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Sepsis response team does not improve mortality/organ dysfunction
A sepsis response team did not have a positive effect on mortality or organ dysfunction in septic patients, compared with standard treatment by a primary care team, according to a study abstract scheduled to be presented at CHEST 2017.
Compared with the primary care team, the sepsis team was more likely to intervene on patients with a quick Sepsis-Related Organ Failure Assessment score greater than 1 (33.8% vs. 22.8%), change or initiate antibiotics within 3 hours (64.6% vs. 37.2%), and obtain blood cultures on time (66.4% vs 45.2%). An additional difference between the two groups was that the sepsis team had better compliance with the 3-hour bundle (15.2% vs 8.4%).
Despite the sepsis team’s higher level of compliance with certain protocols, the combined outcome measure of mortality and organ dysfunction within 28 days was not significantly higher for patients treated by the sepsis team (11.3% vs. 9.8%; P = .6). In fact, there was at least one downside to being treated by the sepsis team, which was having a 14% longer hospital stay.
Chhaya Patel, MD, is scheduled to present the abstract on Sun., Oct. 29th, at 2:30-2:45 p.m. in Convention Center – 602B. This research is part of the Sepsis & Septic Shock session at the CHEST annual meeting, which will run from 1:30 to 3:00 p.m.
A sepsis response team did not have a positive effect on mortality or organ dysfunction in septic patients, compared with standard treatment by a primary care team, according to a study abstract scheduled to be presented at CHEST 2017.
Compared with the primary care team, the sepsis team was more likely to intervene on patients with a quick Sepsis-Related Organ Failure Assessment score greater than 1 (33.8% vs. 22.8%), change or initiate antibiotics within 3 hours (64.6% vs. 37.2%), and obtain blood cultures on time (66.4% vs 45.2%). An additional difference between the two groups was that the sepsis team had better compliance with the 3-hour bundle (15.2% vs 8.4%).
Despite the sepsis team’s higher level of compliance with certain protocols, the combined outcome measure of mortality and organ dysfunction within 28 days was not significantly higher for patients treated by the sepsis team (11.3% vs. 9.8%; P = .6). In fact, there was at least one downside to being treated by the sepsis team, which was having a 14% longer hospital stay.
Chhaya Patel, MD, is scheduled to present the abstract on Sun., Oct. 29th, at 2:30-2:45 p.m. in Convention Center – 602B. This research is part of the Sepsis & Septic Shock session at the CHEST annual meeting, which will run from 1:30 to 3:00 p.m.
A sepsis response team did not have a positive effect on mortality or organ dysfunction in septic patients, compared with standard treatment by a primary care team, according to a study abstract scheduled to be presented at CHEST 2017.
Compared with the primary care team, the sepsis team was more likely to intervene on patients with a quick Sepsis-Related Organ Failure Assessment score greater than 1 (33.8% vs. 22.8%), change or initiate antibiotics within 3 hours (64.6% vs. 37.2%), and obtain blood cultures on time (66.4% vs 45.2%). An additional difference between the two groups was that the sepsis team had better compliance with the 3-hour bundle (15.2% vs 8.4%).
Despite the sepsis team’s higher level of compliance with certain protocols, the combined outcome measure of mortality and organ dysfunction within 28 days was not significantly higher for patients treated by the sepsis team (11.3% vs. 9.8%; P = .6). In fact, there was at least one downside to being treated by the sepsis team, which was having a 14% longer hospital stay.
Chhaya Patel, MD, is scheduled to present the abstract on Sun., Oct. 29th, at 2:30-2:45 p.m. in Convention Center – 602B. This research is part of the Sepsis & Septic Shock session at the CHEST annual meeting, which will run from 1:30 to 3:00 p.m.
FROM CHEST 2017
Robotic-assisted pulmonary lobectomy effective for large tumors
Robotic-assisted pulmonary lobectomy is a safe and effective way to remove large tumors in patients with non–small cell lung cancer (NSCLC), according to the abstract of a study scheduled to be presented at the CHEST annual meeting.
The study covers a retrospective analysis of 345 NSCLC patients with tumors who underwent robotic-assisted pulmonary lobectomy performed by one surgeon from September 2010 through August 2016. The participants were grouped into the following three cohorts: patients with tumors less than 5 cm in diameter, patients with tumors from 5 to 7 cm, and patients with tumors larger than 7 cm. The researchers excluded patients with pulmonary metastases or benign lesions from the study.
Patients with smaller tumors were more likely to have simple lobectomy or lobectomy plus wedge, while patients with larger tumors were more likely to require lobectomy with chest wall resection. Increased tumor size was also associated with increased intraoperative estimated blood loss, skin-to-skin operative time, hospital length of stay, and overall conversion to open lobectomy.
There was no association found between tumor size and increased overall intraoperative or postoperative complications, or in-hospital mortality.
Nirav Patel, MD, FCCP, of the Tampa Bay Sleep Center is scheduled to present his abstract on Sunday Oct. 29th, between 2:15 and 2:30 p.m. in Convention Center – 606. Dr. Patel’s research is part of the Cardiothoracic Surgery session, running from 1:30 p.m. to 3:00 p.m. at the CHEST annual meeting.
Robotic-assisted pulmonary lobectomy is a safe and effective way to remove large tumors in patients with non–small cell lung cancer (NSCLC), according to the abstract of a study scheduled to be presented at the CHEST annual meeting.
The study covers a retrospective analysis of 345 NSCLC patients with tumors who underwent robotic-assisted pulmonary lobectomy performed by one surgeon from September 2010 through August 2016. The participants were grouped into the following three cohorts: patients with tumors less than 5 cm in diameter, patients with tumors from 5 to 7 cm, and patients with tumors larger than 7 cm. The researchers excluded patients with pulmonary metastases or benign lesions from the study.
Patients with smaller tumors were more likely to have simple lobectomy or lobectomy plus wedge, while patients with larger tumors were more likely to require lobectomy with chest wall resection. Increased tumor size was also associated with increased intraoperative estimated blood loss, skin-to-skin operative time, hospital length of stay, and overall conversion to open lobectomy.
There was no association found between tumor size and increased overall intraoperative or postoperative complications, or in-hospital mortality.
Nirav Patel, MD, FCCP, of the Tampa Bay Sleep Center is scheduled to present his abstract on Sunday Oct. 29th, between 2:15 and 2:30 p.m. in Convention Center – 606. Dr. Patel’s research is part of the Cardiothoracic Surgery session, running from 1:30 p.m. to 3:00 p.m. at the CHEST annual meeting.
Robotic-assisted pulmonary lobectomy is a safe and effective way to remove large tumors in patients with non–small cell lung cancer (NSCLC), according to the abstract of a study scheduled to be presented at the CHEST annual meeting.
The study covers a retrospective analysis of 345 NSCLC patients with tumors who underwent robotic-assisted pulmonary lobectomy performed by one surgeon from September 2010 through August 2016. The participants were grouped into the following three cohorts: patients with tumors less than 5 cm in diameter, patients with tumors from 5 to 7 cm, and patients with tumors larger than 7 cm. The researchers excluded patients with pulmonary metastases or benign lesions from the study.
Patients with smaller tumors were more likely to have simple lobectomy or lobectomy plus wedge, while patients with larger tumors were more likely to require lobectomy with chest wall resection. Increased tumor size was also associated with increased intraoperative estimated blood loss, skin-to-skin operative time, hospital length of stay, and overall conversion to open lobectomy.
There was no association found between tumor size and increased overall intraoperative or postoperative complications, or in-hospital mortality.
Nirav Patel, MD, FCCP, of the Tampa Bay Sleep Center is scheduled to present his abstract on Sunday Oct. 29th, between 2:15 and 2:30 p.m. in Convention Center – 606. Dr. Patel’s research is part of the Cardiothoracic Surgery session, running from 1:30 p.m. to 3:00 p.m. at the CHEST annual meeting.
FROM CHEST 2017
Near-fatal asthma treated effectively by ECMO
Extracorporeal membrane oxygenation (ECMO) is an effective way to treat near fatal asthma, but physicians must remember the risk of complications, according to an abstract on a study scheduled to be presented at CHEST 2017.
The study covers a retrospective analysis of 371 children with asthma who were treated with ECMO; it used data collected by the Extracorporeal Life Support Organization registry from 1988 to 2016. The median age of the children in the study was 7.5 years; the participant group was 43% white and 39% black, as well as 56% male, according to the abstract, which is mentioned in the program for the CHEST annual meeting.
About 80% of children experienced at least one complication, with 20% experiencing three or more. Children who had three or more complications were significantly less likely to experience lung recovery.
Of the children who received VV cannulation, 90% experienced lung recovery, whereas only 69% of children who received VA cannulation recovered. (P less than .0001). VA cannulation was also associated with a higher risk of neurological complications, while those who received VV cannulation were significantly more likely to survive.
The abstract is scheduled to be presented on Sunday Oct. 29 from 2:30 p.m. to 2:45 p.m. in Room 603 of Toronto Convention Centre South Building as part of the Acute Lung Injury & Respiratory Failure session, which will run from 1:30 p.m. to 3 p.m.
Extracorporeal membrane oxygenation (ECMO) is an effective way to treat near fatal asthma, but physicians must remember the risk of complications, according to an abstract on a study scheduled to be presented at CHEST 2017.
The study covers a retrospective analysis of 371 children with asthma who were treated with ECMO; it used data collected by the Extracorporeal Life Support Organization registry from 1988 to 2016. The median age of the children in the study was 7.5 years; the participant group was 43% white and 39% black, as well as 56% male, according to the abstract, which is mentioned in the program for the CHEST annual meeting.
About 80% of children experienced at least one complication, with 20% experiencing three or more. Children who had three or more complications were significantly less likely to experience lung recovery.
Of the children who received VV cannulation, 90% experienced lung recovery, whereas only 69% of children who received VA cannulation recovered. (P less than .0001). VA cannulation was also associated with a higher risk of neurological complications, while those who received VV cannulation were significantly more likely to survive.
The abstract is scheduled to be presented on Sunday Oct. 29 from 2:30 p.m. to 2:45 p.m. in Room 603 of Toronto Convention Centre South Building as part of the Acute Lung Injury & Respiratory Failure session, which will run from 1:30 p.m. to 3 p.m.
Extracorporeal membrane oxygenation (ECMO) is an effective way to treat near fatal asthma, but physicians must remember the risk of complications, according to an abstract on a study scheduled to be presented at CHEST 2017.
The study covers a retrospective analysis of 371 children with asthma who were treated with ECMO; it used data collected by the Extracorporeal Life Support Organization registry from 1988 to 2016. The median age of the children in the study was 7.5 years; the participant group was 43% white and 39% black, as well as 56% male, according to the abstract, which is mentioned in the program for the CHEST annual meeting.
About 80% of children experienced at least one complication, with 20% experiencing three or more. Children who had three or more complications were significantly less likely to experience lung recovery.
Of the children who received VV cannulation, 90% experienced lung recovery, whereas only 69% of children who received VA cannulation recovered. (P less than .0001). VA cannulation was also associated with a higher risk of neurological complications, while those who received VV cannulation were significantly more likely to survive.
The abstract is scheduled to be presented on Sunday Oct. 29 from 2:30 p.m. to 2:45 p.m. in Room 603 of Toronto Convention Centre South Building as part of the Acute Lung Injury & Respiratory Failure session, which will run from 1:30 p.m. to 3 p.m.
New assay may aid diagnosis, treatment of DLBCL
A new assay may help improve the diagnosis and treatment of diffuse large B-cell lymphoma (DLBCL), according to researchers.
The gene expression signature assay can be used to classify subtypes of DLBCL and may enhance disease management by helping to match tumors with the appropriate targeted therapy.
Researchers described the assay in the Journal of Molecular Diagnostics.
The assay is a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA).
It can simultaneously evaluate the expression of 21 markers, allowing differentiation of the 3 subtypes of DLBCL—germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal B-cell lymphoma (PMBL)—as well as other individualized disease characteristics, such as Epstein-Barr infection status.
Researchers used the RT-MLPA assay to test 150 samples from DLBCL patients. Forty-two percent of the samples were the ABC subtype, 37% the GCB subtype, and 10% molecular PMBL. Eleven percent of the samples could not be classified.
Overall, the RT-MLPA assay correctly assigned 85.0% of the cases into the expected subtypes, compared to 78.8% of samples assigned via immunohistochemistry.
The RT-MLPA assay was also able to detect the MYD88 L265P mutation, one of the most common genetic abnormalities found in ABC DLBCLs. This information can influence treatment, since the presence of the mutation is thought to be predictive of ibrutinib sensitivity.
The researchers said RT-MLPA is a robust, efficient, rapid, and cost-effective alternative to current methods used in the clinic to establish the cell-of-origin classification of DLBCLs.
RT-MLPA requires only common laboratory equipment and can be applied to formalin-fixed, paraffin-embedded samples. Other types of diagnostic methods may not provide the level of detail needed and may also be limited by poor reproducibility and lack of adaptability to routine use in standard laboratories.
“Because we have provided the classification algorithms, other laboratories will be able to verify our results and adjust the procedures to suit their environment,” said study author Philippe Ruminy, PhD, of the Henri Becquerel Cancer Treatment Center, INSERM U1245 in Rouen, France.
“It is our hope that the assay we have developed, which addresses an important recommendation of the recent WHO classifications, will contribute to better management of these tumors and improved patient outcomes.” 
A new assay may help improve the diagnosis and treatment of diffuse large B-cell lymphoma (DLBCL), according to researchers.
The gene expression signature assay can be used to classify subtypes of DLBCL and may enhance disease management by helping to match tumors with the appropriate targeted therapy.
Researchers described the assay in the Journal of Molecular Diagnostics.
The assay is a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA).
It can simultaneously evaluate the expression of 21 markers, allowing differentiation of the 3 subtypes of DLBCL—germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal B-cell lymphoma (PMBL)—as well as other individualized disease characteristics, such as Epstein-Barr infection status.
Researchers used the RT-MLPA assay to test 150 samples from DLBCL patients. Forty-two percent of the samples were the ABC subtype, 37% the GCB subtype, and 10% molecular PMBL. Eleven percent of the samples could not be classified.
Overall, the RT-MLPA assay correctly assigned 85.0% of the cases into the expected subtypes, compared to 78.8% of samples assigned via immunohistochemistry.
The RT-MLPA assay was also able to detect the MYD88 L265P mutation, one of the most common genetic abnormalities found in ABC DLBCLs. This information can influence treatment, since the presence of the mutation is thought to be predictive of ibrutinib sensitivity.
The researchers said RT-MLPA is a robust, efficient, rapid, and cost-effective alternative to current methods used in the clinic to establish the cell-of-origin classification of DLBCLs.
RT-MLPA requires only common laboratory equipment and can be applied to formalin-fixed, paraffin-embedded samples. Other types of diagnostic methods may not provide the level of detail needed and may also be limited by poor reproducibility and lack of adaptability to routine use in standard laboratories.
“Because we have provided the classification algorithms, other laboratories will be able to verify our results and adjust the procedures to suit their environment,” said study author Philippe Ruminy, PhD, of the Henri Becquerel Cancer Treatment Center, INSERM U1245 in Rouen, France.
“It is our hope that the assay we have developed, which addresses an important recommendation of the recent WHO classifications, will contribute to better management of these tumors and improved patient outcomes.”
A new assay may help improve the diagnosis and treatment of diffuse large B-cell lymphoma (DLBCL), according to researchers.
The gene expression signature assay can be used to classify subtypes of DLBCL and may enhance disease management by helping to match tumors with the appropriate targeted therapy.
Researchers described the assay in the Journal of Molecular Diagnostics.
The assay is a novel gene expression profiling DLBCL classifier based on reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA).
It can simultaneously evaluate the expression of 21 markers, allowing differentiation of the 3 subtypes of DLBCL—germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal B-cell lymphoma (PMBL)—as well as other individualized disease characteristics, such as Epstein-Barr infection status.
Researchers used the RT-MLPA assay to test 150 samples from DLBCL patients. Forty-two percent of the samples were the ABC subtype, 37% the GCB subtype, and 10% molecular PMBL. Eleven percent of the samples could not be classified.
Overall, the RT-MLPA assay correctly assigned 85.0% of the cases into the expected subtypes, compared to 78.8% of samples assigned via immunohistochemistry.
The RT-MLPA assay was also able to detect the MYD88 L265P mutation, one of the most common genetic abnormalities found in ABC DLBCLs. This information can influence treatment, since the presence of the mutation is thought to be predictive of ibrutinib sensitivity.
The researchers said RT-MLPA is a robust, efficient, rapid, and cost-effective alternative to current methods used in the clinic to establish the cell-of-origin classification of DLBCLs.
RT-MLPA requires only common laboratory equipment and can be applied to formalin-fixed, paraffin-embedded samples. Other types of diagnostic methods may not provide the level of detail needed and may also be limited by poor reproducibility and lack of adaptability to routine use in standard laboratories.
“Because we have provided the classification algorithms, other laboratories will be able to verify our results and adjust the procedures to suit their environment,” said study author Philippe Ruminy, PhD, of the Henri Becquerel Cancer Treatment Center, INSERM U1245 in Rouen, France.
“It is our hope that the assay we have developed, which addresses an important recommendation of the recent WHO classifications, will contribute to better management of these tumors and improved patient outcomes.”
Heart Failure Practical Approaches
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The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Psoriasis: Biologics bring potential for long-term remission off treatment
GENEVA – Can potent, highly efficacious biologic therapy induce longstanding remission of moderate to severe plaque psoriasis following discontinuation of all treatment?
The answer appears to be yes, in a minority of patients, based on results of a long-term extension study of two pivotal phase 3 clinical trials of secukinumab (Cosentyx), Mark G. Lebwohl, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
This 2-year extension study provides the first double-blind, long-term evidence regarding the natural history of psoriasis following discontinuation of a contemporary potent targeted therapy.
The results are exciting because spontaneous remission of moderate to severe psoriasis is rare; psoriasis typically reverts to baseline severity following discontinuation of treatment. In the extension study, though, 21% of patients who achieved a 75% reduction in the Psoriasis Area Severity Index (PASI 75) response on secukinumab at the 300-mg dose for 52 weeks and were then crossed over double-blind to placebo remained continuously relapse-free after 12 months on placebo, and 10% remained relapse-free at 2 years, at which point they were unblinded and put back on secukinumab. No psoriasis therapies were permitted during the placebo phase.
Those findings are particularly impressive because participants in the two pivotal trials of secukinumab combined for the treatment withdrawal extension study – ERASURE and FIXTURE – had a mean 14- and 16-year history of psoriasis at baseline.
“Secukinumab appears to have modified the course of chronic moderate to severe psoriasis, despite intervening late in its course. Treating patients early is expected to have an even greater potential for disease modification,” commented Dr. Lebwohl, the Sol and Clara Kest Professor and chair of the department of dermatology at Icahn School of Medicine at Mount Sinai, New York.
That hypothesis is under investigation in the ongoing multinational STEPin trial (Study of the Efficacy of Early Intervention With Secukinumab 300 mg s.c. [subcutaneous] Compared to Narrow-band UVB in Patients With New-onset Moderate to Severe Plaque Psoriasis). STEPin involves about 200 patients with newly diagnosed disease not previously treated with systemic agents or phototherapy.
Dr. Lebwohl focused on the 120 patients in the extension study who had a PASI 75 response to secukinumab at the 300-mg dose and the 100 patients with a PASI 75 response to the 150-mg dose who, after 52 weeks on the fully human anti-interleukin-17A monoclonal antibody, were crossed over double-blind to placebo for 2 years or until relapse occurred. Patients were assessed monthly during the extension study.
Relapse was defined as loss of 50% of the maximum PASI improvement achieved while on secukinumab. The relapse-free rate was better in patients who had been on secukinumab 300 mg than in those on 150 mg. At 1 year on placebo, 21% of patients formerly on secukinumab at the higher dose remained free of relapse, as did 10% at 2 years. In contrast, the 1- and 2-year relapse-free rates in the group formerly on secukinumab 150 mg were lower at 14% and 6%, respectively, even though everyone in the extension study had a PASI 75 response when they went off treatment.
The mean baseline PASI score in the ERASURE and FIXTURE trials was 23. Among patients who remained relapse-free for 1 year, the mean PASI score was dramatically lower, at 0.7; among those in remission for 2 years, it was 0.4.
Importantly, the longer a patient’s history of psoriasis, the less likely a long-term relapse-free experience, the dermatologist observed.
A separate mechanistic study in a different group of psoriasis patients provided a likely explanation for the long relapse-free period seen off therapy in some patients in the extension study. The mechanistic study entailed transcriptional analysis of psoriasis-related genes in lesional and nonlesional skin before and after 1 year of treatment with secukinumab 300 mg. The major finding: 85% of the upregulated genes and 75% of downregulated genes in lesional skin pretreatment reverted to normal levels in healed lesional skin post treatment.
Moreover, global mRNA expression for key genes involved in the interleukin-23/interleukin-17 inflammatory cytokine pathway closely resembled healthy skin following treatment with secukinumab. This is evidence of profound molecular normalization, Dr. Lebwohl said.
These secukinumab studies were sponsored by Novartis. Dr. Lebwohl reported having no personal financial conflicts of interest, although his department receives research funding from Novartis and numerous other pharmaceutical companies.
GENEVA – Can potent, highly efficacious biologic therapy induce longstanding remission of moderate to severe plaque psoriasis following discontinuation of all treatment?
The answer appears to be yes, in a minority of patients, based on results of a long-term extension study of two pivotal phase 3 clinical trials of secukinumab (Cosentyx), Mark G. Lebwohl, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
This 2-year extension study provides the first double-blind, long-term evidence regarding the natural history of psoriasis following discontinuation of a contemporary potent targeted therapy.
The results are exciting because spontaneous remission of moderate to severe psoriasis is rare; psoriasis typically reverts to baseline severity following discontinuation of treatment. In the extension study, though, 21% of patients who achieved a 75% reduction in the Psoriasis Area Severity Index (PASI 75) response on secukinumab at the 300-mg dose for 52 weeks and were then crossed over double-blind to placebo remained continuously relapse-free after 12 months on placebo, and 10% remained relapse-free at 2 years, at which point they were unblinded and put back on secukinumab. No psoriasis therapies were permitted during the placebo phase.
Those findings are particularly impressive because participants in the two pivotal trials of secukinumab combined for the treatment withdrawal extension study – ERASURE and FIXTURE – had a mean 14- and 16-year history of psoriasis at baseline.
“Secukinumab appears to have modified the course of chronic moderate to severe psoriasis, despite intervening late in its course. Treating patients early is expected to have an even greater potential for disease modification,” commented Dr. Lebwohl, the Sol and Clara Kest Professor and chair of the department of dermatology at Icahn School of Medicine at Mount Sinai, New York.
That hypothesis is under investigation in the ongoing multinational STEPin trial (Study of the Efficacy of Early Intervention With Secukinumab 300 mg s.c. [subcutaneous] Compared to Narrow-band UVB in Patients With New-onset Moderate to Severe Plaque Psoriasis). STEPin involves about 200 patients with newly diagnosed disease not previously treated with systemic agents or phototherapy.
Dr. Lebwohl focused on the 120 patients in the extension study who had a PASI 75 response to secukinumab at the 300-mg dose and the 100 patients with a PASI 75 response to the 150-mg dose who, after 52 weeks on the fully human anti-interleukin-17A monoclonal antibody, were crossed over double-blind to placebo for 2 years or until relapse occurred. Patients were assessed monthly during the extension study.
Relapse was defined as loss of 50% of the maximum PASI improvement achieved while on secukinumab. The relapse-free rate was better in patients who had been on secukinumab 300 mg than in those on 150 mg. At 1 year on placebo, 21% of patients formerly on secukinumab at the higher dose remained free of relapse, as did 10% at 2 years. In contrast, the 1- and 2-year relapse-free rates in the group formerly on secukinumab 150 mg were lower at 14% and 6%, respectively, even though everyone in the extension study had a PASI 75 response when they went off treatment.
The mean baseline PASI score in the ERASURE and FIXTURE trials was 23. Among patients who remained relapse-free for 1 year, the mean PASI score was dramatically lower, at 0.7; among those in remission for 2 years, it was 0.4.
Importantly, the longer a patient’s history of psoriasis, the less likely a long-term relapse-free experience, the dermatologist observed.
A separate mechanistic study in a different group of psoriasis patients provided a likely explanation for the long relapse-free period seen off therapy in some patients in the extension study. The mechanistic study entailed transcriptional analysis of psoriasis-related genes in lesional and nonlesional skin before and after 1 year of treatment with secukinumab 300 mg. The major finding: 85% of the upregulated genes and 75% of downregulated genes in lesional skin pretreatment reverted to normal levels in healed lesional skin post treatment.
Moreover, global mRNA expression for key genes involved in the interleukin-23/interleukin-17 inflammatory cytokine pathway closely resembled healthy skin following treatment with secukinumab. This is evidence of profound molecular normalization, Dr. Lebwohl said.
These secukinumab studies were sponsored by Novartis. Dr. Lebwohl reported having no personal financial conflicts of interest, although his department receives research funding from Novartis and numerous other pharmaceutical companies.
GENEVA – Can potent, highly efficacious biologic therapy induce longstanding remission of moderate to severe plaque psoriasis following discontinuation of all treatment?
The answer appears to be yes, in a minority of patients, based on results of a long-term extension study of two pivotal phase 3 clinical trials of secukinumab (Cosentyx), Mark G. Lebwohl, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
This 2-year extension study provides the first double-blind, long-term evidence regarding the natural history of psoriasis following discontinuation of a contemporary potent targeted therapy.
The results are exciting because spontaneous remission of moderate to severe psoriasis is rare; psoriasis typically reverts to baseline severity following discontinuation of treatment. In the extension study, though, 21% of patients who achieved a 75% reduction in the Psoriasis Area Severity Index (PASI 75) response on secukinumab at the 300-mg dose for 52 weeks and were then crossed over double-blind to placebo remained continuously relapse-free after 12 months on placebo, and 10% remained relapse-free at 2 years, at which point they were unblinded and put back on secukinumab. No psoriasis therapies were permitted during the placebo phase.
Those findings are particularly impressive because participants in the two pivotal trials of secukinumab combined for the treatment withdrawal extension study – ERASURE and FIXTURE – had a mean 14- and 16-year history of psoriasis at baseline.
“Secukinumab appears to have modified the course of chronic moderate to severe psoriasis, despite intervening late in its course. Treating patients early is expected to have an even greater potential for disease modification,” commented Dr. Lebwohl, the Sol and Clara Kest Professor and chair of the department of dermatology at Icahn School of Medicine at Mount Sinai, New York.
That hypothesis is under investigation in the ongoing multinational STEPin trial (Study of the Efficacy of Early Intervention With Secukinumab 300 mg s.c. [subcutaneous] Compared to Narrow-band UVB in Patients With New-onset Moderate to Severe Plaque Psoriasis). STEPin involves about 200 patients with newly diagnosed disease not previously treated with systemic agents or phototherapy.
Dr. Lebwohl focused on the 120 patients in the extension study who had a PASI 75 response to secukinumab at the 300-mg dose and the 100 patients with a PASI 75 response to the 150-mg dose who, after 52 weeks on the fully human anti-interleukin-17A monoclonal antibody, were crossed over double-blind to placebo for 2 years or until relapse occurred. Patients were assessed monthly during the extension study.
Relapse was defined as loss of 50% of the maximum PASI improvement achieved while on secukinumab. The relapse-free rate was better in patients who had been on secukinumab 300 mg than in those on 150 mg. At 1 year on placebo, 21% of patients formerly on secukinumab at the higher dose remained free of relapse, as did 10% at 2 years. In contrast, the 1- and 2-year relapse-free rates in the group formerly on secukinumab 150 mg were lower at 14% and 6%, respectively, even though everyone in the extension study had a PASI 75 response when they went off treatment.
The mean baseline PASI score in the ERASURE and FIXTURE trials was 23. Among patients who remained relapse-free for 1 year, the mean PASI score was dramatically lower, at 0.7; among those in remission for 2 years, it was 0.4.
Importantly, the longer a patient’s history of psoriasis, the less likely a long-term relapse-free experience, the dermatologist observed.
A separate mechanistic study in a different group of psoriasis patients provided a likely explanation for the long relapse-free period seen off therapy in some patients in the extension study. The mechanistic study entailed transcriptional analysis of psoriasis-related genes in lesional and nonlesional skin before and after 1 year of treatment with secukinumab 300 mg. The major finding: 85% of the upregulated genes and 75% of downregulated genes in lesional skin pretreatment reverted to normal levels in healed lesional skin post treatment.
Moreover, global mRNA expression for key genes involved in the interleukin-23/interleukin-17 inflammatory cytokine pathway closely resembled healthy skin following treatment with secukinumab. This is evidence of profound molecular normalization, Dr. Lebwohl said.
These secukinumab studies were sponsored by Novartis. Dr. Lebwohl reported having no personal financial conflicts of interest, although his department receives research funding from Novartis and numerous other pharmaceutical companies.
AT THE EADV CONGRESS
Key clinical point: , enabling some patients to experience long-term remission off therapy.
Major finding: After 1 and 2 years without any psoriasis therapy following successful treatment with secukinumab for 52 weeks, 21% and 10% of patients, respectively, remained relapse-free.
Data source: This prospective extension of two phase 3 pivotal trials of secukinumab included 220 psoriasis patients who were taken off the biologic after 52 weeks and crossed over double blind to placebo for up to 2 years.
Disclosures: The study was sponsored by Novartis. Dr. Lebwohl reported having no financial conflicts.
Whiskey bars and Painless Parker
Have you heard of Painless Parker? A flamboyant dentist from a century ago, Parker flouted professional propriety. He wore a top hat and performed what he claimed were painless extractions on street corners, advised by a marketer who once worked for P.T. Barnum. When his dental society objected to Parker’s claims, he legally changed his first name to “Painless.”
I thought of him this week, when a southwestern colleague sent me a glossy ad from a local magazine touting a new Dermatology Cosmetic and Laser Center. It featured “a luxury men’s lounge (Man-Cave), complete with whiskey bar.”
What, asked my correspondent, is our world coming to?
Whatever that is has been coming for some time. In Parker’s day, all professional advertising was frowned upon as unseemly. That injunction seems quaint now, when drug and hospital ads flood our TV screens and pop up on every website we visit.
Medical institutions of great prestige tell the world how the techniques they employ or pioneer lead to unsurpassed outcomes, how their patient-centered focus offers compassion second to none. They post YouTube videos in which academics highlight their expertise and their team’s empathy.
I am old enough to remember when such self-promotion was thought impolite and tasteless. I am also old enough to recall when telling the universe where you’ve been and showing pictures of what you’ve been up to was considered uncouth. Few of today’s young people, hooked on Facebook and Instagram, would have any idea why on earth anybody would think such things.
Aside from the presence or prospect of physical infirmity, growing old means being baffled by new attitudes and ways of doing things that younger folks understand implicitly.
In other words, getting old means accepting that you’re out of it.
This realization suggests to me an update of the Denver Developmental Screening Test of my pediatric youth. 3 months: roll over; 6 months: sit up; 12 months: walk; 50 years: join AARP; 70 years: decry the younger generation. (“Those millennials don’t want to work hard the way we did!”)
Some of us are entering the Golden Years of The-World-is-Going-to-Hell-in-a-Handbasket.
I accept that I will not understand or appreciate social media. Younger folk don’t really care what I think about that, or anything else. Even I don’t care what I think.
Fifteen years ago, I sat late one evening in the elegant, high-ceilinged lobby of a major area medical center. A close friend was dying upstairs after a failed second liver transplant for biliary cirrhosis, the first of which had given her 10 good years.
Absorbed in thought, I leaned back and looked up. Hanging from the ceiling was a banner: “Rated Number 3 in the U.S. for Nephrology by U.S. News and World Report!”
Great, I thought. What number are they for GI?
In the nearly 40 years I’ve worked in dermatology, our field has indeed changed. Cosmetic procedures and skin care products have taken on significant, sometimes dominant roles in various settings. Some changes seem excessive at first, even shady: Botox parties in private homes? Really? With time, these come to feel normal. Man caves and whiskey bars? If the public wants them, maybe they’re the new normal.
Cole Porter wrote:
“In olden days, a glimpse of stocking
Was looked on as something shocking.
But now, God knows,
Anything goes.”
He wrote those lines 80 years ago.
Painless Parker’s self-promotion helped bring some positive changes in professional practice. Pitching to the public means that the profession cares what patients think. Back in the decorous, prudish, paternalistic old days, that was often not the case; the patient was supposed to accept whatever the experts offered and just shut up.
Trying to turn back the tide of social change is as useful as old King Canute trying to turn back the tide on the beach – an effort as pathetic as it is futile. As we age, older folks tend to become faintly ridiculous anyway. Why add negatives you can avoid?
Our office has a large exam room that’s not fully used. It contains a lightly used UVB unit.
Add comfy sofas? High-def flat-screen TVs? The NFL Network? Cigars and single-malt? What say you, colleagues?
Call me Ritzy Rockoff. It sings!
Death might not be proud, but I bet old Painless would.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].
Have you heard of Painless Parker? A flamboyant dentist from a century ago, Parker flouted professional propriety. He wore a top hat and performed what he claimed were painless extractions on street corners, advised by a marketer who once worked for P.T. Barnum. When his dental society objected to Parker’s claims, he legally changed his first name to “Painless.”
I thought of him this week, when a southwestern colleague sent me a glossy ad from a local magazine touting a new Dermatology Cosmetic and Laser Center. It featured “a luxury men’s lounge (Man-Cave), complete with whiskey bar.”
What, asked my correspondent, is our world coming to?
Whatever that is has been coming for some time. In Parker’s day, all professional advertising was frowned upon as unseemly. That injunction seems quaint now, when drug and hospital ads flood our TV screens and pop up on every website we visit.
Medical institutions of great prestige tell the world how the techniques they employ or pioneer lead to unsurpassed outcomes, how their patient-centered focus offers compassion second to none. They post YouTube videos in which academics highlight their expertise and their team’s empathy.
I am old enough to remember when such self-promotion was thought impolite and tasteless. I am also old enough to recall when telling the universe where you’ve been and showing pictures of what you’ve been up to was considered uncouth. Few of today’s young people, hooked on Facebook and Instagram, would have any idea why on earth anybody would think such things.
Aside from the presence or prospect of physical infirmity, growing old means being baffled by new attitudes and ways of doing things that younger folks understand implicitly.
In other words, getting old means accepting that you’re out of it.
This realization suggests to me an update of the Denver Developmental Screening Test of my pediatric youth. 3 months: roll over; 6 months: sit up; 12 months: walk; 50 years: join AARP; 70 years: decry the younger generation. (“Those millennials don’t want to work hard the way we did!”)
Some of us are entering the Golden Years of The-World-is-Going-to-Hell-in-a-Handbasket.
I accept that I will not understand or appreciate social media. Younger folk don’t really care what I think about that, or anything else. Even I don’t care what I think.
Fifteen years ago, I sat late one evening in the elegant, high-ceilinged lobby of a major area medical center. A close friend was dying upstairs after a failed second liver transplant for biliary cirrhosis, the first of which had given her 10 good years.
Absorbed in thought, I leaned back and looked up. Hanging from the ceiling was a banner: “Rated Number 3 in the U.S. for Nephrology by U.S. News and World Report!”
Great, I thought. What number are they for GI?
In the nearly 40 years I’ve worked in dermatology, our field has indeed changed. Cosmetic procedures and skin care products have taken on significant, sometimes dominant roles in various settings. Some changes seem excessive at first, even shady: Botox parties in private homes? Really? With time, these come to feel normal. Man caves and whiskey bars? If the public wants them, maybe they’re the new normal.
Cole Porter wrote:
“In olden days, a glimpse of stocking
Was looked on as something shocking.
But now, God knows,
Anything goes.”
He wrote those lines 80 years ago.
Painless Parker’s self-promotion helped bring some positive changes in professional practice. Pitching to the public means that the profession cares what patients think. Back in the decorous, prudish, paternalistic old days, that was often not the case; the patient was supposed to accept whatever the experts offered and just shut up.
Trying to turn back the tide of social change is as useful as old King Canute trying to turn back the tide on the beach – an effort as pathetic as it is futile. As we age, older folks tend to become faintly ridiculous anyway. Why add negatives you can avoid?
Our office has a large exam room that’s not fully used. It contains a lightly used UVB unit.
Add comfy sofas? High-def flat-screen TVs? The NFL Network? Cigars and single-malt? What say you, colleagues?
Call me Ritzy Rockoff. It sings!
Death might not be proud, but I bet old Painless would.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].
Have you heard of Painless Parker? A flamboyant dentist from a century ago, Parker flouted professional propriety. He wore a top hat and performed what he claimed were painless extractions on street corners, advised by a marketer who once worked for P.T. Barnum. When his dental society objected to Parker’s claims, he legally changed his first name to “Painless.”
I thought of him this week, when a southwestern colleague sent me a glossy ad from a local magazine touting a new Dermatology Cosmetic and Laser Center. It featured “a luxury men’s lounge (Man-Cave), complete with whiskey bar.”
What, asked my correspondent, is our world coming to?
Whatever that is has been coming for some time. In Parker’s day, all professional advertising was frowned upon as unseemly. That injunction seems quaint now, when drug and hospital ads flood our TV screens and pop up on every website we visit.
Medical institutions of great prestige tell the world how the techniques they employ or pioneer lead to unsurpassed outcomes, how their patient-centered focus offers compassion second to none. They post YouTube videos in which academics highlight their expertise and their team’s empathy.
I am old enough to remember when such self-promotion was thought impolite and tasteless. I am also old enough to recall when telling the universe where you’ve been and showing pictures of what you’ve been up to was considered uncouth. Few of today’s young people, hooked on Facebook and Instagram, would have any idea why on earth anybody would think such things.
Aside from the presence or prospect of physical infirmity, growing old means being baffled by new attitudes and ways of doing things that younger folks understand implicitly.
In other words, getting old means accepting that you’re out of it.
This realization suggests to me an update of the Denver Developmental Screening Test of my pediatric youth. 3 months: roll over; 6 months: sit up; 12 months: walk; 50 years: join AARP; 70 years: decry the younger generation. (“Those millennials don’t want to work hard the way we did!”)
Some of us are entering the Golden Years of The-World-is-Going-to-Hell-in-a-Handbasket.
I accept that I will not understand or appreciate social media. Younger folk don’t really care what I think about that, or anything else. Even I don’t care what I think.
Fifteen years ago, I sat late one evening in the elegant, high-ceilinged lobby of a major area medical center. A close friend was dying upstairs after a failed second liver transplant for biliary cirrhosis, the first of which had given her 10 good years.
Absorbed in thought, I leaned back and looked up. Hanging from the ceiling was a banner: “Rated Number 3 in the U.S. for Nephrology by U.S. News and World Report!”
Great, I thought. What number are they for GI?
In the nearly 40 years I’ve worked in dermatology, our field has indeed changed. Cosmetic procedures and skin care products have taken on significant, sometimes dominant roles in various settings. Some changes seem excessive at first, even shady: Botox parties in private homes? Really? With time, these come to feel normal. Man caves and whiskey bars? If the public wants them, maybe they’re the new normal.
Cole Porter wrote:
“In olden days, a glimpse of stocking
Was looked on as something shocking.
But now, God knows,
Anything goes.”
He wrote those lines 80 years ago.
Painless Parker’s self-promotion helped bring some positive changes in professional practice. Pitching to the public means that the profession cares what patients think. Back in the decorous, prudish, paternalistic old days, that was often not the case; the patient was supposed to accept whatever the experts offered and just shut up.
Trying to turn back the tide of social change is as useful as old King Canute trying to turn back the tide on the beach – an effort as pathetic as it is futile. As we age, older folks tend to become faintly ridiculous anyway. Why add negatives you can avoid?
Our office has a large exam room that’s not fully used. It contains a lightly used UVB unit.
Add comfy sofas? High-def flat-screen TVs? The NFL Network? Cigars and single-malt? What say you, colleagues?
Call me Ritzy Rockoff. It sings!
Death might not be proud, but I bet old Painless would.
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].
Add-on mycophenolate boosts efficacy of steroids for Graves’ orbitopathy
VICTORIA, B.C. – Adding a nonsteroidal immunosuppressant to steroid therapy improves control of active, moderate-to-severe Graves’ orbitopathy, according to findings from a randomized controlled trial reported at the annual meeting of the American Thyroid Association.
Relative to counterparts given pulsed intravenous methylprednisolone alone, patients also given oral mycophenolate were twice as likely to achieve reduction of their ophthalmic signs and symptoms, first author George J. Kahaly, MD, PhD, reported in a session on behalf of the European Group on Graves’ Orbitopathy (EUGOGO). And the combination was generally safe and well tolerated.
“Since there is a clear advantage of combination treatment in response rate, in the absence of contraindication to mycophenolate, patients with active and severe orbitopathy may be considered for combination treatment,” he proposed.
A session attendee noted that a similar recent study from China suggests that mycophenolate monotherapy achieves a very high remission rate in this patient population (Clin Endocrinol (Oxf). 2017;86[2]:247-55). “Why don’t we just go for [mycophenolate] alone? Why keep pushing steroids?” he asked.
Methodology of that study was less rigorous, maintained Dr. Kahaly, who is professor of medicine and endocrinology/metabolism, chief physician of the endocrine outpatient clinic, and director of the thyroid research lab at Gutenberg University Medical Center in Mainz, Germany.
“I would say mycophenolate alone is not a powerful enough treatment to observe a response rate of 70%, 80%, 90%,” he stated. “You need more time. This is a lymphocyte-inhibiting agent, so you need the acute effect of the intravenous steroids at the beginning.”
Session cochair Angela M. Leung, MD, assistant professor of medicine at the University of California, Los Angeles, and an endocrinologist at both UCLA and the VA Greater Los Angeles Healthcare System, commented, “This is an intriguing study with very promising data from an active group of investigators.”
At the same time, benefit of add-on mycophenolate remains uncertain, in her opinion. “Clearly, more studies, perhaps longer-duration ones, are needed to assess the true effect and clinical efficacy,” she said.
Introducing the EUGOGO trial, Dr. Kahaly noted that European guidelines recommend intravenous methylprednisolone as first-line therapy for Graves’ orbitopathy that is moderate to severe or sight threatening (Eur Thyroid J. 2016;5:9-26). Some patients, however, do not achieve response on this therapy, and others who do achieve response then go on to experience relapse, underscoring the need for better therapies.
The combination the investigators selected pairs the anti-inflammatory activity of methylprednisolone with the antiproliferative activity of mycophenolate (CellCept), which is mainly used in the transplantation field.
The trial, funded in part by Novartis, was open to patients with Graves’ disease who had been euthyroid for at least 2 months but had untreated, active, moderate-to-severe orbitopathy with involvement of soft tissues and eye muscles. Those with optic neuropathy were excluded.
Patients were randomized to 12 weeks of once-weekly intravenous methylprednisolone either alone or with the addition of 24 weeks of twice-daily oral mycophenolate initiated at the same time.
Blinded observers assessed patients for orbitopathy response, defined as improvement in two or more of six outcome measures (eyelid swelling, clinical activity score, proptosis, lid width, diplopia, and motility) in at least one eye, without deterioration in any of the same measures in either eye.
Results showed that the 24-week rate of response was 71% with methylprednisolone plus mycophenolate and 53% with methylprednisolone alone (odds ratio, 2.16; P = .026).
Dr. Kahaly acknowledged that the rate in the monotherapy group was lower than that in some in past studies and proposed this was due to both a tightening of response criteria and more conservative steroid dosing in recent years.
Benefit was similar across patient subgroups stratified by sex, smoking history, clinical activity score, duration of orbitopathy, and level of antibodies to the thyroid-stimulating hormone receptor.
The group given combination therapy also had a lower 36-week relapse rate, although this difference was not significant (4% vs. 8%; odds ratio, 0.65; P = .613). Quality-of-life scores improved in both the monotherapy group (P = .009) and the combination therapy group (P = .002).
The difference between groups in extent of proptosis was just 1 mm. “This is not enough,” he asserted, noting that teprotumumab, an investigational antibody that inhibits insulin-like growth factor I receptor, was recently found to decrease proptosis in this population by 2.7 mm (N Engl J Med. 2017;376:1748-61). “This is the only drug that has led to a significant decrease of proptosis,” he noted.
“The drugs were well tolerated, and the treatment went smoothly. We didn’t have one single dropout because of drug side effects,” Dr. Kahaly reported.
The incidence of drug-related side effects was 20% with methylprednisolone and 25% with methylprednisolone plus mycophenolate, a nonsignificant difference. In both groups, most side effects were rated as mild or moderate.
Trial limitations included the lack of a placebo control, short duration of follow-up, and missing information about subsequent surgical procedures, such as orbital decompression and squint and lid surgery, acknowledged Dr. Kahaly, who disclosed that he had no relevant conflicts of interest.
VICTORIA, B.C. – Adding a nonsteroidal immunosuppressant to steroid therapy improves control of active, moderate-to-severe Graves’ orbitopathy, according to findings from a randomized controlled trial reported at the annual meeting of the American Thyroid Association.
Relative to counterparts given pulsed intravenous methylprednisolone alone, patients also given oral mycophenolate were twice as likely to achieve reduction of their ophthalmic signs and symptoms, first author George J. Kahaly, MD, PhD, reported in a session on behalf of the European Group on Graves’ Orbitopathy (EUGOGO). And the combination was generally safe and well tolerated.
“Since there is a clear advantage of combination treatment in response rate, in the absence of contraindication to mycophenolate, patients with active and severe orbitopathy may be considered for combination treatment,” he proposed.
A session attendee noted that a similar recent study from China suggests that mycophenolate monotherapy achieves a very high remission rate in this patient population (Clin Endocrinol (Oxf). 2017;86[2]:247-55). “Why don’t we just go for [mycophenolate] alone? Why keep pushing steroids?” he asked.
Methodology of that study was less rigorous, maintained Dr. Kahaly, who is professor of medicine and endocrinology/metabolism, chief physician of the endocrine outpatient clinic, and director of the thyroid research lab at Gutenberg University Medical Center in Mainz, Germany.
“I would say mycophenolate alone is not a powerful enough treatment to observe a response rate of 70%, 80%, 90%,” he stated. “You need more time. This is a lymphocyte-inhibiting agent, so you need the acute effect of the intravenous steroids at the beginning.”
Session cochair Angela M. Leung, MD, assistant professor of medicine at the University of California, Los Angeles, and an endocrinologist at both UCLA and the VA Greater Los Angeles Healthcare System, commented, “This is an intriguing study with very promising data from an active group of investigators.”
At the same time, benefit of add-on mycophenolate remains uncertain, in her opinion. “Clearly, more studies, perhaps longer-duration ones, are needed to assess the true effect and clinical efficacy,” she said.
Introducing the EUGOGO trial, Dr. Kahaly noted that European guidelines recommend intravenous methylprednisolone as first-line therapy for Graves’ orbitopathy that is moderate to severe or sight threatening (Eur Thyroid J. 2016;5:9-26). Some patients, however, do not achieve response on this therapy, and others who do achieve response then go on to experience relapse, underscoring the need for better therapies.
The combination the investigators selected pairs the anti-inflammatory activity of methylprednisolone with the antiproliferative activity of mycophenolate (CellCept), which is mainly used in the transplantation field.
The trial, funded in part by Novartis, was open to patients with Graves’ disease who had been euthyroid for at least 2 months but had untreated, active, moderate-to-severe orbitopathy with involvement of soft tissues and eye muscles. Those with optic neuropathy were excluded.
Patients were randomized to 12 weeks of once-weekly intravenous methylprednisolone either alone or with the addition of 24 weeks of twice-daily oral mycophenolate initiated at the same time.
Blinded observers assessed patients for orbitopathy response, defined as improvement in two or more of six outcome measures (eyelid swelling, clinical activity score, proptosis, lid width, diplopia, and motility) in at least one eye, without deterioration in any of the same measures in either eye.
Results showed that the 24-week rate of response was 71% with methylprednisolone plus mycophenolate and 53% with methylprednisolone alone (odds ratio, 2.16; P = .026).
Dr. Kahaly acknowledged that the rate in the monotherapy group was lower than that in some in past studies and proposed this was due to both a tightening of response criteria and more conservative steroid dosing in recent years.
Benefit was similar across patient subgroups stratified by sex, smoking history, clinical activity score, duration of orbitopathy, and level of antibodies to the thyroid-stimulating hormone receptor.
The group given combination therapy also had a lower 36-week relapse rate, although this difference was not significant (4% vs. 8%; odds ratio, 0.65; P = .613). Quality-of-life scores improved in both the monotherapy group (P = .009) and the combination therapy group (P = .002).
The difference between groups in extent of proptosis was just 1 mm. “This is not enough,” he asserted, noting that teprotumumab, an investigational antibody that inhibits insulin-like growth factor I receptor, was recently found to decrease proptosis in this population by 2.7 mm (N Engl J Med. 2017;376:1748-61). “This is the only drug that has led to a significant decrease of proptosis,” he noted.
“The drugs were well tolerated, and the treatment went smoothly. We didn’t have one single dropout because of drug side effects,” Dr. Kahaly reported.
The incidence of drug-related side effects was 20% with methylprednisolone and 25% with methylprednisolone plus mycophenolate, a nonsignificant difference. In both groups, most side effects were rated as mild or moderate.
Trial limitations included the lack of a placebo control, short duration of follow-up, and missing information about subsequent surgical procedures, such as orbital decompression and squint and lid surgery, acknowledged Dr. Kahaly, who disclosed that he had no relevant conflicts of interest.
VICTORIA, B.C. – Adding a nonsteroidal immunosuppressant to steroid therapy improves control of active, moderate-to-severe Graves’ orbitopathy, according to findings from a randomized controlled trial reported at the annual meeting of the American Thyroid Association.
Relative to counterparts given pulsed intravenous methylprednisolone alone, patients also given oral mycophenolate were twice as likely to achieve reduction of their ophthalmic signs and symptoms, first author George J. Kahaly, MD, PhD, reported in a session on behalf of the European Group on Graves’ Orbitopathy (EUGOGO). And the combination was generally safe and well tolerated.
“Since there is a clear advantage of combination treatment in response rate, in the absence of contraindication to mycophenolate, patients with active and severe orbitopathy may be considered for combination treatment,” he proposed.
A session attendee noted that a similar recent study from China suggests that mycophenolate monotherapy achieves a very high remission rate in this patient population (Clin Endocrinol (Oxf). 2017;86[2]:247-55). “Why don’t we just go for [mycophenolate] alone? Why keep pushing steroids?” he asked.
Methodology of that study was less rigorous, maintained Dr. Kahaly, who is professor of medicine and endocrinology/metabolism, chief physician of the endocrine outpatient clinic, and director of the thyroid research lab at Gutenberg University Medical Center in Mainz, Germany.
“I would say mycophenolate alone is not a powerful enough treatment to observe a response rate of 70%, 80%, 90%,” he stated. “You need more time. This is a lymphocyte-inhibiting agent, so you need the acute effect of the intravenous steroids at the beginning.”
Session cochair Angela M. Leung, MD, assistant professor of medicine at the University of California, Los Angeles, and an endocrinologist at both UCLA and the VA Greater Los Angeles Healthcare System, commented, “This is an intriguing study with very promising data from an active group of investigators.”
At the same time, benefit of add-on mycophenolate remains uncertain, in her opinion. “Clearly, more studies, perhaps longer-duration ones, are needed to assess the true effect and clinical efficacy,” she said.
Introducing the EUGOGO trial, Dr. Kahaly noted that European guidelines recommend intravenous methylprednisolone as first-line therapy for Graves’ orbitopathy that is moderate to severe or sight threatening (Eur Thyroid J. 2016;5:9-26). Some patients, however, do not achieve response on this therapy, and others who do achieve response then go on to experience relapse, underscoring the need for better therapies.
The combination the investigators selected pairs the anti-inflammatory activity of methylprednisolone with the antiproliferative activity of mycophenolate (CellCept), which is mainly used in the transplantation field.
The trial, funded in part by Novartis, was open to patients with Graves’ disease who had been euthyroid for at least 2 months but had untreated, active, moderate-to-severe orbitopathy with involvement of soft tissues and eye muscles. Those with optic neuropathy were excluded.
Patients were randomized to 12 weeks of once-weekly intravenous methylprednisolone either alone or with the addition of 24 weeks of twice-daily oral mycophenolate initiated at the same time.
Blinded observers assessed patients for orbitopathy response, defined as improvement in two or more of six outcome measures (eyelid swelling, clinical activity score, proptosis, lid width, diplopia, and motility) in at least one eye, without deterioration in any of the same measures in either eye.
Results showed that the 24-week rate of response was 71% with methylprednisolone plus mycophenolate and 53% with methylprednisolone alone (odds ratio, 2.16; P = .026).
Dr. Kahaly acknowledged that the rate in the monotherapy group was lower than that in some in past studies and proposed this was due to both a tightening of response criteria and more conservative steroid dosing in recent years.
Benefit was similar across patient subgroups stratified by sex, smoking history, clinical activity score, duration of orbitopathy, and level of antibodies to the thyroid-stimulating hormone receptor.
The group given combination therapy also had a lower 36-week relapse rate, although this difference was not significant (4% vs. 8%; odds ratio, 0.65; P = .613). Quality-of-life scores improved in both the monotherapy group (P = .009) and the combination therapy group (P = .002).
The difference between groups in extent of proptosis was just 1 mm. “This is not enough,” he asserted, noting that teprotumumab, an investigational antibody that inhibits insulin-like growth factor I receptor, was recently found to decrease proptosis in this population by 2.7 mm (N Engl J Med. 2017;376:1748-61). “This is the only drug that has led to a significant decrease of proptosis,” he noted.
“The drugs were well tolerated, and the treatment went smoothly. We didn’t have one single dropout because of drug side effects,” Dr. Kahaly reported.
The incidence of drug-related side effects was 20% with methylprednisolone and 25% with methylprednisolone plus mycophenolate, a nonsignificant difference. In both groups, most side effects were rated as mild or moderate.
Trial limitations included the lack of a placebo control, short duration of follow-up, and missing information about subsequent surgical procedures, such as orbital decompression and squint and lid surgery, acknowledged Dr. Kahaly, who disclosed that he had no relevant conflicts of interest.
AT ATA 2017
Key clinical point:
Major finding: Relative to peers given methylprednisolone alone, patients given methylprednisolone plus mycophenolate were twice as likely to achieve response (odds ratio, 2.16).
Data source: A multicenter randomized controlled trial in 164 patients with Graves’ disease who had active, moderate-to-severe orbitopathy.
Disclosures: Dr. Kahaly disclosed that he had no relevant conflicts of interest. The trial was partly funded by Novartis.
Intubation for upper GI bleeding may increase cardiopulmonary risk
Prophylactic endotracheal intubation (PEI) prior to endoscopy for upper GI bleeding in critically ill adults may actually increase, rather than decrease, the risk of unplanned cardiopulmonary events, according to results of a retrospective cohort study.
In particular, the study showed a significant increase in risk of patients developing pneumonia, according to study author Umar Hayat, MD, Medicine Institute, Cleveland Clinic, and colleagues.
“The practice of PEI could carry significant risks and might be a factor that leads to this dreaded outcome [pneumonia] in patients presenting with upper GI bleeding, instead of preventing it,” Dr. Hayat and colleagues wrote (Gastrointest Endosc. 2017;86:500-9. doi:10.1016/j.gie.2016.12.008).
The role of PEI in mitigating risk of cardiopulmonary adverse events remains controversial for patients presenting with upper GI bleeding, who can have mortality rates as high as 10% for nonvariceal bleeds and 20% for variceal causes, the investigators said.
Dr. Hayat and colleagues reviewed data for a total of 365 patients who had brisk upper GI bleeding, of whom 144 (39.5%) underwent PEI prior to esophagogastroduodenoscopy (EGD). The average patient age was 59 years, and 64% were male.
The composite primary endpoint of the study, cardiopulmonary unplanned events, was defined as occurrence of pneumonia, pulmonary edema, acute respiratory distress syndrome, shock/hypotension, arrhythmia, myocardial infarction, or cardiac arrest within 48 hours of EGD.
The final analysis included 200 intubated and nonintubated patients matched on a 1:1 basis using propensity score matching.
The researchers found that post-EGD adverse outcomes were more common in patients who had undergone PEI prior to EGD (odds ratio, 3.8; 95% confidence interval, 1.4-10.2), published data show. The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008).
Even after adjusting for the presence of esophageal varices, the difference remained significant, Dr. Hayat and colleagues wrote.
Pneumonia in particular was significantly more common in the PEI group: published data show 14% of patients who underwent PEI had pneumonia within 48 hours of EGD, compared with 2% of nonintubated patients (P = .01).
Rates of shock within 48 hours of EGD were also higher in the PEI group (14% vs. 6%), though the finding did not reach statistical significance, the authors added.
Currently, PEI is “variably used” in clinical practice, the authors wrote, and factors that may play into the decision to utilize this strategy include bleeding severity and ongoing hematemesis, among other factors. In survey data cited by Dr. Hayat and associates, 58% of experts said they would consider intubation for patients with ongoing hematemesis, and about one-quarter said they would intubate if they suspected hemodynamic compromise.
Although future prospective, controlled studies are needed to confirm these findings, the authors did advise caution in selecting patients for PEI in critically ill patients presenting with upper GI bleeding.
“The benefits and risks of intubation should be carefully weighed when considering airway protection before an EGD in this group of patients,” they wrote.
The invesigators disclosed no financial relationships relevant to the current study.
Prophylactic endotracheal intubation (PEI) prior to endoscopy for upper GI bleeding in critically ill adults may actually increase, rather than decrease, the risk of unplanned cardiopulmonary events, according to results of a retrospective cohort study.
In particular, the study showed a significant increase in risk of patients developing pneumonia, according to study author Umar Hayat, MD, Medicine Institute, Cleveland Clinic, and colleagues.
“The practice of PEI could carry significant risks and might be a factor that leads to this dreaded outcome [pneumonia] in patients presenting with upper GI bleeding, instead of preventing it,” Dr. Hayat and colleagues wrote (Gastrointest Endosc. 2017;86:500-9. doi:10.1016/j.gie.2016.12.008).
The role of PEI in mitigating risk of cardiopulmonary adverse events remains controversial for patients presenting with upper GI bleeding, who can have mortality rates as high as 10% for nonvariceal bleeds and 20% for variceal causes, the investigators said.
Dr. Hayat and colleagues reviewed data for a total of 365 patients who had brisk upper GI bleeding, of whom 144 (39.5%) underwent PEI prior to esophagogastroduodenoscopy (EGD). The average patient age was 59 years, and 64% were male.
The composite primary endpoint of the study, cardiopulmonary unplanned events, was defined as occurrence of pneumonia, pulmonary edema, acute respiratory distress syndrome, shock/hypotension, arrhythmia, myocardial infarction, or cardiac arrest within 48 hours of EGD.
The final analysis included 200 intubated and nonintubated patients matched on a 1:1 basis using propensity score matching.
The researchers found that post-EGD adverse outcomes were more common in patients who had undergone PEI prior to EGD (odds ratio, 3.8; 95% confidence interval, 1.4-10.2), published data show. The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008).
Even after adjusting for the presence of esophageal varices, the difference remained significant, Dr. Hayat and colleagues wrote.
Pneumonia in particular was significantly more common in the PEI group: published data show 14% of patients who underwent PEI had pneumonia within 48 hours of EGD, compared with 2% of nonintubated patients (P = .01).
Rates of shock within 48 hours of EGD were also higher in the PEI group (14% vs. 6%), though the finding did not reach statistical significance, the authors added.
Currently, PEI is “variably used” in clinical practice, the authors wrote, and factors that may play into the decision to utilize this strategy include bleeding severity and ongoing hematemesis, among other factors. In survey data cited by Dr. Hayat and associates, 58% of experts said they would consider intubation for patients with ongoing hematemesis, and about one-quarter said they would intubate if they suspected hemodynamic compromise.
Although future prospective, controlled studies are needed to confirm these findings, the authors did advise caution in selecting patients for PEI in critically ill patients presenting with upper GI bleeding.
“The benefits and risks of intubation should be carefully weighed when considering airway protection before an EGD in this group of patients,” they wrote.
The invesigators disclosed no financial relationships relevant to the current study.
Prophylactic endotracheal intubation (PEI) prior to endoscopy for upper GI bleeding in critically ill adults may actually increase, rather than decrease, the risk of unplanned cardiopulmonary events, according to results of a retrospective cohort study.
In particular, the study showed a significant increase in risk of patients developing pneumonia, according to study author Umar Hayat, MD, Medicine Institute, Cleveland Clinic, and colleagues.
“The practice of PEI could carry significant risks and might be a factor that leads to this dreaded outcome [pneumonia] in patients presenting with upper GI bleeding, instead of preventing it,” Dr. Hayat and colleagues wrote (Gastrointest Endosc. 2017;86:500-9. doi:10.1016/j.gie.2016.12.008).
The role of PEI in mitigating risk of cardiopulmonary adverse events remains controversial for patients presenting with upper GI bleeding, who can have mortality rates as high as 10% for nonvariceal bleeds and 20% for variceal causes, the investigators said.
Dr. Hayat and colleagues reviewed data for a total of 365 patients who had brisk upper GI bleeding, of whom 144 (39.5%) underwent PEI prior to esophagogastroduodenoscopy (EGD). The average patient age was 59 years, and 64% were male.
The composite primary endpoint of the study, cardiopulmonary unplanned events, was defined as occurrence of pneumonia, pulmonary edema, acute respiratory distress syndrome, shock/hypotension, arrhythmia, myocardial infarction, or cardiac arrest within 48 hours of EGD.
The final analysis included 200 intubated and nonintubated patients matched on a 1:1 basis using propensity score matching.
The researchers found that post-EGD adverse outcomes were more common in patients who had undergone PEI prior to EGD (odds ratio, 3.8; 95% confidence interval, 1.4-10.2), published data show. The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008).
Even after adjusting for the presence of esophageal varices, the difference remained significant, Dr. Hayat and colleagues wrote.
Pneumonia in particular was significantly more common in the PEI group: published data show 14% of patients who underwent PEI had pneumonia within 48 hours of EGD, compared with 2% of nonintubated patients (P = .01).
Rates of shock within 48 hours of EGD were also higher in the PEI group (14% vs. 6%), though the finding did not reach statistical significance, the authors added.
Currently, PEI is “variably used” in clinical practice, the authors wrote, and factors that may play into the decision to utilize this strategy include bleeding severity and ongoing hematemesis, among other factors. In survey data cited by Dr. Hayat and associates, 58% of experts said they would consider intubation for patients with ongoing hematemesis, and about one-quarter said they would intubate if they suspected hemodynamic compromise.
Although future prospective, controlled studies are needed to confirm these findings, the authors did advise caution in selecting patients for PEI in critically ill patients presenting with upper GI bleeding.
“The benefits and risks of intubation should be carefully weighed when considering airway protection before an EGD in this group of patients,” they wrote.
The invesigators disclosed no financial relationships relevant to the current study.
FROM GASTROINTESTINAL ENDOSCOPY
Key clinical point: Although many advocate prophylactic endotracheal intubation in critically ill patients presenting with brisk upper GI bleeding, doing so may actually increase, rather than decrease, risk of cardiopulmonary events.
Major finding: The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008), with the difference remaining significant even after adjusting for the presence of esophageal varices.
Data source: Retrospective cohort study including data on 365 adult patients who presented with brisk upper GI bleeding at a tertiary care center.
Disclosures: The authors disclosed no financial relationships relevant to the current study.
RBCs from previously pregnant women linked to increased mortality in men
By contrast, all-cause mortality was not higher in female transplant recipients who received transfusions from previously pregnant females and was not higher in male or female recipients of transfusions from never-pregnant female donors.
The results need to be replicated in prospective trials. “Further research is needed to replicate these findings, determine their clinical significance, and identify the underlying mechanism,” wrote Camila Caram-Deelder, MSc, of the Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands, and her coauthors (JAMA. 2017;318[15]:1471-78).
The association “may be related to either immunologic phenomena or other mechanisms,” the investigators said. The cause of increased mortality also could be some difference in iron status between the previously pregnant female donors and male donors.
Ms. Caram-Deelder and her associates studied first-time transfusion recipients treated between 2005 and 2015 at six hospitals in the Netherlands. A total of 42,132 patients received 106,641 units of red blood cells. Among this full cohort, 31,118 patients (52% female) received 59,320 units of red blood cells exclusively from one of the three types of donor (88% male, 6% ever-pregnant female, and 6% never-pregnant female) and were followed up for a median of 245 days. During that time, 13% of the cohort died.
For the 14,995 male recipients in the no-donor-mixture cohort, 13% died during follow-up. The hazard ratio for death after 1 additional unit of red blood cells from a never-pregnant female donor, compared with a unit from a male donor, was 0.93 (95% CI, 0.81 to 1.06) for male recipients and 1.01 (95% CI, 0.88 to 1.15) for female recipients. This difference was not significant. Alternatively, for male recipients the HR for death after 1 additional unit of red blood cells from an ever-pregnant female donor, compared with a unit from a male donor, was 1.13 (95% CI, 1.01 to 1.26). The difference was statistically significant (P = .03).
Of the 16,123 female recipients in the no-donor-mixture cohort, 12% died during follow-up. Mortality rates for an ever-pregnant female donor vs. a male donor were 74 and 62 per 1,000 person-years (HR, 0.99; 95% CI, 0.87 to 1.13); for a never-pregnant female donor vs. a male donor, mortality rates were 74 and 62 per 1,000 person-years (HR, 1.01; 95% CI, 0.88-1.15). The difference was not significant.
The highest HRs for death after transfusion of red blood cells from ever-pregnant female donors were observed in male recipients 50 years and younger.
Study funding came from the Dutch Ministry of Health, Welfare and Sports. One investigator in the study reported receiving a speaking fee from Vifor Pharma and serving on the advisory councils of Novartis and Amgen Science.
The provocative finding that men have an increased mortality risk if they receive red blood cell transplants from women with a history of pregnancy could have significant practical implications if proven true in subsequent studies.
Because of the complex methodology of the study, alternative explanations for the association should be considered.
The differences in mortality seem to increase 1 year or more following the transfusion, suggesting that the trigger may be an immunologic mechanism based on maternal immunization to paternal antigens, but until prospective studies confirm that a donor’s sex and pregnancy status are associated with mortality after transplant, “appropriate and conservative use of blood products continues to be the gold standard for safe transfusion.”
Ritchard G. Cable, MD, is with American Red Cross Blood Services, Connecticut Region, Farmington. Gustaf Edgren, MD, PhD, is with the department of hematology at Karolinska University Hospital, Stockholm. These comments are based on their accompanying editorial (JAMA. 2017 Oct 17;318[15]:1445-7). They reported no financial conflicts of interest.
The provocative finding that men have an increased mortality risk if they receive red blood cell transplants from women with a history of pregnancy could have significant practical implications if proven true in subsequent studies.
Because of the complex methodology of the study, alternative explanations for the association should be considered.
The differences in mortality seem to increase 1 year or more following the transfusion, suggesting that the trigger may be an immunologic mechanism based on maternal immunization to paternal antigens, but until prospective studies confirm that a donor’s sex and pregnancy status are associated with mortality after transplant, “appropriate and conservative use of blood products continues to be the gold standard for safe transfusion.”
Ritchard G. Cable, MD, is with American Red Cross Blood Services, Connecticut Region, Farmington. Gustaf Edgren, MD, PhD, is with the department of hematology at Karolinska University Hospital, Stockholm. These comments are based on their accompanying editorial (JAMA. 2017 Oct 17;318[15]:1445-7). They reported no financial conflicts of interest.
The provocative finding that men have an increased mortality risk if they receive red blood cell transplants from women with a history of pregnancy could have significant practical implications if proven true in subsequent studies.
Because of the complex methodology of the study, alternative explanations for the association should be considered.
The differences in mortality seem to increase 1 year or more following the transfusion, suggesting that the trigger may be an immunologic mechanism based on maternal immunization to paternal antigens, but until prospective studies confirm that a donor’s sex and pregnancy status are associated with mortality after transplant, “appropriate and conservative use of blood products continues to be the gold standard for safe transfusion.”
Ritchard G. Cable, MD, is with American Red Cross Blood Services, Connecticut Region, Farmington. Gustaf Edgren, MD, PhD, is with the department of hematology at Karolinska University Hospital, Stockholm. These comments are based on their accompanying editorial (JAMA. 2017 Oct 17;318[15]:1445-7). They reported no financial conflicts of interest.
By contrast, all-cause mortality was not higher in female transplant recipients who received transfusions from previously pregnant females and was not higher in male or female recipients of transfusions from never-pregnant female donors.
The results need to be replicated in prospective trials. “Further research is needed to replicate these findings, determine their clinical significance, and identify the underlying mechanism,” wrote Camila Caram-Deelder, MSc, of the Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands, and her coauthors (JAMA. 2017;318[15]:1471-78).
The association “may be related to either immunologic phenomena or other mechanisms,” the investigators said. The cause of increased mortality also could be some difference in iron status between the previously pregnant female donors and male donors.
Ms. Caram-Deelder and her associates studied first-time transfusion recipients treated between 2005 and 2015 at six hospitals in the Netherlands. A total of 42,132 patients received 106,641 units of red blood cells. Among this full cohort, 31,118 patients (52% female) received 59,320 units of red blood cells exclusively from one of the three types of donor (88% male, 6% ever-pregnant female, and 6% never-pregnant female) and were followed up for a median of 245 days. During that time, 13% of the cohort died.
For the 14,995 male recipients in the no-donor-mixture cohort, 13% died during follow-up. The hazard ratio for death after 1 additional unit of red blood cells from a never-pregnant female donor, compared with a unit from a male donor, was 0.93 (95% CI, 0.81 to 1.06) for male recipients and 1.01 (95% CI, 0.88 to 1.15) for female recipients. This difference was not significant. Alternatively, for male recipients the HR for death after 1 additional unit of red blood cells from an ever-pregnant female donor, compared with a unit from a male donor, was 1.13 (95% CI, 1.01 to 1.26). The difference was statistically significant (P = .03).
Of the 16,123 female recipients in the no-donor-mixture cohort, 12% died during follow-up. Mortality rates for an ever-pregnant female donor vs. a male donor were 74 and 62 per 1,000 person-years (HR, 0.99; 95% CI, 0.87 to 1.13); for a never-pregnant female donor vs. a male donor, mortality rates were 74 and 62 per 1,000 person-years (HR, 1.01; 95% CI, 0.88-1.15). The difference was not significant.
The highest HRs for death after transfusion of red blood cells from ever-pregnant female donors were observed in male recipients 50 years and younger.
Study funding came from the Dutch Ministry of Health, Welfare and Sports. One investigator in the study reported receiving a speaking fee from Vifor Pharma and serving on the advisory councils of Novartis and Amgen Science.
By contrast, all-cause mortality was not higher in female transplant recipients who received transfusions from previously pregnant females and was not higher in male or female recipients of transfusions from never-pregnant female donors.
The results need to be replicated in prospective trials. “Further research is needed to replicate these findings, determine their clinical significance, and identify the underlying mechanism,” wrote Camila Caram-Deelder, MSc, of the Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands, and her coauthors (JAMA. 2017;318[15]:1471-78).
The association “may be related to either immunologic phenomena or other mechanisms,” the investigators said. The cause of increased mortality also could be some difference in iron status between the previously pregnant female donors and male donors.
Ms. Caram-Deelder and her associates studied first-time transfusion recipients treated between 2005 and 2015 at six hospitals in the Netherlands. A total of 42,132 patients received 106,641 units of red blood cells. Among this full cohort, 31,118 patients (52% female) received 59,320 units of red blood cells exclusively from one of the three types of donor (88% male, 6% ever-pregnant female, and 6% never-pregnant female) and were followed up for a median of 245 days. During that time, 13% of the cohort died.
For the 14,995 male recipients in the no-donor-mixture cohort, 13% died during follow-up. The hazard ratio for death after 1 additional unit of red blood cells from a never-pregnant female donor, compared with a unit from a male donor, was 0.93 (95% CI, 0.81 to 1.06) for male recipients and 1.01 (95% CI, 0.88 to 1.15) for female recipients. This difference was not significant. Alternatively, for male recipients the HR for death after 1 additional unit of red blood cells from an ever-pregnant female donor, compared with a unit from a male donor, was 1.13 (95% CI, 1.01 to 1.26). The difference was statistically significant (P = .03).
Of the 16,123 female recipients in the no-donor-mixture cohort, 12% died during follow-up. Mortality rates for an ever-pregnant female donor vs. a male donor were 74 and 62 per 1,000 person-years (HR, 0.99; 95% CI, 0.87 to 1.13); for a never-pregnant female donor vs. a male donor, mortality rates were 74 and 62 per 1,000 person-years (HR, 1.01; 95% CI, 0.88-1.15). The difference was not significant.
The highest HRs for death after transfusion of red blood cells from ever-pregnant female donors were observed in male recipients 50 years and younger.
Study funding came from the Dutch Ministry of Health, Welfare and Sports. One investigator in the study reported receiving a speaking fee from Vifor Pharma and serving on the advisory councils of Novartis and Amgen Science.
FROM JAMA
Key clinical point: Receiving a red blood cell transfusion from a female donor with any history of pregnancy was associated with increased mortality in men, but not in women.
Major finding: Among men, all-cause mortality after transfusion from an ever-pregnant female donor vs. a male donor was 101 vs. 80 deaths per 1000 person-years (hazard ratio, 1.13; 95% confidence interval, 1.01-1.26).
Data source: Retrospective cohort study of 31,118 patients who received red blood cell transfusions exclusively from one of the three types of donor – 88% male, 6% ever-pregnant female, and 6% never-pregnant female – at one of six Dutch hospitals.
Disclosures: Study funding came from the Dutch Ministry of Health, Welfare and Sports. One investigator in the study reported receiving a speaking fee from Vifor Pharma and serving on the advisory councils of Novartis and Amgen Science.