cannabis may be leading to reduced prevalence of steatohepatitis in cannabis users,” said Ikechukwu Achebe, MD, from the John H. Stroger, Jr. Hospital of Cook County in Chicago.

Liver injuries such as nonalcoholic steatohepatitis are characterized by hepatocellular injury and inflammation, which combine to contribute to an increase in the risk for liver failure, cirrhosis, and hepatocellular carcinoma.

“This is where cannabis comes in,” said Dr. Achebe, who presented the study results at the virtual annual meeting of the American College of Gastroenterology. “It is the most commonly used psychoactive substance worldwide and has been shown to reduce hepatic myofibroblast and stellate cell injury. Studies using mouse models have demonstrated reduced liver fibrosis and cirrhosis as a consequence of cannabis exposure.”

Given this possible connection, Dr. Achebe and colleagues set out to determine whether cannabis use affects the prevalence and progression of nonalcoholic fatty liver disease (NAFLD) in obese patients.

To do so, they analyzed the discharge records of 879,952 obese adults in the 2016 Healthcare Cost and Utilization Project National Inpatient Sample. The primary outcome was the prevalence of the four presentations of NAFLD: steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma.

The researchers compared disease stages in cannabis users and nonusers. In the study cohort of 14,236 patients, 1.6% used cannabis. Steatohepatitis was less common among cannabis users than among nonusers (0.4% vs. 0.7%; P < .001), as was cirrhosis (1.1% vs. 1.5%; P < .001).

After propensity matching, the association between cannabis use and lower rates of steatohepatitis remained significant (0.4% vs. 0.5%; P = .035), but the association between cannabis use and the prevalence of nonalcoholic fatty liver, cirrhosis, and hepatocellular carcinoma did not.

These results might be partly explained by the protective effect of cannabis on hepatocytes regulated by the endocannabinoid system, the researchers concluded.

More studies are needed to explore this relation, said Dr. Achebe.
 

The challenge of self-reported use

The study is “incredibly interesting,” said Nancy S. Reau, MD, from Rush Medical College, Chicago. However, the association between cannabis and nonalcoholic fatty liver needs to be further investigated before clinicians can counsel their patients to use the agent to prevent progression.

It is difficult in a study such as this to tease out other lifestyle factors that might be linked to cannabis use, she explained. For example, “is it possible that the cannabis users exercise more, drink more coffee, or eat differently?”

And “self-reported use is challenging,” Dr. Reau said in an interview. “This cannot differentiate someone who occasionally uses from someone who is a heavy daily user. There must be some minimum level of exposure needed for it to have protective effects, if they exist.”

This study was honored at the meeting as an ACG Newsworthy Abstract and an ACG Outstanding Poster Presenter.

Dr. Achebe disclosed no relevant financial relationships. Dr. Reau reported receiving research support from Genfit and having a consultant relationship with Intercept Pharmaceuticals.

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

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

A national effort to perform genotype drug matching across cancer types shows the value of next-generation sequencing and provides a roadmap for future precision oncology trials, according to experts.

Massachusetts General Hospital

The effort is the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial. For this study, researchers performed next-generation sequencing on tumor biopsy specimens to identify therapeutically actionable molecular alterations in patients with “underexplored” cancer types.

The trial included 5,954 patients with cancers that had progressed on standard treatments or rare cancers for which there is no standard treatment. If actionable alterations were found in these patients, they could receive new drugs in development that showed promise in other clinical trials or drugs that were approved by the Food and Drug Administration to treat at least one cancer type.

Data newly reported in the Journal of Clinical Oncology showed that 37.6% of patients had alterations that could be matched to targeted drugs, and 17.8% of patients were assigned to targeted treatment. Multiple actionable tumor mutations were seen in 11.9% of specimens, and resistance-conferring mutations were seen in 71.3% of specimens.

“The bottom line from this report is that next-generation sequencing is an efficient way to identify both approved and promising investigational therapies. For this reason, it should be considered standard of care for patients with advanced cancers,” said study chair Keith T. Flaherty, MD, director of the Henri and Belinda Termeer Center for Targeted Therapy at Massachusetts General Hospital Cancer Center in Boston.

“This study sets the benchmark for the ‘actionability’ of next-generation sequencing,” Dr. Flaherty added. “We expect this number [of actionable alterations] will continue to rise steadily as further advances are made in the development of therapies that target some of the genetic alterations for which we could not offer treatment options in NCI-MATCH.”
 

Relapsed/refractory vs. primary tumors

The NCI-MATCH researchers focused on the most commonly found genetic alterations and performed biopsies at study entry to provide the most accurate picture of the genetic landscape of relapsed/refractory cancer patients. That makes this cohort distinct from The Cancer Genome Atlas (TCGA), a database of patients with mostly untreated primary tumors, and other published cohorts that include genetic analysis of primary tumors and biopsies from the time of initial metastatic recurrence.

The researchers compared the tumor gene makeup of NCI-MATCH and TCGA patients with seven cancer types – breast, bile duct, cervix, colorectal, lung, pancreas, and prostate.

ECOG-ACRIN Cancer Research Group

“Perhaps the biggest surprise was the relatively minimal change in the genetic alterations found in these relapsed/refractory patients, compared to primary tumors,” Dr. Flaherty said. “These findings suggest that it is very reasonable to perform next-generation sequencing at the time of initial metastatic cancer diagnosis and to rely on those findings for the purposes of considering FDA-approved therapies and clinical trial participation.”
 

Multiple alterations and resistance

The complex genetics of cancers has led researchers to explore combinations of targeted and other therapies to address multiple defects at the same time.

“Not surprisingly, the most common collision of multiple genetic alterations within the same tumor was in the commonly altered tumor suppressor genes: TP53, APC, and PTEN,” Dr. Flaherty said.

“An increasing body of evidence supports a role for loss-of-function alterations in these genes to confer resistance to many targeted therapies,” he added. “While we don’t have targeted therapies yet established to directly counter this form of therapeutic resistance, we hypothesize that various types of combination therapy may be able to indirectly undercut resistance and enhance the benefit of many targeted therapies.”

The NCI-MATCH researchers will continue to mine this large dataset to better understand the many small, genetically defined cancer subpopulations.

“We will continue to report the outcome of the individual treatment subprotocols, and combining this genetic analysis with those outcomes will likely inform the next clinical trials,” Dr. Flaherty said.
 

Actionable mutations make a difference

Precision oncology experts agree that NCI-MATCH results are impressive and add a fuller appreciation that actionable mutations make a clinical difference.

“This is a powerful, extremely well-designed study, a tour de force of collaborative science,” said Stephen Gruber, MD, PhD, director of the Center for Precision Medicine at City of Hope National Medical Center in Duarte, Calif.

“The future holds even more promise,” he added. “Our ability to interrogate the genomic landscape of cancer is improving rapidly. Tumor testing helps get the right drug to the right tumor faster than a guidelines-based approach from historical data of combination chemotherapy. This is a likely game changer for the way oncologists will practice in the future, especially as we learn more results of subset trials. The NCI-MATCH researchers have taken a laser-focused look at the current data, but we now know we can look far more comprehensively at genomic profiles of tumors.”

From the viewpoint of the practicing oncologist, co-occurring resistance mutations make a difference in defining what combinations are likely and, more importantly, less likely to be effective. “When we see two mutations and one is likely to confer resistance, we can make a choice to avoid a drug that is not likely to work,” Dr. Gruber said.

“The NCI-MATCH trial allows both approved and investigational agents, which expands the possibility of matching patients to newer agents. This is especially relevant if there are no FDA-approved drugs yet for some molecular aberrations,” said Lillian L. Siu, MD, a senior medical oncologist at the Princess Margaret Cancer Centre in Toronto. “This trial enables such evaluations under the auspice of a clinical trial to provide important knowledge.”

Both experts agree that in-depth biological interrogations of cancer will move the field of precision oncology forward. Dr. Gruber said that “studies have not yet fully addressed the power of germline genetic testing of DNA. Inherited susceptibility will drive therapeutic choices – for example, PARP inhibitors that access homologous recombination deficiency for breast, ovarian, and prostate cancer. We will learn more about treatment choices for those cancers.”

Dr. Siu added: “I truly believe that liquid biopsies [circulating tumor DNA] will help us perform target-drug matching in a less invasive way. We need to explore beyond the genome to look at the transcriptome, proteome, epigenome, and immunome, among others. It is likely that multiomic predictors are going to be able to identify more therapeutic options compared to single genomic predictors.”

Dr. Flaherty noted that all tumor samples from patients assigned to treatment are being subjected to whole-exome sequencing to further the discovery of the genetic features of responsive and nonresponsive tumors.

NCI-MATCH was funded by the National Cancer Institute. Dr. Flaherty disclosed relationships with Clovis Oncology, Loxo, X4 Pharma, and many other companies. His coauthors disclosed many conflicts as well. Dr. Gruber is cofounder of Brogent International. Dr. Siu disclosed relationships with Agios, Treadwell Therapeutics, Merck, Pfizer, and many other companies.

SOURCE: Flaherty KT et al. J Clin Oncol. 2020 Oct 13. doi: 10.1200/JCO.19.03010.

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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