Clinical question: What are the current recommendations for antithrombotic therapy in various venous thromboembolism (VTE) scenarios?

Background: VTE is commonly encountered with a multitude of therapeutic options. Selecting the optimal anticoagulant is as important as making the diagnosis and requires knowledge of individual patient characteristics to initiate the correct therapy. These factors include malignancy, location of thrombus, and history of recurrent VTE despite anticoagulation.

Study design: Guideline.

Setting: Expert panel.

Synopsis: For VTE patients without cancer, non-vitamin K oral anticoagulants (NOAC) are now suggested over vitamin K antagonists (Grade 2B). However, there remains no strong evidence to favor one NOAC over another.

Better evidence now supports the prior recommendation to discourage IVC filters for VTE that is being treated with anticoagulation (Grade 1B).

In pulmonary embolism of the subsegmental type without proximal DVT, clinical surveillance is favored over anticoagulation in lower-risk patients (Grade 2C).

Low-molecular-weight heparin (LMWH) is advised in recurrent VTE treated with non-LMWH, and for recurrences on LMWH, a dose increase of LMWH is advised (Grade 2C).

Finally, routine use of compression stockings for post-thrombotic syndrome prevention is not routinely recommended (Grade 2B).

Limitations include only 20 of the 54 total recommendations being of strong Grade 1 criteria. Additionally, none of the 54 statements are drawn from high-quality evidence.

Further study is needed to continually update our practice in caring for VTE disease as more experience and comparison data are obtained with the use of NOAC drugs.

Bottom line: Anticoagulant therapy recommendations have been updated, but few are strong recommendations and none are based on high-quality evidence.

Citation: Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352.

Clinical question: What are the current recommendations for antithrombotic therapy in various venous thromboembolism (VTE) scenarios?

Background: VTE is commonly encountered with a multitude of therapeutic options. Selecting the optimal anticoagulant is as important as making the diagnosis and requires knowledge of individual patient characteristics to initiate the correct therapy. These factors include malignancy, location of thrombus, and history of recurrent VTE despite anticoagulation.

Study design: Guideline.

Setting: Expert panel.

Synopsis: For VTE patients without cancer, non-vitamin K oral anticoagulants (NOAC) are now suggested over vitamin K antagonists (Grade 2B). However, there remains no strong evidence to favor one NOAC over another.

Better evidence now supports the prior recommendation to discourage IVC filters for VTE that is being treated with anticoagulation (Grade 1B).

In pulmonary embolism of the subsegmental type without proximal DVT, clinical surveillance is favored over anticoagulation in lower-risk patients (Grade 2C).

Low-molecular-weight heparin (LMWH) is advised in recurrent VTE treated with non-LMWH, and for recurrences on LMWH, a dose increase of LMWH is advised (Grade 2C).

Finally, routine use of compression stockings for post-thrombotic syndrome prevention is not routinely recommended (Grade 2B).

Limitations include only 20 of the 54 total recommendations being of strong Grade 1 criteria. Additionally, none of the 54 statements are drawn from high-quality evidence.

Further study is needed to continually update our practice in caring for VTE disease as more experience and comparison data are obtained with the use of NOAC drugs.

Bottom line: Anticoagulant therapy recommendations have been updated, but few are strong recommendations and none are based on high-quality evidence.

Citation: Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352.

Clinical question: What are the current recommendations for antithrombotic therapy in various venous thromboembolism (VTE) scenarios?

Background: VTE is commonly encountered with a multitude of therapeutic options. Selecting the optimal anticoagulant is as important as making the diagnosis and requires knowledge of individual patient characteristics to initiate the correct therapy. These factors include malignancy, location of thrombus, and history of recurrent VTE despite anticoagulation.

Study design: Guideline.

Setting: Expert panel.

Synopsis: For VTE patients without cancer, non-vitamin K oral anticoagulants (NOAC) are now suggested over vitamin K antagonists (Grade 2B). However, there remains no strong evidence to favor one NOAC over another.

Better evidence now supports the prior recommendation to discourage IVC filters for VTE that is being treated with anticoagulation (Grade 1B).

In pulmonary embolism of the subsegmental type without proximal DVT, clinical surveillance is favored over anticoagulation in lower-risk patients (Grade 2C).

Low-molecular-weight heparin (LMWH) is advised in recurrent VTE treated with non-LMWH, and for recurrences on LMWH, a dose increase of LMWH is advised (Grade 2C).

Finally, routine use of compression stockings for post-thrombotic syndrome prevention is not routinely recommended (Grade 2B).

Limitations include only 20 of the 54 total recommendations being of strong Grade 1 criteria. Additionally, none of the 54 statements are drawn from high-quality evidence.

Further study is needed to continually update our practice in caring for VTE disease as more experience and comparison data are obtained with the use of NOAC drugs.

Bottom line: Anticoagulant therapy recommendations have been updated, but few are strong recommendations and none are based on high-quality evidence.

Citation: Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315-352.

Clinical question: Is tamsulosin efficacious as an expulsive therapy for distal ureter stones ≤10 mm in diameter?

Background: Ureteric calculi are a common reason for hospital admission, and use of medical expulsive therapy during observation periods for small caliber stones has gained much attention recently. Specifically, tamsulosin has been suggested as a medical therapy for small stones.

Study design: Randomized, double-blind, placebo-controlled study.

Setting: Five EDs in Australia.

Synopsis: A total of 403 patients participated in the study, based on inclusion criteria of age older than 18 years with symptoms and CT evidence of ureteric stones Exclusion criteria included fever, glomerular filtration rate <60, and calculi >10 mm. Patients were randomized to placebo or 0.4 mg tamsulosin daily for 28 days. The outcome was stone expulsion demonstrated by absence of calculi on repeat CT. Stone passage in the entire group occurred in 87% of the tamsulosin arm and 81.9% of the placebo, with a 95% CI of -3.0% to 13%, which was not a significant difference with P=0.22.

Interestingly, in a subgroup analysis of larger stones 5–10 mm, 83% of tamsulosin subjects compared to 61% of placebo subjects had stone passage that was significant at a 22% difference and P=.03.

Limitations included compliance in both groups, applicability to other populations given study based in Australia, and the lack of follow-through with CT scan at 28 days in 17% of the original group, resulting in missing outcome data.

Bottom line: Patients with ureteric stones 5–10 mm in size demonstrate increased spontaneous stone expulsion with the addition of tamsulosin and should thus be offered this therapy.

Citation: Furyk J, Chu K, Banks C, et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med. 2016;67(1):86-95.e2.

Short Take

Low Diagnostic Yield of Blood Cultures in Hospitalized Medical Patients

Prospective cohort study of patients hospitalized on a medical service demonstrated a true positive rate of blood cultures that was lower than previously studied. Using objective clinical predictors may improve likelihood of true positive blood cultures.

Citation: Linsenmeyer K, Gupta K, Strymish JM, Dhanani M, Brecher SM, Breu AC. Culture if spikes? Indications and yield of blood cultures in hospitalized medical patients [published online ahead of print January 13, 2016]. J Hosp Med. doi:10.1002/jhm.2541.

Clinical question: Is tamsulosin efficacious as an expulsive therapy for distal ureter stones ≤10 mm in diameter?

Background: Ureteric calculi are a common reason for hospital admission, and use of medical expulsive therapy during observation periods for small caliber stones has gained much attention recently. Specifically, tamsulosin has been suggested as a medical therapy for small stones.

Study design: Randomized, double-blind, placebo-controlled study.

Setting: Five EDs in Australia.

Synopsis: A total of 403 patients participated in the study, based on inclusion criteria of age older than 18 years with symptoms and CT evidence of ureteric stones Exclusion criteria included fever, glomerular filtration rate <60, and calculi >10 mm. Patients were randomized to placebo or 0.4 mg tamsulosin daily for 28 days. The outcome was stone expulsion demonstrated by absence of calculi on repeat CT. Stone passage in the entire group occurred in 87% of the tamsulosin arm and 81.9% of the placebo, with a 95% CI of -3.0% to 13%, which was not a significant difference with P=0.22.

Interestingly, in a subgroup analysis of larger stones 5–10 mm, 83% of tamsulosin subjects compared to 61% of placebo subjects had stone passage that was significant at a 22% difference and P=.03.

Limitations included compliance in both groups, applicability to other populations given study based in Australia, and the lack of follow-through with CT scan at 28 days in 17% of the original group, resulting in missing outcome data.

Bottom line: Patients with ureteric stones 5–10 mm in size demonstrate increased spontaneous stone expulsion with the addition of tamsulosin and should thus be offered this therapy.

Citation: Furyk J, Chu K, Banks C, et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med. 2016;67(1):86-95.e2.

Short Take

Low Diagnostic Yield of Blood Cultures in Hospitalized Medical Patients

Prospective cohort study of patients hospitalized on a medical service demonstrated a true positive rate of blood cultures that was lower than previously studied. Using objective clinical predictors may improve likelihood of true positive blood cultures.

Citation: Linsenmeyer K, Gupta K, Strymish JM, Dhanani M, Brecher SM, Breu AC. Culture if spikes? Indications and yield of blood cultures in hospitalized medical patients [published online ahead of print January 13, 2016]. J Hosp Med. doi:10.1002/jhm.2541.

Clinical question: Is tamsulosin efficacious as an expulsive therapy for distal ureter stones ≤10 mm in diameter?

Background: Ureteric calculi are a common reason for hospital admission, and use of medical expulsive therapy during observation periods for small caliber stones has gained much attention recently. Specifically, tamsulosin has been suggested as a medical therapy for small stones.

Study design: Randomized, double-blind, placebo-controlled study.

Setting: Five EDs in Australia.

Synopsis: A total of 403 patients participated in the study, based on inclusion criteria of age older than 18 years with symptoms and CT evidence of ureteric stones Exclusion criteria included fever, glomerular filtration rate <60, and calculi >10 mm. Patients were randomized to placebo or 0.4 mg tamsulosin daily for 28 days. The outcome was stone expulsion demonstrated by absence of calculi on repeat CT. Stone passage in the entire group occurred in 87% of the tamsulosin arm and 81.9% of the placebo, with a 95% CI of -3.0% to 13%, which was not a significant difference with P=0.22.

Interestingly, in a subgroup analysis of larger stones 5–10 mm, 83% of tamsulosin subjects compared to 61% of placebo subjects had stone passage that was significant at a 22% difference and P=.03.

Limitations included compliance in both groups, applicability to other populations given study based in Australia, and the lack of follow-through with CT scan at 28 days in 17% of the original group, resulting in missing outcome data.

Bottom line: Patients with ureteric stones 5–10 mm in size demonstrate increased spontaneous stone expulsion with the addition of tamsulosin and should thus be offered this therapy.

Citation: Furyk J, Chu K, Banks C, et al. Distal ureteric stones and tamsulosin: a double-blind, placebo-controlled, randomized, multicenter trial. Ann Emerg Med. 2016;67(1):86-95.e2.

Short Take

Low Diagnostic Yield of Blood Cultures in Hospitalized Medical Patients

Prospective cohort study of patients hospitalized on a medical service demonstrated a true positive rate of blood cultures that was lower than previously studied. Using objective clinical predictors may improve likelihood of true positive blood cultures.

Citation: Linsenmeyer K, Gupta K, Strymish JM, Dhanani M, Brecher SM, Breu AC. Culture if spikes? Indications and yield of blood cultures in hospitalized medical patients [published online ahead of print January 13, 2016]. J Hosp Med. doi:10.1002/jhm.2541.

Drug release in a cancer cell

Image courtesy of PNAS

Researchers say they have determined how BET inhibitors fight hematologic malignancies.

Previous studies showed that BET inhibitors are effective at halting tumor growth, but it wasn’t clear whether the drugs kill cancer cells outright or merely pause their growth.

The new study provides an answer and reveals potential ways in which cancer cells may develop resistance to BET inhibitors.

The findings have been published in Leukaemia.

Researchers tested the BET inhibitors JQ1 and IBET151 in a range of hematopoietic cancer cell lines (leukemias, lymphomas, and multiple myeloma) and in mice (with and without malignancy).

The team found that JQ1’s ability to kill cancer cells principally relies on the activation of BAX/BAK-dependent mitochondrial apoptosis. They said this is largely triggered by upregulation of the protein BIM when BET inhibitors suppress miR-17-92, a post-transcriptional repressor of BIM expression.

“We found that when apoptosis was impaired—for instance, by loss of BIM—the BET inhibitors were no longer effective,” said study author Zhen Xu, PhD, of Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.

“This suggests that cancer cells that acquire mutations in genes that drive apoptosis will lose sensitivity to BET inhibitors and thus will be able to survive treatment, leading to disease relapse.”

The researchers also found that BET inhibitors could induce apoptosis in normal hematopoietic cells, particularly those of lymphoid origin. The team said this suggests the cells’ susceptibility to BET inhibitors did not arise from oncogenic transformation.

These findings could help researchers improve strategies for using BET inhibitors to treat cancers, according to study author Stefan Glaser, PhD, of the Walter and Eliza Hall Institute of Medical Research.

“Understanding how the drugs work gives us the opportunity to investigate new treatments—for example, by using combination therapies or altering the dosage and timing of treatment to prevent drug resistance from emerging,” Dr Glaser said.

Drug release in a cancer cell

Image courtesy of PNAS

Researchers say they have determined how BET inhibitors fight hematologic malignancies.

Previous studies showed that BET inhibitors are effective at halting tumor growth, but it wasn’t clear whether the drugs kill cancer cells outright or merely pause their growth.

The new study provides an answer and reveals potential ways in which cancer cells may develop resistance to BET inhibitors.

The findings have been published in Leukaemia.

Researchers tested the BET inhibitors JQ1 and IBET151 in a range of hematopoietic cancer cell lines (leukemias, lymphomas, and multiple myeloma) and in mice (with and without malignancy).

The team found that JQ1’s ability to kill cancer cells principally relies on the activation of BAX/BAK-dependent mitochondrial apoptosis. They said this is largely triggered by upregulation of the protein BIM when BET inhibitors suppress miR-17-92, a post-transcriptional repressor of BIM expression.

“We found that when apoptosis was impaired—for instance, by loss of BIM—the BET inhibitors were no longer effective,” said study author Zhen Xu, PhD, of Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.

“This suggests that cancer cells that acquire mutations in genes that drive apoptosis will lose sensitivity to BET inhibitors and thus will be able to survive treatment, leading to disease relapse.”

The researchers also found that BET inhibitors could induce apoptosis in normal hematopoietic cells, particularly those of lymphoid origin. The team said this suggests the cells’ susceptibility to BET inhibitors did not arise from oncogenic transformation.

These findings could help researchers improve strategies for using BET inhibitors to treat cancers, according to study author Stefan Glaser, PhD, of the Walter and Eliza Hall Institute of Medical Research.

“Understanding how the drugs work gives us the opportunity to investigate new treatments—for example, by using combination therapies or altering the dosage and timing of treatment to prevent drug resistance from emerging,” Dr Glaser said.

Drug release in a cancer cell

Image courtesy of PNAS

Researchers say they have determined how BET inhibitors fight hematologic malignancies.

Previous studies showed that BET inhibitors are effective at halting tumor growth, but it wasn’t clear whether the drugs kill cancer cells outright or merely pause their growth.

The new study provides an answer and reveals potential ways in which cancer cells may develop resistance to BET inhibitors.

The findings have been published in Leukaemia.

Researchers tested the BET inhibitors JQ1 and IBET151 in a range of hematopoietic cancer cell lines (leukemias, lymphomas, and multiple myeloma) and in mice (with and without malignancy).

The team found that JQ1’s ability to kill cancer cells principally relies on the activation of BAX/BAK-dependent mitochondrial apoptosis. They said this is largely triggered by upregulation of the protein BIM when BET inhibitors suppress miR-17-92, a post-transcriptional repressor of BIM expression.

“We found that when apoptosis was impaired—for instance, by loss of BIM—the BET inhibitors were no longer effective,” said study author Zhen Xu, PhD, of Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.

“This suggests that cancer cells that acquire mutations in genes that drive apoptosis will lose sensitivity to BET inhibitors and thus will be able to survive treatment, leading to disease relapse.”

The researchers also found that BET inhibitors could induce apoptosis in normal hematopoietic cells, particularly those of lymphoid origin. The team said this suggests the cells’ susceptibility to BET inhibitors did not arise from oncogenic transformation.

These findings could help researchers improve strategies for using BET inhibitors to treat cancers, according to study author Stefan Glaser, PhD, of the Walter and Eliza Hall Institute of Medical Research.

“Understanding how the drugs work gives us the opportunity to investigate new treatments—for example, by using combination therapies or altering the dosage and timing of treatment to prevent drug resistance from emerging,” Dr Glaser said.

Mother and child

Photo by Vera Kratochvil

A new study indicates that many young adult female cancer survivors do not receive adequate information about their fertility as part of their survivorship care, despite having concerns about their ability to bear children in the future.

The research, published in Cancer, suggests a need for better resources to support cancer survivors in making informed decisions about their reproductive options after they complete treatment.

To conduct this study, Catherine Benedict, PhD, of North Shore-Long Island Jewish Medical Center in Manhasset, New York, and her colleagues asked female cancer survivors to complete a web-based, anonymous survey.

There were 346 participants. They had an average age of 29.9 and had completed treatment an average of 4.9 years earlier.

The investigators focused on a subgroup of 179 women with uncertain fertility status who had not previously undergone or attempted fertility preservation, either before or after their cancer treatment, and who either wanted future children or were unsure.

Many of these women said they did not have enough information concerning their risk of infertility (58%), risk of early menopause (60%), options to assess their fertility (62%), options to preserve their fertility (51%), or options for alternative family building (43%).

The women’s greatest reproductive concerns were potential fertility problems and the health of a future child. Sixty-four percent of the women said they were concerned about not being able to have children (or more children), and 59% were worried about passing the risk of cancer on to their future children.

Only 13% of women said they were well informed about options for preserving fertility, and 74% were unclear about their personal values regarding fertility preservation.

Seventy percent of the women said they hadn’t received enough advice on fertility preservation, and 35% said they didn’t have enough support to make a decision about fertility preservation.

The investigators found a significant association between greater unmet information needs and higher levels of decisional conflict about fertility preservation (P<0.001).

On the other hand, having undergone a fertility evaluation after treatment was associated with lower decisional conflict (P=0.02).

The investigators said these findings establish the need for support services to help young female cancer survivors make decisions about fertility preservation and family-building as part of survivorship care.

The literature has largely focused on the clinical and support needs of women making fertility decisions before their treatment begins, but most patients do not preserve their fertility before treatment for a number of reasons, despite wanting children in the future.

“The potential loss of fertility has been described in the literature as being almost as painful, if not more so, than the cancer diagnosis itself,” Dr Benedict said.

“Failure to provide information and address concerns with respect to fertility-related decisions may have lasting consequences for young women who hope to move on from their cancer experience to achieve important life goals such as having children. For women at risk for early menopause, delaying fertility-related decisions may cause them to miss their narrowed window of opportunity to preserve their fertility, if desired.”

Mother and child

Photo by Vera Kratochvil

A new study indicates that many young adult female cancer survivors do not receive adequate information about their fertility as part of their survivorship care, despite having concerns about their ability to bear children in the future.

The research, published in Cancer, suggests a need for better resources to support cancer survivors in making informed decisions about their reproductive options after they complete treatment.

To conduct this study, Catherine Benedict, PhD, of North Shore-Long Island Jewish Medical Center in Manhasset, New York, and her colleagues asked female cancer survivors to complete a web-based, anonymous survey.

There were 346 participants. They had an average age of 29.9 and had completed treatment an average of 4.9 years earlier.

The investigators focused on a subgroup of 179 women with uncertain fertility status who had not previously undergone or attempted fertility preservation, either before or after their cancer treatment, and who either wanted future children or were unsure.

Many of these women said they did not have enough information concerning their risk of infertility (58%), risk of early menopause (60%), options to assess their fertility (62%), options to preserve their fertility (51%), or options for alternative family building (43%).

The women’s greatest reproductive concerns were potential fertility problems and the health of a future child. Sixty-four percent of the women said they were concerned about not being able to have children (or more children), and 59% were worried about passing the risk of cancer on to their future children.

Only 13% of women said they were well informed about options for preserving fertility, and 74% were unclear about their personal values regarding fertility preservation.

Seventy percent of the women said they hadn’t received enough advice on fertility preservation, and 35% said they didn’t have enough support to make a decision about fertility preservation.

The investigators found a significant association between greater unmet information needs and higher levels of decisional conflict about fertility preservation (P<0.001).

On the other hand, having undergone a fertility evaluation after treatment was associated with lower decisional conflict (P=0.02).

The investigators said these findings establish the need for support services to help young female cancer survivors make decisions about fertility preservation and family-building as part of survivorship care.

The literature has largely focused on the clinical and support needs of women making fertility decisions before their treatment begins, but most patients do not preserve their fertility before treatment for a number of reasons, despite wanting children in the future.

“The potential loss of fertility has been described in the literature as being almost as painful, if not more so, than the cancer diagnosis itself,” Dr Benedict said.

“Failure to provide information and address concerns with respect to fertility-related decisions may have lasting consequences for young women who hope to move on from their cancer experience to achieve important life goals such as having children. For women at risk for early menopause, delaying fertility-related decisions may cause them to miss their narrowed window of opportunity to preserve their fertility, if desired.”

Mother and child

Photo by Vera Kratochvil

A new study indicates that many young adult female cancer survivors do not receive adequate information about their fertility as part of their survivorship care, despite having concerns about their ability to bear children in the future.

The research, published in Cancer, suggests a need for better resources to support cancer survivors in making informed decisions about their reproductive options after they complete treatment.

To conduct this study, Catherine Benedict, PhD, of North Shore-Long Island Jewish Medical Center in Manhasset, New York, and her colleagues asked female cancer survivors to complete a web-based, anonymous survey.

There were 346 participants. They had an average age of 29.9 and had completed treatment an average of 4.9 years earlier.

The investigators focused on a subgroup of 179 women with uncertain fertility status who had not previously undergone or attempted fertility preservation, either before or after their cancer treatment, and who either wanted future children or were unsure.

Many of these women said they did not have enough information concerning their risk of infertility (58%), risk of early menopause (60%), options to assess their fertility (62%), options to preserve their fertility (51%), or options for alternative family building (43%).

The women’s greatest reproductive concerns were potential fertility problems and the health of a future child. Sixty-four percent of the women said they were concerned about not being able to have children (or more children), and 59% were worried about passing the risk of cancer on to their future children.

Only 13% of women said they were well informed about options for preserving fertility, and 74% were unclear about their personal values regarding fertility preservation.

Seventy percent of the women said they hadn’t received enough advice on fertility preservation, and 35% said they didn’t have enough support to make a decision about fertility preservation.

The investigators found a significant association between greater unmet information needs and higher levels of decisional conflict about fertility preservation (P<0.001).

On the other hand, having undergone a fertility evaluation after treatment was associated with lower decisional conflict (P=0.02).

The investigators said these findings establish the need for support services to help young female cancer survivors make decisions about fertility preservation and family-building as part of survivorship care.

The literature has largely focused on the clinical and support needs of women making fertility decisions before their treatment begins, but most patients do not preserve their fertility before treatment for a number of reasons, despite wanting children in the future.

“The potential loss of fertility has been described in the literature as being almost as painful, if not more so, than the cancer diagnosis itself,” Dr Benedict said.

“Failure to provide information and address concerns with respect to fertility-related decisions may have lasting consequences for young women who hope to move on from their cancer experience to achieve important life goals such as having children. For women at risk for early menopause, delaying fertility-related decisions may cause them to miss their narrowed window of opportunity to preserve their fertility, if desired.”

ALL patient

Photo by Bill Branson

New research indicates that survivors of pediatric acute lymphoblastic leukemia (ALL) suffer from brain injury even if they have no history of central nervous system disease or cranial radiation.

The study suggests the neurotoxic effects of chemotherapeutic drugs on the developing brains of young ALL patients may impair their cognitive functioning by disrupting the formation of neural networks that connect brain regions and transfer information.

Shelli Kesler, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and her colleagues reported these findings in Brain Connectivity.

The researchers used diffusion tensor imaging to analyze and compare the gray matter connectome of 31 pediatric ALL survivors and 39 matched control subjects.

The team found significantly greater cognitive impairment among the ALL survivors (P=0.027), as well as significantly lower connectivity, based on small-worldness (P=0.007) and network clustering coefficient (P=0.019).

The researchers noted that clustered connectivity was altered in the parietal, frontal, hippocampal, amygdalar, thalamic, and occipital regions in the ALL survivors.

The team also described a model that can be used to predict cognitive impairment in ALL survivors. The model’s classification accuracy was 89.39% (P<0.0001), its sensitivity was 95.83%, and specificity was 85.71%.

“As survival rates for cancer patients increase, issues related to survivorship, such as chemotherapy-induced cognitive impairment, become more important to the cancer research community,” said Christopher Pawela, PhD, co-editor-in-chief of Brain Connectivity and an assistant professor at the Medical College of Wisconsin in Milwaukee.

“Dr Kesler and colleagues are developing new MRI-based biomarkers to measure brain changes associated with the neurotoxic effects of chemotherapy in the brain. These biomarkers may find utility in providing insight into the mechanisms of brain damage caused by chemotherapeutic drugs and could be used to develop neuroprotective therapies to mitigate the harmful effects of these drugs on the brain.”

ALL patient

Photo by Bill Branson

New research indicates that survivors of pediatric acute lymphoblastic leukemia (ALL) suffer from brain injury even if they have no history of central nervous system disease or cranial radiation.

The study suggests the neurotoxic effects of chemotherapeutic drugs on the developing brains of young ALL patients may impair their cognitive functioning by disrupting the formation of neural networks that connect brain regions and transfer information.

Shelli Kesler, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and her colleagues reported these findings in Brain Connectivity.

The researchers used diffusion tensor imaging to analyze and compare the gray matter connectome of 31 pediatric ALL survivors and 39 matched control subjects.

The team found significantly greater cognitive impairment among the ALL survivors (P=0.027), as well as significantly lower connectivity, based on small-worldness (P=0.007) and network clustering coefficient (P=0.019).

The researchers noted that clustered connectivity was altered in the parietal, frontal, hippocampal, amygdalar, thalamic, and occipital regions in the ALL survivors.

The team also described a model that can be used to predict cognitive impairment in ALL survivors. The model’s classification accuracy was 89.39% (P<0.0001), its sensitivity was 95.83%, and specificity was 85.71%.

“As survival rates for cancer patients increase, issues related to survivorship, such as chemotherapy-induced cognitive impairment, become more important to the cancer research community,” said Christopher Pawela, PhD, co-editor-in-chief of Brain Connectivity and an assistant professor at the Medical College of Wisconsin in Milwaukee.

“Dr Kesler and colleagues are developing new MRI-based biomarkers to measure brain changes associated with the neurotoxic effects of chemotherapy in the brain. These biomarkers may find utility in providing insight into the mechanisms of brain damage caused by chemotherapeutic drugs and could be used to develop neuroprotective therapies to mitigate the harmful effects of these drugs on the brain.”

ALL patient

Photo by Bill Branson

New research indicates that survivors of pediatric acute lymphoblastic leukemia (ALL) suffer from brain injury even if they have no history of central nervous system disease or cranial radiation.

The study suggests the neurotoxic effects of chemotherapeutic drugs on the developing brains of young ALL patients may impair their cognitive functioning by disrupting the formation of neural networks that connect brain regions and transfer information.

Shelli Kesler, PhD, of the University of Texas MD Anderson Cancer Center in Houston, and her colleagues reported these findings in Brain Connectivity.

The researchers used diffusion tensor imaging to analyze and compare the gray matter connectome of 31 pediatric ALL survivors and 39 matched control subjects.

The team found significantly greater cognitive impairment among the ALL survivors (P=0.027), as well as significantly lower connectivity, based on small-worldness (P=0.007) and network clustering coefficient (P=0.019).

The researchers noted that clustered connectivity was altered in the parietal, frontal, hippocampal, amygdalar, thalamic, and occipital regions in the ALL survivors.

The team also described a model that can be used to predict cognitive impairment in ALL survivors. The model’s classification accuracy was 89.39% (P<0.0001), its sensitivity was 95.83%, and specificity was 85.71%.

“As survival rates for cancer patients increase, issues related to survivorship, such as chemotherapy-induced cognitive impairment, become more important to the cancer research community,” said Christopher Pawela, PhD, co-editor-in-chief of Brain Connectivity and an assistant professor at the Medical College of Wisconsin in Milwaukee.

“Dr Kesler and colleagues are developing new MRI-based biomarkers to measure brain changes associated with the neurotoxic effects of chemotherapy in the brain. These biomarkers may find utility in providing insight into the mechanisms of brain damage caused by chemotherapeutic drugs and could be used to develop neuroprotective therapies to mitigate the harmful effects of these drugs on the brain.”

SAN FRANCISCO – Focal impulse and rotor modulation-guided ablation for persistent atrial fibrillation – either alone or in conjunction with other procedures – increased procedural times without improving outcomes, according to the first randomized trial to assess its utility.

In fact, enrollment in the rotor ablation-only (RA) arm was halted early for futility. “There was 100% recurrence” of atrial fibrillation (AF), said senior investigator Dr. Andrea Natale, executive medical director of the Texas Cardiac Arrhythmia Institute, Austin.

“I’m surprised it took this long for a randomized study, because this system has been around for 5 or 6 years,” noted Dr. Natale. “Our community should demand these sorts of studies earlier, because it’s not fair for patients to go on with a procedure for years that has not been proven to be effective.

Alex Otto/Frontline Medical News

“For us, unless there is a new version of rotor mapping that I feel is significantly different, this will be the end of rotor ablation in my lab with this system [the Topera Physiologic Rotor Mapping Solution],” Dr. Natale said at the annual scientific sessions of the Heart Rhythm Society.

In the study, his team randomized 29 patients to RA only, 42 to RA plus pulmonary vein antral isolation (PVAI), and 42 to PVAI plus posterior wall and nonpulmonary vein trigger ablation.

At about 1 year, four RA-only patients (14%), 22 RA plus PVAI patients (52%), and 32 patients in the PVAI plus trigger group (76%) were free of AF and atrial tachycardias without antiarrhythmic drugs (P < .0001).

Meanwhile, RA alone and RA plus PVAI cases took about 230 minutes, while the more effective PVAI plus trigger approach took about 130 minutes (P < .001).

There was “a very poor outcome with rotor-only ablation,” Dr. Natale said. “There isn’t a benefit either alone or as an add-on strategy, at least with this mapping software.”

Perhaps “people who think rotors don’t exist are right,” he added. On the other hand, maybe the basket mapping catheter doesn’t touch enough of the left atrium, or the software that makes sense of what the catheter detects needs to be improved, Dr. Natale noted.

All the patients were undergoing their first ablation. They were in their early 60s, on average, and most were men. The mean left atrium diameter was about 47 mm, and mean left ventricle ejection fraction about 55%. There were no statistically significant differences between the study arms, and no significant differences in outcomes between the 70% of patients with persistent AF and the 30% with long-standing persistent AF.

There was no industry funding for the work. Dr. Natale disclosed relationships with Biosense Webster, Boston Scientific, Janssen, Medtronic, and St. Jude Medical.

[email protected]

SAN FRANCISCO – Focal impulse and rotor modulation-guided ablation for persistent atrial fibrillation – either alone or in conjunction with other procedures – increased procedural times without improving outcomes, according to the first randomized trial to assess its utility.

In fact, enrollment in the rotor ablation-only (RA) arm was halted early for futility. “There was 100% recurrence” of atrial fibrillation (AF), said senior investigator Dr. Andrea Natale, executive medical director of the Texas Cardiac Arrhythmia Institute, Austin.

“I’m surprised it took this long for a randomized study, because this system has been around for 5 or 6 years,” noted Dr. Natale. “Our community should demand these sorts of studies earlier, because it’s not fair for patients to go on with a procedure for years that has not been proven to be effective.

Alex Otto/Frontline Medical News

“For us, unless there is a new version of rotor mapping that I feel is significantly different, this will be the end of rotor ablation in my lab with this system [the Topera Physiologic Rotor Mapping Solution],” Dr. Natale said at the annual scientific sessions of the Heart Rhythm Society.

In the study, his team randomized 29 patients to RA only, 42 to RA plus pulmonary vein antral isolation (PVAI), and 42 to PVAI plus posterior wall and nonpulmonary vein trigger ablation.

At about 1 year, four RA-only patients (14%), 22 RA plus PVAI patients (52%), and 32 patients in the PVAI plus trigger group (76%) were free of AF and atrial tachycardias without antiarrhythmic drugs (P < .0001).

Meanwhile, RA alone and RA plus PVAI cases took about 230 minutes, while the more effective PVAI plus trigger approach took about 130 minutes (P < .001).

There was “a very poor outcome with rotor-only ablation,” Dr. Natale said. “There isn’t a benefit either alone or as an add-on strategy, at least with this mapping software.”

Perhaps “people who think rotors don’t exist are right,” he added. On the other hand, maybe the basket mapping catheter doesn’t touch enough of the left atrium, or the software that makes sense of what the catheter detects needs to be improved, Dr. Natale noted.

All the patients were undergoing their first ablation. They were in their early 60s, on average, and most were men. The mean left atrium diameter was about 47 mm, and mean left ventricle ejection fraction about 55%. There were no statistically significant differences between the study arms, and no significant differences in outcomes between the 70% of patients with persistent AF and the 30% with long-standing persistent AF.

There was no industry funding for the work. Dr. Natale disclosed relationships with Biosense Webster, Boston Scientific, Janssen, Medtronic, and St. Jude Medical.

[email protected]

SAN FRANCISCO – Focal impulse and rotor modulation-guided ablation for persistent atrial fibrillation – either alone or in conjunction with other procedures – increased procedural times without improving outcomes, according to the first randomized trial to assess its utility.

In fact, enrollment in the rotor ablation-only (RA) arm was halted early for futility. “There was 100% recurrence” of atrial fibrillation (AF), said senior investigator Dr. Andrea Natale, executive medical director of the Texas Cardiac Arrhythmia Institute, Austin.

“I’m surprised it took this long for a randomized study, because this system has been around for 5 or 6 years,” noted Dr. Natale. “Our community should demand these sorts of studies earlier, because it’s not fair for patients to go on with a procedure for years that has not been proven to be effective.

Alex Otto/Frontline Medical News

“For us, unless there is a new version of rotor mapping that I feel is significantly different, this will be the end of rotor ablation in my lab with this system [the Topera Physiologic Rotor Mapping Solution],” Dr. Natale said at the annual scientific sessions of the Heart Rhythm Society.

In the study, his team randomized 29 patients to RA only, 42 to RA plus pulmonary vein antral isolation (PVAI), and 42 to PVAI plus posterior wall and nonpulmonary vein trigger ablation.

At about 1 year, four RA-only patients (14%), 22 RA plus PVAI patients (52%), and 32 patients in the PVAI plus trigger group (76%) were free of AF and atrial tachycardias without antiarrhythmic drugs (P < .0001).

Meanwhile, RA alone and RA plus PVAI cases took about 230 minutes, while the more effective PVAI plus trigger approach took about 130 minutes (P < .001).

There was “a very poor outcome with rotor-only ablation,” Dr. Natale said. “There isn’t a benefit either alone or as an add-on strategy, at least with this mapping software.”

Perhaps “people who think rotors don’t exist are right,” he added. On the other hand, maybe the basket mapping catheter doesn’t touch enough of the left atrium, or the software that makes sense of what the catheter detects needs to be improved, Dr. Natale noted.

All the patients were undergoing their first ablation. They were in their early 60s, on average, and most were men. The mean left atrium diameter was about 47 mm, and mean left ventricle ejection fraction about 55%. There were no statistically significant differences between the study arms, and no significant differences in outcomes between the 70% of patients with persistent AF and the 30% with long-standing persistent AF.

There was no industry funding for the work. Dr. Natale disclosed relationships with Biosense Webster, Boston Scientific, Janssen, Medtronic, and St. Jude Medical.

[email protected]

FLORENCE, ITALY – A novel intravenous prodrug that results in formation of nitroxyl once inside the body showed several potentially beneficial hemodynamic effects during a single, 6-hour infusion in a controlled proof-of-concept study with 46 patients hospitalized with advanced heart failure with reduced ejection fraction.

While receiving the drug, patients showed “statistically significant and clinically meaningful” reductions in pulmonary capillary wedge pressure and in pulmonary artery diastolic pressure, two of the studies three primary endpoints, Dr. Veselin Mitrovic said at a meeting held by the Heart Failure Association of the ESC.

For the study’s third primary endpoint, a change in cardiac index, treatment with the drug led to increased cardiac output using noninvasive measures, especially at the highest tested dose, as well as in all of the subset of treated patients in whom cardiac index was measured by thermodilution.

On the safety side, the drug appeared safe and well tolerated at all four tested doses, while causing no episodes of symptomatic hypotension and no increase in heart rate. Transient, asymptomatic reductions in blood pressure were similar in the treated and control patients.

Mitchel L. Zoler/Frontline Medical News

“This is a very interesting and exciting drug that went in the right direction,” summed up Dr. Mitrovic, professor of cardiology at Goethe University in Frankfurt, Germany, and head of the department of cardiovascular research at the Kerckhoff Clinic in Bad Nauheim, Germany.

“This is the first demonstration of safety and preliminary efficacy in patients with advanced heart failure,” he said in an interview. “We had a very good clinical signal in a relatively small study. We now need a larger study.”

The drug “improved myocardial function in several ways: inotropy, lusitropy, and unloading. It also causes arterial vasodilation and increased stroke volume,” Dr. Mitrovic said. “Other drugs with a positive inotropic effect increase myocardial oxygen consumption; but with this drug, we see a neutral effect on mixed venous oxygen saturation. It balances myocardial oxygen consumption by its effect on unloading and reduced vascular resistance. This is a big advantage.”

Each molecule of nitroxyl is made from single atoms of hydrogen, nitrogen, and oxygen, and its physiologic action is distinct from nitric monoxide. Nitroxyl improves calcium efficiency and recycling without producing intracellular calcium overload, and its effects are not mediated by cyclic AMP or cyclic GMP.

The dose-ranging study enrolled 34 patients with New York Heart Association class III heart failure and 11 with class IV. All patients had to have a left ventricular ejection fraction of 40% or less, and their actual ejection fractions averaged about 25%.

When measured after 2, 4, and 6 hours of infusion, pulmonary capillary wedge pressure (PCWP) fell by an average of about 5 mm Hg, compared with baseline, among patients who received the three highest-dose infusions of the nitroxyl prodrug, known as CXL-1427, and by an average of about 3 mm Hg in those who received the lowest dose.

That effect had disappeared when PCWP was remeasured 2 hours after the end of the 6-hour infusion, and the 11 patients randomized to placebo showed no change at any time point in PCWP. The average declines in PCWP in each of the four dose groups were statistically significant changes, compared with the control patients.

All the drug-treated patients showed an average drop in pulmonary artery systolic pressure of about 5 mm Hg, compared with baseline, and about 3-4 mm Hg in pulmonary artery diastolic pressure. The patients who received the highest dose of CXL-1427 had an average drop in their right artery pressure of about 4 mm Hg. All of those decreases were statistically significant, compared with the lack of any measurable changes in the control patients.

Total peripheral resistance also showed statistically significant declines relative to baseline in all the treated patients when these decreases were compared with the controls.

CXL-1427 was initially developed by Cardioxyl Pharmaceuticals. Bristol-Myers Squibb acquired the company in late 2015. The study was sponsored by Cardioxyl. Dr. Mitrovic has been a consultant to Bayer, Cardiorentis, and Novartis.

[email protected]

On Twitter @mitchelzoler

FLORENCE, ITALY – A novel intravenous prodrug that results in formation of nitroxyl once inside the body showed several potentially beneficial hemodynamic effects during a single, 6-hour infusion in a controlled proof-of-concept study with 46 patients hospitalized with advanced heart failure with reduced ejection fraction.

While receiving the drug, patients showed “statistically significant and clinically meaningful” reductions in pulmonary capillary wedge pressure and in pulmonary artery diastolic pressure, two of the studies three primary endpoints, Dr. Veselin Mitrovic said at a meeting held by the Heart Failure Association of the ESC.

For the study’s third primary endpoint, a change in cardiac index, treatment with the drug led to increased cardiac output using noninvasive measures, especially at the highest tested dose, as well as in all of the subset of treated patients in whom cardiac index was measured by thermodilution.

On the safety side, the drug appeared safe and well tolerated at all four tested doses, while causing no episodes of symptomatic hypotension and no increase in heart rate. Transient, asymptomatic reductions in blood pressure were similar in the treated and control patients.

Mitchel L. Zoler/Frontline Medical News

“This is a very interesting and exciting drug that went in the right direction,” summed up Dr. Mitrovic, professor of cardiology at Goethe University in Frankfurt, Germany, and head of the department of cardiovascular research at the Kerckhoff Clinic in Bad Nauheim, Germany.

“This is the first demonstration of safety and preliminary efficacy in patients with advanced heart failure,” he said in an interview. “We had a very good clinical signal in a relatively small study. We now need a larger study.”

The drug “improved myocardial function in several ways: inotropy, lusitropy, and unloading. It also causes arterial vasodilation and increased stroke volume,” Dr. Mitrovic said. “Other drugs with a positive inotropic effect increase myocardial oxygen consumption; but with this drug, we see a neutral effect on mixed venous oxygen saturation. It balances myocardial oxygen consumption by its effect on unloading and reduced vascular resistance. This is a big advantage.”

Each molecule of nitroxyl is made from single atoms of hydrogen, nitrogen, and oxygen, and its physiologic action is distinct from nitric monoxide. Nitroxyl improves calcium efficiency and recycling without producing intracellular calcium overload, and its effects are not mediated by cyclic AMP or cyclic GMP.

The dose-ranging study enrolled 34 patients with New York Heart Association class III heart failure and 11 with class IV. All patients had to have a left ventricular ejection fraction of 40% or less, and their actual ejection fractions averaged about 25%.

When measured after 2, 4, and 6 hours of infusion, pulmonary capillary wedge pressure (PCWP) fell by an average of about 5 mm Hg, compared with baseline, among patients who received the three highest-dose infusions of the nitroxyl prodrug, known as CXL-1427, and by an average of about 3 mm Hg in those who received the lowest dose.

That effect had disappeared when PCWP was remeasured 2 hours after the end of the 6-hour infusion, and the 11 patients randomized to placebo showed no change at any time point in PCWP. The average declines in PCWP in each of the four dose groups were statistically significant changes, compared with the control patients.

All the drug-treated patients showed an average drop in pulmonary artery systolic pressure of about 5 mm Hg, compared with baseline, and about 3-4 mm Hg in pulmonary artery diastolic pressure. The patients who received the highest dose of CXL-1427 had an average drop in their right artery pressure of about 4 mm Hg. All of those decreases were statistically significant, compared with the lack of any measurable changes in the control patients.

Total peripheral resistance also showed statistically significant declines relative to baseline in all the treated patients when these decreases were compared with the controls.

CXL-1427 was initially developed by Cardioxyl Pharmaceuticals. Bristol-Myers Squibb acquired the company in late 2015. The study was sponsored by Cardioxyl. Dr. Mitrovic has been a consultant to Bayer, Cardiorentis, and Novartis.

[email protected]

On Twitter @mitchelzoler

FLORENCE, ITALY – A novel intravenous prodrug that results in formation of nitroxyl once inside the body showed several potentially beneficial hemodynamic effects during a single, 6-hour infusion in a controlled proof-of-concept study with 46 patients hospitalized with advanced heart failure with reduced ejection fraction.

While receiving the drug, patients showed “statistically significant and clinically meaningful” reductions in pulmonary capillary wedge pressure and in pulmonary artery diastolic pressure, two of the studies three primary endpoints, Dr. Veselin Mitrovic said at a meeting held by the Heart Failure Association of the ESC.

For the study’s third primary endpoint, a change in cardiac index, treatment with the drug led to increased cardiac output using noninvasive measures, especially at the highest tested dose, as well as in all of the subset of treated patients in whom cardiac index was measured by thermodilution.

On the safety side, the drug appeared safe and well tolerated at all four tested doses, while causing no episodes of symptomatic hypotension and no increase in heart rate. Transient, asymptomatic reductions in blood pressure were similar in the treated and control patients.

Mitchel L. Zoler/Frontline Medical News

“This is a very interesting and exciting drug that went in the right direction,” summed up Dr. Mitrovic, professor of cardiology at Goethe University in Frankfurt, Germany, and head of the department of cardiovascular research at the Kerckhoff Clinic in Bad Nauheim, Germany.

“This is the first demonstration of safety and preliminary efficacy in patients with advanced heart failure,” he said in an interview. “We had a very good clinical signal in a relatively small study. We now need a larger study.”

The drug “improved myocardial function in several ways: inotropy, lusitropy, and unloading. It also causes arterial vasodilation and increased stroke volume,” Dr. Mitrovic said. “Other drugs with a positive inotropic effect increase myocardial oxygen consumption; but with this drug, we see a neutral effect on mixed venous oxygen saturation. It balances myocardial oxygen consumption by its effect on unloading and reduced vascular resistance. This is a big advantage.”

Each molecule of nitroxyl is made from single atoms of hydrogen, nitrogen, and oxygen, and its physiologic action is distinct from nitric monoxide. Nitroxyl improves calcium efficiency and recycling without producing intracellular calcium overload, and its effects are not mediated by cyclic AMP or cyclic GMP.

The dose-ranging study enrolled 34 patients with New York Heart Association class III heart failure and 11 with class IV. All patients had to have a left ventricular ejection fraction of 40% or less, and their actual ejection fractions averaged about 25%.

When measured after 2, 4, and 6 hours of infusion, pulmonary capillary wedge pressure (PCWP) fell by an average of about 5 mm Hg, compared with baseline, among patients who received the three highest-dose infusions of the nitroxyl prodrug, known as CXL-1427, and by an average of about 3 mm Hg in those who received the lowest dose.

That effect had disappeared when PCWP was remeasured 2 hours after the end of the 6-hour infusion, and the 11 patients randomized to placebo showed no change at any time point in PCWP. The average declines in PCWP in each of the four dose groups were statistically significant changes, compared with the control patients.

All the drug-treated patients showed an average drop in pulmonary artery systolic pressure of about 5 mm Hg, compared with baseline, and about 3-4 mm Hg in pulmonary artery diastolic pressure. The patients who received the highest dose of CXL-1427 had an average drop in their right artery pressure of about 4 mm Hg. All of those decreases were statistically significant, compared with the lack of any measurable changes in the control patients.

Total peripheral resistance also showed statistically significant declines relative to baseline in all the treated patients when these decreases were compared with the controls.

CXL-1427 was initially developed by Cardioxyl Pharmaceuticals. Bristol-Myers Squibb acquired the company in late 2015. The study was sponsored by Cardioxyl. Dr. Mitrovic has been a consultant to Bayer, Cardiorentis, and Novartis.

[email protected]

On Twitter @mitchelzoler

SAN DIEGO – In patients with Barrett’s esophagus (BE), acid suppression with proton pump inhibitors (PPIs) and, to a lesser extent, histamine₂ receptor antagonists (H₂RA) reduced the risk of progression to esophageal adenocarcinoma (EAC), according to the findings from a study reported at the annual Digestive Disease Week.

Both treatments were independently associated with reduced risk of progression to cancer in the nested, case-control study. Taking PPIs reduced the risk of developing EAC by 69% and taking H₂RAs reduced the risk by 45%.

“There are no concrete guidelines regarding use of PPIs for patients with Barrett’s esophagus,” said presenting author Dr Mimi C. Tan, a postdoctoral research fellow at Baylor College of Medicine in Houston. “The guidelines for these agents are based on symptoms of reflux. Although this study does not tell us for sure, it looks like taking these medications [in Barrett’s esophagus] prevents cancer. The effect is stronger with PPIs, but H₂RAs still have an effect.”

Alice Goodman

The incidence of BE is increasing in the United States, and BE is the only known risk factor for EAC.

“There is a knowledge gap, with a deficiency of studies of cases with longitudinal follow-up in a cohort of BE patients examining the effects of PPIs and H₂RAs on progression to EAC,” Dr. Tan explained. “We conducted this study in a large cohort of BE patients and hypothesized that acid suppression with PPIs and H₂RAs would decrease the risk of EAC.”

The study included a cohort of 29,536 male veterans diagnosed with BE between 2004 and 2009 identified in the national Veterans Affairs Corporate Data Warehouse. Of those, 760 had an ICD-9 diagnosis of EAC. Cases of incident BE (in patients who developed EAC) were matched with controls with BE who did not develop cancer by the time of each EAC diagnosis in the corresponding case. Cases were followed until 2011.

After exclusions, the final analysis was based on 311 cases with EAC after BE and 856 matched controls with no EAC. Use of acid suppression was based on reports of medications dispensed at a Veteran’s Affairs pharmacy.

In general, patients with EAC were significantly more overweight and obese than controls (86.8% versus 80.6%, respectively, P = .04) and were more often cigarette smokers than controls (19% versus 13%, respectively, P = .02).

Cases were less likely than controls to fill at least one prescription for a PPI: 65% of cases versus 83% of controls. Dr Tan said the number of H₂RA users was much smaller; 8% of cases had at least one prescription for an H₂RA, compared with 14% of controls.

For PPIs, duration of use was not associated with risk, whereas the opposite was true for H₂RA users.

“This was an observational study, not a randomized trial, so we can’t say with certainty that PPI and H₂RA use reduce the risk of cancer,” Dr. Tan cautioned. “But the study suggests that there may be a role for these medications. Further study is needed.”

In a separate interview, Dr Tan noted that the risk of developing EAC in people with BE is low – 0.5% per year.

During the question and answer session following her presentation, an audience member said that it is interesting and disturbing that so many BE patients are not on acid suppression.

“There are no clear cut guidelines that state that BE patients should be on a PPI,” Dr Tan noted. “Maybe that’s why primary care doctors are not prescribing them.”

In a talk after Dr Tan’s presentation, Dr Stuart Spechler of UT Southwestern Medical Center, Dallas, noted that it appears that clonal diversity at diagnosis of BE identifies patients likely to develop EAC.

“This raises a concern: If these cells are predestined to become cancer, can they achieve salvation through good acts?” Dr. Spechler asked. “Dr Tan’s study suggests that they can. The malignant potential of BE may be predetermined, and acid suppression therapy reduces the risk of progression to EAC.”

Dr. Tan had no financial disclosures to report.

SAN DIEGO – In patients with Barrett’s esophagus (BE), acid suppression with proton pump inhibitors (PPIs) and, to a lesser extent, histamine₂ receptor antagonists (H₂RA) reduced the risk of progression to esophageal adenocarcinoma (EAC), according to the findings from a study reported at the annual Digestive Disease Week.

Both treatments were independently associated with reduced risk of progression to cancer in the nested, case-control study. Taking PPIs reduced the risk of developing EAC by 69% and taking H₂RAs reduced the risk by 45%.

“There are no concrete guidelines regarding use of PPIs for patients with Barrett’s esophagus,” said presenting author Dr Mimi C. Tan, a postdoctoral research fellow at Baylor College of Medicine in Houston. “The guidelines for these agents are based on symptoms of reflux. Although this study does not tell us for sure, it looks like taking these medications [in Barrett’s esophagus] prevents cancer. The effect is stronger with PPIs, but H₂RAs still have an effect.”

Alice Goodman

The incidence of BE is increasing in the United States, and BE is the only known risk factor for EAC.

“There is a knowledge gap, with a deficiency of studies of cases with longitudinal follow-up in a cohort of BE patients examining the effects of PPIs and H₂RAs on progression to EAC,” Dr. Tan explained. “We conducted this study in a large cohort of BE patients and hypothesized that acid suppression with PPIs and H₂RAs would decrease the risk of EAC.”

The study included a cohort of 29,536 male veterans diagnosed with BE between 2004 and 2009 identified in the national Veterans Affairs Corporate Data Warehouse. Of those, 760 had an ICD-9 diagnosis of EAC. Cases of incident BE (in patients who developed EAC) were matched with controls with BE who did not develop cancer by the time of each EAC diagnosis in the corresponding case. Cases were followed until 2011.

After exclusions, the final analysis was based on 311 cases with EAC after BE and 856 matched controls with no EAC. Use of acid suppression was based on reports of medications dispensed at a Veteran’s Affairs pharmacy.

In general, patients with EAC were significantly more overweight and obese than controls (86.8% versus 80.6%, respectively, P = .04) and were more often cigarette smokers than controls (19% versus 13%, respectively, P = .02).

Cases were less likely than controls to fill at least one prescription for a PPI: 65% of cases versus 83% of controls. Dr Tan said the number of H₂RA users was much smaller; 8% of cases had at least one prescription for an H₂RA, compared with 14% of controls.

For PPIs, duration of use was not associated with risk, whereas the opposite was true for H₂RA users.

“This was an observational study, not a randomized trial, so we can’t say with certainty that PPI and H₂RA use reduce the risk of cancer,” Dr. Tan cautioned. “But the study suggests that there may be a role for these medications. Further study is needed.”

In a separate interview, Dr Tan noted that the risk of developing EAC in people with BE is low – 0.5% per year.

During the question and answer session following her presentation, an audience member said that it is interesting and disturbing that so many BE patients are not on acid suppression.

“There are no clear cut guidelines that state that BE patients should be on a PPI,” Dr Tan noted. “Maybe that’s why primary care doctors are not prescribing them.”

In a talk after Dr Tan’s presentation, Dr Stuart Spechler of UT Southwestern Medical Center, Dallas, noted that it appears that clonal diversity at diagnosis of BE identifies patients likely to develop EAC.

“This raises a concern: If these cells are predestined to become cancer, can they achieve salvation through good acts?” Dr. Spechler asked. “Dr Tan’s study suggests that they can. The malignant potential of BE may be predetermined, and acid suppression therapy reduces the risk of progression to EAC.”

Dr. Tan had no financial disclosures to report.

SAN DIEGO – In patients with Barrett’s esophagus (BE), acid suppression with proton pump inhibitors (PPIs) and, to a lesser extent, histamine₂ receptor antagonists (H₂RA) reduced the risk of progression to esophageal adenocarcinoma (EAC), according to the findings from a study reported at the annual Digestive Disease Week.

Both treatments were independently associated with reduced risk of progression to cancer in the nested, case-control study. Taking PPIs reduced the risk of developing EAC by 69% and taking H₂RAs reduced the risk by 45%.

“There are no concrete guidelines regarding use of PPIs for patients with Barrett’s esophagus,” said presenting author Dr Mimi C. Tan, a postdoctoral research fellow at Baylor College of Medicine in Houston. “The guidelines for these agents are based on symptoms of reflux. Although this study does not tell us for sure, it looks like taking these medications [in Barrett’s esophagus] prevents cancer. The effect is stronger with PPIs, but H₂RAs still have an effect.”

Alice Goodman

The incidence of BE is increasing in the United States, and BE is the only known risk factor for EAC.

“There is a knowledge gap, with a deficiency of studies of cases with longitudinal follow-up in a cohort of BE patients examining the effects of PPIs and H₂RAs on progression to EAC,” Dr. Tan explained. “We conducted this study in a large cohort of BE patients and hypothesized that acid suppression with PPIs and H₂RAs would decrease the risk of EAC.”

The study included a cohort of 29,536 male veterans diagnosed with BE between 2004 and 2009 identified in the national Veterans Affairs Corporate Data Warehouse. Of those, 760 had an ICD-9 diagnosis of EAC. Cases of incident BE (in patients who developed EAC) were matched with controls with BE who did not develop cancer by the time of each EAC diagnosis in the corresponding case. Cases were followed until 2011.

After exclusions, the final analysis was based on 311 cases with EAC after BE and 856 matched controls with no EAC. Use of acid suppression was based on reports of medications dispensed at a Veteran’s Affairs pharmacy.

In general, patients with EAC were significantly more overweight and obese than controls (86.8% versus 80.6%, respectively, P = .04) and were more often cigarette smokers than controls (19% versus 13%, respectively, P = .02).

Cases were less likely than controls to fill at least one prescription for a PPI: 65% of cases versus 83% of controls. Dr Tan said the number of H₂RA users was much smaller; 8% of cases had at least one prescription for an H₂RA, compared with 14% of controls.

For PPIs, duration of use was not associated with risk, whereas the opposite was true for H₂RA users.

“This was an observational study, not a randomized trial, so we can’t say with certainty that PPI and H₂RA use reduce the risk of cancer,” Dr. Tan cautioned. “But the study suggests that there may be a role for these medications. Further study is needed.”

In a separate interview, Dr Tan noted that the risk of developing EAC in people with BE is low – 0.5% per year.

During the question and answer session following her presentation, an audience member said that it is interesting and disturbing that so many BE patients are not on acid suppression.

“There are no clear cut guidelines that state that BE patients should be on a PPI,” Dr Tan noted. “Maybe that’s why primary care doctors are not prescribing them.”

In a talk after Dr Tan’s presentation, Dr Stuart Spechler of UT Southwestern Medical Center, Dallas, noted that it appears that clonal diversity at diagnosis of BE identifies patients likely to develop EAC.

“This raises a concern: If these cells are predestined to become cancer, can they achieve salvation through good acts?” Dr. Spechler asked. “Dr Tan’s study suggests that they can. The malignant potential of BE may be predetermined, and acid suppression therapy reduces the risk of progression to EAC.”

Dr. Tan had no financial disclosures to report.

SAN DIEGO – Bile acid salts in the stool may be a potential biomarker for recurrent episodes of Clostridium difficile infection, a preliminary study suggests.

Although the finding needs to be validated in a prospective study, it could have therapeutic implications, the study investigators said.

“If our results are validated, we could take bile salt profiles of patients who come in with their first episode of C. difficile infection and, using this biomarker, adjust therapy accordingly,” said study lead author Dr. Jessica Allegretti, who presented the findings at the annual Digestive Disease Week. “A patient at high risk of recurrence could get fecal transplant earlier. Right now, fecal transplant is used for recurrent infection.”

Alice Goodman

C. difficile represents a major public health threat, and recurrent disease complicates 20%-30% of cases.

The disease is communicated by spores that are resistant to heat and antibiotics, and they germinate in the gastrointestinal tract. Bile acids are part of that process. Bile acids assist in the digestion of fat, and a small proportion pass into the colon where primary bile acids undergo transformation into secondary bile acids such as deoxycholate and lithocholate.

In vitro, primary acids can stimulate C. difficile, explained Dr. Allegretti of Brigham and Women’s Hospital, Cambridge, Mass. “Antibiotic therapy may ablate critical members of the microbiota. We aimed to assess bile acid profiles in patients with C. difficile infection, compared with controls, to understand their role in pathogenesis and hopefully identify a biomarker for recurrence.”

The cross-sectional study collected serum and a single stool sample from three groups of 60 patients: patients with a first episode of C. difficile (fCDI) prior to antibiotics (20 patients), patients with a recurrent episode (rCDI) on treatment with chronic vancomycin at the time of sampling (19), and healthy controls who were fecal transplant donors (21).

The researchers sequenced stool microbial components and conducted bile salt metabolomic profiling. Significant differences were revealed in microbial analysis of the stool samples: Primary bile salts (which induce germination) were significantly elevated in rCDI, compared with fCDI and controls – while secondary bile salts in the stool (which are protective) such as deoxycholate and lithocholate were significantly elevated in controls, compared with fCDI and rCDI (P = .0002 and P = .0007, respectively).

“The same trends were seen in the plasma samples, but were less dramatic than in the stool,” Dr. Allegretti noted.

The median predicted bile salt hydrolase (BSH) gene abundance in rCDI was 20% of the median value in controls (P = .001), and it also was significantly lower than fCDI (P = .001). No significant difference was seen between predicted BSH gene abundance between controls and the fCDI groups.

“An association with reduced predicted bacterial bile salt hydrolase gene abundance may be associated with a diminished capacity to metabolize bile acids,” she said.

The difference in BSH gene abundance between controls and rCDI was largely due to changes in the abundance of 10 bacterial taxa, Dr. Allegretti said.

“This study reinforces the importance of bile salts in CDI and demonstrates for the first time in humans that this shift can be appreciated as early as the first episode of CDI in patients who are antibiotic naive,” Dr Allegretti said.

She noted that rCDI samples were collected in patients on chronic antibiotic therapy, and that may explain some of the decrease in biological microdiversity seen in the study.

In search of a biomarker, “secondary bile acids clearly seem to be the winner, and for now, stool seems to make more sense than blood for samples,” she stated.

Dr. Allegretti and her colleagues are conducting a prospective validation study.

The American College of Gastroenterology funded the study.

SAN DIEGO – Bile acid salts in the stool may be a potential biomarker for recurrent episodes of Clostridium difficile infection, a preliminary study suggests.

Although the finding needs to be validated in a prospective study, it could have therapeutic implications, the study investigators said.

“If our results are validated, we could take bile salt profiles of patients who come in with their first episode of C. difficile infection and, using this biomarker, adjust therapy accordingly,” said study lead author Dr. Jessica Allegretti, who presented the findings at the annual Digestive Disease Week. “A patient at high risk of recurrence could get fecal transplant earlier. Right now, fecal transplant is used for recurrent infection.”

Alice Goodman

C. difficile represents a major public health threat, and recurrent disease complicates 20%-30% of cases.

The disease is communicated by spores that are resistant to heat and antibiotics, and they germinate in the gastrointestinal tract. Bile acids are part of that process. Bile acids assist in the digestion of fat, and a small proportion pass into the colon where primary bile acids undergo transformation into secondary bile acids such as deoxycholate and lithocholate.

In vitro, primary acids can stimulate C. difficile, explained Dr. Allegretti of Brigham and Women’s Hospital, Cambridge, Mass. “Antibiotic therapy may ablate critical members of the microbiota. We aimed to assess bile acid profiles in patients with C. difficile infection, compared with controls, to understand their role in pathogenesis and hopefully identify a biomarker for recurrence.”

The cross-sectional study collected serum and a single stool sample from three groups of 60 patients: patients with a first episode of C. difficile (fCDI) prior to antibiotics (20 patients), patients with a recurrent episode (rCDI) on treatment with chronic vancomycin at the time of sampling (19), and healthy controls who were fecal transplant donors (21).

The researchers sequenced stool microbial components and conducted bile salt metabolomic profiling. Significant differences were revealed in microbial analysis of the stool samples: Primary bile salts (which induce germination) were significantly elevated in rCDI, compared with fCDI and controls – while secondary bile salts in the stool (which are protective) such as deoxycholate and lithocholate were significantly elevated in controls, compared with fCDI and rCDI (P = .0002 and P = .0007, respectively).

“The same trends were seen in the plasma samples, but were less dramatic than in the stool,” Dr. Allegretti noted.

The median predicted bile salt hydrolase (BSH) gene abundance in rCDI was 20% of the median value in controls (P = .001), and it also was significantly lower than fCDI (P = .001). No significant difference was seen between predicted BSH gene abundance between controls and the fCDI groups.

“An association with reduced predicted bacterial bile salt hydrolase gene abundance may be associated with a diminished capacity to metabolize bile acids,” she said.

The difference in BSH gene abundance between controls and rCDI was largely due to changes in the abundance of 10 bacterial taxa, Dr. Allegretti said.

“This study reinforces the importance of bile salts in CDI and demonstrates for the first time in humans that this shift can be appreciated as early as the first episode of CDI in patients who are antibiotic naive,” Dr Allegretti said.

She noted that rCDI samples were collected in patients on chronic antibiotic therapy, and that may explain some of the decrease in biological microdiversity seen in the study.

In search of a biomarker, “secondary bile acids clearly seem to be the winner, and for now, stool seems to make more sense than blood for samples,” she stated.

Dr. Allegretti and her colleagues are conducting a prospective validation study.

The American College of Gastroenterology funded the study.

SAN DIEGO – Bile acid salts in the stool may be a potential biomarker for recurrent episodes of Clostridium difficile infection, a preliminary study suggests.

Although the finding needs to be validated in a prospective study, it could have therapeutic implications, the study investigators said.

“If our results are validated, we could take bile salt profiles of patients who come in with their first episode of C. difficile infection and, using this biomarker, adjust therapy accordingly,” said study lead author Dr. Jessica Allegretti, who presented the findings at the annual Digestive Disease Week. “A patient at high risk of recurrence could get fecal transplant earlier. Right now, fecal transplant is used for recurrent infection.”

Alice Goodman

C. difficile represents a major public health threat, and recurrent disease complicates 20%-30% of cases.

The disease is communicated by spores that are resistant to heat and antibiotics, and they germinate in the gastrointestinal tract. Bile acids are part of that process. Bile acids assist in the digestion of fat, and a small proportion pass into the colon where primary bile acids undergo transformation into secondary bile acids such as deoxycholate and lithocholate.

In vitro, primary acids can stimulate C. difficile, explained Dr. Allegretti of Brigham and Women’s Hospital, Cambridge, Mass. “Antibiotic therapy may ablate critical members of the microbiota. We aimed to assess bile acid profiles in patients with C. difficile infection, compared with controls, to understand their role in pathogenesis and hopefully identify a biomarker for recurrence.”

The cross-sectional study collected serum and a single stool sample from three groups of 60 patients: patients with a first episode of C. difficile (fCDI) prior to antibiotics (20 patients), patients with a recurrent episode (rCDI) on treatment with chronic vancomycin at the time of sampling (19), and healthy controls who were fecal transplant donors (21).

The researchers sequenced stool microbial components and conducted bile salt metabolomic profiling. Significant differences were revealed in microbial analysis of the stool samples: Primary bile salts (which induce germination) were significantly elevated in rCDI, compared with fCDI and controls – while secondary bile salts in the stool (which are protective) such as deoxycholate and lithocholate were significantly elevated in controls, compared with fCDI and rCDI (P = .0002 and P = .0007, respectively).

“The same trends were seen in the plasma samples, but were less dramatic than in the stool,” Dr. Allegretti noted.

The median predicted bile salt hydrolase (BSH) gene abundance in rCDI was 20% of the median value in controls (P = .001), and it also was significantly lower than fCDI (P = .001). No significant difference was seen between predicted BSH gene abundance between controls and the fCDI groups.

“An association with reduced predicted bacterial bile salt hydrolase gene abundance may be associated with a diminished capacity to metabolize bile acids,” she said.

The difference in BSH gene abundance between controls and rCDI was largely due to changes in the abundance of 10 bacterial taxa, Dr. Allegretti said.

“This study reinforces the importance of bile salts in CDI and demonstrates for the first time in humans that this shift can be appreciated as early as the first episode of CDI in patients who are antibiotic naive,” Dr Allegretti said.

She noted that rCDI samples were collected in patients on chronic antibiotic therapy, and that may explain some of the decrease in biological microdiversity seen in the study.

In search of a biomarker, “secondary bile acids clearly seem to be the winner, and for now, stool seems to make more sense than blood for samples,” she stated.

Dr. Allegretti and her colleagues are conducting a prospective validation study.

The American College of Gastroenterology funded the study.

SAN DIEGO – The tetracyclic antidepressant mirtazapine significantly improved indicators of functional dyspepsia and psychological distress in a single-center, randomized, placebo-controlled, double-blinded trial of 116 adults.

After 3 months of treatment, the mirtazapine group had significantly less nausea, early satiety, depression, somatization, hostility, and phobic anxiety, compared with the control group (all P values < .05), Dr. Yaoyao Gong reported at the annual Digestive Disease Week. Most patients began improving after 1-2 weeks of mirtazapine therapy, she added.

“We assume that mirtazapine might improve functional dyspepsia by improving depression and anxiety, reducing visceral sensitivity, and through its prokinetic effects on gastrointestinal transit,” said Dr. Gong, who is at the gastroenterology department of Nanjing Medical University, China.

Amy Karon

Mirtazapine is a presynaptic alpha-2 antagonist that also blocks the 5-HT2a, 5-HT2c, 5-HT3, and H-1 receptors. This atypical antidepressant reduced visceral hypersensitivity and increased gastric accommodation, gastric emptying, and colonic transit time in animal studies, and improved weight loss, early satiety, and nausea in a recent U.S. placebo-controlled pilot trial (Clin Gastroenterol Hepatol. 2016 Mar;14[3]:385-92).

As a biopsychosocial disorder, functional dyspepsia involves both physical and psychological symptoms, Dr. Gong noted. To explore how mirtazapine affects both realms, she and her associates randomized outpatients meeting Rome III functional dyspepsia criteria who also been diagnosed by a psychiatrist with anxiety, depression, or somatization disorder to receive either mirtazapine, 15 mg per day (61 patients) or placebo (55 patients). Both groups also received omeprazole, 30 mg per day, and mosapride, 5 mg three times a day. Patients were mostly in their early 40s, none was taking SSRIs or MAOIs, they had no history of abdominal surgery or upper endoscopy lesions, and they had negative ¹³C urea breath tests for Helicobacter pylori infection.

After 3 months of treatment, mirtazapine was associated with significantly lower 7-point Likert scales for nausea and early satiety, compared with standard care alone, said Dr. Gong. Mirtazapine did not significantly improve the other Rome III criteria for functional dyspepsia, but general overall score was significantly lower than for the control group.

In addition, the mirtazapine group had a “markedly better” average Symptom Checklist (SCL)-90 score, compared with the control group, and individual measures of depression, somatization, hostility, and phobic anxiety also were significantly lower than for controls (P < .05).

Mirtazapine did not significantly affect overall anxiety, a frequent psychological feature of functional dyspepsia. Mirtazapine was most often associated with dry mouth, although the researchers did not measure weight gain, another common adverse effect of the medication.

None of the patients stopped treatment because of adverse effects. The study group was too small to look at the separate effects of mirtazapine on epigastric pain and postprandial distress syndrome, Dr. Gong noted.

“We plan to assess these patients again after 12 months of treatment,” she said.

Dr. Gong did not report funding sources and had no disclosures.

SAN DIEGO – The tetracyclic antidepressant mirtazapine significantly improved indicators of functional dyspepsia and psychological distress in a single-center, randomized, placebo-controlled, double-blinded trial of 116 adults.

After 3 months of treatment, the mirtazapine group had significantly less nausea, early satiety, depression, somatization, hostility, and phobic anxiety, compared with the control group (all P values < .05), Dr. Yaoyao Gong reported at the annual Digestive Disease Week. Most patients began improving after 1-2 weeks of mirtazapine therapy, she added.

“We assume that mirtazapine might improve functional dyspepsia by improving depression and anxiety, reducing visceral sensitivity, and through its prokinetic effects on gastrointestinal transit,” said Dr. Gong, who is at the gastroenterology department of Nanjing Medical University, China.

Amy Karon

Mirtazapine is a presynaptic alpha-2 antagonist that also blocks the 5-HT2a, 5-HT2c, 5-HT3, and H-1 receptors. This atypical antidepressant reduced visceral hypersensitivity and increased gastric accommodation, gastric emptying, and colonic transit time in animal studies, and improved weight loss, early satiety, and nausea in a recent U.S. placebo-controlled pilot trial (Clin Gastroenterol Hepatol. 2016 Mar;14[3]:385-92).

As a biopsychosocial disorder, functional dyspepsia involves both physical and psychological symptoms, Dr. Gong noted. To explore how mirtazapine affects both realms, she and her associates randomized outpatients meeting Rome III functional dyspepsia criteria who also been diagnosed by a psychiatrist with anxiety, depression, or somatization disorder to receive either mirtazapine, 15 mg per day (61 patients) or placebo (55 patients). Both groups also received omeprazole, 30 mg per day, and mosapride, 5 mg three times a day. Patients were mostly in their early 40s, none was taking SSRIs or MAOIs, they had no history of abdominal surgery or upper endoscopy lesions, and they had negative ¹³C urea breath tests for Helicobacter pylori infection.

After 3 months of treatment, mirtazapine was associated with significantly lower 7-point Likert scales for nausea and early satiety, compared with standard care alone, said Dr. Gong. Mirtazapine did not significantly improve the other Rome III criteria for functional dyspepsia, but general overall score was significantly lower than for the control group.

In addition, the mirtazapine group had a “markedly better” average Symptom Checklist (SCL)-90 score, compared with the control group, and individual measures of depression, somatization, hostility, and phobic anxiety also were significantly lower than for controls (P < .05).

Mirtazapine did not significantly affect overall anxiety, a frequent psychological feature of functional dyspepsia. Mirtazapine was most often associated with dry mouth, although the researchers did not measure weight gain, another common adverse effect of the medication.

None of the patients stopped treatment because of adverse effects. The study group was too small to look at the separate effects of mirtazapine on epigastric pain and postprandial distress syndrome, Dr. Gong noted.

“We plan to assess these patients again after 12 months of treatment,” she said.

Dr. Gong did not report funding sources and had no disclosures.

SAN DIEGO – The tetracyclic antidepressant mirtazapine significantly improved indicators of functional dyspepsia and psychological distress in a single-center, randomized, placebo-controlled, double-blinded trial of 116 adults.

After 3 months of treatment, the mirtazapine group had significantly less nausea, early satiety, depression, somatization, hostility, and phobic anxiety, compared with the control group (all P values < .05), Dr. Yaoyao Gong reported at the annual Digestive Disease Week. Most patients began improving after 1-2 weeks of mirtazapine therapy, she added.

“We assume that mirtazapine might improve functional dyspepsia by improving depression and anxiety, reducing visceral sensitivity, and through its prokinetic effects on gastrointestinal transit,” said Dr. Gong, who is at the gastroenterology department of Nanjing Medical University, China.

Amy Karon

Mirtazapine is a presynaptic alpha-2 antagonist that also blocks the 5-HT2a, 5-HT2c, 5-HT3, and H-1 receptors. This atypical antidepressant reduced visceral hypersensitivity and increased gastric accommodation, gastric emptying, and colonic transit time in animal studies, and improved weight loss, early satiety, and nausea in a recent U.S. placebo-controlled pilot trial (Clin Gastroenterol Hepatol. 2016 Mar;14[3]:385-92).

As a biopsychosocial disorder, functional dyspepsia involves both physical and psychological symptoms, Dr. Gong noted. To explore how mirtazapine affects both realms, she and her associates randomized outpatients meeting Rome III functional dyspepsia criteria who also been diagnosed by a psychiatrist with anxiety, depression, or somatization disorder to receive either mirtazapine, 15 mg per day (61 patients) or placebo (55 patients). Both groups also received omeprazole, 30 mg per day, and mosapride, 5 mg three times a day. Patients were mostly in their early 40s, none was taking SSRIs or MAOIs, they had no history of abdominal surgery or upper endoscopy lesions, and they had negative ¹³C urea breath tests for Helicobacter pylori infection.

After 3 months of treatment, mirtazapine was associated with significantly lower 7-point Likert scales for nausea and early satiety, compared with standard care alone, said Dr. Gong. Mirtazapine did not significantly improve the other Rome III criteria for functional dyspepsia, but general overall score was significantly lower than for the control group.

In addition, the mirtazapine group had a “markedly better” average Symptom Checklist (SCL)-90 score, compared with the control group, and individual measures of depression, somatization, hostility, and phobic anxiety also were significantly lower than for controls (P < .05).

Mirtazapine did not significantly affect overall anxiety, a frequent psychological feature of functional dyspepsia. Mirtazapine was most often associated with dry mouth, although the researchers did not measure weight gain, another common adverse effect of the medication.

None of the patients stopped treatment because of adverse effects. The study group was too small to look at the separate effects of mirtazapine on epigastric pain and postprandial distress syndrome, Dr. Gong noted.

“We plan to assess these patients again after 12 months of treatment,” she said.

Dr. Gong did not report funding sources and had no disclosures.