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NASHVILLE, TENN. – All women should be assessed for cardiovascular disease in the antepartum and postpartum periods using a specific toolkit algorithm, according to new comprehensive guidance from the American College of Obstetricians and Gynecologists.

The toolkit algorithm is called the California Improving Health Care Response to Cardiovascular Disease in Pregnancy and Postpartum Toolkit. It was developed by the Cardiovascular Disease in Pregnancy Postpartum Task Force to serve as a resource for obstetrics, primary care and emergency medicine providers who provide prenatal care or interact with women during the postpartum period. It incldues an overview of clinical assessment and comprehensive management strategies for cardiovascular disease based on risk factors and presenting symptoms.

The guidance also calls for all pregnant and postpartum women with known or suspected CVD to undergo further evaluation by a “Pregnancy Heart Team that includes a cardiologist and maternal–fetal medicine subspecialist, or both, and other subspecialists as necessary.” The guidance was issued in Practice Bulletin 212, Pregnancy and Heart Disease, which is published in the May edition of Obstetrics & Gynecology (Obstet Gynecol. 2019 May;133[5]:e320-e356).


In all, 27 specific recommendations and conclusions relating to screening, diagnosis, and management of CVD for women during the prepregnancy period through the postpartum period are included in the guidance.

ACOG president Lisa Hollier, MD, convened the task force that developed this guidance to address cardiac contributors to maternal mortality, she said during a press briefing at the ACOG annual clinical and scientific meeting.

“When I began my presidency a year ago, my goal was to bring together a multidisciplinary group of clinicians ... to create clinical guidance that would make a difference in the lives of women," said Dr. Hollier, who is also a professor of obstetrics and gynecology at Baylor College of Medicine, Houston. 

Jovanmandic/Getty Images

[email protected]

SOURCE: Hollier L et al., Obstet Gynecol. 2019 May;133[5]:e320-56.

NASHVILLE, TENN. – All women should be assessed for cardiovascular disease in the antepartum and postpartum periods using a specific toolkit algorithm, according to new comprehensive guidance from the American College of Obstetricians and Gynecologists.

The toolkit algorithm is called the California Improving Health Care Response to Cardiovascular Disease in Pregnancy and Postpartum Toolkit. It was developed by the Cardiovascular Disease in Pregnancy Postpartum Task Force to serve as a resource for obstetrics, primary care and emergency medicine providers who provide prenatal care or interact with women during the postpartum period. It incldues an overview of clinical assessment and comprehensive management strategies for cardiovascular disease based on risk factors and presenting symptoms.

The guidance also calls for all pregnant and postpartum women with known or suspected CVD to undergo further evaluation by a “Pregnancy Heart Team that includes a cardiologist and maternal–fetal medicine subspecialist, or both, and other subspecialists as necessary.” The guidance was issued in Practice Bulletin 212, Pregnancy and Heart Disease, which is published in the May edition of Obstetrics & Gynecology (Obstet Gynecol. 2019 May;133[5]:e320-e356).


In all, 27 specific recommendations and conclusions relating to screening, diagnosis, and management of CVD for women during the prepregnancy period through the postpartum period are included in the guidance.

ACOG president Lisa Hollier, MD, convened the task force that developed this guidance to address cardiac contributors to maternal mortality, she said during a press briefing at the ACOG annual clinical and scientific meeting.

“When I began my presidency a year ago, my goal was to bring together a multidisciplinary group of clinicians ... to create clinical guidance that would make a difference in the lives of women," said Dr. Hollier, who is also a professor of obstetrics and gynecology at Baylor College of Medicine, Houston. 

Jovanmandic/Getty Images

[email protected]

SOURCE: Hollier L et al., Obstet Gynecol. 2019 May;133[5]:e320-56.

NASHVILLE, TENN. – All women should be assessed for cardiovascular disease in the antepartum and postpartum periods using a specific toolkit algorithm, according to new comprehensive guidance from the American College of Obstetricians and Gynecologists.

The toolkit algorithm is called the California Improving Health Care Response to Cardiovascular Disease in Pregnancy and Postpartum Toolkit. It was developed by the Cardiovascular Disease in Pregnancy Postpartum Task Force to serve as a resource for obstetrics, primary care and emergency medicine providers who provide prenatal care or interact with women during the postpartum period. It incldues an overview of clinical assessment and comprehensive management strategies for cardiovascular disease based on risk factors and presenting symptoms.

The guidance also calls for all pregnant and postpartum women with known or suspected CVD to undergo further evaluation by a “Pregnancy Heart Team that includes a cardiologist and maternal–fetal medicine subspecialist, or both, and other subspecialists as necessary.” The guidance was issued in Practice Bulletin 212, Pregnancy and Heart Disease, which is published in the May edition of Obstetrics & Gynecology (Obstet Gynecol. 2019 May;133[5]:e320-e356).


In all, 27 specific recommendations and conclusions relating to screening, diagnosis, and management of CVD for women during the prepregnancy period through the postpartum period are included in the guidance.

ACOG president Lisa Hollier, MD, convened the task force that developed this guidance to address cardiac contributors to maternal mortality, she said during a press briefing at the ACOG annual clinical and scientific meeting.

“When I began my presidency a year ago, my goal was to bring together a multidisciplinary group of clinicians ... to create clinical guidance that would make a difference in the lives of women," said Dr. Hollier, who is also a professor of obstetrics and gynecology at Baylor College of Medicine, Houston. 

Jovanmandic/Getty Images

[email protected]

SOURCE: Hollier L et al., Obstet Gynecol. 2019 May;133[5]:e320-56.

NEWPORT BEACH, CALIF. – The combination of oral rigosertib and azacitidine is proceeding to a phase 3 trial in patients with myelodysplastic syndromes (MDS), but it isn’t clear if the combination will continue to be developed for acute myeloid leukemia (AML).

In a phase 1/2 trial, oral rigosertib plus azacitidine produced a 90% response rate in higher-risk MDS patients who were naive to hypomethylating agents (HMAs), a 54% response rate in higher-risk MDS patients who had failed HMA therapy, and a 50% response rate in patients with AML.

Genitourinary toxicities were initially a concern in this trial, but researchers found ways to mitigate the risk of these toxicities, according to Richard Woodman, MD, chief medical officer and senior vice president of research and development at Onconova Therapeutics, the company developing rigosertib.

Dr. Woodman and his colleagues presented results from the phase 1/2 trial in two posters at the Acute Leukemia Forum of Hemedicus.

Results in AML

The researchers reported phase 1 results in 17 patients with AML. Eleven patients had AML, according to investigator assessment, and six patients had refractory anemia with excess blasts in transformation, according to French American British criteria, as well as least 20% excess blasts at baseline.

The median age of the patients was 73 years, and 53% were men. Two patients had received no prior therapies, six patients had relapsed disease, and nine were refractory to their last therapy.

Patients received oral rigosertib at escalating doses twice daily on days 1-21 of a 28-day cycle. The recommended phase 2 dose was 840 mg daily (560 mg in the morning and 280 mg in the afternoon), but there were two expansion cohorts in which patients received 1,120 mg daily (560 mg twice a day or 840 mg in the morning and 280 mg in the afternoon). The patients also received azacitidine at 75 mg/m² per day subcutaneously or intravenously for 7 days starting on day 8.

Patients received a median of three treatment cycles. Fifteen of the 17 patients (88%) discontinued treatment, most because of progressive disease (n = 5), toxicity (n = 4), or death (n = 3).

Twelve patients were evaluable for response, and six (50%) responded. One patient achieved a morphologic complete remission (CR), three achieved a morphologic leukemia-free state, and two had a partial response.

The most common treatment-emergent adverse events (TEAEs) were fatigue (53%), diarrhea (53%), nausea (53%), constipation (47%), back pain (41%), pyrexia (41%), and pneumonia (35%). Grade 3 or higher TEAEs included pneumonia (35%) and anemia (24%).

These results haven’t provided a clear way forward for oral rigosertib and azacitidine in AML. Dr. Woodman said the researchers will have to review past studies and evaluate how AML patients (with at least 20% blasts) have responded to intravenous rigosertib, consult experts in the field, and then decide how they will move forward with oral rigosertib and azacitidine in AML.

Results in MDS

Dr. Woodman and his colleagues presented data on 74 patients with higher-risk MDS. The median age was 69 years, and 59% were men. Most patients were high risk (n = 23) or very high risk (n = 33), according to the Revised International Prognostic Scoring System.

The patients received oral rigosertib at a dose of 840 mg/day or higher on days 1-21 of a 28-day cycle. They also received azacitidine at 75 mg/m² per day subcutaneously or intravenously for 7 days starting on day 8.

The median duration of treatment was 7.8 months in patients who were HMA naive and 4.9 months in patients who failed HMA therapy. The most common reasons for treatment discontinuation in the HMA-naive patients were toxicity (n = 8), progression (n = 7), and patient request (n = 7). The most common reasons for discontinuation in patients who had failed HMA therapy were progression (n = 12), toxicity (n = 5), and investigator decision (n = 4).

In total, 55 patients were evaluable for response, 26 who had failed HMA therapy and 29 who were HMA naive.

“The best responses, not surprisingly, were in patients that were HMA naive,” Dr. Woodman said.

In the HMA-naive patients, the overall response rate was 90%. Ten patients had a CR, five had a marrow CR with hematologic improvement, three had hematologic improvement alone, eight had a marrow CR alone, and three patients had stable disease. None of the patients progressed.

In the patients who had failed HMA therapy, the overall response rate was 54%. One patient achieved a CR, one had a partial response, five had a marrow CR with hematologic improvement, two had hematologic improvement alone, five had a marrow CR alone, seven had stable disease, and five progressed.

The median duration of response was 10.8 months in patients who failed HMA therapy and 12.2 months in the HMA-naive patients.

The most common TEAEs in the entire MDS cohort were hematuria (45%), constipation (43%), diarrhea (42%), fatigue (42%), dysuria (38%), pyrexia (36%), nausea (35%), neutropenia (31%), and thrombocytopenia (30%).

Grade 3 or higher TEAEs were neutropenia (27%), thrombocytopenia (26%), hematuria (9%), dysuria (9%), diarrhea (5%), fatigue (4%), and pyrexia (1%).

Dr. Woodman said patients who were most likely to be at risk for genitourinary toxicities (hematuria and dysuria) were those who weren’t well hydrated, took rigosertib at night, and didn’t void their bladders before bedtime. He said the researchers’ hypothesis is that there is some local bladder irritation in that setting.

However, the researchers found ways to mitigate the risk of genitourinary toxicities, including:

• Requiring the second dose of rigosertib to be taken in the afternoon rather than evening (about 3 p.m.).
• Asking patients to consume at least 2 liters of fluid per day.
• Having patients empty their bladders before bedtime.
• Assessing urine pH roughly 2 hours after the morning dose of rigosertib and prescribing sodium bicarbonate if the pH is less than 7.5.

Dr. Woodman said the phase 2 results in MDS patients have prompted the development of a phase 3 trial in which researchers will compare oral rigosertib plus azacitidine to azacitidine plus placebo.

Dr. Woodman is employed by Onconova Therapeutics, which sponsored the phase 1/2 trial. The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – The combination of oral rigosertib and azacitidine is proceeding to a phase 3 trial in patients with myelodysplastic syndromes (MDS), but it isn’t clear if the combination will continue to be developed for acute myeloid leukemia (AML).

In a phase 1/2 trial, oral rigosertib plus azacitidine produced a 90% response rate in higher-risk MDS patients who were naive to hypomethylating agents (HMAs), a 54% response rate in higher-risk MDS patients who had failed HMA therapy, and a 50% response rate in patients with AML.

Genitourinary toxicities were initially a concern in this trial, but researchers found ways to mitigate the risk of these toxicities, according to Richard Woodman, MD, chief medical officer and senior vice president of research and development at Onconova Therapeutics, the company developing rigosertib.

Dr. Woodman and his colleagues presented results from the phase 1/2 trial in two posters at the Acute Leukemia Forum of Hemedicus.

Results in AML

The researchers reported phase 1 results in 17 patients with AML. Eleven patients had AML, according to investigator assessment, and six patients had refractory anemia with excess blasts in transformation, according to French American British criteria, as well as least 20% excess blasts at baseline.

The median age of the patients was 73 years, and 53% were men. Two patients had received no prior therapies, six patients had relapsed disease, and nine were refractory to their last therapy.

Patients received oral rigosertib at escalating doses twice daily on days 1-21 of a 28-day cycle. The recommended phase 2 dose was 840 mg daily (560 mg in the morning and 280 mg in the afternoon), but there were two expansion cohorts in which patients received 1,120 mg daily (560 mg twice a day or 840 mg in the morning and 280 mg in the afternoon). The patients also received azacitidine at 75 mg/m² per day subcutaneously or intravenously for 7 days starting on day 8.

Patients received a median of three treatment cycles. Fifteen of the 17 patients (88%) discontinued treatment, most because of progressive disease (n = 5), toxicity (n = 4), or death (n = 3).

Twelve patients were evaluable for response, and six (50%) responded. One patient achieved a morphologic complete remission (CR), three achieved a morphologic leukemia-free state, and two had a partial response.

The most common treatment-emergent adverse events (TEAEs) were fatigue (53%), diarrhea (53%), nausea (53%), constipation (47%), back pain (41%), pyrexia (41%), and pneumonia (35%). Grade 3 or higher TEAEs included pneumonia (35%) and anemia (24%).

These results haven’t provided a clear way forward for oral rigosertib and azacitidine in AML. Dr. Woodman said the researchers will have to review past studies and evaluate how AML patients (with at least 20% blasts) have responded to intravenous rigosertib, consult experts in the field, and then decide how they will move forward with oral rigosertib and azacitidine in AML.

Results in MDS

Dr. Woodman and his colleagues presented data on 74 patients with higher-risk MDS. The median age was 69 years, and 59% were men. Most patients were high risk (n = 23) or very high risk (n = 33), according to the Revised International Prognostic Scoring System.

The patients received oral rigosertib at a dose of 840 mg/day or higher on days 1-21 of a 28-day cycle. They also received azacitidine at 75 mg/m² per day subcutaneously or intravenously for 7 days starting on day 8.

The median duration of treatment was 7.8 months in patients who were HMA naive and 4.9 months in patients who failed HMA therapy. The most common reasons for treatment discontinuation in the HMA-naive patients were toxicity (n = 8), progression (n = 7), and patient request (n = 7). The most common reasons for discontinuation in patients who had failed HMA therapy were progression (n = 12), toxicity (n = 5), and investigator decision (n = 4).

In total, 55 patients were evaluable for response, 26 who had failed HMA therapy and 29 who were HMA naive.

“The best responses, not surprisingly, were in patients that were HMA naive,” Dr. Woodman said.

In the HMA-naive patients, the overall response rate was 90%. Ten patients had a CR, five had a marrow CR with hematologic improvement, three had hematologic improvement alone, eight had a marrow CR alone, and three patients had stable disease. None of the patients progressed.

In the patients who had failed HMA therapy, the overall response rate was 54%. One patient achieved a CR, one had a partial response, five had a marrow CR with hematologic improvement, two had hematologic improvement alone, five had a marrow CR alone, seven had stable disease, and five progressed.

The median duration of response was 10.8 months in patients who failed HMA therapy and 12.2 months in the HMA-naive patients.

The most common TEAEs in the entire MDS cohort were hematuria (45%), constipation (43%), diarrhea (42%), fatigue (42%), dysuria (38%), pyrexia (36%), nausea (35%), neutropenia (31%), and thrombocytopenia (30%).

Grade 3 or higher TEAEs were neutropenia (27%), thrombocytopenia (26%), hematuria (9%), dysuria (9%), diarrhea (5%), fatigue (4%), and pyrexia (1%).

Dr. Woodman said patients who were most likely to be at risk for genitourinary toxicities (hematuria and dysuria) were those who weren’t well hydrated, took rigosertib at night, and didn’t void their bladders before bedtime. He said the researchers’ hypothesis is that there is some local bladder irritation in that setting.

However, the researchers found ways to mitigate the risk of genitourinary toxicities, including:

• Requiring the second dose of rigosertib to be taken in the afternoon rather than evening (about 3 p.m.).
• Asking patients to consume at least 2 liters of fluid per day.
• Having patients empty their bladders before bedtime.
• Assessing urine pH roughly 2 hours after the morning dose of rigosertib and prescribing sodium bicarbonate if the pH is less than 7.5.

Dr. Woodman said the phase 2 results in MDS patients have prompted the development of a phase 3 trial in which researchers will compare oral rigosertib plus azacitidine to azacitidine plus placebo.

Dr. Woodman is employed by Onconova Therapeutics, which sponsored the phase 1/2 trial. The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – The combination of oral rigosertib and azacitidine is proceeding to a phase 3 trial in patients with myelodysplastic syndromes (MDS), but it isn’t clear if the combination will continue to be developed for acute myeloid leukemia (AML).

In a phase 1/2 trial, oral rigosertib plus azacitidine produced a 90% response rate in higher-risk MDS patients who were naive to hypomethylating agents (HMAs), a 54% response rate in higher-risk MDS patients who had failed HMA therapy, and a 50% response rate in patients with AML.

Genitourinary toxicities were initially a concern in this trial, but researchers found ways to mitigate the risk of these toxicities, according to Richard Woodman, MD, chief medical officer and senior vice president of research and development at Onconova Therapeutics, the company developing rigosertib.

Dr. Woodman and his colleagues presented results from the phase 1/2 trial in two posters at the Acute Leukemia Forum of Hemedicus.

Results in AML

The researchers reported phase 1 results in 17 patients with AML. Eleven patients had AML, according to investigator assessment, and six patients had refractory anemia with excess blasts in transformation, according to French American British criteria, as well as least 20% excess blasts at baseline.

The median age of the patients was 73 years, and 53% were men. Two patients had received no prior therapies, six patients had relapsed disease, and nine were refractory to their last therapy.

Patients received oral rigosertib at escalating doses twice daily on days 1-21 of a 28-day cycle. The recommended phase 2 dose was 840 mg daily (560 mg in the morning and 280 mg in the afternoon), but there were two expansion cohorts in which patients received 1,120 mg daily (560 mg twice a day or 840 mg in the morning and 280 mg in the afternoon). The patients also received azacitidine at 75 mg/m² per day subcutaneously or intravenously for 7 days starting on day 8.

Patients received a median of three treatment cycles. Fifteen of the 17 patients (88%) discontinued treatment, most because of progressive disease (n = 5), toxicity (n = 4), or death (n = 3).

Twelve patients were evaluable for response, and six (50%) responded. One patient achieved a morphologic complete remission (CR), three achieved a morphologic leukemia-free state, and two had a partial response.

The most common treatment-emergent adverse events (TEAEs) were fatigue (53%), diarrhea (53%), nausea (53%), constipation (47%), back pain (41%), pyrexia (41%), and pneumonia (35%). Grade 3 or higher TEAEs included pneumonia (35%) and anemia (24%).

These results haven’t provided a clear way forward for oral rigosertib and azacitidine in AML. Dr. Woodman said the researchers will have to review past studies and evaluate how AML patients (with at least 20% blasts) have responded to intravenous rigosertib, consult experts in the field, and then decide how they will move forward with oral rigosertib and azacitidine in AML.

Results in MDS

Dr. Woodman and his colleagues presented data on 74 patients with higher-risk MDS. The median age was 69 years, and 59% were men. Most patients were high risk (n = 23) or very high risk (n = 33), according to the Revised International Prognostic Scoring System.

The patients received oral rigosertib at a dose of 840 mg/day or higher on days 1-21 of a 28-day cycle. They also received azacitidine at 75 mg/m² per day subcutaneously or intravenously for 7 days starting on day 8.

The median duration of treatment was 7.8 months in patients who were HMA naive and 4.9 months in patients who failed HMA therapy. The most common reasons for treatment discontinuation in the HMA-naive patients were toxicity (n = 8), progression (n = 7), and patient request (n = 7). The most common reasons for discontinuation in patients who had failed HMA therapy were progression (n = 12), toxicity (n = 5), and investigator decision (n = 4).

In total, 55 patients were evaluable for response, 26 who had failed HMA therapy and 29 who were HMA naive.

“The best responses, not surprisingly, were in patients that were HMA naive,” Dr. Woodman said.

In the HMA-naive patients, the overall response rate was 90%. Ten patients had a CR, five had a marrow CR with hematologic improvement, three had hematologic improvement alone, eight had a marrow CR alone, and three patients had stable disease. None of the patients progressed.

In the patients who had failed HMA therapy, the overall response rate was 54%. One patient achieved a CR, one had a partial response, five had a marrow CR with hematologic improvement, two had hematologic improvement alone, five had a marrow CR alone, seven had stable disease, and five progressed.

The median duration of response was 10.8 months in patients who failed HMA therapy and 12.2 months in the HMA-naive patients.

The most common TEAEs in the entire MDS cohort were hematuria (45%), constipation (43%), diarrhea (42%), fatigue (42%), dysuria (38%), pyrexia (36%), nausea (35%), neutropenia (31%), and thrombocytopenia (30%).

Grade 3 or higher TEAEs were neutropenia (27%), thrombocytopenia (26%), hematuria (9%), dysuria (9%), diarrhea (5%), fatigue (4%), and pyrexia (1%).

Dr. Woodman said patients who were most likely to be at risk for genitourinary toxicities (hematuria and dysuria) were those who weren’t well hydrated, took rigosertib at night, and didn’t void their bladders before bedtime. He said the researchers’ hypothesis is that there is some local bladder irritation in that setting.

However, the researchers found ways to mitigate the risk of genitourinary toxicities, including:

• Requiring the second dose of rigosertib to be taken in the afternoon rather than evening (about 3 p.m.).
• Asking patients to consume at least 2 liters of fluid per day.
• Having patients empty their bladders before bedtime.
• Assessing urine pH roughly 2 hours after the morning dose of rigosertib and prescribing sodium bicarbonate if the pH is less than 7.5.

Dr. Woodman said the phase 2 results in MDS patients have prompted the development of a phase 3 trial in which researchers will compare oral rigosertib plus azacitidine to azacitidine plus placebo.

Dr. Woodman is employed by Onconova Therapeutics, which sponsored the phase 1/2 trial. The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – Researchers say they’ve found an association between the percentage of cytogenetically abnormal cells at allogeneic stem cell transplant (ASCT) and posttransplant outcomes in patients with myelodysplastic syndromes (MDS).

Patients who had more than 60% cytogenetically abnormal cells at ASCT had significantly inferior overall survival (OS) and relapse-free survival (RFS), compared to patients with fewer abnormal cells.

Dipenkumar Modi, MD, of Barbara Ann Karmanos Cancer Institute at Wayne State University in Detroit, and his colleagues conducted this research and presented the results at the Acute Leukemia Forum of Hemedicus.

The researchers studied 109 adult MDS patients who underwent ASCT from January 2000 through December 2016. The patients were divided into three groups based on the percentage of cytogenetically abnormal cells at ASCT:

• Group 1 had less than 30% (n = 22)
• Group 2 had 30%-60% (n = 23)
• Group 3 had greater than 60% (n = 64).

Baseline characteristics were largely similar between the groups. However, patients in group 3 were significantly more likely than those in groups 1 and 2 to have del(5q) and monosomy 5+7 (P = .048).

Patients in group 1 had a significantly higher percentage of bone marrow transplants (as opposed to peripheral blood stem cell transplants) than patients in groups 2 and 3 (P = .039). And patients in group 1 had significantly fewer blasts at ASCT than patients in groups 2 and 3 (P = .011).

The researchers found no significant between-group differences in relapse and nonrelapse mortality, but there were significant differences in OS and RFS.

Patients in group 3 had inferior RFS compared to patients in group 1, which was the reference group. The hazard ratio (HR) was 2.503 (P = .013) in a univariable analysis and 2.196 (P = .049) in a multivariable analysis.

Group 3 also had inferior OS compared to group 1. The hazard ratio was 2.589 (P = .021) in a univariable analysis and 2.478 (P = .040) in a multivariable analysis.

There was no significant difference in RFS or OS between groups 1 and 2. The HR for RFS in group 2 was 1.879 (P = .148) in a univariable analysis and 1.365 (P = .506) in a multivariable analysis. The HR for OS was 1.997 (P = .155) and 1.413 (P = .511), respectively.

Dr. Modi said these results suggest patients with greater than 60% cytogenetically abnormal cells at ASCT should be monitored more closely after transplant, and their immunosuppressive medication should be tapered as soon as possible.

Dr. Modi and his colleagues reported having no conflicts of interest relevant to this research.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – Researchers say they’ve found an association between the percentage of cytogenetically abnormal cells at allogeneic stem cell transplant (ASCT) and posttransplant outcomes in patients with myelodysplastic syndromes (MDS).

Patients who had more than 60% cytogenetically abnormal cells at ASCT had significantly inferior overall survival (OS) and relapse-free survival (RFS), compared to patients with fewer abnormal cells.

Dipenkumar Modi, MD, of Barbara Ann Karmanos Cancer Institute at Wayne State University in Detroit, and his colleagues conducted this research and presented the results at the Acute Leukemia Forum of Hemedicus.

The researchers studied 109 adult MDS patients who underwent ASCT from January 2000 through December 2016. The patients were divided into three groups based on the percentage of cytogenetically abnormal cells at ASCT:

• Group 1 had less than 30% (n = 22)
• Group 2 had 30%-60% (n = 23)
• Group 3 had greater than 60% (n = 64).

Baseline characteristics were largely similar between the groups. However, patients in group 3 were significantly more likely than those in groups 1 and 2 to have del(5q) and monosomy 5+7 (P = .048).

Patients in group 1 had a significantly higher percentage of bone marrow transplants (as opposed to peripheral blood stem cell transplants) than patients in groups 2 and 3 (P = .039). And patients in group 1 had significantly fewer blasts at ASCT than patients in groups 2 and 3 (P = .011).

The researchers found no significant between-group differences in relapse and nonrelapse mortality, but there were significant differences in OS and RFS.

Patients in group 3 had inferior RFS compared to patients in group 1, which was the reference group. The hazard ratio (HR) was 2.503 (P = .013) in a univariable analysis and 2.196 (P = .049) in a multivariable analysis.

Group 3 also had inferior OS compared to group 1. The hazard ratio was 2.589 (P = .021) in a univariable analysis and 2.478 (P = .040) in a multivariable analysis.

There was no significant difference in RFS or OS between groups 1 and 2. The HR for RFS in group 2 was 1.879 (P = .148) in a univariable analysis and 1.365 (P = .506) in a multivariable analysis. The HR for OS was 1.997 (P = .155) and 1.413 (P = .511), respectively.

Dr. Modi said these results suggest patients with greater than 60% cytogenetically abnormal cells at ASCT should be monitored more closely after transplant, and their immunosuppressive medication should be tapered as soon as possible.

Dr. Modi and his colleagues reported having no conflicts of interest relevant to this research.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – Researchers say they’ve found an association between the percentage of cytogenetically abnormal cells at allogeneic stem cell transplant (ASCT) and posttransplant outcomes in patients with myelodysplastic syndromes (MDS).

Patients who had more than 60% cytogenetically abnormal cells at ASCT had significantly inferior overall survival (OS) and relapse-free survival (RFS), compared to patients with fewer abnormal cells.

Dipenkumar Modi, MD, of Barbara Ann Karmanos Cancer Institute at Wayne State University in Detroit, and his colleagues conducted this research and presented the results at the Acute Leukemia Forum of Hemedicus.

The researchers studied 109 adult MDS patients who underwent ASCT from January 2000 through December 2016. The patients were divided into three groups based on the percentage of cytogenetically abnormal cells at ASCT:

• Group 1 had less than 30% (n = 22)
• Group 2 had 30%-60% (n = 23)
• Group 3 had greater than 60% (n = 64).

Baseline characteristics were largely similar between the groups. However, patients in group 3 were significantly more likely than those in groups 1 and 2 to have del(5q) and monosomy 5+7 (P = .048).

Patients in group 1 had a significantly higher percentage of bone marrow transplants (as opposed to peripheral blood stem cell transplants) than patients in groups 2 and 3 (P = .039). And patients in group 1 had significantly fewer blasts at ASCT than patients in groups 2 and 3 (P = .011).

The researchers found no significant between-group differences in relapse and nonrelapse mortality, but there were significant differences in OS and RFS.

Patients in group 3 had inferior RFS compared to patients in group 1, which was the reference group. The hazard ratio (HR) was 2.503 (P = .013) in a univariable analysis and 2.196 (P = .049) in a multivariable analysis.

Group 3 also had inferior OS compared to group 1. The hazard ratio was 2.589 (P = .021) in a univariable analysis and 2.478 (P = .040) in a multivariable analysis.

There was no significant difference in RFS or OS between groups 1 and 2. The HR for RFS in group 2 was 1.879 (P = .148) in a univariable analysis and 1.365 (P = .506) in a multivariable analysis. The HR for OS was 1.997 (P = .155) and 1.413 (P = .511), respectively.

Dr. Modi said these results suggest patients with greater than 60% cytogenetically abnormal cells at ASCT should be monitored more closely after transplant, and their immunosuppressive medication should be tapered as soon as possible.

Dr. Modi and his colleagues reported having no conflicts of interest relevant to this research.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

LOS ANGELES – In patients with end-stage renal disease, women older than 50 years have a significantly higher mortality, compared with their male counterparts, results from an analysis of national data showed.

“The racial and ethnic disparities in the prevalence, treatment, risks, and outcomes of [hypertension] in patients with CKD [chronic kidney disease], are well recognized,” the study’s senior author, Ricardo Correa, MD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Whites have better control of blood pressure, compared with Hispanics or African Americans with CKD, for example. On the other hand, gender differences in the outcome of blood pressure control and mortality across the different CKD stages have been very poorly studied, with conflicting results.”

The importance of gender difference has been mostly the focus in cardiovascular diseases, he continued, with compelling data revealing a higher incidence in men than in women of similar age, and a menopause-associated increase in cardiovascular disease in women.

“Whether the same can be said for hypertension, remains to be elucidated,” said Dr. Correa, an endocrinologist who directs the diabetes and metabolism fellowship at the University of Arizona in Phoenix.

In what he said is the first study of its kind, Dr. Correa and his colleagues set out to determine if gender in the U.S. population and menopausal age affect the inpatient survival rate in hypertensive patients across different stages of CKD. They drew from the 2005-2012 National Inpatient Sample to identify 2,121,750 hospitalized hypertensive patients and compared a number of factors between men and women, including crude mortality and mortality per CKD stage, menopausal age, length of stay, and total hospital charges.

Of the 2,121,750 patients, 1,092,931 (52%) were men and 1,028,819 (48%) were women; their mean age was 65 years. Among women, 32% had stage 3 CKD, 15% had stage 4 disease, 3% had stage 5 CKD, and 54% had end-stage renal disease (ESRD). Among men, 33% had stage 3 CKD, 13% had stage 4 disease, 3% had stage 5 CKD, and 51% had ESRD. The researchers observed that in-hospital crude mortality was significantly higher for men, compared with a matched group of women at CKD stages 3 and 4 (3.09% vs. 3.29% for CDK 3; P less than .0001 and 4.05% vs. 4.36% for CDK 4; P = .0004), yet was nonsignificant among those with ESRD (4.68% vs. 4.83%; P = .45).

“One could hypothesize that cardiac remodeling in hemodialysis women may be different than that in hemodialysis men to the extent that it affects mortality,” Dr. Correa said. “However, it is unclear if the survival benefit for dialysis men is owing to the possibility of a selection bias or not. Dialysis women may not be receiving equal access to cardiovascular procedures or surgical interventions (arteriovenous fistula, for example) or women may not be offered adequate hemodialysis to the same extent as men are. Further investigations regarding sex-based differences in dialysis treatment are required.”

He acknowledged certain limitations of the study, including its observational design. “We lacked detailed information regarding the cause of death, dialysis efficiency, types of dialysis accesses, and left ventricular hypertrophy measurements. We did not account for transitions between different hemodialysis modalities [and] we do not have information about distances or traveling time to dialysis units.”

The study’s first author was Kelvin Tran, MD. The researchers reported having no financial disclosures.

[email protected]

LOS ANGELES – In patients with end-stage renal disease, women older than 50 years have a significantly higher mortality, compared with their male counterparts, results from an analysis of national data showed.

“The racial and ethnic disparities in the prevalence, treatment, risks, and outcomes of [hypertension] in patients with CKD [chronic kidney disease], are well recognized,” the study’s senior author, Ricardo Correa, MD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Whites have better control of blood pressure, compared with Hispanics or African Americans with CKD, for example. On the other hand, gender differences in the outcome of blood pressure control and mortality across the different CKD stages have been very poorly studied, with conflicting results.”

The importance of gender difference has been mostly the focus in cardiovascular diseases, he continued, with compelling data revealing a higher incidence in men than in women of similar age, and a menopause-associated increase in cardiovascular disease in women.

“Whether the same can be said for hypertension, remains to be elucidated,” said Dr. Correa, an endocrinologist who directs the diabetes and metabolism fellowship at the University of Arizona in Phoenix.

In what he said is the first study of its kind, Dr. Correa and his colleagues set out to determine if gender in the U.S. population and menopausal age affect the inpatient survival rate in hypertensive patients across different stages of CKD. They drew from the 2005-2012 National Inpatient Sample to identify 2,121,750 hospitalized hypertensive patients and compared a number of factors between men and women, including crude mortality and mortality per CKD stage, menopausal age, length of stay, and total hospital charges.

Of the 2,121,750 patients, 1,092,931 (52%) were men and 1,028,819 (48%) were women; their mean age was 65 years. Among women, 32% had stage 3 CKD, 15% had stage 4 disease, 3% had stage 5 CKD, and 54% had end-stage renal disease (ESRD). Among men, 33% had stage 3 CKD, 13% had stage 4 disease, 3% had stage 5 CKD, and 51% had ESRD. The researchers observed that in-hospital crude mortality was significantly higher for men, compared with a matched group of women at CKD stages 3 and 4 (3.09% vs. 3.29% for CDK 3; P less than .0001 and 4.05% vs. 4.36% for CDK 4; P = .0004), yet was nonsignificant among those with ESRD (4.68% vs. 4.83%; P = .45).

“One could hypothesize that cardiac remodeling in hemodialysis women may be different than that in hemodialysis men to the extent that it affects mortality,” Dr. Correa said. “However, it is unclear if the survival benefit for dialysis men is owing to the possibility of a selection bias or not. Dialysis women may not be receiving equal access to cardiovascular procedures or surgical interventions (arteriovenous fistula, for example) or women may not be offered adequate hemodialysis to the same extent as men are. Further investigations regarding sex-based differences in dialysis treatment are required.”

He acknowledged certain limitations of the study, including its observational design. “We lacked detailed information regarding the cause of death, dialysis efficiency, types of dialysis accesses, and left ventricular hypertrophy measurements. We did not account for transitions between different hemodialysis modalities [and] we do not have information about distances or traveling time to dialysis units.”

The study’s first author was Kelvin Tran, MD. The researchers reported having no financial disclosures.

[email protected]

LOS ANGELES – In patients with end-stage renal disease, women older than 50 years have a significantly higher mortality, compared with their male counterparts, results from an analysis of national data showed.

“The racial and ethnic disparities in the prevalence, treatment, risks, and outcomes of [hypertension] in patients with CKD [chronic kidney disease], are well recognized,” the study’s senior author, Ricardo Correa, MD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Whites have better control of blood pressure, compared with Hispanics or African Americans with CKD, for example. On the other hand, gender differences in the outcome of blood pressure control and mortality across the different CKD stages have been very poorly studied, with conflicting results.”

The importance of gender difference has been mostly the focus in cardiovascular diseases, he continued, with compelling data revealing a higher incidence in men than in women of similar age, and a menopause-associated increase in cardiovascular disease in women.

“Whether the same can be said for hypertension, remains to be elucidated,” said Dr. Correa, an endocrinologist who directs the diabetes and metabolism fellowship at the University of Arizona in Phoenix.

In what he said is the first study of its kind, Dr. Correa and his colleagues set out to determine if gender in the U.S. population and menopausal age affect the inpatient survival rate in hypertensive patients across different stages of CKD. They drew from the 2005-2012 National Inpatient Sample to identify 2,121,750 hospitalized hypertensive patients and compared a number of factors between men and women, including crude mortality and mortality per CKD stage, menopausal age, length of stay, and total hospital charges.

Of the 2,121,750 patients, 1,092,931 (52%) were men and 1,028,819 (48%) were women; their mean age was 65 years. Among women, 32% had stage 3 CKD, 15% had stage 4 disease, 3% had stage 5 CKD, and 54% had end-stage renal disease (ESRD). Among men, 33% had stage 3 CKD, 13% had stage 4 disease, 3% had stage 5 CKD, and 51% had ESRD. The researchers observed that in-hospital crude mortality was significantly higher for men, compared with a matched group of women at CKD stages 3 and 4 (3.09% vs. 3.29% for CDK 3; P less than .0001 and 4.05% vs. 4.36% for CDK 4; P = .0004), yet was nonsignificant among those with ESRD (4.68% vs. 4.83%; P = .45).

“One could hypothesize that cardiac remodeling in hemodialysis women may be different than that in hemodialysis men to the extent that it affects mortality,” Dr. Correa said. “However, it is unclear if the survival benefit for dialysis men is owing to the possibility of a selection bias or not. Dialysis women may not be receiving equal access to cardiovascular procedures or surgical interventions (arteriovenous fistula, for example) or women may not be offered adequate hemodialysis to the same extent as men are. Further investigations regarding sex-based differences in dialysis treatment are required.”

He acknowledged certain limitations of the study, including its observational design. “We lacked detailed information regarding the cause of death, dialysis efficiency, types of dialysis accesses, and left ventricular hypertrophy measurements. We did not account for transitions between different hemodialysis modalities [and] we do not have information about distances or traveling time to dialysis units.”

The study’s first author was Kelvin Tran, MD. The researchers reported having no financial disclosures.

[email protected]

NEWPORT BEACH, CALIF. – Researchers say they have identified biomarkers that may help guide early treatment decisions in patients with acute graft-versus-host disease (GVHD).

The biomarkers, ST2 and REG3-alpha, were measured during the first month of GVHD treatment and proved more accurate than clinical response for predicting 6-month nonrelapse mortality (NRM). In fact, biomarker assessment revealed patients who responded to treatment but had a high risk of NRM and nonresponders who had a low risk of NRM.

The researchers also found that biomarkers changed over the first month of treatment but remained significant predictors of NRM. This suggests that modifying treatment according to biomarker findings at various time points could result in better outcomes for patients.

“We think this is going to transform the way we treat graft-versus-host disease,” said James L.M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai, New York.

Dr. Ferrara and Hrishikesh Srinagesh, along with their colleagues at Mount Sinai, have conducted extensive research with these biomarkers and presented some of their findings at the Acute Leukemia Forum of Hemedicus.

Comparing biomarkers and response

In one study, the researchers evaluated 355 patients who had undergone allogeneic hematopoietic stem cell transplant at 1 of 20 Mount Sinai Acute GVHD International Consortium (MAGIC) centers between January 2016 and February 2018. All patients developed acute GVHD and received systemic steroids as treatment.

Patients provided blood samples weekly for the first month of treatment, and concentrations of ST2 and REG3-alpha were measured in each sample. Both biomarker concentrations were used to calculate the biomarker probability of NRM.

“The concentration of those two biomarkers are put into a computer, and we get … a single number, and that gives us the probability of mortality,” Dr. Ferrara said. “[W]e call this the MAGIC algorithm probability, or MAP. And when a MAP is low, the patient has a very low chance of dying from graft-versus-host disease, when it’s intermediate, they have an intermediate risk, and when it’s high, they have a high risk.”

The researchers then compared the MAP and clinical response for their ability to predict 6-month NRM throughout the first month of therapy for acute GVHD.

MAP bests response

After 1 month of therapy, the MAP was more accurate than clinical response for predicting 6-month NRM. The area under the curve was 0.84 and 0.65, respectively (P less than .001).

Likewise, the MAP after 1 week of therapy was more accurate than clinical response at 1 month for predicting 6-month NRM. The area under the curve was 0.80 and 0.65, respectively (P less than .001).

“[T]he clinical responses were good, but not great, at predicting long-term outcome, where the biomarker, the MAP, was significantly better,” Dr. Ferrara said. “[A]t every time point we tested, the biomarkers were better than the clinical responses.”

The researchers also identified subgroups of clinical responders and nonresponders for whom MAP more accurately predicted 6-month NRM.

The team found that 61% of clinical nonresponders were actually low risk according to MAP. And the incidence of 6-month NRM was significantly lower in the MAP-designated low-risk patients than in MAP-designated high-risk patients – 22% and 56%, respectively (P less than .001).

On the other hand, 10% of clinical responders were high risk according to MAP. The incidence of 6-month NRM was significantly higher in the high-risk patients than in the low-risk patients – 40% and 13%, respectively (P less than .001).

Assessing changes over time

The researchers found that patients who were initially high risk by MAP but had not experienced NRM by 6 months had significant decreases in their MAP after 4 weeks of treatment (P = .003). Patients who did experience NRM had a significant increase in their MAP whether their initial MAP was low (P = .007) or high (P = .024).

“What we found was that patients who lived tended to either have low biomarkers at the start of treatment and stay low or start out with high biomarkers and have reductions over the first month of therapy,” Mr. Srinagesh said. “Conversely, patients who tended to do worse were those who had either increases in their biomarkers or stayed high at all time points.”

The researchers identified a threshold – 0.290 – for separating patients by mortality risk.

“Patients who started out above the threshold and then went below it had a 5-fold reduction in mortality, whereas patients who started out below the threshold and rose above it had a 5-fold increase in mortality,” Mr. Srinagesh said.

MAP in clinical trials and practice

Based on these findings and results from related studies, the researchers theorize that MAP would be a better endpoint for clinical trials than clinical response.

At present, there are three trials in which researchers are using MAP as an endpoint to assess the efficacy of treatment for GVHD (NCT02133924, NCT03459040, and NCT03846479). Dr. Ferrara said a fourth trial is set to begin this summer.

Additionally, MAP is being used in clinical practice. A company called Viracor Eurofins Clinical Diagnostics licensed the MAGIC algorithm and provides three related tests for consumer use.

Viracor’s aGVHD Pre-Symptomatic Algorithm assigns patients to high- and low-risk groups based on results from samples collected 7 days after transplant. The aGVHD Symptomatic Onset Algorithm assigns patients to high-, intermediate-, and low-risk groups. The aGVHD Post-Treatment Algorithm, which can be used 7 days or more after GVHD treatment initiation, stratifies steroid-resistant patients into high- or low-risk groups for both NRM and overall survival.

“We are still in early days of figuring out how to use [the biomarker tests], but … what I’ve heard is that people are finding them to be useful in their clinical practice,” Dr. Ferrara said.

Dr. Ferrara has an ownership interest in and receives royalties from Viracor. Mr. Srinagesh reported having no relevant conflicts of interest. The research was supported by grants from the National Cancer Institute and the American Cancer Society.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – Researchers say they have identified biomarkers that may help guide early treatment decisions in patients with acute graft-versus-host disease (GVHD).

The biomarkers, ST2 and REG3-alpha, were measured during the first month of GVHD treatment and proved more accurate than clinical response for predicting 6-month nonrelapse mortality (NRM). In fact, biomarker assessment revealed patients who responded to treatment but had a high risk of NRM and nonresponders who had a low risk of NRM.

The researchers also found that biomarkers changed over the first month of treatment but remained significant predictors of NRM. This suggests that modifying treatment according to biomarker findings at various time points could result in better outcomes for patients.

“We think this is going to transform the way we treat graft-versus-host disease,” said James L.M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai, New York.

Dr. Ferrara and Hrishikesh Srinagesh, along with their colleagues at Mount Sinai, have conducted extensive research with these biomarkers and presented some of their findings at the Acute Leukemia Forum of Hemedicus.

Comparing biomarkers and response

In one study, the researchers evaluated 355 patients who had undergone allogeneic hematopoietic stem cell transplant at 1 of 20 Mount Sinai Acute GVHD International Consortium (MAGIC) centers between January 2016 and February 2018. All patients developed acute GVHD and received systemic steroids as treatment.

Patients provided blood samples weekly for the first month of treatment, and concentrations of ST2 and REG3-alpha were measured in each sample. Both biomarker concentrations were used to calculate the biomarker probability of NRM.

“The concentration of those two biomarkers are put into a computer, and we get … a single number, and that gives us the probability of mortality,” Dr. Ferrara said. “[W]e call this the MAGIC algorithm probability, or MAP. And when a MAP is low, the patient has a very low chance of dying from graft-versus-host disease, when it’s intermediate, they have an intermediate risk, and when it’s high, they have a high risk.”

The researchers then compared the MAP and clinical response for their ability to predict 6-month NRM throughout the first month of therapy for acute GVHD.

MAP bests response

After 1 month of therapy, the MAP was more accurate than clinical response for predicting 6-month NRM. The area under the curve was 0.84 and 0.65, respectively (P less than .001).

Likewise, the MAP after 1 week of therapy was more accurate than clinical response at 1 month for predicting 6-month NRM. The area under the curve was 0.80 and 0.65, respectively (P less than .001).

“[T]he clinical responses were good, but not great, at predicting long-term outcome, where the biomarker, the MAP, was significantly better,” Dr. Ferrara said. “[A]t every time point we tested, the biomarkers were better than the clinical responses.”

The researchers also identified subgroups of clinical responders and nonresponders for whom MAP more accurately predicted 6-month NRM.

The team found that 61% of clinical nonresponders were actually low risk according to MAP. And the incidence of 6-month NRM was significantly lower in the MAP-designated low-risk patients than in MAP-designated high-risk patients – 22% and 56%, respectively (P less than .001).

On the other hand, 10% of clinical responders were high risk according to MAP. The incidence of 6-month NRM was significantly higher in the high-risk patients than in the low-risk patients – 40% and 13%, respectively (P less than .001).

Assessing changes over time

The researchers found that patients who were initially high risk by MAP but had not experienced NRM by 6 months had significant decreases in their MAP after 4 weeks of treatment (P = .003). Patients who did experience NRM had a significant increase in their MAP whether their initial MAP was low (P = .007) or high (P = .024).

“What we found was that patients who lived tended to either have low biomarkers at the start of treatment and stay low or start out with high biomarkers and have reductions over the first month of therapy,” Mr. Srinagesh said. “Conversely, patients who tended to do worse were those who had either increases in their biomarkers or stayed high at all time points.”

The researchers identified a threshold – 0.290 – for separating patients by mortality risk.

“Patients who started out above the threshold and then went below it had a 5-fold reduction in mortality, whereas patients who started out below the threshold and rose above it had a 5-fold increase in mortality,” Mr. Srinagesh said.

MAP in clinical trials and practice

Based on these findings and results from related studies, the researchers theorize that MAP would be a better endpoint for clinical trials than clinical response.

At present, there are three trials in which researchers are using MAP as an endpoint to assess the efficacy of treatment for GVHD (NCT02133924, NCT03459040, and NCT03846479). Dr. Ferrara said a fourth trial is set to begin this summer.

Additionally, MAP is being used in clinical practice. A company called Viracor Eurofins Clinical Diagnostics licensed the MAGIC algorithm and provides three related tests for consumer use.

Viracor’s aGVHD Pre-Symptomatic Algorithm assigns patients to high- and low-risk groups based on results from samples collected 7 days after transplant. The aGVHD Symptomatic Onset Algorithm assigns patients to high-, intermediate-, and low-risk groups. The aGVHD Post-Treatment Algorithm, which can be used 7 days or more after GVHD treatment initiation, stratifies steroid-resistant patients into high- or low-risk groups for both NRM and overall survival.

“We are still in early days of figuring out how to use [the biomarker tests], but … what I’ve heard is that people are finding them to be useful in their clinical practice,” Dr. Ferrara said.

Dr. Ferrara has an ownership interest in and receives royalties from Viracor. Mr. Srinagesh reported having no relevant conflicts of interest. The research was supported by grants from the National Cancer Institute and the American Cancer Society.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – Researchers say they have identified biomarkers that may help guide early treatment decisions in patients with acute graft-versus-host disease (GVHD).

The biomarkers, ST2 and REG3-alpha, were measured during the first month of GVHD treatment and proved more accurate than clinical response for predicting 6-month nonrelapse mortality (NRM). In fact, biomarker assessment revealed patients who responded to treatment but had a high risk of NRM and nonresponders who had a low risk of NRM.

The researchers also found that biomarkers changed over the first month of treatment but remained significant predictors of NRM. This suggests that modifying treatment according to biomarker findings at various time points could result in better outcomes for patients.

“We think this is going to transform the way we treat graft-versus-host disease,” said James L.M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai, New York.

Dr. Ferrara and Hrishikesh Srinagesh, along with their colleagues at Mount Sinai, have conducted extensive research with these biomarkers and presented some of their findings at the Acute Leukemia Forum of Hemedicus.

Comparing biomarkers and response

In one study, the researchers evaluated 355 patients who had undergone allogeneic hematopoietic stem cell transplant at 1 of 20 Mount Sinai Acute GVHD International Consortium (MAGIC) centers between January 2016 and February 2018. All patients developed acute GVHD and received systemic steroids as treatment.

Patients provided blood samples weekly for the first month of treatment, and concentrations of ST2 and REG3-alpha were measured in each sample. Both biomarker concentrations were used to calculate the biomarker probability of NRM.

“The concentration of those two biomarkers are put into a computer, and we get … a single number, and that gives us the probability of mortality,” Dr. Ferrara said. “[W]e call this the MAGIC algorithm probability, or MAP. And when a MAP is low, the patient has a very low chance of dying from graft-versus-host disease, when it’s intermediate, they have an intermediate risk, and when it’s high, they have a high risk.”

The researchers then compared the MAP and clinical response for their ability to predict 6-month NRM throughout the first month of therapy for acute GVHD.

MAP bests response

After 1 month of therapy, the MAP was more accurate than clinical response for predicting 6-month NRM. The area under the curve was 0.84 and 0.65, respectively (P less than .001).

Likewise, the MAP after 1 week of therapy was more accurate than clinical response at 1 month for predicting 6-month NRM. The area under the curve was 0.80 and 0.65, respectively (P less than .001).

“[T]he clinical responses were good, but not great, at predicting long-term outcome, where the biomarker, the MAP, was significantly better,” Dr. Ferrara said. “[A]t every time point we tested, the biomarkers were better than the clinical responses.”

The researchers also identified subgroups of clinical responders and nonresponders for whom MAP more accurately predicted 6-month NRM.

The team found that 61% of clinical nonresponders were actually low risk according to MAP. And the incidence of 6-month NRM was significantly lower in the MAP-designated low-risk patients than in MAP-designated high-risk patients – 22% and 56%, respectively (P less than .001).

On the other hand, 10% of clinical responders were high risk according to MAP. The incidence of 6-month NRM was significantly higher in the high-risk patients than in the low-risk patients – 40% and 13%, respectively (P less than .001).

Assessing changes over time

The researchers found that patients who were initially high risk by MAP but had not experienced NRM by 6 months had significant decreases in their MAP after 4 weeks of treatment (P = .003). Patients who did experience NRM had a significant increase in their MAP whether their initial MAP was low (P = .007) or high (P = .024).

“What we found was that patients who lived tended to either have low biomarkers at the start of treatment and stay low or start out with high biomarkers and have reductions over the first month of therapy,” Mr. Srinagesh said. “Conversely, patients who tended to do worse were those who had either increases in their biomarkers or stayed high at all time points.”

The researchers identified a threshold – 0.290 – for separating patients by mortality risk.

“Patients who started out above the threshold and then went below it had a 5-fold reduction in mortality, whereas patients who started out below the threshold and rose above it had a 5-fold increase in mortality,” Mr. Srinagesh said.

MAP in clinical trials and practice

Based on these findings and results from related studies, the researchers theorize that MAP would be a better endpoint for clinical trials than clinical response.

At present, there are three trials in which researchers are using MAP as an endpoint to assess the efficacy of treatment for GVHD (NCT02133924, NCT03459040, and NCT03846479). Dr. Ferrara said a fourth trial is set to begin this summer.

Additionally, MAP is being used in clinical practice. A company called Viracor Eurofins Clinical Diagnostics licensed the MAGIC algorithm and provides three related tests for consumer use.

Viracor’s aGVHD Pre-Symptomatic Algorithm assigns patients to high- and low-risk groups based on results from samples collected 7 days after transplant. The aGVHD Symptomatic Onset Algorithm assigns patients to high-, intermediate-, and low-risk groups. The aGVHD Post-Treatment Algorithm, which can be used 7 days or more after GVHD treatment initiation, stratifies steroid-resistant patients into high- or low-risk groups for both NRM and overall survival.

“We are still in early days of figuring out how to use [the biomarker tests], but … what I’ve heard is that people are finding them to be useful in their clinical practice,” Dr. Ferrara said.

Dr. Ferrara has an ownership interest in and receives royalties from Viracor. Mr. Srinagesh reported having no relevant conflicts of interest. The research was supported by grants from the National Cancer Institute and the American Cancer Society.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

SAN FRANCISCO – All five innovative startups pitched at the Shark Tank at the 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology, are in advanced stages of development, but only one is given the opportunity to be declared the winner of the competition. The ideas ranged from a smart toilet for early disease detection to a unique strategy for obesity phenotyping, but the winner by both official decision and popular vote was a smartphone app to help patients with inflammatory bowel disease (IBD) manage the condition.

“As always, this year’s Shark Tank was a highlight of the AGA Tech Summit and represents the progress our field is making when it comes to innovation. Our panel of sharks was focused on understanding the problem each innovation solved – that’s the key when determining if an idea is novel or innovation for innovation’s sake. We were impressed with all of the technologies presented, but ultimately chose the Oshi Health IBD app as our winner because of the impact it is already having on improving the health and care of IBD patients,” said V. Raman Muthusamy, MD, AGAF, chair of the AGA Center for GI Innovation and Technology.
 

The winner: Oshi pitches “all-in-one” IBD app

By both popular vote from those attending the AGA Tech Summit as well as the six-member Shark Tank panel, Oshi Health was selected as the 2019 Shark Tank winner for its IBD app. The app was designed to help patients track symptoms, a first step in understanding flare patterns, which differ substantially between patients and emphasize the need for a personalized plan for controlling disease.

Vidyard Video

“Since we launched last June at DDW^® we have had 40,000 downloads. We are the number one IBD management app,” reported Dan Weinstein, MBA, CEO of Oshi Health.

The available app represents the first of three phases as the functionality is expanded. Currently, in addition to using the app as a tracking tool, patients can find resources to learn about their disease and to communicate with other patients about their experiences. In a second phase, information gathered by the app will be made available to physicians to provide accurate current information about disease status to better individualize therapy.

Ultimately, the app is expected to guide treatment based on information it has collected on symptom patterns and other data collected over time, although this application is further down the road and will require regulatory approval if it is designed to provide clinical advice as expected, according to Mr. Weinstein.

However, benefits have already been seen. Mr. Weinstein cited data that associated the app with a 40% improvement in medication adherence and a nearly 60-day reduction in flare duration. Calling the app “the next chapter in treat-to-target” IBD management, he believes that this is an important step forward in digital health that will improve IBD outcomes. The Shark Tank panel agreed.
 

Runners-up: Other potential innovations to improve GI health

With or without Shark Tank endorsement, the other four startups described in the competition are moving forward. Each is designed to address an important unmet need with the potential to improve patient outcomes, which is a criterion for their inclusion in the competition.

 

 

The smart toilet seat

One involves a technologically advanced toilet seat. The new seat is based on the fact that fecal matter provides insight into a broad array of disease states, but specimen collection is a hurdle for a variety of reasons, including patient resistance. A toilet seat developed by Toi Labs, called TrueLoo, is equipped with lighting and cameras that captures images of bowel movements and urination for subsequent analysis.

“The toilet seat sees what the eye cannot,” according to Vikram Kashyap, CEO of Toi Labs. He believes it has major potential for early detection of conditions ranging from dehydration to gastrointestinal cancer.

Vidyard Video

Others agree. According to Mr. Kashyap, executives of a chain of senior living facilities have already expressed interest in installing this seat to better monitor health among residents. The seat is bolted into position in place of any standard toilet seat. It collects images and data that are transmitted directly to a cellular network.

“Using our technology, the goal is to catch disease states early before they progress,” said Mr. Kashyap, who called the surveillance system a low-cost disease-screening tool. He believes the smart toilet seat could be of the most important disease detection devices developed in recent years.

AI to aid screening endoscopy

A third entrant in this year’s Shark Tank described a strategy to employ artificial intelligence (AI) to aid endoscopists in screening for dysplasia. The tool is called Ultivision and is being developed by a startup called Docbot. The CEO, Andrew Ninh, and a senior executive, Jason B. Samarasena, MD, outlined an idea that could be used in either screening colonoscopy or in surveillance of Barrett’s esophagus).

“Dysplasia is difficult to find. It is subtle and it is often missed. With better detection of dysplasia, artificial intelligence offers an opportunity to reduce risk of cancer,” Dr. Samarasena said.

The tool integrates seamlessly with existing endoscopic tools, according to Mr. Ninh. As tissue is visualized, the AI is programmed to highlight suspected dysplasia with a colored box to alert the endoscopist. The colonoscopy application is a more advanced stage of development and might be submitted for regulatory approval this year, he said. The same technology will be adapted for Barrett’s esophagus.

“It is like facial recognition for dysplasia,” said Dr. Samarasena.
 

Obesity phenotyping tool

A fourth Shark Tank entrant employs technology to phenotype obese patients to better tailor therapy. The Pheno Test, developed by Phenomix Sciences, applies “multi-omics” to a blood-based test to separate patients with obesity into four phenotypes. When therapy is tailored to the phenotype, weight loss is greater, according to Andres J. Acosta, MD, PhD, assistant professor of medicine and consultant in gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

In an initial study that compared weight loss in 55 patients treated based on phenotype with 175 patients managed with standard of care, the total body weight loss “more than doubled,” Dr. Acosta reported.

According to Dr. Acosta, obesity is driven by very different mechanisms. He described the four major phenotypes identified with his test as hungry brain (satiation signal is impaired), hungry gut (signals to eat are upregulated), emotional hunger (psychological reasons drive eating behavior), and slow metabolism (failure to burn fat at normal rates).

With the blood test, which utilizes hormones, metabolites, DNA, and other biomarkers to separate these phenotypes, treatment can be tailored appropriately, according to Dr. Acosta. His company is now seeking Food and Drug Administration clearance of the test, which he believes will have a major impact on obesity control.
 

 

 

Capsule diagnostic tool

The final entrant selected to participate in this year’s Shark Tank described an ingestible capsule that diagnoses diseases by detecting gases as it descends the gastrointestinal tract. The Atmo Gas Capsule from Atmo Biosciences measures gases at the source, accelerating the diagnosis of such diseases as irritable bowel syndrome (IBS) and IBD.

“By measuring gases at their source, the accuracy is far better than a breath test,” said Malcolm Hebblewhite, MBA, CEO of Atmo Biosciences. The capsule is an alternative to more invasive and expensive diagnostic tools and it is highly accurate.

Providing examples, Mr. Hebblewhite said that elevated levels of oxygen suggest a disorder of motility while an elevated level of carbon dioxide and hydrogen suggest IBS. The capsule transmits data to a small receiver and then on to a smartphone.

“The real-time data is displayed for the user with more complex information accessible by the practitioner remotely via the cloud,” Mr. Hebblewhite said. He cited several papers that have already been published documenting the potential of this technology.

“The capsule is a single-use disposable device that is not retrieved,” according to Mr. Hebblewhite. He reported that his company plans to pursue the diagnosis of motility as an initial clinical application. The diagnosis of IBS and other GI conditions will follow. Clinical studies are already planned.

SAN FRANCISCO – All five innovative startups pitched at the Shark Tank at the 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology, are in advanced stages of development, but only one is given the opportunity to be declared the winner of the competition. The ideas ranged from a smart toilet for early disease detection to a unique strategy for obesity phenotyping, but the winner by both official decision and popular vote was a smartphone app to help patients with inflammatory bowel disease (IBD) manage the condition.

“As always, this year’s Shark Tank was a highlight of the AGA Tech Summit and represents the progress our field is making when it comes to innovation. Our panel of sharks was focused on understanding the problem each innovation solved – that’s the key when determining if an idea is novel or innovation for innovation’s sake. We were impressed with all of the technologies presented, but ultimately chose the Oshi Health IBD app as our winner because of the impact it is already having on improving the health and care of IBD patients,” said V. Raman Muthusamy, MD, AGAF, chair of the AGA Center for GI Innovation and Technology.
 

The winner: Oshi pitches “all-in-one” IBD app

By both popular vote from those attending the AGA Tech Summit as well as the six-member Shark Tank panel, Oshi Health was selected as the 2019 Shark Tank winner for its IBD app. The app was designed to help patients track symptoms, a first step in understanding flare patterns, which differ substantially between patients and emphasize the need for a personalized plan for controlling disease.

Vidyard Video

“Since we launched last June at DDW^® we have had 40,000 downloads. We are the number one IBD management app,” reported Dan Weinstein, MBA, CEO of Oshi Health.

The available app represents the first of three phases as the functionality is expanded. Currently, in addition to using the app as a tracking tool, patients can find resources to learn about their disease and to communicate with other patients about their experiences. In a second phase, information gathered by the app will be made available to physicians to provide accurate current information about disease status to better individualize therapy.

Ultimately, the app is expected to guide treatment based on information it has collected on symptom patterns and other data collected over time, although this application is further down the road and will require regulatory approval if it is designed to provide clinical advice as expected, according to Mr. Weinstein.

However, benefits have already been seen. Mr. Weinstein cited data that associated the app with a 40% improvement in medication adherence and a nearly 60-day reduction in flare duration. Calling the app “the next chapter in treat-to-target” IBD management, he believes that this is an important step forward in digital health that will improve IBD outcomes. The Shark Tank panel agreed.
 

Runners-up: Other potential innovations to improve GI health

With or without Shark Tank endorsement, the other four startups described in the competition are moving forward. Each is designed to address an important unmet need with the potential to improve patient outcomes, which is a criterion for their inclusion in the competition.

 

 

The smart toilet seat

One involves a technologically advanced toilet seat. The new seat is based on the fact that fecal matter provides insight into a broad array of disease states, but specimen collection is a hurdle for a variety of reasons, including patient resistance. A toilet seat developed by Toi Labs, called TrueLoo, is equipped with lighting and cameras that captures images of bowel movements and urination for subsequent analysis.

“The toilet seat sees what the eye cannot,” according to Vikram Kashyap, CEO of Toi Labs. He believes it has major potential for early detection of conditions ranging from dehydration to gastrointestinal cancer.

Vidyard Video

Others agree. According to Mr. Kashyap, executives of a chain of senior living facilities have already expressed interest in installing this seat to better monitor health among residents. The seat is bolted into position in place of any standard toilet seat. It collects images and data that are transmitted directly to a cellular network.

“Using our technology, the goal is to catch disease states early before they progress,” said Mr. Kashyap, who called the surveillance system a low-cost disease-screening tool. He believes the smart toilet seat could be of the most important disease detection devices developed in recent years.

AI to aid screening endoscopy

A third entrant in this year’s Shark Tank described a strategy to employ artificial intelligence (AI) to aid endoscopists in screening for dysplasia. The tool is called Ultivision and is being developed by a startup called Docbot. The CEO, Andrew Ninh, and a senior executive, Jason B. Samarasena, MD, outlined an idea that could be used in either screening colonoscopy or in surveillance of Barrett’s esophagus).

“Dysplasia is difficult to find. It is subtle and it is often missed. With better detection of dysplasia, artificial intelligence offers an opportunity to reduce risk of cancer,” Dr. Samarasena said.

The tool integrates seamlessly with existing endoscopic tools, according to Mr. Ninh. As tissue is visualized, the AI is programmed to highlight suspected dysplasia with a colored box to alert the endoscopist. The colonoscopy application is a more advanced stage of development and might be submitted for regulatory approval this year, he said. The same technology will be adapted for Barrett’s esophagus.

“It is like facial recognition for dysplasia,” said Dr. Samarasena.
 

Obesity phenotyping tool

A fourth Shark Tank entrant employs technology to phenotype obese patients to better tailor therapy. The Pheno Test, developed by Phenomix Sciences, applies “multi-omics” to a blood-based test to separate patients with obesity into four phenotypes. When therapy is tailored to the phenotype, weight loss is greater, according to Andres J. Acosta, MD, PhD, assistant professor of medicine and consultant in gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

In an initial study that compared weight loss in 55 patients treated based on phenotype with 175 patients managed with standard of care, the total body weight loss “more than doubled,” Dr. Acosta reported.

According to Dr. Acosta, obesity is driven by very different mechanisms. He described the four major phenotypes identified with his test as hungry brain (satiation signal is impaired), hungry gut (signals to eat are upregulated), emotional hunger (psychological reasons drive eating behavior), and slow metabolism (failure to burn fat at normal rates).

With the blood test, which utilizes hormones, metabolites, DNA, and other biomarkers to separate these phenotypes, treatment can be tailored appropriately, according to Dr. Acosta. His company is now seeking Food and Drug Administration clearance of the test, which he believes will have a major impact on obesity control.
 

 

 

Capsule diagnostic tool

The final entrant selected to participate in this year’s Shark Tank described an ingestible capsule that diagnoses diseases by detecting gases as it descends the gastrointestinal tract. The Atmo Gas Capsule from Atmo Biosciences measures gases at the source, accelerating the diagnosis of such diseases as irritable bowel syndrome (IBS) and IBD.

“By measuring gases at their source, the accuracy is far better than a breath test,” said Malcolm Hebblewhite, MBA, CEO of Atmo Biosciences. The capsule is an alternative to more invasive and expensive diagnostic tools and it is highly accurate.

Providing examples, Mr. Hebblewhite said that elevated levels of oxygen suggest a disorder of motility while an elevated level of carbon dioxide and hydrogen suggest IBS. The capsule transmits data to a small receiver and then on to a smartphone.

“The real-time data is displayed for the user with more complex information accessible by the practitioner remotely via the cloud,” Mr. Hebblewhite said. He cited several papers that have already been published documenting the potential of this technology.

“The capsule is a single-use disposable device that is not retrieved,” according to Mr. Hebblewhite. He reported that his company plans to pursue the diagnosis of motility as an initial clinical application. The diagnosis of IBS and other GI conditions will follow. Clinical studies are already planned.

SAN FRANCISCO – All five innovative startups pitched at the Shark Tank at the 2019 AGA Tech Summit, sponsored by the AGA Center for GI Innovation and Technology, are in advanced stages of development, but only one is given the opportunity to be declared the winner of the competition. The ideas ranged from a smart toilet for early disease detection to a unique strategy for obesity phenotyping, but the winner by both official decision and popular vote was a smartphone app to help patients with inflammatory bowel disease (IBD) manage the condition.

“As always, this year’s Shark Tank was a highlight of the AGA Tech Summit and represents the progress our field is making when it comes to innovation. Our panel of sharks was focused on understanding the problem each innovation solved – that’s the key when determining if an idea is novel or innovation for innovation’s sake. We were impressed with all of the technologies presented, but ultimately chose the Oshi Health IBD app as our winner because of the impact it is already having on improving the health and care of IBD patients,” said V. Raman Muthusamy, MD, AGAF, chair of the AGA Center for GI Innovation and Technology.
 

The winner: Oshi pitches “all-in-one” IBD app

By both popular vote from those attending the AGA Tech Summit as well as the six-member Shark Tank panel, Oshi Health was selected as the 2019 Shark Tank winner for its IBD app. The app was designed to help patients track symptoms, a first step in understanding flare patterns, which differ substantially between patients and emphasize the need for a personalized plan for controlling disease.

Vidyard Video

“Since we launched last June at DDW^® we have had 40,000 downloads. We are the number one IBD management app,” reported Dan Weinstein, MBA, CEO of Oshi Health.

The available app represents the first of three phases as the functionality is expanded. Currently, in addition to using the app as a tracking tool, patients can find resources to learn about their disease and to communicate with other patients about their experiences. In a second phase, information gathered by the app will be made available to physicians to provide accurate current information about disease status to better individualize therapy.

Ultimately, the app is expected to guide treatment based on information it has collected on symptom patterns and other data collected over time, although this application is further down the road and will require regulatory approval if it is designed to provide clinical advice as expected, according to Mr. Weinstein.

However, benefits have already been seen. Mr. Weinstein cited data that associated the app with a 40% improvement in medication adherence and a nearly 60-day reduction in flare duration. Calling the app “the next chapter in treat-to-target” IBD management, he believes that this is an important step forward in digital health that will improve IBD outcomes. The Shark Tank panel agreed.
 

Runners-up: Other potential innovations to improve GI health

With or without Shark Tank endorsement, the other four startups described in the competition are moving forward. Each is designed to address an important unmet need with the potential to improve patient outcomes, which is a criterion for their inclusion in the competition.

 

 

The smart toilet seat

One involves a technologically advanced toilet seat. The new seat is based on the fact that fecal matter provides insight into a broad array of disease states, but specimen collection is a hurdle for a variety of reasons, including patient resistance. A toilet seat developed by Toi Labs, called TrueLoo, is equipped with lighting and cameras that captures images of bowel movements and urination for subsequent analysis.

“The toilet seat sees what the eye cannot,” according to Vikram Kashyap, CEO of Toi Labs. He believes it has major potential for early detection of conditions ranging from dehydration to gastrointestinal cancer.

Vidyard Video

Others agree. According to Mr. Kashyap, executives of a chain of senior living facilities have already expressed interest in installing this seat to better monitor health among residents. The seat is bolted into position in place of any standard toilet seat. It collects images and data that are transmitted directly to a cellular network.

“Using our technology, the goal is to catch disease states early before they progress,” said Mr. Kashyap, who called the surveillance system a low-cost disease-screening tool. He believes the smart toilet seat could be of the most important disease detection devices developed in recent years.

AI to aid screening endoscopy

A third entrant in this year’s Shark Tank described a strategy to employ artificial intelligence (AI) to aid endoscopists in screening for dysplasia. The tool is called Ultivision and is being developed by a startup called Docbot. The CEO, Andrew Ninh, and a senior executive, Jason B. Samarasena, MD, outlined an idea that could be used in either screening colonoscopy or in surveillance of Barrett’s esophagus).

“Dysplasia is difficult to find. It is subtle and it is often missed. With better detection of dysplasia, artificial intelligence offers an opportunity to reduce risk of cancer,” Dr. Samarasena said.

The tool integrates seamlessly with existing endoscopic tools, according to Mr. Ninh. As tissue is visualized, the AI is programmed to highlight suspected dysplasia with a colored box to alert the endoscopist. The colonoscopy application is a more advanced stage of development and might be submitted for regulatory approval this year, he said. The same technology will be adapted for Barrett’s esophagus.

“It is like facial recognition for dysplasia,” said Dr. Samarasena.
 

Obesity phenotyping tool

A fourth Shark Tank entrant employs technology to phenotype obese patients to better tailor therapy. The Pheno Test, developed by Phenomix Sciences, applies “multi-omics” to a blood-based test to separate patients with obesity into four phenotypes. When therapy is tailored to the phenotype, weight loss is greater, according to Andres J. Acosta, MD, PhD, assistant professor of medicine and consultant in gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

In an initial study that compared weight loss in 55 patients treated based on phenotype with 175 patients managed with standard of care, the total body weight loss “more than doubled,” Dr. Acosta reported.

According to Dr. Acosta, obesity is driven by very different mechanisms. He described the four major phenotypes identified with his test as hungry brain (satiation signal is impaired), hungry gut (signals to eat are upregulated), emotional hunger (psychological reasons drive eating behavior), and slow metabolism (failure to burn fat at normal rates).

With the blood test, which utilizes hormones, metabolites, DNA, and other biomarkers to separate these phenotypes, treatment can be tailored appropriately, according to Dr. Acosta. His company is now seeking Food and Drug Administration clearance of the test, which he believes will have a major impact on obesity control.
 

 

 

Capsule diagnostic tool

The final entrant selected to participate in this year’s Shark Tank described an ingestible capsule that diagnoses diseases by detecting gases as it descends the gastrointestinal tract. The Atmo Gas Capsule from Atmo Biosciences measures gases at the source, accelerating the diagnosis of such diseases as irritable bowel syndrome (IBS) and IBD.

“By measuring gases at their source, the accuracy is far better than a breath test,” said Malcolm Hebblewhite, MBA, CEO of Atmo Biosciences. The capsule is an alternative to more invasive and expensive diagnostic tools and it is highly accurate.

Providing examples, Mr. Hebblewhite said that elevated levels of oxygen suggest a disorder of motility while an elevated level of carbon dioxide and hydrogen suggest IBS. The capsule transmits data to a small receiver and then on to a smartphone.

“The real-time data is displayed for the user with more complex information accessible by the practitioner remotely via the cloud,” Mr. Hebblewhite said. He cited several papers that have already been published documenting the potential of this technology.

“The capsule is a single-use disposable device that is not retrieved,” according to Mr. Hebblewhite. He reported that his company plans to pursue the diagnosis of motility as an initial clinical application. The diagnosis of IBS and other GI conditions will follow. Clinical studies are already planned.

NEWPORT BEACH, CALIF. — A model that mimics the recommender system used by Netflix and Amazon can help predict outcomes of lenalidomide treatment in patients with non–deletion 5q (non-del[5q]) myelodysplastic syndromes (MDS), according to new research.

The model was used to identify genomic biomarkers that were associated with resistance or response to lenalidomide. Researchers found these associations in 39% of patients with non-del(5q) MDS, and the model predicted response or resistance with 82% accuracy.

Yazan Madanat, MD, of the Cleveland Clinic, and his colleagues presented these findings at the Acute Leukemia Forum of Hemedicus.

Dr. Madanat explained that his group’s model is similar to the recommender system used by Netflix and Amazon, which makes suggestions for new products based on customers’ past behavior. Dr. Madanat and his colleagues used their model to show that patients with certain molecular or cytogenetic abnormalities are likely to respond or not respond to lenalidomide.

The researchers began by looking at 139 patients who had received at least two cycles of lenalidomide treatment. There were 118 patients with MDS, and 108 who had received lenalidomide monotherapy. However, the team focused on the 100 patients who had non-del(5q) MDS, 58 of whom had normal karyotype (NK) and 19 of whom had complex karyotype (CK).

The model revealed several combinations of genomic/cytogenetic abnormalities that could predict resistance to lenalidomide, including the following:

• DNMT3A and SF3B1
• EZH2 and NK
• ASXL1, TET2, and NK
• STAG2, IDH1/2, and NK
• TP53, del(5q), and CK
• BCOR/BCORL1 and NK
• JAK2, TET2, and NK
• U2AF1, +/– ETV6, and NK

However, only the following two combinations could predict response to lenalidomide:

• DDX41 and NK
• MECOM and KDM6A/B

These combinations could be applied to 39% of the patients with non-del(5q) MDS, and the model predicted response or resistance to lenalidomide with 82% accuracy.

Although the biomarkers were found in only a subset of patients, Dr. Madanat said these findings may help physicians tailor therapy for MDS patients, given the high level of accuracy the researchers observed.

“It’s really important to validate the results in a prospective manner and to ensure that we’re able to apply them clinically and potentially change the way we’re treating our patients,” he added.

Dr. Madanat and his colleagues reported having no relevant conflicts of interest.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. — A model that mimics the recommender system used by Netflix and Amazon can help predict outcomes of lenalidomide treatment in patients with non–deletion 5q (non-del[5q]) myelodysplastic syndromes (MDS), according to new research.

The model was used to identify genomic biomarkers that were associated with resistance or response to lenalidomide. Researchers found these associations in 39% of patients with non-del(5q) MDS, and the model predicted response or resistance with 82% accuracy.

Yazan Madanat, MD, of the Cleveland Clinic, and his colleagues presented these findings at the Acute Leukemia Forum of Hemedicus.

Dr. Madanat explained that his group’s model is similar to the recommender system used by Netflix and Amazon, which makes suggestions for new products based on customers’ past behavior. Dr. Madanat and his colleagues used their model to show that patients with certain molecular or cytogenetic abnormalities are likely to respond or not respond to lenalidomide.

The researchers began by looking at 139 patients who had received at least two cycles of lenalidomide treatment. There were 118 patients with MDS, and 108 who had received lenalidomide monotherapy. However, the team focused on the 100 patients who had non-del(5q) MDS, 58 of whom had normal karyotype (NK) and 19 of whom had complex karyotype (CK).

The model revealed several combinations of genomic/cytogenetic abnormalities that could predict resistance to lenalidomide, including the following:

• DNMT3A and SF3B1
• EZH2 and NK
• ASXL1, TET2, and NK
• STAG2, IDH1/2, and NK
• TP53, del(5q), and CK
• BCOR/BCORL1 and NK
• JAK2, TET2, and NK
• U2AF1, +/– ETV6, and NK

However, only the following two combinations could predict response to lenalidomide:

• DDX41 and NK
• MECOM and KDM6A/B

These combinations could be applied to 39% of the patients with non-del(5q) MDS, and the model predicted response or resistance to lenalidomide with 82% accuracy.

Although the biomarkers were found in only a subset of patients, Dr. Madanat said these findings may help physicians tailor therapy for MDS patients, given the high level of accuracy the researchers observed.

“It’s really important to validate the results in a prospective manner and to ensure that we’re able to apply them clinically and potentially change the way we’re treating our patients,” he added.

Dr. Madanat and his colleagues reported having no relevant conflicts of interest.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. — A model that mimics the recommender system used by Netflix and Amazon can help predict outcomes of lenalidomide treatment in patients with non–deletion 5q (non-del[5q]) myelodysplastic syndromes (MDS), according to new research.

The model was used to identify genomic biomarkers that were associated with resistance or response to lenalidomide. Researchers found these associations in 39% of patients with non-del(5q) MDS, and the model predicted response or resistance with 82% accuracy.

Yazan Madanat, MD, of the Cleveland Clinic, and his colleagues presented these findings at the Acute Leukemia Forum of Hemedicus.

Dr. Madanat explained that his group’s model is similar to the recommender system used by Netflix and Amazon, which makes suggestions for new products based on customers’ past behavior. Dr. Madanat and his colleagues used their model to show that patients with certain molecular or cytogenetic abnormalities are likely to respond or not respond to lenalidomide.

The researchers began by looking at 139 patients who had received at least two cycles of lenalidomide treatment. There were 118 patients with MDS, and 108 who had received lenalidomide monotherapy. However, the team focused on the 100 patients who had non-del(5q) MDS, 58 of whom had normal karyotype (NK) and 19 of whom had complex karyotype (CK).

The model revealed several combinations of genomic/cytogenetic abnormalities that could predict resistance to lenalidomide, including the following:

• DNMT3A and SF3B1
• EZH2 and NK
• ASXL1, TET2, and NK
• STAG2, IDH1/2, and NK
• TP53, del(5q), and CK
• BCOR/BCORL1 and NK
• JAK2, TET2, and NK
• U2AF1, +/– ETV6, and NK

However, only the following two combinations could predict response to lenalidomide:

• DDX41 and NK
• MECOM and KDM6A/B

These combinations could be applied to 39% of the patients with non-del(5q) MDS, and the model predicted response or resistance to lenalidomide with 82% accuracy.

Although the biomarkers were found in only a subset of patients, Dr. Madanat said these findings may help physicians tailor therapy for MDS patients, given the high level of accuracy the researchers observed.

“It’s really important to validate the results in a prospective manner and to ensure that we’re able to apply them clinically and potentially change the way we’re treating our patients,” he added.

Dr. Madanat and his colleagues reported having no relevant conflicts of interest.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEW ORLEANS – A well-attended afternoon symposium on transgender medicine gave participants at the annual meeting of the Endocrine Society a solid grounding in transgender care, from prepubescence through adulthood. Here, Joshua Safer, MD, and Michael Irwig, MD, discuss highlights of the symposium, which brought together research, best practices, and clinical practice pearls.

In his presentation, Dr. Safer focused on evidence-based strategies in medical education that can increase knowledge and comfort for trainees who are caring for transgender individuals. The basics, he said, begin with presenting well-established, scientific principles supporting current standards of transgender care.

Dr. Safer, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York, pointed out the critical role of gonadotropin-releasing hormone antagonists in delaying puberty for transgender girls. Blockade of puberty – and elevated testosterone – can forestall otherwise irreversible male secondary sex characteristics. These include laryngeal enlargement and bony changes of facial structure, for example.

Dr. Irwig, director of andrology at George Washington University, Washington, laid out the basics of transgender hormone therapy, including clinical pearls, such as avoiding ethinyl estradiol because of the heightened risk of venous thromboembolism.

Dr. Safer is a member of the editorial advisory board of Clinical Endocrinology News. He reported that he has received consulting fees from Endo Pharmaceuticals and that his spouse is an employee of Parexel. Dr. Irwig reported no relevant conflicts of interest or financial disclosures.

[email protected]

NEW ORLEANS – A well-attended afternoon symposium on transgender medicine gave participants at the annual meeting of the Endocrine Society a solid grounding in transgender care, from prepubescence through adulthood. Here, Joshua Safer, MD, and Michael Irwig, MD, discuss highlights of the symposium, which brought together research, best practices, and clinical practice pearls.

In his presentation, Dr. Safer focused on evidence-based strategies in medical education that can increase knowledge and comfort for trainees who are caring for transgender individuals. The basics, he said, begin with presenting well-established, scientific principles supporting current standards of transgender care.

Dr. Safer, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York, pointed out the critical role of gonadotropin-releasing hormone antagonists in delaying puberty for transgender girls. Blockade of puberty – and elevated testosterone – can forestall otherwise irreversible male secondary sex characteristics. These include laryngeal enlargement and bony changes of facial structure, for example.

Dr. Irwig, director of andrology at George Washington University, Washington, laid out the basics of transgender hormone therapy, including clinical pearls, such as avoiding ethinyl estradiol because of the heightened risk of venous thromboembolism.

Dr. Safer is a member of the editorial advisory board of Clinical Endocrinology News. He reported that he has received consulting fees from Endo Pharmaceuticals and that his spouse is an employee of Parexel. Dr. Irwig reported no relevant conflicts of interest or financial disclosures.

[email protected]

NEW ORLEANS – A well-attended afternoon symposium on transgender medicine gave participants at the annual meeting of the Endocrine Society a solid grounding in transgender care, from prepubescence through adulthood. Here, Joshua Safer, MD, and Michael Irwig, MD, discuss highlights of the symposium, which brought together research, best practices, and clinical practice pearls.

In his presentation, Dr. Safer focused on evidence-based strategies in medical education that can increase knowledge and comfort for trainees who are caring for transgender individuals. The basics, he said, begin with presenting well-established, scientific principles supporting current standards of transgender care.

Dr. Safer, executive director of the Mount Sinai Center for Transgender Medicine and Surgery, New York, pointed out the critical role of gonadotropin-releasing hormone antagonists in delaying puberty for transgender girls. Blockade of puberty – and elevated testosterone – can forestall otherwise irreversible male secondary sex characteristics. These include laryngeal enlargement and bony changes of facial structure, for example.

Dr. Irwig, director of andrology at George Washington University, Washington, laid out the basics of transgender hormone therapy, including clinical pearls, such as avoiding ethinyl estradiol because of the heightened risk of venous thromboembolism.

Dr. Safer is a member of the editorial advisory board of Clinical Endocrinology News. He reported that he has received consulting fees from Endo Pharmaceuticals and that his spouse is an employee of Parexel. Dr. Irwig reported no relevant conflicts of interest or financial disclosures.

[email protected]

SAN FRANCISCO – New York University researchers have found a ninefold increase of the bacterium Ruminococcus gnavus in the intestines of particularly ill lupus patients.

Not only that, but those patients also had highly elevated antibodies to an endotoxin-like antigen released by one particular R. gnavus strain.

That antigen is “very proinflammatory, very immunogenic. We are wondering if this is actually [what drives] the immune activation that results in immune complexes in the glomeruli” of patients with lupus nephritis, said investigator Gregg Silverman, MD, a professor of medicine and pathology and head of the laboratory of B-cell immunobiology at New York University.

R. gnavus is an obligate anaerobe found in the guts of most people, but in lupus, it might be a problem.

“We are finding a very specific relationship with lupus patients and this bacteria – and this particular antibody,” Dr. Silverman explained in an interview at an international congress on systemic lupus erythematosus. “There’s an expansion of this particular bug, but also a contraction of others” as disease activity progresses.

“It speaks to an imbalance,” he added, and it suggests a role for probiotics or even fecal transplants to restore order.

“What if instead of killing the immune system” in lupus treatment, “we should be reducing or removing a single bacterium or a single molecule?” he asked.

Dr. Silverman is one of many researchers working to unravel the role of the human microbiome in both disease and health. His findings are preliminary, and, as he cautioned, correlation is not causation. But the implications are remarkable, Dr. Silverman noted.

SAN FRANCISCO – New York University researchers have found a ninefold increase of the bacterium Ruminococcus gnavus in the intestines of particularly ill lupus patients.

Not only that, but those patients also had highly elevated antibodies to an endotoxin-like antigen released by one particular R. gnavus strain.

That antigen is “very proinflammatory, very immunogenic. We are wondering if this is actually [what drives] the immune activation that results in immune complexes in the glomeruli” of patients with lupus nephritis, said investigator Gregg Silverman, MD, a professor of medicine and pathology and head of the laboratory of B-cell immunobiology at New York University.

R. gnavus is an obligate anaerobe found in the guts of most people, but in lupus, it might be a problem.

“We are finding a very specific relationship with lupus patients and this bacteria – and this particular antibody,” Dr. Silverman explained in an interview at an international congress on systemic lupus erythematosus. “There’s an expansion of this particular bug, but also a contraction of others” as disease activity progresses.

“It speaks to an imbalance,” he added, and it suggests a role for probiotics or even fecal transplants to restore order.

“What if instead of killing the immune system” in lupus treatment, “we should be reducing or removing a single bacterium or a single molecule?” he asked.

Dr. Silverman is one of many researchers working to unravel the role of the human microbiome in both disease and health. His findings are preliminary, and, as he cautioned, correlation is not causation. But the implications are remarkable, Dr. Silverman noted.

SAN FRANCISCO – New York University researchers have found a ninefold increase of the bacterium Ruminococcus gnavus in the intestines of particularly ill lupus patients.

Not only that, but those patients also had highly elevated antibodies to an endotoxin-like antigen released by one particular R. gnavus strain.

That antigen is “very proinflammatory, very immunogenic. We are wondering if this is actually [what drives] the immune activation that results in immune complexes in the glomeruli” of patients with lupus nephritis, said investigator Gregg Silverman, MD, a professor of medicine and pathology and head of the laboratory of B-cell immunobiology at New York University.

R. gnavus is an obligate anaerobe found in the guts of most people, but in lupus, it might be a problem.

“We are finding a very specific relationship with lupus patients and this bacteria – and this particular antibody,” Dr. Silverman explained in an interview at an international congress on systemic lupus erythematosus. “There’s an expansion of this particular bug, but also a contraction of others” as disease activity progresses.

“It speaks to an imbalance,” he added, and it suggests a role for probiotics or even fecal transplants to restore order.

“What if instead of killing the immune system” in lupus treatment, “we should be reducing or removing a single bacterium or a single molecule?” he asked.

Dr. Silverman is one of many researchers working to unravel the role of the human microbiome in both disease and health. His findings are preliminary, and, as he cautioned, correlation is not causation. But the implications are remarkable, Dr. Silverman noted.