Key clinical point: Approximately half of transfusion-dependent MDS patients said they had not discussed ways to reduce the need for transfusions with their doctors and 74% said there were no alternatives to blood transfusions.

Major finding: Among adults with MDS, those with disease duration less than 5 years cited transfusion reactions as their greatest concern; those with longer disease duration cited iron overload. However, a majority of 71% of the patients ranked their quality of life as good or excellent. MDS physicians reported that they would be most likely to offer blood transfusions as primary therapy to patients who were older than 80 years, frail, had lower risk MDS, or had other significant comorbidities.

Study details: The data come from a pair of cross-sectional surveys including 157 myelodysplastic syndrome (MDS) patients and 109 MDS physicians.

Disclosures: The study was supported by the Aplastic Anemia and MDS International Foundation through a grant from Celgene. Lead author Dr. King was supported in part by The Maren Research Award Scholarship through the University of Florida.

Citation: King D et al. Leuk Res. 2020 July 15. doi: 10.1016/j.leukres.2020.106425.

Key clinical point: Approximately half of transfusion-dependent MDS patients said they had not discussed ways to reduce the need for transfusions with their doctors and 74% said there were no alternatives to blood transfusions.

Major finding: Among adults with MDS, those with disease duration less than 5 years cited transfusion reactions as their greatest concern; those with longer disease duration cited iron overload. However, a majority of 71% of the patients ranked their quality of life as good or excellent. MDS physicians reported that they would be most likely to offer blood transfusions as primary therapy to patients who were older than 80 years, frail, had lower risk MDS, or had other significant comorbidities.

Study details: The data come from a pair of cross-sectional surveys including 157 myelodysplastic syndrome (MDS) patients and 109 MDS physicians.

Disclosures: The study was supported by the Aplastic Anemia and MDS International Foundation through a grant from Celgene. Lead author Dr. King was supported in part by The Maren Research Award Scholarship through the University of Florida.

Citation: King D et al. Leuk Res. 2020 July 15. doi: 10.1016/j.leukres.2020.106425.

Key clinical point: Approximately half of transfusion-dependent MDS patients said they had not discussed ways to reduce the need for transfusions with their doctors and 74% said there were no alternatives to blood transfusions.

Major finding: Among adults with MDS, those with disease duration less than 5 years cited transfusion reactions as their greatest concern; those with longer disease duration cited iron overload. However, a majority of 71% of the patients ranked their quality of life as good or excellent. MDS physicians reported that they would be most likely to offer blood transfusions as primary therapy to patients who were older than 80 years, frail, had lower risk MDS, or had other significant comorbidities.

Study details: The data come from a pair of cross-sectional surveys including 157 myelodysplastic syndrome (MDS) patients and 109 MDS physicians.

Disclosures: The study was supported by the Aplastic Anemia and MDS International Foundation through a grant from Celgene. Lead author Dr. King was supported in part by The Maren Research Award Scholarship through the University of Florida.

Citation: King D et al. Leuk Res. 2020 July 15. doi: 10.1016/j.leukres.2020.106425.

Key clinical point: Bronchoscopy was safe for most patients with malignant hematologic disorders with careful monitoring and use of sedatives, particularly midazolam.

Major finding: A total of 12 out of 272 patients (3.8%) experienced prolonged oxygen desaturation; 7 of these recovered and 5 died from lung lesion deterioration. However, midazolam reduced the risk of prolonged oxygen desaturation in the study population.

Study details: The data come from a review of 316 bronchoscopies in 282 adults with malignant hematologic disorders and pulmonary infiltrates who were treated at a single center.

Disclosures: Lead author Dr. Uruga disclosed grant support from Okinaka Memorial Institute for Medical Research.

Citation: Uruga H et al. BMC Pulm Med. 2020 Sep 11. doi: 10.1186/s12890-020-01283-8.

Key clinical point: Bronchoscopy was safe for most patients with malignant hematologic disorders with careful monitoring and use of sedatives, particularly midazolam.

Major finding: A total of 12 out of 272 patients (3.8%) experienced prolonged oxygen desaturation; 7 of these recovered and 5 died from lung lesion deterioration. However, midazolam reduced the risk of prolonged oxygen desaturation in the study population.

Study details: The data come from a review of 316 bronchoscopies in 282 adults with malignant hematologic disorders and pulmonary infiltrates who were treated at a single center.

Disclosures: Lead author Dr. Uruga disclosed grant support from Okinaka Memorial Institute for Medical Research.

Citation: Uruga H et al. BMC Pulm Med. 2020 Sep 11. doi: 10.1186/s12890-020-01283-8.

Key clinical point: Bronchoscopy was safe for most patients with malignant hematologic disorders with careful monitoring and use of sedatives, particularly midazolam.

Major finding: A total of 12 out of 272 patients (3.8%) experienced prolonged oxygen desaturation; 7 of these recovered and 5 died from lung lesion deterioration. However, midazolam reduced the risk of prolonged oxygen desaturation in the study population.

Study details: The data come from a review of 316 bronchoscopies in 282 adults with malignant hematologic disorders and pulmonary infiltrates who were treated at a single center.

Disclosures: Lead author Dr. Uruga disclosed grant support from Okinaka Memorial Institute for Medical Research.

Citation: Uruga H et al. BMC Pulm Med. 2020 Sep 11. doi: 10.1186/s12890-020-01283-8.

Key clinical point: Adults with end-stage renal disease who underwent dialysis for at least six months were at significantly increased risk for MDS compared with healthy controls.

Major finding: Patients with chronic renal failure who underwent dialysis were significantly more likely to develop myelodysplastic syndrome compared to healthy controls (subdistribution hazard ratio 1.60); older age also was significantly associated with increased MDS risk (sHR 1.03).

Study details: The data come from a study of 74,712 adults with chronic renal failure diagnoses between 1997 and 2013 who underwent dialysis, and matched controls. Participants were follow from index date to the first occurrence of MDS, withdrawal from the NHI program, or the last day of 2013.

Disclosures: The study used the National Health Insurance Research Database established by the National Health Research Institutes with the authorization of the Bureau of National Health Insurance, Ministry of Health and Welfare of Taiwan. The researchers had no financial conflicts to disclose.

Citation: Chang M-Y et al. Sci Rep. 2020 Sept 23. doi: 10.1038/s41598-020-72568-5.

Key clinical point: Adults with end-stage renal disease who underwent dialysis for at least six months were at significantly increased risk for MDS compared with healthy controls.

Major finding: Patients with chronic renal failure who underwent dialysis were significantly more likely to develop myelodysplastic syndrome compared to healthy controls (subdistribution hazard ratio 1.60); older age also was significantly associated with increased MDS risk (sHR 1.03).

Study details: The data come from a study of 74,712 adults with chronic renal failure diagnoses between 1997 and 2013 who underwent dialysis, and matched controls. Participants were follow from index date to the first occurrence of MDS, withdrawal from the NHI program, or the last day of 2013.

Disclosures: The study used the National Health Insurance Research Database established by the National Health Research Institutes with the authorization of the Bureau of National Health Insurance, Ministry of Health and Welfare of Taiwan. The researchers had no financial conflicts to disclose.

Citation: Chang M-Y et al. Sci Rep. 2020 Sept 23. doi: 10.1038/s41598-020-72568-5.

Key clinical point: Adults with end-stage renal disease who underwent dialysis for at least six months were at significantly increased risk for MDS compared with healthy controls.

Major finding: Patients with chronic renal failure who underwent dialysis were significantly more likely to develop myelodysplastic syndrome compared to healthy controls (subdistribution hazard ratio 1.60); older age also was significantly associated with increased MDS risk (sHR 1.03).

Study details: The data come from a study of 74,712 adults with chronic renal failure diagnoses between 1997 and 2013 who underwent dialysis, and matched controls. Participants were follow from index date to the first occurrence of MDS, withdrawal from the NHI program, or the last day of 2013.

Disclosures: The study used the National Health Insurance Research Database established by the National Health Research Institutes with the authorization of the Bureau of National Health Insurance, Ministry of Health and Welfare of Taiwan. The researchers had no financial conflicts to disclose.

Citation: Chang M-Y et al. Sci Rep. 2020 Sept 23. doi: 10.1038/s41598-020-72568-5.

The days of using chemotherapy to treat Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) may be numbered.

In a phase 2 trial, upfront chemotherapy-free induction/consolidation with the tyrosine kinase inhibitor dasatinib (Sprycel) and the bispecific T-cell engager antibody blinatumomab (Blincyto) yielded high rates of molecular response, “impressive” survival at 18 months, and few toxic effects of grade 3 or higher, say researchers.

With this approach, “60% of adult Ph+ ALL patients, of all ages, can obtain a molecular response, and this percent can increase further with more cycles of blinatumomab,” lead researcher Robin Foà, MD, from Sapienza University of Rome, said in an interview.

“The rates of disease-free survival and overall survival at 18 months are highly favorable, and the protocol is associated with limited toxicity,” Dr. Foà added.

“I see this chemo-free approach becoming a realistic approach for a substantial proportion of adult Ph+ ALL patients, particularly for the older patients, keeping in mind that the incidence of Ph+ ALL increases with age,” Dr. Foà said.

The results of the study were published Oct. 22 in the New England Journal of Medicine.
 

‘Innovative’ and ‘highly successful’

This “innovative” chemotherapy-free approach proved “highly successful” with “surprisingly” few toxic effects, Dieter Hoelzer, MD, PhD, University of Frankfurt (Germany), wrote in a linked editorial.

The Italian GIMEMA LAL2116 D-ALBA trial enrolled 63 adults (median age, 54 years; range, 24-82 years) with newly diagnosed Ph+ ALL. All patients received a glucocorticoid for 31 days beginning 7 days before starting treatment with dasatinib.

Dasatinib (140 mg once daily) induction therapy lasted 85 days. All patients who completed the induction phase received blinatumomab (28 mcg/d) consolidation therapy. Dexamethasone (20 mg) was administered before each blinatumomab cycle. To prevent central nervous system adverse events, levetiracetam (500 mg twice daily) was administered.

All but two patients completed dasatinib induction. One was a 73-year-old woman who withdrew from the trial because of toxic effects after 10 days of dasatinib treatment. She later died of pneumonia. The other was an 82-year-old woman who had a complete hematologic response but left the trial because of pneumonia and pneumonitis.

At the end of the induction phase, 98% of the patients (62 of 63) had a complete hematologic response, including the patient with a complete hematologic response who withdrew; 29% (17 of 59 patients) had a molecular response.

Of the 61 patients who completed the induction phase, 58 received one cycle of blinatumomab, 56 received two cycles, 45 received three cycles, 37 received four cycles, and 29 received five cycles. At the end of the second blinatumomab cycle, 60% of the patients (33 of 55 patients) had a molecular response.

The percentage of patients with a molecular response increased further after receiving additional cycles of blinatumomab – to 70% (28 of 40 patients) after the third cycle, 81% (29 of 36 patients) after the fourth cycle, and 72% (21 of 29 patients) after the fifth cycle.

At a median follow-up of 18 months, overall survival was 95%, and disease-free survival was 88%.

There were no significant differences in DFS between patients with p190-kd fusion protein (85%) and those with p210-kd fusion protein (95%). However, DFS was lower in patients with IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both).

ABL1 mutations were present in six patients who had increased minimal residual disease during induction therapy. All these mutations were cleared by blinatumomab.

There were six relapses, of which three were hematologic. One occurred in a patient with a major protocol violation (a delay of more than 2 months in receiving blinatumomab), one occurred after 12 months in the patient who discontinued the trial after receiving dasatinib for 12 days, and one occurred in a patient after the second cycle of blinatumomab.

A total of 21 adverse events of grade 3 or higher were noted. They included cytomegalovirus reactivation or infection in six patients; neutropenia in four patients; persistent fever in two patients; and pleural effusion, pulmonary hypertension, and a neurologic disorder in one patient each.

Of the 24 patients who received a stem-cell allograft, two died, but only one death was related to transplant (4%).

The very low nonrelapse mortality among patients who underwent transplant during remission is “remarkable,” Dr. Hoelzer wrote. It suggests that toxicity from induction chemotherapy puts the patient at risk for toxic effects and death from subsequent stem-cell transplant – “a consequence that is avoided with targeted therapy.”
 

Unanswered questions

“Will the excellent outcomes be preserved with longer follow-up? The answer is probably yes, given that the majority of relapses in ALL occur within the first 1.5 to 2.0 years after the initiation of treatment,” Dr. Hoelzer wrote.

He said other outstanding questions include whether long-term outcomes will differ between patients who undergo transplant and those who do not; whether ABL1 mutations emerge; whether minimal residual disease recurs with longer follow-up; and whether this treatment approach can be used for patients with other subtypes of ALL, such as Ph-negative, B-lineage ALL, or even T-cell ALL.

“If these promising trial results hold, chemotherapy-free induction without the immediate and long-term toxic effects of intensive chemotherapy regimens could also be used in adolescents and, finally, in children. These questions will need to be addressed with longer follow-up and large, prospective trials,” Dr. Hoelzer concluded.

The study was supported by grants from the Italian Association for Cancer Research and Sapienza University of Rome.

A version of this article originally appeared on Medscape.com

The days of using chemotherapy to treat Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) may be numbered.

In a phase 2 trial, upfront chemotherapy-free induction/consolidation with the tyrosine kinase inhibitor dasatinib (Sprycel) and the bispecific T-cell engager antibody blinatumomab (Blincyto) yielded high rates of molecular response, “impressive” survival at 18 months, and few toxic effects of grade 3 or higher, say researchers.

With this approach, “60% of adult Ph+ ALL patients, of all ages, can obtain a molecular response, and this percent can increase further with more cycles of blinatumomab,” lead researcher Robin Foà, MD, from Sapienza University of Rome, said in an interview.

“The rates of disease-free survival and overall survival at 18 months are highly favorable, and the protocol is associated with limited toxicity,” Dr. Foà added.

“I see this chemo-free approach becoming a realistic approach for a substantial proportion of adult Ph+ ALL patients, particularly for the older patients, keeping in mind that the incidence of Ph+ ALL increases with age,” Dr. Foà said.

The results of the study were published Oct. 22 in the New England Journal of Medicine.
 

‘Innovative’ and ‘highly successful’

This “innovative” chemotherapy-free approach proved “highly successful” with “surprisingly” few toxic effects, Dieter Hoelzer, MD, PhD, University of Frankfurt (Germany), wrote in a linked editorial.

The Italian GIMEMA LAL2116 D-ALBA trial enrolled 63 adults (median age, 54 years; range, 24-82 years) with newly diagnosed Ph+ ALL. All patients received a glucocorticoid for 31 days beginning 7 days before starting treatment with dasatinib.

Dasatinib (140 mg once daily) induction therapy lasted 85 days. All patients who completed the induction phase received blinatumomab (28 mcg/d) consolidation therapy. Dexamethasone (20 mg) was administered before each blinatumomab cycle. To prevent central nervous system adverse events, levetiracetam (500 mg twice daily) was administered.

All but two patients completed dasatinib induction. One was a 73-year-old woman who withdrew from the trial because of toxic effects after 10 days of dasatinib treatment. She later died of pneumonia. The other was an 82-year-old woman who had a complete hematologic response but left the trial because of pneumonia and pneumonitis.

At the end of the induction phase, 98% of the patients (62 of 63) had a complete hematologic response, including the patient with a complete hematologic response who withdrew; 29% (17 of 59 patients) had a molecular response.

Of the 61 patients who completed the induction phase, 58 received one cycle of blinatumomab, 56 received two cycles, 45 received three cycles, 37 received four cycles, and 29 received five cycles. At the end of the second blinatumomab cycle, 60% of the patients (33 of 55 patients) had a molecular response.

The percentage of patients with a molecular response increased further after receiving additional cycles of blinatumomab – to 70% (28 of 40 patients) after the third cycle, 81% (29 of 36 patients) after the fourth cycle, and 72% (21 of 29 patients) after the fifth cycle.

At a median follow-up of 18 months, overall survival was 95%, and disease-free survival was 88%.

There were no significant differences in DFS between patients with p190-kd fusion protein (85%) and those with p210-kd fusion protein (95%). However, DFS was lower in patients with IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both).

ABL1 mutations were present in six patients who had increased minimal residual disease during induction therapy. All these mutations were cleared by blinatumomab.

There were six relapses, of which three were hematologic. One occurred in a patient with a major protocol violation (a delay of more than 2 months in receiving blinatumomab), one occurred after 12 months in the patient who discontinued the trial after receiving dasatinib for 12 days, and one occurred in a patient after the second cycle of blinatumomab.

A total of 21 adverse events of grade 3 or higher were noted. They included cytomegalovirus reactivation or infection in six patients; neutropenia in four patients; persistent fever in two patients; and pleural effusion, pulmonary hypertension, and a neurologic disorder in one patient each.

Of the 24 patients who received a stem-cell allograft, two died, but only one death was related to transplant (4%).

The very low nonrelapse mortality among patients who underwent transplant during remission is “remarkable,” Dr. Hoelzer wrote. It suggests that toxicity from induction chemotherapy puts the patient at risk for toxic effects and death from subsequent stem-cell transplant – “a consequence that is avoided with targeted therapy.”
 

Unanswered questions

“Will the excellent outcomes be preserved with longer follow-up? The answer is probably yes, given that the majority of relapses in ALL occur within the first 1.5 to 2.0 years after the initiation of treatment,” Dr. Hoelzer wrote.

He said other outstanding questions include whether long-term outcomes will differ between patients who undergo transplant and those who do not; whether ABL1 mutations emerge; whether minimal residual disease recurs with longer follow-up; and whether this treatment approach can be used for patients with other subtypes of ALL, such as Ph-negative, B-lineage ALL, or even T-cell ALL.

“If these promising trial results hold, chemotherapy-free induction without the immediate and long-term toxic effects of intensive chemotherapy regimens could also be used in adolescents and, finally, in children. These questions will need to be addressed with longer follow-up and large, prospective trials,” Dr. Hoelzer concluded.

The study was supported by grants from the Italian Association for Cancer Research and Sapienza University of Rome.

A version of this article originally appeared on Medscape.com

The days of using chemotherapy to treat Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) may be numbered.

In a phase 2 trial, upfront chemotherapy-free induction/consolidation with the tyrosine kinase inhibitor dasatinib (Sprycel) and the bispecific T-cell engager antibody blinatumomab (Blincyto) yielded high rates of molecular response, “impressive” survival at 18 months, and few toxic effects of grade 3 or higher, say researchers.

With this approach, “60% of adult Ph+ ALL patients, of all ages, can obtain a molecular response, and this percent can increase further with more cycles of blinatumomab,” lead researcher Robin Foà, MD, from Sapienza University of Rome, said in an interview.

“The rates of disease-free survival and overall survival at 18 months are highly favorable, and the protocol is associated with limited toxicity,” Dr. Foà added.

“I see this chemo-free approach becoming a realistic approach for a substantial proportion of adult Ph+ ALL patients, particularly for the older patients, keeping in mind that the incidence of Ph+ ALL increases with age,” Dr. Foà said.

The results of the study were published Oct. 22 in the New England Journal of Medicine.
 

‘Innovative’ and ‘highly successful’

This “innovative” chemotherapy-free approach proved “highly successful” with “surprisingly” few toxic effects, Dieter Hoelzer, MD, PhD, University of Frankfurt (Germany), wrote in a linked editorial.

The Italian GIMEMA LAL2116 D-ALBA trial enrolled 63 adults (median age, 54 years; range, 24-82 years) with newly diagnosed Ph+ ALL. All patients received a glucocorticoid for 31 days beginning 7 days before starting treatment with dasatinib.

Dasatinib (140 mg once daily) induction therapy lasted 85 days. All patients who completed the induction phase received blinatumomab (28 mcg/d) consolidation therapy. Dexamethasone (20 mg) was administered before each blinatumomab cycle. To prevent central nervous system adverse events, levetiracetam (500 mg twice daily) was administered.

All but two patients completed dasatinib induction. One was a 73-year-old woman who withdrew from the trial because of toxic effects after 10 days of dasatinib treatment. She later died of pneumonia. The other was an 82-year-old woman who had a complete hematologic response but left the trial because of pneumonia and pneumonitis.

At the end of the induction phase, 98% of the patients (62 of 63) had a complete hematologic response, including the patient with a complete hematologic response who withdrew; 29% (17 of 59 patients) had a molecular response.

Of the 61 patients who completed the induction phase, 58 received one cycle of blinatumomab, 56 received two cycles, 45 received three cycles, 37 received four cycles, and 29 received five cycles. At the end of the second blinatumomab cycle, 60% of the patients (33 of 55 patients) had a molecular response.

The percentage of patients with a molecular response increased further after receiving additional cycles of blinatumomab – to 70% (28 of 40 patients) after the third cycle, 81% (29 of 36 patients) after the fourth cycle, and 72% (21 of 29 patients) after the fifth cycle.

At a median follow-up of 18 months, overall survival was 95%, and disease-free survival was 88%.

There were no significant differences in DFS between patients with p190-kd fusion protein (85%) and those with p210-kd fusion protein (95%). However, DFS was lower in patients with IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both).

ABL1 mutations were present in six patients who had increased minimal residual disease during induction therapy. All these mutations were cleared by blinatumomab.

There were six relapses, of which three were hematologic. One occurred in a patient with a major protocol violation (a delay of more than 2 months in receiving blinatumomab), one occurred after 12 months in the patient who discontinued the trial after receiving dasatinib for 12 days, and one occurred in a patient after the second cycle of blinatumomab.

A total of 21 adverse events of grade 3 or higher were noted. They included cytomegalovirus reactivation or infection in six patients; neutropenia in four patients; persistent fever in two patients; and pleural effusion, pulmonary hypertension, and a neurologic disorder in one patient each.

Of the 24 patients who received a stem-cell allograft, two died, but only one death was related to transplant (4%).

The very low nonrelapse mortality among patients who underwent transplant during remission is “remarkable,” Dr. Hoelzer wrote. It suggests that toxicity from induction chemotherapy puts the patient at risk for toxic effects and death from subsequent stem-cell transplant – “a consequence that is avoided with targeted therapy.”
 

Unanswered questions

“Will the excellent outcomes be preserved with longer follow-up? The answer is probably yes, given that the majority of relapses in ALL occur within the first 1.5 to 2.0 years after the initiation of treatment,” Dr. Hoelzer wrote.

He said other outstanding questions include whether long-term outcomes will differ between patients who undergo transplant and those who do not; whether ABL1 mutations emerge; whether minimal residual disease recurs with longer follow-up; and whether this treatment approach can be used for patients with other subtypes of ALL, such as Ph-negative, B-lineage ALL, or even T-cell ALL.

“If these promising trial results hold, chemotherapy-free induction without the immediate and long-term toxic effects of intensive chemotherapy regimens could also be used in adolescents and, finally, in children. These questions will need to be addressed with longer follow-up and large, prospective trials,” Dr. Hoelzer concluded.

The study was supported by grants from the Italian Association for Cancer Research and Sapienza University of Rome.

A version of this article originally appeared on Medscape.com

Key clinical point: Several long noncoding RNAs (lncRNAs) were strongly associated with disease pathogenesis and prognosis in myelodysplastic syndrome (MDS) patients.

Major finding: Based on genome-wide profiling, lncRNA gene networks with expression of H19, WT1-AS, TCL6, and LEF1-AS1 were associated with higher-risk MDS; of these, H19 also showed promise as a therapeutic target because of its strong predictive value for lower complete remission rate of induction therapy in AML in the presence of H19 overexpression. 

Study details: The data come from a study of genetic profiling including 54 patients with MDS, 14 patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 9 healthy donors.

Disclosures: The study was supported by the Project for Conceptual Development of Research Organization from the Ministry of Health of the Czech Republic. The researchers had no financial conflicts to disclose.

Citation: Szikszai K et al. Cancers. 2020 Sept 23. doi: 10.3390/cancers12102726.

Key clinical point: Several long noncoding RNAs (lncRNAs) were strongly associated with disease pathogenesis and prognosis in myelodysplastic syndrome (MDS) patients.

Major finding: Based on genome-wide profiling, lncRNA gene networks with expression of H19, WT1-AS, TCL6, and LEF1-AS1 were associated with higher-risk MDS; of these, H19 also showed promise as a therapeutic target because of its strong predictive value for lower complete remission rate of induction therapy in AML in the presence of H19 overexpression. 

Study details: The data come from a study of genetic profiling including 54 patients with MDS, 14 patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 9 healthy donors.

Disclosures: The study was supported by the Project for Conceptual Development of Research Organization from the Ministry of Health of the Czech Republic. The researchers had no financial conflicts to disclose.

Citation: Szikszai K et al. Cancers. 2020 Sept 23. doi: 10.3390/cancers12102726.

Key clinical point: Several long noncoding RNAs (lncRNAs) were strongly associated with disease pathogenesis and prognosis in myelodysplastic syndrome (MDS) patients.

Major finding: Based on genome-wide profiling, lncRNA gene networks with expression of H19, WT1-AS, TCL6, and LEF1-AS1 were associated with higher-risk MDS; of these, H19 also showed promise as a therapeutic target because of its strong predictive value for lower complete remission rate of induction therapy in AML in the presence of H19 overexpression. 

Study details: The data come from a study of genetic profiling including 54 patients with MDS, 14 patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 9 healthy donors.

Disclosures: The study was supported by the Project for Conceptual Development of Research Organization from the Ministry of Health of the Czech Republic. The researchers had no financial conflicts to disclose.

Citation: Szikszai K et al. Cancers. 2020 Sept 23. doi: 10.3390/cancers12102726.

Key clinical point: Ferroptosis, a distinct form of regulated cell death process involving iron-dependent lipid peroxidation, may impact the action of chemotherapy drug decitabine.

Major finding: The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in MDS cells upon treatment with decitabine, which could be reversed by ferrostatin-1.

Study details: The data come from a review of cell viability assays, reactive oxygen species assays, gluthiathone assays, and

Disclosures: The study was supported in part by the National Natural Science Foundation of China, Key Technology Research and Development Program of Tianjin, Application Bases and Advanced Technology Research Program of Tianjin, and Key National Natural Science Foundation of Tianjin. The researchers had no financial conflicts to disclose.

Citation: Lv Q et al. Front. Oncol. 2020 Sept 2. doi: 10.3389/fonc.2020.01656.

Key clinical point: Ferroptosis, a distinct form of regulated cell death process involving iron-dependent lipid peroxidation, may impact the action of chemotherapy drug decitabine.

Major finding: The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in MDS cells upon treatment with decitabine, which could be reversed by ferrostatin-1.

Study details: The data come from a review of cell viability assays, reactive oxygen species assays, gluthiathone assays, and

Disclosures: The study was supported in part by the National Natural Science Foundation of China, Key Technology Research and Development Program of Tianjin, Application Bases and Advanced Technology Research Program of Tianjin, and Key National Natural Science Foundation of Tianjin. The researchers had no financial conflicts to disclose.

Citation: Lv Q et al. Front. Oncol. 2020 Sept 2. doi: 10.3389/fonc.2020.01656.

Key clinical point: Ferroptosis, a distinct form of regulated cell death process involving iron-dependent lipid peroxidation, may impact the action of chemotherapy drug decitabine.

Major finding: The level of GSH and the activity of GPX4 decreased, whereas the ROS level increased in MDS cells upon treatment with decitabine, which could be reversed by ferrostatin-1.

Study details: The data come from a review of cell viability assays, reactive oxygen species assays, gluthiathone assays, and

Disclosures: The study was supported in part by the National Natural Science Foundation of China, Key Technology Research and Development Program of Tianjin, Application Bases and Advanced Technology Research Program of Tianjin, and Key National Natural Science Foundation of Tianjin. The researchers had no financial conflicts to disclose.

Citation: Lv Q et al. Front. Oncol. 2020 Sept 2. doi: 10.3389/fonc.2020.01656.

Key clinical point: In a population of MDS patients with COVID-19 symptoms who underwent laboratory testing, 20.6% had confirmed cases.

Major finding: At the time of this analysis, 33 of 63 COVID-19 positive MDS patients were alive, suggesting a higher lethality rate in this population compared to the population at large.

Study details: The data come from a review of 5,326 adults with myelodysplastic syndromes who were symptomatic for COVID-19 between February 24 and April 28, 2020; 305 MDS patients underwent laboratory testing to confirm the infection.

Disclosures: The study was received no outside funding. The researchers had no financial conflicts to disclose.

Citation: Mossuto S et al. HemaSphere. 2020 Oct. doi: 10.1097/HS9.0000000000000483.

Key clinical point: In a population of MDS patients with COVID-19 symptoms who underwent laboratory testing, 20.6% had confirmed cases.

Major finding: At the time of this analysis, 33 of 63 COVID-19 positive MDS patients were alive, suggesting a higher lethality rate in this population compared to the population at large.

Study details: The data come from a review of 5,326 adults with myelodysplastic syndromes who were symptomatic for COVID-19 between February 24 and April 28, 2020; 305 MDS patients underwent laboratory testing to confirm the infection.

Disclosures: The study was received no outside funding. The researchers had no financial conflicts to disclose.

Citation: Mossuto S et al. HemaSphere. 2020 Oct. doi: 10.1097/HS9.0000000000000483.

Key clinical point: In a population of MDS patients with COVID-19 symptoms who underwent laboratory testing, 20.6% had confirmed cases.

Major finding: At the time of this analysis, 33 of 63 COVID-19 positive MDS patients were alive, suggesting a higher lethality rate in this population compared to the population at large.

Study details: The data come from a review of 5,326 adults with myelodysplastic syndromes who were symptomatic for COVID-19 between February 24 and April 28, 2020; 305 MDS patients underwent laboratory testing to confirm the infection.

Disclosures: The study was received no outside funding. The researchers had no financial conflicts to disclose.

Citation: Mossuto S et al. HemaSphere. 2020 Oct. doi: 10.1097/HS9.0000000000000483.

A commonly used newborn hearing test shows promise in the early detection of autism spectrum disorder (ASD), new research shows.  

Results from one of the largest studies of its kind show the auditory brainstem response (ABR) test, which is carried out on most newborns, represents “a huge untapped potential” to detect autism, lead author Oren Miron, research associate, department of biomedical informatics, Harvard Medical School, Boston, and a PhD candidate at Ben Gurion University in Beersheba, Israel, said in an interview.

“The findings further reinforce our understanding that autism, in many cases, has a sensorial and auditory aspect to it,” said Mr. Miron, adding that an adverse response to sound is one of the earliest behavioral signs of autism.

The research was published online Oct. 31 in Autism Research.
 

Early intervention critical

Autism spectrum disorder (ASD), which involves problems in social communication and interaction, affects an estimated 1 in 59 children. Early identification and intervention are critical for improving outcomes and decreasing the economic burden associated with ASD.

The ABR test, which is used for Universal Newborn Hearing Screening (UNHS), uses surface electrodes to measure auditory nerve and brainstem responses to sound.

Previous studies identified abnormal ABR amplitude in children with ASD. However, it’s unclear whether healthy newborns who later develop autism also show ABR differences vs those who don’t develop the disorder.

Researchers used UNHS data, which allowed them to examine a larger, younger, and healthier sample compared with previous studies. The study included 321 newborns later diagnosed with ASD and 138,844 controls without a subsequent ASD diagnosis.

The mean ABR testing age was 1.76 days for newborns later diagnosed with ASD and 1.86 for those in the non-ASD group.

The ASD group was 77% male and the non-ASD group was 51% male. The rate of neonatal intensive care unit admission was 8% in the ASD group and 10% in the non-ASD group.

The hearing test involves placing an earpiece in the baby’s ear and delivering a click sound at 35 dB above normal hearing level (nHL) at a rate of 77 clicks per second in the right ear and 79 clicks per second in the left ear.
 

Brainstem abnormalities?

The clicks create electrical activity, which is recorded by a surface electrode and used to extract the ABR waveform. When a sound reaches the brain stem, it creates five consecutive waveforms – waves I, II, III, IV, and V.

Previous studies focused on wave V, which is easiest to detect. The current study used low intensity sound that resulted in a weaker signal.

To overcome this low intensity issue, researchers focused on the negative drop (latency) after the wave V (Vn), which is easier to detect, and on the ABR phase, or entire waveform. They illustrated the differences between the ASD and non-ASD groups in a series of graphs.

Results showed that the ABR phase in the right ear was significantly prolonged in the ASD vs non-ASD group (P < .001). ABR phase in the left ear was also significantly prolonged in the ASD group (P = .021)

Vn latency in the right ear was significantly prolonged in the ASD group compared with the non-ASD group (P = .048); however, this was not the case in the left ear.

The prolongation could mean that the V-negative wave might appear after 8 ms in normally developing children compared with 8.5 or 9 ms in children with autism, said Mr. Miron.

The new study is the first to show V-negative and phase abnormalities are associated with ASD, the authors note. The brainstem prolongation could be due to anatomical abnormalities in the brainstem in individuals with ASD, the researchers added.
 

Present before birth?

The presence of ABR biomarkers of ASD in the first weeks after birth suggests the disorder is likely present before birth in a large group of these individuals, the researchers note.

It’s possible the ABR test could be modified to use lower intensities not only to detect hearing impairment but autism risk, said Mr. Miron. “The test has been optimized to detect hearing impairment, and it does so brilliantly and helps thousands of children. We want to do the same kind of optimization for autism.”

This could lead to earlier behavioral diagnoses, which, in turn, could lead to earlier treatment and better outcomes for children with ASD, said Mr. Miron.

At this time, the level of prolongation to detect ASD is unclear. “I would think a lot of people would want to make it one standard deviation, but it depends on a lot of factors, including for example, whether a baby is preterm,” said Mr. Miron.

More research and better accuracy and specificity are needed before the newborn hearing test is clinically useful.

He noted that the hearing test is only one marker of autism and that it could potentially be combined with other behavioral signs and genetic markers to facilitate earlier diagnosis and treatment and improve outcomes for patients with ASD.

Future research by his group will investigate whether the degree of auditory prolongation relates to autism severity. They also plan to research ASD subgroups including children with comorbid epilepsy.
 

Terrific, clever research

Jeremy Veenstra-VanderWeele, MD, professor, child and adolescent psychiatry, Columbia University, New York, said in an interview that the study is “terrific” and a “clever use” of an existing dataset.

“They showed a difference between a large group of kids with autism and a large group of kids without.”

However, he added, more research is needed before the test can be used as an autism screening tool.

“In order for this to be a screening test that could be broadly applied you would need to identify a cutoff where you’d think a child was at risk for autism, and if you look at the graphs in the article, there are no clear cutoffs,” said Dr. Veenstra-VanderWeele.

To turn this into a useful test, “you would have to establish sensitivity and specificity, you would have to look not just at the comparison of kids with autism and kids without but apply it in a predictive way in a second population.”

The study authors and Dr. Veenstra-VanderWeele have reported no relevant financial relationships. Veenstra-VanderWeele is an associate editor at Autism Research, which published the article, but he did not handle or view it before being interviewed.

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

A commonly used newborn hearing test shows promise in the early detection of autism spectrum disorder (ASD), new research shows.  

Results from one of the largest studies of its kind show the auditory brainstem response (ABR) test, which is carried out on most newborns, represents “a huge untapped potential” to detect autism, lead author Oren Miron, research associate, department of biomedical informatics, Harvard Medical School, Boston, and a PhD candidate at Ben Gurion University in Beersheba, Israel, said in an interview.

“The findings further reinforce our understanding that autism, in many cases, has a sensorial and auditory aspect to it,” said Mr. Miron, adding that an adverse response to sound is one of the earliest behavioral signs of autism.

The research was published online Oct. 31 in Autism Research.
 

Early intervention critical

Autism spectrum disorder (ASD), which involves problems in social communication and interaction, affects an estimated 1 in 59 children. Early identification and intervention are critical for improving outcomes and decreasing the economic burden associated with ASD.

The ABR test, which is used for Universal Newborn Hearing Screening (UNHS), uses surface electrodes to measure auditory nerve and brainstem responses to sound.

Previous studies identified abnormal ABR amplitude in children with ASD. However, it’s unclear whether healthy newborns who later develop autism also show ABR differences vs those who don’t develop the disorder.

Researchers used UNHS data, which allowed them to examine a larger, younger, and healthier sample compared with previous studies. The study included 321 newborns later diagnosed with ASD and 138,844 controls without a subsequent ASD diagnosis.

The mean ABR testing age was 1.76 days for newborns later diagnosed with ASD and 1.86 for those in the non-ASD group.

The ASD group was 77% male and the non-ASD group was 51% male. The rate of neonatal intensive care unit admission was 8% in the ASD group and 10% in the non-ASD group.

The hearing test involves placing an earpiece in the baby’s ear and delivering a click sound at 35 dB above normal hearing level (nHL) at a rate of 77 clicks per second in the right ear and 79 clicks per second in the left ear.
 

Brainstem abnormalities?

The clicks create electrical activity, which is recorded by a surface electrode and used to extract the ABR waveform. When a sound reaches the brain stem, it creates five consecutive waveforms – waves I, II, III, IV, and V.

Previous studies focused on wave V, which is easiest to detect. The current study used low intensity sound that resulted in a weaker signal.

To overcome this low intensity issue, researchers focused on the negative drop (latency) after the wave V (Vn), which is easier to detect, and on the ABR phase, or entire waveform. They illustrated the differences between the ASD and non-ASD groups in a series of graphs.

Results showed that the ABR phase in the right ear was significantly prolonged in the ASD vs non-ASD group (P < .001). ABR phase in the left ear was also significantly prolonged in the ASD group (P = .021)

Vn latency in the right ear was significantly prolonged in the ASD group compared with the non-ASD group (P = .048); however, this was not the case in the left ear.

The prolongation could mean that the V-negative wave might appear after 8 ms in normally developing children compared with 8.5 or 9 ms in children with autism, said Mr. Miron.

The new study is the first to show V-negative and phase abnormalities are associated with ASD, the authors note. The brainstem prolongation could be due to anatomical abnormalities in the brainstem in individuals with ASD, the researchers added.
 

Present before birth?

The presence of ABR biomarkers of ASD in the first weeks after birth suggests the disorder is likely present before birth in a large group of these individuals, the researchers note.

It’s possible the ABR test could be modified to use lower intensities not only to detect hearing impairment but autism risk, said Mr. Miron. “The test has been optimized to detect hearing impairment, and it does so brilliantly and helps thousands of children. We want to do the same kind of optimization for autism.”

This could lead to earlier behavioral diagnoses, which, in turn, could lead to earlier treatment and better outcomes for children with ASD, said Mr. Miron.

At this time, the level of prolongation to detect ASD is unclear. “I would think a lot of people would want to make it one standard deviation, but it depends on a lot of factors, including for example, whether a baby is preterm,” said Mr. Miron.

More research and better accuracy and specificity are needed before the newborn hearing test is clinically useful.

He noted that the hearing test is only one marker of autism and that it could potentially be combined with other behavioral signs and genetic markers to facilitate earlier diagnosis and treatment and improve outcomes for patients with ASD.

Future research by his group will investigate whether the degree of auditory prolongation relates to autism severity. They also plan to research ASD subgroups including children with comorbid epilepsy.
 

Terrific, clever research

Jeremy Veenstra-VanderWeele, MD, professor, child and adolescent psychiatry, Columbia University, New York, said in an interview that the study is “terrific” and a “clever use” of an existing dataset.

“They showed a difference between a large group of kids with autism and a large group of kids without.”

However, he added, more research is needed before the test can be used as an autism screening tool.

“In order for this to be a screening test that could be broadly applied you would need to identify a cutoff where you’d think a child was at risk for autism, and if you look at the graphs in the article, there are no clear cutoffs,” said Dr. Veenstra-VanderWeele.

To turn this into a useful test, “you would have to establish sensitivity and specificity, you would have to look not just at the comparison of kids with autism and kids without but apply it in a predictive way in a second population.”

The study authors and Dr. Veenstra-VanderWeele have reported no relevant financial relationships. Veenstra-VanderWeele is an associate editor at Autism Research, which published the article, but he did not handle or view it before being interviewed.

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

A commonly used newborn hearing test shows promise in the early detection of autism spectrum disorder (ASD), new research shows.  

Results from one of the largest studies of its kind show the auditory brainstem response (ABR) test, which is carried out on most newborns, represents “a huge untapped potential” to detect autism, lead author Oren Miron, research associate, department of biomedical informatics, Harvard Medical School, Boston, and a PhD candidate at Ben Gurion University in Beersheba, Israel, said in an interview.

“The findings further reinforce our understanding that autism, in many cases, has a sensorial and auditory aspect to it,” said Mr. Miron, adding that an adverse response to sound is one of the earliest behavioral signs of autism.

The research was published online Oct. 31 in Autism Research.
 

Early intervention critical

Autism spectrum disorder (ASD), which involves problems in social communication and interaction, affects an estimated 1 in 59 children. Early identification and intervention are critical for improving outcomes and decreasing the economic burden associated with ASD.

The ABR test, which is used for Universal Newborn Hearing Screening (UNHS), uses surface electrodes to measure auditory nerve and brainstem responses to sound.

Previous studies identified abnormal ABR amplitude in children with ASD. However, it’s unclear whether healthy newborns who later develop autism also show ABR differences vs those who don’t develop the disorder.

Researchers used UNHS data, which allowed them to examine a larger, younger, and healthier sample compared with previous studies. The study included 321 newborns later diagnosed with ASD and 138,844 controls without a subsequent ASD diagnosis.

The mean ABR testing age was 1.76 days for newborns later diagnosed with ASD and 1.86 for those in the non-ASD group.

The ASD group was 77% male and the non-ASD group was 51% male. The rate of neonatal intensive care unit admission was 8% in the ASD group and 10% in the non-ASD group.

The hearing test involves placing an earpiece in the baby’s ear and delivering a click sound at 35 dB above normal hearing level (nHL) at a rate of 77 clicks per second in the right ear and 79 clicks per second in the left ear.
 

Brainstem abnormalities?

The clicks create electrical activity, which is recorded by a surface electrode and used to extract the ABR waveform. When a sound reaches the brain stem, it creates five consecutive waveforms – waves I, II, III, IV, and V.

Previous studies focused on wave V, which is easiest to detect. The current study used low intensity sound that resulted in a weaker signal.

To overcome this low intensity issue, researchers focused on the negative drop (latency) after the wave V (Vn), which is easier to detect, and on the ABR phase, or entire waveform. They illustrated the differences between the ASD and non-ASD groups in a series of graphs.

Results showed that the ABR phase in the right ear was significantly prolonged in the ASD vs non-ASD group (P < .001). ABR phase in the left ear was also significantly prolonged in the ASD group (P = .021)

Vn latency in the right ear was significantly prolonged in the ASD group compared with the non-ASD group (P = .048); however, this was not the case in the left ear.

The prolongation could mean that the V-negative wave might appear after 8 ms in normally developing children compared with 8.5 or 9 ms in children with autism, said Mr. Miron.

The new study is the first to show V-negative and phase abnormalities are associated with ASD, the authors note. The brainstem prolongation could be due to anatomical abnormalities in the brainstem in individuals with ASD, the researchers added.
 

Present before birth?

The presence of ABR biomarkers of ASD in the first weeks after birth suggests the disorder is likely present before birth in a large group of these individuals, the researchers note.

It’s possible the ABR test could be modified to use lower intensities not only to detect hearing impairment but autism risk, said Mr. Miron. “The test has been optimized to detect hearing impairment, and it does so brilliantly and helps thousands of children. We want to do the same kind of optimization for autism.”

This could lead to earlier behavioral diagnoses, which, in turn, could lead to earlier treatment and better outcomes for children with ASD, said Mr. Miron.

At this time, the level of prolongation to detect ASD is unclear. “I would think a lot of people would want to make it one standard deviation, but it depends on a lot of factors, including for example, whether a baby is preterm,” said Mr. Miron.

More research and better accuracy and specificity are needed before the newborn hearing test is clinically useful.

He noted that the hearing test is only one marker of autism and that it could potentially be combined with other behavioral signs and genetic markers to facilitate earlier diagnosis and treatment and improve outcomes for patients with ASD.

Future research by his group will investigate whether the degree of auditory prolongation relates to autism severity. They also plan to research ASD subgroups including children with comorbid epilepsy.
 

Terrific, clever research

Jeremy Veenstra-VanderWeele, MD, professor, child and adolescent psychiatry, Columbia University, New York, said in an interview that the study is “terrific” and a “clever use” of an existing dataset.

“They showed a difference between a large group of kids with autism and a large group of kids without.”

However, he added, more research is needed before the test can be used as an autism screening tool.

“In order for this to be a screening test that could be broadly applied you would need to identify a cutoff where you’d think a child was at risk for autism, and if you look at the graphs in the article, there are no clear cutoffs,” said Dr. Veenstra-VanderWeele.

To turn this into a useful test, “you would have to establish sensitivity and specificity, you would have to look not just at the comparison of kids with autism and kids without but apply it in a predictive way in a second population.”

The study authors and Dr. Veenstra-VanderWeele have reported no relevant financial relationships. Veenstra-VanderWeele is an associate editor at Autism Research, which published the article, but he did not handle or view it before being interviewed.

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

Current evidence is insufficient to assess the balance of benefits and harms of screening for high blood pressure in children and adolescents, the U.S. Preventive Services Task Force reported in JAMA.

©Vishnu Kumar/Thinkstock

However, two experts in this area suggested there is evidence if you know where to look, and pediatric BP testing is crucial now.

In this update to the 2013 statement, the USPSTF’s systematic review focused on evidence surrounding the benefits of screening, test accuracy, treatment effectiveness and harms, and links between hypertension and cardiovascular disease (CVD) markers in childhood and adulthood.

Limited information was available on the accuracy of screening tests. No studies were found that directly evaluated screening for pediatric high BP or reported effectiveness in delayed onset or risk reduction for cardiovascular outcomes related to hypertension. Additionally, no studies were found that addressed screening for secondary hypertension in asymptomatic pediatric patients. No studies were found that evaluated the treatment of primary childhood hypertension and BP reduction or other outcomes in adulthood. The panel also was unable to identify any studies that reported on harms of screening and treatment.

When the adult framework for cardiovascular risk reduction is extended in pediatric patients, there are methodological challenges that make it harder to determine how much of the potential burden can actually be prevented, the panel said. The clinical and epidemiologic significance of percentile thresholds that are used to determine their ties to adult CVD has limited supporting evidence. Inconsistent performance characteristics of current diagnostic methods, of which there are few, tend to yield unfavorable high false-positive rates. Such false positives are potentially harmful, because they lead to “unnecessary secondary evaluations or treatments.” Because pharmacologic management of pediatric hypertension is continued for a much longer period, it is the increased likelihood of adverse events that should be cause for concern.
 

Should the focus for screening be shifted to significant risk factors?

In an accompanying editorial, Joseph T. Flynn, MD, MS, of Seattle Children’s Hospital, said that the outcome of the latest statement is expected, “given how the key questions were framed and the analysis performed.” To begin, he suggested restating the question: “What is the best approach to assess whether childhood BP measurement is associated with adult CVD or whether treatment of high BP in childhood is associated with reducing the burden of adult CVD?” The answer is to tackle these questions with randomized clinical trials that compare screening to no screening and treatment to no treatment. But such studies are likely infeasible, partly because of the required length of follow-up of 5-6 decades.

Perhaps a better question would be: “Does BP measurement in childhood identify children and adolescents who already have markers of CVD or who are at risk of developing them as adults?” Were these youth to be identified, they would become candidates for approaches that seek to prevent disease progression. Reframing the question in this manner better positions physicians to focus on prevention and sidestep “the requirement that the only acceptable outcome is prevention of CVD events in adulthood,” he explained.

The next step would be to identify data already available to address the reframed question. Cross-sectional studies could be used to make the association between BP levels and cardiovascular risk markers already present. For example, several publications from the multicenter Study of High Blood Pressure in Pediatrics: Adult Hypertension Onset in Youth (SHIP-AHOY), which enrolled roughly 400 youth, provided data that reinforce prior single-center studies that essentially proved there are adverse consequences for youth with high BP, and they “set the stage for the institution of measures designed to reverse target-organ damage and reduce cardiovascular risk in youth,” said Dr. Flynn.

More specifically, results from SHIP-AHOY “have demonstrated that increased left ventricular mass can be demonstrated at BP levels currently classified as normotensive and that abnormal left ventricular function can be seen at similar BP levels,” Dr. Flynn noted. In addition, “they have established a substantial association between an abnormal metabolic phenotype and several forms of target-organ damage associated with high BP.”
 

One approach is to analyze longitudinal cohort studies

Because there is a paucity of prospective clinical trials, Dr. Flynn suggested that analyzing longitudinal cohort studies would be the most effective approach for evaluating the potential link between current BP levels and future CVD. Such studies already have “data that address an important point raised in the USPSTF statement, namely whether the pediatric percentile-based BP cut points, such as those in the 2017 AAP [American Academy of Pediatrics] guideline, are associated with adult hypertension and CVD,” noted Dr. Flynn. “In the International Childhood Cardiovascular Cohort Consortium study, the specific childhood BP levels that were associated with increased adult carotid intima-medial thickness were remarkably similar to the BP percentile cut points in the AAP guideline for children of similar ages.”

Analysis of data from the Bogalusa Heart Study found looking at children classified as having high BP by the 2017 AAP guideline had “increased relative risks of having hypertension, left ventricular hypertrophy, or metabolic syndrome as adults 36 years later.”

“The conclusions of the USPSTF statement underscore the need for additional research on childhood high BP and its association with adult CVD. The starting points for such research can be deduced from currently available cross-sectional and longitudinal data, which demonstrate the detrimental outcomes associated with high BP in youth. Using these data to reframe and answer the questions raised by the USPSTF should point the way toward effective prevention of adult CVD,” concluded Dr. Flynn.

In a separate interview, Kristen Sexson Tejtel, MD, PhD, MPH, medical director of the preventive cardiology clinic at Texas Children’s Hospital and Baylor College of Medicine, both in Houston, noted that in spite of USPSTF’s findings, there is actually an association between children with high blood pressure and intermediate outcomes in adults.

“Dr. Flynn suggests reframing the question. In fact, evidence exists that children with high blood pressure are at higher risk of left ventricular hypertrophy, increased arterial stiffness, and changes in retinal arteries,” noted Dr. Sexson Tejtel.
 

Evidence of pediatric heart damage has been documented in autopsies

“It is imperative that children have blood pressure evaluation,” she urged. “There is evidence that there are changes similar to those seen in adults with cardiovascular compromise. It has been shown that children dying of other causes [accidents] who have these problems also have more plaque on autopsy, indicating that those with high blood pressure are more likely to have markers of CVD already present in childhood.

“One of the keys of pediatric medicine is prevention and the counseling for prevention of adult diseases. The duration of study necessary to objectively determine whether treatment of hypertension in childhood reduces the risk of adult cardiac problems is extensive. If nothing is done now, we are putting more future generations in danger. We must provide appropriate counseling for children and their families regarding lifestyle improvements, to have a chance to improve cardiovascular risk factors in adults, including hypertension, hyperlipidemia and/or obesity,” urged Dr. Sexson Tejtel.

All members of the USPSTF received travel reimbursement and honoraria. Dr. Barry received grants and personal fees from Healthwise. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF. Dr. Flynn reported receiving grants from the National Institutes of Health and royalties from UpToDate and Springer outside the submitted work. Dr. Sexson Tejtel said she had no relevant financial disclosures or conflicts of interest.

SOURCE: USPSTF. JAMA. 2020 Nov 10. doi: 10.1001/jama.2020.20122.

Current evidence is insufficient to assess the balance of benefits and harms of screening for high blood pressure in children and adolescents, the U.S. Preventive Services Task Force reported in JAMA.

©Vishnu Kumar/Thinkstock

However, two experts in this area suggested there is evidence if you know where to look, and pediatric BP testing is crucial now.

In this update to the 2013 statement, the USPSTF’s systematic review focused on evidence surrounding the benefits of screening, test accuracy, treatment effectiveness and harms, and links between hypertension and cardiovascular disease (CVD) markers in childhood and adulthood.

Limited information was available on the accuracy of screening tests. No studies were found that directly evaluated screening for pediatric high BP or reported effectiveness in delayed onset or risk reduction for cardiovascular outcomes related to hypertension. Additionally, no studies were found that addressed screening for secondary hypertension in asymptomatic pediatric patients. No studies were found that evaluated the treatment of primary childhood hypertension and BP reduction or other outcomes in adulthood. The panel also was unable to identify any studies that reported on harms of screening and treatment.

When the adult framework for cardiovascular risk reduction is extended in pediatric patients, there are methodological challenges that make it harder to determine how much of the potential burden can actually be prevented, the panel said. The clinical and epidemiologic significance of percentile thresholds that are used to determine their ties to adult CVD has limited supporting evidence. Inconsistent performance characteristics of current diagnostic methods, of which there are few, tend to yield unfavorable high false-positive rates. Such false positives are potentially harmful, because they lead to “unnecessary secondary evaluations or treatments.” Because pharmacologic management of pediatric hypertension is continued for a much longer period, it is the increased likelihood of adverse events that should be cause for concern.
 

Should the focus for screening be shifted to significant risk factors?

In an accompanying editorial, Joseph T. Flynn, MD, MS, of Seattle Children’s Hospital, said that the outcome of the latest statement is expected, “given how the key questions were framed and the analysis performed.” To begin, he suggested restating the question: “What is the best approach to assess whether childhood BP measurement is associated with adult CVD or whether treatment of high BP in childhood is associated with reducing the burden of adult CVD?” The answer is to tackle these questions with randomized clinical trials that compare screening to no screening and treatment to no treatment. But such studies are likely infeasible, partly because of the required length of follow-up of 5-6 decades.

Perhaps a better question would be: “Does BP measurement in childhood identify children and adolescents who already have markers of CVD or who are at risk of developing them as adults?” Were these youth to be identified, they would become candidates for approaches that seek to prevent disease progression. Reframing the question in this manner better positions physicians to focus on prevention and sidestep “the requirement that the only acceptable outcome is prevention of CVD events in adulthood,” he explained.

The next step would be to identify data already available to address the reframed question. Cross-sectional studies could be used to make the association between BP levels and cardiovascular risk markers already present. For example, several publications from the multicenter Study of High Blood Pressure in Pediatrics: Adult Hypertension Onset in Youth (SHIP-AHOY), which enrolled roughly 400 youth, provided data that reinforce prior single-center studies that essentially proved there are adverse consequences for youth with high BP, and they “set the stage for the institution of measures designed to reverse target-organ damage and reduce cardiovascular risk in youth,” said Dr. Flynn.

More specifically, results from SHIP-AHOY “have demonstrated that increased left ventricular mass can be demonstrated at BP levels currently classified as normotensive and that abnormal left ventricular function can be seen at similar BP levels,” Dr. Flynn noted. In addition, “they have established a substantial association between an abnormal metabolic phenotype and several forms of target-organ damage associated with high BP.”
 

One approach is to analyze longitudinal cohort studies

Because there is a paucity of prospective clinical trials, Dr. Flynn suggested that analyzing longitudinal cohort studies would be the most effective approach for evaluating the potential link between current BP levels and future CVD. Such studies already have “data that address an important point raised in the USPSTF statement, namely whether the pediatric percentile-based BP cut points, such as those in the 2017 AAP [American Academy of Pediatrics] guideline, are associated with adult hypertension and CVD,” noted Dr. Flynn. “In the International Childhood Cardiovascular Cohort Consortium study, the specific childhood BP levels that were associated with increased adult carotid intima-medial thickness were remarkably similar to the BP percentile cut points in the AAP guideline for children of similar ages.”

Analysis of data from the Bogalusa Heart Study found looking at children classified as having high BP by the 2017 AAP guideline had “increased relative risks of having hypertension, left ventricular hypertrophy, or metabolic syndrome as adults 36 years later.”

“The conclusions of the USPSTF statement underscore the need for additional research on childhood high BP and its association with adult CVD. The starting points for such research can be deduced from currently available cross-sectional and longitudinal data, which demonstrate the detrimental outcomes associated with high BP in youth. Using these data to reframe and answer the questions raised by the USPSTF should point the way toward effective prevention of adult CVD,” concluded Dr. Flynn.

In a separate interview, Kristen Sexson Tejtel, MD, PhD, MPH, medical director of the preventive cardiology clinic at Texas Children’s Hospital and Baylor College of Medicine, both in Houston, noted that in spite of USPSTF’s findings, there is actually an association between children with high blood pressure and intermediate outcomes in adults.

“Dr. Flynn suggests reframing the question. In fact, evidence exists that children with high blood pressure are at higher risk of left ventricular hypertrophy, increased arterial stiffness, and changes in retinal arteries,” noted Dr. Sexson Tejtel.
 

Evidence of pediatric heart damage has been documented in autopsies

“It is imperative that children have blood pressure evaluation,” she urged. “There is evidence that there are changes similar to those seen in adults with cardiovascular compromise. It has been shown that children dying of other causes [accidents] who have these problems also have more plaque on autopsy, indicating that those with high blood pressure are more likely to have markers of CVD already present in childhood.

“One of the keys of pediatric medicine is prevention and the counseling for prevention of adult diseases. The duration of study necessary to objectively determine whether treatment of hypertension in childhood reduces the risk of adult cardiac problems is extensive. If nothing is done now, we are putting more future generations in danger. We must provide appropriate counseling for children and their families regarding lifestyle improvements, to have a chance to improve cardiovascular risk factors in adults, including hypertension, hyperlipidemia and/or obesity,” urged Dr. Sexson Tejtel.

All members of the USPSTF received travel reimbursement and honoraria. Dr. Barry received grants and personal fees from Healthwise. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF. Dr. Flynn reported receiving grants from the National Institutes of Health and royalties from UpToDate and Springer outside the submitted work. Dr. Sexson Tejtel said she had no relevant financial disclosures or conflicts of interest.

SOURCE: USPSTF. JAMA. 2020 Nov 10. doi: 10.1001/jama.2020.20122.

Current evidence is insufficient to assess the balance of benefits and harms of screening for high blood pressure in children and adolescents, the U.S. Preventive Services Task Force reported in JAMA.

©Vishnu Kumar/Thinkstock

However, two experts in this area suggested there is evidence if you know where to look, and pediatric BP testing is crucial now.

In this update to the 2013 statement, the USPSTF’s systematic review focused on evidence surrounding the benefits of screening, test accuracy, treatment effectiveness and harms, and links between hypertension and cardiovascular disease (CVD) markers in childhood and adulthood.

Limited information was available on the accuracy of screening tests. No studies were found that directly evaluated screening for pediatric high BP or reported effectiveness in delayed onset or risk reduction for cardiovascular outcomes related to hypertension. Additionally, no studies were found that addressed screening for secondary hypertension in asymptomatic pediatric patients. No studies were found that evaluated the treatment of primary childhood hypertension and BP reduction or other outcomes in adulthood. The panel also was unable to identify any studies that reported on harms of screening and treatment.

When the adult framework for cardiovascular risk reduction is extended in pediatric patients, there are methodological challenges that make it harder to determine how much of the potential burden can actually be prevented, the panel said. The clinical and epidemiologic significance of percentile thresholds that are used to determine their ties to adult CVD has limited supporting evidence. Inconsistent performance characteristics of current diagnostic methods, of which there are few, tend to yield unfavorable high false-positive rates. Such false positives are potentially harmful, because they lead to “unnecessary secondary evaluations or treatments.” Because pharmacologic management of pediatric hypertension is continued for a much longer period, it is the increased likelihood of adverse events that should be cause for concern.
 

Should the focus for screening be shifted to significant risk factors?

In an accompanying editorial, Joseph T. Flynn, MD, MS, of Seattle Children’s Hospital, said that the outcome of the latest statement is expected, “given how the key questions were framed and the analysis performed.” To begin, he suggested restating the question: “What is the best approach to assess whether childhood BP measurement is associated with adult CVD or whether treatment of high BP in childhood is associated with reducing the burden of adult CVD?” The answer is to tackle these questions with randomized clinical trials that compare screening to no screening and treatment to no treatment. But such studies are likely infeasible, partly because of the required length of follow-up of 5-6 decades.

Perhaps a better question would be: “Does BP measurement in childhood identify children and adolescents who already have markers of CVD or who are at risk of developing them as adults?” Were these youth to be identified, they would become candidates for approaches that seek to prevent disease progression. Reframing the question in this manner better positions physicians to focus on prevention and sidestep “the requirement that the only acceptable outcome is prevention of CVD events in adulthood,” he explained.

The next step would be to identify data already available to address the reframed question. Cross-sectional studies could be used to make the association between BP levels and cardiovascular risk markers already present. For example, several publications from the multicenter Study of High Blood Pressure in Pediatrics: Adult Hypertension Onset in Youth (SHIP-AHOY), which enrolled roughly 400 youth, provided data that reinforce prior single-center studies that essentially proved there are adverse consequences for youth with high BP, and they “set the stage for the institution of measures designed to reverse target-organ damage and reduce cardiovascular risk in youth,” said Dr. Flynn.

More specifically, results from SHIP-AHOY “have demonstrated that increased left ventricular mass can be demonstrated at BP levels currently classified as normotensive and that abnormal left ventricular function can be seen at similar BP levels,” Dr. Flynn noted. In addition, “they have established a substantial association between an abnormal metabolic phenotype and several forms of target-organ damage associated with high BP.”
 

One approach is to analyze longitudinal cohort studies

Because there is a paucity of prospective clinical trials, Dr. Flynn suggested that analyzing longitudinal cohort studies would be the most effective approach for evaluating the potential link between current BP levels and future CVD. Such studies already have “data that address an important point raised in the USPSTF statement, namely whether the pediatric percentile-based BP cut points, such as those in the 2017 AAP [American Academy of Pediatrics] guideline, are associated with adult hypertension and CVD,” noted Dr. Flynn. “In the International Childhood Cardiovascular Cohort Consortium study, the specific childhood BP levels that were associated with increased adult carotid intima-medial thickness were remarkably similar to the BP percentile cut points in the AAP guideline for children of similar ages.”

Analysis of data from the Bogalusa Heart Study found looking at children classified as having high BP by the 2017 AAP guideline had “increased relative risks of having hypertension, left ventricular hypertrophy, or metabolic syndrome as adults 36 years later.”

“The conclusions of the USPSTF statement underscore the need for additional research on childhood high BP and its association with adult CVD. The starting points for such research can be deduced from currently available cross-sectional and longitudinal data, which demonstrate the detrimental outcomes associated with high BP in youth. Using these data to reframe and answer the questions raised by the USPSTF should point the way toward effective prevention of adult CVD,” concluded Dr. Flynn.

In a separate interview, Kristen Sexson Tejtel, MD, PhD, MPH, medical director of the preventive cardiology clinic at Texas Children’s Hospital and Baylor College of Medicine, both in Houston, noted that in spite of USPSTF’s findings, there is actually an association between children with high blood pressure and intermediate outcomes in adults.

“Dr. Flynn suggests reframing the question. In fact, evidence exists that children with high blood pressure are at higher risk of left ventricular hypertrophy, increased arterial stiffness, and changes in retinal arteries,” noted Dr. Sexson Tejtel.
 

Evidence of pediatric heart damage has been documented in autopsies

“It is imperative that children have blood pressure evaluation,” she urged. “There is evidence that there are changes similar to those seen in adults with cardiovascular compromise. It has been shown that children dying of other causes [accidents] who have these problems also have more plaque on autopsy, indicating that those with high blood pressure are more likely to have markers of CVD already present in childhood.

“One of the keys of pediatric medicine is prevention and the counseling for prevention of adult diseases. The duration of study necessary to objectively determine whether treatment of hypertension in childhood reduces the risk of adult cardiac problems is extensive. If nothing is done now, we are putting more future generations in danger. We must provide appropriate counseling for children and their families regarding lifestyle improvements, to have a chance to improve cardiovascular risk factors in adults, including hypertension, hyperlipidemia and/or obesity,” urged Dr. Sexson Tejtel.

All members of the USPSTF received travel reimbursement and honoraria. Dr. Barry received grants and personal fees from Healthwise. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF. Dr. Flynn reported receiving grants from the National Institutes of Health and royalties from UpToDate and Springer outside the submitted work. Dr. Sexson Tejtel said she had no relevant financial disclosures or conflicts of interest.

SOURCE: USPSTF. JAMA. 2020 Nov 10. doi: 10.1001/jama.2020.20122.

An international autopsy study of 21 patients who died from COVID-19 has shown the presence of multifocal lymphocytic myocarditis in three patients (14%). In an additional six patients, focally increased interstitial T-lymphocytes within the myocardium were noted, with only focal or no myocyte injury.

However, increased interstitial macrophage infiltration, possibly related to cytokine infiltration, was seen in 86% of patients.

“One way to think about this is that, if these patients were having biopsies and not autopsies, there would be myocardial injury in the patients with myocarditis, even after they recovered. But with interstitial macrophages, there may or may not be any injury,” said cardiovascular pathologist James R. Stone, MD, PhD, Massachusetts General Hospital, Boston.

Dr. Stone and colleagues from Mass General, two hospitals in Italy, the University of Amsterdam, and the Mayo Clinic in Rochester, Minn., conducted the autopsies in March and April. The results were published in the October 14 issue of the European Heart Journal.

Their technique was rigorous: a median of 20 full-thickness blocks of myocardium were examined histologically (range, 5-29 blocks).

The presence of myocarditis, defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analyzed by immunohistochemistry.

“I think one of the take-homes from this study is that you have to do a thorough sampling of the heart in order to exclude myocardial injury. You cannot exclude myocarditis with just a biopsy or two,” said Dr. Stone in an interview.

“We looked at multiple different sections of tissue preserved in paraffin for every case and found only 14% had myocarditis. The vast majority of autopsies done on patients dying from COVID-19 have short-changed the autopsy and not been done in a way to exclude myocarditis,” he added.

For all patients, COVID-19 was the underlying cause of death, but the mechanisms of death were acute respiratory distress syndrome in 15, viral pneumonia in 4, cardiogenic shock in 1, and cardiac arrest in 1. Seven patients had a history of cardiovascular disease, including atrial fibrillation in four, coronary artery disease in three, left ventricular hypertrophy in one, and previous valve replacement in one. A total of 16 had hypertension, 7 had diabetes mellitus, and 1 had chronic obstructive pulmonary disease. In four cases, mild pericarditis was present. Acute myocyte injury in the right ventricle, most probably from strain or overload, was also present in four cases.

A nonsignificant trend was seen toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis. There were no reports of disrupted coronary artery plaques, coronary artery aneurysms, or large pulmonary emboli.

Macrophage infiltration rather than myocarditis, myocardial injury?

The study sheds more light on previous cardiac magnetic resonance (CMR) imaging findings that have suggested that many patients who recover from COVID-19 show signs suggestive of myocarditis. These earlier studies include a recent one in competitive athletes and the earlier Puntmann and colleagues study of relatively young COVID-19 patients, which showed ongoing myocardial involvement in a majority of patients.

“It would not surprise me if some or all of the cardiac MR changes seen in some of these recent imaging studies are due to the macrophages,” said Dr. Stone.

“What we saw was not a routine pathology by any means. It was a huge amount of macrophages, higher that what we saw in SARS and more similar to a study published in 2007 that looked at patients with bacterial sepsis,” said Dr. Stone.

In an older study of SARS patients, 35% had the virus detected in myocardial tissue by polymerase chain reaction. In that subset, the degree of myocardial macrophage infiltrate was comparable to that seen in 86% of the COVID-19 cases described in this series.

Another possibility is that the macrophage infiltration reflects underlying disease rather than COVID-19. All but one of the patients had known underlying medical conditions associated with cardiac remodeling, said Nikolaos G. Frangogiannis, MD, a cardiologist who studies the mechanisms of cardiac injury, repair, and remodeling.

Frangogiannis, from Albert Einstein College of Medicine, New York, wrote an editorial that accompanied the autopsy study.

“The problem with this finding of increased macrophage infiltration is that it’s very hard to interpret because as we age, and especially in a less healthy population, the numbers and the density of macrophages in the heart increase, so it’s impossible to interpret as an effect of the infection itself unless you have an appropriate control population that matches the same characteristics, which is almost impossible to ask for,” he said.

“I’ve observed since the beginning of the pandemic that there seemed to be some people who wanted every single case to be myocarditis and others who had a bias toward not wanting COVID-19 to be a cause of myocarditis. I think what we’re seeing is it’s not either/or for anything with this virus, it’s a bit of everything,” said Dr. Stone.

Dr. Stone and Dr. Frangogiannis reported no conflict of interest.
 

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

An international autopsy study of 21 patients who died from COVID-19 has shown the presence of multifocal lymphocytic myocarditis in three patients (14%). In an additional six patients, focally increased interstitial T-lymphocytes within the myocardium were noted, with only focal or no myocyte injury.

However, increased interstitial macrophage infiltration, possibly related to cytokine infiltration, was seen in 86% of patients.

“One way to think about this is that, if these patients were having biopsies and not autopsies, there would be myocardial injury in the patients with myocarditis, even after they recovered. But with interstitial macrophages, there may or may not be any injury,” said cardiovascular pathologist James R. Stone, MD, PhD, Massachusetts General Hospital, Boston.

Dr. Stone and colleagues from Mass General, two hospitals in Italy, the University of Amsterdam, and the Mayo Clinic in Rochester, Minn., conducted the autopsies in March and April. The results were published in the October 14 issue of the European Heart Journal.

Their technique was rigorous: a median of 20 full-thickness blocks of myocardium were examined histologically (range, 5-29 blocks).

The presence of myocarditis, defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analyzed by immunohistochemistry.

“I think one of the take-homes from this study is that you have to do a thorough sampling of the heart in order to exclude myocardial injury. You cannot exclude myocarditis with just a biopsy or two,” said Dr. Stone in an interview.

“We looked at multiple different sections of tissue preserved in paraffin for every case and found only 14% had myocarditis. The vast majority of autopsies done on patients dying from COVID-19 have short-changed the autopsy and not been done in a way to exclude myocarditis,” he added.

For all patients, COVID-19 was the underlying cause of death, but the mechanisms of death were acute respiratory distress syndrome in 15, viral pneumonia in 4, cardiogenic shock in 1, and cardiac arrest in 1. Seven patients had a history of cardiovascular disease, including atrial fibrillation in four, coronary artery disease in three, left ventricular hypertrophy in one, and previous valve replacement in one. A total of 16 had hypertension, 7 had diabetes mellitus, and 1 had chronic obstructive pulmonary disease. In four cases, mild pericarditis was present. Acute myocyte injury in the right ventricle, most probably from strain or overload, was also present in four cases.

A nonsignificant trend was seen toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis. There were no reports of disrupted coronary artery plaques, coronary artery aneurysms, or large pulmonary emboli.

Macrophage infiltration rather than myocarditis, myocardial injury?

The study sheds more light on previous cardiac magnetic resonance (CMR) imaging findings that have suggested that many patients who recover from COVID-19 show signs suggestive of myocarditis. These earlier studies include a recent one in competitive athletes and the earlier Puntmann and colleagues study of relatively young COVID-19 patients, which showed ongoing myocardial involvement in a majority of patients.

“It would not surprise me if some or all of the cardiac MR changes seen in some of these recent imaging studies are due to the macrophages,” said Dr. Stone.

“What we saw was not a routine pathology by any means. It was a huge amount of macrophages, higher that what we saw in SARS and more similar to a study published in 2007 that looked at patients with bacterial sepsis,” said Dr. Stone.

In an older study of SARS patients, 35% had the virus detected in myocardial tissue by polymerase chain reaction. In that subset, the degree of myocardial macrophage infiltrate was comparable to that seen in 86% of the COVID-19 cases described in this series.

Another possibility is that the macrophage infiltration reflects underlying disease rather than COVID-19. All but one of the patients had known underlying medical conditions associated with cardiac remodeling, said Nikolaos G. Frangogiannis, MD, a cardiologist who studies the mechanisms of cardiac injury, repair, and remodeling.

Frangogiannis, from Albert Einstein College of Medicine, New York, wrote an editorial that accompanied the autopsy study.

“The problem with this finding of increased macrophage infiltration is that it’s very hard to interpret because as we age, and especially in a less healthy population, the numbers and the density of macrophages in the heart increase, so it’s impossible to interpret as an effect of the infection itself unless you have an appropriate control population that matches the same characteristics, which is almost impossible to ask for,” he said.

“I’ve observed since the beginning of the pandemic that there seemed to be some people who wanted every single case to be myocarditis and others who had a bias toward not wanting COVID-19 to be a cause of myocarditis. I think what we’re seeing is it’s not either/or for anything with this virus, it’s a bit of everything,” said Dr. Stone.

Dr. Stone and Dr. Frangogiannis reported no conflict of interest.
 

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

An international autopsy study of 21 patients who died from COVID-19 has shown the presence of multifocal lymphocytic myocarditis in three patients (14%). In an additional six patients, focally increased interstitial T-lymphocytes within the myocardium were noted, with only focal or no myocyte injury.

However, increased interstitial macrophage infiltration, possibly related to cytokine infiltration, was seen in 86% of patients.

“One way to think about this is that, if these patients were having biopsies and not autopsies, there would be myocardial injury in the patients with myocarditis, even after they recovered. But with interstitial macrophages, there may or may not be any injury,” said cardiovascular pathologist James R. Stone, MD, PhD, Massachusetts General Hospital, Boston.

Dr. Stone and colleagues from Mass General, two hospitals in Italy, the University of Amsterdam, and the Mayo Clinic in Rochester, Minn., conducted the autopsies in March and April. The results were published in the October 14 issue of the European Heart Journal.

Their technique was rigorous: a median of 20 full-thickness blocks of myocardium were examined histologically (range, 5-29 blocks).

The presence of myocarditis, defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analyzed by immunohistochemistry.

“I think one of the take-homes from this study is that you have to do a thorough sampling of the heart in order to exclude myocardial injury. You cannot exclude myocarditis with just a biopsy or two,” said Dr. Stone in an interview.

“We looked at multiple different sections of tissue preserved in paraffin for every case and found only 14% had myocarditis. The vast majority of autopsies done on patients dying from COVID-19 have short-changed the autopsy and not been done in a way to exclude myocarditis,” he added.

For all patients, COVID-19 was the underlying cause of death, but the mechanisms of death were acute respiratory distress syndrome in 15, viral pneumonia in 4, cardiogenic shock in 1, and cardiac arrest in 1. Seven patients had a history of cardiovascular disease, including atrial fibrillation in four, coronary artery disease in three, left ventricular hypertrophy in one, and previous valve replacement in one. A total of 16 had hypertension, 7 had diabetes mellitus, and 1 had chronic obstructive pulmonary disease. In four cases, mild pericarditis was present. Acute myocyte injury in the right ventricle, most probably from strain or overload, was also present in four cases.

A nonsignificant trend was seen toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis. There were no reports of disrupted coronary artery plaques, coronary artery aneurysms, or large pulmonary emboli.

Macrophage infiltration rather than myocarditis, myocardial injury?

The study sheds more light on previous cardiac magnetic resonance (CMR) imaging findings that have suggested that many patients who recover from COVID-19 show signs suggestive of myocarditis. These earlier studies include a recent one in competitive athletes and the earlier Puntmann and colleagues study of relatively young COVID-19 patients, which showed ongoing myocardial involvement in a majority of patients.

“It would not surprise me if some or all of the cardiac MR changes seen in some of these recent imaging studies are due to the macrophages,” said Dr. Stone.

“What we saw was not a routine pathology by any means. It was a huge amount of macrophages, higher that what we saw in SARS and more similar to a study published in 2007 that looked at patients with bacterial sepsis,” said Dr. Stone.

In an older study of SARS patients, 35% had the virus detected in myocardial tissue by polymerase chain reaction. In that subset, the degree of myocardial macrophage infiltrate was comparable to that seen in 86% of the COVID-19 cases described in this series.

Another possibility is that the macrophage infiltration reflects underlying disease rather than COVID-19. All but one of the patients had known underlying medical conditions associated with cardiac remodeling, said Nikolaos G. Frangogiannis, MD, a cardiologist who studies the mechanisms of cardiac injury, repair, and remodeling.

Frangogiannis, from Albert Einstein College of Medicine, New York, wrote an editorial that accompanied the autopsy study.

“The problem with this finding of increased macrophage infiltration is that it’s very hard to interpret because as we age, and especially in a less healthy population, the numbers and the density of macrophages in the heart increase, so it’s impossible to interpret as an effect of the infection itself unless you have an appropriate control population that matches the same characteristics, which is almost impossible to ask for,” he said.

“I’ve observed since the beginning of the pandemic that there seemed to be some people who wanted every single case to be myocarditis and others who had a bias toward not wanting COVID-19 to be a cause of myocarditis. I think what we’re seeing is it’s not either/or for anything with this virus, it’s a bit of everything,” said Dr. Stone.

Dr. Stone and Dr. Frangogiannis reported no conflict of interest.
 

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