Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:

• Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
• The pain relief of the active treatment was sustained 48 hours post-treatment.
• Incidence of device-related adverse events was low and similar between treatment groups.

Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.

Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:

• Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
• The pain relief of the active treatment was sustained 48 hours post-treatment.
• Incidence of device-related adverse events was low and similar between treatment groups.

Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.

Remote Electrical Neuromodulation (REN) may provide relief of migraine pain and most bothersome symptoms compared to placebo, a new study found. The efficacy and safety of a REN device for acute treatment of migraine was assessed. The randomized, double-blind, multicenter study was conducted at 7 sites in the United States and 5 sites in Israel. The study included 252 adults meeting the International Classification of Headache Disorders criteria for migraine with 2 to 8 migraine headaches per month, and the patients were randomized 1:1 to active or sham stimulation. Among the findings:

• Active stimulation was more effective than sham stimulation in achieving pain relief, pain-free, and MBS relief at 2 hours post-treatment.
• The pain relief of the active treatment was sustained 48 hours post-treatment.
• Incidence of device-related adverse events was low and similar between treatment groups.

Yarnitsky D, et al. Remote electrical neuromodulation (REN) relieves acute migraine: A randomized, double-blind, placebo-controlled, multicenter trial. [Published online ahead of print May 9, 2019]. Headache. doi: 10.1111/head.13551.

Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:

• Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
• Time to benefit was between 0.5 and 33.58 hours.
• Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.

Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121. 

Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:

• Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
• Time to benefit was between 0.5 and 33.58 hours.
• Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.

Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121. 

Multiple cranial nerve blocks may provide an efficacious, well tolerated and reproducible transitional treatment for chronic headache disorders, a new study found. The uncontrolled, open-label study included 119 patients with chronic cluster headache, chronic migraine, short-lasting unilateral neuralgiform attack disorders, new daily persistent headaches, hemicrania continua and chronic paroxysmal hemicrania. All had failed to respond to greater occipital nerve blocks. Researchers found:

• Response rate for the entire cohort was 55.4%: Chronic cluster headache (69.2%), chronic migraine (49%), short-lasting unilateral neuralgiform attack disorders (56.3%), new daily persistent headache (10%), hemicrania continua (83.3%), and chronic paroxysmal hemicrania (25%).
• Time to benefit was between 0.5 and 33.58 hours.
• Benefit was maintained up to 4 weeks in over half of responders in all groups except chronic migraine and paroxysmal hemicrania.

Miller S, et al. Multiple cranial nerve blocks for the transitional treatment of chronic headaches. [Published online ahead of print May 13, 2019]. Cephalalgia. doi: 10.1177/0333102419848121. 

Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:

• There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
• More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
• Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.

Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.

Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:

• There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
• More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
• Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.

Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.

Transcranial sonography (TCS) signal alteration of brainstem raphe (BR) can be a biomarker for depression in migraine but is not associated with migraine headache itself, a new study found. Forty-two patients who had migraine without aura and 40 healthy controls were recruited for the study. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and BR, width of the frontal horns of the lateral ventricles, and the third ventricle were assessed with TCS. Researchers found:

• There were no significant differences between migraineurs and controls in the width of front horn of the lateral ventricle, width of third ventricle, as well as in the echogenicity of SN, CN, LN and BR.
• More patients with migraine were detected with increased echogenicity of CN and LN compared with controls.
• Patients with hypoechogenic BR had significantly higher Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D) scores than those with normal BR signal.

Tao WW, et al. Hypoechogenicity of brainstem raphe correlates with depression in migraine patients. [Published online ahead of print May 15, 2019]. J Headache Pain. doi: 10.1186/s10194-019-1011-2.

Gastric cancer is the fifth most common malignancy worldwide with high mortality and morbidity and an estimated 952,000 cases reported globally in 2012.

In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).

Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.

GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).

Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.

On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.

On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.

Gastric cancer is the fifth most common malignancy worldwide with high mortality and morbidity and an estimated 952,000 cases reported globally in 2012.

In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).

Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.

GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).

Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.

On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.

On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.

Gastric cancer is the fifth most common malignancy worldwide with high mortality and morbidity and an estimated 952,000 cases reported globally in 2012.

In the United States, gastric cancer accounts for 1.6% of all cancers with an estimated 27,510 cases in 2019 per the SEER database. Although the incidence of gastric cancer has been decreasing in the United States, there have been alarming trends, suggesting an increased rate in select populations, especially in the young Hispanic population in the age group of 20-49 years (SEER Cancer Statistics Review [CSR] 1975-2015).

Risk factors for gastric cancer include increasing age, male sex, presence of intestinal metaplasia, and varying degrees of dysplasia (Endoscopy. 2019;51[4]:365-88). Gastric cancer is primarily characterized into two subtypes: intestinal type, which is the more common type associated with gastric intestinal metaplasia (GIM), and the diffuse type, which is genetically determined.

GIM, a precancerous lesion, is defined as the replacement of the normal gastric mucosa by intestinal epithelium and can be limited (confined to one region of the stomach) or extensive (involving more than two regions of the stomach). Risk factors for GIM include Helicobacter pylori infection, age, smoking status, and presence of a first-degree relative with gastric cancer. Histologically, GIM is characterized as either complete – defined as the presence of small intestinal-type mucosa with mature absorptive cells, goblet cells, and a brush border – or incomplete – with columnar “intermediate” cells in various stages of differentiation, irregular mucin droplets, without a brush border. Extensive and incomplete type of GIM is associated with a higher risk of gastric cancer (Endoscopy. 2019;51[4]:365-88).

Gastric cancer screening has been shown to be effective in countries with a high incidence of gastric cancer. However, in low-incidence countries, at-risk patients can be identified based on epidemiology, genetics, and environmental risk factors as well as incidence of H. pylori, and serologic markers of chronic inflammation such as pepsinogen, and gastrin (Am J Gastroenterol. 2017;112[5]:704-15). H. pylori eradication has been shown to reduce the risk of developing gastric adenocarcinoma in patients with H. pylori-associated GIM. For detection of dysplasia and early gastric cancer, patients with GIM should undergo a full systematic endoscopy protocol of the stomach with clear photographic documentation of gastric regions and pathology.

On standard white-light endoscopy, GIM appears as small gray-white, slightly elevated plaques surrounded by mixed patchy pink and pale areas of mucosa causing an irregular uneven surface. Sometimes GIM can present as patchy erythema with mottling.

On the other hand, presence of features such as differences in color, loss of vascularity, elevation or depression, nodularity or thickening, and abnormal convergence or flattening of folds should raise suspicion for gastric dysplasia or early gastric cancer. Presence of GIM on endoscopy should be documented in detail with photographic evidence including the location and extent of GIM, and obtaining mapping biopsies that include at least two biopsies from the antrum (from lesser and greater curve) and from the body (lesser and greater curve). Endoscopic surveillance is recommended every 3 years in patients with extensive GIM affecting the antrum and body, incomplete GIM, and a family history of gastric cancer.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Sharma is professor of medicine and director of fellowship training, division of gastroenterology and hepatology, University of Kansas, Kansas City.

In the upper GI section of the Postgraduate course program, Ikuo Hirano, MD, educated us on the refractory patient with eosinophilic esophagitis, reinforcing the need for chronic maintenance treatment and the complementary role of dilation. Gregory Ginsberg, MD, elucidated the specific strategies needed for gastric polyps with advice on which to leave and which to resect. Sachin Wani, MD, carefully outlined the changing landscape of Barrett’s esophagus with emphasis on our move to ablate rather than observe low-grade dysplasia. In the difficult area of treating gastroparesis, Linda Nguyen, MD, acquainted us with some of the newer medications for this disorder and discussed the emerging role of endoscopic pyloromyotomy. Michael Camilleri, MD, delivered a thorough analysis on the concept of leaky gut with data-driven recommendations on testing and the lack of adequate treatment. Finally, William Chey, MD, gave perspective to diagnosis and treatment of small-bowel bacterial overgrowth, particularly with its role in irritable bowel syndrome.

In the lower GI section of the course, Sunanda Kane, MD, gave a wonderful overview the present and emerging biologics for treatment of inflammatory bowel disease (IBD). David Rubin, MD, shared his expertise and vast experience for best management of ulcerative colitis while Edward Loftus Jr., MD, discussed the fact and fiction of diet-based therapy in IBD. This was followed by a timely lecture by Christina Ha, MD, on the need to think well outside the GI tract in IBD, discussing infections, cancers, and vaccinations in patients with IBD. The IBD section finished with an erudite and timely lecture by Marla Dubinsky, MD, evaluating the controversy over use of biosimilars in our clinical practice. The remainder of the lower GI section started with AGA President David Lieberman, MD, analyzing recent data on the need to move the colonic cancer screening age to 45 years, particularly in African Americans. Following this was a timely talk by Xavie Llor, MD, PhD, on when to suspect and how to test for the expanding definition of Lynch syndrome. Lin Chang, MD, delivered the penultimate clinical lecture on management of irritable bowel syndrome based on her many years of clinical expertise in this area. Finally, Gail Hecht, MD, AGAF, a former AGA president, summarized the exciting world of microbiome research from the recent annual Gut Microbiota for Health World Summit. All in all it was considered one of the best AGA Postgraduate courses by many and we look forward to even greater improvements for 2020.

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Katzka is professor of medicine and head of the Esophageal Interest Group at the Mayo Clinic in Rochester, Minn. He is on the advisory boards for Shire and Celgene.

In the upper GI section of the Postgraduate course program, Ikuo Hirano, MD, educated us on the refractory patient with eosinophilic esophagitis, reinforcing the need for chronic maintenance treatment and the complementary role of dilation. Gregory Ginsberg, MD, elucidated the specific strategies needed for gastric polyps with advice on which to leave and which to resect. Sachin Wani, MD, carefully outlined the changing landscape of Barrett’s esophagus with emphasis on our move to ablate rather than observe low-grade dysplasia. In the difficult area of treating gastroparesis, Linda Nguyen, MD, acquainted us with some of the newer medications for this disorder and discussed the emerging role of endoscopic pyloromyotomy. Michael Camilleri, MD, delivered a thorough analysis on the concept of leaky gut with data-driven recommendations on testing and the lack of adequate treatment. Finally, William Chey, MD, gave perspective to diagnosis and treatment of small-bowel bacterial overgrowth, particularly with its role in irritable bowel syndrome.

In the lower GI section of the course, Sunanda Kane, MD, gave a wonderful overview the present and emerging biologics for treatment of inflammatory bowel disease (IBD). David Rubin, MD, shared his expertise and vast experience for best management of ulcerative colitis while Edward Loftus Jr., MD, discussed the fact and fiction of diet-based therapy in IBD. This was followed by a timely lecture by Christina Ha, MD, on the need to think well outside the GI tract in IBD, discussing infections, cancers, and vaccinations in patients with IBD. The IBD section finished with an erudite and timely lecture by Marla Dubinsky, MD, evaluating the controversy over use of biosimilars in our clinical practice. The remainder of the lower GI section started with AGA President David Lieberman, MD, analyzing recent data on the need to move the colonic cancer screening age to 45 years, particularly in African Americans. Following this was a timely talk by Xavie Llor, MD, PhD, on when to suspect and how to test for the expanding definition of Lynch syndrome. Lin Chang, MD, delivered the penultimate clinical lecture on management of irritable bowel syndrome based on her many years of clinical expertise in this area. Finally, Gail Hecht, MD, AGAF, a former AGA president, summarized the exciting world of microbiome research from the recent annual Gut Microbiota for Health World Summit. All in all it was considered one of the best AGA Postgraduate courses by many and we look forward to even greater improvements for 2020.

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Katzka is professor of medicine and head of the Esophageal Interest Group at the Mayo Clinic in Rochester, Minn. He is on the advisory boards for Shire and Celgene.

In the upper GI section of the Postgraduate course program, Ikuo Hirano, MD, educated us on the refractory patient with eosinophilic esophagitis, reinforcing the need for chronic maintenance treatment and the complementary role of dilation. Gregory Ginsberg, MD, elucidated the specific strategies needed for gastric polyps with advice on which to leave and which to resect. Sachin Wani, MD, carefully outlined the changing landscape of Barrett’s esophagus with emphasis on our move to ablate rather than observe low-grade dysplasia. In the difficult area of treating gastroparesis, Linda Nguyen, MD, acquainted us with some of the newer medications for this disorder and discussed the emerging role of endoscopic pyloromyotomy. Michael Camilleri, MD, delivered a thorough analysis on the concept of leaky gut with data-driven recommendations on testing and the lack of adequate treatment. Finally, William Chey, MD, gave perspective to diagnosis and treatment of small-bowel bacterial overgrowth, particularly with its role in irritable bowel syndrome.

In the lower GI section of the course, Sunanda Kane, MD, gave a wonderful overview the present and emerging biologics for treatment of inflammatory bowel disease (IBD). David Rubin, MD, shared his expertise and vast experience for best management of ulcerative colitis while Edward Loftus Jr., MD, discussed the fact and fiction of diet-based therapy in IBD. This was followed by a timely lecture by Christina Ha, MD, on the need to think well outside the GI tract in IBD, discussing infections, cancers, and vaccinations in patients with IBD. The IBD section finished with an erudite and timely lecture by Marla Dubinsky, MD, evaluating the controversy over use of biosimilars in our clinical practice. The remainder of the lower GI section started with AGA President David Lieberman, MD, analyzing recent data on the need to move the colonic cancer screening age to 45 years, particularly in African Americans. Following this was a timely talk by Xavie Llor, MD, PhD, on when to suspect and how to test for the expanding definition of Lynch syndrome. Lin Chang, MD, delivered the penultimate clinical lecture on management of irritable bowel syndrome based on her many years of clinical expertise in this area. Finally, Gail Hecht, MD, AGAF, a former AGA president, summarized the exciting world of microbiome research from the recent annual Gut Microbiota for Health World Summit. All in all it was considered one of the best AGA Postgraduate courses by many and we look forward to even greater improvements for 2020.

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2019. Dr. Katzka is professor of medicine and head of the Esophageal Interest Group at the Mayo Clinic in Rochester, Minn. He is on the advisory boards for Shire and Celgene.

An investigational agent known as REGN-EB3 has met an early stopping criterion in the protocol of an Ebola therapeutics trial, according to a National Institutes of Health media advisory.

gl0ck/Thinkstock

Preliminary results in 499 study participants showed that individuals receiving either of two treatments, REGN-EB3 or mAb114, had a greater chance of survival, compared with participants in the other two study arms.

The randomized, controlled Pamoja Tulinde Maisha (PALM) study, which began Nov. 20, 2018, was designed to evaluate four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3) for the treatment of patients with Ebola virus disease in the Democratic Republic of the Congo (DRC) as part of the emergency response to an ongoing outbreak in the North Kivu and Ituri provinces.

As of Aug. 9, 2019, the trial had enrolled 681 patients at four Ebola treatment centers in live outbreak regions of the DRC, with the goal of enrolling 725 patients in total.

The trial investigators and study cosponsors accepted the recommendation for early termination, and staff at the trial sites in the DRC were promptly informed, according to the media advisory. Additional patient randomizations in the now-revised trial will be limited to treatment either with REGN-EB3 or mAb114. Patients randomized to the ZMapp or remdesivir arms in the last 10 days of the original trial will be given the option, at the discretion of their treating physician, to receive either of the two more effective treatments, according to the NIH.

“While the final analysis of the data can occur only after all the data are generated and collected (likely late September/early October 2019), the DSMB [Data and Safety Monitoring Board] and the study leadership felt the preliminary analysis of the existing data was compelling enough to recommend and implement these changes in the trial immediately. The complete results will be submitted for publication in the peer-reviewed medical literature as soon as possible,” the NIH stated.

The study is cosponsored and funded by the NIH, carried out by an international research consortium coordinated by the World Health Organization, and supported by four pharmaceutical companies (MappBio, Gilead, Regeneron, and Ridgeback Biotherapeutics).

mlesney@mdedge.com

An investigational agent known as REGN-EB3 has met an early stopping criterion in the protocol of an Ebola therapeutics trial, according to a National Institutes of Health media advisory.

gl0ck/Thinkstock

Preliminary results in 499 study participants showed that individuals receiving either of two treatments, REGN-EB3 or mAb114, had a greater chance of survival, compared with participants in the other two study arms.

The randomized, controlled Pamoja Tulinde Maisha (PALM) study, which began Nov. 20, 2018, was designed to evaluate four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3) for the treatment of patients with Ebola virus disease in the Democratic Republic of the Congo (DRC) as part of the emergency response to an ongoing outbreak in the North Kivu and Ituri provinces.

As of Aug. 9, 2019, the trial had enrolled 681 patients at four Ebola treatment centers in live outbreak regions of the DRC, with the goal of enrolling 725 patients in total.

The trial investigators and study cosponsors accepted the recommendation for early termination, and staff at the trial sites in the DRC were promptly informed, according to the media advisory. Additional patient randomizations in the now-revised trial will be limited to treatment either with REGN-EB3 or mAb114. Patients randomized to the ZMapp or remdesivir arms in the last 10 days of the original trial will be given the option, at the discretion of their treating physician, to receive either of the two more effective treatments, according to the NIH.

“While the final analysis of the data can occur only after all the data are generated and collected (likely late September/early October 2019), the DSMB [Data and Safety Monitoring Board] and the study leadership felt the preliminary analysis of the existing data was compelling enough to recommend and implement these changes in the trial immediately. The complete results will be submitted for publication in the peer-reviewed medical literature as soon as possible,” the NIH stated.

The study is cosponsored and funded by the NIH, carried out by an international research consortium coordinated by the World Health Organization, and supported by four pharmaceutical companies (MappBio, Gilead, Regeneron, and Ridgeback Biotherapeutics).

mlesney@mdedge.com

An investigational agent known as REGN-EB3 has met an early stopping criterion in the protocol of an Ebola therapeutics trial, according to a National Institutes of Health media advisory.

gl0ck/Thinkstock

Preliminary results in 499 study participants showed that individuals receiving either of two treatments, REGN-EB3 or mAb114, had a greater chance of survival, compared with participants in the other two study arms.

The randomized, controlled Pamoja Tulinde Maisha (PALM) study, which began Nov. 20, 2018, was designed to evaluate four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3) for the treatment of patients with Ebola virus disease in the Democratic Republic of the Congo (DRC) as part of the emergency response to an ongoing outbreak in the North Kivu and Ituri provinces.

As of Aug. 9, 2019, the trial had enrolled 681 patients at four Ebola treatment centers in live outbreak regions of the DRC, with the goal of enrolling 725 patients in total.

The trial investigators and study cosponsors accepted the recommendation for early termination, and staff at the trial sites in the DRC were promptly informed, according to the media advisory. Additional patient randomizations in the now-revised trial will be limited to treatment either with REGN-EB3 or mAb114. Patients randomized to the ZMapp or remdesivir arms in the last 10 days of the original trial will be given the option, at the discretion of their treating physician, to receive either of the two more effective treatments, according to the NIH.

“While the final analysis of the data can occur only after all the data are generated and collected (likely late September/early October 2019), the DSMB [Data and Safety Monitoring Board] and the study leadership felt the preliminary analysis of the existing data was compelling enough to recommend and implement these changes in the trial immediately. The complete results will be submitted for publication in the peer-reviewed medical literature as soon as possible,” the NIH stated.

The study is cosponsored and funded by the NIH, carried out by an international research consortium coordinated by the World Health Organization, and supported by four pharmaceutical companies (MappBio, Gilead, Regeneron, and Ridgeback Biotherapeutics).

mlesney@mdedge.com

Fewer than one in five oncologic phase 3 randomized controlled trials (RCTs) had female corresponding authors, but the proportion of women in this authorship role appears to be gradually increasing, investigators report.

“Through identification of the factors associated with gender disparities in RCT leadership, we hope that the academic oncology community will work to better understand and address the underlying reasons for such imbalances,” wrote Ethan B. Ludmir, MD, of the University of Texas MD Anderson Cancer Center, Houston, and associates. The report is in JAMA Oncology.

The authors searched ClinicalTrials.gov in late 2017 for all oncologic phase 3 RCTs. Of the 1,239 they initially turned up, the authors narrowed them down to the 598 that used multiple arms to test a therapeutic intervention, underwent peer review, and published results of primary endpoints. Among the trials, all published between 2003 and 2018, 17.9% had female corresponding authors.

Industry-funded trials, which comprised 77.8% of the sample, had half as many female corresponding authors (14.4%) as those not funded by industry (30.1%) (P less than .001), “possibly reflecting gender biases that are enhanced in the context of industry relationships with academic medicine,” the authors wrote. The opposite trend appeared in cooperative group trials, a quarter of which (25.9%) had female corresponding authors, compared with 14.3% of noncooperative trials (P = .001).

Trials for breast cancer and head and neck cancer were most likely to have female corresponding authors, while the trials with the lowest rates were those for gastrointestinal, genitourinary, and hematologic cancers (P less than .001). The researchers also found gender disparities in the type of intervention tested: Radiotherapy and supportive care studies were more likely to have female corresponding authors, yet none of the surgical trials had any (P less than .001).

In addition, female corresponding authorship was more likely when the institutions were based in the United States (n = 329) than when they were overseas (P = .001). Women were corresponding authors in 22.5% of U.S. studies and 20% of Canadian studies but only 12% of European trials and 2.3% of Asian trials (P = .001).

Within the United States, more than a third of studies from institutions in the Southeast had female corresponding authors (34.1%), followed by those in the Midwest (27.5%) and West (25.9%). Southwestern institutions were least likely to have female corresponding authors (8.7%). Approximately twice as many studies came from Northeastern institutions as from other regions (n = 112), but only 18.8% of these had female corresponding authors (P = .03).

The frequency of female corresponding authors has been increasing, however: The authors calculated a 1.2% increase each year, “echoing data showing an approximate 1.0% annual increase in the number of female academic hematologist-oncologists,” they noted. “However, the absolute female corresponding author rate for these trials is still lower than the percentage of female academic oncologists in this general study period, ranging from 27% in 2000 to 39% in 2015.”

SOURCE: Ludmir EB et al. JAMA Oncology. 8 Aug 2019. doi: 10.1001/jamaoncol.2019.2196.

Fewer than one in five oncologic phase 3 randomized controlled trials (RCTs) had female corresponding authors, but the proportion of women in this authorship role appears to be gradually increasing, investigators report.

“Through identification of the factors associated with gender disparities in RCT leadership, we hope that the academic oncology community will work to better understand and address the underlying reasons for such imbalances,” wrote Ethan B. Ludmir, MD, of the University of Texas MD Anderson Cancer Center, Houston, and associates. The report is in JAMA Oncology.

The authors searched ClinicalTrials.gov in late 2017 for all oncologic phase 3 RCTs. Of the 1,239 they initially turned up, the authors narrowed them down to the 598 that used multiple arms to test a therapeutic intervention, underwent peer review, and published results of primary endpoints. Among the trials, all published between 2003 and 2018, 17.9% had female corresponding authors.

Industry-funded trials, which comprised 77.8% of the sample, had half as many female corresponding authors (14.4%) as those not funded by industry (30.1%) (P less than .001), “possibly reflecting gender biases that are enhanced in the context of industry relationships with academic medicine,” the authors wrote. The opposite trend appeared in cooperative group trials, a quarter of which (25.9%) had female corresponding authors, compared with 14.3% of noncooperative trials (P = .001).

Trials for breast cancer and head and neck cancer were most likely to have female corresponding authors, while the trials with the lowest rates were those for gastrointestinal, genitourinary, and hematologic cancers (P less than .001). The researchers also found gender disparities in the type of intervention tested: Radiotherapy and supportive care studies were more likely to have female corresponding authors, yet none of the surgical trials had any (P less than .001).

In addition, female corresponding authorship was more likely when the institutions were based in the United States (n = 329) than when they were overseas (P = .001). Women were corresponding authors in 22.5% of U.S. studies and 20% of Canadian studies but only 12% of European trials and 2.3% of Asian trials (P = .001).

Within the United States, more than a third of studies from institutions in the Southeast had female corresponding authors (34.1%), followed by those in the Midwest (27.5%) and West (25.9%). Southwestern institutions were least likely to have female corresponding authors (8.7%). Approximately twice as many studies came from Northeastern institutions as from other regions (n = 112), but only 18.8% of these had female corresponding authors (P = .03).

The frequency of female corresponding authors has been increasing, however: The authors calculated a 1.2% increase each year, “echoing data showing an approximate 1.0% annual increase in the number of female academic hematologist-oncologists,” they noted. “However, the absolute female corresponding author rate for these trials is still lower than the percentage of female academic oncologists in this general study period, ranging from 27% in 2000 to 39% in 2015.”

SOURCE: Ludmir EB et al. JAMA Oncology. 8 Aug 2019. doi: 10.1001/jamaoncol.2019.2196.

Fewer than one in five oncologic phase 3 randomized controlled trials (RCTs) had female corresponding authors, but the proportion of women in this authorship role appears to be gradually increasing, investigators report.

“Through identification of the factors associated with gender disparities in RCT leadership, we hope that the academic oncology community will work to better understand and address the underlying reasons for such imbalances,” wrote Ethan B. Ludmir, MD, of the University of Texas MD Anderson Cancer Center, Houston, and associates. The report is in JAMA Oncology.

The authors searched ClinicalTrials.gov in late 2017 for all oncologic phase 3 RCTs. Of the 1,239 they initially turned up, the authors narrowed them down to the 598 that used multiple arms to test a therapeutic intervention, underwent peer review, and published results of primary endpoints. Among the trials, all published between 2003 and 2018, 17.9% had female corresponding authors.

Industry-funded trials, which comprised 77.8% of the sample, had half as many female corresponding authors (14.4%) as those not funded by industry (30.1%) (P less than .001), “possibly reflecting gender biases that are enhanced in the context of industry relationships with academic medicine,” the authors wrote. The opposite trend appeared in cooperative group trials, a quarter of which (25.9%) had female corresponding authors, compared with 14.3% of noncooperative trials (P = .001).

Trials for breast cancer and head and neck cancer were most likely to have female corresponding authors, while the trials with the lowest rates were those for gastrointestinal, genitourinary, and hematologic cancers (P less than .001). The researchers also found gender disparities in the type of intervention tested: Radiotherapy and supportive care studies were more likely to have female corresponding authors, yet none of the surgical trials had any (P less than .001).

In addition, female corresponding authorship was more likely when the institutions were based in the United States (n = 329) than when they were overseas (P = .001). Women were corresponding authors in 22.5% of U.S. studies and 20% of Canadian studies but only 12% of European trials and 2.3% of Asian trials (P = .001).

Within the United States, more than a third of studies from institutions in the Southeast had female corresponding authors (34.1%), followed by those in the Midwest (27.5%) and West (25.9%). Southwestern institutions were least likely to have female corresponding authors (8.7%). Approximately twice as many studies came from Northeastern institutions as from other regions (n = 112), but only 18.8% of these had female corresponding authors (P = .03).

The frequency of female corresponding authors has been increasing, however: The authors calculated a 1.2% increase each year, “echoing data showing an approximate 1.0% annual increase in the number of female academic hematologist-oncologists,” they noted. “However, the absolute female corresponding author rate for these trials is still lower than the percentage of female academic oncologists in this general study period, ranging from 27% in 2000 to 39% in 2015.”

SOURCE: Ludmir EB et al. JAMA Oncology. 8 Aug 2019. doi: 10.1001/jamaoncol.2019.2196.

Adding electrocardiogram findings and clinical assessment to high-sensitivity cardiac troponin measurements in patients presenting with chest pain could improve predictions of their risk of 30-day major adverse cardiac events, particularly unstable angina, research suggests.

Investigators reported outcomes of a prospective study involving 3,123 patients with suspected acute myocardial infarction. The findings are in the Journal of the American College of Cardiology.

The aim of the researchers was to validate an extended algorithm that combined the European Society of Cardiology’s high-sensitivity cardiac troponin measurement at presentation and after 1 hour (ESC hs-cTn 0/1 h algorithm) with clinical assessment and ECG findings to aid prediction of major adverse cardiac events (MACE) within 30 days.

The clinical assessment involved the treating ED physician’s use of a visual analog scale to assess the patient’s pretest probability for an acute coronary syndrome (ACS), with a score above 70% qualifying as high likelihood.

The researchers found that the ESC hs-cTn 0/1 h algorithm alone triaged significantly more patients toward rule-out for MACE than did the extended algorithm (60% vs. 45%, P less than .001). This resulted in 487 patients being reclassified toward “observe” by the extended algorithm, and among this group the 30-day MACE rate was 1.1%.

However, the 30-day MACE rates were similar in the two groups – 0.6% among those ruled out by the ESC hs-cTn 0/1 h algorithm alone and 0.4% in those ruled out by the extended algorithm – resulting in a similar negative predictive value.

“These estimates will help clinicians to appropriately manage patients triaged toward rule-out according to the ESC hs-cTnT 0/1 h algorithm, in whom either the [visual analog scale] for ACS or the ECG still suggests the presence of an ACS,” wrote Thomas Nestelberger, MD, of the Cardiovascular Research Institute Basel (Switzerland) at the University of Basel, and coinvestigators.

The ESC hs-cTn 0/1 h algorithm also ruled in fewer patients than did the extended algorithm (16% vs. 26%, P less than .001), giving it a higher positive predictive value.


When the researchers added unstable angina to the major adverse cardiac event outcome, they found the ESC hs-cTn 0/1 h algorithm had a lower negative predictive value and a higher negative likelihood ratio compared with the extended algorithm for patients ruled out, but a higher positive predictive value and positive likelihood ratio for patients ruled in.

“Our findings corroborate and extend previous research regarding the development and validation of algorithms for the safe and effective rule-out and rule-in of MACE in patients with symptoms suggestive of AMI,” the authors wrote.

This study was supported by the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, the Cardiovascular Research Foundation Basel, the University Hospital Basel, Abbott, Beckman Coulter, Biomerieux, BRAHMS, Roche, Nanosphere, Siemens, Ortho Diagnostics, and Singulex. Several authors reported grants and support from the pharmaceutical sector.

SOURCE: Nestelberger T et al. J Am Coll Cardiol. 2019 Aug 20. doi: 10.1016/j.jacc.2019.06.025.

Adding electrocardiogram findings and clinical assessment to high-sensitivity cardiac troponin measurements in patients presenting with chest pain could improve predictions of their risk of 30-day major adverse cardiac events, particularly unstable angina, research suggests.

Investigators reported outcomes of a prospective study involving 3,123 patients with suspected acute myocardial infarction. The findings are in the Journal of the American College of Cardiology.

The aim of the researchers was to validate an extended algorithm that combined the European Society of Cardiology’s high-sensitivity cardiac troponin measurement at presentation and after 1 hour (ESC hs-cTn 0/1 h algorithm) with clinical assessment and ECG findings to aid prediction of major adverse cardiac events (MACE) within 30 days.

The clinical assessment involved the treating ED physician’s use of a visual analog scale to assess the patient’s pretest probability for an acute coronary syndrome (ACS), with a score above 70% qualifying as high likelihood.

The researchers found that the ESC hs-cTn 0/1 h algorithm alone triaged significantly more patients toward rule-out for MACE than did the extended algorithm (60% vs. 45%, P less than .001). This resulted in 487 patients being reclassified toward “observe” by the extended algorithm, and among this group the 30-day MACE rate was 1.1%.

However, the 30-day MACE rates were similar in the two groups – 0.6% among those ruled out by the ESC hs-cTn 0/1 h algorithm alone and 0.4% in those ruled out by the extended algorithm – resulting in a similar negative predictive value.

“These estimates will help clinicians to appropriately manage patients triaged toward rule-out according to the ESC hs-cTnT 0/1 h algorithm, in whom either the [visual analog scale] for ACS or the ECG still suggests the presence of an ACS,” wrote Thomas Nestelberger, MD, of the Cardiovascular Research Institute Basel (Switzerland) at the University of Basel, and coinvestigators.

The ESC hs-cTn 0/1 h algorithm also ruled in fewer patients than did the extended algorithm (16% vs. 26%, P less than .001), giving it a higher positive predictive value.


When the researchers added unstable angina to the major adverse cardiac event outcome, they found the ESC hs-cTn 0/1 h algorithm had a lower negative predictive value and a higher negative likelihood ratio compared with the extended algorithm for patients ruled out, but a higher positive predictive value and positive likelihood ratio for patients ruled in.

“Our findings corroborate and extend previous research regarding the development and validation of algorithms for the safe and effective rule-out and rule-in of MACE in patients with symptoms suggestive of AMI,” the authors wrote.

This study was supported by the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, the Cardiovascular Research Foundation Basel, the University Hospital Basel, Abbott, Beckman Coulter, Biomerieux, BRAHMS, Roche, Nanosphere, Siemens, Ortho Diagnostics, and Singulex. Several authors reported grants and support from the pharmaceutical sector.

SOURCE: Nestelberger T et al. J Am Coll Cardiol. 2019 Aug 20. doi: 10.1016/j.jacc.2019.06.025.

Adding electrocardiogram findings and clinical assessment to high-sensitivity cardiac troponin measurements in patients presenting with chest pain could improve predictions of their risk of 30-day major adverse cardiac events, particularly unstable angina, research suggests.

Investigators reported outcomes of a prospective study involving 3,123 patients with suspected acute myocardial infarction. The findings are in the Journal of the American College of Cardiology.

The aim of the researchers was to validate an extended algorithm that combined the European Society of Cardiology’s high-sensitivity cardiac troponin measurement at presentation and after 1 hour (ESC hs-cTn 0/1 h algorithm) with clinical assessment and ECG findings to aid prediction of major adverse cardiac events (MACE) within 30 days.

The clinical assessment involved the treating ED physician’s use of a visual analog scale to assess the patient’s pretest probability for an acute coronary syndrome (ACS), with a score above 70% qualifying as high likelihood.

The researchers found that the ESC hs-cTn 0/1 h algorithm alone triaged significantly more patients toward rule-out for MACE than did the extended algorithm (60% vs. 45%, P less than .001). This resulted in 487 patients being reclassified toward “observe” by the extended algorithm, and among this group the 30-day MACE rate was 1.1%.

However, the 30-day MACE rates were similar in the two groups – 0.6% among those ruled out by the ESC hs-cTn 0/1 h algorithm alone and 0.4% in those ruled out by the extended algorithm – resulting in a similar negative predictive value.

“These estimates will help clinicians to appropriately manage patients triaged toward rule-out according to the ESC hs-cTnT 0/1 h algorithm, in whom either the [visual analog scale] for ACS or the ECG still suggests the presence of an ACS,” wrote Thomas Nestelberger, MD, of the Cardiovascular Research Institute Basel (Switzerland) at the University of Basel, and coinvestigators.

The ESC hs-cTn 0/1 h algorithm also ruled in fewer patients than did the extended algorithm (16% vs. 26%, P less than .001), giving it a higher positive predictive value.


When the researchers added unstable angina to the major adverse cardiac event outcome, they found the ESC hs-cTn 0/1 h algorithm had a lower negative predictive value and a higher negative likelihood ratio compared with the extended algorithm for patients ruled out, but a higher positive predictive value and positive likelihood ratio for patients ruled in.

“Our findings corroborate and extend previous research regarding the development and validation of algorithms for the safe and effective rule-out and rule-in of MACE in patients with symptoms suggestive of AMI,” the authors wrote.

This study was supported by the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, the Cardiovascular Research Foundation Basel, the University Hospital Basel, Abbott, Beckman Coulter, Biomerieux, BRAHMS, Roche, Nanosphere, Siemens, Ortho Diagnostics, and Singulex. Several authors reported grants and support from the pharmaceutical sector.

SOURCE: Nestelberger T et al. J Am Coll Cardiol. 2019 Aug 20. doi: 10.1016/j.jacc.2019.06.025.

BANGKOK – Neonatal and early infantile epileptic syndromes are more common than previously thought, accounting for nearly one in six cases of severe epilepsies of infancy in a comprehensive Australian population-based study, Katherine B. Howell, MD, reported at the International Epilepsy Congress.

“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.

She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.

“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.

She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.

“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.

The full spectrum of SEI

With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.

The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.


“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.

About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.

SEI etiologies

A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.

The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.

In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.

Outcomes

“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.

However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.

Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.

bjancin@mdedge.com

SOURCE: Howell KB et al. IEC 2019, Abstract P053.

BANGKOK – Neonatal and early infantile epileptic syndromes are more common than previously thought, accounting for nearly one in six cases of severe epilepsies of infancy in a comprehensive Australian population-based study, Katherine B. Howell, MD, reported at the International Epilepsy Congress.

“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.

She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.

“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.

She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.

“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.

The full spectrum of SEI

With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.

The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.


“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.

About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.

SEI etiologies

A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.

The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.

In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.

Outcomes

“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.

However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.

Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.

bjancin@mdedge.com

SOURCE: Howell KB et al. IEC 2019, Abstract P053.

BANGKOK – Neonatal and early infantile epileptic syndromes are more common than previously thought, accounting for nearly one in six cases of severe epilepsies of infancy in a comprehensive Australian population-based study, Katherine B. Howell, MD, reported at the International Epilepsy Congress.

“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.

She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.

“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.

She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.

“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.

The full spectrum of SEI

With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.

The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.


“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.

About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.

SEI etiologies

A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.

The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.

In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.

Outcomes

“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.

However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.

Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.

bjancin@mdedge.com

SOURCE: Howell KB et al. IEC 2019, Abstract P053.

LUGANO, SWITZERLAND – The chemotherapy-free combination of ibrutinib (Imbruvica) and rituximab is highly effective as frontline therapy for older, transplant-ineligible patients with nonblastoid mantle cell lymphoma, according to investigators.

Neil Osterweil/MDedge News

In a phase 2 study of patients with a median age of 71 years, 38 of 41 patients (93%) had an objective response, and the regimen was both safe and easy to administer, reported Preetesh Jain, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.

“The adverse event profile was generally favorable, with specific monitoring recommended for patients with cardiovascular comorbidities and a history of atrial fibrillation,” he said at the International Conference on Malignant Lymphoma.

The investigators enrolled 48 patients aged 65 years and older with previously untreated mantle cell lymphoma (MCL), of whom 41 were evaluable for the primary endpoints of overall response rate (ORR) and safety. The patients had good performance status and normal organ function, with the largest tumor size less than 10 cm. Patients with atrial fibrillation could participate, if the fibrillation was controlled. Patients with Ki-67 protein levels of 50% or greater and blastoid/pleomorphic histology were excluded.

Patients were treated with ibrutinib 560 mg orally daily for each 28-day cycle, with therapy continued until disease progression, or until therapy was stopped for any other reason. Patients also received intravenous rituximab 375 mg/m² on days 1, 8, 15 and 22, plus or minus one day for cycle 1, on day 1 of cycles 3-8, and on day 1 of every other cycle for up to 2 years.

Of the 41 patients evaluable for response, 26 (64%) had a complete response (CR) and 12 (29%) had a partial response. Three additional patients had stable disease, for an objective response rate of 93%.

Of 34 patients with PET scans, all had negative scans. Of 37 patients evaluable for minimal residual disease (MRD) by flow cytometry, 21 (58%) were MRD negative.

Patients with low or intermediate Mantle Cell Lymphoma International Prognostic Index (MIPI) scores had a higher ORR (100% vs. 89% for patients with high MIPI scores), and patients with low Ki-67 levels had a higher response rate than that of patients with KI-67 of 30% or greater (80% vs. 87%).

Neither median 3-year progression-free survival nor median 3-year overall survival have been reached, with respective 3-year rates of 87% and 95%.

Four patients experienced disease progression at 4, 10, 13 and 33 months of treatment. Three of these patients had disease that had transformed to blastoid/pleomorphic variant, two had Ki-67 of 30% or greater, one had mutations in TP53, and one had FAT1 and SF3B1 mutations.


Two patients died after ibrutinib therapy, one who had discontinued therapy because of bleeding, and the other who died on treatment at 13 months from transformed disease. Both of these patients had high Ki-67 levels.

Grade 3 or 4 hematological adverse events were neutropenia in four patients, and thrombocytopenia in two patients. There were no cases of grade 3 or 4 anemia.

Grade 3 or 4 nonhematological adverse events were fatigue, myalgia, and atrial fibrillation in seven patients each, diarrhea in six patients, and petechiae/bleeding in three patients.

Patients will continue to be followed for late adverse events, secondary cancers, and relapses, and further studies on clonal evolution, mutation profiling, and MRD are ongoing and will be reported at a later date, Dr. Jain said.

The National Cancer Institute supported the study. Dr. Jain reported having no financial disclosures.

SOURCE: Jain P et al. 15-ICML. Abstract 011.

LUGANO, SWITZERLAND – The chemotherapy-free combination of ibrutinib (Imbruvica) and rituximab is highly effective as frontline therapy for older, transplant-ineligible patients with nonblastoid mantle cell lymphoma, according to investigators.

Neil Osterweil/MDedge News

In a phase 2 study of patients with a median age of 71 years, 38 of 41 patients (93%) had an objective response, and the regimen was both safe and easy to administer, reported Preetesh Jain, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.

“The adverse event profile was generally favorable, with specific monitoring recommended for patients with cardiovascular comorbidities and a history of atrial fibrillation,” he said at the International Conference on Malignant Lymphoma.

The investigators enrolled 48 patients aged 65 years and older with previously untreated mantle cell lymphoma (MCL), of whom 41 were evaluable for the primary endpoints of overall response rate (ORR) and safety. The patients had good performance status and normal organ function, with the largest tumor size less than 10 cm. Patients with atrial fibrillation could participate, if the fibrillation was controlled. Patients with Ki-67 protein levels of 50% or greater and blastoid/pleomorphic histology were excluded.

Patients were treated with ibrutinib 560 mg orally daily for each 28-day cycle, with therapy continued until disease progression, or until therapy was stopped for any other reason. Patients also received intravenous rituximab 375 mg/m² on days 1, 8, 15 and 22, plus or minus one day for cycle 1, on day 1 of cycles 3-8, and on day 1 of every other cycle for up to 2 years.

Of the 41 patients evaluable for response, 26 (64%) had a complete response (CR) and 12 (29%) had a partial response. Three additional patients had stable disease, for an objective response rate of 93%.

Of 34 patients with PET scans, all had negative scans. Of 37 patients evaluable for minimal residual disease (MRD) by flow cytometry, 21 (58%) were MRD negative.

Patients with low or intermediate Mantle Cell Lymphoma International Prognostic Index (MIPI) scores had a higher ORR (100% vs. 89% for patients with high MIPI scores), and patients with low Ki-67 levels had a higher response rate than that of patients with KI-67 of 30% or greater (80% vs. 87%).

Neither median 3-year progression-free survival nor median 3-year overall survival have been reached, with respective 3-year rates of 87% and 95%.

Four patients experienced disease progression at 4, 10, 13 and 33 months of treatment. Three of these patients had disease that had transformed to blastoid/pleomorphic variant, two had Ki-67 of 30% or greater, one had mutations in TP53, and one had FAT1 and SF3B1 mutations.


Two patients died after ibrutinib therapy, one who had discontinued therapy because of bleeding, and the other who died on treatment at 13 months from transformed disease. Both of these patients had high Ki-67 levels.

Grade 3 or 4 hematological adverse events were neutropenia in four patients, and thrombocytopenia in two patients. There were no cases of grade 3 or 4 anemia.

Grade 3 or 4 nonhematological adverse events were fatigue, myalgia, and atrial fibrillation in seven patients each, diarrhea in six patients, and petechiae/bleeding in three patients.

Patients will continue to be followed for late adverse events, secondary cancers, and relapses, and further studies on clonal evolution, mutation profiling, and MRD are ongoing and will be reported at a later date, Dr. Jain said.

The National Cancer Institute supported the study. Dr. Jain reported having no financial disclosures.

SOURCE: Jain P et al. 15-ICML. Abstract 011.

LUGANO, SWITZERLAND – The chemotherapy-free combination of ibrutinib (Imbruvica) and rituximab is highly effective as frontline therapy for older, transplant-ineligible patients with nonblastoid mantle cell lymphoma, according to investigators.

Neil Osterweil/MDedge News

In a phase 2 study of patients with a median age of 71 years, 38 of 41 patients (93%) had an objective response, and the regimen was both safe and easy to administer, reported Preetesh Jain, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.

“The adverse event profile was generally favorable, with specific monitoring recommended for patients with cardiovascular comorbidities and a history of atrial fibrillation,” he said at the International Conference on Malignant Lymphoma.

The investigators enrolled 48 patients aged 65 years and older with previously untreated mantle cell lymphoma (MCL), of whom 41 were evaluable for the primary endpoints of overall response rate (ORR) and safety. The patients had good performance status and normal organ function, with the largest tumor size less than 10 cm. Patients with atrial fibrillation could participate, if the fibrillation was controlled. Patients with Ki-67 protein levels of 50% or greater and blastoid/pleomorphic histology were excluded.

Patients were treated with ibrutinib 560 mg orally daily for each 28-day cycle, with therapy continued until disease progression, or until therapy was stopped for any other reason. Patients also received intravenous rituximab 375 mg/m² on days 1, 8, 15 and 22, plus or minus one day for cycle 1, on day 1 of cycles 3-8, and on day 1 of every other cycle for up to 2 years.

Of the 41 patients evaluable for response, 26 (64%) had a complete response (CR) and 12 (29%) had a partial response. Three additional patients had stable disease, for an objective response rate of 93%.

Of 34 patients with PET scans, all had negative scans. Of 37 patients evaluable for minimal residual disease (MRD) by flow cytometry, 21 (58%) were MRD negative.

Patients with low or intermediate Mantle Cell Lymphoma International Prognostic Index (MIPI) scores had a higher ORR (100% vs. 89% for patients with high MIPI scores), and patients with low Ki-67 levels had a higher response rate than that of patients with KI-67 of 30% or greater (80% vs. 87%).

Neither median 3-year progression-free survival nor median 3-year overall survival have been reached, with respective 3-year rates of 87% and 95%.

Four patients experienced disease progression at 4, 10, 13 and 33 months of treatment. Three of these patients had disease that had transformed to blastoid/pleomorphic variant, two had Ki-67 of 30% or greater, one had mutations in TP53, and one had FAT1 and SF3B1 mutations.


Two patients died after ibrutinib therapy, one who had discontinued therapy because of bleeding, and the other who died on treatment at 13 months from transformed disease. Both of these patients had high Ki-67 levels.

Grade 3 or 4 hematological adverse events were neutropenia in four patients, and thrombocytopenia in two patients. There were no cases of grade 3 or 4 anemia.

Grade 3 or 4 nonhematological adverse events were fatigue, myalgia, and atrial fibrillation in seven patients each, diarrhea in six patients, and petechiae/bleeding in three patients.

Patients will continue to be followed for late adverse events, secondary cancers, and relapses, and further studies on clonal evolution, mutation profiling, and MRD are ongoing and will be reported at a later date, Dr. Jain said.

The National Cancer Institute supported the study. Dr. Jain reported having no financial disclosures.

SOURCE: Jain P et al. 15-ICML. Abstract 011.