The time it takes for patients with systemic lupus erythematosus to achieve remission greatly depends on how remission is defined, and such episodes are usually short-lasting, according to an analysis of more than 2,000 patients in the Hopkins Lupus Cohort.

“Our results concerning durability of remission show the relapsing-remitting nature of SLE [systemic lupus erythematosus]. The median duration of remission was only about 3 months for all [four] definitions [used in the study]. This was the time to the next quarterly cohort visit. Even though achieving remission was frequent, durable remission was rare,” wrote the authors, led by Theresa R. Wilhelm, MD, of Johns Hopkins University in Baltimore.

Dr. Wilhelm and her coauthors chose to examine remission in SLE based on four DORIS (Definitions Of Remission In SLE) working group clinical definitions: clinical remission, complete remission, clinical ROT (Remission on Treatment), and complete ROT. To define them, a clinical SLE Disease Activity Index (cSLEDAI) score of 0 and a Physician Global Assessment of less than 0.5 were applicable to all definitions. Zero prednisone was applicable to clinical and complete remission, while clinical ROT and complete ROT allowed for 5 mg or less daily. Immunosuppressive drugs were not allowed for a patient to be deemed in either clinical or complete remission, but were allowed for both ROT definitions. Serologically negative results were deemed permissible for both complete remission and ROT, but not for clinical remission or clinical ROT (Ann Rheum Dis. 2016 Aug 24. doi: 10.1136/annrheumdis-2016-209489).

For a total of 2,307 SLE patients who were enrolled into the Hopkins Lupus Cohort during 1987-2014, the median time for clinical remission to be achieved was 8.7 years, while complete remission took 11.0 years, clinical ROT took 1.8 years, and complete ROT took 3.1 years. These Kaplan-Meier estimates of the distribution of time to remission after entry into the cohort did not include patients who had a gap in their follow-up or dropped out before satisfying the definition of remission.

However, across all four definitions, the median length of remission was only 3 months, as sustained remission proved elusive. Those with high disease activity and greater treatment had longer median times to achieve remission than did those with low disease activity and less treatment.

“Not surprisingly, we found that the level of baseline treatment and baseline disease activity were strongly associated with the time to remission for all definitions,” Dr. Wilhelm and her coauthors noted.

“Testing definitions of remission is of great relevance for clinical practice, as much as for clinical trials,” the authors concluded. “Our future goal is to find out which definitions are most successful in predicting the best possible outcome for our patients.”

The Hopkins Lupus Cohort receives funding from the National Institutes of Health. Dr. Wilhelm and her coauthors did not report any relevant financial disclosures.

[email protected]

The time it takes for patients with systemic lupus erythematosus to achieve remission greatly depends on how remission is defined, and such episodes are usually short-lasting, according to an analysis of more than 2,000 patients in the Hopkins Lupus Cohort.

“Our results concerning durability of remission show the relapsing-remitting nature of SLE [systemic lupus erythematosus]. The median duration of remission was only about 3 months for all [four] definitions [used in the study]. This was the time to the next quarterly cohort visit. Even though achieving remission was frequent, durable remission was rare,” wrote the authors, led by Theresa R. Wilhelm, MD, of Johns Hopkins University in Baltimore.

Dr. Wilhelm and her coauthors chose to examine remission in SLE based on four DORIS (Definitions Of Remission In SLE) working group clinical definitions: clinical remission, complete remission, clinical ROT (Remission on Treatment), and complete ROT. To define them, a clinical SLE Disease Activity Index (cSLEDAI) score of 0 and a Physician Global Assessment of less than 0.5 were applicable to all definitions. Zero prednisone was applicable to clinical and complete remission, while clinical ROT and complete ROT allowed for 5 mg or less daily. Immunosuppressive drugs were not allowed for a patient to be deemed in either clinical or complete remission, but were allowed for both ROT definitions. Serologically negative results were deemed permissible for both complete remission and ROT, but not for clinical remission or clinical ROT (Ann Rheum Dis. 2016 Aug 24. doi: 10.1136/annrheumdis-2016-209489).

For a total of 2,307 SLE patients who were enrolled into the Hopkins Lupus Cohort during 1987-2014, the median time for clinical remission to be achieved was 8.7 years, while complete remission took 11.0 years, clinical ROT took 1.8 years, and complete ROT took 3.1 years. These Kaplan-Meier estimates of the distribution of time to remission after entry into the cohort did not include patients who had a gap in their follow-up or dropped out before satisfying the definition of remission.

However, across all four definitions, the median length of remission was only 3 months, as sustained remission proved elusive. Those with high disease activity and greater treatment had longer median times to achieve remission than did those with low disease activity and less treatment.

“Not surprisingly, we found that the level of baseline treatment and baseline disease activity were strongly associated with the time to remission for all definitions,” Dr. Wilhelm and her coauthors noted.

“Testing definitions of remission is of great relevance for clinical practice, as much as for clinical trials,” the authors concluded. “Our future goal is to find out which definitions are most successful in predicting the best possible outcome for our patients.”

The Hopkins Lupus Cohort receives funding from the National Institutes of Health. Dr. Wilhelm and her coauthors did not report any relevant financial disclosures.

[email protected]

The time it takes for patients with systemic lupus erythematosus to achieve remission greatly depends on how remission is defined, and such episodes are usually short-lasting, according to an analysis of more than 2,000 patients in the Hopkins Lupus Cohort.

“Our results concerning durability of remission show the relapsing-remitting nature of SLE [systemic lupus erythematosus]. The median duration of remission was only about 3 months for all [four] definitions [used in the study]. This was the time to the next quarterly cohort visit. Even though achieving remission was frequent, durable remission was rare,” wrote the authors, led by Theresa R. Wilhelm, MD, of Johns Hopkins University in Baltimore.

Dr. Wilhelm and her coauthors chose to examine remission in SLE based on four DORIS (Definitions Of Remission In SLE) working group clinical definitions: clinical remission, complete remission, clinical ROT (Remission on Treatment), and complete ROT. To define them, a clinical SLE Disease Activity Index (cSLEDAI) score of 0 and a Physician Global Assessment of less than 0.5 were applicable to all definitions. Zero prednisone was applicable to clinical and complete remission, while clinical ROT and complete ROT allowed for 5 mg or less daily. Immunosuppressive drugs were not allowed for a patient to be deemed in either clinical or complete remission, but were allowed for both ROT definitions. Serologically negative results were deemed permissible for both complete remission and ROT, but not for clinical remission or clinical ROT (Ann Rheum Dis. 2016 Aug 24. doi: 10.1136/annrheumdis-2016-209489).

For a total of 2,307 SLE patients who were enrolled into the Hopkins Lupus Cohort during 1987-2014, the median time for clinical remission to be achieved was 8.7 years, while complete remission took 11.0 years, clinical ROT took 1.8 years, and complete ROT took 3.1 years. These Kaplan-Meier estimates of the distribution of time to remission after entry into the cohort did not include patients who had a gap in their follow-up or dropped out before satisfying the definition of remission.

However, across all four definitions, the median length of remission was only 3 months, as sustained remission proved elusive. Those with high disease activity and greater treatment had longer median times to achieve remission than did those with low disease activity and less treatment.

“Not surprisingly, we found that the level of baseline treatment and baseline disease activity were strongly associated with the time to remission for all definitions,” Dr. Wilhelm and her coauthors noted.

“Testing definitions of remission is of great relevance for clinical practice, as much as for clinical trials,” the authors concluded. “Our future goal is to find out which definitions are most successful in predicting the best possible outcome for our patients.”

The Hopkins Lupus Cohort receives funding from the National Institutes of Health. Dr. Wilhelm and her coauthors did not report any relevant financial disclosures.

[email protected]

Officials at the Centers for Disease Control and Prevention have confirmed a case of Zika virus infection in a nonpregnant Maryland woman who likely contracted the virus through sexual intercourse with her asymptomatic male partner.

“To date, only one other case has been reported in which a man without symptoms might have sexually transmitted Zika virus to his female partner,” Richard B. Brooks, MD, and his colleagues wrote Aug. 26 in the Morbidity and Mortality Weekly Report (doi:10.15585/mmwr.mm6534e2). “However, in that reported case, both the man and the woman had traveled to a country with ongoing Zika virus transmission where they were likely exposed to mosquitoes.”

In the current case, the couple had condomless vaginal sex 10 days and 14 days after his return from the Dominican Republic, along with oral sex on day 14. Two days after the last encounter, the woman began exhibiting symptoms of Zika virus infection, namely, a maculopapular rash and a fever. She sought medical care 3 days later (19 days after her partner returned to the United States). She had no other sexual partners during this time. Meanwhile, the male sex partner reported no symptoms of a Zika virus infection, other than simply being tired from his recent travel.

“The findings in this report indicate that it might be appropriate to consider persons who have condomless sex with partners returning from areas with ongoing Zika virus transmission as exposed to Zika virus, regardless of whether the returning traveler reports symptoms of Zika virus infection,” the researchers wrote.

©Tomasz Gierygowski/thinkstockphotos.com

Transmission of Zika virus through blood transfusions is also a growing concern, particularly if an asymptomatic individual donated blood.

On Aug. 26, the Food and Drug Administration announced recommendations to test all donated blood and blood components across the United States and its territories for the Zika virus, to mitigate the chances of transmitting the virus through transfusions. In February, the FDA first issued guidance recommending that only areas with active Zika virus transmission screen donated blood.

“As new scientific and epidemiological information regarding Zika virus has become available, it’s clear that additional precautionary measures are necessary,” Luciana Borio, MD, FDA’s acting chief scientist, said in a statement. “We are issuing revised guidance for immediate implementation in order to help maintain the safety of the U.S. blood supply.”

In a conference call with reporters, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said that while there have not yet been any confirmed cases of such transmission, donors and health care workers must be vigilant. “Given the frequency of travel of individuals within the United States, there is the risk that people without symptoms who are infected with Zika virus could potentially donate blood and thereby transmit Zika virus,” he said.

The CDC also published new numbers on Guillain-Barré syndrome (GBS), which has been on the rise in countries affected by Zika virus.

Individuals who began exhibiting any neurologic symptoms between Jan. 1, 2016, and July 31, 2016, and were suspected of possible GBS total 56. Of those 56 patients, 34 (61%) were found to have evidence of either Zika or another related flavivirus. Ten (18%) of those 56 were confirmed to have Zika virus, and 1 patient who received treatment for GBS died of septic shock. Thirty (88%) of the 34 found to have evidence of flavivirus also reported having an acute illness of some kind before the onset of neurologic symptoms. The figures come from the GBS Passive Surveillance System (MMWR. 2016 Aug 26. doi:10.15585/mmwr.mm6534e1).

“Persons with signs or symptoms consistent with GBS should promptly seek medical attention,” the CDC urged. “Health care providers who evaluate patients with neurologic illnesses should consider GBS and report suspected cases to public health authorities. Residents of and travelers to Puerto Rico are advised to follow existing recommendations for prevention of Zika virus infection.”

[email protected]

Officials at the Centers for Disease Control and Prevention have confirmed a case of Zika virus infection in a nonpregnant Maryland woman who likely contracted the virus through sexual intercourse with her asymptomatic male partner.

“To date, only one other case has been reported in which a man without symptoms might have sexually transmitted Zika virus to his female partner,” Richard B. Brooks, MD, and his colleagues wrote Aug. 26 in the Morbidity and Mortality Weekly Report (doi:10.15585/mmwr.mm6534e2). “However, in that reported case, both the man and the woman had traveled to a country with ongoing Zika virus transmission where they were likely exposed to mosquitoes.”

In the current case, the couple had condomless vaginal sex 10 days and 14 days after his return from the Dominican Republic, along with oral sex on day 14. Two days after the last encounter, the woman began exhibiting symptoms of Zika virus infection, namely, a maculopapular rash and a fever. She sought medical care 3 days later (19 days after her partner returned to the United States). She had no other sexual partners during this time. Meanwhile, the male sex partner reported no symptoms of a Zika virus infection, other than simply being tired from his recent travel.

“The findings in this report indicate that it might be appropriate to consider persons who have condomless sex with partners returning from areas with ongoing Zika virus transmission as exposed to Zika virus, regardless of whether the returning traveler reports symptoms of Zika virus infection,” the researchers wrote.

©Tomasz Gierygowski/thinkstockphotos.com

Transmission of Zika virus through blood transfusions is also a growing concern, particularly if an asymptomatic individual donated blood.

On Aug. 26, the Food and Drug Administration announced recommendations to test all donated blood and blood components across the United States and its territories for the Zika virus, to mitigate the chances of transmitting the virus through transfusions. In February, the FDA first issued guidance recommending that only areas with active Zika virus transmission screen donated blood.

“As new scientific and epidemiological information regarding Zika virus has become available, it’s clear that additional precautionary measures are necessary,” Luciana Borio, MD, FDA’s acting chief scientist, said in a statement. “We are issuing revised guidance for immediate implementation in order to help maintain the safety of the U.S. blood supply.”

In a conference call with reporters, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said that while there have not yet been any confirmed cases of such transmission, donors and health care workers must be vigilant. “Given the frequency of travel of individuals within the United States, there is the risk that people without symptoms who are infected with Zika virus could potentially donate blood and thereby transmit Zika virus,” he said.

The CDC also published new numbers on Guillain-Barré syndrome (GBS), which has been on the rise in countries affected by Zika virus.

Individuals who began exhibiting any neurologic symptoms between Jan. 1, 2016, and July 31, 2016, and were suspected of possible GBS total 56. Of those 56 patients, 34 (61%) were found to have evidence of either Zika or another related flavivirus. Ten (18%) of those 56 were confirmed to have Zika virus, and 1 patient who received treatment for GBS died of septic shock. Thirty (88%) of the 34 found to have evidence of flavivirus also reported having an acute illness of some kind before the onset of neurologic symptoms. The figures come from the GBS Passive Surveillance System (MMWR. 2016 Aug 26. doi:10.15585/mmwr.mm6534e1).

“Persons with signs or symptoms consistent with GBS should promptly seek medical attention,” the CDC urged. “Health care providers who evaluate patients with neurologic illnesses should consider GBS and report suspected cases to public health authorities. Residents of and travelers to Puerto Rico are advised to follow existing recommendations for prevention of Zika virus infection.”

[email protected]

Officials at the Centers for Disease Control and Prevention have confirmed a case of Zika virus infection in a nonpregnant Maryland woman who likely contracted the virus through sexual intercourse with her asymptomatic male partner.

“To date, only one other case has been reported in which a man without symptoms might have sexually transmitted Zika virus to his female partner,” Richard B. Brooks, MD, and his colleagues wrote Aug. 26 in the Morbidity and Mortality Weekly Report (doi:10.15585/mmwr.mm6534e2). “However, in that reported case, both the man and the woman had traveled to a country with ongoing Zika virus transmission where they were likely exposed to mosquitoes.”

In the current case, the couple had condomless vaginal sex 10 days and 14 days after his return from the Dominican Republic, along with oral sex on day 14. Two days after the last encounter, the woman began exhibiting symptoms of Zika virus infection, namely, a maculopapular rash and a fever. She sought medical care 3 days later (19 days after her partner returned to the United States). She had no other sexual partners during this time. Meanwhile, the male sex partner reported no symptoms of a Zika virus infection, other than simply being tired from his recent travel.

“The findings in this report indicate that it might be appropriate to consider persons who have condomless sex with partners returning from areas with ongoing Zika virus transmission as exposed to Zika virus, regardless of whether the returning traveler reports symptoms of Zika virus infection,” the researchers wrote.

©Tomasz Gierygowski/thinkstockphotos.com

Transmission of Zika virus through blood transfusions is also a growing concern, particularly if an asymptomatic individual donated blood.

On Aug. 26, the Food and Drug Administration announced recommendations to test all donated blood and blood components across the United States and its territories for the Zika virus, to mitigate the chances of transmitting the virus through transfusions. In February, the FDA first issued guidance recommending that only areas with active Zika virus transmission screen donated blood.

“As new scientific and epidemiological information regarding Zika virus has become available, it’s clear that additional precautionary measures are necessary,” Luciana Borio, MD, FDA’s acting chief scientist, said in a statement. “We are issuing revised guidance for immediate implementation in order to help maintain the safety of the U.S. blood supply.”

In a conference call with reporters, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said that while there have not yet been any confirmed cases of such transmission, donors and health care workers must be vigilant. “Given the frequency of travel of individuals within the United States, there is the risk that people without symptoms who are infected with Zika virus could potentially donate blood and thereby transmit Zika virus,” he said.

The CDC also published new numbers on Guillain-Barré syndrome (GBS), which has been on the rise in countries affected by Zika virus.

Individuals who began exhibiting any neurologic symptoms between Jan. 1, 2016, and July 31, 2016, and were suspected of possible GBS total 56. Of those 56 patients, 34 (61%) were found to have evidence of either Zika or another related flavivirus. Ten (18%) of those 56 were confirmed to have Zika virus, and 1 patient who received treatment for GBS died of septic shock. Thirty (88%) of the 34 found to have evidence of flavivirus also reported having an acute illness of some kind before the onset of neurologic symptoms. The figures come from the GBS Passive Surveillance System (MMWR. 2016 Aug 26. doi:10.15585/mmwr.mm6534e1).

“Persons with signs or symptoms consistent with GBS should promptly seek medical attention,” the CDC urged. “Health care providers who evaluate patients with neurologic illnesses should consider GBS and report suspected cases to public health authorities. Residents of and travelers to Puerto Rico are advised to follow existing recommendations for prevention of Zika virus infection.”

[email protected]

For the Spring Postgraduate Course session on inflammatory bowel disease (IBD), we were fortunate to secure four of the best educators on IBD in the American Gastroenterological Association.

William Sandborn, MD, of the University of California, San Diego, led the session with an overview of the immunomodulators and biologics that are employed for the treatment of Crohn’s disease and ulcerative colitis in 2016, including the thiopurines, methotrexate, calcineurin inhibitors, anti–tumor necrosis factor (TNF) agents, anti-integrins, and upcoming therapies such as ustekinumab (anti-interleukins 12 and 23) and tofacitinib (Janus kinase antagonist).

The evidence base for thiopurine monotherapy in IBD is weaker than we had once assumed, and the combination of infliximab and azathioprine remains the gold standard in efficacy with respect to steroid-free remission. Methotrexate remains a reasonable option as an immunomodulator, especially for patients who can’t tolerate thiopurines or who are risk averse. Cyclosporine has a niche indication for the treatment of acute severe colitis, and is at least equivalent to infliximab for that indication.

We have a total of four anti-TNF agents approved for the treatment of moderate to severe Crohn’s disease and ulcerative colitis, including infliximab, adalimumab, certolizumab pegol (Crohn’s only), and golimumab (ulcerative colitis only). The infliximab biosimilar CT-P13 is approved for IBD in several countries. The anti-integrin, vedolizumab, is approved for both moderate to severe ulcerative colitis and Crohn’s disease. Ustekinumab was shown to be more effective than placebo in inducing clinical response and remission in moderate to severe Crohn’s disease patients who were either refractory/intolerant to or naive to anti-TNF therapy. Tofacitinib was recently shown in two trials to be more effective than placebo in inducing clinical remission and mucosal healing in patients with moderate to severe ulcerative colitis.

Maria Abreu, MD, from the University of Miami highlighted the fact that although our current therapies are far more effective than previous ones, they can be problematic, and dose adjustment is often needed. We should tailor our treatment plan based on our assessment of the patient’s risk for intestinal complications or surgery – patients with multiple risk factors such as young age at diagnosis, extensive involvement, deep ulcers, previous surgeries, or penetrating/stricturing behavior at baseline should be treated more aggressively, perhaps with a top-down approach. In general, biologics will be more effective when used in combination with immunomodulators. Monotherapy can be considered in patients with low inflammatory burden, few risk factors for more severe disease, or in those at high risk for complications from combination therapy.

At least one way in which concomitant immunomodulator therapy exerts its beneficial effect is by increasing trough levels of the biologic. One recent study of the relationship between adalimumab levels and endoscopic inflammation suggested that the median adalimumab trough level associated with mucosal healing was 13.5 mcg/mL. Patients with low drug levels and no or low levels of anti-drug antibodies should undergo dose escalation. Those with absent drug levels and high levels of antibodies should switch to a different agent. If the drug level is considered adequate and yet inflammation is still present, consideration should be given to switching to a biologic with a different mechanism of action. In some patients with low levels of antibodies who are on monotherapy, there may be a role for adding an immunomodulator in an attempt to suppress antibody formation. The importance of vedolizumab and ustekinumab as biologics with different mechanisms of action was also highlighted. An exciting class of biologics currently under development is the anti–IL-23 class, including drugs such as risankizumab and MEDI-2070.

David T. Rubin, MD, from the University of Chicago reviewed the various complications associated with IBD and its therapies. Disease-related complications include clinical flares, bowel obstruction, fistula/abscess formation, intestinal cancer, the need for surgery (sometimes more than one), and extraintestinal manifestations. More accurate diagnosis and earlier effective therapies may help to reduce the risk of these complications. Certain infections such as herpes zoster, pneumonia, and Clostridium difficile infection appear to occur more commonly in IBD patients. The TREAT registry showed that the use of corticosteroids is associated with an increased risk of serious infections and mortality, and the use of infliximab is associated with an increased risk of serious infection. C. difficile infection in particular can be problematic, and should be treated aggressively. Thiopurines appear to increase the risk of lymphoma and nonmelanoma skin cancer. Lymphoma risk quickly reverts to baseline after thiopurines are discontinued. Overall, no increased risk of cancer can be demonstrated among patients on anti-TNF therapy, and patients with a history of cancer do not have an increased risk of recurrent or new cancers on anti-TNF therapy. There may be an association between anti-TNF use and melanoma, although this bears further study.

Miguel Regueiro, MD, from the University of Pittsburgh wrapped up the session with a talk on managing postoperative IBD patients. Although the ileal pouch–anal anastomosis (IPAA) broadened access to proctocolectomy, it is associated with several disorders, including pelvic sepsis, pouchitis, Crohn’s disease of the ileoanal pouch, cuffitis, and irritable pouch syndrome. At least 50% of IPAA patients will develop at least one episode of pouchitis. Most patients will respond to ciprofloxacin or metronidazole, but a small percentage will develop chronic pouchitis. Ileocecal resection for the complications of Crohn’s disease generally results in immediate improvements in quality of life, but unfortunately, most patients will develop endoscopic and eventually clinical recurrence. At 6-12 months after surgery, a Rutgeerts score of i2 or higher (at least five aphthous lesions in the neoterminal ileum) is associated with a high risk of clinical recurrence, and this finding can be used as a trigger for escalation of therapy.

Infliximab was associated with a markedly decreased risk of endoscopic recurrence in a small investigator-initiated trial, and subsequent studies have strongly suggested that infliximab and adalimumab reduce the risk of recurrence. Although the primary endpoint of clinical recurrence was not met in the large multicenter PREVENT trial, infliximab was shown to significantly decrease endoscopic recurrence. The POCER study showed that a slightly less proactive approach of watchful waiting in lower-risk patients and making decisions about therapy at the 6-month colonoscopy was a reasonable one. The risk factors one must consider in stratifying postop patients include early age at surgery, short time between diagnosis and surgery, cigarette smoking, penetrating disease behavior, and a history of previous resections.

Dr. Loftus is professor of medicine in the division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn. He has consulted for and has received research support from Janssen, UCB, Takeda, and AbbVie.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

For the Spring Postgraduate Course session on inflammatory bowel disease (IBD), we were fortunate to secure four of the best educators on IBD in the American Gastroenterological Association.

William Sandborn, MD, of the University of California, San Diego, led the session with an overview of the immunomodulators and biologics that are employed for the treatment of Crohn’s disease and ulcerative colitis in 2016, including the thiopurines, methotrexate, calcineurin inhibitors, anti–tumor necrosis factor (TNF) agents, anti-integrins, and upcoming therapies such as ustekinumab (anti-interleukins 12 and 23) and tofacitinib (Janus kinase antagonist).

The evidence base for thiopurine monotherapy in IBD is weaker than we had once assumed, and the combination of infliximab and azathioprine remains the gold standard in efficacy with respect to steroid-free remission. Methotrexate remains a reasonable option as an immunomodulator, especially for patients who can’t tolerate thiopurines or who are risk averse. Cyclosporine has a niche indication for the treatment of acute severe colitis, and is at least equivalent to infliximab for that indication.

We have a total of four anti-TNF agents approved for the treatment of moderate to severe Crohn’s disease and ulcerative colitis, including infliximab, adalimumab, certolizumab pegol (Crohn’s only), and golimumab (ulcerative colitis only). The infliximab biosimilar CT-P13 is approved for IBD in several countries. The anti-integrin, vedolizumab, is approved for both moderate to severe ulcerative colitis and Crohn’s disease. Ustekinumab was shown to be more effective than placebo in inducing clinical response and remission in moderate to severe Crohn’s disease patients who were either refractory/intolerant to or naive to anti-TNF therapy. Tofacitinib was recently shown in two trials to be more effective than placebo in inducing clinical remission and mucosal healing in patients with moderate to severe ulcerative colitis.

Maria Abreu, MD, from the University of Miami highlighted the fact that although our current therapies are far more effective than previous ones, they can be problematic, and dose adjustment is often needed. We should tailor our treatment plan based on our assessment of the patient’s risk for intestinal complications or surgery – patients with multiple risk factors such as young age at diagnosis, extensive involvement, deep ulcers, previous surgeries, or penetrating/stricturing behavior at baseline should be treated more aggressively, perhaps with a top-down approach. In general, biologics will be more effective when used in combination with immunomodulators. Monotherapy can be considered in patients with low inflammatory burden, few risk factors for more severe disease, or in those at high risk for complications from combination therapy.

At least one way in which concomitant immunomodulator therapy exerts its beneficial effect is by increasing trough levels of the biologic. One recent study of the relationship between adalimumab levels and endoscopic inflammation suggested that the median adalimumab trough level associated with mucosal healing was 13.5 mcg/mL. Patients with low drug levels and no or low levels of anti-drug antibodies should undergo dose escalation. Those with absent drug levels and high levels of antibodies should switch to a different agent. If the drug level is considered adequate and yet inflammation is still present, consideration should be given to switching to a biologic with a different mechanism of action. In some patients with low levels of antibodies who are on monotherapy, there may be a role for adding an immunomodulator in an attempt to suppress antibody formation. The importance of vedolizumab and ustekinumab as biologics with different mechanisms of action was also highlighted. An exciting class of biologics currently under development is the anti–IL-23 class, including drugs such as risankizumab and MEDI-2070.

David T. Rubin, MD, from the University of Chicago reviewed the various complications associated with IBD and its therapies. Disease-related complications include clinical flares, bowel obstruction, fistula/abscess formation, intestinal cancer, the need for surgery (sometimes more than one), and extraintestinal manifestations. More accurate diagnosis and earlier effective therapies may help to reduce the risk of these complications. Certain infections such as herpes zoster, pneumonia, and Clostridium difficile infection appear to occur more commonly in IBD patients. The TREAT registry showed that the use of corticosteroids is associated with an increased risk of serious infections and mortality, and the use of infliximab is associated with an increased risk of serious infection. C. difficile infection in particular can be problematic, and should be treated aggressively. Thiopurines appear to increase the risk of lymphoma and nonmelanoma skin cancer. Lymphoma risk quickly reverts to baseline after thiopurines are discontinued. Overall, no increased risk of cancer can be demonstrated among patients on anti-TNF therapy, and patients with a history of cancer do not have an increased risk of recurrent or new cancers on anti-TNF therapy. There may be an association between anti-TNF use and melanoma, although this bears further study.

Miguel Regueiro, MD, from the University of Pittsburgh wrapped up the session with a talk on managing postoperative IBD patients. Although the ileal pouch–anal anastomosis (IPAA) broadened access to proctocolectomy, it is associated with several disorders, including pelvic sepsis, pouchitis, Crohn’s disease of the ileoanal pouch, cuffitis, and irritable pouch syndrome. At least 50% of IPAA patients will develop at least one episode of pouchitis. Most patients will respond to ciprofloxacin or metronidazole, but a small percentage will develop chronic pouchitis. Ileocecal resection for the complications of Crohn’s disease generally results in immediate improvements in quality of life, but unfortunately, most patients will develop endoscopic and eventually clinical recurrence. At 6-12 months after surgery, a Rutgeerts score of i2 or higher (at least five aphthous lesions in the neoterminal ileum) is associated with a high risk of clinical recurrence, and this finding can be used as a trigger for escalation of therapy.

Infliximab was associated with a markedly decreased risk of endoscopic recurrence in a small investigator-initiated trial, and subsequent studies have strongly suggested that infliximab and adalimumab reduce the risk of recurrence. Although the primary endpoint of clinical recurrence was not met in the large multicenter PREVENT trial, infliximab was shown to significantly decrease endoscopic recurrence. The POCER study showed that a slightly less proactive approach of watchful waiting in lower-risk patients and making decisions about therapy at the 6-month colonoscopy was a reasonable one. The risk factors one must consider in stratifying postop patients include early age at surgery, short time between diagnosis and surgery, cigarette smoking, penetrating disease behavior, and a history of previous resections.

Dr. Loftus is professor of medicine in the division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn. He has consulted for and has received research support from Janssen, UCB, Takeda, and AbbVie.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

For the Spring Postgraduate Course session on inflammatory bowel disease (IBD), we were fortunate to secure four of the best educators on IBD in the American Gastroenterological Association.

William Sandborn, MD, of the University of California, San Diego, led the session with an overview of the immunomodulators and biologics that are employed for the treatment of Crohn’s disease and ulcerative colitis in 2016, including the thiopurines, methotrexate, calcineurin inhibitors, anti–tumor necrosis factor (TNF) agents, anti-integrins, and upcoming therapies such as ustekinumab (anti-interleukins 12 and 23) and tofacitinib (Janus kinase antagonist).

The evidence base for thiopurine monotherapy in IBD is weaker than we had once assumed, and the combination of infliximab and azathioprine remains the gold standard in efficacy with respect to steroid-free remission. Methotrexate remains a reasonable option as an immunomodulator, especially for patients who can’t tolerate thiopurines or who are risk averse. Cyclosporine has a niche indication for the treatment of acute severe colitis, and is at least equivalent to infliximab for that indication.

We have a total of four anti-TNF agents approved for the treatment of moderate to severe Crohn’s disease and ulcerative colitis, including infliximab, adalimumab, certolizumab pegol (Crohn’s only), and golimumab (ulcerative colitis only). The infliximab biosimilar CT-P13 is approved for IBD in several countries. The anti-integrin, vedolizumab, is approved for both moderate to severe ulcerative colitis and Crohn’s disease. Ustekinumab was shown to be more effective than placebo in inducing clinical response and remission in moderate to severe Crohn’s disease patients who were either refractory/intolerant to or naive to anti-TNF therapy. Tofacitinib was recently shown in two trials to be more effective than placebo in inducing clinical remission and mucosal healing in patients with moderate to severe ulcerative colitis.

Maria Abreu, MD, from the University of Miami highlighted the fact that although our current therapies are far more effective than previous ones, they can be problematic, and dose adjustment is often needed. We should tailor our treatment plan based on our assessment of the patient’s risk for intestinal complications or surgery – patients with multiple risk factors such as young age at diagnosis, extensive involvement, deep ulcers, previous surgeries, or penetrating/stricturing behavior at baseline should be treated more aggressively, perhaps with a top-down approach. In general, biologics will be more effective when used in combination with immunomodulators. Monotherapy can be considered in patients with low inflammatory burden, few risk factors for more severe disease, or in those at high risk for complications from combination therapy.

At least one way in which concomitant immunomodulator therapy exerts its beneficial effect is by increasing trough levels of the biologic. One recent study of the relationship between adalimumab levels and endoscopic inflammation suggested that the median adalimumab trough level associated with mucosal healing was 13.5 mcg/mL. Patients with low drug levels and no or low levels of anti-drug antibodies should undergo dose escalation. Those with absent drug levels and high levels of antibodies should switch to a different agent. If the drug level is considered adequate and yet inflammation is still present, consideration should be given to switching to a biologic with a different mechanism of action. In some patients with low levels of antibodies who are on monotherapy, there may be a role for adding an immunomodulator in an attempt to suppress antibody formation. The importance of vedolizumab and ustekinumab as biologics with different mechanisms of action was also highlighted. An exciting class of biologics currently under development is the anti–IL-23 class, including drugs such as risankizumab and MEDI-2070.

David T. Rubin, MD, from the University of Chicago reviewed the various complications associated with IBD and its therapies. Disease-related complications include clinical flares, bowel obstruction, fistula/abscess formation, intestinal cancer, the need for surgery (sometimes more than one), and extraintestinal manifestations. More accurate diagnosis and earlier effective therapies may help to reduce the risk of these complications. Certain infections such as herpes zoster, pneumonia, and Clostridium difficile infection appear to occur more commonly in IBD patients. The TREAT registry showed that the use of corticosteroids is associated with an increased risk of serious infections and mortality, and the use of infliximab is associated with an increased risk of serious infection. C. difficile infection in particular can be problematic, and should be treated aggressively. Thiopurines appear to increase the risk of lymphoma and nonmelanoma skin cancer. Lymphoma risk quickly reverts to baseline after thiopurines are discontinued. Overall, no increased risk of cancer can be demonstrated among patients on anti-TNF therapy, and patients with a history of cancer do not have an increased risk of recurrent or new cancers on anti-TNF therapy. There may be an association between anti-TNF use and melanoma, although this bears further study.

Miguel Regueiro, MD, from the University of Pittsburgh wrapped up the session with a talk on managing postoperative IBD patients. Although the ileal pouch–anal anastomosis (IPAA) broadened access to proctocolectomy, it is associated with several disorders, including pelvic sepsis, pouchitis, Crohn’s disease of the ileoanal pouch, cuffitis, and irritable pouch syndrome. At least 50% of IPAA patients will develop at least one episode of pouchitis. Most patients will respond to ciprofloxacin or metronidazole, but a small percentage will develop chronic pouchitis. Ileocecal resection for the complications of Crohn’s disease generally results in immediate improvements in quality of life, but unfortunately, most patients will develop endoscopic and eventually clinical recurrence. At 6-12 months after surgery, a Rutgeerts score of i2 or higher (at least five aphthous lesions in the neoterminal ileum) is associated with a high risk of clinical recurrence, and this finding can be used as a trigger for escalation of therapy.

Infliximab was associated with a markedly decreased risk of endoscopic recurrence in a small investigator-initiated trial, and subsequent studies have strongly suggested that infliximab and adalimumab reduce the risk of recurrence. Although the primary endpoint of clinical recurrence was not met in the large multicenter PREVENT trial, infliximab was shown to significantly decrease endoscopic recurrence. The POCER study showed that a slightly less proactive approach of watchful waiting in lower-risk patients and making decisions about therapy at the 6-month colonoscopy was a reasonable one. The risk factors one must consider in stratifying postop patients include early age at surgery, short time between diagnosis and surgery, cigarette smoking, penetrating disease behavior, and a history of previous resections.

Dr. Loftus is professor of medicine in the division of gastroenterology and hepatology, Mayo Clinic, Rochester, Minn. He has consulted for and has received research support from Janssen, UCB, Takeda, and AbbVie.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

CHICAGO – Does eradicating Helicobacter pylori prevent gastric cancer?

The answer is yes, sometimes, but it depends on where you live, and what other bacteria coexist in your gut microbiome.

The overall view is a positive one, Richard M. Peek Jr., MD, said at the at the meeting sponsored by the American Gastroenterological Association. A very large, recent meta-analysis confirms it (Gastroenterology. 2016. doi:10.1053/j.gastro.2016.01.028). Comprising 24 studies and 48,000 subjects, the meta-analysis determined that eradicating the bacteria in infected people cut gastric cancer incidence significantly.

That’s great news – but there’s a big caveat, said Dr. Peek of Vanderbilt University, Nashville. “The benefit was dependent on what your baseline risk was. For those with a high baseline risk, the benefit was tremendous. For those with a low baseline risk, it was not statistically significant.”

There are long-term data suggesting that treating H. pylori sooner rather than later is the way to go. A 2005 study followed more than 700 patients with preneoplastic gastric lesions for 12 years. It found that the treatment effect was cumulative: The longer the patient was free of H. pylori, the more reliably healing occurred (Gut. 2005. doi:10.1136/gut.2005.072009).

At baseline, the patients were randomized to nutritional supplements or to a combination of amoxicillin, metronidazole, and bismuth subsalicylate. At 6 years, the trial was unblinded and all patients were offered treatment. Patients were followed for another 6 years. Those who were H. pylori negative at 12 years had 15% more regression and 14% less progression than subjects who were positive at 12 years. Among those who received anti–H. pylori treatment at the 6-year mark, the effect was smaller and nonsignificant.

Perhaps surprisingly, though, the biggest bang for H. pylori treatment is seen in the antrum of the stomach, not in the corpus. Another meta-analysis, this one of 16 studies, found very consistent reductions in the severity of intestinal metaplasia in the antrum after antibiotic treatment – but no difference at all in corpus metaplasia. The reason for that finding isn’t at all clear, the authors of that paper noted (World J Gastro. 2014. doi:10.3748/wjg.v20.i19.5903).

The bacteria-metaplasia cancer link gets even more complicated when H. pylori is viewed as a contributing member of society, rather than a hermit. The bacterium seems to be a bully in the neighborhood, radically altering the normal gastric microbiome, Dr. Peek said.

In the absence of H. pylori, the gastric microbiome is much more diverse, consisting of about 50% Actinobacteria and 25% Firmicutes species. Bacteroides and Proteobacteria species make up the remainder, with a small population of Cyanobacteria as well. In its presence, Proteobacteria – a gram-negative genus that includes a wide variety of pathogens – almost completely subsume beneficial bacteria.

Researchers saw this change in action in 2011, when a group at the Massachusetts Institute of Technology, Cambridge, inoculated two mouse populations with H. pylori and followed them for gastric neoplasms (Gastroenterology. 2011. doi:10.1053/j.gastro.2010.09.048). All the mice were genetically engineered to overexpress human gastrin, a characteristic that invariably leads them to develop gastric cancers.

One group comprised germ-free mice raised in sterile environments. The control group was free of pathogens, but lived in a conventional environment and so had normal gastric flora. Both groups were inoculated with H. pylori.

By 11 months, the microbiome of the control group was strikingly different. It showed a significant increase in the number of Firmicutes bacteria in the stomach, with an associated decrease in the number and variety of other bacteria including Bacteroides. This was especially interesting when viewed in relation to the rate of gastric neoplasia, Dr. Peek said.

These mice are programmed to develop gastric cancer by 6 months of age – and this is what happened in the control mice, which had H. pylori plus other gastric microbes. But the germ-free mice who were monoinfected with H. pylori showed a much different progression of disease. At 7 months, most showed only a mild hypergastrinemia. Conversely, at 7 months, all of the H. pylori–infected control mice had developed gastric intraepithelial neoplasia, 80% of it high grade. Only 10% of the monoinfected mice developed cancer, and all of it was low grade.

“It looks like there is active collaboration between H. pylori and other bacteria in the stomach,” resulting in this increased cancer risk, Dr. Peek said.

It’s a collaboration that reaches deep into the tumors themselves, he said. “A very interesting study a couple of years ago searched cancer genomes for the presence of bacterial DNA, and found that gastric cancers incorporated the second-highest amount of microbial DNA into their cancer genomes. But it wasn’t just H. pylori. Many other species had integrated their DNA into these tumors.”

That study, published in 2013, was the first to prove that bacterial DNA can impact carcinogenesis. Acute myeloid leukemia showed the highest integration of bacterial DNA, but gastric adenocarcinoma was a close second. Most of the species were of the Proteobacteria lineages (83%), with a third of that represented by Pseudomonas, particularly P. fluorescens and P. aeruginosa. Both of those species have been shown to promote gastric tumorigenesis in rats. All of the DNA integrations occurred in five genes; four of these are already known to be upregulated in gastric cancer (PLOS Comp Biol. 2013;9[6]:e1003107).

Interestingly, only a few of the sample reads turned up DNA integration with H. pylori.

This reduction in gastric microbial diversity could be an important key to H. pylori’s relation to gastric cancer, Dr. Peek said. He examined this in residents of two towns in Colombia, South America: Tumaco, where the risk of gastric cancer is low, and Tuquerres, where it’s 25 times higher (Sci Rep. 2016. doi:10.1038/srep18594).

What was different was the gastric microbiome of residents. Those living in low-risk Tumaco had much more microbial diversity: 361 varieties, compared with 194 in Tuquerres. And 16 of these groups – representative of what’s usually considered a healthy microbiome – were absent in the high-risk subjects. But Tuquerres residents had two bacteria that weren’t found in Tumaco residents, including Leptorichia wadei, which has been associated with necrotizing enterocolitis.

There was no difference, however, in the prevalence of H. pylori between these high- and low-risk groups.

These new findings illustrate an increasingly complicated interplay of bacteria and gastric cancer, Dr. Peek said. But they also provide a new direction for research.

“We have a framework now where we can move forward and try to understand how some of these other strains impact gastric cancer risk,” he said.

Dr. Peek had no relevant financial disclosures.

[email protected]

On Twitter @Alz_Gal

CHICAGO – Does eradicating Helicobacter pylori prevent gastric cancer?

The answer is yes, sometimes, but it depends on where you live, and what other bacteria coexist in your gut microbiome.

The overall view is a positive one, Richard M. Peek Jr., MD, said at the at the meeting sponsored by the American Gastroenterological Association. A very large, recent meta-analysis confirms it (Gastroenterology. 2016. doi:10.1053/j.gastro.2016.01.028). Comprising 24 studies and 48,000 subjects, the meta-analysis determined that eradicating the bacteria in infected people cut gastric cancer incidence significantly.

That’s great news – but there’s a big caveat, said Dr. Peek of Vanderbilt University, Nashville. “The benefit was dependent on what your baseline risk was. For those with a high baseline risk, the benefit was tremendous. For those with a low baseline risk, it was not statistically significant.”

There are long-term data suggesting that treating H. pylori sooner rather than later is the way to go. A 2005 study followed more than 700 patients with preneoplastic gastric lesions for 12 years. It found that the treatment effect was cumulative: The longer the patient was free of H. pylori, the more reliably healing occurred (Gut. 2005. doi:10.1136/gut.2005.072009).

At baseline, the patients were randomized to nutritional supplements or to a combination of amoxicillin, metronidazole, and bismuth subsalicylate. At 6 years, the trial was unblinded and all patients were offered treatment. Patients were followed for another 6 years. Those who were H. pylori negative at 12 years had 15% more regression and 14% less progression than subjects who were positive at 12 years. Among those who received anti–H. pylori treatment at the 6-year mark, the effect was smaller and nonsignificant.

Perhaps surprisingly, though, the biggest bang for H. pylori treatment is seen in the antrum of the stomach, not in the corpus. Another meta-analysis, this one of 16 studies, found very consistent reductions in the severity of intestinal metaplasia in the antrum after antibiotic treatment – but no difference at all in corpus metaplasia. The reason for that finding isn’t at all clear, the authors of that paper noted (World J Gastro. 2014. doi:10.3748/wjg.v20.i19.5903).

The bacteria-metaplasia cancer link gets even more complicated when H. pylori is viewed as a contributing member of society, rather than a hermit. The bacterium seems to be a bully in the neighborhood, radically altering the normal gastric microbiome, Dr. Peek said.

In the absence of H. pylori, the gastric microbiome is much more diverse, consisting of about 50% Actinobacteria and 25% Firmicutes species. Bacteroides and Proteobacteria species make up the remainder, with a small population of Cyanobacteria as well. In its presence, Proteobacteria – a gram-negative genus that includes a wide variety of pathogens – almost completely subsume beneficial bacteria.

Researchers saw this change in action in 2011, when a group at the Massachusetts Institute of Technology, Cambridge, inoculated two mouse populations with H. pylori and followed them for gastric neoplasms (Gastroenterology. 2011. doi:10.1053/j.gastro.2010.09.048). All the mice were genetically engineered to overexpress human gastrin, a characteristic that invariably leads them to develop gastric cancers.

One group comprised germ-free mice raised in sterile environments. The control group was free of pathogens, but lived in a conventional environment and so had normal gastric flora. Both groups were inoculated with H. pylori.

By 11 months, the microbiome of the control group was strikingly different. It showed a significant increase in the number of Firmicutes bacteria in the stomach, with an associated decrease in the number and variety of other bacteria including Bacteroides. This was especially interesting when viewed in relation to the rate of gastric neoplasia, Dr. Peek said.

These mice are programmed to develop gastric cancer by 6 months of age – and this is what happened in the control mice, which had H. pylori plus other gastric microbes. But the germ-free mice who were monoinfected with H. pylori showed a much different progression of disease. At 7 months, most showed only a mild hypergastrinemia. Conversely, at 7 months, all of the H. pylori–infected control mice had developed gastric intraepithelial neoplasia, 80% of it high grade. Only 10% of the monoinfected mice developed cancer, and all of it was low grade.

“It looks like there is active collaboration between H. pylori and other bacteria in the stomach,” resulting in this increased cancer risk, Dr. Peek said.

It’s a collaboration that reaches deep into the tumors themselves, he said. “A very interesting study a couple of years ago searched cancer genomes for the presence of bacterial DNA, and found that gastric cancers incorporated the second-highest amount of microbial DNA into their cancer genomes. But it wasn’t just H. pylori. Many other species had integrated their DNA into these tumors.”

That study, published in 2013, was the first to prove that bacterial DNA can impact carcinogenesis. Acute myeloid leukemia showed the highest integration of bacterial DNA, but gastric adenocarcinoma was a close second. Most of the species were of the Proteobacteria lineages (83%), with a third of that represented by Pseudomonas, particularly P. fluorescens and P. aeruginosa. Both of those species have been shown to promote gastric tumorigenesis in rats. All of the DNA integrations occurred in five genes; four of these are already known to be upregulated in gastric cancer (PLOS Comp Biol. 2013;9[6]:e1003107).

Interestingly, only a few of the sample reads turned up DNA integration with H. pylori.

This reduction in gastric microbial diversity could be an important key to H. pylori’s relation to gastric cancer, Dr. Peek said. He examined this in residents of two towns in Colombia, South America: Tumaco, where the risk of gastric cancer is low, and Tuquerres, where it’s 25 times higher (Sci Rep. 2016. doi:10.1038/srep18594).

What was different was the gastric microbiome of residents. Those living in low-risk Tumaco had much more microbial diversity: 361 varieties, compared with 194 in Tuquerres. And 16 of these groups – representative of what’s usually considered a healthy microbiome – were absent in the high-risk subjects. But Tuquerres residents had two bacteria that weren’t found in Tumaco residents, including Leptorichia wadei, which has been associated with necrotizing enterocolitis.

There was no difference, however, in the prevalence of H. pylori between these high- and low-risk groups.

These new findings illustrate an increasingly complicated interplay of bacteria and gastric cancer, Dr. Peek said. But they also provide a new direction for research.

“We have a framework now where we can move forward and try to understand how some of these other strains impact gastric cancer risk,” he said.

Dr. Peek had no relevant financial disclosures.

[email protected]

On Twitter @Alz_Gal

CHICAGO – Does eradicating Helicobacter pylori prevent gastric cancer?

The answer is yes, sometimes, but it depends on where you live, and what other bacteria coexist in your gut microbiome.

The overall view is a positive one, Richard M. Peek Jr., MD, said at the at the meeting sponsored by the American Gastroenterological Association. A very large, recent meta-analysis confirms it (Gastroenterology. 2016. doi:10.1053/j.gastro.2016.01.028). Comprising 24 studies and 48,000 subjects, the meta-analysis determined that eradicating the bacteria in infected people cut gastric cancer incidence significantly.

That’s great news – but there’s a big caveat, said Dr. Peek of Vanderbilt University, Nashville. “The benefit was dependent on what your baseline risk was. For those with a high baseline risk, the benefit was tremendous. For those with a low baseline risk, it was not statistically significant.”

There are long-term data suggesting that treating H. pylori sooner rather than later is the way to go. A 2005 study followed more than 700 patients with preneoplastic gastric lesions for 12 years. It found that the treatment effect was cumulative: The longer the patient was free of H. pylori, the more reliably healing occurred (Gut. 2005. doi:10.1136/gut.2005.072009).

At baseline, the patients were randomized to nutritional supplements or to a combination of amoxicillin, metronidazole, and bismuth subsalicylate. At 6 years, the trial was unblinded and all patients were offered treatment. Patients were followed for another 6 years. Those who were H. pylori negative at 12 years had 15% more regression and 14% less progression than subjects who were positive at 12 years. Among those who received anti–H. pylori treatment at the 6-year mark, the effect was smaller and nonsignificant.

Perhaps surprisingly, though, the biggest bang for H. pylori treatment is seen in the antrum of the stomach, not in the corpus. Another meta-analysis, this one of 16 studies, found very consistent reductions in the severity of intestinal metaplasia in the antrum after antibiotic treatment – but no difference at all in corpus metaplasia. The reason for that finding isn’t at all clear, the authors of that paper noted (World J Gastro. 2014. doi:10.3748/wjg.v20.i19.5903).

The bacteria-metaplasia cancer link gets even more complicated when H. pylori is viewed as a contributing member of society, rather than a hermit. The bacterium seems to be a bully in the neighborhood, radically altering the normal gastric microbiome, Dr. Peek said.

In the absence of H. pylori, the gastric microbiome is much more diverse, consisting of about 50% Actinobacteria and 25% Firmicutes species. Bacteroides and Proteobacteria species make up the remainder, with a small population of Cyanobacteria as well. In its presence, Proteobacteria – a gram-negative genus that includes a wide variety of pathogens – almost completely subsume beneficial bacteria.

Researchers saw this change in action in 2011, when a group at the Massachusetts Institute of Technology, Cambridge, inoculated two mouse populations with H. pylori and followed them for gastric neoplasms (Gastroenterology. 2011. doi:10.1053/j.gastro.2010.09.048). All the mice were genetically engineered to overexpress human gastrin, a characteristic that invariably leads them to develop gastric cancers.

One group comprised germ-free mice raised in sterile environments. The control group was free of pathogens, but lived in a conventional environment and so had normal gastric flora. Both groups were inoculated with H. pylori.

By 11 months, the microbiome of the control group was strikingly different. It showed a significant increase in the number of Firmicutes bacteria in the stomach, with an associated decrease in the number and variety of other bacteria including Bacteroides. This was especially interesting when viewed in relation to the rate of gastric neoplasia, Dr. Peek said.

These mice are programmed to develop gastric cancer by 6 months of age – and this is what happened in the control mice, which had H. pylori plus other gastric microbes. But the germ-free mice who were monoinfected with H. pylori showed a much different progression of disease. At 7 months, most showed only a mild hypergastrinemia. Conversely, at 7 months, all of the H. pylori–infected control mice had developed gastric intraepithelial neoplasia, 80% of it high grade. Only 10% of the monoinfected mice developed cancer, and all of it was low grade.

“It looks like there is active collaboration between H. pylori and other bacteria in the stomach,” resulting in this increased cancer risk, Dr. Peek said.

It’s a collaboration that reaches deep into the tumors themselves, he said. “A very interesting study a couple of years ago searched cancer genomes for the presence of bacterial DNA, and found that gastric cancers incorporated the second-highest amount of microbial DNA into their cancer genomes. But it wasn’t just H. pylori. Many other species had integrated their DNA into these tumors.”

That study, published in 2013, was the first to prove that bacterial DNA can impact carcinogenesis. Acute myeloid leukemia showed the highest integration of bacterial DNA, but gastric adenocarcinoma was a close second. Most of the species were of the Proteobacteria lineages (83%), with a third of that represented by Pseudomonas, particularly P. fluorescens and P. aeruginosa. Both of those species have been shown to promote gastric tumorigenesis in rats. All of the DNA integrations occurred in five genes; four of these are already known to be upregulated in gastric cancer (PLOS Comp Biol. 2013;9[6]:e1003107).

Interestingly, only a few of the sample reads turned up DNA integration with H. pylori.

This reduction in gastric microbial diversity could be an important key to H. pylori’s relation to gastric cancer, Dr. Peek said. He examined this in residents of two towns in Colombia, South America: Tumaco, where the risk of gastric cancer is low, and Tuquerres, where it’s 25 times higher (Sci Rep. 2016. doi:10.1038/srep18594).

What was different was the gastric microbiome of residents. Those living in low-risk Tumaco had much more microbial diversity: 361 varieties, compared with 194 in Tuquerres. And 16 of these groups – representative of what’s usually considered a healthy microbiome – were absent in the high-risk subjects. But Tuquerres residents had two bacteria that weren’t found in Tumaco residents, including Leptorichia wadei, which has been associated with necrotizing enterocolitis.

There was no difference, however, in the prevalence of H. pylori between these high- and low-risk groups.

These new findings illustrate an increasingly complicated interplay of bacteria and gastric cancer, Dr. Peek said. But they also provide a new direction for research.

“We have a framework now where we can move forward and try to understand how some of these other strains impact gastric cancer risk,” he said.

Dr. Peek had no relevant financial disclosures.

[email protected]

On Twitter @Alz_Gal

Fecal microbiota transplant (FMT) and esophageal disease were strange bedfellows in a series of informative lectures by world experts in their respective fields.

FMT breaks the cycle of resistant Clostridium difficile infection, where resistant bacteria overwhelm innate gut flora following antibiotic use. FMT introduces competition for nutrients and microbiota-derived bacteriocins targeting resistant bacteria, restores secondary bile salt metabolism, and stimulates mucosal immunity against resistant bacteria. The potential for FMT to benefit diseases other than recurrent C. difficile infection continues to be explored.

Eosinophilic esophagitis (EoE) is characterized clinically by dysphagia and food impaction, and pathologically by eosinophil-dominant inflammation (at least 15 eosinophils/high-power field on biopsy). Esophageal subepithelial fibrosis contributes to a narrow caliber, poorly distensible esophagus. Alternative causes of esophageal eosinophilia, particularly that induced by reflux, need to be excluded. Proton pump inhibitor (PPI) response does not distinguish EoE from reflux disease, but management starts with these drugs. Swallowed topical steroids, and the six-food elimination diet are alternative effective therapies. Biologic agents are being evaluated as future therapeutic options.

High-resolution manometry (HRM) has improved acquisition and display of esophageal pressure data, simplifying interpretation using three software tools, integrated relaxation pressure, distal contractile integral, and distal latency. Stationary impedance with HRM (high-resolution impedance manometry, HRIM) provides further gains in esophageal bolus transit assessment. Automated impedance manometry analysis, esophageal impedance integral ratio, bolus flow time, and functional lumen imaging probe–derived metrics add to esophageal physiologic assessments and esophageal function testing.

Rare disorders such as esophageal lichen planus can manifest with dysphagia and esophageal inflammation and strictures; these disorders are managed with immunosuppressive agents and cautious endoscopic dilation. Rumination (regurgitation of recently ingested food) and belching (with aerophagy) mimic reflux disease. These are distinguished using HRIM and pH-impedance monitoring, and treated with diaphragmatic breathing. Early postfundoplication dysphagia is common and responds to dilation; peptic strictures or slipped fundoplication needing wrap revision can cause late dysphagia. Scleroderma esophagus can be difficult to differentiate from advanced achalasia. Pneumatic dilation can benefit postmyotomy dysphagia.

Low-grade dysplasia within Barrett’s esophagus has a variable natural history, primarily from overdiagnosis and interobserver variation; many patients are down-staged upon review. Progression to high-grade dysplasia or intramucosal cancer (0.5%-1.7% per annum) is higher with confirmed low-grade dysplasia. Consequently, guidelines recommend review by expert pathologists and surveillance after 6-12 months. Evidence for radiofrequency ablation in carefully selected patients continues to grow. Radiofrequency ablation eliminates dysplasia and reduces the risk of progression to high-grade dysplasia. Better markers for diagnosis and prognosis continue to be studied.

Dr. Gyawali is professor of medicine, division of gastroenterology, Washington University in St. Louis. He has consulted for and received speaking fees or research funding from Medtronic, Torax, Ironwood, and Allergan.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

Fecal microbiota transplant (FMT) and esophageal disease were strange bedfellows in a series of informative lectures by world experts in their respective fields.

FMT breaks the cycle of resistant Clostridium difficile infection, where resistant bacteria overwhelm innate gut flora following antibiotic use. FMT introduces competition for nutrients and microbiota-derived bacteriocins targeting resistant bacteria, restores secondary bile salt metabolism, and stimulates mucosal immunity against resistant bacteria. The potential for FMT to benefit diseases other than recurrent C. difficile infection continues to be explored.

Eosinophilic esophagitis (EoE) is characterized clinically by dysphagia and food impaction, and pathologically by eosinophil-dominant inflammation (at least 15 eosinophils/high-power field on biopsy). Esophageal subepithelial fibrosis contributes to a narrow caliber, poorly distensible esophagus. Alternative causes of esophageal eosinophilia, particularly that induced by reflux, need to be excluded. Proton pump inhibitor (PPI) response does not distinguish EoE from reflux disease, but management starts with these drugs. Swallowed topical steroids, and the six-food elimination diet are alternative effective therapies. Biologic agents are being evaluated as future therapeutic options.

High-resolution manometry (HRM) has improved acquisition and display of esophageal pressure data, simplifying interpretation using three software tools, integrated relaxation pressure, distal contractile integral, and distal latency. Stationary impedance with HRM (high-resolution impedance manometry, HRIM) provides further gains in esophageal bolus transit assessment. Automated impedance manometry analysis, esophageal impedance integral ratio, bolus flow time, and functional lumen imaging probe–derived metrics add to esophageal physiologic assessments and esophageal function testing.

Rare disorders such as esophageal lichen planus can manifest with dysphagia and esophageal inflammation and strictures; these disorders are managed with immunosuppressive agents and cautious endoscopic dilation. Rumination (regurgitation of recently ingested food) and belching (with aerophagy) mimic reflux disease. These are distinguished using HRIM and pH-impedance monitoring, and treated with diaphragmatic breathing. Early postfundoplication dysphagia is common and responds to dilation; peptic strictures or slipped fundoplication needing wrap revision can cause late dysphagia. Scleroderma esophagus can be difficult to differentiate from advanced achalasia. Pneumatic dilation can benefit postmyotomy dysphagia.

Low-grade dysplasia within Barrett’s esophagus has a variable natural history, primarily from overdiagnosis and interobserver variation; many patients are down-staged upon review. Progression to high-grade dysplasia or intramucosal cancer (0.5%-1.7% per annum) is higher with confirmed low-grade dysplasia. Consequently, guidelines recommend review by expert pathologists and surveillance after 6-12 months. Evidence for radiofrequency ablation in carefully selected patients continues to grow. Radiofrequency ablation eliminates dysplasia and reduces the risk of progression to high-grade dysplasia. Better markers for diagnosis and prognosis continue to be studied.

Dr. Gyawali is professor of medicine, division of gastroenterology, Washington University in St. Louis. He has consulted for and received speaking fees or research funding from Medtronic, Torax, Ironwood, and Allergan.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

Fecal microbiota transplant (FMT) and esophageal disease were strange bedfellows in a series of informative lectures by world experts in their respective fields.

FMT breaks the cycle of resistant Clostridium difficile infection, where resistant bacteria overwhelm innate gut flora following antibiotic use. FMT introduces competition for nutrients and microbiota-derived bacteriocins targeting resistant bacteria, restores secondary bile salt metabolism, and stimulates mucosal immunity against resistant bacteria. The potential for FMT to benefit diseases other than recurrent C. difficile infection continues to be explored.

Eosinophilic esophagitis (EoE) is characterized clinically by dysphagia and food impaction, and pathologically by eosinophil-dominant inflammation (at least 15 eosinophils/high-power field on biopsy). Esophageal subepithelial fibrosis contributes to a narrow caliber, poorly distensible esophagus. Alternative causes of esophageal eosinophilia, particularly that induced by reflux, need to be excluded. Proton pump inhibitor (PPI) response does not distinguish EoE from reflux disease, but management starts with these drugs. Swallowed topical steroids, and the six-food elimination diet are alternative effective therapies. Biologic agents are being evaluated as future therapeutic options.

High-resolution manometry (HRM) has improved acquisition and display of esophageal pressure data, simplifying interpretation using three software tools, integrated relaxation pressure, distal contractile integral, and distal latency. Stationary impedance with HRM (high-resolution impedance manometry, HRIM) provides further gains in esophageal bolus transit assessment. Automated impedance manometry analysis, esophageal impedance integral ratio, bolus flow time, and functional lumen imaging probe–derived metrics add to esophageal physiologic assessments and esophageal function testing.

Rare disorders such as esophageal lichen planus can manifest with dysphagia and esophageal inflammation and strictures; these disorders are managed with immunosuppressive agents and cautious endoscopic dilation. Rumination (regurgitation of recently ingested food) and belching (with aerophagy) mimic reflux disease. These are distinguished using HRIM and pH-impedance monitoring, and treated with diaphragmatic breathing. Early postfundoplication dysphagia is common and responds to dilation; peptic strictures or slipped fundoplication needing wrap revision can cause late dysphagia. Scleroderma esophagus can be difficult to differentiate from advanced achalasia. Pneumatic dilation can benefit postmyotomy dysphagia.

Low-grade dysplasia within Barrett’s esophagus has a variable natural history, primarily from overdiagnosis and interobserver variation; many patients are down-staged upon review. Progression to high-grade dysplasia or intramucosal cancer (0.5%-1.7% per annum) is higher with confirmed low-grade dysplasia. Consequently, guidelines recommend review by expert pathologists and surveillance after 6-12 months. Evidence for radiofrequency ablation in carefully selected patients continues to grow. Radiofrequency ablation eliminates dysplasia and reduces the risk of progression to high-grade dysplasia. Better markers for diagnosis and prognosis continue to be studied.

Dr. Gyawali is professor of medicine, division of gastroenterology, Washington University in St. Louis. He has consulted for and received speaking fees or research funding from Medtronic, Torax, Ironwood, and Allergan.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

Kicking off the 2016 AGA Spring Postgraduate Course, this symposium encouraged attendees to embrace multidisciplinary approaches to managing patients with common gastrointestinal symptoms of nonstructural origin. My talk on “Managing the Big Four – Dyspepsia, Constipation, Diarrhea, and Abdominal Pain” reviewed the pathophysiology and management of these conditions. Thereafter, Sheila Crowe, MD, AGAF, Laurie Keefer, PhD, and Michael Camilleri, MD, AGAF, respectively, reviewed dietary approaches, psychological, and behavioral therapies, and overlooked, overused, and emerging pharmacotherapy for managing these conditions.

The clinical evaluation enables a precise symptom-based diagnosis of these conditions (e.g., dyspepsia, diarrhea-predominant irritable bowel syndrome [IBS], chronic constipation, defecatory disorders, and chronic abdominal pain). Dr. Keefer emphasized the importance of setting a pro-solution agenda early in the interview as well as listening, understanding, and believing symptoms. Empathy is essential. At the same time, patients need to assume personal responsibility and contribute to their own wellness. Expectations and a treatment plan should be negotiated. Bowel symptom questionnaires and, if necessary, bowel diaries ensure that symptoms are addressed comprehensively and save time. A meticulous digital rectal exam is essential since defecatory disorders are associated with not only lower but also upper GI symptoms. Only selected diagnostic tests, guided by the clinical features, should be performed.

Our understanding of the pathophysiology is evolving. Functional dyspepsia is implicated to impaired gastric accommodation, delayed gastric emptying, and increased gastric as well as duodenal sensitivity. Peripheral irritation (e.g., due to persistent low-grade inflammation after resolution of acute gastroenteritis or bile acids) and central dysfunctions (e.g., resulting from anxiety or depression) can alter GI transit and sensitivity resulting in IBS. Slow colon transit and impaired defecation (i.e., defecatory disorders) can cause chronic constipation.

Initially, therapy should utilize inexpensive, over-the-counter agents (loperamide for diarrhea). Dr. Camilleri also highlighted the utility of bile acid binding agents (e.g., cholestyramine and colesevelam) and when necessary, alosteron for diarrhea and cautioned attendees to use rifaximin as recommended by the Food and Drug Administration (i.e., up to three courses of 2 weeks) and not for long-term therapy. Several newer agents for these disorders are being developed. Dr. Crowe reminded the audience that foods often induce symptoms. In a recent study, a “common-sense” IBS diet was as effective as was a low-FODMAP diet for IBS. Eliminating gluten or wheat starch may benefit some patients with IBS without celiac disease but more evidence is required. Dr. Keefer highlighted the utility of diaphragmatic breathing for rumination, pelvic floor biofeedback therapy for defecatory disorders, and psychological therapies, especially cognitive behavioral therapy, for patients with a variety of GI symptoms.

Dr. Bharucha is with the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

Kicking off the 2016 AGA Spring Postgraduate Course, this symposium encouraged attendees to embrace multidisciplinary approaches to managing patients with common gastrointestinal symptoms of nonstructural origin. My talk on “Managing the Big Four – Dyspepsia, Constipation, Diarrhea, and Abdominal Pain” reviewed the pathophysiology and management of these conditions. Thereafter, Sheila Crowe, MD, AGAF, Laurie Keefer, PhD, and Michael Camilleri, MD, AGAF, respectively, reviewed dietary approaches, psychological, and behavioral therapies, and overlooked, overused, and emerging pharmacotherapy for managing these conditions.

The clinical evaluation enables a precise symptom-based diagnosis of these conditions (e.g., dyspepsia, diarrhea-predominant irritable bowel syndrome [IBS], chronic constipation, defecatory disorders, and chronic abdominal pain). Dr. Keefer emphasized the importance of setting a pro-solution agenda early in the interview as well as listening, understanding, and believing symptoms. Empathy is essential. At the same time, patients need to assume personal responsibility and contribute to their own wellness. Expectations and a treatment plan should be negotiated. Bowel symptom questionnaires and, if necessary, bowel diaries ensure that symptoms are addressed comprehensively and save time. A meticulous digital rectal exam is essential since defecatory disorders are associated with not only lower but also upper GI symptoms. Only selected diagnostic tests, guided by the clinical features, should be performed.

Our understanding of the pathophysiology is evolving. Functional dyspepsia is implicated to impaired gastric accommodation, delayed gastric emptying, and increased gastric as well as duodenal sensitivity. Peripheral irritation (e.g., due to persistent low-grade inflammation after resolution of acute gastroenteritis or bile acids) and central dysfunctions (e.g., resulting from anxiety or depression) can alter GI transit and sensitivity resulting in IBS. Slow colon transit and impaired defecation (i.e., defecatory disorders) can cause chronic constipation.

Initially, therapy should utilize inexpensive, over-the-counter agents (loperamide for diarrhea). Dr. Camilleri also highlighted the utility of bile acid binding agents (e.g., cholestyramine and colesevelam) and when necessary, alosteron for diarrhea and cautioned attendees to use rifaximin as recommended by the Food and Drug Administration (i.e., up to three courses of 2 weeks) and not for long-term therapy. Several newer agents for these disorders are being developed. Dr. Crowe reminded the audience that foods often induce symptoms. In a recent study, a “common-sense” IBS diet was as effective as was a low-FODMAP diet for IBS. Eliminating gluten or wheat starch may benefit some patients with IBS without celiac disease but more evidence is required. Dr. Keefer highlighted the utility of diaphragmatic breathing for rumination, pelvic floor biofeedback therapy for defecatory disorders, and psychological therapies, especially cognitive behavioral therapy, for patients with a variety of GI symptoms.

Dr. Bharucha is with the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

Kicking off the 2016 AGA Spring Postgraduate Course, this symposium encouraged attendees to embrace multidisciplinary approaches to managing patients with common gastrointestinal symptoms of nonstructural origin. My talk on “Managing the Big Four – Dyspepsia, Constipation, Diarrhea, and Abdominal Pain” reviewed the pathophysiology and management of these conditions. Thereafter, Sheila Crowe, MD, AGAF, Laurie Keefer, PhD, and Michael Camilleri, MD, AGAF, respectively, reviewed dietary approaches, psychological, and behavioral therapies, and overlooked, overused, and emerging pharmacotherapy for managing these conditions.

The clinical evaluation enables a precise symptom-based diagnosis of these conditions (e.g., dyspepsia, diarrhea-predominant irritable bowel syndrome [IBS], chronic constipation, defecatory disorders, and chronic abdominal pain). Dr. Keefer emphasized the importance of setting a pro-solution agenda early in the interview as well as listening, understanding, and believing symptoms. Empathy is essential. At the same time, patients need to assume personal responsibility and contribute to their own wellness. Expectations and a treatment plan should be negotiated. Bowel symptom questionnaires and, if necessary, bowel diaries ensure that symptoms are addressed comprehensively and save time. A meticulous digital rectal exam is essential since defecatory disorders are associated with not only lower but also upper GI symptoms. Only selected diagnostic tests, guided by the clinical features, should be performed.

Our understanding of the pathophysiology is evolving. Functional dyspepsia is implicated to impaired gastric accommodation, delayed gastric emptying, and increased gastric as well as duodenal sensitivity. Peripheral irritation (e.g., due to persistent low-grade inflammation after resolution of acute gastroenteritis or bile acids) and central dysfunctions (e.g., resulting from anxiety or depression) can alter GI transit and sensitivity resulting in IBS. Slow colon transit and impaired defecation (i.e., defecatory disorders) can cause chronic constipation.

Initially, therapy should utilize inexpensive, over-the-counter agents (loperamide for diarrhea). Dr. Camilleri also highlighted the utility of bile acid binding agents (e.g., cholestyramine and colesevelam) and when necessary, alosteron for diarrhea and cautioned attendees to use rifaximin as recommended by the Food and Drug Administration (i.e., up to three courses of 2 weeks) and not for long-term therapy. Several newer agents for these disorders are being developed. Dr. Crowe reminded the audience that foods often induce symptoms. In a recent study, a “common-sense” IBS diet was as effective as was a low-FODMAP diet for IBS. Eliminating gluten or wheat starch may benefit some patients with IBS without celiac disease but more evidence is required. Dr. Keefer highlighted the utility of diaphragmatic breathing for rumination, pelvic floor biofeedback therapy for defecatory disorders, and psychological therapies, especially cognitive behavioral therapy, for patients with a variety of GI symptoms.

Dr. Bharucha is with the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn.

This is a summary provided by the moderator of one of the spring postgraduate course sessions held at DDW 2016.

The September 2016 edition of GI & Hepatology News will be the last under the current editorial team. After 5 years, it is time for us to step aside and make way for a new group of editors. I am personally delighted that editorship of the paper will be in the safe hands of John I. Allen, MD, MBA, AGAF, who served as the AGA Institute’s president from 2014 to 2015. The Associate Editors and I wish him and his team every success. My own involvement with GI & Hepatology News actually precedes my time as Editor in Chief (EIC). I was privileged to serve on the selection committee that recommended the appointment of Charles J. Lightdale, MD, AGAF as the inaugural editor of the paper. He did an outstanding job and was a very tough act to follow. Now, it is time for Dr. Allen to take control of the paper, and I am confident that he will do a similarly excellent job.

The title of this piece is taken from a longer quote of Alfred Lord Tennyson. Although a bit of a cliché, it initially seemed an appropriate choice. However, if you look it up in full, it might seem inordinately gloomy, which was not my intention since there is certainly no need for pessimism. (After all, change is inevitable – except from a vending machine, of course.) The newspaper has been highly rated by its readers in the various surveys conducted by AGA, our publisher, and others. The Associate Editors and I have tried to feature articles on a broad range of issues that we hoped would have been among the most relevant for our predominantly clinical readership. It has been an exciting time in gastroenterology; serving as EIC of GI & Hepatology News has brought a number of issues to my attention that I might have otherwise missed. I would like to take this opportunity to thank Lora T. McGlade and the contributing writers from Frontline Medical Communications who prepared our news coverage. Sometimes it was difficult to rank the priority of the articles on offer but I hope that we chose many that were newsworthy and relevant.

AGA Institute

I am extremely grateful to the Associate Editors; all did an outstanding job and managed to keep to necessarily strict deadlines. Joel V. Brill, MD, AGAF, has been a terrific source of information about practice management and legislative issues and has made enormous contributions to the newspaper. Barbara H. Jung, MD, AGAF, who had responsibility for the broad topic of gastrointestinal oncology, frequently provided expert commentary and was extremely helpful in selecting articles to publish and in attracting commentary and perspective from other experts within AGA. John A. Martin, MD, took responsibility for endoscopy, obesity management, and pancreatic/biliary disease and frequently produced useful and succinct commentaries on some of the articles we published. Hepatology was the bailiwick of Kevin D. Mullen, MD, FRCPI, who helped select the most relevant articles and suggested experts to comment on the most important ones. David T. Rubin, MD, AGAF, handled IBD and intestinal disorders. Clearly there have been major advances in IBD management in recent years, with numerous new and emerging treatments. Dr. Rubin skillfully steered us through this maze, and gave much thoughtful guidance and expert input. With the Associate Editors’ help, I hope you will agree that we managed to keep the information in the paper as topical as possible for a monthly publication.

Thanks are also due to the team at AGA. Brook A. Simpson, as the lead staff member, has been responsible for managing all of the operations of GI & Hepatology News. Working with Brook was a distinct pleasure; she always provided excellent advice about AGA matters and its positions on key issues. I am also grateful to Erin C. Dubnansky, Lindsey M. Brounstein, and Jillian L. Schweitzer for their support.

In conclusion, it has been a privilege to serve as EIC of GI & Hepatology News over the past 5 years. I know that the paper is in good hands with Dr. Allen. I look forward to seeing the improvements and changes that he and his team will introduce.

Dr. Howden is Hyman Professor of Medicine, chief, division of gastroenterology, University of Tennessee Health Science Center, Memphis, and Editor in Chief, GI & Hepatology News.

The September 2016 edition of GI & Hepatology News will be the last under the current editorial team. After 5 years, it is time for us to step aside and make way for a new group of editors. I am personally delighted that editorship of the paper will be in the safe hands of John I. Allen, MD, MBA, AGAF, who served as the AGA Institute’s president from 2014 to 2015. The Associate Editors and I wish him and his team every success. My own involvement with GI & Hepatology News actually precedes my time as Editor in Chief (EIC). I was privileged to serve on the selection committee that recommended the appointment of Charles J. Lightdale, MD, AGAF as the inaugural editor of the paper. He did an outstanding job and was a very tough act to follow. Now, it is time for Dr. Allen to take control of the paper, and I am confident that he will do a similarly excellent job.

The title of this piece is taken from a longer quote of Alfred Lord Tennyson. Although a bit of a cliché, it initially seemed an appropriate choice. However, if you look it up in full, it might seem inordinately gloomy, which was not my intention since there is certainly no need for pessimism. (After all, change is inevitable – except from a vending machine, of course.) The newspaper has been highly rated by its readers in the various surveys conducted by AGA, our publisher, and others. The Associate Editors and I have tried to feature articles on a broad range of issues that we hoped would have been among the most relevant for our predominantly clinical readership. It has been an exciting time in gastroenterology; serving as EIC of GI & Hepatology News has brought a number of issues to my attention that I might have otherwise missed. I would like to take this opportunity to thank Lora T. McGlade and the contributing writers from Frontline Medical Communications who prepared our news coverage. Sometimes it was difficult to rank the priority of the articles on offer but I hope that we chose many that were newsworthy and relevant.

AGA Institute

I am extremely grateful to the Associate Editors; all did an outstanding job and managed to keep to necessarily strict deadlines. Joel V. Brill, MD, AGAF, has been a terrific source of information about practice management and legislative issues and has made enormous contributions to the newspaper. Barbara H. Jung, MD, AGAF, who had responsibility for the broad topic of gastrointestinal oncology, frequently provided expert commentary and was extremely helpful in selecting articles to publish and in attracting commentary and perspective from other experts within AGA. John A. Martin, MD, took responsibility for endoscopy, obesity management, and pancreatic/biliary disease and frequently produced useful and succinct commentaries on some of the articles we published. Hepatology was the bailiwick of Kevin D. Mullen, MD, FRCPI, who helped select the most relevant articles and suggested experts to comment on the most important ones. David T. Rubin, MD, AGAF, handled IBD and intestinal disorders. Clearly there have been major advances in IBD management in recent years, with numerous new and emerging treatments. Dr. Rubin skillfully steered us through this maze, and gave much thoughtful guidance and expert input. With the Associate Editors’ help, I hope you will agree that we managed to keep the information in the paper as topical as possible for a monthly publication.

Thanks are also due to the team at AGA. Brook A. Simpson, as the lead staff member, has been responsible for managing all of the operations of GI & Hepatology News. Working with Brook was a distinct pleasure; she always provided excellent advice about AGA matters and its positions on key issues. I am also grateful to Erin C. Dubnansky, Lindsey M. Brounstein, and Jillian L. Schweitzer for their support.

In conclusion, it has been a privilege to serve as EIC of GI & Hepatology News over the past 5 years. I know that the paper is in good hands with Dr. Allen. I look forward to seeing the improvements and changes that he and his team will introduce.

Dr. Howden is Hyman Professor of Medicine, chief, division of gastroenterology, University of Tennessee Health Science Center, Memphis, and Editor in Chief, GI & Hepatology News.

The September 2016 edition of GI & Hepatology News will be the last under the current editorial team. After 5 years, it is time for us to step aside and make way for a new group of editors. I am personally delighted that editorship of the paper will be in the safe hands of John I. Allen, MD, MBA, AGAF, who served as the AGA Institute’s president from 2014 to 2015. The Associate Editors and I wish him and his team every success. My own involvement with GI & Hepatology News actually precedes my time as Editor in Chief (EIC). I was privileged to serve on the selection committee that recommended the appointment of Charles J. Lightdale, MD, AGAF as the inaugural editor of the paper. He did an outstanding job and was a very tough act to follow. Now, it is time for Dr. Allen to take control of the paper, and I am confident that he will do a similarly excellent job.

The title of this piece is taken from a longer quote of Alfred Lord Tennyson. Although a bit of a cliché, it initially seemed an appropriate choice. However, if you look it up in full, it might seem inordinately gloomy, which was not my intention since there is certainly no need for pessimism. (After all, change is inevitable – except from a vending machine, of course.) The newspaper has been highly rated by its readers in the various surveys conducted by AGA, our publisher, and others. The Associate Editors and I have tried to feature articles on a broad range of issues that we hoped would have been among the most relevant for our predominantly clinical readership. It has been an exciting time in gastroenterology; serving as EIC of GI & Hepatology News has brought a number of issues to my attention that I might have otherwise missed. I would like to take this opportunity to thank Lora T. McGlade and the contributing writers from Frontline Medical Communications who prepared our news coverage. Sometimes it was difficult to rank the priority of the articles on offer but I hope that we chose many that were newsworthy and relevant.

AGA Institute

I am extremely grateful to the Associate Editors; all did an outstanding job and managed to keep to necessarily strict deadlines. Joel V. Brill, MD, AGAF, has been a terrific source of information about practice management and legislative issues and has made enormous contributions to the newspaper. Barbara H. Jung, MD, AGAF, who had responsibility for the broad topic of gastrointestinal oncology, frequently provided expert commentary and was extremely helpful in selecting articles to publish and in attracting commentary and perspective from other experts within AGA. John A. Martin, MD, took responsibility for endoscopy, obesity management, and pancreatic/biliary disease and frequently produced useful and succinct commentaries on some of the articles we published. Hepatology was the bailiwick of Kevin D. Mullen, MD, FRCPI, who helped select the most relevant articles and suggested experts to comment on the most important ones. David T. Rubin, MD, AGAF, handled IBD and intestinal disorders. Clearly there have been major advances in IBD management in recent years, with numerous new and emerging treatments. Dr. Rubin skillfully steered us through this maze, and gave much thoughtful guidance and expert input. With the Associate Editors’ help, I hope you will agree that we managed to keep the information in the paper as topical as possible for a monthly publication.

Thanks are also due to the team at AGA. Brook A. Simpson, as the lead staff member, has been responsible for managing all of the operations of GI & Hepatology News. Working with Brook was a distinct pleasure; she always provided excellent advice about AGA matters and its positions on key issues. I am also grateful to Erin C. Dubnansky, Lindsey M. Brounstein, and Jillian L. Schweitzer for their support.

In conclusion, it has been a privilege to serve as EIC of GI & Hepatology News over the past 5 years. I know that the paper is in good hands with Dr. Allen. I look forward to seeing the improvements and changes that he and his team will introduce.

Dr. Howden is Hyman Professor of Medicine, chief, division of gastroenterology, University of Tennessee Health Science Center, Memphis, and Editor in Chief, GI & Hepatology News.

Hospitalization of patients with stroke in primary stroke centers, compared with noncertified hospitals, is associated with decreased seven-day and 30-day case fatality, according to a study published online ahead of print July 25 in JAMA Internal Medicine. Among 865,184 elderly patients with stroke (mean age, 78.9; 55.5% female), 53.9% were treated in primary stroke centers. Admission to primary stroke centers was associated with 1.8% lower seven-day and 1.8% lower 30-day case fatality. Fifty-six patients with stroke needed to be treated in primary stroke centers to save one life at 30 days. Overall, receiving treatment in primary stroke centers was associated with a 30-day survival benefit for patients traveling less than 90 minutes, but traveling at least 90 minutes offset any benefit of care in primary stroke centers.

Obesity may increase the risk of neurodegeneration, according to a study published online ahead of print July 27 in Neurobiology of Aging. Participants were a population-based cohort of cognitively healthy adults recruited over a five-year period. In all, 527 subjects with an age range of 20 to 87 were included. Researchers performed a cross-sectional analysis of MRI-based brain structure and found a statistically significant interaction between age and BMI. Cortical reconstruction techniques were used to generate measures of whole brain cerebral white matter volume, cortical thickness, and surface area. Cerebral white matter volume in overweight and obese individuals was associated with a greater degree of atrophy, with maximal effects in middle age corresponding to an estimated increase in brain age of 10 years.

Thymectomy improves clinical outcomes over a three-year period in patients with nonthymomatous myasthenia gravis, according to a study published August 11 in the New England Journal of Medicine. Researchers randomized 126 patients to thymectomy plus alternate-day prednisone or alternate-day prednisone alone. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a three-year period than those who received prednisone alone. Patients in the thymectomy group also had a lower average requirement for alternate-day prednisone. Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine or were hospitalized for exacerbations. The number of patients with treatment-associated complications did not differ significantly between groups. However, patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications.

Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease, according to a study published online ahead of print August 17 in Neurology. This longitudinal population-based study included 700 women without dementia between ages 70 and 92. At baseline and at five-year follow-up, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan also was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Women treated with calcium supplements had a higher risk of developing dementia and the subtype of stroke-related dementia. Calcium supplementation was associated with the development of dementia in groups with a history of stroke or presence of white matter lesions, but not in groups without these conditions.

Exposure to bright light during the day may help combat sleep disturbances associated with the evening use of electronic devices emitting blue light, according to a study published online ahead of print June 16 in Sleep Medicine. Following a constant bright light exposure over 6.5 hours, 14 participants read a novel either on a tablet or as a physical book for two hours. Evening concentrations of saliva melatonin were measured repeatedly. Sleepiness was assessed before and after nocturnal sleep. About one week later, experiments were repeated. Participants who had read the novel on a tablet in the first experimental session continued reading the same novel as a physical book, and vice versa. There were no differences in sleep parameters and presleep saliva melatonin levels between the tablet reading and physical book reading conditions.

Treatment immediately after clinically isolated syndrome (CIS) is more beneficial than delayed treatment, according to a study published online ahead of print August 10 in Neurology. Researchers randomized 278 people with CIS to interferon beta-1b or placebo. After two years or a diagnosis of multiple sclerosis (MS), patients receiving placebo could receive treatment. After 11 years, risk of clinically definite MS remained lower in the early-treatment arm, compared with the delayed-treatment arm, with longer time to first relapse and lower overall annualized relapse rate. Twenty-five patients converted to secondary progressive MS. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms. The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores. Health resource utilization was low in both groups.

Patients with anemia have increased mortality after stroke, according to a study published online ahead of print August 17 in the Journal of the American Heart Association. Researchers analyzed data from a cohort of 8,013 patients with stroke who were consecutively admitted over 11 years. Anemia was present in 24.5% of the cohort on admission and was associated with increased odds of mortality at most of the time points examined up to one year following stroke. Elevated hemoglobin also was associated with increased mortality. In addition, investigators conducted a systematic review using various databases. When combined with the cohort from the current study, the pooled population had 29,943 patients with stroke. Anemia on admission was associated with an increased risk of mortality in ischemic stroke and hemorrhagic stroke.

Bedside EEG methods may indicate the level of awareness of patients in a vegetative state, according to a study published online ahead of print August 4 in Annals of Neurology. Fourteen patients with severe brain injuries were evaluated with an EEG vibrotactile attention task designed to identify a hierarchy of residual somatosensory and cognitive abilities. Each patient also was assessed with a clinical behavioral scale and two fMRI assessments of covert command following. Six patients produced only sensory responses, with no evidence of cognitive event-related potentials. Furthermore, eight patients demonstrated reliable bottom-up attention-orienting responses. No patient showed evidence of top-down attention. Only patients who followed commands, whether overtly with behavior or covertly with functional neuroimaging, also demonstrated event-related potential evidence of attentional orienting.

The PET tracer [18F]-AV-1451 may help identify the stages of the preclinical and clinical phases of Alzheimer's disease, according to a study published online ahead of print July 25 in JAMA Neurology. In all, 59 participants (64% male; mean age, 74) underwent PET imaging. The [18F]-AV-1451 standardized uptake value ratio (SUVR) in the hippocampus and Alzheimer's disease cortical signature regions distinguished participants with Alzheimer's disease from cognitively normal participants. A SUVR cutoff value of 1.19 from Alzheimer's disease cortical signature regions best distinguished these groups. Amyloid β-positivity was associated with an elevated [18F]-AV-1451 SUVR in Alzheimer's disease cortical signature regions, but not in the hippocampus. Amyloid β-positivity alone was not related to hippocampal volume or Alzheimer's disease signature cortical thickness. An elevated [18F]-AV-1451 SUVR was associated with brain volumetric loss.

Symptom exacerbations after concussion are common among children and may not impede recovery, according to a study published online ahead of print August 1 in JAMA Pediatrics. Eligible participants were between ages 11 and 18 and had sustained a concussion that did not result in an abnormal CT scan or require hospital admission. The mean age of the 63 participants (34.9% girls) was 13.8. Symptom spikes occurred in 31.7% of the sample. An abrupt increase in mental activity from one day to the next increased the risk of a symptom spike. Patients with symptom spikes were initially more symptomatic in the emergency department and throughout the observation period, but did not differ from the group without symptom spikes on cognition or balance 10 days following injury.

The FDA has approved the supplemental Biologics License Application from Ipsen Biopharmaceuticals for Dysport (abobotulinumtoxinA) for injection in the treatment of lower limb spasticity in pediatric patients age 2 and older. This approval is based on a phase III pivotal study of 235 pediatric patients ages 2 to 17 with lower limb spasticity because of cerebral palsy causing dynamic equinus foot deformity. Patients treated with Dysport showed statistically significant improvement in ankle plantar flexor muscle tone. Like all botulinum toxin products, Dysport has a boxed warning stating that the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism. Ipsen Biopharmaceuticals is headquartered in Basking Ridge, New Jersey.

Lower BMI in late life is associated with greater cortical amyloid burden, according to a study published June 18 in the Journal of Alzheimer's Disease. The study entailed cross-sectional analyses that were completed using baseline data from the Harvard Aging Brain Study, which included 280 cognitively normal adults ages 62 to 90. Assessments included medical histories and physical exams, Pittsburgh compound B (PiB) PET amyloid imaging, and APOE4 genotyping. In the primary analysis, greater PiB retention was associated with lower BMI. In the secondary analyses, APOE4 carrier status and normal BMI, as opposed to overweight or obese BMI, were associated with greater PiB retention. The interaction between BMI and APOE4 also was significant. Future studies should seek to clarify the mechanism of this association, said the researchers.

Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome, according to a literature review published online ahead of print August 3 in Neurology. Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in patients with transient ischemic attack or stroke are recommended in view of the high prevalence of SDB, said the researchers. Treatment of obstructive SDB with continuous positive airway pressure is recommended, given the strength of the evidence that supports the treatment's benefit. Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB, said the researchers. Experimental studies found that SWD may impair neuroplasticity and functional stroke recovery.

—Kimberly Williams

Hospitalization of patients with stroke in primary stroke centers, compared with noncertified hospitals, is associated with decreased seven-day and 30-day case fatality, according to a study published online ahead of print July 25 in JAMA Internal Medicine. Among 865,184 elderly patients with stroke (mean age, 78.9; 55.5% female), 53.9% were treated in primary stroke centers. Admission to primary stroke centers was associated with 1.8% lower seven-day and 1.8% lower 30-day case fatality. Fifty-six patients with stroke needed to be treated in primary stroke centers to save one life at 30 days. Overall, receiving treatment in primary stroke centers was associated with a 30-day survival benefit for patients traveling less than 90 minutes, but traveling at least 90 minutes offset any benefit of care in primary stroke centers.

Obesity may increase the risk of neurodegeneration, according to a study published online ahead of print July 27 in Neurobiology of Aging. Participants were a population-based cohort of cognitively healthy adults recruited over a five-year period. In all, 527 subjects with an age range of 20 to 87 were included. Researchers performed a cross-sectional analysis of MRI-based brain structure and found a statistically significant interaction between age and BMI. Cortical reconstruction techniques were used to generate measures of whole brain cerebral white matter volume, cortical thickness, and surface area. Cerebral white matter volume in overweight and obese individuals was associated with a greater degree of atrophy, with maximal effects in middle age corresponding to an estimated increase in brain age of 10 years.

Thymectomy improves clinical outcomes over a three-year period in patients with nonthymomatous myasthenia gravis, according to a study published August 11 in the New England Journal of Medicine. Researchers randomized 126 patients to thymectomy plus alternate-day prednisone or alternate-day prednisone alone. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a three-year period than those who received prednisone alone. Patients in the thymectomy group also had a lower average requirement for alternate-day prednisone. Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine or were hospitalized for exacerbations. The number of patients with treatment-associated complications did not differ significantly between groups. However, patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications.

Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease, according to a study published online ahead of print August 17 in Neurology. This longitudinal population-based study included 700 women without dementia between ages 70 and 92. At baseline and at five-year follow-up, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan also was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Women treated with calcium supplements had a higher risk of developing dementia and the subtype of stroke-related dementia. Calcium supplementation was associated with the development of dementia in groups with a history of stroke or presence of white matter lesions, but not in groups without these conditions.

Exposure to bright light during the day may help combat sleep disturbances associated with the evening use of electronic devices emitting blue light, according to a study published online ahead of print June 16 in Sleep Medicine. Following a constant bright light exposure over 6.5 hours, 14 participants read a novel either on a tablet or as a physical book for two hours. Evening concentrations of saliva melatonin were measured repeatedly. Sleepiness was assessed before and after nocturnal sleep. About one week later, experiments were repeated. Participants who had read the novel on a tablet in the first experimental session continued reading the same novel as a physical book, and vice versa. There were no differences in sleep parameters and presleep saliva melatonin levels between the tablet reading and physical book reading conditions.

Treatment immediately after clinically isolated syndrome (CIS) is more beneficial than delayed treatment, according to a study published online ahead of print August 10 in Neurology. Researchers randomized 278 people with CIS to interferon beta-1b or placebo. After two years or a diagnosis of multiple sclerosis (MS), patients receiving placebo could receive treatment. After 11 years, risk of clinically definite MS remained lower in the early-treatment arm, compared with the delayed-treatment arm, with longer time to first relapse and lower overall annualized relapse rate. Twenty-five patients converted to secondary progressive MS. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms. The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores. Health resource utilization was low in both groups.

Patients with anemia have increased mortality after stroke, according to a study published online ahead of print August 17 in the Journal of the American Heart Association. Researchers analyzed data from a cohort of 8,013 patients with stroke who were consecutively admitted over 11 years. Anemia was present in 24.5% of the cohort on admission and was associated with increased odds of mortality at most of the time points examined up to one year following stroke. Elevated hemoglobin also was associated with increased mortality. In addition, investigators conducted a systematic review using various databases. When combined with the cohort from the current study, the pooled population had 29,943 patients with stroke. Anemia on admission was associated with an increased risk of mortality in ischemic stroke and hemorrhagic stroke.

Bedside EEG methods may indicate the level of awareness of patients in a vegetative state, according to a study published online ahead of print August 4 in Annals of Neurology. Fourteen patients with severe brain injuries were evaluated with an EEG vibrotactile attention task designed to identify a hierarchy of residual somatosensory and cognitive abilities. Each patient also was assessed with a clinical behavioral scale and two fMRI assessments of covert command following. Six patients produced only sensory responses, with no evidence of cognitive event-related potentials. Furthermore, eight patients demonstrated reliable bottom-up attention-orienting responses. No patient showed evidence of top-down attention. Only patients who followed commands, whether overtly with behavior or covertly with functional neuroimaging, also demonstrated event-related potential evidence of attentional orienting.

The PET tracer [18F]-AV-1451 may help identify the stages of the preclinical and clinical phases of Alzheimer's disease, according to a study published online ahead of print July 25 in JAMA Neurology. In all, 59 participants (64% male; mean age, 74) underwent PET imaging. The [18F]-AV-1451 standardized uptake value ratio (SUVR) in the hippocampus and Alzheimer's disease cortical signature regions distinguished participants with Alzheimer's disease from cognitively normal participants. A SUVR cutoff value of 1.19 from Alzheimer's disease cortical signature regions best distinguished these groups. Amyloid β-positivity was associated with an elevated [18F]-AV-1451 SUVR in Alzheimer's disease cortical signature regions, but not in the hippocampus. Amyloid β-positivity alone was not related to hippocampal volume or Alzheimer's disease signature cortical thickness. An elevated [18F]-AV-1451 SUVR was associated with brain volumetric loss.

Symptom exacerbations after concussion are common among children and may not impede recovery, according to a study published online ahead of print August 1 in JAMA Pediatrics. Eligible participants were between ages 11 and 18 and had sustained a concussion that did not result in an abnormal CT scan or require hospital admission. The mean age of the 63 participants (34.9% girls) was 13.8. Symptom spikes occurred in 31.7% of the sample. An abrupt increase in mental activity from one day to the next increased the risk of a symptom spike. Patients with symptom spikes were initially more symptomatic in the emergency department and throughout the observation period, but did not differ from the group without symptom spikes on cognition or balance 10 days following injury.

The FDA has approved the supplemental Biologics License Application from Ipsen Biopharmaceuticals for Dysport (abobotulinumtoxinA) for injection in the treatment of lower limb spasticity in pediatric patients age 2 and older. This approval is based on a phase III pivotal study of 235 pediatric patients ages 2 to 17 with lower limb spasticity because of cerebral palsy causing dynamic equinus foot deformity. Patients treated with Dysport showed statistically significant improvement in ankle plantar flexor muscle tone. Like all botulinum toxin products, Dysport has a boxed warning stating that the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism. Ipsen Biopharmaceuticals is headquartered in Basking Ridge, New Jersey.

Lower BMI in late life is associated with greater cortical amyloid burden, according to a study published June 18 in the Journal of Alzheimer's Disease. The study entailed cross-sectional analyses that were completed using baseline data from the Harvard Aging Brain Study, which included 280 cognitively normal adults ages 62 to 90. Assessments included medical histories and physical exams, Pittsburgh compound B (PiB) PET amyloid imaging, and APOE4 genotyping. In the primary analysis, greater PiB retention was associated with lower BMI. In the secondary analyses, APOE4 carrier status and normal BMI, as opposed to overweight or obese BMI, were associated with greater PiB retention. The interaction between BMI and APOE4 also was significant. Future studies should seek to clarify the mechanism of this association, said the researchers.

Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome, according to a literature review published online ahead of print August 3 in Neurology. Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in patients with transient ischemic attack or stroke are recommended in view of the high prevalence of SDB, said the researchers. Treatment of obstructive SDB with continuous positive airway pressure is recommended, given the strength of the evidence that supports the treatment's benefit. Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB, said the researchers. Experimental studies found that SWD may impair neuroplasticity and functional stroke recovery.

—Kimberly Williams

Hospitalization of patients with stroke in primary stroke centers, compared with noncertified hospitals, is associated with decreased seven-day and 30-day case fatality, according to a study published online ahead of print July 25 in JAMA Internal Medicine. Among 865,184 elderly patients with stroke (mean age, 78.9; 55.5% female), 53.9% were treated in primary stroke centers. Admission to primary stroke centers was associated with 1.8% lower seven-day and 1.8% lower 30-day case fatality. Fifty-six patients with stroke needed to be treated in primary stroke centers to save one life at 30 days. Overall, receiving treatment in primary stroke centers was associated with a 30-day survival benefit for patients traveling less than 90 minutes, but traveling at least 90 minutes offset any benefit of care in primary stroke centers.

Obesity may increase the risk of neurodegeneration, according to a study published online ahead of print July 27 in Neurobiology of Aging. Participants were a population-based cohort of cognitively healthy adults recruited over a five-year period. In all, 527 subjects with an age range of 20 to 87 were included. Researchers performed a cross-sectional analysis of MRI-based brain structure and found a statistically significant interaction between age and BMI. Cortical reconstruction techniques were used to generate measures of whole brain cerebral white matter volume, cortical thickness, and surface area. Cerebral white matter volume in overweight and obese individuals was associated with a greater degree of atrophy, with maximal effects in middle age corresponding to an estimated increase in brain age of 10 years.

Thymectomy improves clinical outcomes over a three-year period in patients with nonthymomatous myasthenia gravis, according to a study published August 11 in the New England Journal of Medicine. Researchers randomized 126 patients to thymectomy plus alternate-day prednisone or alternate-day prednisone alone. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a three-year period than those who received prednisone alone. Patients in the thymectomy group also had a lower average requirement for alternate-day prednisone. Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine or were hospitalized for exacerbations. The number of patients with treatment-associated complications did not differ significantly between groups. However, patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications.

Calcium supplementation may increase the risk of developing dementia in elderly women with cerebrovascular disease, according to a study published online ahead of print August 17 in Neurology. This longitudinal population-based study included 700 women without dementia between ages 70 and 92. At baseline and at five-year follow-up, the women underwent comprehensive neuropsychiatric and somatic examinations. A CT scan also was performed in 447 participants at baseline. Information on the use and dosage of calcium supplements was collected. Women treated with calcium supplements had a higher risk of developing dementia and the subtype of stroke-related dementia. Calcium supplementation was associated with the development of dementia in groups with a history of stroke or presence of white matter lesions, but not in groups without these conditions.

Exposure to bright light during the day may help combat sleep disturbances associated with the evening use of electronic devices emitting blue light, according to a study published online ahead of print June 16 in Sleep Medicine. Following a constant bright light exposure over 6.5 hours, 14 participants read a novel either on a tablet or as a physical book for two hours. Evening concentrations of saliva melatonin were measured repeatedly. Sleepiness was assessed before and after nocturnal sleep. About one week later, experiments were repeated. Participants who had read the novel on a tablet in the first experimental session continued reading the same novel as a physical book, and vice versa. There were no differences in sleep parameters and presleep saliva melatonin levels between the tablet reading and physical book reading conditions.

Treatment immediately after clinically isolated syndrome (CIS) is more beneficial than delayed treatment, according to a study published online ahead of print August 10 in Neurology. Researchers randomized 278 people with CIS to interferon beta-1b or placebo. After two years or a diagnosis of multiple sclerosis (MS), patients receiving placebo could receive treatment. After 11 years, risk of clinically definite MS remained lower in the early-treatment arm, compared with the delayed-treatment arm, with longer time to first relapse and lower overall annualized relapse rate. Twenty-five patients converted to secondary progressive MS. Expanded Disability Status Scale scores remained low and stable, with no difference between treatment arms. The early-treatment group had better Paced Auditory Serial Addition Task-3 total scores. Health resource utilization was low in both groups.

Patients with anemia have increased mortality after stroke, according to a study published online ahead of print August 17 in the Journal of the American Heart Association. Researchers analyzed data from a cohort of 8,013 patients with stroke who were consecutively admitted over 11 years. Anemia was present in 24.5% of the cohort on admission and was associated with increased odds of mortality at most of the time points examined up to one year following stroke. Elevated hemoglobin also was associated with increased mortality. In addition, investigators conducted a systematic review using various databases. When combined with the cohort from the current study, the pooled population had 29,943 patients with stroke. Anemia on admission was associated with an increased risk of mortality in ischemic stroke and hemorrhagic stroke.

Bedside EEG methods may indicate the level of awareness of patients in a vegetative state, according to a study published online ahead of print August 4 in Annals of Neurology. Fourteen patients with severe brain injuries were evaluated with an EEG vibrotactile attention task designed to identify a hierarchy of residual somatosensory and cognitive abilities. Each patient also was assessed with a clinical behavioral scale and two fMRI assessments of covert command following. Six patients produced only sensory responses, with no evidence of cognitive event-related potentials. Furthermore, eight patients demonstrated reliable bottom-up attention-orienting responses. No patient showed evidence of top-down attention. Only patients who followed commands, whether overtly with behavior or covertly with functional neuroimaging, also demonstrated event-related potential evidence of attentional orienting.

The PET tracer [18F]-AV-1451 may help identify the stages of the preclinical and clinical phases of Alzheimer's disease, according to a study published online ahead of print July 25 in JAMA Neurology. In all, 59 participants (64% male; mean age, 74) underwent PET imaging. The [18F]-AV-1451 standardized uptake value ratio (SUVR) in the hippocampus and Alzheimer's disease cortical signature regions distinguished participants with Alzheimer's disease from cognitively normal participants. A SUVR cutoff value of 1.19 from Alzheimer's disease cortical signature regions best distinguished these groups. Amyloid β-positivity was associated with an elevated [18F]-AV-1451 SUVR in Alzheimer's disease cortical signature regions, but not in the hippocampus. Amyloid β-positivity alone was not related to hippocampal volume or Alzheimer's disease signature cortical thickness. An elevated [18F]-AV-1451 SUVR was associated with brain volumetric loss.

Symptom exacerbations after concussion are common among children and may not impede recovery, according to a study published online ahead of print August 1 in JAMA Pediatrics. Eligible participants were between ages 11 and 18 and had sustained a concussion that did not result in an abnormal CT scan or require hospital admission. The mean age of the 63 participants (34.9% girls) was 13.8. Symptom spikes occurred in 31.7% of the sample. An abrupt increase in mental activity from one day to the next increased the risk of a symptom spike. Patients with symptom spikes were initially more symptomatic in the emergency department and throughout the observation period, but did not differ from the group without symptom spikes on cognition or balance 10 days following injury.

The FDA has approved the supplemental Biologics License Application from Ipsen Biopharmaceuticals for Dysport (abobotulinumtoxinA) for injection in the treatment of lower limb spasticity in pediatric patients age 2 and older. This approval is based on a phase III pivotal study of 235 pediatric patients ages 2 to 17 with lower limb spasticity because of cerebral palsy causing dynamic equinus foot deformity. Patients treated with Dysport showed statistically significant improvement in ankle plantar flexor muscle tone. Like all botulinum toxin products, Dysport has a boxed warning stating that the effects of the botulinum toxin may spread from the area of injection to other areas of the body, causing symptoms similar to those of botulism. Ipsen Biopharmaceuticals is headquartered in Basking Ridge, New Jersey.

Lower BMI in late life is associated with greater cortical amyloid burden, according to a study published June 18 in the Journal of Alzheimer's Disease. The study entailed cross-sectional analyses that were completed using baseline data from the Harvard Aging Brain Study, which included 280 cognitively normal adults ages 62 to 90. Assessments included medical histories and physical exams, Pittsburgh compound B (PiB) PET amyloid imaging, and APOE4 genotyping. In the primary analysis, greater PiB retention was associated with lower BMI. In the secondary analyses, APOE4 carrier status and normal BMI, as opposed to overweight or obese BMI, were associated with greater PiB retention. The interaction between BMI and APOE4 also was significant. Future studies should seek to clarify the mechanism of this association, said the researchers.

Sleep-disordered breathing (SDB) and sleep-wake disturbances (SWD) increase the risk of stroke in the general population and affect short- and long-term stroke recovery and outcome, according to a literature review published online ahead of print August 3 in Neurology. Several studies have proven SDB to represent an independent risk factor for stroke. Sleep studies in patients with transient ischemic attack or stroke are recommended in view of the high prevalence of SDB, said the researchers. Treatment of obstructive SDB with continuous positive airway pressure is recommended, given the strength of the evidence that supports the treatment's benefit. Oxygen, biphasic positive airway pressure, and adaptive servoventilation may be considered in patients with central SDB, said the researchers. Experimental studies found that SWD may impair neuroplasticity and functional stroke recovery.

—Kimberly Williams

The number of new cases of pregnant women with laboratory evidence of Zika infection in the 50 states and the District of Columbia took a big jump during the week ending Aug. 18, 2016, while U.S. territories continued the strong increase that started the previous week, according to the Centers for Disease Control and Prevention.

There were 55 new cases of Zika virus infection among pregnant women in the 50 states and D.C. reported the week ending Aug. 18. The number of new cases had been dropping, with 19 new cases the week of Aug. 11, 31 the week ending Aug. 4, and 46 the week ending July 28.

The territories had 121 new cases in the week ending Aug. 18, for a total of 176 new U.S. cases. For the year, there have been 1,396 cases of Zika in pregnant women in the United States: 584 in the states/D.C. and 812 in the territories, the CDC reported on Aug. 25. Among all Americans, there have been 11,528 cases of Zika virus in 2015-2016: 2,517 in the states/D.C. and 9,011 in the territories, of which 8,788 have occurred in Puerto Rico.

There were no new cases of Zika-related poor outcomes reported during the week ending Aug. 18, so the numbers of live-born infants who were born with birth defects remained at 16 in the states/D.C. and 1 in the territories, and pregnancy losses with birth defects held at five in the states/D.C. and one in the territories, the CDC said. State- or territorial-level data are not being reported to protect the privacy of affected women and children.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

Zika virus–related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

[email protected]

The number of new cases of pregnant women with laboratory evidence of Zika infection in the 50 states and the District of Columbia took a big jump during the week ending Aug. 18, 2016, while U.S. territories continued the strong increase that started the previous week, according to the Centers for Disease Control and Prevention.

There were 55 new cases of Zika virus infection among pregnant women in the 50 states and D.C. reported the week ending Aug. 18. The number of new cases had been dropping, with 19 new cases the week of Aug. 11, 31 the week ending Aug. 4, and 46 the week ending July 28.

The territories had 121 new cases in the week ending Aug. 18, for a total of 176 new U.S. cases. For the year, there have been 1,396 cases of Zika in pregnant women in the United States: 584 in the states/D.C. and 812 in the territories, the CDC reported on Aug. 25. Among all Americans, there have been 11,528 cases of Zika virus in 2015-2016: 2,517 in the states/D.C. and 9,011 in the territories, of which 8,788 have occurred in Puerto Rico.

There were no new cases of Zika-related poor outcomes reported during the week ending Aug. 18, so the numbers of live-born infants who were born with birth defects remained at 16 in the states/D.C. and 1 in the territories, and pregnancy losses with birth defects held at five in the states/D.C. and one in the territories, the CDC said. State- or territorial-level data are not being reported to protect the privacy of affected women and children.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

Zika virus–related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

[email protected]

The number of new cases of pregnant women with laboratory evidence of Zika infection in the 50 states and the District of Columbia took a big jump during the week ending Aug. 18, 2016, while U.S. territories continued the strong increase that started the previous week, according to the Centers for Disease Control and Prevention.

There were 55 new cases of Zika virus infection among pregnant women in the 50 states and D.C. reported the week ending Aug. 18. The number of new cases had been dropping, with 19 new cases the week of Aug. 11, 31 the week ending Aug. 4, and 46 the week ending July 28.

The territories had 121 new cases in the week ending Aug. 18, for a total of 176 new U.S. cases. For the year, there have been 1,396 cases of Zika in pregnant women in the United States: 584 in the states/D.C. and 812 in the territories, the CDC reported on Aug. 25. Among all Americans, there have been 11,528 cases of Zika virus in 2015-2016: 2,517 in the states/D.C. and 9,011 in the territories, of which 8,788 have occurred in Puerto Rico.

There were no new cases of Zika-related poor outcomes reported during the week ending Aug. 18, so the numbers of live-born infants who were born with birth defects remained at 16 in the states/D.C. and 1 in the territories, and pregnancy losses with birth defects held at five in the states/D.C. and one in the territories, the CDC said. State- or territorial-level data are not being reported to protect the privacy of affected women and children.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

Zika virus–related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

[email protected]