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Sharon Worcester is an award-winning medical journalist for MDedge News. She has been with the company since 1996, first as the Southeast Bureau Chief (1996-2009) when the company was known as International Medical News Group, then as a freelance writer (2010-2015) before returning as a reporter in 2015. She previously worked as a daily newspaper reporter covering health and local government. Sharon currently reports primarily on oncology and hematology. She has a BA from Eckerd College and an MA in Mass Communication/Print Journalism from the University of Florida. Connect with her via LinkedIn and follow her on twitter @SW_MedReporter.
Combo elicits responses in advanced cervical cancer
regardless of programmed death–ligand 1 (PD-L1) expression, according to preliminary findings from a phase 2 study.
Apatinib, an inhibitor of vascular endothelial growth factor receptor-2, and camrelizumab, an anti-PD-1 monoclonal antibody, produced an objective response rate of 60% in evaluable patients.
Chunyan Lan, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, and colleagues reported these results in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic. The following data differ somewhat from the abstract.
Dr. Lan and colleagues reported results in 45 patients who had progressed after at least one line of systemic chemotherapy for metastatic, recurrent, or persistent cervical cancer, and had measurable disease. Patients had a median age of 51 years and an Eastern Cooperative Oncology Group performance status of 0-1. They were enrolled at four centers in China between Jan. 21 and Aug. 1, 2019.
Treatment consisted of oral apatinib at a dose of 250 mg once daily and intravenous camrelizumab at a dose of 200 mg every 2 weeks until disease progression, unacceptable toxicity, or consent withdrawal.
As of Jan. 22, 2020, 25 of 42 efficacy-evaluable patients had achieved a response. Two patients had a complete response, 23 had a partial response, and 12 had stable disease.
“We saw responses in patients regardless of PD-L1 expression,” Dr. Lan said. “In our study, 34% were PD-L1 negative, and the response rate is 65% in PD-L1-positive and 50% in PD-L1-negative [patients].”
The median duration of response was not reached, she added.
The median follow-up was 9.2 months, with the last patient enrolled having 6 months of follow-up. At the data cutoff, 19 patients had disease progression, and 8 had died of their disease.
The median overall survival also was not reached, Dr. Lan said, but overall survival at 9 months was 80%. The median progression-free survival was 7.6 months, and the 6-month progression-free survival rate was 58%.
Grade 3 or greater treatment-related adverse events occurred in 68.9% of patients; adverse events occurring in at least 5% of patients included hypertension (22.2%), fatigue (15.6%), anemia (13.3%), and thrombocytopenia (6.7%).
“Nineteen patients were still on treatment at the data cutoff date, and 26 patients discontinued the study,” Dr. Lan said. “The most common reason to discontinue was disease progression, and three patients discontinued the study due to adverse events.”
“These preliminary results are very encouraging,” Dr. Lan said. “As we know, pembrolizumab is approved as the second-line therapy in recurrent cervical cancer [in] PD-L1-positive patients, and the objective response rate with pembrolizumab monotherapy for recurrent cervical cancer is only 17%, as reported in KEYNOTE-028 [J Clin Oncol. 2017 Dec 20;35(36):4035-41].”
Furthermore, apatinib monotherapy has been studied with only modest results.
“But in our study, this combination is really effective in recurrent cervical cancer, and we see a very durable response,” she said, again emphasizing that those responses occurred regardless of PD-L1 expression. “So this is important. ... We think our findings expand the opportunity of patients with recurrent cervical cancer to receive immune therapy.”
Study participants will be followed for 2 years, Dr. Lan noted.
She reported having no disclosures. The study is sponsored by Sun Yat-sen University.
[email protected]
SOURCE: Lan C et al. SGO 2020, Abstract 55.
regardless of programmed death–ligand 1 (PD-L1) expression, according to preliminary findings from a phase 2 study.
Apatinib, an inhibitor of vascular endothelial growth factor receptor-2, and camrelizumab, an anti-PD-1 monoclonal antibody, produced an objective response rate of 60% in evaluable patients.
Chunyan Lan, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, and colleagues reported these results in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic. The following data differ somewhat from the abstract.
Dr. Lan and colleagues reported results in 45 patients who had progressed after at least one line of systemic chemotherapy for metastatic, recurrent, or persistent cervical cancer, and had measurable disease. Patients had a median age of 51 years and an Eastern Cooperative Oncology Group performance status of 0-1. They were enrolled at four centers in China between Jan. 21 and Aug. 1, 2019.
Treatment consisted of oral apatinib at a dose of 250 mg once daily and intravenous camrelizumab at a dose of 200 mg every 2 weeks until disease progression, unacceptable toxicity, or consent withdrawal.
As of Jan. 22, 2020, 25 of 42 efficacy-evaluable patients had achieved a response. Two patients had a complete response, 23 had a partial response, and 12 had stable disease.
“We saw responses in patients regardless of PD-L1 expression,” Dr. Lan said. “In our study, 34% were PD-L1 negative, and the response rate is 65% in PD-L1-positive and 50% in PD-L1-negative [patients].”
The median duration of response was not reached, she added.
The median follow-up was 9.2 months, with the last patient enrolled having 6 months of follow-up. At the data cutoff, 19 patients had disease progression, and 8 had died of their disease.
The median overall survival also was not reached, Dr. Lan said, but overall survival at 9 months was 80%. The median progression-free survival was 7.6 months, and the 6-month progression-free survival rate was 58%.
Grade 3 or greater treatment-related adverse events occurred in 68.9% of patients; adverse events occurring in at least 5% of patients included hypertension (22.2%), fatigue (15.6%), anemia (13.3%), and thrombocytopenia (6.7%).
“Nineteen patients were still on treatment at the data cutoff date, and 26 patients discontinued the study,” Dr. Lan said. “The most common reason to discontinue was disease progression, and three patients discontinued the study due to adverse events.”
“These preliminary results are very encouraging,” Dr. Lan said. “As we know, pembrolizumab is approved as the second-line therapy in recurrent cervical cancer [in] PD-L1-positive patients, and the objective response rate with pembrolizumab monotherapy for recurrent cervical cancer is only 17%, as reported in KEYNOTE-028 [J Clin Oncol. 2017 Dec 20;35(36):4035-41].”
Furthermore, apatinib monotherapy has been studied with only modest results.
“But in our study, this combination is really effective in recurrent cervical cancer, and we see a very durable response,” she said, again emphasizing that those responses occurred regardless of PD-L1 expression. “So this is important. ... We think our findings expand the opportunity of patients with recurrent cervical cancer to receive immune therapy.”
Study participants will be followed for 2 years, Dr. Lan noted.
She reported having no disclosures. The study is sponsored by Sun Yat-sen University.
[email protected]
SOURCE: Lan C et al. SGO 2020, Abstract 55.
regardless of programmed death–ligand 1 (PD-L1) expression, according to preliminary findings from a phase 2 study.
Apatinib, an inhibitor of vascular endothelial growth factor receptor-2, and camrelizumab, an anti-PD-1 monoclonal antibody, produced an objective response rate of 60% in evaluable patients.
Chunyan Lan, MD, of Sun Yat-sen University Cancer Center in Guangzhou, China, and colleagues reported these results in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic. The following data differ somewhat from the abstract.
Dr. Lan and colleagues reported results in 45 patients who had progressed after at least one line of systemic chemotherapy for metastatic, recurrent, or persistent cervical cancer, and had measurable disease. Patients had a median age of 51 years and an Eastern Cooperative Oncology Group performance status of 0-1. They were enrolled at four centers in China between Jan. 21 and Aug. 1, 2019.
Treatment consisted of oral apatinib at a dose of 250 mg once daily and intravenous camrelizumab at a dose of 200 mg every 2 weeks until disease progression, unacceptable toxicity, or consent withdrawal.
As of Jan. 22, 2020, 25 of 42 efficacy-evaluable patients had achieved a response. Two patients had a complete response, 23 had a partial response, and 12 had stable disease.
“We saw responses in patients regardless of PD-L1 expression,” Dr. Lan said. “In our study, 34% were PD-L1 negative, and the response rate is 65% in PD-L1-positive and 50% in PD-L1-negative [patients].”
The median duration of response was not reached, she added.
The median follow-up was 9.2 months, with the last patient enrolled having 6 months of follow-up. At the data cutoff, 19 patients had disease progression, and 8 had died of their disease.
The median overall survival also was not reached, Dr. Lan said, but overall survival at 9 months was 80%. The median progression-free survival was 7.6 months, and the 6-month progression-free survival rate was 58%.
Grade 3 or greater treatment-related adverse events occurred in 68.9% of patients; adverse events occurring in at least 5% of patients included hypertension (22.2%), fatigue (15.6%), anemia (13.3%), and thrombocytopenia (6.7%).
“Nineteen patients were still on treatment at the data cutoff date, and 26 patients discontinued the study,” Dr. Lan said. “The most common reason to discontinue was disease progression, and three patients discontinued the study due to adverse events.”
“These preliminary results are very encouraging,” Dr. Lan said. “As we know, pembrolizumab is approved as the second-line therapy in recurrent cervical cancer [in] PD-L1-positive patients, and the objective response rate with pembrolizumab monotherapy for recurrent cervical cancer is only 17%, as reported in KEYNOTE-028 [J Clin Oncol. 2017 Dec 20;35(36):4035-41].”
Furthermore, apatinib monotherapy has been studied with only modest results.
“But in our study, this combination is really effective in recurrent cervical cancer, and we see a very durable response,” she said, again emphasizing that those responses occurred regardless of PD-L1 expression. “So this is important. ... We think our findings expand the opportunity of patients with recurrent cervical cancer to receive immune therapy.”
Study participants will be followed for 2 years, Dr. Lan noted.
She reported having no disclosures. The study is sponsored by Sun Yat-sen University.
[email protected]
SOURCE: Lan C et al. SGO 2020, Abstract 55.
FROM SGO 2020
Weight loss intervention fails in endometrial cancer survivors
Of 358 endometrial cancer survivors with a body mass index of at least 30 kg/m2 who were approached for participation in the randomized ScaleDown trial, 80 participated and 278 declined. The results of that study, which compared a “high-tech” weight loss intervention to “enhanced usual care,” were reported last year (Gynecol Oncol. 2019 Jun;154[1]:20).
The goal of the ScaleDown trial was to identify a “better mechanism of weight loss encouragement for our patients,” said Abigail Zamorano, MD, of Washington University, St. Louis. “Unfortunately, we found that there was no difference in those two groups. It was rather disappointing.”
Dr. Zamorano and colleagues hypothesized that although the women who participated in the study failed to lose weight, perhaps they gained less weight than women who did not participate. Therefore, the researchers performed a retrospective study comparing the two groups.
The researchers reported results from this study in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
Retrospective results
At both 6 months and 12 months of follow-up, there were no significant differences between the ScaleDown participants and nonparticipants with respect to BMI change from baseline (P = .77 and P = .76, respectively).
“In essence, we unfortunately found no difference in BMI change in these two groups either,” Dr. Zamorano said.
At 12 months, rates of weight loss and weight gain were similar in ScaleDown participants and nonparticipants:
- 49.2% and 47%, respectively, gained weight.
- 13.9% and 23.2%, respectively, lost 0% to 2.5% of weight.
- 10.8% and 7.1%, respectively, lost 2.5% to 4% of weight.
- 3.1% and 4.8%, respectively, lost 4% to 5% of weight.
- 23.1% and 17.9%, respectively, lost 5% or more of weight.
Compared with participants, the nonparticipants were significantly more likely to be white and were older (63.4 years vs. 59.3 years), on more medications (median of 7 vs. 4), had a lower median BMI (39.1 kg/m2 vs. 41.7 kg/m2), were more likely to have recurrent cancer (15.2% vs. 5.1%), and were less likely to have had genetic counseling (10.8% vs. 20%). There were no differences between the groups in cancer histology, stage, or receipt of initial chemotherapy or radiation therapy.
How can oncologists help patients lose weight?
“Overall, I would say that the findings for the primary endpoint were not particularly encouraging,” Dr. Zamorano said.
However, she said an important message emerged from some of the survey results: Patients were very frustrated with their weight loss journey. Many said that, despite having a desire to lose weight, they didn’t know how, and nothing seemed to work. This suggests that, with the right strategies, oncologists are in a position to help, Dr. Zamorano said.
“As their oncologists who see them really regularly for years and years, even after they’ve completed their primary cancer therapy ... we have a unique relationship with them,” she explained. “We have this very unique role that we can play, so we should think a little outside the box about how else we can help our patients potentially lose weight.”
It’s important to try because thousands of women are diagnosed with endometrial cancer in the United States each year, and although many will be “successfully treated from a cancer perspective because they are diagnosed at early stages,” they also can have significant comorbidities – most often obesity, Dr. Zamorano said.
“And in conjunction with that ... diabetes and cardiovascular disease,” she added. “That means they have very high risk of long-term complications of obesity, and even though we are addressing their cancer, we weren’t addressing those other complications.”
One potential solution is bariatric surgery. Weight loss surgery has been shown to improve health care outcomes and reduce mortality rates and costs, yet 89% of ScaleDown participants said they had never considered it, and 67% said they would decline a referral.
This suggests that, despite the available evidence of benefit in patients who are candidates, there is a knowledge gap in awareness of the effectiveness and safety of bariatric surgery in this population, Dr. Zamorano said.
“Given the obesity-related health problems that this population has, we should really address weight as part of the essential cancer management strategy rather than as an afterthought,” she said, adding that it should be incorporated at the start and should potentially include a referral to surgical weight loss.
Dr. Zamorano reported having no disclosures. The research was funded by Washington University.
SOURCE: Zamorano A et al. SGO 2020, Abstract 20.
Of 358 endometrial cancer survivors with a body mass index of at least 30 kg/m2 who were approached for participation in the randomized ScaleDown trial, 80 participated and 278 declined. The results of that study, which compared a “high-tech” weight loss intervention to “enhanced usual care,” were reported last year (Gynecol Oncol. 2019 Jun;154[1]:20).
The goal of the ScaleDown trial was to identify a “better mechanism of weight loss encouragement for our patients,” said Abigail Zamorano, MD, of Washington University, St. Louis. “Unfortunately, we found that there was no difference in those two groups. It was rather disappointing.”
Dr. Zamorano and colleagues hypothesized that although the women who participated in the study failed to lose weight, perhaps they gained less weight than women who did not participate. Therefore, the researchers performed a retrospective study comparing the two groups.
The researchers reported results from this study in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
Retrospective results
At both 6 months and 12 months of follow-up, there were no significant differences between the ScaleDown participants and nonparticipants with respect to BMI change from baseline (P = .77 and P = .76, respectively).
“In essence, we unfortunately found no difference in BMI change in these two groups either,” Dr. Zamorano said.
At 12 months, rates of weight loss and weight gain were similar in ScaleDown participants and nonparticipants:
- 49.2% and 47%, respectively, gained weight.
- 13.9% and 23.2%, respectively, lost 0% to 2.5% of weight.
- 10.8% and 7.1%, respectively, lost 2.5% to 4% of weight.
- 3.1% and 4.8%, respectively, lost 4% to 5% of weight.
- 23.1% and 17.9%, respectively, lost 5% or more of weight.
Compared with participants, the nonparticipants were significantly more likely to be white and were older (63.4 years vs. 59.3 years), on more medications (median of 7 vs. 4), had a lower median BMI (39.1 kg/m2 vs. 41.7 kg/m2), were more likely to have recurrent cancer (15.2% vs. 5.1%), and were less likely to have had genetic counseling (10.8% vs. 20%). There were no differences between the groups in cancer histology, stage, or receipt of initial chemotherapy or radiation therapy.
How can oncologists help patients lose weight?
“Overall, I would say that the findings for the primary endpoint were not particularly encouraging,” Dr. Zamorano said.
However, she said an important message emerged from some of the survey results: Patients were very frustrated with their weight loss journey. Many said that, despite having a desire to lose weight, they didn’t know how, and nothing seemed to work. This suggests that, with the right strategies, oncologists are in a position to help, Dr. Zamorano said.
“As their oncologists who see them really regularly for years and years, even after they’ve completed their primary cancer therapy ... we have a unique relationship with them,” she explained. “We have this very unique role that we can play, so we should think a little outside the box about how else we can help our patients potentially lose weight.”
It’s important to try because thousands of women are diagnosed with endometrial cancer in the United States each year, and although many will be “successfully treated from a cancer perspective because they are diagnosed at early stages,” they also can have significant comorbidities – most often obesity, Dr. Zamorano said.
“And in conjunction with that ... diabetes and cardiovascular disease,” she added. “That means they have very high risk of long-term complications of obesity, and even though we are addressing their cancer, we weren’t addressing those other complications.”
One potential solution is bariatric surgery. Weight loss surgery has been shown to improve health care outcomes and reduce mortality rates and costs, yet 89% of ScaleDown participants said they had never considered it, and 67% said they would decline a referral.
This suggests that, despite the available evidence of benefit in patients who are candidates, there is a knowledge gap in awareness of the effectiveness and safety of bariatric surgery in this population, Dr. Zamorano said.
“Given the obesity-related health problems that this population has, we should really address weight as part of the essential cancer management strategy rather than as an afterthought,” she said, adding that it should be incorporated at the start and should potentially include a referral to surgical weight loss.
Dr. Zamorano reported having no disclosures. The research was funded by Washington University.
SOURCE: Zamorano A et al. SGO 2020, Abstract 20.
Of 358 endometrial cancer survivors with a body mass index of at least 30 kg/m2 who were approached for participation in the randomized ScaleDown trial, 80 participated and 278 declined. The results of that study, which compared a “high-tech” weight loss intervention to “enhanced usual care,” were reported last year (Gynecol Oncol. 2019 Jun;154[1]:20).
The goal of the ScaleDown trial was to identify a “better mechanism of weight loss encouragement for our patients,” said Abigail Zamorano, MD, of Washington University, St. Louis. “Unfortunately, we found that there was no difference in those two groups. It was rather disappointing.”
Dr. Zamorano and colleagues hypothesized that although the women who participated in the study failed to lose weight, perhaps they gained less weight than women who did not participate. Therefore, the researchers performed a retrospective study comparing the two groups.
The researchers reported results from this study in an abstract that had been slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
Retrospective results
At both 6 months and 12 months of follow-up, there were no significant differences between the ScaleDown participants and nonparticipants with respect to BMI change from baseline (P = .77 and P = .76, respectively).
“In essence, we unfortunately found no difference in BMI change in these two groups either,” Dr. Zamorano said.
At 12 months, rates of weight loss and weight gain were similar in ScaleDown participants and nonparticipants:
- 49.2% and 47%, respectively, gained weight.
- 13.9% and 23.2%, respectively, lost 0% to 2.5% of weight.
- 10.8% and 7.1%, respectively, lost 2.5% to 4% of weight.
- 3.1% and 4.8%, respectively, lost 4% to 5% of weight.
- 23.1% and 17.9%, respectively, lost 5% or more of weight.
Compared with participants, the nonparticipants were significantly more likely to be white and were older (63.4 years vs. 59.3 years), on more medications (median of 7 vs. 4), had a lower median BMI (39.1 kg/m2 vs. 41.7 kg/m2), were more likely to have recurrent cancer (15.2% vs. 5.1%), and were less likely to have had genetic counseling (10.8% vs. 20%). There were no differences between the groups in cancer histology, stage, or receipt of initial chemotherapy or radiation therapy.
How can oncologists help patients lose weight?
“Overall, I would say that the findings for the primary endpoint were not particularly encouraging,” Dr. Zamorano said.
However, she said an important message emerged from some of the survey results: Patients were very frustrated with their weight loss journey. Many said that, despite having a desire to lose weight, they didn’t know how, and nothing seemed to work. This suggests that, with the right strategies, oncologists are in a position to help, Dr. Zamorano said.
“As their oncologists who see them really regularly for years and years, even after they’ve completed their primary cancer therapy ... we have a unique relationship with them,” she explained. “We have this very unique role that we can play, so we should think a little outside the box about how else we can help our patients potentially lose weight.”
It’s important to try because thousands of women are diagnosed with endometrial cancer in the United States each year, and although many will be “successfully treated from a cancer perspective because they are diagnosed at early stages,” they also can have significant comorbidities – most often obesity, Dr. Zamorano said.
“And in conjunction with that ... diabetes and cardiovascular disease,” she added. “That means they have very high risk of long-term complications of obesity, and even though we are addressing their cancer, we weren’t addressing those other complications.”
One potential solution is bariatric surgery. Weight loss surgery has been shown to improve health care outcomes and reduce mortality rates and costs, yet 89% of ScaleDown participants said they had never considered it, and 67% said they would decline a referral.
This suggests that, despite the available evidence of benefit in patients who are candidates, there is a knowledge gap in awareness of the effectiveness and safety of bariatric surgery in this population, Dr. Zamorano said.
“Given the obesity-related health problems that this population has, we should really address weight as part of the essential cancer management strategy rather than as an afterthought,” she said, adding that it should be incorporated at the start and should potentially include a referral to surgical weight loss.
Dr. Zamorano reported having no disclosures. The research was funded by Washington University.
SOURCE: Zamorano A et al. SGO 2020, Abstract 20.
FROM SGO 2020
Is protocol-driven COVID-19 respiratory therapy doing more harm than good?
Physicians in the COVID-19 trenches are beginning to question whether standard respiratory therapy protocols for acute respiratory distress syndrome (ARDS) are the best approach for treating patients with COVID-19 pneumonia.
At issue is the standard use of ventilators for a virus whose presentation has not followed the standard for ARDS, but is looking more like high-altitude pulmonary edema (HAPE) in some patients.
In a letter to the editor published in the American Journal of Respiratory and Critical Care Medicine on March 30, and in an editorial accepted for publication in Intensive Care Medicine, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany and colleagues make the case that protocol-driven ventilator use for patients with COVID-19 could be doing more harm than good.
Dr. Gattinoni noted that COVID-19 patients in ICUs in northern Italy had an atypical ARDS presentation with severe hypoxemia and well-preserved lung gas volume. He and colleagues suggested that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation–practicing patience to “buy time with minimum additional damage.”
Similar observations were made by Cameron Kyle-Sidell, MD, a critical care physician working in New York City, who has been speaking out about this issue on Twitter and who shared his own experiences in this video interview with WebMD chief medical officer John Whyte, MD.
The bottom line, as Dr. Kyle-Sidell and Dr. Gattinoni agree, is that protocol-driven ventilator use may be causing lung injury in COVID-19 patients.
Consider disease phenotype
In the editorial, Dr. Gattinoni and colleagues explained further that ventilator settings should be based on physiological findings – with different respiratory treatment based on disease phenotype rather than using standard protocols.
‘“This, of course, is a conceptual model, but based on the observations we have this far, I don’t know of any model which is better,” he said in an interview.
Anecdotal evidence has increasingly demonstrated that this proposed physiological approach is associated with much lower mortality rates among COVID-19 patients, he said.
While not willing to name the hospitals at this time, he said that one center in Europe has had a 0% mortality rate among COVID-19 patients in the ICU when using this approach, compared with a 60% mortality rate at a nearby hospital using a protocol-driven approach.
In his editorial, Dr. Gattinoni disputed the recently published recommendation from the Surviving Sepsis Campaign that “mechanically ventilated patients with COVID-19 should be managed similarly to other patients with acute respiratory failure in the ICU.”
“Yet, COVID-19 pneumonia, despite falling in most of the circumstances under the Berlin definition of ARDS, is a specific disease, whose distinctive features are severe hypoxemia often associated with near normal respiratory system compliance,” Dr. Gattinoni and colleagues wrote, noting that this was true for more than half of the 150 patients he and his colleagues had assessed, and that several other colleagues in northern Italy reported similar findings. “This remarkable combination is almost never seen in severe ARDS.”
Dr. Gattinoni and colleagues hypothesized that COVID-19 patterns at patient presentation depend on interaction between three sets of factors: 1) disease severity, host response, physiological reserve and comorbidities; 2) ventilatory responsiveness of the patient to hypoxemia; and 3) time elapsed between disease onset and hospitalization.
They identified two primary phenotypes based on the interaction of these factors: Type L, characterized by low elastance, low ventilator perfusion ratio, low lung weight, and low recruitability; and Type H, characterized by high elastance, high right-to-left shunt, high lung weight, and high recruitability.
“Given this conceptual model, it follows that the respiratory treatment offered to Type L and Type H patients must be different,” Dr. Gattinoni said.
Patients may transition between phenotypes as their disease evolves. “If you start with the wrong protocol, at the end they become similar,” he said.
Rather, it is important to identify the phenotype at presentation to understand the pathophysiology and treat accordingly, he advised.
The phenotypes are best identified by CT scan, but signs implicit in each of the phenotypes, including respiratory system elastance and recruitability, can be used as surrogates if CT is unavailable, he noted.
“This is a kind of disease in which you don’t have to follow the protocol – you have to follow the physiology,” he said. “Unfortunately, many, many doctors around the world cannot think outside the protocol.”
In his interview with Dr. Whyte, Dr. Kyle-Sidell stressed that doctors must begin to consider other approaches. “We are desperate now, in the sense that everything we are doing does not seem to be working,” Dr. Kyle-Sidell said, noting that the first step toward improving outcomes is admitting that “this is something new.”
“I think it all starts from there, and I think we have the kind of scientific technology and the human capital in this country to solve this or at least have a very good shot at it,” he said.
Proposed treatment model
Dr. Gattinoni and his colleagues offered a proposed treatment model based on their conceptualization:
- Reverse hypoxemia through an increase in FiO2 to a level at which the Type L patient responds well, particularly for Type L patients who are not experiencing dyspnea.
- In Type L patients with dyspnea, try noninvasive options such as high-flow nasal cannula, continuous positive airway pressure, or noninvasive ventilation, and be sure to measure inspiratory esophageal pressure using esophageal manometry or surrogate measures. In intubated patients, determine P0.1 and P occlusion. High PEEP may decrease pleural pressure swings “and stop the vicious cycle that exacerbates lung injury,” but may be associated with high failure rates and delayed intubation.
- Intubate as soon as possible for esophageal pressure swings that increase from 5-10 cm H2O to above 15 cm H2O, which marks a transition from Type L to Type H phenotype and represents the level at which lung injury risk increases.
- For intubated and deeply sedated Type L patients who are hypercapnic, ventilate with volumes greater than 6 mL/kg up to 8-9 mL/kg as this high compliance results in tolerable strain without risk of ventilator-associated lung injury. Prone positioning should be used only as a rescue maneuver. Reduce PEEP to 8-10 cm H2O, given that the recruitability is low and the risk of hemodynamic failure increases at higher levels. Early intubation may avert the transition to Type H phenotype.
- Treat Type H phenotype like severe ARDS, including with higher PEEP if compatible with hemodynamics, and with prone positioning and extracorporeal support.
Dr. Gattinoni reported having no financial disclosures.
[email protected]
Physicians in the COVID-19 trenches are beginning to question whether standard respiratory therapy protocols for acute respiratory distress syndrome (ARDS) are the best approach for treating patients with COVID-19 pneumonia.
At issue is the standard use of ventilators for a virus whose presentation has not followed the standard for ARDS, but is looking more like high-altitude pulmonary edema (HAPE) in some patients.
In a letter to the editor published in the American Journal of Respiratory and Critical Care Medicine on March 30, and in an editorial accepted for publication in Intensive Care Medicine, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany and colleagues make the case that protocol-driven ventilator use for patients with COVID-19 could be doing more harm than good.
Dr. Gattinoni noted that COVID-19 patients in ICUs in northern Italy had an atypical ARDS presentation with severe hypoxemia and well-preserved lung gas volume. He and colleagues suggested that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation–practicing patience to “buy time with minimum additional damage.”
Similar observations were made by Cameron Kyle-Sidell, MD, a critical care physician working in New York City, who has been speaking out about this issue on Twitter and who shared his own experiences in this video interview with WebMD chief medical officer John Whyte, MD.
The bottom line, as Dr. Kyle-Sidell and Dr. Gattinoni agree, is that protocol-driven ventilator use may be causing lung injury in COVID-19 patients.
Consider disease phenotype
In the editorial, Dr. Gattinoni and colleagues explained further that ventilator settings should be based on physiological findings – with different respiratory treatment based on disease phenotype rather than using standard protocols.
‘“This, of course, is a conceptual model, but based on the observations we have this far, I don’t know of any model which is better,” he said in an interview.
Anecdotal evidence has increasingly demonstrated that this proposed physiological approach is associated with much lower mortality rates among COVID-19 patients, he said.
While not willing to name the hospitals at this time, he said that one center in Europe has had a 0% mortality rate among COVID-19 patients in the ICU when using this approach, compared with a 60% mortality rate at a nearby hospital using a protocol-driven approach.
In his editorial, Dr. Gattinoni disputed the recently published recommendation from the Surviving Sepsis Campaign that “mechanically ventilated patients with COVID-19 should be managed similarly to other patients with acute respiratory failure in the ICU.”
“Yet, COVID-19 pneumonia, despite falling in most of the circumstances under the Berlin definition of ARDS, is a specific disease, whose distinctive features are severe hypoxemia often associated with near normal respiratory system compliance,” Dr. Gattinoni and colleagues wrote, noting that this was true for more than half of the 150 patients he and his colleagues had assessed, and that several other colleagues in northern Italy reported similar findings. “This remarkable combination is almost never seen in severe ARDS.”
Dr. Gattinoni and colleagues hypothesized that COVID-19 patterns at patient presentation depend on interaction between three sets of factors: 1) disease severity, host response, physiological reserve and comorbidities; 2) ventilatory responsiveness of the patient to hypoxemia; and 3) time elapsed between disease onset and hospitalization.
They identified two primary phenotypes based on the interaction of these factors: Type L, characterized by low elastance, low ventilator perfusion ratio, low lung weight, and low recruitability; and Type H, characterized by high elastance, high right-to-left shunt, high lung weight, and high recruitability.
“Given this conceptual model, it follows that the respiratory treatment offered to Type L and Type H patients must be different,” Dr. Gattinoni said.
Patients may transition between phenotypes as their disease evolves. “If you start with the wrong protocol, at the end they become similar,” he said.
Rather, it is important to identify the phenotype at presentation to understand the pathophysiology and treat accordingly, he advised.
The phenotypes are best identified by CT scan, but signs implicit in each of the phenotypes, including respiratory system elastance and recruitability, can be used as surrogates if CT is unavailable, he noted.
“This is a kind of disease in which you don’t have to follow the protocol – you have to follow the physiology,” he said. “Unfortunately, many, many doctors around the world cannot think outside the protocol.”
In his interview with Dr. Whyte, Dr. Kyle-Sidell stressed that doctors must begin to consider other approaches. “We are desperate now, in the sense that everything we are doing does not seem to be working,” Dr. Kyle-Sidell said, noting that the first step toward improving outcomes is admitting that “this is something new.”
“I think it all starts from there, and I think we have the kind of scientific technology and the human capital in this country to solve this or at least have a very good shot at it,” he said.
Proposed treatment model
Dr. Gattinoni and his colleagues offered a proposed treatment model based on their conceptualization:
- Reverse hypoxemia through an increase in FiO2 to a level at which the Type L patient responds well, particularly for Type L patients who are not experiencing dyspnea.
- In Type L patients with dyspnea, try noninvasive options such as high-flow nasal cannula, continuous positive airway pressure, or noninvasive ventilation, and be sure to measure inspiratory esophageal pressure using esophageal manometry or surrogate measures. In intubated patients, determine P0.1 and P occlusion. High PEEP may decrease pleural pressure swings “and stop the vicious cycle that exacerbates lung injury,” but may be associated with high failure rates and delayed intubation.
- Intubate as soon as possible for esophageal pressure swings that increase from 5-10 cm H2O to above 15 cm H2O, which marks a transition from Type L to Type H phenotype and represents the level at which lung injury risk increases.
- For intubated and deeply sedated Type L patients who are hypercapnic, ventilate with volumes greater than 6 mL/kg up to 8-9 mL/kg as this high compliance results in tolerable strain without risk of ventilator-associated lung injury. Prone positioning should be used only as a rescue maneuver. Reduce PEEP to 8-10 cm H2O, given that the recruitability is low and the risk of hemodynamic failure increases at higher levels. Early intubation may avert the transition to Type H phenotype.
- Treat Type H phenotype like severe ARDS, including with higher PEEP if compatible with hemodynamics, and with prone positioning and extracorporeal support.
Dr. Gattinoni reported having no financial disclosures.
[email protected]
Physicians in the COVID-19 trenches are beginning to question whether standard respiratory therapy protocols for acute respiratory distress syndrome (ARDS) are the best approach for treating patients with COVID-19 pneumonia.
At issue is the standard use of ventilators for a virus whose presentation has not followed the standard for ARDS, but is looking more like high-altitude pulmonary edema (HAPE) in some patients.
In a letter to the editor published in the American Journal of Respiratory and Critical Care Medicine on March 30, and in an editorial accepted for publication in Intensive Care Medicine, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany and colleagues make the case that protocol-driven ventilator use for patients with COVID-19 could be doing more harm than good.
Dr. Gattinoni noted that COVID-19 patients in ICUs in northern Italy had an atypical ARDS presentation with severe hypoxemia and well-preserved lung gas volume. He and colleagues suggested that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation–practicing patience to “buy time with minimum additional damage.”
Similar observations were made by Cameron Kyle-Sidell, MD, a critical care physician working in New York City, who has been speaking out about this issue on Twitter and who shared his own experiences in this video interview with WebMD chief medical officer John Whyte, MD.
The bottom line, as Dr. Kyle-Sidell and Dr. Gattinoni agree, is that protocol-driven ventilator use may be causing lung injury in COVID-19 patients.
Consider disease phenotype
In the editorial, Dr. Gattinoni and colleagues explained further that ventilator settings should be based on physiological findings – with different respiratory treatment based on disease phenotype rather than using standard protocols.
‘“This, of course, is a conceptual model, but based on the observations we have this far, I don’t know of any model which is better,” he said in an interview.
Anecdotal evidence has increasingly demonstrated that this proposed physiological approach is associated with much lower mortality rates among COVID-19 patients, he said.
While not willing to name the hospitals at this time, he said that one center in Europe has had a 0% mortality rate among COVID-19 patients in the ICU when using this approach, compared with a 60% mortality rate at a nearby hospital using a protocol-driven approach.
In his editorial, Dr. Gattinoni disputed the recently published recommendation from the Surviving Sepsis Campaign that “mechanically ventilated patients with COVID-19 should be managed similarly to other patients with acute respiratory failure in the ICU.”
“Yet, COVID-19 pneumonia, despite falling in most of the circumstances under the Berlin definition of ARDS, is a specific disease, whose distinctive features are severe hypoxemia often associated with near normal respiratory system compliance,” Dr. Gattinoni and colleagues wrote, noting that this was true for more than half of the 150 patients he and his colleagues had assessed, and that several other colleagues in northern Italy reported similar findings. “This remarkable combination is almost never seen in severe ARDS.”
Dr. Gattinoni and colleagues hypothesized that COVID-19 patterns at patient presentation depend on interaction between three sets of factors: 1) disease severity, host response, physiological reserve and comorbidities; 2) ventilatory responsiveness of the patient to hypoxemia; and 3) time elapsed between disease onset and hospitalization.
They identified two primary phenotypes based on the interaction of these factors: Type L, characterized by low elastance, low ventilator perfusion ratio, low lung weight, and low recruitability; and Type H, characterized by high elastance, high right-to-left shunt, high lung weight, and high recruitability.
“Given this conceptual model, it follows that the respiratory treatment offered to Type L and Type H patients must be different,” Dr. Gattinoni said.
Patients may transition between phenotypes as their disease evolves. “If you start with the wrong protocol, at the end they become similar,” he said.
Rather, it is important to identify the phenotype at presentation to understand the pathophysiology and treat accordingly, he advised.
The phenotypes are best identified by CT scan, but signs implicit in each of the phenotypes, including respiratory system elastance and recruitability, can be used as surrogates if CT is unavailable, he noted.
“This is a kind of disease in which you don’t have to follow the protocol – you have to follow the physiology,” he said. “Unfortunately, many, many doctors around the world cannot think outside the protocol.”
In his interview with Dr. Whyte, Dr. Kyle-Sidell stressed that doctors must begin to consider other approaches. “We are desperate now, in the sense that everything we are doing does not seem to be working,” Dr. Kyle-Sidell said, noting that the first step toward improving outcomes is admitting that “this is something new.”
“I think it all starts from there, and I think we have the kind of scientific technology and the human capital in this country to solve this or at least have a very good shot at it,” he said.
Proposed treatment model
Dr. Gattinoni and his colleagues offered a proposed treatment model based on their conceptualization:
- Reverse hypoxemia through an increase in FiO2 to a level at which the Type L patient responds well, particularly for Type L patients who are not experiencing dyspnea.
- In Type L patients with dyspnea, try noninvasive options such as high-flow nasal cannula, continuous positive airway pressure, or noninvasive ventilation, and be sure to measure inspiratory esophageal pressure using esophageal manometry or surrogate measures. In intubated patients, determine P0.1 and P occlusion. High PEEP may decrease pleural pressure swings “and stop the vicious cycle that exacerbates lung injury,” but may be associated with high failure rates and delayed intubation.
- Intubate as soon as possible for esophageal pressure swings that increase from 5-10 cm H2O to above 15 cm H2O, which marks a transition from Type L to Type H phenotype and represents the level at which lung injury risk increases.
- For intubated and deeply sedated Type L patients who are hypercapnic, ventilate with volumes greater than 6 mL/kg up to 8-9 mL/kg as this high compliance results in tolerable strain without risk of ventilator-associated lung injury. Prone positioning should be used only as a rescue maneuver. Reduce PEEP to 8-10 cm H2O, given that the recruitability is low and the risk of hemodynamic failure increases at higher levels. Early intubation may avert the transition to Type H phenotype.
- Treat Type H phenotype like severe ARDS, including with higher PEEP if compatible with hemodynamics, and with prone positioning and extracorporeal support.
Dr. Gattinoni reported having no financial disclosures.
[email protected]
Reports increasingly suggest anosmia/hyposmia can signal early COVID-19 infection
Unexplained anosmia, hyposmia, and dysgeusia should be added to the list of possible COVID-19 symptoms for screening purposes, and individuals with such symptoms should consider self-isolation, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) has proposed.
However, a World Health Organization expert said during a March 23 daily briefing on the novel coronavirus pandemic that the jury is still out on that.
The AAO-HNS proposal is based on “rapidly accumulating” anecdotal evidence that such symptoms – in the absence of other symptoms suggestive of COVID-19 – have sometimes preceded a COVID-19 diagnosis.
“ ... anosmia, hyposmia, and dysgeusia in the absence of other respiratory disease such as allergic rhinitis, acute rhinosinusitis, or chronic rhinosinusitis should alert physicians to the possibility of COVID-19 infection and warrant serious consideration for self-isolation and testing of these individuals,” the AAO-HNS said in a statement on the proposal.
ENT UK, an organization representing Ear, Nose, and Throat surgery and its related specialties in the UK, also is emphasizing the potential importance of these symptoms. In a March 21 letter, ENT UK experts cited “good evidence from South Korea, China and Italy that significant numbers of patients with proven COVID-19 infection have developed anosmia/hyposmia.”
Claire Hopkins, BMBCh, president of the British Rhinological Society and a professor of Rhinology at King’s College London, along with ENT UK president Nirmal Kumar, also noted in the letter that two of every three cases in Germany, and 30% of patients testing positive in South Korea, had anosmia as their first symptom.
“While there is a chance the apparent increase in incidence could merely reflect the attention COVID-19 has attracted in the media, and that such cases may be caused by typical rhinovirus and coronavirus strains, it could potentially be used as a screening tool to help identify otherwise asymptomatic patients, who could then be better instructed on self-isolation,” they wrote.
Maria Van Kerkhove, MD, technical lead of the WHO Medical Emergencies Program, acknowledged the anecdotal evidence during the WHO briefing.
“Yes, we’ve seen quite a few reports ... but this is something that we need to look into to really capture if this is one of the early signs and symptoms of COVID-19,” she said, noting that WHO is working with more than a dozen countries that are systematically collecting data using molecular and serological testing to “capture more robustly” the early signs and symptoms, and is “reaching out to a number of countries and looking at the cases that have already been reported to see if [anosmia] is a common feature.”
“We don’t have the answer to that,” she said, adding that, in addition to the major symptoms – including dry cough, fever, and shortness of breath – that are well known at this point, “there are likely to be many signs and symptoms that people have.”
“A loss of smell or a loss of taste is something that we’re looking into, and we’re looking forward to the results of these early investigations ... so that we have a more evidence-based approach and we can add that to the list.”
Unexplained anosmia, hyposmia, and dysgeusia should be added to the list of possible COVID-19 symptoms for screening purposes, and individuals with such symptoms should consider self-isolation, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) has proposed.
However, a World Health Organization expert said during a March 23 daily briefing on the novel coronavirus pandemic that the jury is still out on that.
The AAO-HNS proposal is based on “rapidly accumulating” anecdotal evidence that such symptoms – in the absence of other symptoms suggestive of COVID-19 – have sometimes preceded a COVID-19 diagnosis.
“ ... anosmia, hyposmia, and dysgeusia in the absence of other respiratory disease such as allergic rhinitis, acute rhinosinusitis, or chronic rhinosinusitis should alert physicians to the possibility of COVID-19 infection and warrant serious consideration for self-isolation and testing of these individuals,” the AAO-HNS said in a statement on the proposal.
ENT UK, an organization representing Ear, Nose, and Throat surgery and its related specialties in the UK, also is emphasizing the potential importance of these symptoms. In a March 21 letter, ENT UK experts cited “good evidence from South Korea, China and Italy that significant numbers of patients with proven COVID-19 infection have developed anosmia/hyposmia.”
Claire Hopkins, BMBCh, president of the British Rhinological Society and a professor of Rhinology at King’s College London, along with ENT UK president Nirmal Kumar, also noted in the letter that two of every three cases in Germany, and 30% of patients testing positive in South Korea, had anosmia as their first symptom.
“While there is a chance the apparent increase in incidence could merely reflect the attention COVID-19 has attracted in the media, and that such cases may be caused by typical rhinovirus and coronavirus strains, it could potentially be used as a screening tool to help identify otherwise asymptomatic patients, who could then be better instructed on self-isolation,” they wrote.
Maria Van Kerkhove, MD, technical lead of the WHO Medical Emergencies Program, acknowledged the anecdotal evidence during the WHO briefing.
“Yes, we’ve seen quite a few reports ... but this is something that we need to look into to really capture if this is one of the early signs and symptoms of COVID-19,” she said, noting that WHO is working with more than a dozen countries that are systematically collecting data using molecular and serological testing to “capture more robustly” the early signs and symptoms, and is “reaching out to a number of countries and looking at the cases that have already been reported to see if [anosmia] is a common feature.”
“We don’t have the answer to that,” she said, adding that, in addition to the major symptoms – including dry cough, fever, and shortness of breath – that are well known at this point, “there are likely to be many signs and symptoms that people have.”
“A loss of smell or a loss of taste is something that we’re looking into, and we’re looking forward to the results of these early investigations ... so that we have a more evidence-based approach and we can add that to the list.”
Unexplained anosmia, hyposmia, and dysgeusia should be added to the list of possible COVID-19 symptoms for screening purposes, and individuals with such symptoms should consider self-isolation, the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) has proposed.
However, a World Health Organization expert said during a March 23 daily briefing on the novel coronavirus pandemic that the jury is still out on that.
The AAO-HNS proposal is based on “rapidly accumulating” anecdotal evidence that such symptoms – in the absence of other symptoms suggestive of COVID-19 – have sometimes preceded a COVID-19 diagnosis.
“ ... anosmia, hyposmia, and dysgeusia in the absence of other respiratory disease such as allergic rhinitis, acute rhinosinusitis, or chronic rhinosinusitis should alert physicians to the possibility of COVID-19 infection and warrant serious consideration for self-isolation and testing of these individuals,” the AAO-HNS said in a statement on the proposal.
ENT UK, an organization representing Ear, Nose, and Throat surgery and its related specialties in the UK, also is emphasizing the potential importance of these symptoms. In a March 21 letter, ENT UK experts cited “good evidence from South Korea, China and Italy that significant numbers of patients with proven COVID-19 infection have developed anosmia/hyposmia.”
Claire Hopkins, BMBCh, president of the British Rhinological Society and a professor of Rhinology at King’s College London, along with ENT UK president Nirmal Kumar, also noted in the letter that two of every three cases in Germany, and 30% of patients testing positive in South Korea, had anosmia as their first symptom.
“While there is a chance the apparent increase in incidence could merely reflect the attention COVID-19 has attracted in the media, and that such cases may be caused by typical rhinovirus and coronavirus strains, it could potentially be used as a screening tool to help identify otherwise asymptomatic patients, who could then be better instructed on self-isolation,” they wrote.
Maria Van Kerkhove, MD, technical lead of the WHO Medical Emergencies Program, acknowledged the anecdotal evidence during the WHO briefing.
“Yes, we’ve seen quite a few reports ... but this is something that we need to look into to really capture if this is one of the early signs and symptoms of COVID-19,” she said, noting that WHO is working with more than a dozen countries that are systematically collecting data using molecular and serological testing to “capture more robustly” the early signs and symptoms, and is “reaching out to a number of countries and looking at the cases that have already been reported to see if [anosmia] is a common feature.”
“We don’t have the answer to that,” she said, adding that, in addition to the major symptoms – including dry cough, fever, and shortness of breath – that are well known at this point, “there are likely to be many signs and symptoms that people have.”
“A loss of smell or a loss of taste is something that we’re looking into, and we’re looking forward to the results of these early investigations ... so that we have a more evidence-based approach and we can add that to the list.”
COVID-19 in China: Children have less severe disease, but are vulnerable
Clinical manifestations of COVID-19 infection among children in mainland China generally have been less severe than those among adults, but children of all ages – and infants in particular – are vulnerable to infection, according to a review of 2,143 cases.
Further, infection patterns in the nationwide series of all pediatric patients reported to the Chinese Center for Disease Control and Prevention from Jan. 16 to Feb. 8, 2020, provide strong evidence of human-to-human transmission, Yuanyuan Dong, MPH, a research assistant at Shanghai Children’s Medical Center, Shanghai Jiao Tong University, China, and colleagues reported in Pediatrics.
Of the 2,143 patients included in the review, 57% were boys and the median age was 7 years; 34% had laboratory-confirmed infection and 67% had suspected infection. More than 90% had asymptomatic, mild, or moderate disease (4%, 51%, and 39%, respectively), and 46% were from Hubei Province, where the first cases were reported, the investigators found.
The median time from illness onset to diagnosis was 2 days, and there was a trend of rapid increase of disease at the early stage of the epidemic – with rapid spread from Hubei Province to surrounding provinces – followed by a gradual and steady decrease, they noted.
“The total number of pediatric patients increased remarkably between mid-January and early February, peaked around February 1, and then declined since early February 2020,” they wrote. The proportion of severe and critical cases was 11% for infants under 1 year of age, compared with 7% for those aged 1-5 years; 4% for those aged 6-10 years; 4% for those 11-15 years; and 3% for those 16 years and older.
As of Feb. 8, 2020, only one child in this group of study patients died and most cases of COVID-19 symptoms were mild. There were many fewer severe and critical cases among the children (6%), compared with those reported in adult patients in other studies (19%). “It suggests that, compared with adult patients, clinical manifestations of children’s COVID-19 may be less severe,” the investigators suggested.
“As most of these children were likely to expose themselves to family members and/or other children with COVID-19, it clearly indicates person-to-person transmission ” of novel coronavirus 2019, they said, adding that similar evidence of such transmission also has been reported from studies of adult patients.
The reasons for reduced severity in children versus adults remain unclear, but may be related to both exposure and host factors, Ms. Dong and associates said. “Children were usually well cared for at home and might have relatively [fewer] opportunities to expose themselves to pathogens and/or sick patients.”
The findings demonstrate a pediatric distribution that varied across time and space, with most cases concentrated in the Hubei province and surrounding areas. No significant gender-related difference in infection rates was observed, and although the median patient age was 7 years, the range was 1 day to 18 years, suggesting that “all ages at childhood were susceptible” to the virus, they added.
The declining number of cases over time further suggests that disease control measures implemented by the government were effective, and that cases will “continue to decline, and finally stop in the near future unless sustained human-to-human transmissions occur,” Ms. Dong and associates concluded.
In an accompanying editorial, Andrea T. Cruz, MD, of Baylor College of Medicine, Houston, and Steven L. Zeichner, MD, PhD, of the University of Virginia, Charlottesville, said the findings regarding reduced severity among children versus adults with novel coronavirus 2019 infection are consistent with data on non-COVID-19 coronavirus.
They pointed out that Ms. Dong and associates did find that 13% of virologically-confirmed cases had asymptomatic infection, “a rate that almost certainly understates the true rate of asymptomatic infection, since many asymptomatic children are unlikely to be tested.”
Of the symptomatic children, “5% had dyspnea or hypoxemia (a substantially lower percentage than what has been reported for adults) and 0.6% progressed to acute respiratory distress syndrome (ARDS) or multiorgan system dysfunction”; this also is at a lower rate than seen in adults, they said.
Very young children –infants or children in preschool – were more likely to have severe clinical manifestations than children who were older.
Thus, it appears that certain subpopulations of children are at increased risk for more significant COVID-19 illness: “younger age, underlying pulmonary pathology, and immunocompromising conditions,” Dr. Cruz and Dr. Zeichner suggested.
The two editorialists said the findings suggest children “may play a major role in community-based viral transmission.” Evidence suggests that children may have more upper respiratory tract involvement and that fecal shedding may occur for several weeks after diagnosis; this raises concerns about fecal-oral transmission, particularly for infants and children, and about viral replication in the gastrointestinal tract, they said. This has substantial implications for community spread in day care centers, schools, and in the home.
A great deal has been learned about COVID-19 in a short time, but there still is much to learn about the effect of the virus on children, the impact of children on viral spread, and about possible vertical transmission, they said.
“Widespread availability of testing will allow for us to more accurately describe the spectrum of illness and may result in adjustment of the apparent morbidity and mortality rate as fewer ill individuals are diagnosed,” Dr. Cruz and Dr. Zeichner wrote, adding that “rigorously gauging the impact of COVID-19 on children will be important to accurately model the pandemic and to ensure that appropriate resources are allocated to children requiring care.”
They noted that understanding differences in children versus adults with COVID-19 “can yield important insights into disease pathogenesis, informing management and the development of therapeutics.”
This study was partially supported by the Science and Technology Commission of Shanghai Municipality. The authors reported having no disclosures. Dr. Cruz and Dr. Zeichner are associate editors for Pediatrics. Dr. Cruz reported having no disclosures. Dr. Zeichner is an inventor of new technologies for the rapid production of vaccines, for which the University of Virginia has filed patent applications.
SOURCE: Dong Y et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0702; Cruz A and Zeichner S. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0834.
Clinical manifestations of COVID-19 infection among children in mainland China generally have been less severe than those among adults, but children of all ages – and infants in particular – are vulnerable to infection, according to a review of 2,143 cases.
Further, infection patterns in the nationwide series of all pediatric patients reported to the Chinese Center for Disease Control and Prevention from Jan. 16 to Feb. 8, 2020, provide strong evidence of human-to-human transmission, Yuanyuan Dong, MPH, a research assistant at Shanghai Children’s Medical Center, Shanghai Jiao Tong University, China, and colleagues reported in Pediatrics.
Of the 2,143 patients included in the review, 57% were boys and the median age was 7 years; 34% had laboratory-confirmed infection and 67% had suspected infection. More than 90% had asymptomatic, mild, or moderate disease (4%, 51%, and 39%, respectively), and 46% were from Hubei Province, where the first cases were reported, the investigators found.
The median time from illness onset to diagnosis was 2 days, and there was a trend of rapid increase of disease at the early stage of the epidemic – with rapid spread from Hubei Province to surrounding provinces – followed by a gradual and steady decrease, they noted.
“The total number of pediatric patients increased remarkably between mid-January and early February, peaked around February 1, and then declined since early February 2020,” they wrote. The proportion of severe and critical cases was 11% for infants under 1 year of age, compared with 7% for those aged 1-5 years; 4% for those aged 6-10 years; 4% for those 11-15 years; and 3% for those 16 years and older.
As of Feb. 8, 2020, only one child in this group of study patients died and most cases of COVID-19 symptoms were mild. There were many fewer severe and critical cases among the children (6%), compared with those reported in adult patients in other studies (19%). “It suggests that, compared with adult patients, clinical manifestations of children’s COVID-19 may be less severe,” the investigators suggested.
“As most of these children were likely to expose themselves to family members and/or other children with COVID-19, it clearly indicates person-to-person transmission ” of novel coronavirus 2019, they said, adding that similar evidence of such transmission also has been reported from studies of adult patients.
The reasons for reduced severity in children versus adults remain unclear, but may be related to both exposure and host factors, Ms. Dong and associates said. “Children were usually well cared for at home and might have relatively [fewer] opportunities to expose themselves to pathogens and/or sick patients.”
The findings demonstrate a pediatric distribution that varied across time and space, with most cases concentrated in the Hubei province and surrounding areas. No significant gender-related difference in infection rates was observed, and although the median patient age was 7 years, the range was 1 day to 18 years, suggesting that “all ages at childhood were susceptible” to the virus, they added.
The declining number of cases over time further suggests that disease control measures implemented by the government were effective, and that cases will “continue to decline, and finally stop in the near future unless sustained human-to-human transmissions occur,” Ms. Dong and associates concluded.
In an accompanying editorial, Andrea T. Cruz, MD, of Baylor College of Medicine, Houston, and Steven L. Zeichner, MD, PhD, of the University of Virginia, Charlottesville, said the findings regarding reduced severity among children versus adults with novel coronavirus 2019 infection are consistent with data on non-COVID-19 coronavirus.
They pointed out that Ms. Dong and associates did find that 13% of virologically-confirmed cases had asymptomatic infection, “a rate that almost certainly understates the true rate of asymptomatic infection, since many asymptomatic children are unlikely to be tested.”
Of the symptomatic children, “5% had dyspnea or hypoxemia (a substantially lower percentage than what has been reported for adults) and 0.6% progressed to acute respiratory distress syndrome (ARDS) or multiorgan system dysfunction”; this also is at a lower rate than seen in adults, they said.
Very young children –infants or children in preschool – were more likely to have severe clinical manifestations than children who were older.
Thus, it appears that certain subpopulations of children are at increased risk for more significant COVID-19 illness: “younger age, underlying pulmonary pathology, and immunocompromising conditions,” Dr. Cruz and Dr. Zeichner suggested.
The two editorialists said the findings suggest children “may play a major role in community-based viral transmission.” Evidence suggests that children may have more upper respiratory tract involvement and that fecal shedding may occur for several weeks after diagnosis; this raises concerns about fecal-oral transmission, particularly for infants and children, and about viral replication in the gastrointestinal tract, they said. This has substantial implications for community spread in day care centers, schools, and in the home.
A great deal has been learned about COVID-19 in a short time, but there still is much to learn about the effect of the virus on children, the impact of children on viral spread, and about possible vertical transmission, they said.
“Widespread availability of testing will allow for us to more accurately describe the spectrum of illness and may result in adjustment of the apparent morbidity and mortality rate as fewer ill individuals are diagnosed,” Dr. Cruz and Dr. Zeichner wrote, adding that “rigorously gauging the impact of COVID-19 on children will be important to accurately model the pandemic and to ensure that appropriate resources are allocated to children requiring care.”
They noted that understanding differences in children versus adults with COVID-19 “can yield important insights into disease pathogenesis, informing management and the development of therapeutics.”
This study was partially supported by the Science and Technology Commission of Shanghai Municipality. The authors reported having no disclosures. Dr. Cruz and Dr. Zeichner are associate editors for Pediatrics. Dr. Cruz reported having no disclosures. Dr. Zeichner is an inventor of new technologies for the rapid production of vaccines, for which the University of Virginia has filed patent applications.
SOURCE: Dong Y et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0702; Cruz A and Zeichner S. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0834.
Clinical manifestations of COVID-19 infection among children in mainland China generally have been less severe than those among adults, but children of all ages – and infants in particular – are vulnerable to infection, according to a review of 2,143 cases.
Further, infection patterns in the nationwide series of all pediatric patients reported to the Chinese Center for Disease Control and Prevention from Jan. 16 to Feb. 8, 2020, provide strong evidence of human-to-human transmission, Yuanyuan Dong, MPH, a research assistant at Shanghai Children’s Medical Center, Shanghai Jiao Tong University, China, and colleagues reported in Pediatrics.
Of the 2,143 patients included in the review, 57% were boys and the median age was 7 years; 34% had laboratory-confirmed infection and 67% had suspected infection. More than 90% had asymptomatic, mild, or moderate disease (4%, 51%, and 39%, respectively), and 46% were from Hubei Province, where the first cases were reported, the investigators found.
The median time from illness onset to diagnosis was 2 days, and there was a trend of rapid increase of disease at the early stage of the epidemic – with rapid spread from Hubei Province to surrounding provinces – followed by a gradual and steady decrease, they noted.
“The total number of pediatric patients increased remarkably between mid-January and early February, peaked around February 1, and then declined since early February 2020,” they wrote. The proportion of severe and critical cases was 11% for infants under 1 year of age, compared with 7% for those aged 1-5 years; 4% for those aged 6-10 years; 4% for those 11-15 years; and 3% for those 16 years and older.
As of Feb. 8, 2020, only one child in this group of study patients died and most cases of COVID-19 symptoms were mild. There were many fewer severe and critical cases among the children (6%), compared with those reported in adult patients in other studies (19%). “It suggests that, compared with adult patients, clinical manifestations of children’s COVID-19 may be less severe,” the investigators suggested.
“As most of these children were likely to expose themselves to family members and/or other children with COVID-19, it clearly indicates person-to-person transmission ” of novel coronavirus 2019, they said, adding that similar evidence of such transmission also has been reported from studies of adult patients.
The reasons for reduced severity in children versus adults remain unclear, but may be related to both exposure and host factors, Ms. Dong and associates said. “Children were usually well cared for at home and might have relatively [fewer] opportunities to expose themselves to pathogens and/or sick patients.”
The findings demonstrate a pediatric distribution that varied across time and space, with most cases concentrated in the Hubei province and surrounding areas. No significant gender-related difference in infection rates was observed, and although the median patient age was 7 years, the range was 1 day to 18 years, suggesting that “all ages at childhood were susceptible” to the virus, they added.
The declining number of cases over time further suggests that disease control measures implemented by the government were effective, and that cases will “continue to decline, and finally stop in the near future unless sustained human-to-human transmissions occur,” Ms. Dong and associates concluded.
In an accompanying editorial, Andrea T. Cruz, MD, of Baylor College of Medicine, Houston, and Steven L. Zeichner, MD, PhD, of the University of Virginia, Charlottesville, said the findings regarding reduced severity among children versus adults with novel coronavirus 2019 infection are consistent with data on non-COVID-19 coronavirus.
They pointed out that Ms. Dong and associates did find that 13% of virologically-confirmed cases had asymptomatic infection, “a rate that almost certainly understates the true rate of asymptomatic infection, since many asymptomatic children are unlikely to be tested.”
Of the symptomatic children, “5% had dyspnea or hypoxemia (a substantially lower percentage than what has been reported for adults) and 0.6% progressed to acute respiratory distress syndrome (ARDS) or multiorgan system dysfunction”; this also is at a lower rate than seen in adults, they said.
Very young children –infants or children in preschool – were more likely to have severe clinical manifestations than children who were older.
Thus, it appears that certain subpopulations of children are at increased risk for more significant COVID-19 illness: “younger age, underlying pulmonary pathology, and immunocompromising conditions,” Dr. Cruz and Dr. Zeichner suggested.
The two editorialists said the findings suggest children “may play a major role in community-based viral transmission.” Evidence suggests that children may have more upper respiratory tract involvement and that fecal shedding may occur for several weeks after diagnosis; this raises concerns about fecal-oral transmission, particularly for infants and children, and about viral replication in the gastrointestinal tract, they said. This has substantial implications for community spread in day care centers, schools, and in the home.
A great deal has been learned about COVID-19 in a short time, but there still is much to learn about the effect of the virus on children, the impact of children on viral spread, and about possible vertical transmission, they said.
“Widespread availability of testing will allow for us to more accurately describe the spectrum of illness and may result in adjustment of the apparent morbidity and mortality rate as fewer ill individuals are diagnosed,” Dr. Cruz and Dr. Zeichner wrote, adding that “rigorously gauging the impact of COVID-19 on children will be important to accurately model the pandemic and to ensure that appropriate resources are allocated to children requiring care.”
They noted that understanding differences in children versus adults with COVID-19 “can yield important insights into disease pathogenesis, informing management and the development of therapeutics.”
This study was partially supported by the Science and Technology Commission of Shanghai Municipality. The authors reported having no disclosures. Dr. Cruz and Dr. Zeichner are associate editors for Pediatrics. Dr. Cruz reported having no disclosures. Dr. Zeichner is an inventor of new technologies for the rapid production of vaccines, for which the University of Virginia has filed patent applications.
SOURCE: Dong Y et al. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0702; Cruz A and Zeichner S. Pediatrics. 2020 Mar 16. doi: 10.1542/peds.2020-0834.
FROM PEDIATRICS
Maternal mortality: A national crisis
This article is the first in a series on maternal mortality.
“You’re in really bad shape, kid. I don’t know if you’re gonna live through the night. I’m going to do everything I can to save your life, but the truth is you might die.”
If Timoria McQueen Saba imagined the words she would hear in the moments after she gave birth, those likely weren’t among them. But then she started to bleed. The energy around her shifted; she felt the urgency and intensity in the room, and she could see it – reflected from the television monitor over her bed – in the faces of her care team. After her husband and newborn daughter were led from the room, she did, in fact, hear those words.
They were spoken by a surgeon called in after efforts to control the bleeding failed – emetic words that joined forces with her hemorrhaging and confusion and fear, and as she began to vomit, her eyelids felt heavy. She fought to keep them open, sensing that if she closed them they might never open again.
In 2018 alone, similar words perhaps were spoken to the 658 U.S. women who suffered maternal complications and whose eyes never did open again. This is the latest official maternal mortality data from the Centers for Disease Control and Prevention.
Ms. Saba’s eyes, however, remained open through her birth trauma and through the PTSD that followed. A fierce advocate for maternal health, she shares her story often, as she did during a panel discussion at the American College of Obstetricians and Gynecologists’ annual meeting in May 2019, in an effort to improve outcomes for other women and families.
But her story unfolded nearly a decade ago and those eyes still are seeing women die from childbirth. Despite her efforts and the efforts of countless other individuals and organizations working to improve maternal outcomes, the new CDC data show that the United States has the highest maternal mortality rate of any similarly wealthy industrialized nation.
“I cannot believe I’m still talking about this issue,” Ms. Saba told a standing-room-only crowd and her copanelists Neel T. Shah, MD, and Charles S. Johnson IV, whose wife, Kira, died in 2016 during surgery for bleeding complications following the birth of their second child. “If all the people who I’d written to had just listened maybe once and tried to propel my message forward back then, Charles would be in a much better situation and so would his children.”
Mr. Johnson said that for 10 hours he and other family members pleaded for help for Kira, a healthy, vibrant women he described as “sunshine personified.”
She showed signs of postpartum bleeding after delivering a healthy baby boy by C-section, but a “STAT CT” order went unheeded for hours before she was finally taken for surgery.
“You’re walking down this corridor, you get to this point, these double doors open, and you just can’t go any further – and that was the last time I saw my wife alive,” he said. “When they took Kira back into the operating room, there were three-and-a-half liters of blood in her abdomen, and her heart stopped immediately.
Kira Johnson died April 13, 2016.
“I’m not here to tell you what I think, I’m here to tell you what I know, and that’s that Kira deserved so much better, and that Kira’s not alone, and that women all over this country deserve so much better.”
The U.S. maternal mortality crisis
Dr. Shah, an ob.gyn. at Beth Israel Deaconess Medical Center and director of the Delivery Decisions Initiative at Harvard Medical School’s Ariadne Labs, both in Boston, where he has “been on this mission to improve safety in childbirth for years now,” echoed Ms. Saba’s dismay regarding the pace of progress.
“It’s not just about the present, it’s about the future, it’s about the pact that every generation ought to have with the next one to leave things at least as well as they found them. And when it comes to the health of our moms in this country, we are not doing that,” he said. “An American mom today is 50% more likely to die in childbirth than her own mother was, and 3-4 times more likely to die if she’s black than if she’s white.”
Indeed, the data released Jan. 30 by the CDC’s National Center for Health Statistics (NCHS) – the first on maternal mortality released by the agency since 2007 – show a U.S. maternal mortality rate of 17.4 maternal deaths per 100,000 live births in 2018.
The rate is higher than the 12.7 per 100,000 live births reported in 2007, but the increase is attributable mostly to changes in data collection and reporting methods. In 2003, “a consensus process recommended that all states add a standardized ‘checkbox’ to improve the identification of maternal deaths,” and implementation wasn’t complete until 2017 as “funding, technology, and state laws allowed,” meaning 2018 was the first year that data were reported in a standardized fashion across states, the CDC explained in a press release.
The data demonstrate ongoing wide racial/ethnic disparities: the maternal mortality rates for non-Hispanic black women, non-Hispanic white women, and Hispanic women were 37.1, 14.7, and 11.8 per 100,000 live births, consistent with earlier data.
Further, the rates for women aged 40 years and over were nearly eightfold higher than for those under age 25 years (81.9 vs. 10.6 per 100,000 live births).
CDC officials noted, however, that inconsistencies in reporting still leave some question about the accuracy of the data, stating in the release that “NCHS has identified instances where application of the checkbox information according to coding rules led to misclassification of maternal deaths.”
The agency is making changes in rules and reporting to ensure greater accuracy, but the numbers nevertheless reveal a startling truth: “The United States is the most dangerous place to deliver a baby in the industrialized world.”
Progress and challenges
Rebekah Gee, MD, an ob.gyn. who served for 4 years as Secretary of the Louisiana Department of Health before leaving the position in January, made that statement during another panel discussion at ACOG 2019 – The President’s Panel: Maternal Mortality: Progress Toward Prevention – which was moderated by Lisa M. Hollier, MD, now the immediate past president of ACOG.
That’s not to say progress hasn’t been or can’t be made, Dr. Gee said.
In fact, quality improvement measures she facilitated in Louisiana led to a 25% reduction in infant mortality and a 10% reduction in neonatal intensive care unit admissions, demonstrating the potential for improvement with such initiatives, but addressing maternal issues is a greater challenge, she said.
“I think part of the sad truth is that we really focus on babies first, not moms ... and that needs to change,” Dr. Gee said.
Dr. Hollier focused much of her attention during her tenure as ACOG president on doing just that, particularly through an emphasis on heart disease, which is the leading cause of U.S. maternal deaths in pregnancy and the postpartum period.
In an interview, she shared her thoughts on the progress achieved and the work that remains.
ACOG was instrumental in the enactment of the Preventing Maternal Deaths Act of 2018, which appropriated funding for Enhancing Reviews and Surveillance to Eliminate Maternal Mortality (ERASE MM), a CDC initiative to support state-based maternal mortality review committees, said Dr. Hollier, professor of obstetrics and gynecology at Baylor College of Medicine, Houston.
“The really great news is that almost immediately after passage of the legislation, the CDC put out the notice of the funding opportunity, and they were able to provide 24 awards supporting 25 states,” she said.
ERASE MM will enhance state data collection and availability and enable a level of data sharing that “will really add strength and depth to reporting from the maternal mortality review committees, which really provides us with the best information we have to truly understand the causes, the contributing factors, and the strategies that can be put in place to prevent future maternal deaths.”
Further, the Alliance for Innovation on Maternal Health (AIM) program, a cooperative agreement with the Health Resources and Services Administration (HRSA) Maternal and Child Health Bureau to improve safety and outcomes through evidence-based patient safety bundles, was extended, and in May 2019, ACOG updated its guidance on managing cardiac contributors to maternal mortality, releasing its “Pregnancy and Heart Disease” Practice Bulletin, she said.
Dr. Hollier continues in her quest for improved maternal outcomes. She is slated to deliver a keynote address at the American College of Cardiology/World Congress of Cardiology conference March 28 in Chicago.
“I’m so excited ... to talk about the new guidelines that we’ve put out and to really talk about how cardiologists and ob.gyns. can work together to improve women’s health outcomes,” she said, adding that she already is seeing a strengthening of such partnerships.
A number of academic institutions are developing “pregnancy heart teams” to identify and care for women who have or develop heart disease during pregnancy.
“This type of collaboration ... is going to be essential to address mortality from cardiovascular causes and from cardiomyopathy, which accounts for about 25% of all maternal mortality,” she said. “The next area where we really need some buy-in is from our emergency physicians.”
Enhanced collaboration with emergency physicians and other specialties present opportunities to better identify and address pregnancy-related complications and sequelae, she said.
“Women are dying because they’re not being diagnosed,” she added. “We have to raise that level of awareness – it’s just absolutely critical.”
Identifying and addressing drivers of the crisis
Dr. Gee further emphasized the importance of addressing maternal health, noting that for every woman who dies from maternal causes, 100 experience maternal morbidity.
“It’s startling and it’s scary,” she said. “We are looking at this not just as a problem of outcomes, but a problem of racial inequity and racial bias and implicit bias.”
When she and her team assessed maternal mortality in Louisiana, they looked specifically at whether each death could have been prevented if, for example, blood was given sooner, cardiomyopathy was recognized sooner, or hypertension was treated on time.
“When we looked at these numbers ... when we looked at white women, 9% of the time we could have done better with our medical care; with black women, 59% of the time we could have saved her life with better care,” said Dr Gee, who is a gratis assistant professor of obstetrics and gynecology at Louisiana State University, New Orleans. “And if that doesn’t convince you that racial bias is an incredibly important thing to address – that we need to have a conversation about and address at a national level – I don’t know what would.”
In fact, numerous health, societal, socioeconomic, and other factors – some known, some yet to be identified, and many inter-related – are among the drivers of the U.S. maternal mortality crisis. In the coming months, an Ob.Gyn. News team will examine several of these drivers in depth. We’ll look specifically at the role of racism and bias, and at urban-rural disparities in access and outcomes – especially for women of color and indigenous women. We’ll address the scope and impact of each, successes and failures in addressing the problems, and ongoing initiatives.
Follow us for insights from experts, researchers, practicing physicians, and patients and families affected by the maternal mortality crisis, and stay with us through coverage of ACOG 2020 for perspective on what, specifically, ob.gyns. can do about it.
Mr. Johnson proposed a starting point:
“Here’s the good news – you guys ready for this? We can fix this,” he said, adding that the solution starts with “speaking Timoria’s name ... speaking the name of Kira Dixon Johnson ... speaking the names of these women and then asking the people that are around you, ‘What are we prepared to do to make sure that this doesn’t happen to other women.’ ”
This article is the first in a series on maternal mortality.
“You’re in really bad shape, kid. I don’t know if you’re gonna live through the night. I’m going to do everything I can to save your life, but the truth is you might die.”
If Timoria McQueen Saba imagined the words she would hear in the moments after she gave birth, those likely weren’t among them. But then she started to bleed. The energy around her shifted; she felt the urgency and intensity in the room, and she could see it – reflected from the television monitor over her bed – in the faces of her care team. After her husband and newborn daughter were led from the room, she did, in fact, hear those words.
They were spoken by a surgeon called in after efforts to control the bleeding failed – emetic words that joined forces with her hemorrhaging and confusion and fear, and as she began to vomit, her eyelids felt heavy. She fought to keep them open, sensing that if she closed them they might never open again.
In 2018 alone, similar words perhaps were spoken to the 658 U.S. women who suffered maternal complications and whose eyes never did open again. This is the latest official maternal mortality data from the Centers for Disease Control and Prevention.
Ms. Saba’s eyes, however, remained open through her birth trauma and through the PTSD that followed. A fierce advocate for maternal health, she shares her story often, as she did during a panel discussion at the American College of Obstetricians and Gynecologists’ annual meeting in May 2019, in an effort to improve outcomes for other women and families.
But her story unfolded nearly a decade ago and those eyes still are seeing women die from childbirth. Despite her efforts and the efforts of countless other individuals and organizations working to improve maternal outcomes, the new CDC data show that the United States has the highest maternal mortality rate of any similarly wealthy industrialized nation.
“I cannot believe I’m still talking about this issue,” Ms. Saba told a standing-room-only crowd and her copanelists Neel T. Shah, MD, and Charles S. Johnson IV, whose wife, Kira, died in 2016 during surgery for bleeding complications following the birth of their second child. “If all the people who I’d written to had just listened maybe once and tried to propel my message forward back then, Charles would be in a much better situation and so would his children.”
Mr. Johnson said that for 10 hours he and other family members pleaded for help for Kira, a healthy, vibrant women he described as “sunshine personified.”
She showed signs of postpartum bleeding after delivering a healthy baby boy by C-section, but a “STAT CT” order went unheeded for hours before she was finally taken for surgery.
“You’re walking down this corridor, you get to this point, these double doors open, and you just can’t go any further – and that was the last time I saw my wife alive,” he said. “When they took Kira back into the operating room, there were three-and-a-half liters of blood in her abdomen, and her heart stopped immediately.
Kira Johnson died April 13, 2016.
“I’m not here to tell you what I think, I’m here to tell you what I know, and that’s that Kira deserved so much better, and that Kira’s not alone, and that women all over this country deserve so much better.”
The U.S. maternal mortality crisis
Dr. Shah, an ob.gyn. at Beth Israel Deaconess Medical Center and director of the Delivery Decisions Initiative at Harvard Medical School’s Ariadne Labs, both in Boston, where he has “been on this mission to improve safety in childbirth for years now,” echoed Ms. Saba’s dismay regarding the pace of progress.
“It’s not just about the present, it’s about the future, it’s about the pact that every generation ought to have with the next one to leave things at least as well as they found them. And when it comes to the health of our moms in this country, we are not doing that,” he said. “An American mom today is 50% more likely to die in childbirth than her own mother was, and 3-4 times more likely to die if she’s black than if she’s white.”
Indeed, the data released Jan. 30 by the CDC’s National Center for Health Statistics (NCHS) – the first on maternal mortality released by the agency since 2007 – show a U.S. maternal mortality rate of 17.4 maternal deaths per 100,000 live births in 2018.
The rate is higher than the 12.7 per 100,000 live births reported in 2007, but the increase is attributable mostly to changes in data collection and reporting methods. In 2003, “a consensus process recommended that all states add a standardized ‘checkbox’ to improve the identification of maternal deaths,” and implementation wasn’t complete until 2017 as “funding, technology, and state laws allowed,” meaning 2018 was the first year that data were reported in a standardized fashion across states, the CDC explained in a press release.
The data demonstrate ongoing wide racial/ethnic disparities: the maternal mortality rates for non-Hispanic black women, non-Hispanic white women, and Hispanic women were 37.1, 14.7, and 11.8 per 100,000 live births, consistent with earlier data.
Further, the rates for women aged 40 years and over were nearly eightfold higher than for those under age 25 years (81.9 vs. 10.6 per 100,000 live births).
CDC officials noted, however, that inconsistencies in reporting still leave some question about the accuracy of the data, stating in the release that “NCHS has identified instances where application of the checkbox information according to coding rules led to misclassification of maternal deaths.”
The agency is making changes in rules and reporting to ensure greater accuracy, but the numbers nevertheless reveal a startling truth: “The United States is the most dangerous place to deliver a baby in the industrialized world.”
Progress and challenges
Rebekah Gee, MD, an ob.gyn. who served for 4 years as Secretary of the Louisiana Department of Health before leaving the position in January, made that statement during another panel discussion at ACOG 2019 – The President’s Panel: Maternal Mortality: Progress Toward Prevention – which was moderated by Lisa M. Hollier, MD, now the immediate past president of ACOG.
That’s not to say progress hasn’t been or can’t be made, Dr. Gee said.
In fact, quality improvement measures she facilitated in Louisiana led to a 25% reduction in infant mortality and a 10% reduction in neonatal intensive care unit admissions, demonstrating the potential for improvement with such initiatives, but addressing maternal issues is a greater challenge, she said.
“I think part of the sad truth is that we really focus on babies first, not moms ... and that needs to change,” Dr. Gee said.
Dr. Hollier focused much of her attention during her tenure as ACOG president on doing just that, particularly through an emphasis on heart disease, which is the leading cause of U.S. maternal deaths in pregnancy and the postpartum period.
In an interview, she shared her thoughts on the progress achieved and the work that remains.
ACOG was instrumental in the enactment of the Preventing Maternal Deaths Act of 2018, which appropriated funding for Enhancing Reviews and Surveillance to Eliminate Maternal Mortality (ERASE MM), a CDC initiative to support state-based maternal mortality review committees, said Dr. Hollier, professor of obstetrics and gynecology at Baylor College of Medicine, Houston.
“The really great news is that almost immediately after passage of the legislation, the CDC put out the notice of the funding opportunity, and they were able to provide 24 awards supporting 25 states,” she said.
ERASE MM will enhance state data collection and availability and enable a level of data sharing that “will really add strength and depth to reporting from the maternal mortality review committees, which really provides us with the best information we have to truly understand the causes, the contributing factors, and the strategies that can be put in place to prevent future maternal deaths.”
Further, the Alliance for Innovation on Maternal Health (AIM) program, a cooperative agreement with the Health Resources and Services Administration (HRSA) Maternal and Child Health Bureau to improve safety and outcomes through evidence-based patient safety bundles, was extended, and in May 2019, ACOG updated its guidance on managing cardiac contributors to maternal mortality, releasing its “Pregnancy and Heart Disease” Practice Bulletin, she said.
Dr. Hollier continues in her quest for improved maternal outcomes. She is slated to deliver a keynote address at the American College of Cardiology/World Congress of Cardiology conference March 28 in Chicago.
“I’m so excited ... to talk about the new guidelines that we’ve put out and to really talk about how cardiologists and ob.gyns. can work together to improve women’s health outcomes,” she said, adding that she already is seeing a strengthening of such partnerships.
A number of academic institutions are developing “pregnancy heart teams” to identify and care for women who have or develop heart disease during pregnancy.
“This type of collaboration ... is going to be essential to address mortality from cardiovascular causes and from cardiomyopathy, which accounts for about 25% of all maternal mortality,” she said. “The next area where we really need some buy-in is from our emergency physicians.”
Enhanced collaboration with emergency physicians and other specialties present opportunities to better identify and address pregnancy-related complications and sequelae, she said.
“Women are dying because they’re not being diagnosed,” she added. “We have to raise that level of awareness – it’s just absolutely critical.”
Identifying and addressing drivers of the crisis
Dr. Gee further emphasized the importance of addressing maternal health, noting that for every woman who dies from maternal causes, 100 experience maternal morbidity.
“It’s startling and it’s scary,” she said. “We are looking at this not just as a problem of outcomes, but a problem of racial inequity and racial bias and implicit bias.”
When she and her team assessed maternal mortality in Louisiana, they looked specifically at whether each death could have been prevented if, for example, blood was given sooner, cardiomyopathy was recognized sooner, or hypertension was treated on time.
“When we looked at these numbers ... when we looked at white women, 9% of the time we could have done better with our medical care; with black women, 59% of the time we could have saved her life with better care,” said Dr Gee, who is a gratis assistant professor of obstetrics and gynecology at Louisiana State University, New Orleans. “And if that doesn’t convince you that racial bias is an incredibly important thing to address – that we need to have a conversation about and address at a national level – I don’t know what would.”
In fact, numerous health, societal, socioeconomic, and other factors – some known, some yet to be identified, and many inter-related – are among the drivers of the U.S. maternal mortality crisis. In the coming months, an Ob.Gyn. News team will examine several of these drivers in depth. We’ll look specifically at the role of racism and bias, and at urban-rural disparities in access and outcomes – especially for women of color and indigenous women. We’ll address the scope and impact of each, successes and failures in addressing the problems, and ongoing initiatives.
Follow us for insights from experts, researchers, practicing physicians, and patients and families affected by the maternal mortality crisis, and stay with us through coverage of ACOG 2020 for perspective on what, specifically, ob.gyns. can do about it.
Mr. Johnson proposed a starting point:
“Here’s the good news – you guys ready for this? We can fix this,” he said, adding that the solution starts with “speaking Timoria’s name ... speaking the name of Kira Dixon Johnson ... speaking the names of these women and then asking the people that are around you, ‘What are we prepared to do to make sure that this doesn’t happen to other women.’ ”
This article is the first in a series on maternal mortality.
“You’re in really bad shape, kid. I don’t know if you’re gonna live through the night. I’m going to do everything I can to save your life, but the truth is you might die.”
If Timoria McQueen Saba imagined the words she would hear in the moments after she gave birth, those likely weren’t among them. But then she started to bleed. The energy around her shifted; she felt the urgency and intensity in the room, and she could see it – reflected from the television monitor over her bed – in the faces of her care team. After her husband and newborn daughter were led from the room, she did, in fact, hear those words.
They were spoken by a surgeon called in after efforts to control the bleeding failed – emetic words that joined forces with her hemorrhaging and confusion and fear, and as she began to vomit, her eyelids felt heavy. She fought to keep them open, sensing that if she closed them they might never open again.
In 2018 alone, similar words perhaps were spoken to the 658 U.S. women who suffered maternal complications and whose eyes never did open again. This is the latest official maternal mortality data from the Centers for Disease Control and Prevention.
Ms. Saba’s eyes, however, remained open through her birth trauma and through the PTSD that followed. A fierce advocate for maternal health, she shares her story often, as she did during a panel discussion at the American College of Obstetricians and Gynecologists’ annual meeting in May 2019, in an effort to improve outcomes for other women and families.
But her story unfolded nearly a decade ago and those eyes still are seeing women die from childbirth. Despite her efforts and the efforts of countless other individuals and organizations working to improve maternal outcomes, the new CDC data show that the United States has the highest maternal mortality rate of any similarly wealthy industrialized nation.
“I cannot believe I’m still talking about this issue,” Ms. Saba told a standing-room-only crowd and her copanelists Neel T. Shah, MD, and Charles S. Johnson IV, whose wife, Kira, died in 2016 during surgery for bleeding complications following the birth of their second child. “If all the people who I’d written to had just listened maybe once and tried to propel my message forward back then, Charles would be in a much better situation and so would his children.”
Mr. Johnson said that for 10 hours he and other family members pleaded for help for Kira, a healthy, vibrant women he described as “sunshine personified.”
She showed signs of postpartum bleeding after delivering a healthy baby boy by C-section, but a “STAT CT” order went unheeded for hours before she was finally taken for surgery.
“You’re walking down this corridor, you get to this point, these double doors open, and you just can’t go any further – and that was the last time I saw my wife alive,” he said. “When they took Kira back into the operating room, there were three-and-a-half liters of blood in her abdomen, and her heart stopped immediately.
Kira Johnson died April 13, 2016.
“I’m not here to tell you what I think, I’m here to tell you what I know, and that’s that Kira deserved so much better, and that Kira’s not alone, and that women all over this country deserve so much better.”
The U.S. maternal mortality crisis
Dr. Shah, an ob.gyn. at Beth Israel Deaconess Medical Center and director of the Delivery Decisions Initiative at Harvard Medical School’s Ariadne Labs, both in Boston, where he has “been on this mission to improve safety in childbirth for years now,” echoed Ms. Saba’s dismay regarding the pace of progress.
“It’s not just about the present, it’s about the future, it’s about the pact that every generation ought to have with the next one to leave things at least as well as they found them. And when it comes to the health of our moms in this country, we are not doing that,” he said. “An American mom today is 50% more likely to die in childbirth than her own mother was, and 3-4 times more likely to die if she’s black than if she’s white.”
Indeed, the data released Jan. 30 by the CDC’s National Center for Health Statistics (NCHS) – the first on maternal mortality released by the agency since 2007 – show a U.S. maternal mortality rate of 17.4 maternal deaths per 100,000 live births in 2018.
The rate is higher than the 12.7 per 100,000 live births reported in 2007, but the increase is attributable mostly to changes in data collection and reporting methods. In 2003, “a consensus process recommended that all states add a standardized ‘checkbox’ to improve the identification of maternal deaths,” and implementation wasn’t complete until 2017 as “funding, technology, and state laws allowed,” meaning 2018 was the first year that data were reported in a standardized fashion across states, the CDC explained in a press release.
The data demonstrate ongoing wide racial/ethnic disparities: the maternal mortality rates for non-Hispanic black women, non-Hispanic white women, and Hispanic women were 37.1, 14.7, and 11.8 per 100,000 live births, consistent with earlier data.
Further, the rates for women aged 40 years and over were nearly eightfold higher than for those under age 25 years (81.9 vs. 10.6 per 100,000 live births).
CDC officials noted, however, that inconsistencies in reporting still leave some question about the accuracy of the data, stating in the release that “NCHS has identified instances where application of the checkbox information according to coding rules led to misclassification of maternal deaths.”
The agency is making changes in rules and reporting to ensure greater accuracy, but the numbers nevertheless reveal a startling truth: “The United States is the most dangerous place to deliver a baby in the industrialized world.”
Progress and challenges
Rebekah Gee, MD, an ob.gyn. who served for 4 years as Secretary of the Louisiana Department of Health before leaving the position in January, made that statement during another panel discussion at ACOG 2019 – The President’s Panel: Maternal Mortality: Progress Toward Prevention – which was moderated by Lisa M. Hollier, MD, now the immediate past president of ACOG.
That’s not to say progress hasn’t been or can’t be made, Dr. Gee said.
In fact, quality improvement measures she facilitated in Louisiana led to a 25% reduction in infant mortality and a 10% reduction in neonatal intensive care unit admissions, demonstrating the potential for improvement with such initiatives, but addressing maternal issues is a greater challenge, she said.
“I think part of the sad truth is that we really focus on babies first, not moms ... and that needs to change,” Dr. Gee said.
Dr. Hollier focused much of her attention during her tenure as ACOG president on doing just that, particularly through an emphasis on heart disease, which is the leading cause of U.S. maternal deaths in pregnancy and the postpartum period.
In an interview, she shared her thoughts on the progress achieved and the work that remains.
ACOG was instrumental in the enactment of the Preventing Maternal Deaths Act of 2018, which appropriated funding for Enhancing Reviews and Surveillance to Eliminate Maternal Mortality (ERASE MM), a CDC initiative to support state-based maternal mortality review committees, said Dr. Hollier, professor of obstetrics and gynecology at Baylor College of Medicine, Houston.
“The really great news is that almost immediately after passage of the legislation, the CDC put out the notice of the funding opportunity, and they were able to provide 24 awards supporting 25 states,” she said.
ERASE MM will enhance state data collection and availability and enable a level of data sharing that “will really add strength and depth to reporting from the maternal mortality review committees, which really provides us with the best information we have to truly understand the causes, the contributing factors, and the strategies that can be put in place to prevent future maternal deaths.”
Further, the Alliance for Innovation on Maternal Health (AIM) program, a cooperative agreement with the Health Resources and Services Administration (HRSA) Maternal and Child Health Bureau to improve safety and outcomes through evidence-based patient safety bundles, was extended, and in May 2019, ACOG updated its guidance on managing cardiac contributors to maternal mortality, releasing its “Pregnancy and Heart Disease” Practice Bulletin, she said.
Dr. Hollier continues in her quest for improved maternal outcomes. She is slated to deliver a keynote address at the American College of Cardiology/World Congress of Cardiology conference March 28 in Chicago.
“I’m so excited ... to talk about the new guidelines that we’ve put out and to really talk about how cardiologists and ob.gyns. can work together to improve women’s health outcomes,” she said, adding that she already is seeing a strengthening of such partnerships.
A number of academic institutions are developing “pregnancy heart teams” to identify and care for women who have or develop heart disease during pregnancy.
“This type of collaboration ... is going to be essential to address mortality from cardiovascular causes and from cardiomyopathy, which accounts for about 25% of all maternal mortality,” she said. “The next area where we really need some buy-in is from our emergency physicians.”
Enhanced collaboration with emergency physicians and other specialties present opportunities to better identify and address pregnancy-related complications and sequelae, she said.
“Women are dying because they’re not being diagnosed,” she added. “We have to raise that level of awareness – it’s just absolutely critical.”
Identifying and addressing drivers of the crisis
Dr. Gee further emphasized the importance of addressing maternal health, noting that for every woman who dies from maternal causes, 100 experience maternal morbidity.
“It’s startling and it’s scary,” she said. “We are looking at this not just as a problem of outcomes, but a problem of racial inequity and racial bias and implicit bias.”
When she and her team assessed maternal mortality in Louisiana, they looked specifically at whether each death could have been prevented if, for example, blood was given sooner, cardiomyopathy was recognized sooner, or hypertension was treated on time.
“When we looked at these numbers ... when we looked at white women, 9% of the time we could have done better with our medical care; with black women, 59% of the time we could have saved her life with better care,” said Dr Gee, who is a gratis assistant professor of obstetrics and gynecology at Louisiana State University, New Orleans. “And if that doesn’t convince you that racial bias is an incredibly important thing to address – that we need to have a conversation about and address at a national level – I don’t know what would.”
In fact, numerous health, societal, socioeconomic, and other factors – some known, some yet to be identified, and many inter-related – are among the drivers of the U.S. maternal mortality crisis. In the coming months, an Ob.Gyn. News team will examine several of these drivers in depth. We’ll look specifically at the role of racism and bias, and at urban-rural disparities in access and outcomes – especially for women of color and indigenous women. We’ll address the scope and impact of each, successes and failures in addressing the problems, and ongoing initiatives.
Follow us for insights from experts, researchers, practicing physicians, and patients and families affected by the maternal mortality crisis, and stay with us through coverage of ACOG 2020 for perspective on what, specifically, ob.gyns. can do about it.
Mr. Johnson proposed a starting point:
“Here’s the good news – you guys ready for this? We can fix this,” he said, adding that the solution starts with “speaking Timoria’s name ... speaking the name of Kira Dixon Johnson ... speaking the names of these women and then asking the people that are around you, ‘What are we prepared to do to make sure that this doesn’t happen to other women.’ ”
PPI use linked with increased fracture risk in children
under 18 years.
The fracture incidence rates among 115,933 pairs of children under age 18 years matched based on propensity score and age were 20.2 versus 18.3 per 1,000 person-years among those who did and did not receive proton pump inhibitor (PPI) therapy, respectively (hazard ratio, 1.11), Yun-Han Wang of Karolinska Institute, Stockholm and colleagues reported in JAMA Pediatrics.
Increases in risk with PPI use were seen for upper-limb fracture (HR, 1.08), lower-limb fracture (HR, 1.19) and other fractures (HR, 1.51), but not head fractures (HR, 0.93). The risks increased nominally in tandem with cumulative duration of PPI use (HR, 1.08, 1.14, and 1.34 for 30 days or less, 31-364 days, and 365 days or more, respectively), the investigators found.
After subgroup and sensitivity analyses, Mr. Wang and associates stated that PPI use in children “was associated with a statistically significant 11% relative increase in risk of any fracture. The association was driven by fractures of upper limbs, lower limbs, and other sites; appeared to be mainly restricted to children 6 years and older; and seemed to be somewhat more pronounced with a longer cumulative duration of PPI use.”
“Risk of fracture should be taken into account when weighing the benefits and risks of PPI treatment in children, they concluded.
This study was funded by the Swedish Research Council and Frimurare Barnhuset Foundation; one coauthor was supported by a grant from the Strategic Research Area Epidemiology program at Karolinska Institutet. Two coauthors reported associations with pharmaceutical companies, and one of them with a health care data company. Dr. Wang and the remaining coauthors reported having no disclosures.
SOURCE: Wang Y et al. JAMA Pediatr. 2020 Mar 16. doi: 101001/jamapediatrics.2020.0007.
under 18 years.
The fracture incidence rates among 115,933 pairs of children under age 18 years matched based on propensity score and age were 20.2 versus 18.3 per 1,000 person-years among those who did and did not receive proton pump inhibitor (PPI) therapy, respectively (hazard ratio, 1.11), Yun-Han Wang of Karolinska Institute, Stockholm and colleagues reported in JAMA Pediatrics.
Increases in risk with PPI use were seen for upper-limb fracture (HR, 1.08), lower-limb fracture (HR, 1.19) and other fractures (HR, 1.51), but not head fractures (HR, 0.93). The risks increased nominally in tandem with cumulative duration of PPI use (HR, 1.08, 1.14, and 1.34 for 30 days or less, 31-364 days, and 365 days or more, respectively), the investigators found.
After subgroup and sensitivity analyses, Mr. Wang and associates stated that PPI use in children “was associated with a statistically significant 11% relative increase in risk of any fracture. The association was driven by fractures of upper limbs, lower limbs, and other sites; appeared to be mainly restricted to children 6 years and older; and seemed to be somewhat more pronounced with a longer cumulative duration of PPI use.”
“Risk of fracture should be taken into account when weighing the benefits and risks of PPI treatment in children, they concluded.
This study was funded by the Swedish Research Council and Frimurare Barnhuset Foundation; one coauthor was supported by a grant from the Strategic Research Area Epidemiology program at Karolinska Institutet. Two coauthors reported associations with pharmaceutical companies, and one of them with a health care data company. Dr. Wang and the remaining coauthors reported having no disclosures.
SOURCE: Wang Y et al. JAMA Pediatr. 2020 Mar 16. doi: 101001/jamapediatrics.2020.0007.
under 18 years.
The fracture incidence rates among 115,933 pairs of children under age 18 years matched based on propensity score and age were 20.2 versus 18.3 per 1,000 person-years among those who did and did not receive proton pump inhibitor (PPI) therapy, respectively (hazard ratio, 1.11), Yun-Han Wang of Karolinska Institute, Stockholm and colleagues reported in JAMA Pediatrics.
Increases in risk with PPI use were seen for upper-limb fracture (HR, 1.08), lower-limb fracture (HR, 1.19) and other fractures (HR, 1.51), but not head fractures (HR, 0.93). The risks increased nominally in tandem with cumulative duration of PPI use (HR, 1.08, 1.14, and 1.34 for 30 days or less, 31-364 days, and 365 days or more, respectively), the investigators found.
After subgroup and sensitivity analyses, Mr. Wang and associates stated that PPI use in children “was associated with a statistically significant 11% relative increase in risk of any fracture. The association was driven by fractures of upper limbs, lower limbs, and other sites; appeared to be mainly restricted to children 6 years and older; and seemed to be somewhat more pronounced with a longer cumulative duration of PPI use.”
“Risk of fracture should be taken into account when weighing the benefits and risks of PPI treatment in children, they concluded.
This study was funded by the Swedish Research Council and Frimurare Barnhuset Foundation; one coauthor was supported by a grant from the Strategic Research Area Epidemiology program at Karolinska Institutet. Two coauthors reported associations with pharmaceutical companies, and one of them with a health care data company. Dr. Wang and the remaining coauthors reported having no disclosures.
SOURCE: Wang Y et al. JAMA Pediatr. 2020 Mar 16. doi: 101001/jamapediatrics.2020.0007.
FROM JAMA PEDIATRICS
Wuhan case review: COVID-19 characteristics differ in children vs. adults
Pediatric cases of COVID-19 infection are typically mild, but underlying coinfection may be more common in children than in adults, according to an analysis of clinical, laboratory, and chest CT features of pediatric inpatients in Wuhan, China.
The findings point toward a need for early chest CT with corresponding pathogen detection in children with suspected COVID-19 infection, Wei Xia, MD, of Huazhong University of Science and Technology, Wuhan, China, and colleagues reported in Pediatric Pulmonology.
The most common symptoms in 20 pediatric patients hospitalized between Jan. 23 and Feb. 8, 2020, with COVID-19 infection confirmed by the pharyngeal swab COVID-19 nucleic acid test were fever and cough, which occurred in 60% and 65% of patients, respectively. Coinfection was detected in eight patients (40%), they noted.
Clinical manifestations were similar to those seen in adults, but overall symptoms were relatively mild and overall prognosis was good. Of particular note, 7 of the 20 (35%) patients had a previously diagnosed congenital or acquired diseases, suggesting that children with underlying conditions may be more susceptible, Dr. Xia and colleagues wrote.
Laboratory findings also were notable in that 80% of the children had procalcitonin (PCT) elevations not typically seen in adults with COVID-19. PCT is a marker for bacterial infection and “[this finding] may suggest that routine antibacterial treatment should be considered in pediatric patients,” the investigators wrote.
As for imaging results, chest CT findings in children were similar to those in adults.“The typical manifestations were unilateral or bilateral subpleural ground-glass opacities, and consolidations with surrounding halo signs,” Dr. Xia and associates wrote, adding that consolidations with surrounding halo sign accounted for about half the pediatric cases and should be considered as “typical signs in pediatric patients.”
Pediatric cases were “rather rare” in the early days of the COVID-19 outbreak in Wuhan, where the first cases of infection were reported.
“As a pediatric group is usually susceptible to upper respiratory tract infection, because of their developing immune system, the delayed presence of pediatric patients is confusing,” the investigators wrote, noting that a low detection rate of pharyngeal swab COVID-19 nucleic acid test, distinguishing the virus from other common respiratory tract infectious pathogens in pediatric patients, “is still a problem.”
To better characterize the clinical and imaging features in children versus adults with COVID-19, Dr. Xia and associates reviewed these 20 pediatric cases, including 13 boys and 7 girls with ages ranging from less than 1 month to 14 years, 7 months (median 2 years, 1.5 months). Thirteen had an identified close contact with a COVID-19–diagnosed family member, and all were treated in an isolation ward. A total of 18 children were cured and discharged after an average stay of 13 days, and 2 neonates remained under observation because of positive swab results with negative CT findings. The investigators speculated that the different findings in neonates were perhaps caused by the influence of delivery on sampling or the specific CT manifestations for neonates, adding that more samples are needed for further clarification.
Based on these findings, “the CT imaging of COVID-19 infection should be differentiated with other virus pneumonias such as influenza virus, parainfluenza virus, respiratory syncytial virus, and adenovirus,” they concluded. It also should “be differentiated from bacterial pneumonia, mycoplasma pneumonia, and chlamydia pneumonia ... the density of pneumonia lesions caused by the latter pathogens is relatively higher.”
However, Dr. Xia and colleagues noted that chest CT manifestations of pneumonia caused by different pathogens overlap, and COVID-19 pneumonia “can be superimposed with serious and complex imaging manifestations, so epidemiological and etiological examinations should be combined.”
The investigators concluded that COVID-19 virus pneumonia in children is generally mild, and that the characteristic changes of subpleural ground-glass opacities and consolidations with surrounding halo on chest CT provide an “effective means for follow-up and evaluating the changes of lung lesions.”
“In the case that the positive rate of COVID-19 nucleic acid test from pharyngeal swab samples is not high, the early detection of lesions by CT is conducive to reasonable management and early treatment for pediatric patients. However, the diagnosis of COVID-19 pneumonia by CT imaging alone is not sufficient enough, especially in the case of coinfection with other pathogens,” Dr. Xia and associates wrote. “Therefore, early chest CT screening and timely follow-up, combined with corresponding pathogen detection, is a feasible clinical protocol in children.”
An early study
In a separate retrospective analysis described in a letter to the editor of the New England Journal of Medicine, Weiyong Liu, PhD, of Tongji Hospital of Huazhong University of Science and Technology and colleagues found that the most frequently detected pathogens in 366 children under the age of 16 years hospitalized with respiratory infections in Wuhan during Jan. 7-15, 2020, were influenza A virus (6.3% of cases) and influenza B virus (5.5% of cases), whereas COVID-19 was detected in 1.6% of cases.
The median age of the COVID-19 patients in that series was 3 years (range 1-7 years), and in contrast to the findings of Xia et al., all previously had been “completely healthy.” Common characteristics were high fever and cough in all six patients, and vomiting in four patients. Five had pneumonia as assessed by X-ray, and CTs showed typical viral pneumonia patterns.
One patient was admitted to a pediatric ICU. All patients received antiviral agents, antibiotic agents, and supportive therapies; all recovered after a median hospital stay of 7.5 days (median range, 5-13 days).
In contrast with the findings of Xia et al., the findings of Liu et al. showed COVID-19 caused moderate to severe respiratory illness in children, and that infections in children were occurring early in the epidemic.
Some perspective
In an interview regarding the findings by Xia et al., Stephen I. Pelton, MD, professor of pediatrics and epidemiology at Boston University, and director of pediatric infectious diseases at Boston Medical Center, noted the absence of fever in 40% of cases.
“This is important, as the criteria for testing by public health departments has been high fever, cough, and shortness of breath,” he said. “The absence of fever is not inconsistent with COVID-19 disease.”
Another important point regarding the findings by Xia et al. is that the highest attack rates appear to be in children under 1 year of age, he said, further noting that the finding of concurrent influenza A, influenza B, or respiratory syncytial virus underscores that “concurrent infection can occur, and the presence of another virus in diagnostic tests does not mean that COVID-19 is not causal.”
As for whether the finding of elevated procalcitonin levels in 80% of cases reflects COVID-19 disease or coinfection with bacteria, the answer is unclear. But none of the children in the study were proven to have bacterial disease, he said, adding that “this marker will need to be interpreted with caution in the setting of COVID-19 disease.”
Dr. Xia and colleagues reported having no disclosures. Dr. Liu and associates also reported having no disclosures. The study by Liu et al. was supported by the Ministry of Science and Technology of China, the National Mega Project on Major Infectious Disease Prevention, and the National Key Research and Development Program of China.
SOURCES: Xia W et al. Ped Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718; Liu W et al. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.
Pediatric cases of COVID-19 infection are typically mild, but underlying coinfection may be more common in children than in adults, according to an analysis of clinical, laboratory, and chest CT features of pediatric inpatients in Wuhan, China.
The findings point toward a need for early chest CT with corresponding pathogen detection in children with suspected COVID-19 infection, Wei Xia, MD, of Huazhong University of Science and Technology, Wuhan, China, and colleagues reported in Pediatric Pulmonology.
The most common symptoms in 20 pediatric patients hospitalized between Jan. 23 and Feb. 8, 2020, with COVID-19 infection confirmed by the pharyngeal swab COVID-19 nucleic acid test were fever and cough, which occurred in 60% and 65% of patients, respectively. Coinfection was detected in eight patients (40%), they noted.
Clinical manifestations were similar to those seen in adults, but overall symptoms were relatively mild and overall prognosis was good. Of particular note, 7 of the 20 (35%) patients had a previously diagnosed congenital or acquired diseases, suggesting that children with underlying conditions may be more susceptible, Dr. Xia and colleagues wrote.
Laboratory findings also were notable in that 80% of the children had procalcitonin (PCT) elevations not typically seen in adults with COVID-19. PCT is a marker for bacterial infection and “[this finding] may suggest that routine antibacterial treatment should be considered in pediatric patients,” the investigators wrote.
As for imaging results, chest CT findings in children were similar to those in adults.“The typical manifestations were unilateral or bilateral subpleural ground-glass opacities, and consolidations with surrounding halo signs,” Dr. Xia and associates wrote, adding that consolidations with surrounding halo sign accounted for about half the pediatric cases and should be considered as “typical signs in pediatric patients.”
Pediatric cases were “rather rare” in the early days of the COVID-19 outbreak in Wuhan, where the first cases of infection were reported.
“As a pediatric group is usually susceptible to upper respiratory tract infection, because of their developing immune system, the delayed presence of pediatric patients is confusing,” the investigators wrote, noting that a low detection rate of pharyngeal swab COVID-19 nucleic acid test, distinguishing the virus from other common respiratory tract infectious pathogens in pediatric patients, “is still a problem.”
To better characterize the clinical and imaging features in children versus adults with COVID-19, Dr. Xia and associates reviewed these 20 pediatric cases, including 13 boys and 7 girls with ages ranging from less than 1 month to 14 years, 7 months (median 2 years, 1.5 months). Thirteen had an identified close contact with a COVID-19–diagnosed family member, and all were treated in an isolation ward. A total of 18 children were cured and discharged after an average stay of 13 days, and 2 neonates remained under observation because of positive swab results with negative CT findings. The investigators speculated that the different findings in neonates were perhaps caused by the influence of delivery on sampling or the specific CT manifestations for neonates, adding that more samples are needed for further clarification.
Based on these findings, “the CT imaging of COVID-19 infection should be differentiated with other virus pneumonias such as influenza virus, parainfluenza virus, respiratory syncytial virus, and adenovirus,” they concluded. It also should “be differentiated from bacterial pneumonia, mycoplasma pneumonia, and chlamydia pneumonia ... the density of pneumonia lesions caused by the latter pathogens is relatively higher.”
However, Dr. Xia and colleagues noted that chest CT manifestations of pneumonia caused by different pathogens overlap, and COVID-19 pneumonia “can be superimposed with serious and complex imaging manifestations, so epidemiological and etiological examinations should be combined.”
The investigators concluded that COVID-19 virus pneumonia in children is generally mild, and that the characteristic changes of subpleural ground-glass opacities and consolidations with surrounding halo on chest CT provide an “effective means for follow-up and evaluating the changes of lung lesions.”
“In the case that the positive rate of COVID-19 nucleic acid test from pharyngeal swab samples is not high, the early detection of lesions by CT is conducive to reasonable management and early treatment for pediatric patients. However, the diagnosis of COVID-19 pneumonia by CT imaging alone is not sufficient enough, especially in the case of coinfection with other pathogens,” Dr. Xia and associates wrote. “Therefore, early chest CT screening and timely follow-up, combined with corresponding pathogen detection, is a feasible clinical protocol in children.”
An early study
In a separate retrospective analysis described in a letter to the editor of the New England Journal of Medicine, Weiyong Liu, PhD, of Tongji Hospital of Huazhong University of Science and Technology and colleagues found that the most frequently detected pathogens in 366 children under the age of 16 years hospitalized with respiratory infections in Wuhan during Jan. 7-15, 2020, were influenza A virus (6.3% of cases) and influenza B virus (5.5% of cases), whereas COVID-19 was detected in 1.6% of cases.
The median age of the COVID-19 patients in that series was 3 years (range 1-7 years), and in contrast to the findings of Xia et al., all previously had been “completely healthy.” Common characteristics were high fever and cough in all six patients, and vomiting in four patients. Five had pneumonia as assessed by X-ray, and CTs showed typical viral pneumonia patterns.
One patient was admitted to a pediatric ICU. All patients received antiviral agents, antibiotic agents, and supportive therapies; all recovered after a median hospital stay of 7.5 days (median range, 5-13 days).
In contrast with the findings of Xia et al., the findings of Liu et al. showed COVID-19 caused moderate to severe respiratory illness in children, and that infections in children were occurring early in the epidemic.
Some perspective
In an interview regarding the findings by Xia et al., Stephen I. Pelton, MD, professor of pediatrics and epidemiology at Boston University, and director of pediatric infectious diseases at Boston Medical Center, noted the absence of fever in 40% of cases.
“This is important, as the criteria for testing by public health departments has been high fever, cough, and shortness of breath,” he said. “The absence of fever is not inconsistent with COVID-19 disease.”
Another important point regarding the findings by Xia et al. is that the highest attack rates appear to be in children under 1 year of age, he said, further noting that the finding of concurrent influenza A, influenza B, or respiratory syncytial virus underscores that “concurrent infection can occur, and the presence of another virus in diagnostic tests does not mean that COVID-19 is not causal.”
As for whether the finding of elevated procalcitonin levels in 80% of cases reflects COVID-19 disease or coinfection with bacteria, the answer is unclear. But none of the children in the study were proven to have bacterial disease, he said, adding that “this marker will need to be interpreted with caution in the setting of COVID-19 disease.”
Dr. Xia and colleagues reported having no disclosures. Dr. Liu and associates also reported having no disclosures. The study by Liu et al. was supported by the Ministry of Science and Technology of China, the National Mega Project on Major Infectious Disease Prevention, and the National Key Research and Development Program of China.
SOURCES: Xia W et al. Ped Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718; Liu W et al. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.
Pediatric cases of COVID-19 infection are typically mild, but underlying coinfection may be more common in children than in adults, according to an analysis of clinical, laboratory, and chest CT features of pediatric inpatients in Wuhan, China.
The findings point toward a need for early chest CT with corresponding pathogen detection in children with suspected COVID-19 infection, Wei Xia, MD, of Huazhong University of Science and Technology, Wuhan, China, and colleagues reported in Pediatric Pulmonology.
The most common symptoms in 20 pediatric patients hospitalized between Jan. 23 and Feb. 8, 2020, with COVID-19 infection confirmed by the pharyngeal swab COVID-19 nucleic acid test were fever and cough, which occurred in 60% and 65% of patients, respectively. Coinfection was detected in eight patients (40%), they noted.
Clinical manifestations were similar to those seen in adults, but overall symptoms were relatively mild and overall prognosis was good. Of particular note, 7 of the 20 (35%) patients had a previously diagnosed congenital or acquired diseases, suggesting that children with underlying conditions may be more susceptible, Dr. Xia and colleagues wrote.
Laboratory findings also were notable in that 80% of the children had procalcitonin (PCT) elevations not typically seen in adults with COVID-19. PCT is a marker for bacterial infection and “[this finding] may suggest that routine antibacterial treatment should be considered in pediatric patients,” the investigators wrote.
As for imaging results, chest CT findings in children were similar to those in adults.“The typical manifestations were unilateral or bilateral subpleural ground-glass opacities, and consolidations with surrounding halo signs,” Dr. Xia and associates wrote, adding that consolidations with surrounding halo sign accounted for about half the pediatric cases and should be considered as “typical signs in pediatric patients.”
Pediatric cases were “rather rare” in the early days of the COVID-19 outbreak in Wuhan, where the first cases of infection were reported.
“As a pediatric group is usually susceptible to upper respiratory tract infection, because of their developing immune system, the delayed presence of pediatric patients is confusing,” the investigators wrote, noting that a low detection rate of pharyngeal swab COVID-19 nucleic acid test, distinguishing the virus from other common respiratory tract infectious pathogens in pediatric patients, “is still a problem.”
To better characterize the clinical and imaging features in children versus adults with COVID-19, Dr. Xia and associates reviewed these 20 pediatric cases, including 13 boys and 7 girls with ages ranging from less than 1 month to 14 years, 7 months (median 2 years, 1.5 months). Thirteen had an identified close contact with a COVID-19–diagnosed family member, and all were treated in an isolation ward. A total of 18 children were cured and discharged after an average stay of 13 days, and 2 neonates remained under observation because of positive swab results with negative CT findings. The investigators speculated that the different findings in neonates were perhaps caused by the influence of delivery on sampling or the specific CT manifestations for neonates, adding that more samples are needed for further clarification.
Based on these findings, “the CT imaging of COVID-19 infection should be differentiated with other virus pneumonias such as influenza virus, parainfluenza virus, respiratory syncytial virus, and adenovirus,” they concluded. It also should “be differentiated from bacterial pneumonia, mycoplasma pneumonia, and chlamydia pneumonia ... the density of pneumonia lesions caused by the latter pathogens is relatively higher.”
However, Dr. Xia and colleagues noted that chest CT manifestations of pneumonia caused by different pathogens overlap, and COVID-19 pneumonia “can be superimposed with serious and complex imaging manifestations, so epidemiological and etiological examinations should be combined.”
The investigators concluded that COVID-19 virus pneumonia in children is generally mild, and that the characteristic changes of subpleural ground-glass opacities and consolidations with surrounding halo on chest CT provide an “effective means for follow-up and evaluating the changes of lung lesions.”
“In the case that the positive rate of COVID-19 nucleic acid test from pharyngeal swab samples is not high, the early detection of lesions by CT is conducive to reasonable management and early treatment for pediatric patients. However, the diagnosis of COVID-19 pneumonia by CT imaging alone is not sufficient enough, especially in the case of coinfection with other pathogens,” Dr. Xia and associates wrote. “Therefore, early chest CT screening and timely follow-up, combined with corresponding pathogen detection, is a feasible clinical protocol in children.”
An early study
In a separate retrospective analysis described in a letter to the editor of the New England Journal of Medicine, Weiyong Liu, PhD, of Tongji Hospital of Huazhong University of Science and Technology and colleagues found that the most frequently detected pathogens in 366 children under the age of 16 years hospitalized with respiratory infections in Wuhan during Jan. 7-15, 2020, were influenza A virus (6.3% of cases) and influenza B virus (5.5% of cases), whereas COVID-19 was detected in 1.6% of cases.
The median age of the COVID-19 patients in that series was 3 years (range 1-7 years), and in contrast to the findings of Xia et al., all previously had been “completely healthy.” Common characteristics were high fever and cough in all six patients, and vomiting in four patients. Five had pneumonia as assessed by X-ray, and CTs showed typical viral pneumonia patterns.
One patient was admitted to a pediatric ICU. All patients received antiviral agents, antibiotic agents, and supportive therapies; all recovered after a median hospital stay of 7.5 days (median range, 5-13 days).
In contrast with the findings of Xia et al., the findings of Liu et al. showed COVID-19 caused moderate to severe respiratory illness in children, and that infections in children were occurring early in the epidemic.
Some perspective
In an interview regarding the findings by Xia et al., Stephen I. Pelton, MD, professor of pediatrics and epidemiology at Boston University, and director of pediatric infectious diseases at Boston Medical Center, noted the absence of fever in 40% of cases.
“This is important, as the criteria for testing by public health departments has been high fever, cough, and shortness of breath,” he said. “The absence of fever is not inconsistent with COVID-19 disease.”
Another important point regarding the findings by Xia et al. is that the highest attack rates appear to be in children under 1 year of age, he said, further noting that the finding of concurrent influenza A, influenza B, or respiratory syncytial virus underscores that “concurrent infection can occur, and the presence of another virus in diagnostic tests does not mean that COVID-19 is not causal.”
As for whether the finding of elevated procalcitonin levels in 80% of cases reflects COVID-19 disease or coinfection with bacteria, the answer is unclear. But none of the children in the study were proven to have bacterial disease, he said, adding that “this marker will need to be interpreted with caution in the setting of COVID-19 disease.”
Dr. Xia and colleagues reported having no disclosures. Dr. Liu and associates also reported having no disclosures. The study by Liu et al. was supported by the Ministry of Science and Technology of China, the National Mega Project on Major Infectious Disease Prevention, and the National Key Research and Development Program of China.
SOURCES: Xia W et al. Ped Pulmonol. 2020 Mar 5. doi: 10.1002/ppul.24718; Liu W et al. N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMc2003717.
FROM PEDIATRIC PULMONOLOGY
Lymphopenia linked to worse response in RCC, bladder cancer patients on checkpoint inhibitors
ORLANDO – treated in a real-world setting.
In a retrospective study of 20 patients, those with lower pALCs and higher pNLRs were less likely to respond to checkpoint inhibitors.
Tonjeh Bah, MD, of Feist-Weiller Cancer Center at LSU Health Shreveport in Louisiana, and colleagues reported these results in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.
Response rates were 75% in patients with pALC greater than 1,000 and 25% in patients with pALC less than 1,000. This difference was statistically significant (P = .027), Dr. Bah noted, adding that the groups were comparable with respect to age, sex, race, and type of checkpoint inhibitors used.
Similarly, response rates were 80% in patients with pNLR less than 3 (the established upper limit of normal) and 30% in patients with pNLR greater than 3 (P = .024).
Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 and programmed death-1 and its ligand are essential components of therapy across multiple cancer types, Dr. Bah noted in an interview. She explained that prior studies – mostly in patients with lung cancer and head and neck cancers – have also shown pALC and pNLR to be independently associated with poor checkpoint inhibitor response and worse progression-free survival.
“But this is the first study to look at the connection in kidney and bladder cancer in a real-world setting,” she said.
Dr. Bah and colleagues conducted the study to test the hypothesis that “lymphopenia is a marker of immune exhaustion, which is characterized by dysfunctional T cells that have a limited antitumor effect even in the presence of [checkpoint inhibitors] and by the eventual depletion of antitumor lymphocytes,” they wrote in the poster.
Patients included in the study were all those with renal cell carcinoma (n = 13) or bladder-urothelial cancers (n = 7) who received checkpoint inhibitors at one of two medical centers in Louisiana during 2015-2019 and who had outcomes reported. Patients who attained stable disease or had partial or complete responses were categorized as responders. Patients who progressed on checkpoint inhibitors were considered nonresponders.
“Our findings were not a surprise, but they do document, for the first time and in a real-world setting, that pALC and pNLR may have prognostic utility in patients with kidney and bladder cancers who are treated with [checkpoint inhibitors],” Dr. Bah said.
She added that the findings could help determine which patients are candidates for checkpoint inhibitors, but the results require confirmation in a large, prospective study. Dr. Bah reported having no disclosures, and there was no sponsor for this study.
SOURCE: Bah T et al. ASCO-SITC 2020. Abstract 31.
ORLANDO – treated in a real-world setting.
In a retrospective study of 20 patients, those with lower pALCs and higher pNLRs were less likely to respond to checkpoint inhibitors.
Tonjeh Bah, MD, of Feist-Weiller Cancer Center at LSU Health Shreveport in Louisiana, and colleagues reported these results in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.
Response rates were 75% in patients with pALC greater than 1,000 and 25% in patients with pALC less than 1,000. This difference was statistically significant (P = .027), Dr. Bah noted, adding that the groups were comparable with respect to age, sex, race, and type of checkpoint inhibitors used.
Similarly, response rates were 80% in patients with pNLR less than 3 (the established upper limit of normal) and 30% in patients with pNLR greater than 3 (P = .024).
Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 and programmed death-1 and its ligand are essential components of therapy across multiple cancer types, Dr. Bah noted in an interview. She explained that prior studies – mostly in patients with lung cancer and head and neck cancers – have also shown pALC and pNLR to be independently associated with poor checkpoint inhibitor response and worse progression-free survival.
“But this is the first study to look at the connection in kidney and bladder cancer in a real-world setting,” she said.
Dr. Bah and colleagues conducted the study to test the hypothesis that “lymphopenia is a marker of immune exhaustion, which is characterized by dysfunctional T cells that have a limited antitumor effect even in the presence of [checkpoint inhibitors] and by the eventual depletion of antitumor lymphocytes,” they wrote in the poster.
Patients included in the study were all those with renal cell carcinoma (n = 13) or bladder-urothelial cancers (n = 7) who received checkpoint inhibitors at one of two medical centers in Louisiana during 2015-2019 and who had outcomes reported. Patients who attained stable disease or had partial or complete responses were categorized as responders. Patients who progressed on checkpoint inhibitors were considered nonresponders.
“Our findings were not a surprise, but they do document, for the first time and in a real-world setting, that pALC and pNLR may have prognostic utility in patients with kidney and bladder cancers who are treated with [checkpoint inhibitors],” Dr. Bah said.
She added that the findings could help determine which patients are candidates for checkpoint inhibitors, but the results require confirmation in a large, prospective study. Dr. Bah reported having no disclosures, and there was no sponsor for this study.
SOURCE: Bah T et al. ASCO-SITC 2020. Abstract 31.
ORLANDO – treated in a real-world setting.
In a retrospective study of 20 patients, those with lower pALCs and higher pNLRs were less likely to respond to checkpoint inhibitors.
Tonjeh Bah, MD, of Feist-Weiller Cancer Center at LSU Health Shreveport in Louisiana, and colleagues reported these results in a poster at the ASCO-SITC Clinical Immuno-Oncology Symposium.
Response rates were 75% in patients with pALC greater than 1,000 and 25% in patients with pALC less than 1,000. This difference was statistically significant (P = .027), Dr. Bah noted, adding that the groups were comparable with respect to age, sex, race, and type of checkpoint inhibitors used.
Similarly, response rates were 80% in patients with pNLR less than 3 (the established upper limit of normal) and 30% in patients with pNLR greater than 3 (P = .024).
Checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 and programmed death-1 and its ligand are essential components of therapy across multiple cancer types, Dr. Bah noted in an interview. She explained that prior studies – mostly in patients with lung cancer and head and neck cancers – have also shown pALC and pNLR to be independently associated with poor checkpoint inhibitor response and worse progression-free survival.
“But this is the first study to look at the connection in kidney and bladder cancer in a real-world setting,” she said.
Dr. Bah and colleagues conducted the study to test the hypothesis that “lymphopenia is a marker of immune exhaustion, which is characterized by dysfunctional T cells that have a limited antitumor effect even in the presence of [checkpoint inhibitors] and by the eventual depletion of antitumor lymphocytes,” they wrote in the poster.
Patients included in the study were all those with renal cell carcinoma (n = 13) or bladder-urothelial cancers (n = 7) who received checkpoint inhibitors at one of two medical centers in Louisiana during 2015-2019 and who had outcomes reported. Patients who attained stable disease or had partial or complete responses were categorized as responders. Patients who progressed on checkpoint inhibitors were considered nonresponders.
“Our findings were not a surprise, but they do document, for the first time and in a real-world setting, that pALC and pNLR may have prognostic utility in patients with kidney and bladder cancers who are treated with [checkpoint inhibitors],” Dr. Bah said.
She added that the findings could help determine which patients are candidates for checkpoint inhibitors, but the results require confirmation in a large, prospective study. Dr. Bah reported having no disclosures, and there was no sponsor for this study.
SOURCE: Bah T et al. ASCO-SITC 2020. Abstract 31.
REPORTING FROM THE CLINICAL IMMUNO-ONCOLOGY SYMPOSIUM
Review reveals shorter OS, RFS in young colorectal cancer patients
Colorectal cancer patients aged 10-25 years have significantly worse survival rates than those of older patients, findings from a retrospective review suggest.
Overall survival (OS) at 3 years was 42% among patients aged 10-25 years and 90% among patients older than 25 years of age (P less than .0001). Recurrence-free survival (RFS) rates were 32% and 78%, respectively (P less than .0001).
Andrea A. Hayes-Jordan, MD, of the University of North Carolina at Chapel Hill, and colleagues reported these findings in the Journal of the American College of Surgeons.
The researchers reviewed patients treated at MD Anderson Cancer Center in Houston between 1991 and 2017 who were part of a prospectively maintained database. The cohort comprised 94 patients ages 10-25 years and 765 patients who were older than 25 years of age.
RFS and OS data were available for all of the older patients. For the younger group, RFS data were available for 77 patients, and OS data were available for 80 patients.
Five-year OS rates by disease stage in the younger and older groups, respectively, were:
100% and 96% for stage 1.
64% and 90% for stage 2 (P less than .0001).
58% and 85% for stage 3 (P less than .0001).
16% and 55% for stage 4 (P less than .0001).
Five-year RFS rates by disease stage in the younger and older groups, respectively, were:
100% and 95% for stage 1.
55% and 85% for stage 2 (P = .0002).
31% and 73% for stage 3 (P less than .0001).
5% and 27% for stage 4 (P less than .0001).
On multivariate analysis, patients aged 10-25 years had a significantly higher risk of recurrence or death (hazard ratio, 2.312; P less than .0001) and a higher risk of death (HR, 3.592; P less than .0001) compared with older patients.
Of note, peritoneal metastasis occurred significantly more often in the younger group (P = .00001), but predisposing conditions such as polyposis or congenital colon disease did not account for this difference.
“Besides age, mucinous and signet ring histology, poorly differentiated histology, [and] microsatellite instability were statistically significantly more prevalent in this [young] population,” the researchers wrote. “Although other authors have noted similar differences, none have identified peritoneal metastasis to be statistically significantly more prevalent in patients under 25 years.”
The reason for this finding “most certainly lies in the biology in this age group and propensity to develop peritoneal metastasis based on a yet unknown genetic factor,” the researchers added. They reported having no disclosures.
SOURCE: Hayes-Jordan A et al. J Am Coll Surg. 2020 Feb 21. doi: 10.1016/j.jamcollsurg.2019.12.043.
Colorectal cancer patients aged 10-25 years have significantly worse survival rates than those of older patients, findings from a retrospective review suggest.
Overall survival (OS) at 3 years was 42% among patients aged 10-25 years and 90% among patients older than 25 years of age (P less than .0001). Recurrence-free survival (RFS) rates were 32% and 78%, respectively (P less than .0001).
Andrea A. Hayes-Jordan, MD, of the University of North Carolina at Chapel Hill, and colleagues reported these findings in the Journal of the American College of Surgeons.
The researchers reviewed patients treated at MD Anderson Cancer Center in Houston between 1991 and 2017 who were part of a prospectively maintained database. The cohort comprised 94 patients ages 10-25 years and 765 patients who were older than 25 years of age.
RFS and OS data were available for all of the older patients. For the younger group, RFS data were available for 77 patients, and OS data were available for 80 patients.
Five-year OS rates by disease stage in the younger and older groups, respectively, were:
100% and 96% for stage 1.
64% and 90% for stage 2 (P less than .0001).
58% and 85% for stage 3 (P less than .0001).
16% and 55% for stage 4 (P less than .0001).
Five-year RFS rates by disease stage in the younger and older groups, respectively, were:
100% and 95% for stage 1.
55% and 85% for stage 2 (P = .0002).
31% and 73% for stage 3 (P less than .0001).
5% and 27% for stage 4 (P less than .0001).
On multivariate analysis, patients aged 10-25 years had a significantly higher risk of recurrence or death (hazard ratio, 2.312; P less than .0001) and a higher risk of death (HR, 3.592; P less than .0001) compared with older patients.
Of note, peritoneal metastasis occurred significantly more often in the younger group (P = .00001), but predisposing conditions such as polyposis or congenital colon disease did not account for this difference.
“Besides age, mucinous and signet ring histology, poorly differentiated histology, [and] microsatellite instability were statistically significantly more prevalent in this [young] population,” the researchers wrote. “Although other authors have noted similar differences, none have identified peritoneal metastasis to be statistically significantly more prevalent in patients under 25 years.”
The reason for this finding “most certainly lies in the biology in this age group and propensity to develop peritoneal metastasis based on a yet unknown genetic factor,” the researchers added. They reported having no disclosures.
SOURCE: Hayes-Jordan A et al. J Am Coll Surg. 2020 Feb 21. doi: 10.1016/j.jamcollsurg.2019.12.043.
Colorectal cancer patients aged 10-25 years have significantly worse survival rates than those of older patients, findings from a retrospective review suggest.
Overall survival (OS) at 3 years was 42% among patients aged 10-25 years and 90% among patients older than 25 years of age (P less than .0001). Recurrence-free survival (RFS) rates were 32% and 78%, respectively (P less than .0001).
Andrea A. Hayes-Jordan, MD, of the University of North Carolina at Chapel Hill, and colleagues reported these findings in the Journal of the American College of Surgeons.
The researchers reviewed patients treated at MD Anderson Cancer Center in Houston between 1991 and 2017 who were part of a prospectively maintained database. The cohort comprised 94 patients ages 10-25 years and 765 patients who were older than 25 years of age.
RFS and OS data were available for all of the older patients. For the younger group, RFS data were available for 77 patients, and OS data were available for 80 patients.
Five-year OS rates by disease stage in the younger and older groups, respectively, were:
100% and 96% for stage 1.
64% and 90% for stage 2 (P less than .0001).
58% and 85% for stage 3 (P less than .0001).
16% and 55% for stage 4 (P less than .0001).
Five-year RFS rates by disease stage in the younger and older groups, respectively, were:
100% and 95% for stage 1.
55% and 85% for stage 2 (P = .0002).
31% and 73% for stage 3 (P less than .0001).
5% and 27% for stage 4 (P less than .0001).
On multivariate analysis, patients aged 10-25 years had a significantly higher risk of recurrence or death (hazard ratio, 2.312; P less than .0001) and a higher risk of death (HR, 3.592; P less than .0001) compared with older patients.
Of note, peritoneal metastasis occurred significantly more often in the younger group (P = .00001), but predisposing conditions such as polyposis or congenital colon disease did not account for this difference.
“Besides age, mucinous and signet ring histology, poorly differentiated histology, [and] microsatellite instability were statistically significantly more prevalent in this [young] population,” the researchers wrote. “Although other authors have noted similar differences, none have identified peritoneal metastasis to be statistically significantly more prevalent in patients under 25 years.”
The reason for this finding “most certainly lies in the biology in this age group and propensity to develop peritoneal metastasis based on a yet unknown genetic factor,” the researchers added. They reported having no disclosures.
SOURCE: Hayes-Jordan A et al. J Am Coll Surg. 2020 Feb 21. doi: 10.1016/j.jamcollsurg.2019.12.043.
FROM JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS