From the Cleveland Clinic Journal of Medicine

This article has been removed from the website. The article was prepared by the editorial staff based on a transcript of the proceedings of a conference, and errors occurred during this process that were subsequently published. A clarification of the errors will be published in a future issue.

A review of this topic was published in the December 2017 issue of the Journal (Donnelly JP, Hanna M. Cardiac amyloidosis: An update on diagnosis and treatment. Cleve Clin J Med 2017;84[12suppl 3]:12–26). doi:10.3949/ccjm.84.s3.02

From the Cleveland Clinic Journal of Medicine

This article has been removed from the website. The article was prepared by the editorial staff based on a transcript of the proceedings of a conference, and errors occurred during this process that were subsequently published. A clarification of the errors will be published in a future issue.

A review of this topic was published in the December 2017 issue of the Journal (Donnelly JP, Hanna M. Cardiac amyloidosis: An update on diagnosis and treatment. Cleve Clin J Med 2017;84[12suppl 3]:12–26). doi:10.3949/ccjm.84.s3.02

From the Cleveland Clinic Journal of Medicine

This article has been removed from the website. The article was prepared by the editorial staff based on a transcript of the proceedings of a conference, and errors occurred during this process that were subsequently published. A clarification of the errors will be published in a future issue.

A review of this topic was published in the December 2017 issue of the Journal (Donnelly JP, Hanna M. Cardiac amyloidosis: An update on diagnosis and treatment. Cleve Clin J Med 2017;84[12suppl 3]:12–26). doi:10.3949/ccjm.84.s3.02

The FP recognized this as a probable squamous cell carcinoma (SCC) arising in a burn, known as a Marjolin ulcer.

The combination of the burn and the location on the lower lip made it extremely likely that this lesion was an SCC. The FP suggested the patient get a biopsy and have surgery for treatment. Unfortunately, the patient lived in poverty with no health insurance, financial means, running water, or electricity and stated that she could not afford any medical treatment. Her local hospital required cash payments, and she did not believe they would help her without funding and hoped that the medical mission team could help her. The FP was saddened by this news, but suggested that she do her best to access treatment in the near future. The FP did not have access to a pathologist (even if he could do the biopsy). Ultimately, the patient would need an experienced surgeon to excise this SCC.

With close to 1 billion people living in extreme poverty in the world, this is one sad example of a person that likely went without medical care for a serious, but treatable, illness.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP recognized this as a probable squamous cell carcinoma (SCC) arising in a burn, known as a Marjolin ulcer.

The combination of the burn and the location on the lower lip made it extremely likely that this lesion was an SCC. The FP suggested the patient get a biopsy and have surgery for treatment. Unfortunately, the patient lived in poverty with no health insurance, financial means, running water, or electricity and stated that she could not afford any medical treatment. Her local hospital required cash payments, and she did not believe they would help her without funding and hoped that the medical mission team could help her. The FP was saddened by this news, but suggested that she do her best to access treatment in the near future. The FP did not have access to a pathologist (even if he could do the biopsy). Ultimately, the patient would need an experienced surgeon to excise this SCC.

With close to 1 billion people living in extreme poverty in the world, this is one sad example of a person that likely went without medical care for a serious, but treatable, illness.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The FP recognized this as a probable squamous cell carcinoma (SCC) arising in a burn, known as a Marjolin ulcer.

The combination of the burn and the location on the lower lip made it extremely likely that this lesion was an SCC. The FP suggested the patient get a biopsy and have surgery for treatment. Unfortunately, the patient lived in poverty with no health insurance, financial means, running water, or electricity and stated that she could not afford any medical treatment. Her local hospital required cash payments, and she did not believe they would help her without funding and hoped that the medical mission team could help her. The FP was saddened by this news, but suggested that she do her best to access treatment in the near future. The FP did not have access to a pathologist (even if he could do the biopsy). Ultimately, the patient would need an experienced surgeon to excise this SCC.

With close to 1 billion people living in extreme poverty in the world, this is one sad example of a person that likely went without medical care for a serious, but treatable, illness.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Squamous cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:999-1007.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

In this masterclass edition, Joseph Goldberg, MD, gives a talk on the first episode of major depression. Dr. Goldberg is a clinical professor of psychiatry at the Ichan school of medicine at Mount Sinai in New York City.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

In this masterclass edition, Joseph Goldberg, MD, gives a talk on the first episode of major depression. Dr. Goldberg is a clinical professor of psychiatry at the Ichan school of medicine at Mount Sinai in New York City.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

In this masterclass edition, Joseph Goldberg, MD, gives a talk on the first episode of major depression. Dr. Goldberg is a clinical professor of psychiatry at the Ichan school of medicine at Mount Sinai in New York City.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Electronic health records predict physician burnout. Also today, a new risk-prediction model for diabetes under development, firibastat is looking good for difficult-to-treat hypertension, and differences in gut bacteria can distinguish IBD from IBS.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Electronic health records predict physician burnout. Also today, a new risk-prediction model for diabetes under development, firibastat is looking good for difficult-to-treat hypertension, and differences in gut bacteria can distinguish IBD from IBS.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Electronic health records predict physician burnout. Also today, a new risk-prediction model for diabetes under development, firibastat is looking good for difficult-to-treat hypertension, and differences in gut bacteria can distinguish IBD from IBS.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Photo by Bill Branson

The U.S. Food and Drug Administration (FDA) has approved a second pediatric indication for dasatinib (Sprycel®).

The tyrosine kinase inhibitor is now approved for use in combination with chemotherapy to treat pediatric patients age 1 year and older who have newly diagnosed, Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).

Dasatinib is also FDA-approved for use in children age 1 year and older who have chronic phase, Ph+ chronic myeloid leukemia (CML).

In adults, dasatinib is FDA-approved to treat:

• Newly diagnosed, Ph+, chronic phase CML
• Chronic, accelerated, or myeloid/lymphoid blast phase, Ph+ CML with resistance or intolerance to prior therapy including imatinib
• Ph+ ALL with resistance or intolerance to prior therapy.

Trial results

The FDA’s approval of dasatinib in children with Ph+ ALL is based on data from a phase 2 study (CA180-372, NCT01460160).

In this trial, researchers evaluated dasatinib in combination with the AIEOP-BFM ALL 2000 chemotherapy protocol in patients (ages 1 to 17) with newly diagnosed, B-cell precursor, Ph+ ALL.

There were 78 patients evaluated for efficacy in cohort 1. They had a median age of 10.4 years (range, 2.6 to 17.9 years). They received dasatinib at a daily dose of 60 mg/m² for up to 24 months.

Patients with central nervous system 3 disease received cranial irradiation, and patients were assigned to stem cell transplant based on minimal residual disease if they were thought to have a high risk of relapse.

The 3-year event-free survival rate in the 78 patients was 64.1%.

There were 81 patients evaluable for safety who received dasatinib continuously in combination with chemotherapy. Their median duration of treatment was 24 months (range, 2 to 27 months).

The most common adverse events (AEs) in these patients were mucositis (93%), febrile neutropenia (86%), pyrexia (85%), diarrhea (84%), nausea (84%), vomiting (83%), musculoskeletal pain (83%), abdominal pain (78%), cough (78%), headache (77%), rash (68%), fatigue (59%), and constipation (57%).

Eight (10%) patients had AEs leading to treatment discontinuation. These included fungal sepsis, hepatotoxicity in the setting of graft-versus-host disease, thrombocytopenia, cytomegalovirus infection, pneumonia, nausea, enteritis, and drug hypersensitivity.

Three patients (4%) had fatal AEs, all infections.

This trial was sponsored by Bristol-Myers Squibb. Additional data are available in the prescribing information for dasatinib.

Photo by Bill Branson

The U.S. Food and Drug Administration (FDA) has approved a second pediatric indication for dasatinib (Sprycel®).

The tyrosine kinase inhibitor is now approved for use in combination with chemotherapy to treat pediatric patients age 1 year and older who have newly diagnosed, Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).

Dasatinib is also FDA-approved for use in children age 1 year and older who have chronic phase, Ph+ chronic myeloid leukemia (CML).

In adults, dasatinib is FDA-approved to treat:

• Newly diagnosed, Ph+, chronic phase CML
• Chronic, accelerated, or myeloid/lymphoid blast phase, Ph+ CML with resistance or intolerance to prior therapy including imatinib
• Ph+ ALL with resistance or intolerance to prior therapy.

Trial results

The FDA’s approval of dasatinib in children with Ph+ ALL is based on data from a phase 2 study (CA180-372, NCT01460160).

In this trial, researchers evaluated dasatinib in combination with the AIEOP-BFM ALL 2000 chemotherapy protocol in patients (ages 1 to 17) with newly diagnosed, B-cell precursor, Ph+ ALL.

There were 78 patients evaluated for efficacy in cohort 1. They had a median age of 10.4 years (range, 2.6 to 17.9 years). They received dasatinib at a daily dose of 60 mg/m² for up to 24 months.

Patients with central nervous system 3 disease received cranial irradiation, and patients were assigned to stem cell transplant based on minimal residual disease if they were thought to have a high risk of relapse.

The 3-year event-free survival rate in the 78 patients was 64.1%.

There were 81 patients evaluable for safety who received dasatinib continuously in combination with chemotherapy. Their median duration of treatment was 24 months (range, 2 to 27 months).

The most common adverse events (AEs) in these patients were mucositis (93%), febrile neutropenia (86%), pyrexia (85%), diarrhea (84%), nausea (84%), vomiting (83%), musculoskeletal pain (83%), abdominal pain (78%), cough (78%), headache (77%), rash (68%), fatigue (59%), and constipation (57%).

Eight (10%) patients had AEs leading to treatment discontinuation. These included fungal sepsis, hepatotoxicity in the setting of graft-versus-host disease, thrombocytopenia, cytomegalovirus infection, pneumonia, nausea, enteritis, and drug hypersensitivity.

Three patients (4%) had fatal AEs, all infections.

This trial was sponsored by Bristol-Myers Squibb. Additional data are available in the prescribing information for dasatinib.

Photo by Bill Branson

The U.S. Food and Drug Administration (FDA) has approved a second pediatric indication for dasatinib (Sprycel®).

The tyrosine kinase inhibitor is now approved for use in combination with chemotherapy to treat pediatric patients age 1 year and older who have newly diagnosed, Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL).

Dasatinib is also FDA-approved for use in children age 1 year and older who have chronic phase, Ph+ chronic myeloid leukemia (CML).

In adults, dasatinib is FDA-approved to treat:

• Newly diagnosed, Ph+, chronic phase CML
• Chronic, accelerated, or myeloid/lymphoid blast phase, Ph+ CML with resistance or intolerance to prior therapy including imatinib
• Ph+ ALL with resistance or intolerance to prior therapy.

Trial results

The FDA’s approval of dasatinib in children with Ph+ ALL is based on data from a phase 2 study (CA180-372, NCT01460160).

In this trial, researchers evaluated dasatinib in combination with the AIEOP-BFM ALL 2000 chemotherapy protocol in patients (ages 1 to 17) with newly diagnosed, B-cell precursor, Ph+ ALL.

There were 78 patients evaluated for efficacy in cohort 1. They had a median age of 10.4 years (range, 2.6 to 17.9 years). They received dasatinib at a daily dose of 60 mg/m² for up to 24 months.

Patients with central nervous system 3 disease received cranial irradiation, and patients were assigned to stem cell transplant based on minimal residual disease if they were thought to have a high risk of relapse.

The 3-year event-free survival rate in the 78 patients was 64.1%.

There were 81 patients evaluable for safety who received dasatinib continuously in combination with chemotherapy. Their median duration of treatment was 24 months (range, 2 to 27 months).

The most common adverse events (AEs) in these patients were mucositis (93%), febrile neutropenia (86%), pyrexia (85%), diarrhea (84%), nausea (84%), vomiting (83%), musculoskeletal pain (83%), abdominal pain (78%), cough (78%), headache (77%), rash (68%), fatigue (59%), and constipation (57%).

Eight (10%) patients had AEs leading to treatment discontinuation. These included fungal sepsis, hepatotoxicity in the setting of graft-versus-host disease, thrombocytopenia, cytomegalovirus infection, pneumonia, nausea, enteritis, and drug hypersensitivity.

Three patients (4%) had fatal AEs, all infections.

This trial was sponsored by Bristol-Myers Squibb. Additional data are available in the prescribing information for dasatinib.

Photo from Penn Medicine

A group of experts has proposed new consensus definitions and grading systems for cytokine release syndrome (CRS) and neurotoxicity related to immune effector cell therapies.

The group hopes their recommendations will be widely accepted and used in both trials and the clinical setting.

The recommendations were devised by 49 experts at a meeting supported by the American Society for Blood and Marrow Transplantation (ASBMT), compiled by a writing group, and reviewed by stakeholders.

Daniel W. Lee, MD, of the University of Virginia School of Medicine in Charlottesville, and his colleagues described the ASBMT consensus definitions and grading systems in Biology of Blood and Marrow Transplantation.

CRS

The ASBMT consensus definition for CRS is “a supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells.”

To be diagnosed with CRS, a patient must have a fever and may have the following symptoms:

• Hypotension
• Capillary leak (hypoxia)
• End organ dysfunction.

The ASBMT consensus for grading CRS is as follows:

• Grade 1—Patient has a fever, defined as a temperature of 38.0°C or higher
• Grade 2—Patient has a fever, hypotension that doesn’t require vasopressors, and/or hypoxia that requires oxygen delivered by low-flow nasal cannula (≤6 L/min) or blow-by
• Grade 3—Patient has a fever, hypotension requiring one vasopressor (with or without vasopressin), and/or hypoxia (not attributable to any other cause) that requires high-flow nasal cannula (>6 L/min), facemask, non-rebreather mask, or venturi mask
• Grade 4—Patient has a fever, hypotension requiring multiple vasopressors (excluding vasopressin), and/or hypoxia (not attributable to any other cause) requiring positive-pressure ventilation
• Grade 5—Death due to CRS when there is no other “principle factor” leading to death.

Typically, severe CRS can be considered resolved if “fever, oxygen, and pressor requirements have resolved,” Dr. Lee and his coauthors said.

The authors also stressed that neurotoxicity that occurs with or after CRS “does not inform the grade of CRS but is instead captured separately in the neurotoxicity scale.”

Neurotoxicity

Dr. Lee and his coauthors said neurotoxicity in this setting is called “immune effector cell-associated neurotoxicity syndrome (ICANS).”

The ASBMT consensus definition for ICANs is “a disorder characterized by a pathologic process involving the central nervous system following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells.”

Symptoms of ICANS may include:

• Aphasia
• Altered level of consciousness
• Impairment of cognitive skills
• Motor weakness
• Seizures
• Cerebral edema.

The ASBMT consensus for grading ICANS in adults and children age 12 and older is as follows:

• Grade 1—Patient has a score of 7-9 on the 10-point immune effector cell-associated encephalopathy (ICE) assessment and awakens spontaneously
• Grade 2—Patient has a score of 3-6 on the ICE assessment and will awaken to the sound of a voice
• Grade 3—Patient has a score of 0-2 on the ICE assessment, awakens only to tactile stimulus, has any clinical seizure that resolves rapidly or non-convulsive seizures that resolve with intervention, has focal/local edema on neuroimaging
• Grade 4—Patient is unable to perform the ICE assessment, is unarousable or requires “vigorous stimuli” to be aroused, has life-threatening seizure (lasting more than 5 minutes) or repetitive clinical or electrical seizures without return to baseline in between, has deep focal motor weakness, and/or has decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, Cushing’s triad, or signs of diffuse cerebral edema on neuroimaging
• Grade 5—Death due to ICANS when there is no other “principle factor” leading to death.

Dr. Lee and his coauthors noted that the ICE assessment is not suitable for children younger than 12. For these patients (and older patients with baseline developmental delays), ICANS can be assessed using the Cornell Assessment of Pediatric Delirium (CAPD).

The ASBMT consensus for grading ICANS in children younger than 12 (or older patients with developmental delays) is as follows:

• Grade 1—Patient has a CAPD score lower than 9 and awakens spontaneously
• Grade 2—Patient has a CAPD score lower than 9 and will awaken to the sound of a voice
• Grade 3—Patient has a CAPD score of 9 or higher, awakens only to tactile stimulus, has any clinical seizure that resolves rapidly or non-convulsive seizures that resolve with intervention, and/or has focal/local edema on neuroimaging
• Grade 4—Patient is unable to perform CAPD, is unarousable or requires “vigorous stimuli” to be aroused, has life-threatening seizure (lasting more than 5 minutes) or repetitive clinical or electrical seizures without return to baseline in between, has deep focal motor weakness, and/or has decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, Cushing’s triad, or signs of diffuse cerebral edema on neuroimaging
• Grade 5—Death due to ICANS when there is no other “principle factor” leading to death.

Dr. Lee and his coauthors reported relationships with a range of companies. 

Photo from Penn Medicine

A group of experts has proposed new consensus definitions and grading systems for cytokine release syndrome (CRS) and neurotoxicity related to immune effector cell therapies.

The group hopes their recommendations will be widely accepted and used in both trials and the clinical setting.

The recommendations were devised by 49 experts at a meeting supported by the American Society for Blood and Marrow Transplantation (ASBMT), compiled by a writing group, and reviewed by stakeholders.

Daniel W. Lee, MD, of the University of Virginia School of Medicine in Charlottesville, and his colleagues described the ASBMT consensus definitions and grading systems in Biology of Blood and Marrow Transplantation.

CRS

The ASBMT consensus definition for CRS is “a supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells.”

To be diagnosed with CRS, a patient must have a fever and may have the following symptoms:

• Hypotension
• Capillary leak (hypoxia)
• End organ dysfunction.

The ASBMT consensus for grading CRS is as follows:

• Grade 1—Patient has a fever, defined as a temperature of 38.0°C or higher
• Grade 2—Patient has a fever, hypotension that doesn’t require vasopressors, and/or hypoxia that requires oxygen delivered by low-flow nasal cannula (≤6 L/min) or blow-by
• Grade 3—Patient has a fever, hypotension requiring one vasopressor (with or without vasopressin), and/or hypoxia (not attributable to any other cause) that requires high-flow nasal cannula (>6 L/min), facemask, non-rebreather mask, or venturi mask
• Grade 4—Patient has a fever, hypotension requiring multiple vasopressors (excluding vasopressin), and/or hypoxia (not attributable to any other cause) requiring positive-pressure ventilation
• Grade 5—Death due to CRS when there is no other “principle factor” leading to death.

Typically, severe CRS can be considered resolved if “fever, oxygen, and pressor requirements have resolved,” Dr. Lee and his coauthors said.

The authors also stressed that neurotoxicity that occurs with or after CRS “does not inform the grade of CRS but is instead captured separately in the neurotoxicity scale.”

Neurotoxicity

Dr. Lee and his coauthors said neurotoxicity in this setting is called “immune effector cell-associated neurotoxicity syndrome (ICANS).”

The ASBMT consensus definition for ICANs is “a disorder characterized by a pathologic process involving the central nervous system following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells.”

Symptoms of ICANS may include:

• Aphasia
• Altered level of consciousness
• Impairment of cognitive skills
• Motor weakness
• Seizures
• Cerebral edema.

The ASBMT consensus for grading ICANS in adults and children age 12 and older is as follows:

• Grade 1—Patient has a score of 7-9 on the 10-point immune effector cell-associated encephalopathy (ICE) assessment and awakens spontaneously
• Grade 2—Patient has a score of 3-6 on the ICE assessment and will awaken to the sound of a voice
• Grade 3—Patient has a score of 0-2 on the ICE assessment, awakens only to tactile stimulus, has any clinical seizure that resolves rapidly or non-convulsive seizures that resolve with intervention, has focal/local edema on neuroimaging
• Grade 4—Patient is unable to perform the ICE assessment, is unarousable or requires “vigorous stimuli” to be aroused, has life-threatening seizure (lasting more than 5 minutes) or repetitive clinical or electrical seizures without return to baseline in between, has deep focal motor weakness, and/or has decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, Cushing’s triad, or signs of diffuse cerebral edema on neuroimaging
• Grade 5—Death due to ICANS when there is no other “principle factor” leading to death.

Dr. Lee and his coauthors noted that the ICE assessment is not suitable for children younger than 12. For these patients (and older patients with baseline developmental delays), ICANS can be assessed using the Cornell Assessment of Pediatric Delirium (CAPD).

The ASBMT consensus for grading ICANS in children younger than 12 (or older patients with developmental delays) is as follows:

• Grade 1—Patient has a CAPD score lower than 9 and awakens spontaneously
• Grade 2—Patient has a CAPD score lower than 9 and will awaken to the sound of a voice
• Grade 3—Patient has a CAPD score of 9 or higher, awakens only to tactile stimulus, has any clinical seizure that resolves rapidly or non-convulsive seizures that resolve with intervention, and/or has focal/local edema on neuroimaging
• Grade 4—Patient is unable to perform CAPD, is unarousable or requires “vigorous stimuli” to be aroused, has life-threatening seizure (lasting more than 5 minutes) or repetitive clinical or electrical seizures without return to baseline in between, has deep focal motor weakness, and/or has decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, Cushing’s triad, or signs of diffuse cerebral edema on neuroimaging
• Grade 5—Death due to ICANS when there is no other “principle factor” leading to death.

Dr. Lee and his coauthors reported relationships with a range of companies. 

Photo from Penn Medicine

A group of experts has proposed new consensus definitions and grading systems for cytokine release syndrome (CRS) and neurotoxicity related to immune effector cell therapies.

The group hopes their recommendations will be widely accepted and used in both trials and the clinical setting.

The recommendations were devised by 49 experts at a meeting supported by the American Society for Blood and Marrow Transplantation (ASBMT), compiled by a writing group, and reviewed by stakeholders.

Daniel W. Lee, MD, of the University of Virginia School of Medicine in Charlottesville, and his colleagues described the ASBMT consensus definitions and grading systems in Biology of Blood and Marrow Transplantation.

CRS

The ASBMT consensus definition for CRS is “a supraphysiologic response following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells.”

To be diagnosed with CRS, a patient must have a fever and may have the following symptoms:

• Hypotension
• Capillary leak (hypoxia)
• End organ dysfunction.

The ASBMT consensus for grading CRS is as follows:

• Grade 1—Patient has a fever, defined as a temperature of 38.0°C or higher
• Grade 2—Patient has a fever, hypotension that doesn’t require vasopressors, and/or hypoxia that requires oxygen delivered by low-flow nasal cannula (≤6 L/min) or blow-by
• Grade 3—Patient has a fever, hypotension requiring one vasopressor (with or without vasopressin), and/or hypoxia (not attributable to any other cause) that requires high-flow nasal cannula (>6 L/min), facemask, non-rebreather mask, or venturi mask
• Grade 4—Patient has a fever, hypotension requiring multiple vasopressors (excluding vasopressin), and/or hypoxia (not attributable to any other cause) requiring positive-pressure ventilation
• Grade 5—Death due to CRS when there is no other “principle factor” leading to death.

Typically, severe CRS can be considered resolved if “fever, oxygen, and pressor requirements have resolved,” Dr. Lee and his coauthors said.

The authors also stressed that neurotoxicity that occurs with or after CRS “does not inform the grade of CRS but is instead captured separately in the neurotoxicity scale.”

Neurotoxicity

Dr. Lee and his coauthors said neurotoxicity in this setting is called “immune effector cell-associated neurotoxicity syndrome (ICANS).”

The ASBMT consensus definition for ICANs is “a disorder characterized by a pathologic process involving the central nervous system following any immune therapy that results in the activation or engagement of endogenous or infused T cells and/or other immune effector cells.”

Symptoms of ICANS may include:

• Aphasia
• Altered level of consciousness
• Impairment of cognitive skills
• Motor weakness
• Seizures
• Cerebral edema.

The ASBMT consensus for grading ICANS in adults and children age 12 and older is as follows:

• Grade 1—Patient has a score of 7-9 on the 10-point immune effector cell-associated encephalopathy (ICE) assessment and awakens spontaneously
• Grade 2—Patient has a score of 3-6 on the ICE assessment and will awaken to the sound of a voice
• Grade 3—Patient has a score of 0-2 on the ICE assessment, awakens only to tactile stimulus, has any clinical seizure that resolves rapidly or non-convulsive seizures that resolve with intervention, has focal/local edema on neuroimaging
• Grade 4—Patient is unable to perform the ICE assessment, is unarousable or requires “vigorous stimuli” to be aroused, has life-threatening seizure (lasting more than 5 minutes) or repetitive clinical or electrical seizures without return to baseline in between, has deep focal motor weakness, and/or has decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, Cushing’s triad, or signs of diffuse cerebral edema on neuroimaging
• Grade 5—Death due to ICANS when there is no other “principle factor” leading to death.

Dr. Lee and his coauthors noted that the ICE assessment is not suitable for children younger than 12. For these patients (and older patients with baseline developmental delays), ICANS can be assessed using the Cornell Assessment of Pediatric Delirium (CAPD).

The ASBMT consensus for grading ICANS in children younger than 12 (or older patients with developmental delays) is as follows:

• Grade 1—Patient has a CAPD score lower than 9 and awakens spontaneously
• Grade 2—Patient has a CAPD score lower than 9 and will awaken to the sound of a voice
• Grade 3—Patient has a CAPD score of 9 or higher, awakens only to tactile stimulus, has any clinical seizure that resolves rapidly or non-convulsive seizures that resolve with intervention, and/or has focal/local edema on neuroimaging
• Grade 4—Patient is unable to perform CAPD, is unarousable or requires “vigorous stimuli” to be aroused, has life-threatening seizure (lasting more than 5 minutes) or repetitive clinical or electrical seizures without return to baseline in between, has deep focal motor weakness, and/or has decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, Cushing’s triad, or signs of diffuse cerebral edema on neuroimaging
• Grade 5—Death due to ICANS when there is no other “principle factor” leading to death.

Dr. Lee and his coauthors reported relationships with a range of companies. 

Photo courtesy of Janssen

The European Commission (EC) has granted marketing authorization for a split dosing regimen for daratumumab (Darzalex®).

The approval provides healthcare professionals with the option to split the first infusion of daratumumab over 2 consecutive days.

“We are hopeful that the availability of this more flexible dosing option will make the first infusion of Darzalex more convenient for European multiple myeloma patients,” said Jan van de Winkel, PhD, chief executive officer of Genmab, which licensed daratumumab to Janssen Biotech, Inc.

Daratumumab is currently EC-approved for the following indications:

• For use in combination with bortezomib, melphalan, and prednisone to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant
• For use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with MM who have received at least one prior therapy
• As monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The EC’s approval of a split dosing regimen for daratumumab was based on data from the phase 1b EQUULEUS trial (MMY1001, NCT01998971), which was sponsored by Janssen.

This trial was designed to evaluate daratumumab in combination with bortezomib-dexamethasone, bortezomib-melphalan-prednisone, bortezomib-thalidomide-dexamethasone, pomalidomide-dexamethasone, carfilzomib-dexamethasone, and carfilzomib-lenalidomide-dexamethasone.

At the 2018 ASH Annual Meeting (abstract 1970), researchers presented data from this trial in MM patients who received their first 16 mg/kg daratumumab dose as a split dose of 8 mg/kg on day 1 of cycle 1 and 8 mg/kg on day 2 of cycle 1, compared to patients who received the full 16 mg/kg dose on day 1 of cycle 1.

The researchers said they observed “virtually identical” pharmacokinetics between the dosing groups.

C_max on the first day of cycle 1 was lower in the split-dose group than in the full-dose group. However, after patients in the split-dose group received the second 8 mg/kg dose on day 2, concentrations were similar between the groups.

The researchers said they do not expect the initial difference they observed to have any impact on clinical outcomes.

The team also pointed out that there was no increase in infusion-related reactions among patients who received the split dose.

The researchers said split dosing of daratumumab is still being investigated in ongoing studies of MM patients, including CANDOR (NCT03158688) and LYRA (NCT02951819).

Photo courtesy of Janssen

The European Commission (EC) has granted marketing authorization for a split dosing regimen for daratumumab (Darzalex®).

The approval provides healthcare professionals with the option to split the first infusion of daratumumab over 2 consecutive days.

“We are hopeful that the availability of this more flexible dosing option will make the first infusion of Darzalex more convenient for European multiple myeloma patients,” said Jan van de Winkel, PhD, chief executive officer of Genmab, which licensed daratumumab to Janssen Biotech, Inc.

Daratumumab is currently EC-approved for the following indications:

• For use in combination with bortezomib, melphalan, and prednisone to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant
• For use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with MM who have received at least one prior therapy
• As monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The EC’s approval of a split dosing regimen for daratumumab was based on data from the phase 1b EQUULEUS trial (MMY1001, NCT01998971), which was sponsored by Janssen.

This trial was designed to evaluate daratumumab in combination with bortezomib-dexamethasone, bortezomib-melphalan-prednisone, bortezomib-thalidomide-dexamethasone, pomalidomide-dexamethasone, carfilzomib-dexamethasone, and carfilzomib-lenalidomide-dexamethasone.

At the 2018 ASH Annual Meeting (abstract 1970), researchers presented data from this trial in MM patients who received their first 16 mg/kg daratumumab dose as a split dose of 8 mg/kg on day 1 of cycle 1 and 8 mg/kg on day 2 of cycle 1, compared to patients who received the full 16 mg/kg dose on day 1 of cycle 1.

The researchers said they observed “virtually identical” pharmacokinetics between the dosing groups.

C_max on the first day of cycle 1 was lower in the split-dose group than in the full-dose group. However, after patients in the split-dose group received the second 8 mg/kg dose on day 2, concentrations were similar between the groups.

The researchers said they do not expect the initial difference they observed to have any impact on clinical outcomes.

The team also pointed out that there was no increase in infusion-related reactions among patients who received the split dose.

The researchers said split dosing of daratumumab is still being investigated in ongoing studies of MM patients, including CANDOR (NCT03158688) and LYRA (NCT02951819).

Photo courtesy of Janssen

The European Commission (EC) has granted marketing authorization for a split dosing regimen for daratumumab (Darzalex®).

The approval provides healthcare professionals with the option to split the first infusion of daratumumab over 2 consecutive days.

“We are hopeful that the availability of this more flexible dosing option will make the first infusion of Darzalex more convenient for European multiple myeloma patients,” said Jan van de Winkel, PhD, chief executive officer of Genmab, which licensed daratumumab to Janssen Biotech, Inc.

Daratumumab is currently EC-approved for the following indications:

• For use in combination with bortezomib, melphalan, and prednisone to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant
• For use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with MM who have received at least one prior therapy
• As monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.

The EC’s approval of a split dosing regimen for daratumumab was based on data from the phase 1b EQUULEUS trial (MMY1001, NCT01998971), which was sponsored by Janssen.

This trial was designed to evaluate daratumumab in combination with bortezomib-dexamethasone, bortezomib-melphalan-prednisone, bortezomib-thalidomide-dexamethasone, pomalidomide-dexamethasone, carfilzomib-dexamethasone, and carfilzomib-lenalidomide-dexamethasone.

At the 2018 ASH Annual Meeting (abstract 1970), researchers presented data from this trial in MM patients who received their first 16 mg/kg daratumumab dose as a split dose of 8 mg/kg on day 1 of cycle 1 and 8 mg/kg on day 2 of cycle 1, compared to patients who received the full 16 mg/kg dose on day 1 of cycle 1.

The researchers said they observed “virtually identical” pharmacokinetics between the dosing groups.

C_max on the first day of cycle 1 was lower in the split-dose group than in the full-dose group. However, after patients in the split-dose group received the second 8 mg/kg dose on day 2, concentrations were similar between the groups.

The researchers said they do not expect the initial difference they observed to have any impact on clinical outcomes.

The team also pointed out that there was no increase in infusion-related reactions among patients who received the split dose.

The researchers said split dosing of daratumumab is still being investigated in ongoing studies of MM patients, including CANDOR (NCT03158688) and LYRA (NCT02951819).

BARCELONA – The therapeutic setting for individual psychotherapy has shifted over the years from the analytic couch, with the therapist discretely tucked out of sight, to facing chairs, a similarly sedentary format. The next evolutionary development might be to plop a patient with posttraumatic stress disorder on an exercise treadmill and don a virtual reality helmet to engage in an interactive motion-assisted form of psychotherapy in which the therapist stands alongside the walking patient while providing guidance on processing traumatic memories, Eric Vermetten, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

He and his colleagues have developed an innovative approach to delivering trauma-focused psychotherapy. They call it Multimodular Motion-Assisted Memory Desensitization and Reconsolidation (3MDR), or more informally, “walk and talk therapy,” explained Dr. Vermetten, professor of psychiatry at Leiden (the Netherlands) University and a military mental health researcher for the Dutch Ministry of Defense.

3MDR is a combination of personalized virtual reality using a headset, multisensory input using self-selected trauma-related pictures, and a dual-attention task borrowed from eye movement desensitization and reprocessing therapy, with treadmill walking throughout the treatment session.

The goal is to facilitate retrieval of fear memories and then reconsolidate them in a benign form. 3MDR is designed to boost this process of memory retrieval and reconsolidation by creating a more totally immersive patient experience intended to enhance treatment engagement and overcome behavioral avoidance. Through virtual reality, the PTSD patient literally walks toward his personal fear-related images.

Dr. Vermetten and his coinvestigators came up with 3MDR as a treatment designed for military veterans with chronic, combat-related, treatment-resistant PTSD. The impetus was the evident need for new and better forms of psychotherapy for such patients. Even though an array of evidence-based psychotherapies are available as guideline-recommended first-line treatments for PTSD, individuals with combat-related PTSD have a notoriously low response rate to these interventions, presumably because of the intensity and repetitive nature of their traumatic experiences. Indeed, up to two-thirds of veterans with PTSD experience substantial residual symptoms post treatment such that they still meet diagnostic criteria for the disorder.

3MDR is an amped up form of exposure-based therapy in which patients walk through a personalized virtual reality installation toward self-chosen trauma-related pictures of their deployment. The investigators developed this intensely immersive type of psychotherapy because they believe avoidance and lack of emotional engagement figure prominently in the low success rate of established forms of psychotherapy in combat-related PTSD. The treadmill walking aspect is considered key because of the large body of research showing that walking entails cognitive-motor interactions that facilitate problem solving, the psychiatrist explained.

The investigators recently published a detailed description of the therapeutic rationale for 3MDR and the nuts and bolts of the novel therapy (Front Psychiatry. 2018 May 4;9:176. doi: 10.3389/fpsyt.2018.00176). Early anecdotal experience has been positive. However, as cochair of the ECNP Traumatic Stress Network, Dr. Vermetten is acutely aware of the need to demonstrate efficacy in rigorous randomized controlled trials.

“This is a way psychotherapy can be shaped in the future. We’re collaborating with various centers across the globe now to see whether this is effective for treatment-resistant PTSD patients,” Dr. Vermetten said.

If those studies prove positive, it will be worthwhile to determine whether 3MDR also has a role as a first-line treatment for earlier-stage PTSD and for forms of the disorder unrelated to military combat, he added.

Funding for the project has been provided by the Dutch Ministry of Defense.

[email protected]

BARCELONA – The therapeutic setting for individual psychotherapy has shifted over the years from the analytic couch, with the therapist discretely tucked out of sight, to facing chairs, a similarly sedentary format. The next evolutionary development might be to plop a patient with posttraumatic stress disorder on an exercise treadmill and don a virtual reality helmet to engage in an interactive motion-assisted form of psychotherapy in which the therapist stands alongside the walking patient while providing guidance on processing traumatic memories, Eric Vermetten, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

He and his colleagues have developed an innovative approach to delivering trauma-focused psychotherapy. They call it Multimodular Motion-Assisted Memory Desensitization and Reconsolidation (3MDR), or more informally, “walk and talk therapy,” explained Dr. Vermetten, professor of psychiatry at Leiden (the Netherlands) University and a military mental health researcher for the Dutch Ministry of Defense.

3MDR is a combination of personalized virtual reality using a headset, multisensory input using self-selected trauma-related pictures, and a dual-attention task borrowed from eye movement desensitization and reprocessing therapy, with treadmill walking throughout the treatment session.

The goal is to facilitate retrieval of fear memories and then reconsolidate them in a benign form. 3MDR is designed to boost this process of memory retrieval and reconsolidation by creating a more totally immersive patient experience intended to enhance treatment engagement and overcome behavioral avoidance. Through virtual reality, the PTSD patient literally walks toward his personal fear-related images.

Dr. Vermetten and his coinvestigators came up with 3MDR as a treatment designed for military veterans with chronic, combat-related, treatment-resistant PTSD. The impetus was the evident need for new and better forms of psychotherapy for such patients. Even though an array of evidence-based psychotherapies are available as guideline-recommended first-line treatments for PTSD, individuals with combat-related PTSD have a notoriously low response rate to these interventions, presumably because of the intensity and repetitive nature of their traumatic experiences. Indeed, up to two-thirds of veterans with PTSD experience substantial residual symptoms post treatment such that they still meet diagnostic criteria for the disorder.

3MDR is an amped up form of exposure-based therapy in which patients walk through a personalized virtual reality installation toward self-chosen trauma-related pictures of their deployment. The investigators developed this intensely immersive type of psychotherapy because they believe avoidance and lack of emotional engagement figure prominently in the low success rate of established forms of psychotherapy in combat-related PTSD. The treadmill walking aspect is considered key because of the large body of research showing that walking entails cognitive-motor interactions that facilitate problem solving, the psychiatrist explained.

The investigators recently published a detailed description of the therapeutic rationale for 3MDR and the nuts and bolts of the novel therapy (Front Psychiatry. 2018 May 4;9:176. doi: 10.3389/fpsyt.2018.00176). Early anecdotal experience has been positive. However, as cochair of the ECNP Traumatic Stress Network, Dr. Vermetten is acutely aware of the need to demonstrate efficacy in rigorous randomized controlled trials.

“This is a way psychotherapy can be shaped in the future. We’re collaborating with various centers across the globe now to see whether this is effective for treatment-resistant PTSD patients,” Dr. Vermetten said.

If those studies prove positive, it will be worthwhile to determine whether 3MDR also has a role as a first-line treatment for earlier-stage PTSD and for forms of the disorder unrelated to military combat, he added.

Funding for the project has been provided by the Dutch Ministry of Defense.

[email protected]

BARCELONA – The therapeutic setting for individual psychotherapy has shifted over the years from the analytic couch, with the therapist discretely tucked out of sight, to facing chairs, a similarly sedentary format. The next evolutionary development might be to plop a patient with posttraumatic stress disorder on an exercise treadmill and don a virtual reality helmet to engage in an interactive motion-assisted form of psychotherapy in which the therapist stands alongside the walking patient while providing guidance on processing traumatic memories, Eric Vermetten, MD, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

He and his colleagues have developed an innovative approach to delivering trauma-focused psychotherapy. They call it Multimodular Motion-Assisted Memory Desensitization and Reconsolidation (3MDR), or more informally, “walk and talk therapy,” explained Dr. Vermetten, professor of psychiatry at Leiden (the Netherlands) University and a military mental health researcher for the Dutch Ministry of Defense.

3MDR is a combination of personalized virtual reality using a headset, multisensory input using self-selected trauma-related pictures, and a dual-attention task borrowed from eye movement desensitization and reprocessing therapy, with treadmill walking throughout the treatment session.

The goal is to facilitate retrieval of fear memories and then reconsolidate them in a benign form. 3MDR is designed to boost this process of memory retrieval and reconsolidation by creating a more totally immersive patient experience intended to enhance treatment engagement and overcome behavioral avoidance. Through virtual reality, the PTSD patient literally walks toward his personal fear-related images.

Dr. Vermetten and his coinvestigators came up with 3MDR as a treatment designed for military veterans with chronic, combat-related, treatment-resistant PTSD. The impetus was the evident need for new and better forms of psychotherapy for such patients. Even though an array of evidence-based psychotherapies are available as guideline-recommended first-line treatments for PTSD, individuals with combat-related PTSD have a notoriously low response rate to these interventions, presumably because of the intensity and repetitive nature of their traumatic experiences. Indeed, up to two-thirds of veterans with PTSD experience substantial residual symptoms post treatment such that they still meet diagnostic criteria for the disorder.

3MDR is an amped up form of exposure-based therapy in which patients walk through a personalized virtual reality installation toward self-chosen trauma-related pictures of their deployment. The investigators developed this intensely immersive type of psychotherapy because they believe avoidance and lack of emotional engagement figure prominently in the low success rate of established forms of psychotherapy in combat-related PTSD. The treadmill walking aspect is considered key because of the large body of research showing that walking entails cognitive-motor interactions that facilitate problem solving, the psychiatrist explained.

The investigators recently published a detailed description of the therapeutic rationale for 3MDR and the nuts and bolts of the novel therapy (Front Psychiatry. 2018 May 4;9:176. doi: 10.3389/fpsyt.2018.00176). Early anecdotal experience has been positive. However, as cochair of the ECNP Traumatic Stress Network, Dr. Vermetten is acutely aware of the need to demonstrate efficacy in rigorous randomized controlled trials.

“This is a way psychotherapy can be shaped in the future. We’re collaborating with various centers across the globe now to see whether this is effective for treatment-resistant PTSD patients,” Dr. Vermetten said.

If those studies prove positive, it will be worthwhile to determine whether 3MDR also has a role as a first-line treatment for earlier-stage PTSD and for forms of the disorder unrelated to military combat, he added.

Funding for the project has been provided by the Dutch Ministry of Defense.

[email protected]

LAS VEGAS – It’s the number of uterine incisions and fibroids removed that increase the risk of miscarriage after fibroid treatment, not the type of procedure, according to a review of 252 cases at Northwestern University, Chicago.

Surgeons feel terrible when a woman loses a pregnancy after fibroid treatment, and wonder if they “caused it, or if it was just a bad uterus or a bad initial pathology,” said lead investigator Laura M. Glaser, MD, an ob.gyn. in private practice in Lake Forest, Ill.

Her study, which was presented at a meeting sponsored by AAGL, suggests that miscarriage occurs mostly from complex pathology, as indicated by the number of fibroids and the degree of uterine cutting needed to remove them. The team reviewed outcomes among women who conceived after treatment; 28 had robotic-assisted myomectomies; 208 had open, abdominal myomectomies; and 16 had uterine fibroid embolization (UFE). Miscarriage was defined as pregnancy loss before 24 weeks.

After the researchers adjusted for age, body mass index, and parity, there were no statistically significant differences in miscarriage rates among the three groups (31% after UFE, 29% after robotic myomectomy, and 22% after abdominal myomectomy).

Open cases had the largest dominant fibroid at a mean of 8.5 cm, the most fibroids removed at 4.5, and the highest rate of cavity entry, 42%. Even so, at 22%, open cases were the least likely to miscarry.

Uterine size, specimen weight, time from procedure to pregnancy, and fibroid location didn’t seem to matter otherwise. The only risk factors that reached statistical significance were among women who had myomectomies; an increasing number of uterine cuts (odds ratio, 1.558; P = .004) and fibroids removed (OR, 1.11; P = .033) increased the odds of miscarriage.

More than 40% of women in the UFE group had previous fibroid surgery, versus 5% among women who had myomectomies. UFE women also were far more likely to have had a previous birth (50% versus 17%), but less likely to have subserosal fibroids (13% versus 33%), and their dominant fibroid was a few centimeters smaller.

Subjects were in their mid-30s, on average, with a mean body mass index of about 28 kg/m². Just over 40% of the women who had myomectomies were white, versus 19% of women who had UFE.

There was no outside funding for the work, and the investigators didn’t have any disclosures.

[email protected]

SOURCE: Glaser LM et al. 2018 AAGL Global Congress, Abstract 160

LAS VEGAS – It’s the number of uterine incisions and fibroids removed that increase the risk of miscarriage after fibroid treatment, not the type of procedure, according to a review of 252 cases at Northwestern University, Chicago.

Surgeons feel terrible when a woman loses a pregnancy after fibroid treatment, and wonder if they “caused it, or if it was just a bad uterus or a bad initial pathology,” said lead investigator Laura M. Glaser, MD, an ob.gyn. in private practice in Lake Forest, Ill.

Her study, which was presented at a meeting sponsored by AAGL, suggests that miscarriage occurs mostly from complex pathology, as indicated by the number of fibroids and the degree of uterine cutting needed to remove them. The team reviewed outcomes among women who conceived after treatment; 28 had robotic-assisted myomectomies; 208 had open, abdominal myomectomies; and 16 had uterine fibroid embolization (UFE). Miscarriage was defined as pregnancy loss before 24 weeks.

After the researchers adjusted for age, body mass index, and parity, there were no statistically significant differences in miscarriage rates among the three groups (31% after UFE, 29% after robotic myomectomy, and 22% after abdominal myomectomy).

Open cases had the largest dominant fibroid at a mean of 8.5 cm, the most fibroids removed at 4.5, and the highest rate of cavity entry, 42%. Even so, at 22%, open cases were the least likely to miscarry.

Uterine size, specimen weight, time from procedure to pregnancy, and fibroid location didn’t seem to matter otherwise. The only risk factors that reached statistical significance were among women who had myomectomies; an increasing number of uterine cuts (odds ratio, 1.558; P = .004) and fibroids removed (OR, 1.11; P = .033) increased the odds of miscarriage.

More than 40% of women in the UFE group had previous fibroid surgery, versus 5% among women who had myomectomies. UFE women also were far more likely to have had a previous birth (50% versus 17%), but less likely to have subserosal fibroids (13% versus 33%), and their dominant fibroid was a few centimeters smaller.

Subjects were in their mid-30s, on average, with a mean body mass index of about 28 kg/m². Just over 40% of the women who had myomectomies were white, versus 19% of women who had UFE.

There was no outside funding for the work, and the investigators didn’t have any disclosures.

[email protected]

SOURCE: Glaser LM et al. 2018 AAGL Global Congress, Abstract 160

LAS VEGAS – It’s the number of uterine incisions and fibroids removed that increase the risk of miscarriage after fibroid treatment, not the type of procedure, according to a review of 252 cases at Northwestern University, Chicago.

Surgeons feel terrible when a woman loses a pregnancy after fibroid treatment, and wonder if they “caused it, or if it was just a bad uterus or a bad initial pathology,” said lead investigator Laura M. Glaser, MD, an ob.gyn. in private practice in Lake Forest, Ill.

Her study, which was presented at a meeting sponsored by AAGL, suggests that miscarriage occurs mostly from complex pathology, as indicated by the number of fibroids and the degree of uterine cutting needed to remove them. The team reviewed outcomes among women who conceived after treatment; 28 had robotic-assisted myomectomies; 208 had open, abdominal myomectomies; and 16 had uterine fibroid embolization (UFE). Miscarriage was defined as pregnancy loss before 24 weeks.

After the researchers adjusted for age, body mass index, and parity, there were no statistically significant differences in miscarriage rates among the three groups (31% after UFE, 29% after robotic myomectomy, and 22% after abdominal myomectomy).

Open cases had the largest dominant fibroid at a mean of 8.5 cm, the most fibroids removed at 4.5, and the highest rate of cavity entry, 42%. Even so, at 22%, open cases were the least likely to miscarry.

Uterine size, specimen weight, time from procedure to pregnancy, and fibroid location didn’t seem to matter otherwise. The only risk factors that reached statistical significance were among women who had myomectomies; an increasing number of uterine cuts (odds ratio, 1.558; P = .004) and fibroids removed (OR, 1.11; P = .033) increased the odds of miscarriage.

More than 40% of women in the UFE group had previous fibroid surgery, versus 5% among women who had myomectomies. UFE women also were far more likely to have had a previous birth (50% versus 17%), but less likely to have subserosal fibroids (13% versus 33%), and their dominant fibroid was a few centimeters smaller.

Subjects were in their mid-30s, on average, with a mean body mass index of about 28 kg/m². Just over 40% of the women who had myomectomies were white, versus 19% of women who had UFE.

There was no outside funding for the work, and the investigators didn’t have any disclosures.

[email protected]

SOURCE: Glaser LM et al. 2018 AAGL Global Congress, Abstract 160

The use of anticoagulation in patients with comorbid lupus nephritis and thrombotic microangiopathy was linked with a greater rate of clinical response after 12 months of therapy, according to results from a study published in Annals of the Rheumatic Diseases.

copyright HYWARDS/Thinkstock

“The purpose of this multicenter retrospective study was to analyze the impact of anticoagulation (vitamin K antagonists and/or heparins), in addition to conventional immunosuppression on kidney outcomes, according to the Kidney Disease: Improving Global Outcomes guidelines,” wrote first author Savino Sciascia, MD, PhD, of the University of Turin (Italy), along with his colleagues.

The researchers analyzed data from 97 patients with biopsy-confirmed lupus nephritis (LN) and thrombotic microangiopathy (TMA) who were diagnosed during 2007-2017. The entire cohort was administered standard immunosuppressive agents, including corticosteroids, cyclophosphamide, and mycophenolate, among others. After 12 months of therapy, the patients were assessed for degree of clinical response, measured using complete, partial, or no response to therapy.

“Sixty-one patients (62.9%) were [antiphospholipid antibody] positive and 37 (38.1%) of these patients received anticoagulation with a vitamin K antagonist and/or heparins,” the investigators wrote. “Mean duration of anticoagulation therapy after TMA and LN diagnosis was 7.7 months,” they added.

After statistical analysis, the researchers found that patients treated with anticoagulation therapy experienced a greater rate of clinical response, compared with those not treated. The investigators saw a complete response to therapy in 22 (59.5%) patients given anticoagulation, compared with 15 (25.0%) patients without anticoagulation. Partial treatment responses were comparable, occurring in 7 (18.9%) with anticoagulation and 15 (25.0%) without. Without anticoagulation, 30 (50%) had no response to therapy, compared with 8 (21.6%) patients given anticoagulation.

“When limiting the analysis to patients with antiphospholipid antibodies, we observed a rate of any response (either complete response [or] partial response) as high as 66% in patients receiving anticoagulant treatment compared with those receiving immunosuppression alone (34%),” they added.

The authors acknowledged a major limitation of the study was the short duration of follow-up, which limited the ability to evaluate relapse rate.

“Despite its limitations, this study represents the largest available multicenter cohort of real-life systemic lupus erythematosus patients,” said Dr. Sciascia and his colleagues. “The use of anticoagulation appeared protective and warrants further investigation as a therapeutic tool,” they concluded.

The authors reported no conflicts of interest, and no specific study funding was declared.

SOURCE: Sciascia S et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214559.

The use of anticoagulation in patients with comorbid lupus nephritis and thrombotic microangiopathy was linked with a greater rate of clinical response after 12 months of therapy, according to results from a study published in Annals of the Rheumatic Diseases.

copyright HYWARDS/Thinkstock

“The purpose of this multicenter retrospective study was to analyze the impact of anticoagulation (vitamin K antagonists and/or heparins), in addition to conventional immunosuppression on kidney outcomes, according to the Kidney Disease: Improving Global Outcomes guidelines,” wrote first author Savino Sciascia, MD, PhD, of the University of Turin (Italy), along with his colleagues.

The researchers analyzed data from 97 patients with biopsy-confirmed lupus nephritis (LN) and thrombotic microangiopathy (TMA) who were diagnosed during 2007-2017. The entire cohort was administered standard immunosuppressive agents, including corticosteroids, cyclophosphamide, and mycophenolate, among others. After 12 months of therapy, the patients were assessed for degree of clinical response, measured using complete, partial, or no response to therapy.

“Sixty-one patients (62.9%) were [antiphospholipid antibody] positive and 37 (38.1%) of these patients received anticoagulation with a vitamin K antagonist and/or heparins,” the investigators wrote. “Mean duration of anticoagulation therapy after TMA and LN diagnosis was 7.7 months,” they added.

After statistical analysis, the researchers found that patients treated with anticoagulation therapy experienced a greater rate of clinical response, compared with those not treated. The investigators saw a complete response to therapy in 22 (59.5%) patients given anticoagulation, compared with 15 (25.0%) patients without anticoagulation. Partial treatment responses were comparable, occurring in 7 (18.9%) with anticoagulation and 15 (25.0%) without. Without anticoagulation, 30 (50%) had no response to therapy, compared with 8 (21.6%) patients given anticoagulation.

“When limiting the analysis to patients with antiphospholipid antibodies, we observed a rate of any response (either complete response [or] partial response) as high as 66% in patients receiving anticoagulant treatment compared with those receiving immunosuppression alone (34%),” they added.

The authors acknowledged a major limitation of the study was the short duration of follow-up, which limited the ability to evaluate relapse rate.

“Despite its limitations, this study represents the largest available multicenter cohort of real-life systemic lupus erythematosus patients,” said Dr. Sciascia and his colleagues. “The use of anticoagulation appeared protective and warrants further investigation as a therapeutic tool,” they concluded.

The authors reported no conflicts of interest, and no specific study funding was declared.

SOURCE: Sciascia S et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214559.

The use of anticoagulation in patients with comorbid lupus nephritis and thrombotic microangiopathy was linked with a greater rate of clinical response after 12 months of therapy, according to results from a study published in Annals of the Rheumatic Diseases.

copyright HYWARDS/Thinkstock

“The purpose of this multicenter retrospective study was to analyze the impact of anticoagulation (vitamin K antagonists and/or heparins), in addition to conventional immunosuppression on kidney outcomes, according to the Kidney Disease: Improving Global Outcomes guidelines,” wrote first author Savino Sciascia, MD, PhD, of the University of Turin (Italy), along with his colleagues.

The researchers analyzed data from 97 patients with biopsy-confirmed lupus nephritis (LN) and thrombotic microangiopathy (TMA) who were diagnosed during 2007-2017. The entire cohort was administered standard immunosuppressive agents, including corticosteroids, cyclophosphamide, and mycophenolate, among others. After 12 months of therapy, the patients were assessed for degree of clinical response, measured using complete, partial, or no response to therapy.

“Sixty-one patients (62.9%) were [antiphospholipid antibody] positive and 37 (38.1%) of these patients received anticoagulation with a vitamin K antagonist and/or heparins,” the investigators wrote. “Mean duration of anticoagulation therapy after TMA and LN diagnosis was 7.7 months,” they added.

After statistical analysis, the researchers found that patients treated with anticoagulation therapy experienced a greater rate of clinical response, compared with those not treated. The investigators saw a complete response to therapy in 22 (59.5%) patients given anticoagulation, compared with 15 (25.0%) patients without anticoagulation. Partial treatment responses were comparable, occurring in 7 (18.9%) with anticoagulation and 15 (25.0%) without. Without anticoagulation, 30 (50%) had no response to therapy, compared with 8 (21.6%) patients given anticoagulation.

“When limiting the analysis to patients with antiphospholipid antibodies, we observed a rate of any response (either complete response [or] partial response) as high as 66% in patients receiving anticoagulant treatment compared with those receiving immunosuppression alone (34%),” they added.

The authors acknowledged a major limitation of the study was the short duration of follow-up, which limited the ability to evaluate relapse rate.

“Despite its limitations, this study represents the largest available multicenter cohort of real-life systemic lupus erythematosus patients,” said Dr. Sciascia and his colleagues. “The use of anticoagulation appeared protective and warrants further investigation as a therapeutic tool,” they concluded.

The authors reported no conflicts of interest, and no specific study funding was declared.

SOURCE: Sciascia S et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214559.