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Drug granted fast track designation for MF
mycosis fungoides
The US Food and Drug Administration (FDA) has granted fast track designation to Resimmune® (A-dmDT390-bisFv[UCHT1]) for the treatment of mycosis fungoides (MF).
Resimmune is an anti-CD3 immunotoxin that targets and transiently depletes a high percentage of malignant and normal T cells.
Researchers believe this high rate of T-cell depletion may “reset” a patient’s immune system, leading to immunomodulation. However, the safety and efficacy of Resimmune has not been established.
Resimmune is being developed by Angimmune LLC.
Resimmune research
The FDA’s fast track designation for Resimmune is based on results from a phase 1 trial, which were published in haematologica last year.
The trial included 25 patients with cutaneous T-cell lymphoma (CTCL)—17 with stage IB-IIB disease and 8 with stage III-IV disease. The patients received Resimmune at varying doses—between 2.5 µg/kg and 11.25 µg/kg.
Safety
Drug-related adverse events for the entire study cohort (n=30) included:
- Grade 2-3 AST/ALT elevations (n=6)
- Grade 2 chills (n=10)
- Grade 5 EBV infection (n=1)
- Grade 3 EBV/CMV infection (n=5)
- Grade 2 fever (n=6)
- Grade 5 heart failure (n=2)
- Grade 2-3 hypoalbuminemia (n=11)
- Grade 2 hypomagnesemia (n=1)
- Grade 3 hypophosphatemia (n=3)
- Grade 2-4 hypotension (n=3)
- Grade 4 hypoxia (n=1)
- Grade 4 liver failure (n=1)
- Grade 4 metabolic acidosis (n=1)
- Grade 3 supraventricular tachycardia (n=2)
- Grade 3-4 uremia (n=3)
- Grade 2-4 vascular leak syndrome (n=5).
Efficacy and phase 2
Nine of the CTCL patients (36%) responded to Resimmune, and 4 (16%) had complete responses (CRs). The duration of CR was more than 38 months for 1 patient, more than 60 months for another, and more than 72 months for 2 patients.
Of the 5 partial responses, 2 lasted 3 months, 1 lasted more than 3 months, 1 lasted more than 6 months, and the longest lasted 14 months.
The researchers said this trial revealed a subgroup of CTCL patients with a very high response rate.
When they excluded patients whose mSWAT scores never exceeded 50 and who never had lymph node involvement or stage III disease, the researchers were left with 9 patients. This subgroup had an overall response rate of 89% and a CR rate of 50% (at 6 months of follow-up).
“Results from our phase 1 trial demonstrated a particularly robust response among certain patients with early stage disease, and the randomized phase 2 trial is designed to further explore this potential therapeutic benefit,” said David Neville, MD, president and chief scientific officer of Angimmune.
The objective of this phase 2 trial is to document the incidence of CRs with Resimmune compared to oral vorinostat after a maximum of 12 months of treatment. The trial will enroll patients with stage IB/IIB MF with mSWAT < 50 who have never had lymphoid disease or a prior hematopoietic stem cell transplant.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers. 
mycosis fungoides
The US Food and Drug Administration (FDA) has granted fast track designation to Resimmune® (A-dmDT390-bisFv[UCHT1]) for the treatment of mycosis fungoides (MF).
Resimmune is an anti-CD3 immunotoxin that targets and transiently depletes a high percentage of malignant and normal T cells.
Researchers believe this high rate of T-cell depletion may “reset” a patient’s immune system, leading to immunomodulation. However, the safety and efficacy of Resimmune has not been established.
Resimmune is being developed by Angimmune LLC.
Resimmune research
The FDA’s fast track designation for Resimmune is based on results from a phase 1 trial, which were published in haematologica last year.
The trial included 25 patients with cutaneous T-cell lymphoma (CTCL)—17 with stage IB-IIB disease and 8 with stage III-IV disease. The patients received Resimmune at varying doses—between 2.5 µg/kg and 11.25 µg/kg.
Safety
Drug-related adverse events for the entire study cohort (n=30) included:
- Grade 2-3 AST/ALT elevations (n=6)
- Grade 2 chills (n=10)
- Grade 5 EBV infection (n=1)
- Grade 3 EBV/CMV infection (n=5)
- Grade 2 fever (n=6)
- Grade 5 heart failure (n=2)
- Grade 2-3 hypoalbuminemia (n=11)
- Grade 2 hypomagnesemia (n=1)
- Grade 3 hypophosphatemia (n=3)
- Grade 2-4 hypotension (n=3)
- Grade 4 hypoxia (n=1)
- Grade 4 liver failure (n=1)
- Grade 4 metabolic acidosis (n=1)
- Grade 3 supraventricular tachycardia (n=2)
- Grade 3-4 uremia (n=3)
- Grade 2-4 vascular leak syndrome (n=5).
Efficacy and phase 2
Nine of the CTCL patients (36%) responded to Resimmune, and 4 (16%) had complete responses (CRs). The duration of CR was more than 38 months for 1 patient, more than 60 months for another, and more than 72 months for 2 patients.
Of the 5 partial responses, 2 lasted 3 months, 1 lasted more than 3 months, 1 lasted more than 6 months, and the longest lasted 14 months.
The researchers said this trial revealed a subgroup of CTCL patients with a very high response rate.
When they excluded patients whose mSWAT scores never exceeded 50 and who never had lymph node involvement or stage III disease, the researchers were left with 9 patients. This subgroup had an overall response rate of 89% and a CR rate of 50% (at 6 months of follow-up).
“Results from our phase 1 trial demonstrated a particularly robust response among certain patients with early stage disease, and the randomized phase 2 trial is designed to further explore this potential therapeutic benefit,” said David Neville, MD, president and chief scientific officer of Angimmune.
The objective of this phase 2 trial is to document the incidence of CRs with Resimmune compared to oral vorinostat after a maximum of 12 months of treatment. The trial will enroll patients with stage IB/IIB MF with mSWAT < 50 who have never had lymphoid disease or a prior hematopoietic stem cell transplant.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.
mycosis fungoides
The US Food and Drug Administration (FDA) has granted fast track designation to Resimmune® (A-dmDT390-bisFv[UCHT1]) for the treatment of mycosis fungoides (MF).
Resimmune is an anti-CD3 immunotoxin that targets and transiently depletes a high percentage of malignant and normal T cells.
Researchers believe this high rate of T-cell depletion may “reset” a patient’s immune system, leading to immunomodulation. However, the safety and efficacy of Resimmune has not been established.
Resimmune is being developed by Angimmune LLC.
Resimmune research
The FDA’s fast track designation for Resimmune is based on results from a phase 1 trial, which were published in haematologica last year.
The trial included 25 patients with cutaneous T-cell lymphoma (CTCL)—17 with stage IB-IIB disease and 8 with stage III-IV disease. The patients received Resimmune at varying doses—between 2.5 µg/kg and 11.25 µg/kg.
Safety
Drug-related adverse events for the entire study cohort (n=30) included:
- Grade 2-3 AST/ALT elevations (n=6)
- Grade 2 chills (n=10)
- Grade 5 EBV infection (n=1)
- Grade 3 EBV/CMV infection (n=5)
- Grade 2 fever (n=6)
- Grade 5 heart failure (n=2)
- Grade 2-3 hypoalbuminemia (n=11)
- Grade 2 hypomagnesemia (n=1)
- Grade 3 hypophosphatemia (n=3)
- Grade 2-4 hypotension (n=3)
- Grade 4 hypoxia (n=1)
- Grade 4 liver failure (n=1)
- Grade 4 metabolic acidosis (n=1)
- Grade 3 supraventricular tachycardia (n=2)
- Grade 3-4 uremia (n=3)
- Grade 2-4 vascular leak syndrome (n=5).
Efficacy and phase 2
Nine of the CTCL patients (36%) responded to Resimmune, and 4 (16%) had complete responses (CRs). The duration of CR was more than 38 months for 1 patient, more than 60 months for another, and more than 72 months for 2 patients.
Of the 5 partial responses, 2 lasted 3 months, 1 lasted more than 3 months, 1 lasted more than 6 months, and the longest lasted 14 months.
The researchers said this trial revealed a subgroup of CTCL patients with a very high response rate.
When they excluded patients whose mSWAT scores never exceeded 50 and who never had lymph node involvement or stage III disease, the researchers were left with 9 patients. This subgroup had an overall response rate of 89% and a CR rate of 50% (at 6 months of follow-up).
“Results from our phase 1 trial demonstrated a particularly robust response among certain patients with early stage disease, and the randomized phase 2 trial is designed to further explore this potential therapeutic benefit,” said David Neville, MD, president and chief scientific officer of Angimmune.
The objective of this phase 2 trial is to document the incidence of CRs with Resimmune compared to oral vorinostat after a maximum of 12 months of treatment. The trial will enroll patients with stage IB/IIB MF with mSWAT < 50 who have never had lymphoid disease or a prior hematopoietic stem cell transplant.
About fast track designation
The FDA’s fast track program is designed to facilitate and expedite the development and review of new drugs intended to treat serious or life-threatening conditions and address unmet medical need.
Through the fast track program, a product may be eligible for priority review. In addition, the company developing the drug may be allowed to submit sections of the biologic license application or new drug application on a rolling basis as data become available.
Fast track designation also provides the company with opportunities for more frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of the appropriate data needed to support drug approval. And the designation allows for more frequent written communication from the FDA about things such as the design of proposed clinical trials and the use of biomarkers.
Studies reveal potential therapeutic targets for resistant AML
Image by NIGMS
A pair of studies suggest the DNA replication checkpoint pathway could be targeted to treat resistant acute myeloid leukemia (AML).
One study indicated that the kinase CHK1, which coordinates the DNA damage response and cell-cycle checkpoint response, might be targeted to overcome cytarabine resistance in AML.
The other study suggested that ATR, a kinase that activates CHK1, and ATM, a second upstream kinase in the DNA damage response, might be therapeutic targets in MLL-rearranged AML.
Both studies were published in Science Sigaling.
Laure David, of La Ligue Contre Le Cancer in Toulouse, France, and colleagues conducted this study.
The researchers integrated gene expression data with survival data from 198 AML patients who were previously treated with cytarabine-based chemotherapy.
The data showed that patients with high expression of CHEK1, the gene that encodes CHK1, had poor survival. And patient cells with high CHK1 abundance were resistant to cytarabine.
However, when the researchers exposed the cells with high CHK1 abundance to the CHK1 inhibitor SCH900776, they observed “reduced clonogenic ability and progression of DNA replication in the presence of cytarabine.”
The team therefore concluded that treatment with a CHK1 inhibitor might overcome resistance to cytarabine-based treatments in AML. They also said that monitoring CHEK1 expression in AML patients could potentially predict outcomes and reveal patients who might benefit from treatment with a CHK1 inhibitor.
The second study was conducted by Isabel Morgado-Palacin, of the Spanish National Cancer Research Center in Madrid, and colleagues.
The researchers investigated ATR, which is the primary sensor of DNA replication stress, and ATM, a kinase that senses DNA double-strand breaks, as possible therapeutic targets in MLL-rearranged AML.
The team found that inhibiting ATR induced chromosomal breakage and death in murine AML-MLL cells in vitro. And inhibiting ATR in vivo reduced the tumor burden and prevented tumors from growing.
The researchers also found that inhibiting ATM prolonged survival in the mouse model of AML-MLL, which suggests that both ATR and ATM might be therapeutic targets in MLL-rearranged AML.
Image by NIGMS
A pair of studies suggest the DNA replication checkpoint pathway could be targeted to treat resistant acute myeloid leukemia (AML).
One study indicated that the kinase CHK1, which coordinates the DNA damage response and cell-cycle checkpoint response, might be targeted to overcome cytarabine resistance in AML.
The other study suggested that ATR, a kinase that activates CHK1, and ATM, a second upstream kinase in the DNA damage response, might be therapeutic targets in MLL-rearranged AML.
Both studies were published in Science Sigaling.
Laure David, of La Ligue Contre Le Cancer in Toulouse, France, and colleagues conducted this study.
The researchers integrated gene expression data with survival data from 198 AML patients who were previously treated with cytarabine-based chemotherapy.
The data showed that patients with high expression of CHEK1, the gene that encodes CHK1, had poor survival. And patient cells with high CHK1 abundance were resistant to cytarabine.
However, when the researchers exposed the cells with high CHK1 abundance to the CHK1 inhibitor SCH900776, they observed “reduced clonogenic ability and progression of DNA replication in the presence of cytarabine.”
The team therefore concluded that treatment with a CHK1 inhibitor might overcome resistance to cytarabine-based treatments in AML. They also said that monitoring CHEK1 expression in AML patients could potentially predict outcomes and reveal patients who might benefit from treatment with a CHK1 inhibitor.
The second study was conducted by Isabel Morgado-Palacin, of the Spanish National Cancer Research Center in Madrid, and colleagues.
The researchers investigated ATR, which is the primary sensor of DNA replication stress, and ATM, a kinase that senses DNA double-strand breaks, as possible therapeutic targets in MLL-rearranged AML.
The team found that inhibiting ATR induced chromosomal breakage and death in murine AML-MLL cells in vitro. And inhibiting ATR in vivo reduced the tumor burden and prevented tumors from growing.
The researchers also found that inhibiting ATM prolonged survival in the mouse model of AML-MLL, which suggests that both ATR and ATM might be therapeutic targets in MLL-rearranged AML.
Image by NIGMS
A pair of studies suggest the DNA replication checkpoint pathway could be targeted to treat resistant acute myeloid leukemia (AML).
One study indicated that the kinase CHK1, which coordinates the DNA damage response and cell-cycle checkpoint response, might be targeted to overcome cytarabine resistance in AML.
The other study suggested that ATR, a kinase that activates CHK1, and ATM, a second upstream kinase in the DNA damage response, might be therapeutic targets in MLL-rearranged AML.
Both studies were published in Science Sigaling.
Laure David, of La Ligue Contre Le Cancer in Toulouse, France, and colleagues conducted this study.
The researchers integrated gene expression data with survival data from 198 AML patients who were previously treated with cytarabine-based chemotherapy.
The data showed that patients with high expression of CHEK1, the gene that encodes CHK1, had poor survival. And patient cells with high CHK1 abundance were resistant to cytarabine.
However, when the researchers exposed the cells with high CHK1 abundance to the CHK1 inhibitor SCH900776, they observed “reduced clonogenic ability and progression of DNA replication in the presence of cytarabine.”
The team therefore concluded that treatment with a CHK1 inhibitor might overcome resistance to cytarabine-based treatments in AML. They also said that monitoring CHEK1 expression in AML patients could potentially predict outcomes and reveal patients who might benefit from treatment with a CHK1 inhibitor.
The second study was conducted by Isabel Morgado-Palacin, of the Spanish National Cancer Research Center in Madrid, and colleagues.
The researchers investigated ATR, which is the primary sensor of DNA replication stress, and ATM, a kinase that senses DNA double-strand breaks, as possible therapeutic targets in MLL-rearranged AML.
The team found that inhibiting ATR induced chromosomal breakage and death in murine AML-MLL cells in vitro. And inhibiting ATR in vivo reduced the tumor burden and prevented tumors from growing.
The researchers also found that inhibiting ATM prolonged survival in the mouse model of AML-MLL, which suggests that both ATR and ATM might be therapeutic targets in MLL-rearranged AML.
Drug warrants further investigation in ATLL, team says
Researchers say lenalidomide exhibited clinically meaningful antitumor activity and an acceptable safety profile in a phase 2 study of patients with relapsed adult T-cell leukemia/lymphoma (ATLL).
Of the 26 patients enrolled in the trial, 42% responded to lenalidomide, and 35% experienced serious adverse events (AEs).
Results from this trial were published in the Journal of Clinical Oncology. Data were previously presented at the 8th Annual T-cell Lymphoma Forum. The study was sponsored by Celgene K.K.
Patients and treatment
All 26 patients had relapsed ATLL—15 with the acute subtype, 7 with the lymphoma subtype, and 4 with the unfavorable chronic subtype. The patients’ median age was 68.5 (range, 53-81), all were Japanese, and 54% were male.
The median number of prior treatment regimens was 2 (range, 1-4). Thirty-five percent of patients had prior mogamulizumab (n=9), 35% had received LSG15 (n=3) or modified LSG15 (n=6), and 27% had prior CHOP (n=7).
The patients received lenalidomide at 25 mg per day, given continuously until disease progression or intolerability.
Results
Five patients (19%) were still receiving lenalidomide at the data cutoff, which was November 20, 2014.
Thirteen patients (50%) stopped treatment due to progression, 6 (23%) because of AEs, 1 (4%) due to investigator decision, and 1 (4%) because of concerns about the increased possibility of disease recurrence.
The median follow-up was 3.9 months. Eleven patients (42%) responded to lenalidomide, including 4 complete responses and 1 unconfirmed complete response.
The median duration of response was not reached (range, 0.5 months to not reached), and the mean duration of response was 5.2 months (range, 0 to 16.6 months).
The median progression-free survival was 3.8 months (range, 1.9 months to not reached), and the median overall survival was 20.3 months (range, 9.1 months to not reached).
Nine patients (35%) experienced serious AEs. The only serious AE that occurred in more than 1 patient was thrombocytopenia, which occurred in 2 patients.
The most frequent AEs of any grade were thrombocytopenia (77%), neutropenia (73%), lymphopenia (69%), anemia (54%), and leukopenia (50%).
The most frequent grade 3 or higher AEs were neutropenia (65%), leukopenia (38%), lymphopenia (38%), and thrombocytopenia (23%). These events were all manageable and reversible, according to the researchers.
Based on these results, the team concluded that lenalidomide warrants further investigation as a treatment for ATLL.
Researchers say lenalidomide exhibited clinically meaningful antitumor activity and an acceptable safety profile in a phase 2 study of patients with relapsed adult T-cell leukemia/lymphoma (ATLL).
Of the 26 patients enrolled in the trial, 42% responded to lenalidomide, and 35% experienced serious adverse events (AEs).
Results from this trial were published in the Journal of Clinical Oncology. Data were previously presented at the 8th Annual T-cell Lymphoma Forum. The study was sponsored by Celgene K.K.
Patients and treatment
All 26 patients had relapsed ATLL—15 with the acute subtype, 7 with the lymphoma subtype, and 4 with the unfavorable chronic subtype. The patients’ median age was 68.5 (range, 53-81), all were Japanese, and 54% were male.
The median number of prior treatment regimens was 2 (range, 1-4). Thirty-five percent of patients had prior mogamulizumab (n=9), 35% had received LSG15 (n=3) or modified LSG15 (n=6), and 27% had prior CHOP (n=7).
The patients received lenalidomide at 25 mg per day, given continuously until disease progression or intolerability.
Results
Five patients (19%) were still receiving lenalidomide at the data cutoff, which was November 20, 2014.
Thirteen patients (50%) stopped treatment due to progression, 6 (23%) because of AEs, 1 (4%) due to investigator decision, and 1 (4%) because of concerns about the increased possibility of disease recurrence.
The median follow-up was 3.9 months. Eleven patients (42%) responded to lenalidomide, including 4 complete responses and 1 unconfirmed complete response.
The median duration of response was not reached (range, 0.5 months to not reached), and the mean duration of response was 5.2 months (range, 0 to 16.6 months).
The median progression-free survival was 3.8 months (range, 1.9 months to not reached), and the median overall survival was 20.3 months (range, 9.1 months to not reached).
Nine patients (35%) experienced serious AEs. The only serious AE that occurred in more than 1 patient was thrombocytopenia, which occurred in 2 patients.
The most frequent AEs of any grade were thrombocytopenia (77%), neutropenia (73%), lymphopenia (69%), anemia (54%), and leukopenia (50%).
The most frequent grade 3 or higher AEs were neutropenia (65%), leukopenia (38%), lymphopenia (38%), and thrombocytopenia (23%). These events were all manageable and reversible, according to the researchers.
Based on these results, the team concluded that lenalidomide warrants further investigation as a treatment for ATLL.
Researchers say lenalidomide exhibited clinically meaningful antitumor activity and an acceptable safety profile in a phase 2 study of patients with relapsed adult T-cell leukemia/lymphoma (ATLL).
Of the 26 patients enrolled in the trial, 42% responded to lenalidomide, and 35% experienced serious adverse events (AEs).
Results from this trial were published in the Journal of Clinical Oncology. Data were previously presented at the 8th Annual T-cell Lymphoma Forum. The study was sponsored by Celgene K.K.
Patients and treatment
All 26 patients had relapsed ATLL—15 with the acute subtype, 7 with the lymphoma subtype, and 4 with the unfavorable chronic subtype. The patients’ median age was 68.5 (range, 53-81), all were Japanese, and 54% were male.
The median number of prior treatment regimens was 2 (range, 1-4). Thirty-five percent of patients had prior mogamulizumab (n=9), 35% had received LSG15 (n=3) or modified LSG15 (n=6), and 27% had prior CHOP (n=7).
The patients received lenalidomide at 25 mg per day, given continuously until disease progression or intolerability.
Results
Five patients (19%) were still receiving lenalidomide at the data cutoff, which was November 20, 2014.
Thirteen patients (50%) stopped treatment due to progression, 6 (23%) because of AEs, 1 (4%) due to investigator decision, and 1 (4%) because of concerns about the increased possibility of disease recurrence.
The median follow-up was 3.9 months. Eleven patients (42%) responded to lenalidomide, including 4 complete responses and 1 unconfirmed complete response.
The median duration of response was not reached (range, 0.5 months to not reached), and the mean duration of response was 5.2 months (range, 0 to 16.6 months).
The median progression-free survival was 3.8 months (range, 1.9 months to not reached), and the median overall survival was 20.3 months (range, 9.1 months to not reached).
Nine patients (35%) experienced serious AEs. The only serious AE that occurred in more than 1 patient was thrombocytopenia, which occurred in 2 patients.
The most frequent AEs of any grade were thrombocytopenia (77%), neutropenia (73%), lymphopenia (69%), anemia (54%), and leukopenia (50%).
The most frequent grade 3 or higher AEs were neutropenia (65%), leukopenia (38%), lymphopenia (38%), and thrombocytopenia (23%). These events were all manageable and reversible, according to the researchers.
Based on these results, the team concluded that lenalidomide warrants further investigation as a treatment for ATLL.
SpHb monitoring may reduce use of RBC transfusion
Photo by Elisa Amendola
HONG KONG—Continuous and noninvasive hemoglobin monitoring may reduce the excessive use of intraoperative red blood cell (RBC) transfusion, according to researchers.
The team conducted a retrospective study of patients who received intraoperative RBC transfusions at a single institution, comparing patients who had noninvasive and continuous monitoring of hemoglobin concentrations by spectrophotometry (SpHb) to those who did not.
The results showed a significantly lower mean RBC transfusion volume per 1 g of blood loss in the SpHb group than in the control group.
The researchers presented these findings at the 16th World Congress of Anaesthesiologists (abstract PR607).
The study included 371 patients who received intraoperative RBC transfusions between 2012 and 2014 at Fukushima Medical University in Japan.
The researchers compared 94 patients who had SpHb with the Radical-7® Pulse CO-Oximeter (a product of Masimo) to 277 patients who did not.
The team noted that measured SpHb values are similar to the Hb concentration values obtained by blood sampling, and the procedure allows for continuous monitoring of changes in SpHb levels over time.
The median blood loss during surgery was 1160 g in the SpHb group and 900 g in the control group.
There was no significant difference in the average RBC transfusion volume between the SpHb group and the control group—815 ± 819 mL and 785 ± 773 mL, respectively (P=0.75).
Likewise, there was no significant difference in the preoperative hemoglobin concentration in the SpHb group and the control group—10.4 ± 1.9 g/dL and 10.2 ± 2.4 g/dL, respectively (P=0.27).
However, the researchers did find that patients in the SpHb group had a significantly lower mean RBC transfusion volume per 1 g of blood loss when compared to controls—0.9 ± 1.0 mL/g blood loss and 2.4 ± 5.9 mL/g blood loss, respectively (P<0.01).
“This is the third study, published by different researchers on 3 continents (US1, Egypt2, and now Japan) that has shown that, in addition to other clinical tools, SpHb may be used to help clinicians make informed transfusion decisions during different types of surgery,” said Steven Barker, MD, PhD, chief science officer of Masimo.
Though Masimo’s Radical-7® Pulse CO-Oximeter was used in this study, the researchers declared no conflicts of interest.
Photo by Elisa Amendola
HONG KONG—Continuous and noninvasive hemoglobin monitoring may reduce the excessive use of intraoperative red blood cell (RBC) transfusion, according to researchers.
The team conducted a retrospective study of patients who received intraoperative RBC transfusions at a single institution, comparing patients who had noninvasive and continuous monitoring of hemoglobin concentrations by spectrophotometry (SpHb) to those who did not.
The results showed a significantly lower mean RBC transfusion volume per 1 g of blood loss in the SpHb group than in the control group.
The researchers presented these findings at the 16th World Congress of Anaesthesiologists (abstract PR607).
The study included 371 patients who received intraoperative RBC transfusions between 2012 and 2014 at Fukushima Medical University in Japan.
The researchers compared 94 patients who had SpHb with the Radical-7® Pulse CO-Oximeter (a product of Masimo) to 277 patients who did not.
The team noted that measured SpHb values are similar to the Hb concentration values obtained by blood sampling, and the procedure allows for continuous monitoring of changes in SpHb levels over time.
The median blood loss during surgery was 1160 g in the SpHb group and 900 g in the control group.
There was no significant difference in the average RBC transfusion volume between the SpHb group and the control group—815 ± 819 mL and 785 ± 773 mL, respectively (P=0.75).
Likewise, there was no significant difference in the preoperative hemoglobin concentration in the SpHb group and the control group—10.4 ± 1.9 g/dL and 10.2 ± 2.4 g/dL, respectively (P=0.27).
However, the researchers did find that patients in the SpHb group had a significantly lower mean RBC transfusion volume per 1 g of blood loss when compared to controls—0.9 ± 1.0 mL/g blood loss and 2.4 ± 5.9 mL/g blood loss, respectively (P<0.01).
“This is the third study, published by different researchers on 3 continents (US1, Egypt2, and now Japan) that has shown that, in addition to other clinical tools, SpHb may be used to help clinicians make informed transfusion decisions during different types of surgery,” said Steven Barker, MD, PhD, chief science officer of Masimo.
Though Masimo’s Radical-7® Pulse CO-Oximeter was used in this study, the researchers declared no conflicts of interest.
Photo by Elisa Amendola
HONG KONG—Continuous and noninvasive hemoglobin monitoring may reduce the excessive use of intraoperative red blood cell (RBC) transfusion, according to researchers.
The team conducted a retrospective study of patients who received intraoperative RBC transfusions at a single institution, comparing patients who had noninvasive and continuous monitoring of hemoglobin concentrations by spectrophotometry (SpHb) to those who did not.
The results showed a significantly lower mean RBC transfusion volume per 1 g of blood loss in the SpHb group than in the control group.
The researchers presented these findings at the 16th World Congress of Anaesthesiologists (abstract PR607).
The study included 371 patients who received intraoperative RBC transfusions between 2012 and 2014 at Fukushima Medical University in Japan.
The researchers compared 94 patients who had SpHb with the Radical-7® Pulse CO-Oximeter (a product of Masimo) to 277 patients who did not.
The team noted that measured SpHb values are similar to the Hb concentration values obtained by blood sampling, and the procedure allows for continuous monitoring of changes in SpHb levels over time.
The median blood loss during surgery was 1160 g in the SpHb group and 900 g in the control group.
There was no significant difference in the average RBC transfusion volume between the SpHb group and the control group—815 ± 819 mL and 785 ± 773 mL, respectively (P=0.75).
Likewise, there was no significant difference in the preoperative hemoglobin concentration in the SpHb group and the control group—10.4 ± 1.9 g/dL and 10.2 ± 2.4 g/dL, respectively (P=0.27).
However, the researchers did find that patients in the SpHb group had a significantly lower mean RBC transfusion volume per 1 g of blood loss when compared to controls—0.9 ± 1.0 mL/g blood loss and 2.4 ± 5.9 mL/g blood loss, respectively (P<0.01).
“This is the third study, published by different researchers on 3 continents (US1, Egypt2, and now Japan) that has shown that, in addition to other clinical tools, SpHb may be used to help clinicians make informed transfusion decisions during different types of surgery,” said Steven Barker, MD, PhD, chief science officer of Masimo.
Though Masimo’s Radical-7® Pulse CO-Oximeter was used in this study, the researchers declared no conflicts of interest.
Both prepregnancy and gestational diabetes bode ill for babies
MUNICH – Pregestational maternal diabetes is even riskier for newborns than gestational diabetes, increasing the chance of neonatal hypoglycemia by 36 times over a normal pregnancy.
Baby’s blood sugar isn’t the only thing in danger, though, Basilio Pintaudi, MD, said at the European Association for the Study of Diabetes conference. Women with prepregnancy diabetes are significantly more likely to have babies that are either small or large for gestational age; become jaundiced; have congenital malformations; and experience respiratory distress, hypocalcemia, and hypomagnesemia, said Dr. Pintaudi of Niguarda Ca’ Granda Hospital, Milan.
“Everyone involved in the care of pregnant women should realize there are very real risks for severe neonatal outcomes, for all forms of diabetes – whether it exists before pregnancy or develops during pregnancy,” Dr. Pintaudi said in an interview. “It’s very important to detect both prepregnancy and gestational diabetes early and optimize maternal glucose levels as quickly as possible.”
He and his colleagues studied outcomes in 135,000 pregnancies included in an administrative database in the Italian Puglia region from 2002 to 2012. They found 1,357 singleton pregnancies complicated by gestational diabetes, and 234 by pregestational diabetes. They computed the risks of a number of neonatal outcomes in a multivariate analysis that controlled for hypertensive and thyroid disorders and for several drugs, including antithrombotics, antiplatelets, and ticlopidine. These drugs were chosen as indicators of high-risk pregnancy.
Both gestational and pregestational diabetes were associated with significantly higher risks of neonatal hypoglycemia (odds ratios, 10 and 36, respectively). They were also associated with significantly increased risks of a small for gestational age infant (ORs, 1.7 and 5.8), and large for gestational age infant (ORs, 1.7 and 7.9).
The risk of jaundice was also increased for both gestational and pregestational diabetes (ORs, 1.7 and 2.6).
Fetal malformations were more common in both disorders (ORs, 2.2 and 3.5). The database didn’t include specifics on what type of malformations occurred, but Dr. Pintaudi said prior studies show increases in cardiac and neural tube defects. This problem in particular illustrates the need for early screening and management of pregestational diabetes, he said in an interview.
“The pathophysiology of these malformations is such that they occur in the very early stages of pregnancy, before some women even know they might be pregnant,” he said.
Hypocalcemia and hypomagnesemia of the newborn were more likely in both gestational and pregestational diabetes (ORs, 1.8 and 9.2), as was Cesarean delivery (ORs, 1.9 and 8.5).
Pregestational diabetes alone was also associated with an increased risk of respiratory distress (OR, 2.7) and polyhydramnios (OR, 46.5).
Dr. Pintaudi said that Italy does not recommend universal diabetes screening for women who are or wish to become pregnant. The first evaluation occurs at 16-18 weeks’ gestation, with a repeat evaluation at 24-28 weeks.
He had no financial disclosures.
On Twitter @Alz_Gal
MUNICH – Pregestational maternal diabetes is even riskier for newborns than gestational diabetes, increasing the chance of neonatal hypoglycemia by 36 times over a normal pregnancy.
Baby’s blood sugar isn’t the only thing in danger, though, Basilio Pintaudi, MD, said at the European Association for the Study of Diabetes conference. Women with prepregnancy diabetes are significantly more likely to have babies that are either small or large for gestational age; become jaundiced; have congenital malformations; and experience respiratory distress, hypocalcemia, and hypomagnesemia, said Dr. Pintaudi of Niguarda Ca’ Granda Hospital, Milan.
“Everyone involved in the care of pregnant women should realize there are very real risks for severe neonatal outcomes, for all forms of diabetes – whether it exists before pregnancy or develops during pregnancy,” Dr. Pintaudi said in an interview. “It’s very important to detect both prepregnancy and gestational diabetes early and optimize maternal glucose levels as quickly as possible.”
He and his colleagues studied outcomes in 135,000 pregnancies included in an administrative database in the Italian Puglia region from 2002 to 2012. They found 1,357 singleton pregnancies complicated by gestational diabetes, and 234 by pregestational diabetes. They computed the risks of a number of neonatal outcomes in a multivariate analysis that controlled for hypertensive and thyroid disorders and for several drugs, including antithrombotics, antiplatelets, and ticlopidine. These drugs were chosen as indicators of high-risk pregnancy.
Both gestational and pregestational diabetes were associated with significantly higher risks of neonatal hypoglycemia (odds ratios, 10 and 36, respectively). They were also associated with significantly increased risks of a small for gestational age infant (ORs, 1.7 and 5.8), and large for gestational age infant (ORs, 1.7 and 7.9).
The risk of jaundice was also increased for both gestational and pregestational diabetes (ORs, 1.7 and 2.6).
Fetal malformations were more common in both disorders (ORs, 2.2 and 3.5). The database didn’t include specifics on what type of malformations occurred, but Dr. Pintaudi said prior studies show increases in cardiac and neural tube defects. This problem in particular illustrates the need for early screening and management of pregestational diabetes, he said in an interview.
“The pathophysiology of these malformations is such that they occur in the very early stages of pregnancy, before some women even know they might be pregnant,” he said.
Hypocalcemia and hypomagnesemia of the newborn were more likely in both gestational and pregestational diabetes (ORs, 1.8 and 9.2), as was Cesarean delivery (ORs, 1.9 and 8.5).
Pregestational diabetes alone was also associated with an increased risk of respiratory distress (OR, 2.7) and polyhydramnios (OR, 46.5).
Dr. Pintaudi said that Italy does not recommend universal diabetes screening for women who are or wish to become pregnant. The first evaluation occurs at 16-18 weeks’ gestation, with a repeat evaluation at 24-28 weeks.
He had no financial disclosures.
On Twitter @Alz_Gal
MUNICH – Pregestational maternal diabetes is even riskier for newborns than gestational diabetes, increasing the chance of neonatal hypoglycemia by 36 times over a normal pregnancy.
Baby’s blood sugar isn’t the only thing in danger, though, Basilio Pintaudi, MD, said at the European Association for the Study of Diabetes conference. Women with prepregnancy diabetes are significantly more likely to have babies that are either small or large for gestational age; become jaundiced; have congenital malformations; and experience respiratory distress, hypocalcemia, and hypomagnesemia, said Dr. Pintaudi of Niguarda Ca’ Granda Hospital, Milan.
“Everyone involved in the care of pregnant women should realize there are very real risks for severe neonatal outcomes, for all forms of diabetes – whether it exists before pregnancy or develops during pregnancy,” Dr. Pintaudi said in an interview. “It’s very important to detect both prepregnancy and gestational diabetes early and optimize maternal glucose levels as quickly as possible.”
He and his colleagues studied outcomes in 135,000 pregnancies included in an administrative database in the Italian Puglia region from 2002 to 2012. They found 1,357 singleton pregnancies complicated by gestational diabetes, and 234 by pregestational diabetes. They computed the risks of a number of neonatal outcomes in a multivariate analysis that controlled for hypertensive and thyroid disorders and for several drugs, including antithrombotics, antiplatelets, and ticlopidine. These drugs were chosen as indicators of high-risk pregnancy.
Both gestational and pregestational diabetes were associated with significantly higher risks of neonatal hypoglycemia (odds ratios, 10 and 36, respectively). They were also associated with significantly increased risks of a small for gestational age infant (ORs, 1.7 and 5.8), and large for gestational age infant (ORs, 1.7 and 7.9).
The risk of jaundice was also increased for both gestational and pregestational diabetes (ORs, 1.7 and 2.6).
Fetal malformations were more common in both disorders (ORs, 2.2 and 3.5). The database didn’t include specifics on what type of malformations occurred, but Dr. Pintaudi said prior studies show increases in cardiac and neural tube defects. This problem in particular illustrates the need for early screening and management of pregestational diabetes, he said in an interview.
“The pathophysiology of these malformations is such that they occur in the very early stages of pregnancy, before some women even know they might be pregnant,” he said.
Hypocalcemia and hypomagnesemia of the newborn were more likely in both gestational and pregestational diabetes (ORs, 1.8 and 9.2), as was Cesarean delivery (ORs, 1.9 and 8.5).
Pregestational diabetes alone was also associated with an increased risk of respiratory distress (OR, 2.7) and polyhydramnios (OR, 46.5).
Dr. Pintaudi said that Italy does not recommend universal diabetes screening for women who are or wish to become pregnant. The first evaluation occurs at 16-18 weeks’ gestation, with a repeat evaluation at 24-28 weeks.
He had no financial disclosures.
On Twitter @Alz_Gal
AT EASD 2016
Key clinical point: Pregestational and gestational diabetes increase the risk of a several poor neonatal outcomes.
Major finding: Pregestational diabetes increased the risk of neonatal hypoglycemia by 36 times; gestational diabetes by 10 times.
Data source: The database review comprised 135,000 singleton pregnancies.
Disclosures: Dr. Pintaudi had no financial disclosures.
Low doses may revive targeted therapy for chronic cough
LONDON – AF-219, a promising targeted therapy for chronic cough derailed by taste disturbances, has been revived by new studies suggesting that there is a therapeutic window that preserves benefits but reduces the risk of the adverse effect, according to new data presented at the annual congress of the European Respiratory Society.
The median duration of chronic cough of the patients on which the new data is based was 13 years. For patients with this type of durable cough history, there is a major unmet need for effective agents, reported Dr. Jacky Smith, MB, ChB, PhD, and professor of respiratory medicine at the University of Manchester (England).
The P2X3 antagonist AF-219 “is showing real promise as an antitussive agent when used at low doses,” Dr. Smith said.
P2X3 receptors are expressed by afferent neurons on the vagus nerves and appear to be a strong trigger of cough when stimulated, according to previous work by Dr. Smith and others. AF-219 is an oral antagonist of P2X3 and produced a 75% reduction in cough frequency when administered in a dose of 600 mg twice daily in a previously reported double-blind, placebo-controlled pilot study (Abdulqawi R et al. Lancet. 2015;385:1198-205). “However, there was a small wrinkle. All of the patients had taste disturbances. At this dose, it was primarily loss of taste,” Dr. Smith explained. As P2X3 is also found on neurons mediating taste, the adverse event was consistent with the mechanism of AF-219.
A series of studies have since been conducted to show that much lower doses than the twice-daily 600 mg dose employed in the original trial provide an antitussive effect but impose a much reduced risk of affecting taste.
In the latest dose-ranging study, 30 patients, who on average were aged 60 years, were randomized in a crossover design to receive placebo or active therapy in sequential doses over 4 days each of 7.5 mg, 15 mg, 30 mg, or 50 mg twice daily. At the end of the initial 16-day study period and a washout of 14 to 21 days, the patients who were initially randomized to placebo were evaluated on the sequential doses of active therapy, and those previously treated with active therapy took placebo.
On placebo, there was no change in cough frequency. On active therapy, there were incremental reductions in cough at 7.5 and 15 mg, but the differences relative to placebo did not reach statistical significance. Significant reductions in cough frequency relative to placebo were reached on both the 30 mg (P = 0.001) and the 50 mg dose (P = 0.002). The reductions on these two doses, however, were not significantly different from each other, suggesting that 30 mg may be an adequate dose to achieve clinically relevant antitussive benefits.
Taste disturbances, which were reported in 6.7% of patients taking both the 7.5 mg and 15 mg dose, increased to 46.7% in those taking the 30 mg dose and then to 53.3% of those taking the 50 mg dose. Lack of taste was only reported by 6.7% of those taking the 50 mg dose and none of those taking lower doses. Other adverse events, such as nasal dryness and rhinitis, were infrequent (less than 10%) and not dose related.
“Significantly lower doses than we originally tested appear to provide near maximum antitussive effects but with a much reduced risk of changes in taste,” Dr. Smith reported.
She added that in this dose-ranging study, there was a correlation between increasing dose and increasing cough-specific measures of quality of life.
“These data support a separation of the dose response relationships for antitussive effects and taste disturbance,” Dr. Smith reported. “Studies of longer duration are needed to test sustained efficacy and tolerability.”
LONDON – AF-219, a promising targeted therapy for chronic cough derailed by taste disturbances, has been revived by new studies suggesting that there is a therapeutic window that preserves benefits but reduces the risk of the adverse effect, according to new data presented at the annual congress of the European Respiratory Society.
The median duration of chronic cough of the patients on which the new data is based was 13 years. For patients with this type of durable cough history, there is a major unmet need for effective agents, reported Dr. Jacky Smith, MB, ChB, PhD, and professor of respiratory medicine at the University of Manchester (England).
The P2X3 antagonist AF-219 “is showing real promise as an antitussive agent when used at low doses,” Dr. Smith said.
P2X3 receptors are expressed by afferent neurons on the vagus nerves and appear to be a strong trigger of cough when stimulated, according to previous work by Dr. Smith and others. AF-219 is an oral antagonist of P2X3 and produced a 75% reduction in cough frequency when administered in a dose of 600 mg twice daily in a previously reported double-blind, placebo-controlled pilot study (Abdulqawi R et al. Lancet. 2015;385:1198-205). “However, there was a small wrinkle. All of the patients had taste disturbances. At this dose, it was primarily loss of taste,” Dr. Smith explained. As P2X3 is also found on neurons mediating taste, the adverse event was consistent with the mechanism of AF-219.
A series of studies have since been conducted to show that much lower doses than the twice-daily 600 mg dose employed in the original trial provide an antitussive effect but impose a much reduced risk of affecting taste.
In the latest dose-ranging study, 30 patients, who on average were aged 60 years, were randomized in a crossover design to receive placebo or active therapy in sequential doses over 4 days each of 7.5 mg, 15 mg, 30 mg, or 50 mg twice daily. At the end of the initial 16-day study period and a washout of 14 to 21 days, the patients who were initially randomized to placebo were evaluated on the sequential doses of active therapy, and those previously treated with active therapy took placebo.
On placebo, there was no change in cough frequency. On active therapy, there were incremental reductions in cough at 7.5 and 15 mg, but the differences relative to placebo did not reach statistical significance. Significant reductions in cough frequency relative to placebo were reached on both the 30 mg (P = 0.001) and the 50 mg dose (P = 0.002). The reductions on these two doses, however, were not significantly different from each other, suggesting that 30 mg may be an adequate dose to achieve clinically relevant antitussive benefits.
Taste disturbances, which were reported in 6.7% of patients taking both the 7.5 mg and 15 mg dose, increased to 46.7% in those taking the 30 mg dose and then to 53.3% of those taking the 50 mg dose. Lack of taste was only reported by 6.7% of those taking the 50 mg dose and none of those taking lower doses. Other adverse events, such as nasal dryness and rhinitis, were infrequent (less than 10%) and not dose related.
“Significantly lower doses than we originally tested appear to provide near maximum antitussive effects but with a much reduced risk of changes in taste,” Dr. Smith reported.
She added that in this dose-ranging study, there was a correlation between increasing dose and increasing cough-specific measures of quality of life.
“These data support a separation of the dose response relationships for antitussive effects and taste disturbance,” Dr. Smith reported. “Studies of longer duration are needed to test sustained efficacy and tolerability.”
LONDON – AF-219, a promising targeted therapy for chronic cough derailed by taste disturbances, has been revived by new studies suggesting that there is a therapeutic window that preserves benefits but reduces the risk of the adverse effect, according to new data presented at the annual congress of the European Respiratory Society.
The median duration of chronic cough of the patients on which the new data is based was 13 years. For patients with this type of durable cough history, there is a major unmet need for effective agents, reported Dr. Jacky Smith, MB, ChB, PhD, and professor of respiratory medicine at the University of Manchester (England).
The P2X3 antagonist AF-219 “is showing real promise as an antitussive agent when used at low doses,” Dr. Smith said.
P2X3 receptors are expressed by afferent neurons on the vagus nerves and appear to be a strong trigger of cough when stimulated, according to previous work by Dr. Smith and others. AF-219 is an oral antagonist of P2X3 and produced a 75% reduction in cough frequency when administered in a dose of 600 mg twice daily in a previously reported double-blind, placebo-controlled pilot study (Abdulqawi R et al. Lancet. 2015;385:1198-205). “However, there was a small wrinkle. All of the patients had taste disturbances. At this dose, it was primarily loss of taste,” Dr. Smith explained. As P2X3 is also found on neurons mediating taste, the adverse event was consistent with the mechanism of AF-219.
A series of studies have since been conducted to show that much lower doses than the twice-daily 600 mg dose employed in the original trial provide an antitussive effect but impose a much reduced risk of affecting taste.
In the latest dose-ranging study, 30 patients, who on average were aged 60 years, were randomized in a crossover design to receive placebo or active therapy in sequential doses over 4 days each of 7.5 mg, 15 mg, 30 mg, or 50 mg twice daily. At the end of the initial 16-day study period and a washout of 14 to 21 days, the patients who were initially randomized to placebo were evaluated on the sequential doses of active therapy, and those previously treated with active therapy took placebo.
On placebo, there was no change in cough frequency. On active therapy, there were incremental reductions in cough at 7.5 and 15 mg, but the differences relative to placebo did not reach statistical significance. Significant reductions in cough frequency relative to placebo were reached on both the 30 mg (P = 0.001) and the 50 mg dose (P = 0.002). The reductions on these two doses, however, were not significantly different from each other, suggesting that 30 mg may be an adequate dose to achieve clinically relevant antitussive benefits.
Taste disturbances, which were reported in 6.7% of patients taking both the 7.5 mg and 15 mg dose, increased to 46.7% in those taking the 30 mg dose and then to 53.3% of those taking the 50 mg dose. Lack of taste was only reported by 6.7% of those taking the 50 mg dose and none of those taking lower doses. Other adverse events, such as nasal dryness and rhinitis, were infrequent (less than 10%) and not dose related.
“Significantly lower doses than we originally tested appear to provide near maximum antitussive effects but with a much reduced risk of changes in taste,” Dr. Smith reported.
She added that in this dose-ranging study, there was a correlation between increasing dose and increasing cough-specific measures of quality of life.
“These data support a separation of the dose response relationships for antitussive effects and taste disturbance,” Dr. Smith reported. “Studies of longer duration are needed to test sustained efficacy and tolerability.”
AT THE EUROPEAN RESPIRATORY SOCIETY INTERNATIONAL CONGRESS 2016
Key clinical point: An effective therapy for chronic cough derailed for taste disturbances may be resurrected with low doses.
Major finding: The acceptable dose for the targeted P2X3 antagonist AF-219 appears to be 30 mg – a fraction of the dose evaluated in phase II trials.
Data source: A randomized, double-blind, placebo-controlled, crossover, dose-ranging study of 30 patients with a median cough duration of 13 years.
Disclosures: Dr. Smith reports that she has no relevant financial relationships.
Smoking thickens LV wall, worsens function
Current smoking, as well as higher levels of cumulative cigarette exposure from past smoking, were both associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function in an elderly community-based population with no overt indications of coronary artery disease or heart failure, according to a report published online Sept. 13 in Circulation: Cardiovascular Imaging.
“These findings suggest that smoking is associated with subtle alterations in LV structure and function, which might help explain the higher risk of heart failure [HF] reported for smokers, independent of coronary artery disease [CAD],” said Wilson Nadruz Jr., MD, of the cardiovascular division, Brigham and Women’s Hospital, Boston, and his associates.
They analyzed links between smoking and echocardiographic features using data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective observational study involving community-dwelling adults who were aged 45-64 years at baseline in 1987-1989. For their study, Dr. Nadruz and his colleagues assessed echocardiographic images taken for 4,580 ARIC participants at follow-up roughly 25 years later. None of these adults had any indication of CAD or HF; 287 (6.3%) were current smokers, 2,316 (50.5%) were former smokers, and 1,977 (43.2%) never smoked.
Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%), as well as a higher prevalence of concentric LV hypertrophy and worse LV diastolic function. The same association was found between never smokers and former smokers who had higher levels of cumulative cigarette exposure, the investigators said (Circ Cardiovasc Imag. 2016 Sep 13. doi: 10.1161/circimaging.116.004950).
This association between smoking and altered LV structure and function remained robust after the data were adjusted to account for numerous cardiac risk factors such as older age, higher BMI, diabetes, hypertension, greater alcohol consumption, and higher heart rate. It also didn’t vary by patient sex, race, or income level. In contrast, there was no association between smoking and right ventricular structure or function.
“These data suggest that smoking can independently lead to thickening of the heart and worsening of heart function, which may lead to a higher risk for heart failure, even in people who don’t have heart attacks,” Dr. Nadruz said in a statement.
Looking at the results in a more positive light, senior author Scott D. Solomon, MD, professor of medicine at Harvard University, Boston, said “The good news is that former smokers had similar heart structure and function, compared with never smokers,” suggesting that “the potential effects of tobacco on the myocardium might be reversible after smoking cessation.”
Current smoking, as well as higher levels of cumulative cigarette exposure from past smoking, were both associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function in an elderly community-based population with no overt indications of coronary artery disease or heart failure, according to a report published online Sept. 13 in Circulation: Cardiovascular Imaging.
“These findings suggest that smoking is associated with subtle alterations in LV structure and function, which might help explain the higher risk of heart failure [HF] reported for smokers, independent of coronary artery disease [CAD],” said Wilson Nadruz Jr., MD, of the cardiovascular division, Brigham and Women’s Hospital, Boston, and his associates.
They analyzed links between smoking and echocardiographic features using data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective observational study involving community-dwelling adults who were aged 45-64 years at baseline in 1987-1989. For their study, Dr. Nadruz and his colleagues assessed echocardiographic images taken for 4,580 ARIC participants at follow-up roughly 25 years later. None of these adults had any indication of CAD or HF; 287 (6.3%) were current smokers, 2,316 (50.5%) were former smokers, and 1,977 (43.2%) never smoked.
Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%), as well as a higher prevalence of concentric LV hypertrophy and worse LV diastolic function. The same association was found between never smokers and former smokers who had higher levels of cumulative cigarette exposure, the investigators said (Circ Cardiovasc Imag. 2016 Sep 13. doi: 10.1161/circimaging.116.004950).
This association between smoking and altered LV structure and function remained robust after the data were adjusted to account for numerous cardiac risk factors such as older age, higher BMI, diabetes, hypertension, greater alcohol consumption, and higher heart rate. It also didn’t vary by patient sex, race, or income level. In contrast, there was no association between smoking and right ventricular structure or function.
“These data suggest that smoking can independently lead to thickening of the heart and worsening of heart function, which may lead to a higher risk for heart failure, even in people who don’t have heart attacks,” Dr. Nadruz said in a statement.
Looking at the results in a more positive light, senior author Scott D. Solomon, MD, professor of medicine at Harvard University, Boston, said “The good news is that former smokers had similar heart structure and function, compared with never smokers,” suggesting that “the potential effects of tobacco on the myocardium might be reversible after smoking cessation.”
Current smoking, as well as higher levels of cumulative cigarette exposure from past smoking, were both associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function in an elderly community-based population with no overt indications of coronary artery disease or heart failure, according to a report published online Sept. 13 in Circulation: Cardiovascular Imaging.
“These findings suggest that smoking is associated with subtle alterations in LV structure and function, which might help explain the higher risk of heart failure [HF] reported for smokers, independent of coronary artery disease [CAD],” said Wilson Nadruz Jr., MD, of the cardiovascular division, Brigham and Women’s Hospital, Boston, and his associates.
They analyzed links between smoking and echocardiographic features using data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing prospective observational study involving community-dwelling adults who were aged 45-64 years at baseline in 1987-1989. For their study, Dr. Nadruz and his colleagues assessed echocardiographic images taken for 4,580 ARIC participants at follow-up roughly 25 years later. None of these adults had any indication of CAD or HF; 287 (6.3%) were current smokers, 2,316 (50.5%) were former smokers, and 1,977 (43.2%) never smoked.
Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%), as well as a higher prevalence of concentric LV hypertrophy and worse LV diastolic function. The same association was found between never smokers and former smokers who had higher levels of cumulative cigarette exposure, the investigators said (Circ Cardiovasc Imag. 2016 Sep 13. doi: 10.1161/circimaging.116.004950).
This association between smoking and altered LV structure and function remained robust after the data were adjusted to account for numerous cardiac risk factors such as older age, higher BMI, diabetes, hypertension, greater alcohol consumption, and higher heart rate. It also didn’t vary by patient sex, race, or income level. In contrast, there was no association between smoking and right ventricular structure or function.
“These data suggest that smoking can independently lead to thickening of the heart and worsening of heart function, which may lead to a higher risk for heart failure, even in people who don’t have heart attacks,” Dr. Nadruz said in a statement.
Looking at the results in a more positive light, senior author Scott D. Solomon, MD, professor of medicine at Harvard University, Boston, said “The good news is that former smokers had similar heart structure and function, compared with never smokers,” suggesting that “the potential effects of tobacco on the myocardium might be reversible after smoking cessation.”
FROM CIRCULATION: CARDIOVASCULAR IMAGING
Key clinical point: Current smoking was associated with higher left ventricular mass, a higher LV mass-to-volume ratio, and worse diastolic function.
Major finding: Compared with never smokers, current smokers showed a greater LV mass index (80.4 vs. 76.7), a greater LV mass-to-volume ratio (1.93 vs. 1.83), and a higher prevalence of LV hypertrophy (15% vs. 9%).
Data source: A secondary analysis of data for 4,580 elderly participants in ARIC, a large community-based cohort.
Disclosures: This study was supported by Brigham and Women’s Hospital, Boston. Dr. Nadruz and his associates reported having no relevant financial disclosures.
HIV research update: Late August 2016
A large volume of HIV and AIDS research enters the medical literature every month. It can be difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.
Emotion dysregulation in people with HIV/AIDS may interact with HIV symptom severity to negatively impact certain aspects of quality of life, according to a study in AIDS Care.
Concurrent multitype HPV infection is common in HIV-seropositive women and frequency rises as CD4 count declines, a recent study revealed, but multitype infection does not increase precancer risk.
A study published in HIV Clinical Trials found an association between increased homocysteine plasma level and shortened prothrombin time in HIV-infected patients.
Lower levels of gamma-linolenic acid are associated with lower CD4 counts in HIV patients and an increased risk of death or hospitalization, a recent study revealed. The authors said the results suggest a potential for using n6-fatty acids to improve outcomes from antiretroviral therapy.
A recent study found that the early spread of HIV virus from blood plasma to genital tract, and the complex viral interplay between these compartments, suggests that viral eradication efforts will require monitoring viral subpopulations in anatomic sites and viral trafficking during the course of infection.
A study of aviremic HIV-2–infected individuals in Guinea-Bissau revealed that increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men could be effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in selected hepatitis C virus mono- and HIV-HCV–coinfected patients in a real-world setting.
A study of antiretroviral treatment in Swaziland found the attrition rate to be 10.3% in 16,423 participants that initiated ART in 2012.
Mycobacterium tuberculosis in HIV-infected patients had lower expression of the DosR regulon genes, a critical metabolic and immunomodulatory switch induced by nitric oxide, carbon monoxide, and hypoxia, according to a study in the Journal of Infectious Diseases.
The influence of the Affordable Care Act on insurance coverage for HIV patients and other factors affecting HIV care likely varies by jurisdiction, reported a study in AIDS Care.
A Danish study found that HIV-exposed uninfected children had an increased risk of overall hospital admission mainly due to observation/nonspecific diagnoses, not to infectious disease.
A recent study found that mobile technology is a promising approach to intervention delivery for both younger and older HIV-positive black men who have sex with men.
Interventions or programmatic decisions regarding preconception counseling methods for young women living with HIV are necessary and potentially transferable between populations, new research suggests.
A meta-analysis in HIV Medicine found that the life expectancy of HIV-positive people after starting combination antiretroviral therapy (cART) improved over time. The authors said monitoring life expectancy into the future is important to assess how changes to cART guidelines will affect patient long-term outcomes.
Involving people living with HIV/AIDS as patient instructors (PHA-PIs) reduced HIV-related stigma among medical students and increased comfort in providing HIV-related care, according to a study published in AIDS Care.
A recent study found a benefit of antidepressant treatment in people with HIV, depression, and alcohol use, and found no evidence that either alcohol use or illicit drug use moderates the antidepressant treatment response.
It is possible to successfully integrate a patient retention protocol into the existing infrastructure of an HIV clinic and reengage a majority of out-of-care patients into medical care, according to investigators in North Carolina.
On Twitter @richpizzi
A large volume of HIV and AIDS research enters the medical literature every month. It can be difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.
Emotion dysregulation in people with HIV/AIDS may interact with HIV symptom severity to negatively impact certain aspects of quality of life, according to a study in AIDS Care.
Concurrent multitype HPV infection is common in HIV-seropositive women and frequency rises as CD4 count declines, a recent study revealed, but multitype infection does not increase precancer risk.
A study published in HIV Clinical Trials found an association between increased homocysteine plasma level and shortened prothrombin time in HIV-infected patients.
Lower levels of gamma-linolenic acid are associated with lower CD4 counts in HIV patients and an increased risk of death or hospitalization, a recent study revealed. The authors said the results suggest a potential for using n6-fatty acids to improve outcomes from antiretroviral therapy.
A recent study found that the early spread of HIV virus from blood plasma to genital tract, and the complex viral interplay between these compartments, suggests that viral eradication efforts will require monitoring viral subpopulations in anatomic sites and viral trafficking during the course of infection.
A study of aviremic HIV-2–infected individuals in Guinea-Bissau revealed that increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men could be effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in selected hepatitis C virus mono- and HIV-HCV–coinfected patients in a real-world setting.
A study of antiretroviral treatment in Swaziland found the attrition rate to be 10.3% in 16,423 participants that initiated ART in 2012.
Mycobacterium tuberculosis in HIV-infected patients had lower expression of the DosR regulon genes, a critical metabolic and immunomodulatory switch induced by nitric oxide, carbon monoxide, and hypoxia, according to a study in the Journal of Infectious Diseases.
The influence of the Affordable Care Act on insurance coverage for HIV patients and other factors affecting HIV care likely varies by jurisdiction, reported a study in AIDS Care.
A Danish study found that HIV-exposed uninfected children had an increased risk of overall hospital admission mainly due to observation/nonspecific diagnoses, not to infectious disease.
A recent study found that mobile technology is a promising approach to intervention delivery for both younger and older HIV-positive black men who have sex with men.
Interventions or programmatic decisions regarding preconception counseling methods for young women living with HIV are necessary and potentially transferable between populations, new research suggests.
A meta-analysis in HIV Medicine found that the life expectancy of HIV-positive people after starting combination antiretroviral therapy (cART) improved over time. The authors said monitoring life expectancy into the future is important to assess how changes to cART guidelines will affect patient long-term outcomes.
Involving people living with HIV/AIDS as patient instructors (PHA-PIs) reduced HIV-related stigma among medical students and increased comfort in providing HIV-related care, according to a study published in AIDS Care.
A recent study found a benefit of antidepressant treatment in people with HIV, depression, and alcohol use, and found no evidence that either alcohol use or illicit drug use moderates the antidepressant treatment response.
It is possible to successfully integrate a patient retention protocol into the existing infrastructure of an HIV clinic and reengage a majority of out-of-care patients into medical care, according to investigators in North Carolina.
On Twitter @richpizzi
A large volume of HIV and AIDS research enters the medical literature every month. It can be difficult to monitor everything, so here’s a quick look at some notable news items and journal articles published over the past few weeks.
Emotion dysregulation in people with HIV/AIDS may interact with HIV symptom severity to negatively impact certain aspects of quality of life, according to a study in AIDS Care.
Concurrent multitype HPV infection is common in HIV-seropositive women and frequency rises as CD4 count declines, a recent study revealed, but multitype infection does not increase precancer risk.
A study published in HIV Clinical Trials found an association between increased homocysteine plasma level and shortened prothrombin time in HIV-infected patients.
Lower levels of gamma-linolenic acid are associated with lower CD4 counts in HIV patients and an increased risk of death or hospitalization, a recent study revealed. The authors said the results suggest a potential for using n6-fatty acids to improve outcomes from antiretroviral therapy.
A recent study found that the early spread of HIV virus from blood plasma to genital tract, and the complex viral interplay between these compartments, suggests that viral eradication efforts will require monitoring viral subpopulations in anatomic sites and viral trafficking during the course of infection.
A study of aviremic HIV-2–infected individuals in Guinea-Bissau revealed that increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency.
Treatment interventions to curb the hepatitis C virus epidemic among HIV-infected men who have sex with men could be effective if high-risk behavior does not increase as it has during the last decade, according to a study in Hepatology.
A German study found that short treatment with 8 weeks of sofosbuvir and ledipasvir seems highly effective and safe in selected hepatitis C virus mono- and HIV-HCV–coinfected patients in a real-world setting.
A study of antiretroviral treatment in Swaziland found the attrition rate to be 10.3% in 16,423 participants that initiated ART in 2012.
Mycobacterium tuberculosis in HIV-infected patients had lower expression of the DosR regulon genes, a critical metabolic and immunomodulatory switch induced by nitric oxide, carbon monoxide, and hypoxia, according to a study in the Journal of Infectious Diseases.
The influence of the Affordable Care Act on insurance coverage for HIV patients and other factors affecting HIV care likely varies by jurisdiction, reported a study in AIDS Care.
A Danish study found that HIV-exposed uninfected children had an increased risk of overall hospital admission mainly due to observation/nonspecific diagnoses, not to infectious disease.
A recent study found that mobile technology is a promising approach to intervention delivery for both younger and older HIV-positive black men who have sex with men.
Interventions or programmatic decisions regarding preconception counseling methods for young women living with HIV are necessary and potentially transferable between populations, new research suggests.
A meta-analysis in HIV Medicine found that the life expectancy of HIV-positive people after starting combination antiretroviral therapy (cART) improved over time. The authors said monitoring life expectancy into the future is important to assess how changes to cART guidelines will affect patient long-term outcomes.
Involving people living with HIV/AIDS as patient instructors (PHA-PIs) reduced HIV-related stigma among medical students and increased comfort in providing HIV-related care, according to a study published in AIDS Care.
A recent study found a benefit of antidepressant treatment in people with HIV, depression, and alcohol use, and found no evidence that either alcohol use or illicit drug use moderates the antidepressant treatment response.
It is possible to successfully integrate a patient retention protocol into the existing infrastructure of an HIV clinic and reengage a majority of out-of-care patients into medical care, according to investigators in North Carolina.
On Twitter @richpizzi
Alternative options for visualizing ureteral patency during intraoperative cystoscopy
For more videos from the Society of Gynecologic Surgeons, click here
Visit the Society of Gynecologic Surgeons online: sgsonline.org
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- Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
- Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
- Laparoscopic cystectomy for large, bilateral ovarian dermoids
For more videos from the Society of Gynecologic Surgeons, click here
Visit the Society of Gynecologic Surgeons online: sgsonline.org
Related Articles:
- Use of suprapubic Carter-Thomason needle to assist in cystoscopic excision of an intravesical foreign object
- Uterine artery ligation: Advanced techniques and considerations for the difficult laparoscopic hysterectomy
- Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
- Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
- Laparoscopic cystectomy for large, bilateral ovarian dermoids
For more videos from the Society of Gynecologic Surgeons, click here
Visit the Society of Gynecologic Surgeons online: sgsonline.org
Related Articles:
- Use of suprapubic Carter-Thomason needle to assist in cystoscopic excision of an intravesical foreign object
- Uterine artery ligation: Advanced techniques and considerations for the difficult laparoscopic hysterectomy
- Cervical injection of methylene blue for identification of sentinel lymph nodes in cervical cancer
- Misplaced hysteroscopic sterilization micro-insert in the peritoneal cavity: A corpus alienum
- Laparoscopic cystectomy for large, bilateral ovarian dermoids
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Meta-analysis suggests earlier twin delivery to prevent stillbirth
Delivery for uncomplicated dichorionic twin pregnancies should be considered at 37 weeks’ gestation, a week earlier than is generally recommended in the United States, according to a systematic review and meta-analysis of studies that reported rates of stillbirth and neonatal mortality at various gestational ages.
The researchers assessed the competing risks in twin pregnancies of stillbirth from expectant management versus neonatal death from early delivery, looking for an optimal gestational age at which these risks were balanced.
In dichorionic pregnancies continuing beyond 34 weeks, these perinatal risks were balanced at 37 weeks. Beyond that, “the risks of stillbirth significantly outweighed the risk of neonatal death from delivery,” with a 1-week delay in delivery (to 38 weeks’ gestation) leading to an additional 8.8 perinatal deaths per 1,000 pregnancies due to an increase in stillbirth, Fiona Cheong-See, MD, of the Queen Mary University of London and her colleagues reported (BMJ 2016;354:i4353. doi: 10.1136/bmj.i4353).
The review included 32 studies published in the past 10 years (observational cohort studies and cohorts nested in randomized studies) that reported rates of stillbirth and/or neonatal outcomes, including neonatal mortality, in monochorionic and/or dichorionic twins. Neonatal death was defined as death up to 28 days after delivery.
The study authors shared unpublished aggregate and individual patient data with the meta-analysis researchers, which enabled an analysis at weekly intervals. The data included in the review covered 35,171 women with twin gestations (29,685 dichorionic and 5,486 monochorionic pregnancies).
Pregnancies with unclear chorionicity, monoamnionity, and twin-to-twin transfusion syndrome were excluded from the analysis.
In monochorionic pregnancies continuing beyond 34 weeks (2,149 pregnancies), there was a trend after 36 weeks toward stillbirth risk being higher than the risk of neonatal death, but the risk difference was not significant.
More data are needed, the researchers said, but “based on our findings, there is no clear evidence to recommend early preterm delivery routinely before 36 weeks in monochorionic pregnancies.”
A committee opinion published by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine (ACOG-SMFM) on medically indicated late-preterm and early-term deliveries states that decisions regarding the timing of delivery should be individualized and should take into account relative maternal and newborn risks, practice environment, and patient preferences (Obstet Gynecol. 2013;121:908-10).
Still, the ACOG-SMFM document offers delivery recommendations: 38 0/7-38 6/7 weeks of gestation for dichorionic-diamniotic pregnancies, and 34 0/7-36 6/7 weeks of gestation for monochorionic-diamniotic pregnancies.
The opinion was published in 2013 and reflects recommendations made 2 years earlier by the National Institute of Child Health and Human Development and SMFM after a workshop on indicated preterm birth (Obstet Gynecol 2011;118:323-33). ACOG and SMFM reaffirmed their document in 2015.
Brigid McCue, MD, chief of ob.gyn. at Beth Israel Deaconess Hospital–Plymouth (Mass.) and a member of ACOG’s Committee on Obstetric Practice, said the meta-analysis is of “high quality,” with “helpful and valid” findings for dichorionic twins.
The risk of stillbirth was 1.2/1,000 pregnancies at 34 weeks’ gestation, while the risk of neonatal death from delivery was 6.7/1,000 pregnancies. The risk of stillbirth remained significantly lower than the risk of neonatal death from delivery at 35 weeks, and was lower at 36 weeks as well. At 37 weeks, the two categories of perinatal death risk were basically balanced, with the risk of stillbirth at 3.4/1,000 pregnancies.
Beyond that, at 38 weeks’ gestation, the risk of stillbirth (10.6/1,000) significantly outweighed the risk of neonatal death from delivery (1.5/1,000) for a pooled risk difference of 8.8.
“The finding that stillbirth risk is higher when you allow someone to go from 37 to 38 weeks – I think this is true,” Dr. McCue said in an interview.
Further research needs to account, however, for the risks of neonatal morbidity at 37 and 38 weeks. “The next question in coming up with a point of inflection is to ask, What are other contributors to the balance of timing of the delivery?” Dr. McCue said. “There’s a bigger picture that needs more analysis.”
“We don’t induce singletons prior to 39 weeks because they can have more respiratory distress, more hypoglycemia, more temperature instability, and less success breastfeeding, for example,” she added. “These complications pale in comparison to a stillbirth, but the numbers of stillbirth are so low and the numbers for [these other morbidities] are much higher.”
The authors of the meta-analysis noted that their findings were limited by the common policy of planned delivery beyond 37 and 38 weeks’ gestation. “This reduced the sample size near term, particularly in monochorionic pregnancies, and could have led to underestimation of risk of stillbirth in the last weeks of pregnancy,” they wrote.
The rates of assisted ventilation, respiratory distress syndrome, admission to the neonatal intensive care unit, and septicemia showed a consistent reduction with increasing gestational age in babies of both monochorionic and dichorionic pregnancies, the researchers noted.
The researchers reported that they received no funding support from any organization and had no relevant financial disclosures.
Delivery for uncomplicated dichorionic twin pregnancies should be considered at 37 weeks’ gestation, a week earlier than is generally recommended in the United States, according to a systematic review and meta-analysis of studies that reported rates of stillbirth and neonatal mortality at various gestational ages.
The researchers assessed the competing risks in twin pregnancies of stillbirth from expectant management versus neonatal death from early delivery, looking for an optimal gestational age at which these risks were balanced.
In dichorionic pregnancies continuing beyond 34 weeks, these perinatal risks were balanced at 37 weeks. Beyond that, “the risks of stillbirth significantly outweighed the risk of neonatal death from delivery,” with a 1-week delay in delivery (to 38 weeks’ gestation) leading to an additional 8.8 perinatal deaths per 1,000 pregnancies due to an increase in stillbirth, Fiona Cheong-See, MD, of the Queen Mary University of London and her colleagues reported (BMJ 2016;354:i4353. doi: 10.1136/bmj.i4353).
The review included 32 studies published in the past 10 years (observational cohort studies and cohorts nested in randomized studies) that reported rates of stillbirth and/or neonatal outcomes, including neonatal mortality, in monochorionic and/or dichorionic twins. Neonatal death was defined as death up to 28 days after delivery.
The study authors shared unpublished aggregate and individual patient data with the meta-analysis researchers, which enabled an analysis at weekly intervals. The data included in the review covered 35,171 women with twin gestations (29,685 dichorionic and 5,486 monochorionic pregnancies).
Pregnancies with unclear chorionicity, monoamnionity, and twin-to-twin transfusion syndrome were excluded from the analysis.
In monochorionic pregnancies continuing beyond 34 weeks (2,149 pregnancies), there was a trend after 36 weeks toward stillbirth risk being higher than the risk of neonatal death, but the risk difference was not significant.
More data are needed, the researchers said, but “based on our findings, there is no clear evidence to recommend early preterm delivery routinely before 36 weeks in monochorionic pregnancies.”
A committee opinion published by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine (ACOG-SMFM) on medically indicated late-preterm and early-term deliveries states that decisions regarding the timing of delivery should be individualized and should take into account relative maternal and newborn risks, practice environment, and patient preferences (Obstet Gynecol. 2013;121:908-10).
Still, the ACOG-SMFM document offers delivery recommendations: 38 0/7-38 6/7 weeks of gestation for dichorionic-diamniotic pregnancies, and 34 0/7-36 6/7 weeks of gestation for monochorionic-diamniotic pregnancies.
The opinion was published in 2013 and reflects recommendations made 2 years earlier by the National Institute of Child Health and Human Development and SMFM after a workshop on indicated preterm birth (Obstet Gynecol 2011;118:323-33). ACOG and SMFM reaffirmed their document in 2015.
Brigid McCue, MD, chief of ob.gyn. at Beth Israel Deaconess Hospital–Plymouth (Mass.) and a member of ACOG’s Committee on Obstetric Practice, said the meta-analysis is of “high quality,” with “helpful and valid” findings for dichorionic twins.
The risk of stillbirth was 1.2/1,000 pregnancies at 34 weeks’ gestation, while the risk of neonatal death from delivery was 6.7/1,000 pregnancies. The risk of stillbirth remained significantly lower than the risk of neonatal death from delivery at 35 weeks, and was lower at 36 weeks as well. At 37 weeks, the two categories of perinatal death risk were basically balanced, with the risk of stillbirth at 3.4/1,000 pregnancies.
Beyond that, at 38 weeks’ gestation, the risk of stillbirth (10.6/1,000) significantly outweighed the risk of neonatal death from delivery (1.5/1,000) for a pooled risk difference of 8.8.
“The finding that stillbirth risk is higher when you allow someone to go from 37 to 38 weeks – I think this is true,” Dr. McCue said in an interview.
Further research needs to account, however, for the risks of neonatal morbidity at 37 and 38 weeks. “The next question in coming up with a point of inflection is to ask, What are other contributors to the balance of timing of the delivery?” Dr. McCue said. “There’s a bigger picture that needs more analysis.”
“We don’t induce singletons prior to 39 weeks because they can have more respiratory distress, more hypoglycemia, more temperature instability, and less success breastfeeding, for example,” she added. “These complications pale in comparison to a stillbirth, but the numbers of stillbirth are so low and the numbers for [these other morbidities] are much higher.”
The authors of the meta-analysis noted that their findings were limited by the common policy of planned delivery beyond 37 and 38 weeks’ gestation. “This reduced the sample size near term, particularly in monochorionic pregnancies, and could have led to underestimation of risk of stillbirth in the last weeks of pregnancy,” they wrote.
The rates of assisted ventilation, respiratory distress syndrome, admission to the neonatal intensive care unit, and septicemia showed a consistent reduction with increasing gestational age in babies of both monochorionic and dichorionic pregnancies, the researchers noted.
The researchers reported that they received no funding support from any organization and had no relevant financial disclosures.
Delivery for uncomplicated dichorionic twin pregnancies should be considered at 37 weeks’ gestation, a week earlier than is generally recommended in the United States, according to a systematic review and meta-analysis of studies that reported rates of stillbirth and neonatal mortality at various gestational ages.
The researchers assessed the competing risks in twin pregnancies of stillbirth from expectant management versus neonatal death from early delivery, looking for an optimal gestational age at which these risks were balanced.
In dichorionic pregnancies continuing beyond 34 weeks, these perinatal risks were balanced at 37 weeks. Beyond that, “the risks of stillbirth significantly outweighed the risk of neonatal death from delivery,” with a 1-week delay in delivery (to 38 weeks’ gestation) leading to an additional 8.8 perinatal deaths per 1,000 pregnancies due to an increase in stillbirth, Fiona Cheong-See, MD, of the Queen Mary University of London and her colleagues reported (BMJ 2016;354:i4353. doi: 10.1136/bmj.i4353).
The review included 32 studies published in the past 10 years (observational cohort studies and cohorts nested in randomized studies) that reported rates of stillbirth and/or neonatal outcomes, including neonatal mortality, in monochorionic and/or dichorionic twins. Neonatal death was defined as death up to 28 days after delivery.
The study authors shared unpublished aggregate and individual patient data with the meta-analysis researchers, which enabled an analysis at weekly intervals. The data included in the review covered 35,171 women with twin gestations (29,685 dichorionic and 5,486 monochorionic pregnancies).
Pregnancies with unclear chorionicity, monoamnionity, and twin-to-twin transfusion syndrome were excluded from the analysis.
In monochorionic pregnancies continuing beyond 34 weeks (2,149 pregnancies), there was a trend after 36 weeks toward stillbirth risk being higher than the risk of neonatal death, but the risk difference was not significant.
More data are needed, the researchers said, but “based on our findings, there is no clear evidence to recommend early preterm delivery routinely before 36 weeks in monochorionic pregnancies.”
A committee opinion published by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine (ACOG-SMFM) on medically indicated late-preterm and early-term deliveries states that decisions regarding the timing of delivery should be individualized and should take into account relative maternal and newborn risks, practice environment, and patient preferences (Obstet Gynecol. 2013;121:908-10).
Still, the ACOG-SMFM document offers delivery recommendations: 38 0/7-38 6/7 weeks of gestation for dichorionic-diamniotic pregnancies, and 34 0/7-36 6/7 weeks of gestation for monochorionic-diamniotic pregnancies.
The opinion was published in 2013 and reflects recommendations made 2 years earlier by the National Institute of Child Health and Human Development and SMFM after a workshop on indicated preterm birth (Obstet Gynecol 2011;118:323-33). ACOG and SMFM reaffirmed their document in 2015.
Brigid McCue, MD, chief of ob.gyn. at Beth Israel Deaconess Hospital–Plymouth (Mass.) and a member of ACOG’s Committee on Obstetric Practice, said the meta-analysis is of “high quality,” with “helpful and valid” findings for dichorionic twins.
The risk of stillbirth was 1.2/1,000 pregnancies at 34 weeks’ gestation, while the risk of neonatal death from delivery was 6.7/1,000 pregnancies. The risk of stillbirth remained significantly lower than the risk of neonatal death from delivery at 35 weeks, and was lower at 36 weeks as well. At 37 weeks, the two categories of perinatal death risk were basically balanced, with the risk of stillbirth at 3.4/1,000 pregnancies.
Beyond that, at 38 weeks’ gestation, the risk of stillbirth (10.6/1,000) significantly outweighed the risk of neonatal death from delivery (1.5/1,000) for a pooled risk difference of 8.8.
“The finding that stillbirth risk is higher when you allow someone to go from 37 to 38 weeks – I think this is true,” Dr. McCue said in an interview.
Further research needs to account, however, for the risks of neonatal morbidity at 37 and 38 weeks. “The next question in coming up with a point of inflection is to ask, What are other contributors to the balance of timing of the delivery?” Dr. McCue said. “There’s a bigger picture that needs more analysis.”
“We don’t induce singletons prior to 39 weeks because they can have more respiratory distress, more hypoglycemia, more temperature instability, and less success breastfeeding, for example,” she added. “These complications pale in comparison to a stillbirth, but the numbers of stillbirth are so low and the numbers for [these other morbidities] are much higher.”
The authors of the meta-analysis noted that their findings were limited by the common policy of planned delivery beyond 37 and 38 weeks’ gestation. “This reduced the sample size near term, particularly in monochorionic pregnancies, and could have led to underestimation of risk of stillbirth in the last weeks of pregnancy,” they wrote.
The rates of assisted ventilation, respiratory distress syndrome, admission to the neonatal intensive care unit, and septicemia showed a consistent reduction with increasing gestational age in babies of both monochorionic and dichorionic pregnancies, the researchers noted.
The researchers reported that they received no funding support from any organization and had no relevant financial disclosures.
FROM BMJ
Key clinical point: Delivery of uncomplicated dichorionic twin pregnancies at 37 weeks’ gestation could minimize perinatal deaths.
Major finding: A delay in delivery to 38 weeks’ gestation led to an additional 8.8 perinatal deaths per 1,000 pregnancies because of an increase in stillbirth.
Data source: A systematic review and meta-analysis of 32 studies.
Disclosures: The researchers reported that they received no funding support from any organization and had no relevant financial disclosures.
