SAN DIEGO – Lansoprazole and famotidine are comparable for the prevention of recurrent ulcer bleeding in patients with a history of Helicobacter pylori–negative idiopathic bleeding ulcers, results from a double-blind, randomized trial showed. However, these patients face a considerable risk of overall mortality, despite a low incidence of recurrent GI bleeding.

Doug Brunk/MDedge News

“Peptic ulcer disease is a commonly encountered condition in our daily clinical practice,” one of the study authors, Louis Lau, MD, said at the annual Digestive Disease Week. “Most of the ulcers are due to H. pylori and NSAIDs or aspirin. However, idiopathic peptic ulcers remain an area to be investigated.”

According to Dr. Lau of the division of gastroenterology and hepatology at Prince of Wales Hospital, Hong Kong, H. pylori–negative idiopathic ulcers have increased in prevalence in the Asian Pacific region, from 1%-4% in 2000 to up to 20% in recent data. These ulcers have been shown to have a bleeding rate of up to 13% within 1 year (Gastroenterology. 2005;128:1845-50) and have been associated with a mortality rate of up to 88% in 7 years of follow-up (Gastroenterology. 2009;137:525-31).

“There is no consensus for the optimal management of this particular ulcer,” he continued. “One proposed management was maintenance PPI [proton pump inhibitors]. However, we would like to look for the best optimal prevention strategy.”

Dr. Lau and associates conducted a double-blind, randomized trial at Prince of Wales Hospital to determine if there were any differences between the PPI lansoprazole and the histamine₂ receptor antagonist famotidine for the prevention of recurrent bleeding in patients with H. pylori–negative idiopathic peptic ulcers. It involved a 2-year follow-up period and included a screening and end-of-study esophagogastroduodenoscopy. The drugs were repackaged into identical green capsules.

The researchers limited the analysis to 228 patients over the age 18 with H. pylori–negative idiopathic ulcers, defined as having endoscopic biopsies negative for both rapid urease test and histology for H. pylori; no exposure to aspirin, NSAIDs, or drugs of unknown nature including traditional Chinese medicine within 4 weeks; and no other causes of ulceration identified. Exclusion criteria included patients with a strong indication for maintenance therapy with PPIs, those with prior gastric surgery, pregnant patients, and those with advanced malignancy or comorbidity.

The primary endpoint was clinical GI bleeding or reduction in hemoglobin level of 2 g/dL or more and confirmation of peptic ulcers by endoscopy. The secondary endpoint was recurrent ulcer detected by end-of-study endoscopy, with or without clinical symptoms.

Of the 228 patients, 114 received lansoprazole 30 mg daily and 114 received famotidine 40 mg daily. Recurrent upper GI bleeding was suspected in 10 patients in each of the treatment groups. Ulcer confirmation via endoscopy detected one ulcer in the lansoprazole group and three in the famotidine group (0.9% vs. 2.6%, respectively; P = .62). For the secondary endpoint, there were five recurrent ulcers in the lansoprazole group and nine in the famotidine group, (4.4% vs. 7.9%, respectively; P = .27).

Dr. Lau and colleagues observed eight deaths in the lansoprazole group (7%), compared with five (4.4%) in the famotidine group (P = .39), mainly caused by pneumonia, renal failure, and other chronic medical conditions. Intention-to-treat analysis at 2 years found that both groups were comparable in terms of time to analysis of recurrent upper GI bleeding, adjusted for death as a competing risk (Gray’s test, P = .313).

“In this randomized, controlled trial, we found that both a PPI and an H₂ blocker are comparable in the prevention of idiopathic ulcer recurrent bleeding,” Dr. Lau concluded. “The rebleeding rate was five times lower than a previous cohort reported with no or irregular acid suppression therapy [Gastroenterology. 2005;128[7]:1845-50]. With all this, there is still a considerable risk of recurrent ulcers and death. We postulate that there is an underlying mechanism for this type of idiopathic ulcer.”

The study was funded in part by the General Research Fund–Research Grant Council. Dr. Lau reported having no financial disclosures. Many of his coauthors reported having numerous financial ties to the pharmaceutical industry.

dbrunk@mdedge.com

SOURCE: Lau L et al. DDW 2019, Abstract 322.

SAN DIEGO – Lansoprazole and famotidine are comparable for the prevention of recurrent ulcer bleeding in patients with a history of Helicobacter pylori–negative idiopathic bleeding ulcers, results from a double-blind, randomized trial showed. However, these patients face a considerable risk of overall mortality, despite a low incidence of recurrent GI bleeding.

Doug Brunk/MDedge News

“Peptic ulcer disease is a commonly encountered condition in our daily clinical practice,” one of the study authors, Louis Lau, MD, said at the annual Digestive Disease Week. “Most of the ulcers are due to H. pylori and NSAIDs or aspirin. However, idiopathic peptic ulcers remain an area to be investigated.”

According to Dr. Lau of the division of gastroenterology and hepatology at Prince of Wales Hospital, Hong Kong, H. pylori–negative idiopathic ulcers have increased in prevalence in the Asian Pacific region, from 1%-4% in 2000 to up to 20% in recent data. These ulcers have been shown to have a bleeding rate of up to 13% within 1 year (Gastroenterology. 2005;128:1845-50) and have been associated with a mortality rate of up to 88% in 7 years of follow-up (Gastroenterology. 2009;137:525-31).

“There is no consensus for the optimal management of this particular ulcer,” he continued. “One proposed management was maintenance PPI [proton pump inhibitors]. However, we would like to look for the best optimal prevention strategy.”

Dr. Lau and associates conducted a double-blind, randomized trial at Prince of Wales Hospital to determine if there were any differences between the PPI lansoprazole and the histamine₂ receptor antagonist famotidine for the prevention of recurrent bleeding in patients with H. pylori–negative idiopathic peptic ulcers. It involved a 2-year follow-up period and included a screening and end-of-study esophagogastroduodenoscopy. The drugs were repackaged into identical green capsules.

The researchers limited the analysis to 228 patients over the age 18 with H. pylori–negative idiopathic ulcers, defined as having endoscopic biopsies negative for both rapid urease test and histology for H. pylori; no exposure to aspirin, NSAIDs, or drugs of unknown nature including traditional Chinese medicine within 4 weeks; and no other causes of ulceration identified. Exclusion criteria included patients with a strong indication for maintenance therapy with PPIs, those with prior gastric surgery, pregnant patients, and those with advanced malignancy or comorbidity.

The primary endpoint was clinical GI bleeding or reduction in hemoglobin level of 2 g/dL or more and confirmation of peptic ulcers by endoscopy. The secondary endpoint was recurrent ulcer detected by end-of-study endoscopy, with or without clinical symptoms.

Of the 228 patients, 114 received lansoprazole 30 mg daily and 114 received famotidine 40 mg daily. Recurrent upper GI bleeding was suspected in 10 patients in each of the treatment groups. Ulcer confirmation via endoscopy detected one ulcer in the lansoprazole group and three in the famotidine group (0.9% vs. 2.6%, respectively; P = .62). For the secondary endpoint, there were five recurrent ulcers in the lansoprazole group and nine in the famotidine group, (4.4% vs. 7.9%, respectively; P = .27).

Dr. Lau and colleagues observed eight deaths in the lansoprazole group (7%), compared with five (4.4%) in the famotidine group (P = .39), mainly caused by pneumonia, renal failure, and other chronic medical conditions. Intention-to-treat analysis at 2 years found that both groups were comparable in terms of time to analysis of recurrent upper GI bleeding, adjusted for death as a competing risk (Gray’s test, P = .313).

“In this randomized, controlled trial, we found that both a PPI and an H₂ blocker are comparable in the prevention of idiopathic ulcer recurrent bleeding,” Dr. Lau concluded. “The rebleeding rate was five times lower than a previous cohort reported with no or irregular acid suppression therapy [Gastroenterology. 2005;128[7]:1845-50]. With all this, there is still a considerable risk of recurrent ulcers and death. We postulate that there is an underlying mechanism for this type of idiopathic ulcer.”

The study was funded in part by the General Research Fund–Research Grant Council. Dr. Lau reported having no financial disclosures. Many of his coauthors reported having numerous financial ties to the pharmaceutical industry.

dbrunk@mdedge.com

SOURCE: Lau L et al. DDW 2019, Abstract 322.

SAN DIEGO – Lansoprazole and famotidine are comparable for the prevention of recurrent ulcer bleeding in patients with a history of Helicobacter pylori–negative idiopathic bleeding ulcers, results from a double-blind, randomized trial showed. However, these patients face a considerable risk of overall mortality, despite a low incidence of recurrent GI bleeding.

Doug Brunk/MDedge News

“Peptic ulcer disease is a commonly encountered condition in our daily clinical practice,” one of the study authors, Louis Lau, MD, said at the annual Digestive Disease Week. “Most of the ulcers are due to H. pylori and NSAIDs or aspirin. However, idiopathic peptic ulcers remain an area to be investigated.”

According to Dr. Lau of the division of gastroenterology and hepatology at Prince of Wales Hospital, Hong Kong, H. pylori–negative idiopathic ulcers have increased in prevalence in the Asian Pacific region, from 1%-4% in 2000 to up to 20% in recent data. These ulcers have been shown to have a bleeding rate of up to 13% within 1 year (Gastroenterology. 2005;128:1845-50) and have been associated with a mortality rate of up to 88% in 7 years of follow-up (Gastroenterology. 2009;137:525-31).

“There is no consensus for the optimal management of this particular ulcer,” he continued. “One proposed management was maintenance PPI [proton pump inhibitors]. However, we would like to look for the best optimal prevention strategy.”

Dr. Lau and associates conducted a double-blind, randomized trial at Prince of Wales Hospital to determine if there were any differences between the PPI lansoprazole and the histamine₂ receptor antagonist famotidine for the prevention of recurrent bleeding in patients with H. pylori–negative idiopathic peptic ulcers. It involved a 2-year follow-up period and included a screening and end-of-study esophagogastroduodenoscopy. The drugs were repackaged into identical green capsules.

The researchers limited the analysis to 228 patients over the age 18 with H. pylori–negative idiopathic ulcers, defined as having endoscopic biopsies negative for both rapid urease test and histology for H. pylori; no exposure to aspirin, NSAIDs, or drugs of unknown nature including traditional Chinese medicine within 4 weeks; and no other causes of ulceration identified. Exclusion criteria included patients with a strong indication for maintenance therapy with PPIs, those with prior gastric surgery, pregnant patients, and those with advanced malignancy or comorbidity.

The primary endpoint was clinical GI bleeding or reduction in hemoglobin level of 2 g/dL or more and confirmation of peptic ulcers by endoscopy. The secondary endpoint was recurrent ulcer detected by end-of-study endoscopy, with or without clinical symptoms.

Of the 228 patients, 114 received lansoprazole 30 mg daily and 114 received famotidine 40 mg daily. Recurrent upper GI bleeding was suspected in 10 patients in each of the treatment groups. Ulcer confirmation via endoscopy detected one ulcer in the lansoprazole group and three in the famotidine group (0.9% vs. 2.6%, respectively; P = .62). For the secondary endpoint, there were five recurrent ulcers in the lansoprazole group and nine in the famotidine group, (4.4% vs. 7.9%, respectively; P = .27).

Dr. Lau and colleagues observed eight deaths in the lansoprazole group (7%), compared with five (4.4%) in the famotidine group (P = .39), mainly caused by pneumonia, renal failure, and other chronic medical conditions. Intention-to-treat analysis at 2 years found that both groups were comparable in terms of time to analysis of recurrent upper GI bleeding, adjusted for death as a competing risk (Gray’s test, P = .313).

“In this randomized, controlled trial, we found that both a PPI and an H₂ blocker are comparable in the prevention of idiopathic ulcer recurrent bleeding,” Dr. Lau concluded. “The rebleeding rate was five times lower than a previous cohort reported with no or irregular acid suppression therapy [Gastroenterology. 2005;128[7]:1845-50]. With all this, there is still a considerable risk of recurrent ulcers and death. We postulate that there is an underlying mechanism for this type of idiopathic ulcer.”

The study was funded in part by the General Research Fund–Research Grant Council. Dr. Lau reported having no financial disclosures. Many of his coauthors reported having numerous financial ties to the pharmaceutical industry.

dbrunk@mdedge.com

SOURCE: Lau L et al. DDW 2019, Abstract 322.

This year’s VAM features an exhibit pavilion, special Vascular Live presentations, and a breakfast session geared specifically to clinicians who work in office and outpatient settings.

The Office Vascular Care Pavilion is in Exhibit Hall B, on the lower level of the Gaylord National Resort & Convention Center, across from the SVS Booth. Office Vascular Care Live presentations (not eligible for CME credit) include:
 

Thursday, June 13

12:30 to 1 p.m. OBL 101; Krishna M. Jain, MD

3 to 3:30 p.m. OBL Chatter, industry presentations by Cordis®, A Cardinal Health company, Philips and Vein Care iGuide
Sessions include: Coming to a town near you! Life Cycle of an OBL, Factors Influencing Behavior of an OBL, and Industry Partnership, sponsored by Cordis®, A Cardinal Health company
Keys to Success and Methods of Failure in Today’s OBL, David Baker, sponsored by Philips
 

Friday, June 14

12:30 to 1 p.m. OBL Tips and Tools; R. Clement Darling III, MD

3 to 3:30 p.m. OBL Quality and Safety; Robert G. Molnar, MD 

8:30 to 9:30 a.m. Ticket Required - The SVS also has a new member section focused on the move to outpatient and office-based settings, the Section on Outpatient and Office Vascular Care (SOOVC), which will hold its first meeting Friday in National Harbor 3. Tickets are available at Registration. Prospective members are welcome.

Saturday, June 15

6:30 to 8 a.m. Breakfast Session 9 will cover “Complications in Office-Based Procedures: Their Prevention and Management.” It is being presented in collaboration with the Outpatient Endovascular and Interventional Society. 

This year’s VAM features an exhibit pavilion, special Vascular Live presentations, and a breakfast session geared specifically to clinicians who work in office and outpatient settings.

The Office Vascular Care Pavilion is in Exhibit Hall B, on the lower level of the Gaylord National Resort & Convention Center, across from the SVS Booth. Office Vascular Care Live presentations (not eligible for CME credit) include:
 

Thursday, June 13

12:30 to 1 p.m. OBL 101; Krishna M. Jain, MD

3 to 3:30 p.m. OBL Chatter, industry presentations by Cordis®, A Cardinal Health company, Philips and Vein Care iGuide
Sessions include: Coming to a town near you! Life Cycle of an OBL, Factors Influencing Behavior of an OBL, and Industry Partnership, sponsored by Cordis®, A Cardinal Health company
Keys to Success and Methods of Failure in Today’s OBL, David Baker, sponsored by Philips
 

Friday, June 14

12:30 to 1 p.m. OBL Tips and Tools; R. Clement Darling III, MD

3 to 3:30 p.m. OBL Quality and Safety; Robert G. Molnar, MD 

8:30 to 9:30 a.m. Ticket Required - The SVS also has a new member section focused on the move to outpatient and office-based settings, the Section on Outpatient and Office Vascular Care (SOOVC), which will hold its first meeting Friday in National Harbor 3. Tickets are available at Registration. Prospective members are welcome.

Saturday, June 15

6:30 to 8 a.m. Breakfast Session 9 will cover “Complications in Office-Based Procedures: Their Prevention and Management.” It is being presented in collaboration with the Outpatient Endovascular and Interventional Society. 

This year’s VAM features an exhibit pavilion, special Vascular Live presentations, and a breakfast session geared specifically to clinicians who work in office and outpatient settings.

The Office Vascular Care Pavilion is in Exhibit Hall B, on the lower level of the Gaylord National Resort & Convention Center, across from the SVS Booth. Office Vascular Care Live presentations (not eligible for CME credit) include:
 

Thursday, June 13

12:30 to 1 p.m. OBL 101; Krishna M. Jain, MD

3 to 3:30 p.m. OBL Chatter, industry presentations by Cordis®, A Cardinal Health company, Philips and Vein Care iGuide
Sessions include: Coming to a town near you! Life Cycle of an OBL, Factors Influencing Behavior of an OBL, and Industry Partnership, sponsored by Cordis®, A Cardinal Health company
Keys to Success and Methods of Failure in Today’s OBL, David Baker, sponsored by Philips
 

Friday, June 14

12:30 to 1 p.m. OBL Tips and Tools; R. Clement Darling III, MD

3 to 3:30 p.m. OBL Quality and Safety; Robert G. Molnar, MD 

8:30 to 9:30 a.m. Ticket Required - The SVS also has a new member section focused on the move to outpatient and office-based settings, the Section on Outpatient and Office Vascular Care (SOOVC), which will hold its first meeting Friday in National Harbor 3. Tickets are available at Registration. Prospective members are welcome.

Saturday, June 15

6:30 to 8 a.m. Breakfast Session 9 will cover “Complications in Office-Based Procedures: Their Prevention and Management.” It is being presented in collaboration with the Outpatient Endovascular and Interventional Society. 

Working memory may not function properly during the reappraisal process of emotion regulation in patients with bipolar disorder, according to Dong Hun Oh of the department of psychiatry at Yonsei University, Seoul, South Korea, and associates.

For the study, published in the Journal of Affective Disorders, 43 patients with euthymic bipolar I disorder were recruited from a psychiatric outpatient clinic in Seoul and compared with 48 healthy controls. The Korean versions of the operation span task (OSPAN), emotion regulation questionnaire (K-ERQ), ruminative response scale (K-RRS), and Difficulties in Emotion Regulation Scale (K-DERS) were administered to all the patients.

In a between-group comparison of scores on the four scales measured, patients with bipolar disorder had significantly lower scores on OSPAN (P = .031), on the brooding section of the K-RRS (P =.016), and on the nonacceptance section of the K-DERS (P = .039). In a regression analysis of the interaction between working memory and the four components of emotion regulation (reappraisal, expressive suppression, brooding, and reflective pondering), a significant interaction was found in OSPAN scores for reappraisal between healthy controls and the BD group (P = .007). Brooding scores were significantly lower in the control group, but the interaction was not significant.

A simple slope analysis showed that, while working memory was worse in patients with bipolar disorder, a relationship between cognitive capacity and the efficacy of reappraisal was found only in healthy controls, the investigators noted.

“The absence of interaction between [working memory capacity] and reappraisal in euthymic [bipolar disorder] patients that we report may indicate that the positive effects of cognitive remediation or [working memory] training previously reported for healthy people, may not effectively improve [emotion regulation] for patients with [bipolar disorder],” they wrote.

This could mean that “top-down regulation of emotion is impaired” in patients with bipolar disorder. Furthermore, if this is the case, cognitive interventions aimed at improving emotion regulation in patients with bipolar disorder might not work.

The investigators cited several limitations. One limitation was the small sample size; another was the use of self-administered questionnaires.

The study was supported by a faculty research grant from Yonsei University. The authors did not report any conflicts of interest.

lfranki@mdedge.com

SOURCE: Oh DH et al. J Affect Disord. 2019 Apr 8. doi: 10.1016/j.jad.2019.04.042.

Working memory may not function properly during the reappraisal process of emotion regulation in patients with bipolar disorder, according to Dong Hun Oh of the department of psychiatry at Yonsei University, Seoul, South Korea, and associates.

For the study, published in the Journal of Affective Disorders, 43 patients with euthymic bipolar I disorder were recruited from a psychiatric outpatient clinic in Seoul and compared with 48 healthy controls. The Korean versions of the operation span task (OSPAN), emotion regulation questionnaire (K-ERQ), ruminative response scale (K-RRS), and Difficulties in Emotion Regulation Scale (K-DERS) were administered to all the patients.

In a between-group comparison of scores on the four scales measured, patients with bipolar disorder had significantly lower scores on OSPAN (P = .031), on the brooding section of the K-RRS (P =.016), and on the nonacceptance section of the K-DERS (P = .039). In a regression analysis of the interaction between working memory and the four components of emotion regulation (reappraisal, expressive suppression, brooding, and reflective pondering), a significant interaction was found in OSPAN scores for reappraisal between healthy controls and the BD group (P = .007). Brooding scores were significantly lower in the control group, but the interaction was not significant.

A simple slope analysis showed that, while working memory was worse in patients with bipolar disorder, a relationship between cognitive capacity and the efficacy of reappraisal was found only in healthy controls, the investigators noted.

“The absence of interaction between [working memory capacity] and reappraisal in euthymic [bipolar disorder] patients that we report may indicate that the positive effects of cognitive remediation or [working memory] training previously reported for healthy people, may not effectively improve [emotion regulation] for patients with [bipolar disorder],” they wrote.

This could mean that “top-down regulation of emotion is impaired” in patients with bipolar disorder. Furthermore, if this is the case, cognitive interventions aimed at improving emotion regulation in patients with bipolar disorder might not work.

The investigators cited several limitations. One limitation was the small sample size; another was the use of self-administered questionnaires.

The study was supported by a faculty research grant from Yonsei University. The authors did not report any conflicts of interest.

lfranki@mdedge.com

SOURCE: Oh DH et al. J Affect Disord. 2019 Apr 8. doi: 10.1016/j.jad.2019.04.042.

Working memory may not function properly during the reappraisal process of emotion regulation in patients with bipolar disorder, according to Dong Hun Oh of the department of psychiatry at Yonsei University, Seoul, South Korea, and associates.

For the study, published in the Journal of Affective Disorders, 43 patients with euthymic bipolar I disorder were recruited from a psychiatric outpatient clinic in Seoul and compared with 48 healthy controls. The Korean versions of the operation span task (OSPAN), emotion regulation questionnaire (K-ERQ), ruminative response scale (K-RRS), and Difficulties in Emotion Regulation Scale (K-DERS) were administered to all the patients.

In a between-group comparison of scores on the four scales measured, patients with bipolar disorder had significantly lower scores on OSPAN (P = .031), on the brooding section of the K-RRS (P =.016), and on the nonacceptance section of the K-DERS (P = .039). In a regression analysis of the interaction between working memory and the four components of emotion regulation (reappraisal, expressive suppression, brooding, and reflective pondering), a significant interaction was found in OSPAN scores for reappraisal between healthy controls and the BD group (P = .007). Brooding scores were significantly lower in the control group, but the interaction was not significant.

A simple slope analysis showed that, while working memory was worse in patients with bipolar disorder, a relationship between cognitive capacity and the efficacy of reappraisal was found only in healthy controls, the investigators noted.

“The absence of interaction between [working memory capacity] and reappraisal in euthymic [bipolar disorder] patients that we report may indicate that the positive effects of cognitive remediation or [working memory] training previously reported for healthy people, may not effectively improve [emotion regulation] for patients with [bipolar disorder],” they wrote.

This could mean that “top-down regulation of emotion is impaired” in patients with bipolar disorder. Furthermore, if this is the case, cognitive interventions aimed at improving emotion regulation in patients with bipolar disorder might not work.

The investigators cited several limitations. One limitation was the small sample size; another was the use of self-administered questionnaires.

The study was supported by a faculty research grant from Yonsei University. The authors did not report any conflicts of interest.

lfranki@mdedge.com

SOURCE: Oh DH et al. J Affect Disord. 2019 Apr 8. doi: 10.1016/j.jad.2019.04.042.

Nonhealing wounds in patients with diabetes are a major cause of morbidity and mortality in the United States and are increasing at an alarming rate. Equally concerning, the current “standard of care” leaves 70% of diabetic wounds unhealed. Given this substantial impact on patient outcomes and health care expenditure, a critical unmet need exists for improved understanding of the pathophysiology of diabetic wounds to develop effective treatments.

This year’s SVS Foundation’s Resident Research Award is being presented to Frank M. Davis, MD, of the University of Michigan, Ann Arbor, for his research on the epigenetic regulation of the prostaglandin pathway in macrophages during type 2 diabetic wound healing. Dr. Davis, and his mentor Katherine Gallagher, MD, also from the University of Michigan, investigated how impairments in the innate immune system in patients with diabetes promote chronic inflammation and impair wound healing.

Dr. Davis will present his award-winning research in the von Liebig Forum, Thursday, June 13, discussing the role of specific epigenetic enzymes in the dictation of macrophage phenotype in wound tissue. The talk will cover how diabetes alters those enzymes to influence a deleterious phenotype that promotes inflammation and delays wound healing. “Our laboratory specifically looks at the role of monocytes/macrophages in the inflammatory phase of wound healing and how perturbation in the local environment – such as those seen in diabetes – affects monocyte/macrophage phenotype and ultimately wound healing” said Dr. Davis.

The talk will specifically cover the cyclo-oxygenase (COX)-2/prostaglandin E₂ (PGE₂) axis. Using both a murine model and human wound samples Dr. Davis demonstrates that PGE₂ is substantially elevated in diabetic wound macrophages. Further, aberrant PGE₂ production in diabetic macrophages depended on epigenetic alterations to key enzymes in the PGE₂ pathway.

Specifically, MLL1, a histone methyltransferase, increased H3K4 trimethylation resulting in upregulation of PGE₂ in diabetic wound macrophages. Additionally, the authors found that augmentation to miR-29b and DNA methyltransferases in diabetic macrophage result in increased COX-2 expression. Overall, the increased COX-2/PGE₂ production in diabetic macrophages impairs bacterial killing, predisposing diabetic wounds to chronic infection.

“Our research provides insight into the prostaglandin E₂ axis and its role in macrophage inflammation, which has previously been an unrecognized pathway leading to delayed diabetic wound healing” added Dr. Gallagher.

Finally, in his presentation, Dr. Davis will discuss translational therapies as inhibition of the PGE₂ pathway through macrophage targeted nanoparticles decreased diabetic inflammation and improved healing. “Together, our results indicate the COX-2/PGE₂ pathway is a critical regulator of macrophage phenotype and impaired diabetic wound healing. This work identifies therapeutic targets for negating dysregulated inflammation in diabetic wounds and identifies macrophage-targeted local therapy as an effective means of improving wound healing,” Dr. Davis concluded.

Nonhealing wounds in patients with diabetes are a major cause of morbidity and mortality in the United States and are increasing at an alarming rate. Equally concerning, the current “standard of care” leaves 70% of diabetic wounds unhealed. Given this substantial impact on patient outcomes and health care expenditure, a critical unmet need exists for improved understanding of the pathophysiology of diabetic wounds to develop effective treatments.

This year’s SVS Foundation’s Resident Research Award is being presented to Frank M. Davis, MD, of the University of Michigan, Ann Arbor, for his research on the epigenetic regulation of the prostaglandin pathway in macrophages during type 2 diabetic wound healing. Dr. Davis, and his mentor Katherine Gallagher, MD, also from the University of Michigan, investigated how impairments in the innate immune system in patients with diabetes promote chronic inflammation and impair wound healing.

Dr. Davis will present his award-winning research in the von Liebig Forum, Thursday, June 13, discussing the role of specific epigenetic enzymes in the dictation of macrophage phenotype in wound tissue. The talk will cover how diabetes alters those enzymes to influence a deleterious phenotype that promotes inflammation and delays wound healing. “Our laboratory specifically looks at the role of monocytes/macrophages in the inflammatory phase of wound healing and how perturbation in the local environment – such as those seen in diabetes – affects monocyte/macrophage phenotype and ultimately wound healing” said Dr. Davis.

The talk will specifically cover the cyclo-oxygenase (COX)-2/prostaglandin E₂ (PGE₂) axis. Using both a murine model and human wound samples Dr. Davis demonstrates that PGE₂ is substantially elevated in diabetic wound macrophages. Further, aberrant PGE₂ production in diabetic macrophages depended on epigenetic alterations to key enzymes in the PGE₂ pathway.

Specifically, MLL1, a histone methyltransferase, increased H3K4 trimethylation resulting in upregulation of PGE₂ in diabetic wound macrophages. Additionally, the authors found that augmentation to miR-29b and DNA methyltransferases in diabetic macrophage result in increased COX-2 expression. Overall, the increased COX-2/PGE₂ production in diabetic macrophages impairs bacterial killing, predisposing diabetic wounds to chronic infection.

“Our research provides insight into the prostaglandin E₂ axis and its role in macrophage inflammation, which has previously been an unrecognized pathway leading to delayed diabetic wound healing” added Dr. Gallagher.

Finally, in his presentation, Dr. Davis will discuss translational therapies as inhibition of the PGE₂ pathway through macrophage targeted nanoparticles decreased diabetic inflammation and improved healing. “Together, our results indicate the COX-2/PGE₂ pathway is a critical regulator of macrophage phenotype and impaired diabetic wound healing. This work identifies therapeutic targets for negating dysregulated inflammation in diabetic wounds and identifies macrophage-targeted local therapy as an effective means of improving wound healing,” Dr. Davis concluded.

Nonhealing wounds in patients with diabetes are a major cause of morbidity and mortality in the United States and are increasing at an alarming rate. Equally concerning, the current “standard of care” leaves 70% of diabetic wounds unhealed. Given this substantial impact on patient outcomes and health care expenditure, a critical unmet need exists for improved understanding of the pathophysiology of diabetic wounds to develop effective treatments.

This year’s SVS Foundation’s Resident Research Award is being presented to Frank M. Davis, MD, of the University of Michigan, Ann Arbor, for his research on the epigenetic regulation of the prostaglandin pathway in macrophages during type 2 diabetic wound healing. Dr. Davis, and his mentor Katherine Gallagher, MD, also from the University of Michigan, investigated how impairments in the innate immune system in patients with diabetes promote chronic inflammation and impair wound healing.

Dr. Davis will present his award-winning research in the von Liebig Forum, Thursday, June 13, discussing the role of specific epigenetic enzymes in the dictation of macrophage phenotype in wound tissue. The talk will cover how diabetes alters those enzymes to influence a deleterious phenotype that promotes inflammation and delays wound healing. “Our laboratory specifically looks at the role of monocytes/macrophages in the inflammatory phase of wound healing and how perturbation in the local environment – such as those seen in diabetes – affects monocyte/macrophage phenotype and ultimately wound healing” said Dr. Davis.

The talk will specifically cover the cyclo-oxygenase (COX)-2/prostaglandin E₂ (PGE₂) axis. Using both a murine model and human wound samples Dr. Davis demonstrates that PGE₂ is substantially elevated in diabetic wound macrophages. Further, aberrant PGE₂ production in diabetic macrophages depended on epigenetic alterations to key enzymes in the PGE₂ pathway.

Specifically, MLL1, a histone methyltransferase, increased H3K4 trimethylation resulting in upregulation of PGE₂ in diabetic wound macrophages. Additionally, the authors found that augmentation to miR-29b and DNA methyltransferases in diabetic macrophage result in increased COX-2 expression. Overall, the increased COX-2/PGE₂ production in diabetic macrophages impairs bacterial killing, predisposing diabetic wounds to chronic infection.

“Our research provides insight into the prostaglandin E₂ axis and its role in macrophage inflammation, which has previously been an unrecognized pathway leading to delayed diabetic wound healing” added Dr. Gallagher.

Finally, in his presentation, Dr. Davis will discuss translational therapies as inhibition of the PGE₂ pathway through macrophage targeted nanoparticles decreased diabetic inflammation and improved healing. “Together, our results indicate the COX-2/PGE₂ pathway is a critical regulator of macrophage phenotype and impaired diabetic wound healing. This work identifies therapeutic targets for negating dysregulated inflammation in diabetic wounds and identifies macrophage-targeted local therapy as an effective means of improving wound healing,” Dr. Davis concluded.

LJUBLJANA, SLOVENIA – Pediatricians in the south of England are so concerned about the recent national increase in the diagnosis of syphilis in adults and its ramifications for neonates that they’ve ditched the traditional TORCH newborn screen because the acronym doesn’t specifically remind clinicians to think about congenital syphilis, Mildred A. Iro, MD, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“We recommend a relabeling of the TORCH screen to ‘the congenital infection screen’ in order to include syphilis, which is now our local practice,” explained Dr. Iro of the University of Southampton (England).

She highlighted salient features of three recent cases of congenital syphilis managed at Southampton Children’s Hospital.

“The key message that we’d like to share is that we just need to be more aware about congenital syphilis. Retest mothers if their risk factor status changes, and test suspected infants and children,” Dr. Iro said.

As a practical matter, however, even though current guidelines recommend retesting mothers whose risk factor status becomes heightened following an initial negative syphilis serology result early in pregnancy, clinicians often are unaware that a mother’s risk status has changed. And retesting all mothers during pregnancy isn’t attractive from a cost-benefit standpoint. This makes scrupulous screening of newborns all the more important. And yet TORCH, which stands for Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes infections, isn’t an acronym that promotes awareness of congenital syphilis, a disease which occupies an obscure position in TORCH under the “O” for “Other” heading. That’s why the term “congenital infection screen” has become the new norm in the south of England, she explained.

However, one pediatrician who didn’t consider congenital infection screen to be an improvement in terminology over TORCH had an alternative suggestion, which struck a favorable chord with his fellow audience members: Simply change the acronym to TORCHS, with the S standing for syphilis.

Dr. Iro noted that two of the three affected children were diagnosed at age 7-8 weeks. The third wasn’t diagnosed until age 15 months, when the mother tested positive for syphilis in a subsequent pregnancy. As is typical of the disease known as “the great masquerader,” while all three of the affected children were unwell early in infancy, they presented with a wide range of symptoms. Among the more prominent features were prolonged irritability, respiratory distress, odd rashes, anemia, hepatomegaly, and tachypnea. One infant had reduced movement and pain in one arm.

All three children underwent extensive testing. None had neurosyphilis. All achieved good outcomes on standard guideline-directed therapy.

As for the mothers, they were aged 19, 21, and 23 years when diagnosed with syphilis. All were Caucasian, and antenatal blood testing was negative in all three. None were retested during pregnancy, even though two of them had a male partner or former partner who was positive for syphilis, and the partner of the third disclosed to her that he had sex with men.

At diagnosis, all three women had a strongly positive Treponema pallidum particle agglutination assay, a high rapid plasma reagin, and a positive syphilis IgM assay.

Dr. Iro reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – Pediatricians in the south of England are so concerned about the recent national increase in the diagnosis of syphilis in adults and its ramifications for neonates that they’ve ditched the traditional TORCH newborn screen because the acronym doesn’t specifically remind clinicians to think about congenital syphilis, Mildred A. Iro, MD, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“We recommend a relabeling of the TORCH screen to ‘the congenital infection screen’ in order to include syphilis, which is now our local practice,” explained Dr. Iro of the University of Southampton (England).

She highlighted salient features of three recent cases of congenital syphilis managed at Southampton Children’s Hospital.

“The key message that we’d like to share is that we just need to be more aware about congenital syphilis. Retest mothers if their risk factor status changes, and test suspected infants and children,” Dr. Iro said.

As a practical matter, however, even though current guidelines recommend retesting mothers whose risk factor status becomes heightened following an initial negative syphilis serology result early in pregnancy, clinicians often are unaware that a mother’s risk status has changed. And retesting all mothers during pregnancy isn’t attractive from a cost-benefit standpoint. This makes scrupulous screening of newborns all the more important. And yet TORCH, which stands for Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes infections, isn’t an acronym that promotes awareness of congenital syphilis, a disease which occupies an obscure position in TORCH under the “O” for “Other” heading. That’s why the term “congenital infection screen” has become the new norm in the south of England, she explained.

However, one pediatrician who didn’t consider congenital infection screen to be an improvement in terminology over TORCH had an alternative suggestion, which struck a favorable chord with his fellow audience members: Simply change the acronym to TORCHS, with the S standing for syphilis.

Dr. Iro noted that two of the three affected children were diagnosed at age 7-8 weeks. The third wasn’t diagnosed until age 15 months, when the mother tested positive for syphilis in a subsequent pregnancy. As is typical of the disease known as “the great masquerader,” while all three of the affected children were unwell early in infancy, they presented with a wide range of symptoms. Among the more prominent features were prolonged irritability, respiratory distress, odd rashes, anemia, hepatomegaly, and tachypnea. One infant had reduced movement and pain in one arm.

All three children underwent extensive testing. None had neurosyphilis. All achieved good outcomes on standard guideline-directed therapy.

As for the mothers, they were aged 19, 21, and 23 years when diagnosed with syphilis. All were Caucasian, and antenatal blood testing was negative in all three. None were retested during pregnancy, even though two of them had a male partner or former partner who was positive for syphilis, and the partner of the third disclosed to her that he had sex with men.

At diagnosis, all three women had a strongly positive Treponema pallidum particle agglutination assay, a high rapid plasma reagin, and a positive syphilis IgM assay.

Dr. Iro reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

LJUBLJANA, SLOVENIA – Pediatricians in the south of England are so concerned about the recent national increase in the diagnosis of syphilis in adults and its ramifications for neonates that they’ve ditched the traditional TORCH newborn screen because the acronym doesn’t specifically remind clinicians to think about congenital syphilis, Mildred A. Iro, MD, PhD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

“We recommend a relabeling of the TORCH screen to ‘the congenital infection screen’ in order to include syphilis, which is now our local practice,” explained Dr. Iro of the University of Southampton (England).

She highlighted salient features of three recent cases of congenital syphilis managed at Southampton Children’s Hospital.

“The key message that we’d like to share is that we just need to be more aware about congenital syphilis. Retest mothers if their risk factor status changes, and test suspected infants and children,” Dr. Iro said.

As a practical matter, however, even though current guidelines recommend retesting mothers whose risk factor status becomes heightened following an initial negative syphilis serology result early in pregnancy, clinicians often are unaware that a mother’s risk status has changed. And retesting all mothers during pregnancy isn’t attractive from a cost-benefit standpoint. This makes scrupulous screening of newborns all the more important. And yet TORCH, which stands for Toxoplasmosis, Other, Rubella, Cytomegalovirus, and Herpes infections, isn’t an acronym that promotes awareness of congenital syphilis, a disease which occupies an obscure position in TORCH under the “O” for “Other” heading. That’s why the term “congenital infection screen” has become the new norm in the south of England, she explained.

However, one pediatrician who didn’t consider congenital infection screen to be an improvement in terminology over TORCH had an alternative suggestion, which struck a favorable chord with his fellow audience members: Simply change the acronym to TORCHS, with the S standing for syphilis.

Dr. Iro noted that two of the three affected children were diagnosed at age 7-8 weeks. The third wasn’t diagnosed until age 15 months, when the mother tested positive for syphilis in a subsequent pregnancy. As is typical of the disease known as “the great masquerader,” while all three of the affected children were unwell early in infancy, they presented with a wide range of symptoms. Among the more prominent features were prolonged irritability, respiratory distress, odd rashes, anemia, hepatomegaly, and tachypnea. One infant had reduced movement and pain in one arm.

All three children underwent extensive testing. None had neurosyphilis. All achieved good outcomes on standard guideline-directed therapy.

As for the mothers, they were aged 19, 21, and 23 years when diagnosed with syphilis. All were Caucasian, and antenatal blood testing was negative in all three. None were retested during pregnancy, even though two of them had a male partner or former partner who was positive for syphilis, and the partner of the third disclosed to her that he had sex with men.

At diagnosis, all three women had a strongly positive Treponema pallidum particle agglutination assay, a high rapid plasma reagin, and a positive syphilis IgM assay.

Dr. Iro reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

As I watched my grandson and his team warm up for their Saturday morning lacrosse game, a long parade of mostly purple-shirted adults and children of all ages began to weave its way around the periphery of the athletic field complex. A quick reading of the hand-lettered and machine-printed shirts made it clear that I was watching a charity walk for cystic fibrosis. There must have been several hundred walkers strolling by, laughing and chatting with one another. It lent a festive atmosphere to the park. I suspect that for most of the participants this was not their first fundraising event for cystic fibrosis.

Salima Senyavskaya/iStock Unreleased

The motley mix of marchers probably included several handfuls of parents of children with cystic fibrosis. I wonder how many of those parents realized how fortunate they were. Cystic fibrosis isn’t a great diagnosis. But at least it is a diagnosis, and with the diagnosis comes a community.

Reading a front-page article on DNA testing in a recent Wall Street Journal issue had primed me to reconsider how even an unfortunate diagnosis can be extremely valuable for a family (“The Unfulfilled Promise of DNA Testing,” by Amy Dockser Marcus, May 18, 2019).The focus of the article was on the confusion and disappointment that are the predictable consequences of our current inability to accurately correlate genetic code “mistakes” with phenotypic abnormalities. Of course there have been a few successes, but we aren’t even close to the promise that many have predicted in the wake of sequencing the human genome. The family featured in the article has a ridden roller coaster ride through two failed attributions of genetic syndromes that appeared to provide their now 8-year-old daughter with a diagnosis for her epilepsy and developmental delay.

In each case, the mother had searched out other families with children who shared the same genetic code errors. She formed support groups and created foundations to promote research for these rare disorders only to learn that her daughter didn’t really fit into the phenotype exhibited by the other children. As the article indicates this mother had “found a genetic home, only to feel that she no longer belonged.” She had made “intense friendships” and for “2 years, the community was her main emotional support.” Since the second diagnosis has evaporated, she has struggled with whether to remain with that community, having already left one behind. She has been encouraged to stay involved by another mother whose son does have the diagnosis. Understandably, she is still seeking the correct diagnosis, and I suspect will form or join a new community when she finds it.

We all want to belong to a community. Having a diagnosis, even if there is no reasonable hope for cure in the near future, is the ticket into that community. And with that ticket comes the opportunity to share the frustrations and difficulties unique to children with that diagnosis, and the comfort that there are other people who look, behave, and feel the way we do. We hear repeatedly about the value of diversity and how wonderful it is to be all inclusive. And certainly we should continue to be as accepting as we can of people who are different. But the truth is that we will always fall short because we seem to be hardwired to notice what is different. And the power of the longing to belong is often stronger than our will to be inclusive.

The revolution that resulted in the disappearance of the label “mental retardation” and the widespread adoption of the diagnosis of autism are examples of how a community can form around a diagnosis. But not every child who is labeled as autistic will actually fit the diagnosis. Yet even a less-than-perfect attribution can provide a place where a family and a patient can feel that they belong.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

As I watched my grandson and his team warm up for their Saturday morning lacrosse game, a long parade of mostly purple-shirted adults and children of all ages began to weave its way around the periphery of the athletic field complex. A quick reading of the hand-lettered and machine-printed shirts made it clear that I was watching a charity walk for cystic fibrosis. There must have been several hundred walkers strolling by, laughing and chatting with one another. It lent a festive atmosphere to the park. I suspect that for most of the participants this was not their first fundraising event for cystic fibrosis.

Salima Senyavskaya/iStock Unreleased

The motley mix of marchers probably included several handfuls of parents of children with cystic fibrosis. I wonder how many of those parents realized how fortunate they were. Cystic fibrosis isn’t a great diagnosis. But at least it is a diagnosis, and with the diagnosis comes a community.

Reading a front-page article on DNA testing in a recent Wall Street Journal issue had primed me to reconsider how even an unfortunate diagnosis can be extremely valuable for a family (“The Unfulfilled Promise of DNA Testing,” by Amy Dockser Marcus, May 18, 2019).The focus of the article was on the confusion and disappointment that are the predictable consequences of our current inability to accurately correlate genetic code “mistakes” with phenotypic abnormalities. Of course there have been a few successes, but we aren’t even close to the promise that many have predicted in the wake of sequencing the human genome. The family featured in the article has a ridden roller coaster ride through two failed attributions of genetic syndromes that appeared to provide their now 8-year-old daughter with a diagnosis for her epilepsy and developmental delay.

In each case, the mother had searched out other families with children who shared the same genetic code errors. She formed support groups and created foundations to promote research for these rare disorders only to learn that her daughter didn’t really fit into the phenotype exhibited by the other children. As the article indicates this mother had “found a genetic home, only to feel that she no longer belonged.” She had made “intense friendships” and for “2 years, the community was her main emotional support.” Since the second diagnosis has evaporated, she has struggled with whether to remain with that community, having already left one behind. She has been encouraged to stay involved by another mother whose son does have the diagnosis. Understandably, she is still seeking the correct diagnosis, and I suspect will form or join a new community when she finds it.

We all want to belong to a community. Having a diagnosis, even if there is no reasonable hope for cure in the near future, is the ticket into that community. And with that ticket comes the opportunity to share the frustrations and difficulties unique to children with that diagnosis, and the comfort that there are other people who look, behave, and feel the way we do. We hear repeatedly about the value of diversity and how wonderful it is to be all inclusive. And certainly we should continue to be as accepting as we can of people who are different. But the truth is that we will always fall short because we seem to be hardwired to notice what is different. And the power of the longing to belong is often stronger than our will to be inclusive.

The revolution that resulted in the disappearance of the label “mental retardation” and the widespread adoption of the diagnosis of autism are examples of how a community can form around a diagnosis. But not every child who is labeled as autistic will actually fit the diagnosis. Yet even a less-than-perfect attribution can provide a place where a family and a patient can feel that they belong.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

As I watched my grandson and his team warm up for their Saturday morning lacrosse game, a long parade of mostly purple-shirted adults and children of all ages began to weave its way around the periphery of the athletic field complex. A quick reading of the hand-lettered and machine-printed shirts made it clear that I was watching a charity walk for cystic fibrosis. There must have been several hundred walkers strolling by, laughing and chatting with one another. It lent a festive atmosphere to the park. I suspect that for most of the participants this was not their first fundraising event for cystic fibrosis.

Salima Senyavskaya/iStock Unreleased

The motley mix of marchers probably included several handfuls of parents of children with cystic fibrosis. I wonder how many of those parents realized how fortunate they were. Cystic fibrosis isn’t a great diagnosis. But at least it is a diagnosis, and with the diagnosis comes a community.

Reading a front-page article on DNA testing in a recent Wall Street Journal issue had primed me to reconsider how even an unfortunate diagnosis can be extremely valuable for a family (“The Unfulfilled Promise of DNA Testing,” by Amy Dockser Marcus, May 18, 2019).The focus of the article was on the confusion and disappointment that are the predictable consequences of our current inability to accurately correlate genetic code “mistakes” with phenotypic abnormalities. Of course there have been a few successes, but we aren’t even close to the promise that many have predicted in the wake of sequencing the human genome. The family featured in the article has a ridden roller coaster ride through two failed attributions of genetic syndromes that appeared to provide their now 8-year-old daughter with a diagnosis for her epilepsy and developmental delay.

In each case, the mother had searched out other families with children who shared the same genetic code errors. She formed support groups and created foundations to promote research for these rare disorders only to learn that her daughter didn’t really fit into the phenotype exhibited by the other children. As the article indicates this mother had “found a genetic home, only to feel that she no longer belonged.” She had made “intense friendships” and for “2 years, the community was her main emotional support.” Since the second diagnosis has evaporated, she has struggled with whether to remain with that community, having already left one behind. She has been encouraged to stay involved by another mother whose son does have the diagnosis. Understandably, she is still seeking the correct diagnosis, and I suspect will form or join a new community when she finds it.

We all want to belong to a community. Having a diagnosis, even if there is no reasonable hope for cure in the near future, is the ticket into that community. And with that ticket comes the opportunity to share the frustrations and difficulties unique to children with that diagnosis, and the comfort that there are other people who look, behave, and feel the way we do. We hear repeatedly about the value of diversity and how wonderful it is to be all inclusive. And certainly we should continue to be as accepting as we can of people who are different. But the truth is that we will always fall short because we seem to be hardwired to notice what is different. And the power of the longing to belong is often stronger than our will to be inclusive.

The revolution that resulted in the disappearance of the label “mental retardation” and the widespread adoption of the diagnosis of autism are examples of how a community can form around a diagnosis. But not every child who is labeled as autistic will actually fit the diagnosis. Yet even a less-than-perfect attribution can provide a place where a family and a patient can feel that they belong.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

The Centers for Disease Control and Prevention has created a first-of-its-kind interactive training module to help physicians both recognize and diagnose Rocky Mountain spotted fever (RMSF).

CDC

A record number of cases of RMSF were reported to the CDC in 2017 (6,248, up from 4,269 in 2016), but less than 1% of those cases had sufficient laboratory evidence to be confirmed. The CDC education module includes scenarios based on real cases to aid providers in recognizing RMSF and differentiating it from similar diseases. CME is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators.

The standard treatment for people of all ages with RMSF is doxycycline, preferably within the first 5 days of illness to prevent disability and death. The disease initially presents with nonspecific symptoms such as fever, headache, or rash, but if left untreated, patients may require the amputation of fingers, toes, or limbs because of low blood flow; heart and lung specialty care; and ICU management. About 20% of untreated cases are fatal; half of these deaths occur within 8 days of initial presentation.

“Rocky Mountain spotted fever can be deadly if not treated early – yet cases often go unrecognized because the signs and symptoms are similar to those of many other diseases. With tickborne diseases on the rise in the U.S., this training will better equip health care providers to identify, diagnose, and treat this potentially fatal disease,” said CDC director Robert R. Redfield, MD.

Find the full press release on the CDC website.

lfranki@mdedge.com

The Centers for Disease Control and Prevention has created a first-of-its-kind interactive training module to help physicians both recognize and diagnose Rocky Mountain spotted fever (RMSF).

CDC

A record number of cases of RMSF were reported to the CDC in 2017 (6,248, up from 4,269 in 2016), but less than 1% of those cases had sufficient laboratory evidence to be confirmed. The CDC education module includes scenarios based on real cases to aid providers in recognizing RMSF and differentiating it from similar diseases. CME is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators.

The standard treatment for people of all ages with RMSF is doxycycline, preferably within the first 5 days of illness to prevent disability and death. The disease initially presents with nonspecific symptoms such as fever, headache, or rash, but if left untreated, patients may require the amputation of fingers, toes, or limbs because of low blood flow; heart and lung specialty care; and ICU management. About 20% of untreated cases are fatal; half of these deaths occur within 8 days of initial presentation.

“Rocky Mountain spotted fever can be deadly if not treated early – yet cases often go unrecognized because the signs and symptoms are similar to those of many other diseases. With tickborne diseases on the rise in the U.S., this training will better equip health care providers to identify, diagnose, and treat this potentially fatal disease,” said CDC director Robert R. Redfield, MD.

Find the full press release on the CDC website.

lfranki@mdedge.com

The Centers for Disease Control and Prevention has created a first-of-its-kind interactive training module to help physicians both recognize and diagnose Rocky Mountain spotted fever (RMSF).

CDC

A record number of cases of RMSF were reported to the CDC in 2017 (6,248, up from 4,269 in 2016), but less than 1% of those cases had sufficient laboratory evidence to be confirmed. The CDC education module includes scenarios based on real cases to aid providers in recognizing RMSF and differentiating it from similar diseases. CME is available for physicians, nurse practitioners, physician assistants, veterinarians, nurses, epidemiologists, public health professionals, educators, and health communicators.

The standard treatment for people of all ages with RMSF is doxycycline, preferably within the first 5 days of illness to prevent disability and death. The disease initially presents with nonspecific symptoms such as fever, headache, or rash, but if left untreated, patients may require the amputation of fingers, toes, or limbs because of low blood flow; heart and lung specialty care; and ICU management. About 20% of untreated cases are fatal; half of these deaths occur within 8 days of initial presentation.

“Rocky Mountain spotted fever can be deadly if not treated early – yet cases often go unrecognized because the signs and symptoms are similar to those of many other diseases. With tickborne diseases on the rise in the U.S., this training will better equip health care providers to identify, diagnose, and treat this potentially fatal disease,” said CDC director Robert R. Redfield, MD.

Find the full press release on the CDC website.

lfranki@mdedge.com

Researchers have found they can screen pediatric cancer patients for genetic alterations and match those patients to appropriate targeted therapies.

Thus far, 24% of the patients screened have been matched and assigned to a treatment, and 10% have been enrolled on treatment protocols.

The patients were screened and matched as part of the National Cancer Institute–Children’s Oncology Group Pediatric MATCH (Molecular Analysis for Therapy Choice) trial.

Results from this trial are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Donald Williams Parsons, MD, PhD, of Baylor College of Medicine in Houston, Tex., presented some results at a press briefing in advance of the meeting. “[T]he last 10 years have been an incredible time in terms of learning more about the genetics and underlying molecular basis of both adult and pediatric cancers,” Dr. Parsons said.

He pointed out, however, that it is not yet known if this information will be useful in guiding the treatment of pediatric cancers. Specifically, how many pediatric patients can be matched to targeted therapies, and how effective will those therapies be?

The Pediatric MATCH trial (NCT03155620) was developed to answer these questions. Researchers plan to enroll at least 1,000 patients in this trial. Patients are eligible if they are 1-21 years of age and have refractory or recurrent solid tumors, non-Hodgkin lymphomas, or histiocytic disorders.

After patients are enrolled in the trial, their tumor samples undergo DNA and RNA sequencing, and the results are used to match each patient to a targeted therapy. At present, the trial can match patients to one of 10 drugs:

• larotrectinib (targeting NTRK fusions).
• erdafitinib (targeting FGFR1/2/3/4).
• tazemetostat (targeting EZH2 or members of the SWI/SNF complex).
• LY3023414 (targeting the PI3K/MTOR pathway).
• selumetinib (targeting the MAPK pathway).
• ensartinib (targeting ALK or ROS1).
• vemurafenib (targeting BRAF V600 mutations).
• olaparib (targeting defects in DNA damage repair).
• palbociclib (targeting alterations in cell cycle genes).
• ulixertinib (targeting MAPK pathway mutations).

Early results

From July 2017 through December 2018, 422 patients were enrolled in the trial. The patients had more than 60 different diagnoses, including brain tumors, sarcomas, neuroblastoma, renal and liver cancers, and other malignancies.

The researchers received tumor samples from 390 patients, attempted sequencing of 370 samples (95%), and completed sequencing of 357 samples (92%).

A treatment target was found in 112 (29%) patients, 95 (24%) of those patients were assigned to a treatment, and 39 (10%) were enrolled in a protocol. The median turnaround time from sample receipt to treatment assignment was 15 days.

“In addition to the sequencing being successful, the patients are being matched to the different treatments,” Dr. Parsons said. He added that the study is ongoing, so more of the matched and assigned patients will be enrolled in protocols in the future.

Dr. Parsons also presented results by tumor type. A targetable alteration was identified in 26% (67/255) of all non–central nervous system solid tumors, 13% (10/75) of osteosarcomas, 50% (18/36) of rhabdomyosarcomas, 21% (7/33) of Ewing sarcomas, 25% (9/36) of other sarcomas, 19% (5/26) of renal cancers, 16% (3/19) of carcinomas, 44% (8/18) of neuroblastomas, 43% (3/7) of liver cancers, and 29% (4/14) of “other” tumors.

Drilling down further, Dr. Parsons presented details on specific alterations in one cancer type: astrocytomas. Targetable alterations were found in 74% (29/39) of astrocytomas. This includes NF1 mutations (18%), BRAF V600E (15%), FGFR1 fusions/mutations (10%), BRAF fusions (10%), PIK3CA mutations (8%), NRAS/KRAS mutations (5%), and other alterations.

“Pretty remarkably, in this one diagnosis, there are patients who have been matched to nine of the ten different treatment arms,” Dr. Parsons said. “This study is allowing us to evaluate targeted therapies – specific types of investigational drugs – in patients with many different cancer types, some common, some very rare. So, hopefully, we can study these agents and identify signals of activity where some of these drugs may work for our patients.”

The Pediatric MATCH trial is sponsored by the National Cancer Institute. Dr. Parsons has patents, royalties, and other intellectual property related to genes discovered through sequencing of several adult cancer types.

jensmith@mdedge.com

SOURCE: Parsons DW et al. ASCO 2019, Abstract 10011.

Researchers have found they can screen pediatric cancer patients for genetic alterations and match those patients to appropriate targeted therapies.

Thus far, 24% of the patients screened have been matched and assigned to a treatment, and 10% have been enrolled on treatment protocols.

The patients were screened and matched as part of the National Cancer Institute–Children’s Oncology Group Pediatric MATCH (Molecular Analysis for Therapy Choice) trial.

Results from this trial are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Donald Williams Parsons, MD, PhD, of Baylor College of Medicine in Houston, Tex., presented some results at a press briefing in advance of the meeting. “[T]he last 10 years have been an incredible time in terms of learning more about the genetics and underlying molecular basis of both adult and pediatric cancers,” Dr. Parsons said.

He pointed out, however, that it is not yet known if this information will be useful in guiding the treatment of pediatric cancers. Specifically, how many pediatric patients can be matched to targeted therapies, and how effective will those therapies be?

The Pediatric MATCH trial (NCT03155620) was developed to answer these questions. Researchers plan to enroll at least 1,000 patients in this trial. Patients are eligible if they are 1-21 years of age and have refractory or recurrent solid tumors, non-Hodgkin lymphomas, or histiocytic disorders.

After patients are enrolled in the trial, their tumor samples undergo DNA and RNA sequencing, and the results are used to match each patient to a targeted therapy. At present, the trial can match patients to one of 10 drugs:

• larotrectinib (targeting NTRK fusions).
• erdafitinib (targeting FGFR1/2/3/4).
• tazemetostat (targeting EZH2 or members of the SWI/SNF complex).
• LY3023414 (targeting the PI3K/MTOR pathway).
• selumetinib (targeting the MAPK pathway).
• ensartinib (targeting ALK or ROS1).
• vemurafenib (targeting BRAF V600 mutations).
• olaparib (targeting defects in DNA damage repair).
• palbociclib (targeting alterations in cell cycle genes).
• ulixertinib (targeting MAPK pathway mutations).

Early results

From July 2017 through December 2018, 422 patients were enrolled in the trial. The patients had more than 60 different diagnoses, including brain tumors, sarcomas, neuroblastoma, renal and liver cancers, and other malignancies.

The researchers received tumor samples from 390 patients, attempted sequencing of 370 samples (95%), and completed sequencing of 357 samples (92%).

A treatment target was found in 112 (29%) patients, 95 (24%) of those patients were assigned to a treatment, and 39 (10%) were enrolled in a protocol. The median turnaround time from sample receipt to treatment assignment was 15 days.

“In addition to the sequencing being successful, the patients are being matched to the different treatments,” Dr. Parsons said. He added that the study is ongoing, so more of the matched and assigned patients will be enrolled in protocols in the future.

Dr. Parsons also presented results by tumor type. A targetable alteration was identified in 26% (67/255) of all non–central nervous system solid tumors, 13% (10/75) of osteosarcomas, 50% (18/36) of rhabdomyosarcomas, 21% (7/33) of Ewing sarcomas, 25% (9/36) of other sarcomas, 19% (5/26) of renal cancers, 16% (3/19) of carcinomas, 44% (8/18) of neuroblastomas, 43% (3/7) of liver cancers, and 29% (4/14) of “other” tumors.

Drilling down further, Dr. Parsons presented details on specific alterations in one cancer type: astrocytomas. Targetable alterations were found in 74% (29/39) of astrocytomas. This includes NF1 mutations (18%), BRAF V600E (15%), FGFR1 fusions/mutations (10%), BRAF fusions (10%), PIK3CA mutations (8%), NRAS/KRAS mutations (5%), and other alterations.

“Pretty remarkably, in this one diagnosis, there are patients who have been matched to nine of the ten different treatment arms,” Dr. Parsons said. “This study is allowing us to evaluate targeted therapies – specific types of investigational drugs – in patients with many different cancer types, some common, some very rare. So, hopefully, we can study these agents and identify signals of activity where some of these drugs may work for our patients.”

The Pediatric MATCH trial is sponsored by the National Cancer Institute. Dr. Parsons has patents, royalties, and other intellectual property related to genes discovered through sequencing of several adult cancer types.

jensmith@mdedge.com

SOURCE: Parsons DW et al. ASCO 2019, Abstract 10011.

Researchers have found they can screen pediatric cancer patients for genetic alterations and match those patients to appropriate targeted therapies.

Thus far, 24% of the patients screened have been matched and assigned to a treatment, and 10% have been enrolled on treatment protocols.

The patients were screened and matched as part of the National Cancer Institute–Children’s Oncology Group Pediatric MATCH (Molecular Analysis for Therapy Choice) trial.

Results from this trial are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Donald Williams Parsons, MD, PhD, of Baylor College of Medicine in Houston, Tex., presented some results at a press briefing in advance of the meeting. “[T]he last 10 years have been an incredible time in terms of learning more about the genetics and underlying molecular basis of both adult and pediatric cancers,” Dr. Parsons said.

He pointed out, however, that it is not yet known if this information will be useful in guiding the treatment of pediatric cancers. Specifically, how many pediatric patients can be matched to targeted therapies, and how effective will those therapies be?

The Pediatric MATCH trial (NCT03155620) was developed to answer these questions. Researchers plan to enroll at least 1,000 patients in this trial. Patients are eligible if they are 1-21 years of age and have refractory or recurrent solid tumors, non-Hodgkin lymphomas, or histiocytic disorders.

After patients are enrolled in the trial, their tumor samples undergo DNA and RNA sequencing, and the results are used to match each patient to a targeted therapy. At present, the trial can match patients to one of 10 drugs:

• larotrectinib (targeting NTRK fusions).
• erdafitinib (targeting FGFR1/2/3/4).
• tazemetostat (targeting EZH2 or members of the SWI/SNF complex).
• LY3023414 (targeting the PI3K/MTOR pathway).
• selumetinib (targeting the MAPK pathway).
• ensartinib (targeting ALK or ROS1).
• vemurafenib (targeting BRAF V600 mutations).
• olaparib (targeting defects in DNA damage repair).
• palbociclib (targeting alterations in cell cycle genes).
• ulixertinib (targeting MAPK pathway mutations).

Early results

From July 2017 through December 2018, 422 patients were enrolled in the trial. The patients had more than 60 different diagnoses, including brain tumors, sarcomas, neuroblastoma, renal and liver cancers, and other malignancies.

The researchers received tumor samples from 390 patients, attempted sequencing of 370 samples (95%), and completed sequencing of 357 samples (92%).

A treatment target was found in 112 (29%) patients, 95 (24%) of those patients were assigned to a treatment, and 39 (10%) were enrolled in a protocol. The median turnaround time from sample receipt to treatment assignment was 15 days.

“In addition to the sequencing being successful, the patients are being matched to the different treatments,” Dr. Parsons said. He added that the study is ongoing, so more of the matched and assigned patients will be enrolled in protocols in the future.

Dr. Parsons also presented results by tumor type. A targetable alteration was identified in 26% (67/255) of all non–central nervous system solid tumors, 13% (10/75) of osteosarcomas, 50% (18/36) of rhabdomyosarcomas, 21% (7/33) of Ewing sarcomas, 25% (9/36) of other sarcomas, 19% (5/26) of renal cancers, 16% (3/19) of carcinomas, 44% (8/18) of neuroblastomas, 43% (3/7) of liver cancers, and 29% (4/14) of “other” tumors.

Drilling down further, Dr. Parsons presented details on specific alterations in one cancer type: astrocytomas. Targetable alterations were found in 74% (29/39) of astrocytomas. This includes NF1 mutations (18%), BRAF V600E (15%), FGFR1 fusions/mutations (10%), BRAF fusions (10%), PIK3CA mutations (8%), NRAS/KRAS mutations (5%), and other alterations.

“Pretty remarkably, in this one diagnosis, there are patients who have been matched to nine of the ten different treatment arms,” Dr. Parsons said. “This study is allowing us to evaluate targeted therapies – specific types of investigational drugs – in patients with many different cancer types, some common, some very rare. So, hopefully, we can study these agents and identify signals of activity where some of these drugs may work for our patients.”

The Pediatric MATCH trial is sponsored by the National Cancer Institute. Dr. Parsons has patents, royalties, and other intellectual property related to genes discovered through sequencing of several adult cancer types.

jensmith@mdedge.com

SOURCE: Parsons DW et al. ASCO 2019, Abstract 10011.

BIRMINGHAM, ENGLAND – Proinflammatory diets are associated with increased C-reactive protein (CRP) and subsequent rheumatoid arthritis (RA), according to combined data from the European Prospective Investigation of Cancer and Nutrition (EPIC) and Norfolk Arthritis Register (NOAR).

Sara Freeman/MDedge News

“There has always been a debate around this topic,” Max Yates, MBBS, PhD, said at the annual conference of the British Society for Rheumatology. “A quick online search will reveal a plethora of texts claiming to give definitive or the best advice for arthritis” and diet, he said, often from “questionable experts.”

“I think we’re all interested in diet,” observed Dr. Yates, of the University of East Anglia in Norwich (England), and “although the association between diet and arthritis is open to debate, previous studies have shown an association with those who have a lower intake of vitamin C and fiber.” The problem is one of credibility, he noted, so this was something that the NOAR investigators decided to look into with data from the Dietary Inflammatory Index (DII) collected from the EPIC cohort.

The DII is a literature-based, population-derived tool that has been used to determine the inflammatory potential of diet, Dr. Yates explained. Data show that inflammatory diets are is associated with increased levels of inflammatory markers including C-reactive protein (CRP) and interleukin (IL)-6. These diets include items such as trans and saturated fats, and fats from animal protein versus more anti-inflammatory items such as black tea, thyme, turmeric, and saffron.

“We are fortunate that NOAR is in the same geographic location as EPIC,” Dr. Yates said, and the two cohorts have been running alongside each other since the early 1990s. While NOAR has been collecting data on incident inflammatory polyarthritis since 1989, EPIC has been “intensively” collecting information on dietary and lifestyle factors and blood samples from its participants since 1993.

EPIC investigators have been “trailblazers” in recording of dietary data, Dr. Yates said. First using paper-based questionnaires and now smartphone apps that allow people to upload photos of what they are eating. Data are linked to both primary care practice and hospital records.

For the present study, data on 159 patients who participated in both NOAR and EPIC were used. Participants had RA according to the 2010 American College of Rheumatology criteria and had an average disease onset of 7 years after enrollment into NOAR and EPIC.

“Quite pleasingly, the dietary inflammatory index scores were associated with high-sensitivity CRP taken at baseline enrollment in 1993 to 1997, further validating the index again within another population,” Dr. Yates said.

Results showed that there was a significant association between the baseline DII score and subsequent development of RA, with an odds ratio of 1.90 comparing individuals with the highest and lowest DII scores (P less than .01).

When cases were matched by age, sex, and body mass index, however, there was only a trend for an association between inflammatory diets and RA onset. “We hope to identify more patients within EPIC to strengthen this association,” Dr. Yates said.

The results are consistent with data from the Nurses’ Health Study, Dr. Yates noted, adding that future research is needed to address whether dietary modification can demonstrate causality.

“Diet is one of the modifiable risk factors that we can use to tackle RA, and I think it’s about time we as a community take over this area and gave definitive advice.”

Dr. Yates presented the work on behalf of PhD student Ellie Sayer. Neither Dr. Yates nor Ms. Sayer had any conflicts of interests to disclose.

SOURCE: Sayer E et al. Rheumatology. 2019;58(suppl 3), Abstract 014.

BIRMINGHAM, ENGLAND – Proinflammatory diets are associated with increased C-reactive protein (CRP) and subsequent rheumatoid arthritis (RA), according to combined data from the European Prospective Investigation of Cancer and Nutrition (EPIC) and Norfolk Arthritis Register (NOAR).

Sara Freeman/MDedge News

“There has always been a debate around this topic,” Max Yates, MBBS, PhD, said at the annual conference of the British Society for Rheumatology. “A quick online search will reveal a plethora of texts claiming to give definitive or the best advice for arthritis” and diet, he said, often from “questionable experts.”

“I think we’re all interested in diet,” observed Dr. Yates, of the University of East Anglia in Norwich (England), and “although the association between diet and arthritis is open to debate, previous studies have shown an association with those who have a lower intake of vitamin C and fiber.” The problem is one of credibility, he noted, so this was something that the NOAR investigators decided to look into with data from the Dietary Inflammatory Index (DII) collected from the EPIC cohort.

The DII is a literature-based, population-derived tool that has been used to determine the inflammatory potential of diet, Dr. Yates explained. Data show that inflammatory diets are is associated with increased levels of inflammatory markers including C-reactive protein (CRP) and interleukin (IL)-6. These diets include items such as trans and saturated fats, and fats from animal protein versus more anti-inflammatory items such as black tea, thyme, turmeric, and saffron.

“We are fortunate that NOAR is in the same geographic location as EPIC,” Dr. Yates said, and the two cohorts have been running alongside each other since the early 1990s. While NOAR has been collecting data on incident inflammatory polyarthritis since 1989, EPIC has been “intensively” collecting information on dietary and lifestyle factors and blood samples from its participants since 1993.

EPIC investigators have been “trailblazers” in recording of dietary data, Dr. Yates said. First using paper-based questionnaires and now smartphone apps that allow people to upload photos of what they are eating. Data are linked to both primary care practice and hospital records.

For the present study, data on 159 patients who participated in both NOAR and EPIC were used. Participants had RA according to the 2010 American College of Rheumatology criteria and had an average disease onset of 7 years after enrollment into NOAR and EPIC.

“Quite pleasingly, the dietary inflammatory index scores were associated with high-sensitivity CRP taken at baseline enrollment in 1993 to 1997, further validating the index again within another population,” Dr. Yates said.

Results showed that there was a significant association between the baseline DII score and subsequent development of RA, with an odds ratio of 1.90 comparing individuals with the highest and lowest DII scores (P less than .01).

When cases were matched by age, sex, and body mass index, however, there was only a trend for an association between inflammatory diets and RA onset. “We hope to identify more patients within EPIC to strengthen this association,” Dr. Yates said.

The results are consistent with data from the Nurses’ Health Study, Dr. Yates noted, adding that future research is needed to address whether dietary modification can demonstrate causality.

“Diet is one of the modifiable risk factors that we can use to tackle RA, and I think it’s about time we as a community take over this area and gave definitive advice.”

Dr. Yates presented the work on behalf of PhD student Ellie Sayer. Neither Dr. Yates nor Ms. Sayer had any conflicts of interests to disclose.

SOURCE: Sayer E et al. Rheumatology. 2019;58(suppl 3), Abstract 014.

BIRMINGHAM, ENGLAND – Proinflammatory diets are associated with increased C-reactive protein (CRP) and subsequent rheumatoid arthritis (RA), according to combined data from the European Prospective Investigation of Cancer and Nutrition (EPIC) and Norfolk Arthritis Register (NOAR).

Sara Freeman/MDedge News

“There has always been a debate around this topic,” Max Yates, MBBS, PhD, said at the annual conference of the British Society for Rheumatology. “A quick online search will reveal a plethora of texts claiming to give definitive or the best advice for arthritis” and diet, he said, often from “questionable experts.”

“I think we’re all interested in diet,” observed Dr. Yates, of the University of East Anglia in Norwich (England), and “although the association between diet and arthritis is open to debate, previous studies have shown an association with those who have a lower intake of vitamin C and fiber.” The problem is one of credibility, he noted, so this was something that the NOAR investigators decided to look into with data from the Dietary Inflammatory Index (DII) collected from the EPIC cohort.

The DII is a literature-based, population-derived tool that has been used to determine the inflammatory potential of diet, Dr. Yates explained. Data show that inflammatory diets are is associated with increased levels of inflammatory markers including C-reactive protein (CRP) and interleukin (IL)-6. These diets include items such as trans and saturated fats, and fats from animal protein versus more anti-inflammatory items such as black tea, thyme, turmeric, and saffron.

“We are fortunate that NOAR is in the same geographic location as EPIC,” Dr. Yates said, and the two cohorts have been running alongside each other since the early 1990s. While NOAR has been collecting data on incident inflammatory polyarthritis since 1989, EPIC has been “intensively” collecting information on dietary and lifestyle factors and blood samples from its participants since 1993.

EPIC investigators have been “trailblazers” in recording of dietary data, Dr. Yates said. First using paper-based questionnaires and now smartphone apps that allow people to upload photos of what they are eating. Data are linked to both primary care practice and hospital records.

For the present study, data on 159 patients who participated in both NOAR and EPIC were used. Participants had RA according to the 2010 American College of Rheumatology criteria and had an average disease onset of 7 years after enrollment into NOAR and EPIC.

“Quite pleasingly, the dietary inflammatory index scores were associated with high-sensitivity CRP taken at baseline enrollment in 1993 to 1997, further validating the index again within another population,” Dr. Yates said.

Results showed that there was a significant association between the baseline DII score and subsequent development of RA, with an odds ratio of 1.90 comparing individuals with the highest and lowest DII scores (P less than .01).

When cases were matched by age, sex, and body mass index, however, there was only a trend for an association between inflammatory diets and RA onset. “We hope to identify more patients within EPIC to strengthen this association,” Dr. Yates said.

The results are consistent with data from the Nurses’ Health Study, Dr. Yates noted, adding that future research is needed to address whether dietary modification can demonstrate causality.

“Diet is one of the modifiable risk factors that we can use to tackle RA, and I think it’s about time we as a community take over this area and gave definitive advice.”

Dr. Yates presented the work on behalf of PhD student Ellie Sayer. Neither Dr. Yates nor Ms. Sayer had any conflicts of interests to disclose.

SOURCE: Sayer E et al. Rheumatology. 2019;58(suppl 3), Abstract 014.

DALLAS – Warfarin appears to increase the risk of lung transplant or death for patients with fibrotic lung disease who need anticoagulation therapy, Christopher King, MD, said at the American Thoracic Society’s international conference.

Michele G. Sullivan/MDedge News

Compared with direct oral anticoagulation (DOAC), warfarin doubled the risk of those outcomes, even after the researchers controlled for multiple morbidities that accompany the need for anticoagulation, said Dr. King, medical director of the transplant and advanced lung disease critical care program at Inova Fairfax (Va.) Hospital.

“The need for anticoagulation in patients with interstitial lung disease is already associated with an increased risk of death or transplant,” he said. Warfarin – but not oral anticoagulation – seems to increase that risk even more “no matter how you analyze it,” he said.

“We know now that fibrosis and coagulation are entwined, and there’s background epidemiologic data showing an increased incidence of venous thromboembolism and acute coronary syndrome in patients with pulmonary fibrosis. This suggests that a dysregulated coagulation cascade may play a role in the pathogenesis of fibrosis.”

The relationship has been explored for the last decade or so. Two recent meta-analyses came to similar conclusions.

In 2013, a 125-patient retrospective cohort study compared clinical characteristics and survival among patients with idiopathic pulmonary fibrosis (IPF) who received anticoagulant therapy with those who did not (Sarcoidosis Vasc Diffuse Lung Dis. 2013 Aug 1;30[2]:121-7). Those who got the treatment had worse survival outcomes at 1 and 3 years than did those who received no therapy (84% vs. 53% and 89% vs. 64%, respectively).

In 2016, a post hoc analysis of three placebo-controlled studies determined that any anticoagulant use independently increased the risk of death among patients with IPF, compared with nonuse: 15.6% vs 6.3% all-cause mortality (Eur Respir J. 2016. doi: 10.1183/13993003.02087-2015).

But these investigations didn’t parse out the types of anticoagulation. Direct oral anticoagulation (DOAC) is much more common now, however, and Dr. King and colleagues wanted to find out how warfarin and DOAC compared.

They retrospectively analyzed data from the Pulmonary Fibrosis Foundation’s database and compared the risk of lung transplant and death for patients on anticoagulation or no anticoagulation and for those receiving DOACs versus warfarin versus no anticoagulation.

The study comprised 1,918 patients, 91% of whom were not on anticoagulation therapy. The remaining 164 were either taking DOAC (n = 83) or warfarin (n = 81). Both of these groups were significantly older than those not on anticoagulation (70 vs. 67 years). As expected , they were significantly more likely to have cardiac arrhythmias, heart failure, or pulmonary embolism or deep vein thrombosis and significantly more likely to be on immunosuppressant therapy or steroids. Their diffusing capacity of lung for carbon dioxide was also significantly lower.

There were no significant lung disease–related differences in anticoagulation therapy, other than a trend toward more use among those with connective tissue disease–associated interstitial lung disease.

Over 2 years, the entire cohort experienced 110 deaths (5.7%), 52 transplants (2.7%), and 29 withdrawals (1.5%). Among patients with IPF, there were 80 deaths (6.7%), 43 transplants (3.6%) and 20 withdrawals (1.7%).

In an unadjusted analysis, anticoagulation more than doubled the risk of an event, compared with no anticoagulation (hazard ratio, 2.4). This was slightly attenuated, but still significant, in a multivariate model that controlled for age, gender, oxygen use, gastroesophageal reflux disease, obstructive sleep apnea, arrhythmia, cancer, heart failure, obesity, venous thromboembolism, and antifibrotics (HR, 1.88).

A second whole-cohort analysis looked at the survival ratios for both warfarin and DOAC, compared with no treatment. In the fully adjusted model, warfarin was associated with a significantly increased risk HR (2.28) but DOAC was not.

The investigators then examined risk in only patients with lung disease. Among those with IPF, the fully adjusted model showed that warfarin nearly tripled the risk of transplant or death (HR, 2.8), while DOAC had no significant effect.

The reason for this association remains unclear, Dr. King said. “Renal failure may be a big reason patients get warfarin instead of DOAC. It’s difficult to say whether these patients were frail or prone to bleeding. Even something like the care team not being as up to date with treatment could be affecting the numbers. And is it the direct effect of warfarin on fibrotic lung disease? Or maybe DOAC has some beneficial effect on pulmonary fibrosis? We don’t know.

“But what we can take away from this is that warfarin is associated with worse outcomes than DOAC in patients with IPF. It seems reasonable to use DOAC over warfarin if there’s no specific contraindication to DOAC. If you have a patient with pulmonary thrombosis who has indications for anticoagulation I would use DOAC, based on the evidence that we now have available.”

Dr. King had no disclosures.

msullivan@mdedge.com

DALLAS – Warfarin appears to increase the risk of lung transplant or death for patients with fibrotic lung disease who need anticoagulation therapy, Christopher King, MD, said at the American Thoracic Society’s international conference.

Michele G. Sullivan/MDedge News

Compared with direct oral anticoagulation (DOAC), warfarin doubled the risk of those outcomes, even after the researchers controlled for multiple morbidities that accompany the need for anticoagulation, said Dr. King, medical director of the transplant and advanced lung disease critical care program at Inova Fairfax (Va.) Hospital.

“The need for anticoagulation in patients with interstitial lung disease is already associated with an increased risk of death or transplant,” he said. Warfarin – but not oral anticoagulation – seems to increase that risk even more “no matter how you analyze it,” he said.

“We know now that fibrosis and coagulation are entwined, and there’s background epidemiologic data showing an increased incidence of venous thromboembolism and acute coronary syndrome in patients with pulmonary fibrosis. This suggests that a dysregulated coagulation cascade may play a role in the pathogenesis of fibrosis.”

The relationship has been explored for the last decade or so. Two recent meta-analyses came to similar conclusions.

In 2013, a 125-patient retrospective cohort study compared clinical characteristics and survival among patients with idiopathic pulmonary fibrosis (IPF) who received anticoagulant therapy with those who did not (Sarcoidosis Vasc Diffuse Lung Dis. 2013 Aug 1;30[2]:121-7). Those who got the treatment had worse survival outcomes at 1 and 3 years than did those who received no therapy (84% vs. 53% and 89% vs. 64%, respectively).

In 2016, a post hoc analysis of three placebo-controlled studies determined that any anticoagulant use independently increased the risk of death among patients with IPF, compared with nonuse: 15.6% vs 6.3% all-cause mortality (Eur Respir J. 2016. doi: 10.1183/13993003.02087-2015).

But these investigations didn’t parse out the types of anticoagulation. Direct oral anticoagulation (DOAC) is much more common now, however, and Dr. King and colleagues wanted to find out how warfarin and DOAC compared.

They retrospectively analyzed data from the Pulmonary Fibrosis Foundation’s database and compared the risk of lung transplant and death for patients on anticoagulation or no anticoagulation and for those receiving DOACs versus warfarin versus no anticoagulation.

The study comprised 1,918 patients, 91% of whom were not on anticoagulation therapy. The remaining 164 were either taking DOAC (n = 83) or warfarin (n = 81). Both of these groups were significantly older than those not on anticoagulation (70 vs. 67 years). As expected , they were significantly more likely to have cardiac arrhythmias, heart failure, or pulmonary embolism or deep vein thrombosis and significantly more likely to be on immunosuppressant therapy or steroids. Their diffusing capacity of lung for carbon dioxide was also significantly lower.

There were no significant lung disease–related differences in anticoagulation therapy, other than a trend toward more use among those with connective tissue disease–associated interstitial lung disease.

Over 2 years, the entire cohort experienced 110 deaths (5.7%), 52 transplants (2.7%), and 29 withdrawals (1.5%). Among patients with IPF, there were 80 deaths (6.7%), 43 transplants (3.6%) and 20 withdrawals (1.7%).

In an unadjusted analysis, anticoagulation more than doubled the risk of an event, compared with no anticoagulation (hazard ratio, 2.4). This was slightly attenuated, but still significant, in a multivariate model that controlled for age, gender, oxygen use, gastroesophageal reflux disease, obstructive sleep apnea, arrhythmia, cancer, heart failure, obesity, venous thromboembolism, and antifibrotics (HR, 1.88).

A second whole-cohort analysis looked at the survival ratios for both warfarin and DOAC, compared with no treatment. In the fully adjusted model, warfarin was associated with a significantly increased risk HR (2.28) but DOAC was not.

The investigators then examined risk in only patients with lung disease. Among those with IPF, the fully adjusted model showed that warfarin nearly tripled the risk of transplant or death (HR, 2.8), while DOAC had no significant effect.

The reason for this association remains unclear, Dr. King said. “Renal failure may be a big reason patients get warfarin instead of DOAC. It’s difficult to say whether these patients were frail or prone to bleeding. Even something like the care team not being as up to date with treatment could be affecting the numbers. And is it the direct effect of warfarin on fibrotic lung disease? Or maybe DOAC has some beneficial effect on pulmonary fibrosis? We don’t know.

“But what we can take away from this is that warfarin is associated with worse outcomes than DOAC in patients with IPF. It seems reasonable to use DOAC over warfarin if there’s no specific contraindication to DOAC. If you have a patient with pulmonary thrombosis who has indications for anticoagulation I would use DOAC, based on the evidence that we now have available.”

Dr. King had no disclosures.

msullivan@mdedge.com

DALLAS – Warfarin appears to increase the risk of lung transplant or death for patients with fibrotic lung disease who need anticoagulation therapy, Christopher King, MD, said at the American Thoracic Society’s international conference.

Michele G. Sullivan/MDedge News

Compared with direct oral anticoagulation (DOAC), warfarin doubled the risk of those outcomes, even after the researchers controlled for multiple morbidities that accompany the need for anticoagulation, said Dr. King, medical director of the transplant and advanced lung disease critical care program at Inova Fairfax (Va.) Hospital.

“The need for anticoagulation in patients with interstitial lung disease is already associated with an increased risk of death or transplant,” he said. Warfarin – but not oral anticoagulation – seems to increase that risk even more “no matter how you analyze it,” he said.

“We know now that fibrosis and coagulation are entwined, and there’s background epidemiologic data showing an increased incidence of venous thromboembolism and acute coronary syndrome in patients with pulmonary fibrosis. This suggests that a dysregulated coagulation cascade may play a role in the pathogenesis of fibrosis.”

The relationship has been explored for the last decade or so. Two recent meta-analyses came to similar conclusions.

In 2013, a 125-patient retrospective cohort study compared clinical characteristics and survival among patients with idiopathic pulmonary fibrosis (IPF) who received anticoagulant therapy with those who did not (Sarcoidosis Vasc Diffuse Lung Dis. 2013 Aug 1;30[2]:121-7). Those who got the treatment had worse survival outcomes at 1 and 3 years than did those who received no therapy (84% vs. 53% and 89% vs. 64%, respectively).

In 2016, a post hoc analysis of three placebo-controlled studies determined that any anticoagulant use independently increased the risk of death among patients with IPF, compared with nonuse: 15.6% vs 6.3% all-cause mortality (Eur Respir J. 2016. doi: 10.1183/13993003.02087-2015).

But these investigations didn’t parse out the types of anticoagulation. Direct oral anticoagulation (DOAC) is much more common now, however, and Dr. King and colleagues wanted to find out how warfarin and DOAC compared.

They retrospectively analyzed data from the Pulmonary Fibrosis Foundation’s database and compared the risk of lung transplant and death for patients on anticoagulation or no anticoagulation and for those receiving DOACs versus warfarin versus no anticoagulation.

The study comprised 1,918 patients, 91% of whom were not on anticoagulation therapy. The remaining 164 were either taking DOAC (n = 83) or warfarin (n = 81). Both of these groups were significantly older than those not on anticoagulation (70 vs. 67 years). As expected , they were significantly more likely to have cardiac arrhythmias, heart failure, or pulmonary embolism or deep vein thrombosis and significantly more likely to be on immunosuppressant therapy or steroids. Their diffusing capacity of lung for carbon dioxide was also significantly lower.

There were no significant lung disease–related differences in anticoagulation therapy, other than a trend toward more use among those with connective tissue disease–associated interstitial lung disease.

Over 2 years, the entire cohort experienced 110 deaths (5.7%), 52 transplants (2.7%), and 29 withdrawals (1.5%). Among patients with IPF, there were 80 deaths (6.7%), 43 transplants (3.6%) and 20 withdrawals (1.7%).

In an unadjusted analysis, anticoagulation more than doubled the risk of an event, compared with no anticoagulation (hazard ratio, 2.4). This was slightly attenuated, but still significant, in a multivariate model that controlled for age, gender, oxygen use, gastroesophageal reflux disease, obstructive sleep apnea, arrhythmia, cancer, heart failure, obesity, venous thromboembolism, and antifibrotics (HR, 1.88).

A second whole-cohort analysis looked at the survival ratios for both warfarin and DOAC, compared with no treatment. In the fully adjusted model, warfarin was associated with a significantly increased risk HR (2.28) but DOAC was not.

The investigators then examined risk in only patients with lung disease. Among those with IPF, the fully adjusted model showed that warfarin nearly tripled the risk of transplant or death (HR, 2.8), while DOAC had no significant effect.

The reason for this association remains unclear, Dr. King said. “Renal failure may be a big reason patients get warfarin instead of DOAC. It’s difficult to say whether these patients were frail or prone to bleeding. Even something like the care team not being as up to date with treatment could be affecting the numbers. And is it the direct effect of warfarin on fibrotic lung disease? Or maybe DOAC has some beneficial effect on pulmonary fibrosis? We don’t know.

“But what we can take away from this is that warfarin is associated with worse outcomes than DOAC in patients with IPF. It seems reasonable to use DOAC over warfarin if there’s no specific contraindication to DOAC. If you have a patient with pulmonary thrombosis who has indications for anticoagulation I would use DOAC, based on the evidence that we now have available.”

Dr. King had no disclosures.

msullivan@mdedge.com