Patients with PTSD already face difficulties, but the diagnosis of a serious illness, such as cancer, can have an effect on their symptoms in a treatment-hindering way. Matthew Cordova, PhD, a staff psychologist at the VA Northern California Martinez Outpatient Clinic, explained how PTSD can create difficulties for patients when they are diagnosed with a life-threating illness like cancer. 

“Clinically what we see is that these patients are triggered to experience anxiety and avoidance specifically because of their cancer experience,” explained Dr. Cordova. Patients’ symptoms also worsen with “button pushers” such as the uncertainties of a treatment setting, diagnosis, and of people who will be around them.

Dr. Cordova also spoke about the challenge in creating trust between the patient and practitioner, which requires extra effort by the practitioner. Some best practices, he suggested, were focusing on the emotional safety of the patient, being emotionally and physically present during their time together, and creating a sense of predictability.

Another important way to make treatment transitions easier for patients is having a mental health team always present at the oncology and hematology clinics. In the video below Dr. Cordova elaborated on other best practices caregivers should be aware of when treating a patient with cancer and preexisting PTSD.

 Patients with PTSD already face difficulties, but the diagnosis of a serious illness, such as cancer, can have an effect on their symptoms in a treatment-hindering way. Matthew Cordova, PhD, a staff psychologist at the VA Northern California Martinez Outpatient Clinic, explained how PTSD can create difficulties for patients when they are diagnosed with a life-threating illness like cancer. 

“Clinically what we see is that these patients are triggered to experience anxiety and avoidance specifically because of their cancer experience,” explained Dr. Cordova. Patients’ symptoms also worsen with “button pushers” such as the uncertainties of a treatment setting, diagnosis, and of people who will be around them.

Dr. Cordova also spoke about the challenge in creating trust between the patient and practitioner, which requires extra effort by the practitioner. Some best practices, he suggested, were focusing on the emotional safety of the patient, being emotionally and physically present during their time together, and creating a sense of predictability.

Another important way to make treatment transitions easier for patients is having a mental health team always present at the oncology and hematology clinics. In the video below Dr. Cordova elaborated on other best practices caregivers should be aware of when treating a patient with cancer and preexisting PTSD.

 Patients with PTSD already face difficulties, but the diagnosis of a serious illness, such as cancer, can have an effect on their symptoms in a treatment-hindering way. Matthew Cordova, PhD, a staff psychologist at the VA Northern California Martinez Outpatient Clinic, explained how PTSD can create difficulties for patients when they are diagnosed with a life-threating illness like cancer. 

“Clinically what we see is that these patients are triggered to experience anxiety and avoidance specifically because of their cancer experience,” explained Dr. Cordova. Patients’ symptoms also worsen with “button pushers” such as the uncertainties of a treatment setting, diagnosis, and of people who will be around them.

Dr. Cordova also spoke about the challenge in creating trust between the patient and practitioner, which requires extra effort by the practitioner. Some best practices, he suggested, were focusing on the emotional safety of the patient, being emotionally and physically present during their time together, and creating a sense of predictability.

Another important way to make treatment transitions easier for patients is having a mental health team always present at the oncology and hematology clinics. In the video below Dr. Cordova elaborated on other best practices caregivers should be aware of when treating a patient with cancer and preexisting PTSD.

Two years ago, I was approached when I was president of the International Headache Society (IHS) to help arrange for the Iranian Headache Association (IHA) to become a member society in the IHS. This was not hard to do, but had to be arranged correctly. After it was done, Dr. Togha, the leading headache specialist from Iran, got in touch with me to ask me to be the featured speaker at their first meeting under the auspices of the IHS in Tehran. I was a bit concerned because of what I read in the papers and saw on TV about Iran and what it thinks of America and Israel. Many friends were shocked that I was willing to go, but I thought I should go to Iran and forge the way for a good relationship, at least on the headache level, between Iran and the Western world. The Iranians helped me with my visa and travel plans and arranged a wonderful scientific program in which I and other invited guests participated.

I was treated very well and was impressed by the turnout and the high level of talks and discussion. On my first day, we made rounds at the oldest hospital in Tehran, Sina Hospital, enjoyed high-level presentations of unusual cases, and were taken on tours of several neurologic departments. The research going on was impressive, and results are published in major journals. The three-day headache meeting covered a large number of headache issues, and the presentations were detailed and accurate. The hands-on clinics were overflowing their rooms. The Iranians’ headache knowledge is on a par with that in Western societies, and I found myself learning facts I did not know. One lecture by a PhD-level pharmacologist about headache drug–drug interactions was the best I have seen on that topic.

I never felt worried about my safety and, in fact, had a wonderful trip. I enjoyed the food and the long ride to the ancient city of Isfahan with its magnificent architecture and mosaics. The Iranian neurologists and the people I met on the street seem to love Americans and Western ways. The Iranians are nice and friendly people, and I strongly encourage many Americans to visit Iran on a tour.

I look forward to many contributions of the Iranian headache doctors over the next few years and expect to see their papers in Cephalalgia and Headache and to welcome them at international conferences. Maybe Iran will sponsor a regional headache conference for members of their neighboring countries in the future. I expect neurologic and headache medicine diplomacy will advance more quickly than international diplomacy.

—Alan M. Rapoport, MD
Clinical Professor of Neurology, David Geffen School of Medicine at UCLA
and Immediate Past President of the International Headache Society.

Two years ago, I was approached when I was president of the International Headache Society (IHS) to help arrange for the Iranian Headache Association (IHA) to become a member society in the IHS. This was not hard to do, but had to be arranged correctly. After it was done, Dr. Togha, the leading headache specialist from Iran, got in touch with me to ask me to be the featured speaker at their first meeting under the auspices of the IHS in Tehran. I was a bit concerned because of what I read in the papers and saw on TV about Iran and what it thinks of America and Israel. Many friends were shocked that I was willing to go, but I thought I should go to Iran and forge the way for a good relationship, at least on the headache level, between Iran and the Western world. The Iranians helped me with my visa and travel plans and arranged a wonderful scientific program in which I and other invited guests participated.

I was treated very well and was impressed by the turnout and the high level of talks and discussion. On my first day, we made rounds at the oldest hospital in Tehran, Sina Hospital, enjoyed high-level presentations of unusual cases, and were taken on tours of several neurologic departments. The research going on was impressive, and results are published in major journals. The three-day headache meeting covered a large number of headache issues, and the presentations were detailed and accurate. The hands-on clinics were overflowing their rooms. The Iranians’ headache knowledge is on a par with that in Western societies, and I found myself learning facts I did not know. One lecture by a PhD-level pharmacologist about headache drug–drug interactions was the best I have seen on that topic.

I never felt worried about my safety and, in fact, had a wonderful trip. I enjoyed the food and the long ride to the ancient city of Isfahan with its magnificent architecture and mosaics. The Iranian neurologists and the people I met on the street seem to love Americans and Western ways. The Iranians are nice and friendly people, and I strongly encourage many Americans to visit Iran on a tour.

I look forward to many contributions of the Iranian headache doctors over the next few years and expect to see their papers in Cephalalgia and Headache and to welcome them at international conferences. Maybe Iran will sponsor a regional headache conference for members of their neighboring countries in the future. I expect neurologic and headache medicine diplomacy will advance more quickly than international diplomacy.

—Alan M. Rapoport, MD
Clinical Professor of Neurology, David Geffen School of Medicine at UCLA
and Immediate Past President of the International Headache Society.

Two years ago, I was approached when I was president of the International Headache Society (IHS) to help arrange for the Iranian Headache Association (IHA) to become a member society in the IHS. This was not hard to do, but had to be arranged correctly. After it was done, Dr. Togha, the leading headache specialist from Iran, got in touch with me to ask me to be the featured speaker at their first meeting under the auspices of the IHS in Tehran. I was a bit concerned because of what I read in the papers and saw on TV about Iran and what it thinks of America and Israel. Many friends were shocked that I was willing to go, but I thought I should go to Iran and forge the way for a good relationship, at least on the headache level, between Iran and the Western world. The Iranians helped me with my visa and travel plans and arranged a wonderful scientific program in which I and other invited guests participated.

I was treated very well and was impressed by the turnout and the high level of talks and discussion. On my first day, we made rounds at the oldest hospital in Tehran, Sina Hospital, enjoyed high-level presentations of unusual cases, and were taken on tours of several neurologic departments. The research going on was impressive, and results are published in major journals. The three-day headache meeting covered a large number of headache issues, and the presentations were detailed and accurate. The hands-on clinics were overflowing their rooms. The Iranians’ headache knowledge is on a par with that in Western societies, and I found myself learning facts I did not know. One lecture by a PhD-level pharmacologist about headache drug–drug interactions was the best I have seen on that topic.

I never felt worried about my safety and, in fact, had a wonderful trip. I enjoyed the food and the long ride to the ancient city of Isfahan with its magnificent architecture and mosaics. The Iranian neurologists and the people I met on the street seem to love Americans and Western ways. The Iranians are nice and friendly people, and I strongly encourage many Americans to visit Iran on a tour.

I look forward to many contributions of the Iranian headache doctors over the next few years and expect to see their papers in Cephalalgia and Headache and to welcome them at international conferences. Maybe Iran will sponsor a regional headache conference for members of their neighboring countries in the future. I expect neurologic and headache medicine diplomacy will advance more quickly than international diplomacy.

—Alan M. Rapoport, MD
Clinical Professor of Neurology, David Geffen School of Medicine at UCLA
and Immediate Past President of the International Headache Society.

To the Editor:

We read with great interest the article, 
“Omphalith-Associated Relapsing Umbilical Cellulitis: Recurrent Omphalitis Secondary to a 
Hair-Containing Belly Button Bezoar” (Cutis. 2010;86:199-202), which introduced the terms omphalotrich and tricomphalith to describe the pilar composition of a hair-containing umbilical foreign body in an 18-year-old man. We report a similar case.

A 38-year-old man presented with a 10-year history of an unusual odor in the umbilical region with recurrent discharge. He diligently maintained proper hygiene of the umbilicus using cotton swabs and had received recurrent cycles of oral antibiotics prescribed by his general practitioner with temporary improvement of the odor and amount of discharge. Physical examination revealed a normal umbilicus with a deep and tight umbilical cleft that required the use of curved mosquito forceps for further examination (Figure 1). A bezoar comprised of a compact collection of terminal hair shafts was noted deep in the umbilicus (Figure 2). A considerable amount of terminal hairs also were noted on the skin of the abdominal area. Following removal of the bezoar, no umbilical fistula was observed, and the presence of embryologic abnormalities (eg, omphalomesenteric duct remnants) was ruled out on magnetic resonance imaging. A diagnosis of recurrent omphalitis secondary to a hair-containing bezoar was made. Following extraction of the bezoar, the odor and discharge promptly resolved, thereby avoiding the need for oral antibiotics; however, a smaller bezoar comprised of a collection of terminal hair shafts was removed 
4 months later.

Figure 1. Deep and narrow umbilical cleft with serous exudate in the umbilicus after removal of the foreign body.		Figure 2. A section of the umbilical foreign body composed of a collection of terminal hair shafts.

An omphalith is an umbilical foreign body that results from the accumulation of keratinous and amorphous sebaceous material.² Several predisposing factors have been proposed for its pathogenesis, such as the anatomical disposition of the umbilicus and the patient’s hygiene. We hypothesize that a deep umbilicus and a large amount of terminal hairs in the abdominal area were predisposing factors in our patient. Cohen et al¹ proposed the terms omphalotrich and trichomphalith to describe the pilar composition of a hair-containing umbilical foreign body that did not have the characteristic stonelike presentation of a traditional omphalith. The authors also referred to the umbilical foreign body in their patient as a trichobezoar, a term used to describe exogenous foreign bodies composed of ingested hair in the gastrointestinal tract, given the embryologic origin of the umbilicus and epithelium of the 
gastrointestinal tract. We agree that the terms omphalotrich and trichomphalith appropriately describe the current presentation; we also propose the terms omphalitrichia or thricomphalia to describe the findings seen in our patient, which should always be ruled 
out in patients with recurrent omphalitis that is unresponsive to antibiotics.

To the Editor:

We read with great interest the article, 
“Omphalith-Associated Relapsing Umbilical Cellulitis: Recurrent Omphalitis Secondary to a 
Hair-Containing Belly Button Bezoar” (Cutis. 2010;86:199-202), which introduced the terms omphalotrich and tricomphalith to describe the pilar composition of a hair-containing umbilical foreign body in an 18-year-old man. We report a similar case.

A 38-year-old man presented with a 10-year history of an unusual odor in the umbilical region with recurrent discharge. He diligently maintained proper hygiene of the umbilicus using cotton swabs and had received recurrent cycles of oral antibiotics prescribed by his general practitioner with temporary improvement of the odor and amount of discharge. Physical examination revealed a normal umbilicus with a deep and tight umbilical cleft that required the use of curved mosquito forceps for further examination (Figure 1). A bezoar comprised of a compact collection of terminal hair shafts was noted deep in the umbilicus (Figure 2). A considerable amount of terminal hairs also were noted on the skin of the abdominal area. Following removal of the bezoar, no umbilical fistula was observed, and the presence of embryologic abnormalities (eg, omphalomesenteric duct remnants) was ruled out on magnetic resonance imaging. A diagnosis of recurrent omphalitis secondary to a hair-containing bezoar was made. Following extraction of the bezoar, the odor and discharge promptly resolved, thereby avoiding the need for oral antibiotics; however, a smaller bezoar comprised of a collection of terminal hair shafts was removed 
4 months later.

Figure 1. Deep and narrow umbilical cleft with serous exudate in the umbilicus after removal of the foreign body.		Figure 2. A section of the umbilical foreign body composed of a collection of terminal hair shafts.

An omphalith is an umbilical foreign body that results from the accumulation of keratinous and amorphous sebaceous material.² Several predisposing factors have been proposed for its pathogenesis, such as the anatomical disposition of the umbilicus and the patient’s hygiene. We hypothesize that a deep umbilicus and a large amount of terminal hairs in the abdominal area were predisposing factors in our patient. Cohen et al¹ proposed the terms omphalotrich and trichomphalith to describe the pilar composition of a hair-containing umbilical foreign body that did not have the characteristic stonelike presentation of a traditional omphalith. The authors also referred to the umbilical foreign body in their patient as a trichobezoar, a term used to describe exogenous foreign bodies composed of ingested hair in the gastrointestinal tract, given the embryologic origin of the umbilicus and epithelium of the 
gastrointestinal tract. We agree that the terms omphalotrich and trichomphalith appropriately describe the current presentation; we also propose the terms omphalitrichia or thricomphalia to describe the findings seen in our patient, which should always be ruled 
out in patients with recurrent omphalitis that is unresponsive to antibiotics.

To the Editor:

We read with great interest the article, 
“Omphalith-Associated Relapsing Umbilical Cellulitis: Recurrent Omphalitis Secondary to a 
Hair-Containing Belly Button Bezoar” (Cutis. 2010;86:199-202), which introduced the terms omphalotrich and tricomphalith to describe the pilar composition of a hair-containing umbilical foreign body in an 18-year-old man. We report a similar case.

A 38-year-old man presented with a 10-year history of an unusual odor in the umbilical region with recurrent discharge. He diligently maintained proper hygiene of the umbilicus using cotton swabs and had received recurrent cycles of oral antibiotics prescribed by his general practitioner with temporary improvement of the odor and amount of discharge. Physical examination revealed a normal umbilicus with a deep and tight umbilical cleft that required the use of curved mosquito forceps for further examination (Figure 1). A bezoar comprised of a compact collection of terminal hair shafts was noted deep in the umbilicus (Figure 2). A considerable amount of terminal hairs also were noted on the skin of the abdominal area. Following removal of the bezoar, no umbilical fistula was observed, and the presence of embryologic abnormalities (eg, omphalomesenteric duct remnants) was ruled out on magnetic resonance imaging. A diagnosis of recurrent omphalitis secondary to a hair-containing bezoar was made. Following extraction of the bezoar, the odor and discharge promptly resolved, thereby avoiding the need for oral antibiotics; however, a smaller bezoar comprised of a collection of terminal hair shafts was removed 
4 months later.

Figure 1. Deep and narrow umbilical cleft with serous exudate in the umbilicus after removal of the foreign body.		Figure 2. A section of the umbilical foreign body composed of a collection of terminal hair shafts.

An omphalith is an umbilical foreign body that results from the accumulation of keratinous and amorphous sebaceous material.² Several predisposing factors have been proposed for its pathogenesis, such as the anatomical disposition of the umbilicus and the patient’s hygiene. We hypothesize that a deep umbilicus and a large amount of terminal hairs in the abdominal area were predisposing factors in our patient. Cohen et al¹ proposed the terms omphalotrich and trichomphalith to describe the pilar composition of a hair-containing umbilical foreign body that did not have the characteristic stonelike presentation of a traditional omphalith. The authors also referred to the umbilical foreign body in their patient as a trichobezoar, a term used to describe exogenous foreign bodies composed of ingested hair in the gastrointestinal tract, given the embryologic origin of the umbilicus and epithelium of the 
gastrointestinal tract. We agree that the terms omphalotrich and trichomphalith appropriately describe the current presentation; we also propose the terms omphalitrichia or thricomphalia to describe the findings seen in our patient, which should always be ruled 
out in patients with recurrent omphalitis that is unresponsive to antibiotics.

Functional, a.k.a. “nonulcer,” dyspepsia is a challenging diagnosis and likely afflicts many more patients than we have identified in our practices. Functional dyspepsia (FD) is defined by the presence of postprandial fullness, early satiety, epigastric pain or burning, and no evidence of structural disease. These are the patients who do not get better with proton pump inhibitors or feel better after a bowel movement.

After a negative upper endoscopy and Helicobacter pylori stool antigen test, the task turns to symptom control. But what’s the best treatment?

Dr. Nicholas J. Talley of the University of Newcastle in Callaghan, Australia, and colleagues conducted a multicenter, randomized trial evaluating the comparative efficacy of amitriptyline or escitalopram for symptom control, gastric emptying, and meal-induced satiety in patients with FD (Gastroenterology. 2015;149(2):340-9.e2).

Participants were enrolled if they met Rome II criteria for FD requiring that folks in the preceding 12 months have at least 12 weeks of dyspepsia, absence of organic disease, and no relationship to defecation. Patients were randomized to placebo, amitriptyline 50 mg (titrated), or escitalopram 10 mg. Medication was given for 10 weeks. The primary endpoint was adequate relief of symptoms for at least 5 weeks.

A total of 292 patients (most of whom [75%] were female) with an average age of 44 years were randomized. Seventy percent had dysmotility-like FD and 30% had ulcer-like FD.

Patients with ulcer-like FD receiving amitriptyline were more likely to report adequate relief (odds ratio, 3.1; 95% confidence interval, 1.1-9.0). Neither medication affected gastric emptying or meal-induced satiety. Both medications improved overall quality of life.

The data support the use of amitriptyline for ulcer-like FD. Some of these patients may have comorbid psychiatric illness that may be improved with escitalopram. Perhaps this is what is impacting the quality-of-life metric that taps into dimensions above and beyond relief of symptoms (such as sleep disturbance or work/study).

Proton pump inhibitors tend to be overused, and many of our patients take them indefinitely without trying to see how they do off of them. Some patients for whom we have not considered a diagnosis of FD may be on PPIs because we have had nothing else to offer them. Maybe they felt better because of a PPI placebo effect and we have continued them.

If we can, we should review the diagnosis of dyspepsia, consider FD as a possibility etiology for gastrointestinal distress, stop the PPIs, and try amitriptyline.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

Functional, a.k.a. “nonulcer,” dyspepsia is a challenging diagnosis and likely afflicts many more patients than we have identified in our practices. Functional dyspepsia (FD) is defined by the presence of postprandial fullness, early satiety, epigastric pain or burning, and no evidence of structural disease. These are the patients who do not get better with proton pump inhibitors or feel better after a bowel movement.

After a negative upper endoscopy and Helicobacter pylori stool antigen test, the task turns to symptom control. But what’s the best treatment?

Dr. Nicholas J. Talley of the University of Newcastle in Callaghan, Australia, and colleagues conducted a multicenter, randomized trial evaluating the comparative efficacy of amitriptyline or escitalopram for symptom control, gastric emptying, and meal-induced satiety in patients with FD (Gastroenterology. 2015;149(2):340-9.e2).

Participants were enrolled if they met Rome II criteria for FD requiring that folks in the preceding 12 months have at least 12 weeks of dyspepsia, absence of organic disease, and no relationship to defecation. Patients were randomized to placebo, amitriptyline 50 mg (titrated), or escitalopram 10 mg. Medication was given for 10 weeks. The primary endpoint was adequate relief of symptoms for at least 5 weeks.

A total of 292 patients (most of whom [75%] were female) with an average age of 44 years were randomized. Seventy percent had dysmotility-like FD and 30% had ulcer-like FD.

Patients with ulcer-like FD receiving amitriptyline were more likely to report adequate relief (odds ratio, 3.1; 95% confidence interval, 1.1-9.0). Neither medication affected gastric emptying or meal-induced satiety. Both medications improved overall quality of life.

The data support the use of amitriptyline for ulcer-like FD. Some of these patients may have comorbid psychiatric illness that may be improved with escitalopram. Perhaps this is what is impacting the quality-of-life metric that taps into dimensions above and beyond relief of symptoms (such as sleep disturbance or work/study).

Proton pump inhibitors tend to be overused, and many of our patients take them indefinitely without trying to see how they do off of them. Some patients for whom we have not considered a diagnosis of FD may be on PPIs because we have had nothing else to offer them. Maybe they felt better because of a PPI placebo effect and we have continued them.

If we can, we should review the diagnosis of dyspepsia, consider FD as a possibility etiology for gastrointestinal distress, stop the PPIs, and try amitriptyline.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

Functional, a.k.a. “nonulcer,” dyspepsia is a challenging diagnosis and likely afflicts many more patients than we have identified in our practices. Functional dyspepsia (FD) is defined by the presence of postprandial fullness, early satiety, epigastric pain or burning, and no evidence of structural disease. These are the patients who do not get better with proton pump inhibitors or feel better after a bowel movement.

After a negative upper endoscopy and Helicobacter pylori stool antigen test, the task turns to symptom control. But what’s the best treatment?

Dr. Nicholas J. Talley of the University of Newcastle in Callaghan, Australia, and colleagues conducted a multicenter, randomized trial evaluating the comparative efficacy of amitriptyline or escitalopram for symptom control, gastric emptying, and meal-induced satiety in patients with FD (Gastroenterology. 2015;149(2):340-9.e2).

Participants were enrolled if they met Rome II criteria for FD requiring that folks in the preceding 12 months have at least 12 weeks of dyspepsia, absence of organic disease, and no relationship to defecation. Patients were randomized to placebo, amitriptyline 50 mg (titrated), or escitalopram 10 mg. Medication was given for 10 weeks. The primary endpoint was adequate relief of symptoms for at least 5 weeks.

A total of 292 patients (most of whom [75%] were female) with an average age of 44 years were randomized. Seventy percent had dysmotility-like FD and 30% had ulcer-like FD.

Patients with ulcer-like FD receiving amitriptyline were more likely to report adequate relief (odds ratio, 3.1; 95% confidence interval, 1.1-9.0). Neither medication affected gastric emptying or meal-induced satiety. Both medications improved overall quality of life.

The data support the use of amitriptyline for ulcer-like FD. Some of these patients may have comorbid psychiatric illness that may be improved with escitalopram. Perhaps this is what is impacting the quality-of-life metric that taps into dimensions above and beyond relief of symptoms (such as sleep disturbance or work/study).

Proton pump inhibitors tend to be overused, and many of our patients take them indefinitely without trying to see how they do off of them. Some patients for whom we have not considered a diagnosis of FD may be on PPIs because we have had nothing else to offer them. Maybe they felt better because of a PPI placebo effect and we have continued them.

If we can, we should review the diagnosis of dyspepsia, consider FD as a possibility etiology for gastrointestinal distress, stop the PPIs, and try amitriptyline.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

TEHRAN—For the first time, the International Headache Society (IHS) and the Iranian Headache Association (IHA) collaborated to host the Fourth Iranian International Headache Congress. IHS helped facilitate the conference, which took place from September 16 to 18, 2015, as part of its visiting professor program. The gathering marked the first such meeting since the IHA became affiliated with IHS in January 2015.

The IHA organized the congress, which was sponsored by Sanofi (Paris) and Dr. Abidi Pharmaceuticals (Tehran). A total of 340 physicians and researchers participated in the congress. Guest speakers included Robert Cowan, MD, Clinical Professor of Neurology and Neurological Sciences at Stanford School of Medicine in California; Hossein Ansari, MD, Director of the Headache Clinic at the University of California, San Diego; Hayrunnisa Bolay, MD, PhD, Professor of Neurology and Algology at Gazi University in Ankara, Turkey; and Farooq Maniyar, MD, Lead for Headache Medicine at the Royal London Hospital.

The congress took place in the Olympic Hotel, one of the largest conference centers in Tehran. Its main aims were to familiarize neurologists and other specialists with the latest scientific achievements in the field of headache and to provide guidance about diagnosing and treating various headache types. During the opening ceremony, Mansoureh Togha, MD, Chair of the IHA, and Hossein Pakdaman, MD, President of the Iranian Neurological Association and Professor of Neurology at Beheshtee University School of Medicine in Tehran, welcomed attendees.

Alan M. Rapoport, MD, Clinical Professor of Neurology at David Geffen School of Medicine at the University of California, Los Angeles, was an honorary guest speaker. During his term as president of IHS, Dr. Rapoport helped IHA to become an affiliate of IHS. He briefly reviewed the benefits of IHA’s new affiliation and the services now available to IHA members. He welcomed the IHA into the international community of the IHS and discussed ways that Iranians could join the IHS and access Cephalalgia. In addition, Dr. Rapoport discussed the various travel grants, scholarships, and fellowships that the IHS makes available to its members. He expressed regret that several young Iranians had received travel grants to attend the IHS Congress in Valencia, Spain, in May 2015, but could not attend because they were unable to obtain visas. He expressed hope that the neurologists would be able to attend the next IHS Congress in Vancouver in 2017.

Abstracts and most full texts of presented lectures at the Iranian International Headache Congress were available online on the IHA website on the first day of the congress. In addition, printed copies of the abstracts were offered to all participants upon registration.

Main Lectures

Headache specialists and physicians who were considered experts in a specific field related to primary or secondary headaches presented a total of 35 lectures. Some of the highlights included Dr. Bolay’s lecture on how neurologists can use animal models and Dr. Rapoport’s lecture on the pathophysiology of migraine, which emphasized the role of calcitonin gene-related peptide (CGRP).

In addition, various lectures presenting updates in the diagnosis and treatment of primary headaches were presented, including Dr. Cowan’s talk about noncephalic migraine equivalents, Dr. Maniyar’s presentation about optimizing the treatment of acute migraine attacks, and Dr. Ansari’s review of cluster headache.

Several neurologists gave presentations about migraine variants, secondary headaches, and related subjects, such as metabolic headache and ictal epileptic headache. Dr. Togha spoke about migraine and vertigo, and Dr. Ansari provided an overview of cervicogenic headache. In addition, Leila Kuti, PhD, talked about drug interactions in headache treatment.

In his first lecture, Dr. Rapoport discussed the importance of an organized, widely used hierarchical classification for headache. He described the new International Classification of Headache Disorders III beta and indicated its changes from the previous version, as well as its potentially problematic areas.

In his final talk, Dr. Cowan used case presentations to discuss how technology can help neurologists bring expert diagnosis and treatment to patients with headache. He reviewed recent advances in technology that promise to make headache diagnosis and treatment more accurate and shorten the time that physicians spend collecting detailed histories.

In one of her three presentations, Dr. Bolay discussed the challenges in pediatric headache. She used case presentations to illustrate key points and clarify diagnostic and management challenges.

Case Presentations

Seyed Masood Nabavi, MD, Professor of Neurology at Beheshtee University School of Medicine, moderated a session dedicated to case presentations, which was one of the most popular portions of the congress. During this time, neurologists presented five challenging cases and invited responses from the audience. Attendees discussed differential diagnoses and management strategies for each case.

Workshops

Another part of the congress was devoted to workshops. Dr. Ansari moderated two workshops, the first of which was intended for younger neurologists and provided training on techniques of onabotulinumtoxinA injection for chronic migraine. The second workshop focused on peripheral nerve block techniques for headache, including sphenopalatine ganglion blocks. All participants had the opportunity to acquire hands-on experience in injection techniques and were given time to ask questions.

Panel Discussions

The congress also included two panel discussions. The first discussion examined various aspects of headache in idiopathic intracranial hypertension and idiopathic intracranial hypotension (ie, low CSF pressure headache). The panel spoke about challenging aspects of the diagnosis and management of these two secondary headache disorders. Drs. Rapoport, Cowan, and Bolay oversaw the panel and answered attendees’ questions.

The second panel, presented by Dr. Ansari and colleagues, reviewed several unapproved but potentially effective treatment modalities for headache, including migraine surgery (ie, trigger-point deactivation), nutritional treatments, exercise, and the techniques of Iranian traditional medicine.

Residents Scientific Competition

Neurology residents from 13 Iranian universities participated in a competition. First-, second-, and third-place winners were awarded valuable prizes.

In addition, 21 exhibitors presented their products and books in the exhibit hall.

The Future of Iranian 
Headache Medicine

The Fourth Iranian International Headache Congress was intended to advance the status of headache medicine in Iran. Positive feedback from attendees suggested that the congress had achieved its primary goal, which was to present high-quality programs and inspire neurologists and headache doctors to continue their already advanced headache work and care.

The attendance of distinguished international headache specialists, the cooperation of the International Headache Association, the participation of esteemed Iranian neurologists as lecturers, and the attendance of participants from various parts of Iran have all contributed to the establishment of a positive working relationship between the Iranian Headache Association and IHS.

The next step in the advancement of headache medicine in Iran could be a regional headache congress with the participation of the country’s neighbors. The conference’s organizers hope to replicate their successful planning, organization, and execution by hosting such a regional event in the future.

—Hossein Ansari, MD, and Mansoureh Togha, MD

TEHRAN—For the first time, the International Headache Society (IHS) and the Iranian Headache Association (IHA) collaborated to host the Fourth Iranian International Headache Congress. IHS helped facilitate the conference, which took place from September 16 to 18, 2015, as part of its visiting professor program. The gathering marked the first such meeting since the IHA became affiliated with IHS in January 2015.

The IHA organized the congress, which was sponsored by Sanofi (Paris) and Dr. Abidi Pharmaceuticals (Tehran). A total of 340 physicians and researchers participated in the congress. Guest speakers included Robert Cowan, MD, Clinical Professor of Neurology and Neurological Sciences at Stanford School of Medicine in California; Hossein Ansari, MD, Director of the Headache Clinic at the University of California, San Diego; Hayrunnisa Bolay, MD, PhD, Professor of Neurology and Algology at Gazi University in Ankara, Turkey; and Farooq Maniyar, MD, Lead for Headache Medicine at the Royal London Hospital.

The congress took place in the Olympic Hotel, one of the largest conference centers in Tehran. Its main aims were to familiarize neurologists and other specialists with the latest scientific achievements in the field of headache and to provide guidance about diagnosing and treating various headache types. During the opening ceremony, Mansoureh Togha, MD, Chair of the IHA, and Hossein Pakdaman, MD, President of the Iranian Neurological Association and Professor of Neurology at Beheshtee University School of Medicine in Tehran, welcomed attendees.

Alan M. Rapoport, MD, Clinical Professor of Neurology at David Geffen School of Medicine at the University of California, Los Angeles, was an honorary guest speaker. During his term as president of IHS, Dr. Rapoport helped IHA to become an affiliate of IHS. He briefly reviewed the benefits of IHA’s new affiliation and the services now available to IHA members. He welcomed the IHA into the international community of the IHS and discussed ways that Iranians could join the IHS and access Cephalalgia. In addition, Dr. Rapoport discussed the various travel grants, scholarships, and fellowships that the IHS makes available to its members. He expressed regret that several young Iranians had received travel grants to attend the IHS Congress in Valencia, Spain, in May 2015, but could not attend because they were unable to obtain visas. He expressed hope that the neurologists would be able to attend the next IHS Congress in Vancouver in 2017.

Abstracts and most full texts of presented lectures at the Iranian International Headache Congress were available online on the IHA website on the first day of the congress. In addition, printed copies of the abstracts were offered to all participants upon registration.

Main Lectures

Headache specialists and physicians who were considered experts in a specific field related to primary or secondary headaches presented a total of 35 lectures. Some of the highlights included Dr. Bolay’s lecture on how neurologists can use animal models and Dr. Rapoport’s lecture on the pathophysiology of migraine, which emphasized the role of calcitonin gene-related peptide (CGRP).

In addition, various lectures presenting updates in the diagnosis and treatment of primary headaches were presented, including Dr. Cowan’s talk about noncephalic migraine equivalents, Dr. Maniyar’s presentation about optimizing the treatment of acute migraine attacks, and Dr. Ansari’s review of cluster headache.

Several neurologists gave presentations about migraine variants, secondary headaches, and related subjects, such as metabolic headache and ictal epileptic headache. Dr. Togha spoke about migraine and vertigo, and Dr. Ansari provided an overview of cervicogenic headache. In addition, Leila Kuti, PhD, talked about drug interactions in headache treatment.

In his first lecture, Dr. Rapoport discussed the importance of an organized, widely used hierarchical classification for headache. He described the new International Classification of Headache Disorders III beta and indicated its changes from the previous version, as well as its potentially problematic areas.

In his final talk, Dr. Cowan used case presentations to discuss how technology can help neurologists bring expert diagnosis and treatment to patients with headache. He reviewed recent advances in technology that promise to make headache diagnosis and treatment more accurate and shorten the time that physicians spend collecting detailed histories.

In one of her three presentations, Dr. Bolay discussed the challenges in pediatric headache. She used case presentations to illustrate key points and clarify diagnostic and management challenges.

Case Presentations

Seyed Masood Nabavi, MD, Professor of Neurology at Beheshtee University School of Medicine, moderated a session dedicated to case presentations, which was one of the most popular portions of the congress. During this time, neurologists presented five challenging cases and invited responses from the audience. Attendees discussed differential diagnoses and management strategies for each case.

Workshops

Another part of the congress was devoted to workshops. Dr. Ansari moderated two workshops, the first of which was intended for younger neurologists and provided training on techniques of onabotulinumtoxinA injection for chronic migraine. The second workshop focused on peripheral nerve block techniques for headache, including sphenopalatine ganglion blocks. All participants had the opportunity to acquire hands-on experience in injection techniques and were given time to ask questions.

Panel Discussions

The congress also included two panel discussions. The first discussion examined various aspects of headache in idiopathic intracranial hypertension and idiopathic intracranial hypotension (ie, low CSF pressure headache). The panel spoke about challenging aspects of the diagnosis and management of these two secondary headache disorders. Drs. Rapoport, Cowan, and Bolay oversaw the panel and answered attendees’ questions.

The second panel, presented by Dr. Ansari and colleagues, reviewed several unapproved but potentially effective treatment modalities for headache, including migraine surgery (ie, trigger-point deactivation), nutritional treatments, exercise, and the techniques of Iranian traditional medicine.

Residents Scientific Competition

Neurology residents from 13 Iranian universities participated in a competition. First-, second-, and third-place winners were awarded valuable prizes.

In addition, 21 exhibitors presented their products and books in the exhibit hall.

The Future of Iranian 
Headache Medicine

The Fourth Iranian International Headache Congress was intended to advance the status of headache medicine in Iran. Positive feedback from attendees suggested that the congress had achieved its primary goal, which was to present high-quality programs and inspire neurologists and headache doctors to continue their already advanced headache work and care.

The attendance of distinguished international headache specialists, the cooperation of the International Headache Association, the participation of esteemed Iranian neurologists as lecturers, and the attendance of participants from various parts of Iran have all contributed to the establishment of a positive working relationship between the Iranian Headache Association and IHS.

The next step in the advancement of headache medicine in Iran could be a regional headache congress with the participation of the country’s neighbors. The conference’s organizers hope to replicate their successful planning, organization, and execution by hosting such a regional event in the future.

—Hossein Ansari, MD, and Mansoureh Togha, MD

TEHRAN—For the first time, the International Headache Society (IHS) and the Iranian Headache Association (IHA) collaborated to host the Fourth Iranian International Headache Congress. IHS helped facilitate the conference, which took place from September 16 to 18, 2015, as part of its visiting professor program. The gathering marked the first such meeting since the IHA became affiliated with IHS in January 2015.

The IHA organized the congress, which was sponsored by Sanofi (Paris) and Dr. Abidi Pharmaceuticals (Tehran). A total of 340 physicians and researchers participated in the congress. Guest speakers included Robert Cowan, MD, Clinical Professor of Neurology and Neurological Sciences at Stanford School of Medicine in California; Hossein Ansari, MD, Director of the Headache Clinic at the University of California, San Diego; Hayrunnisa Bolay, MD, PhD, Professor of Neurology and Algology at Gazi University in Ankara, Turkey; and Farooq Maniyar, MD, Lead for Headache Medicine at the Royal London Hospital.

The congress took place in the Olympic Hotel, one of the largest conference centers in Tehran. Its main aims were to familiarize neurologists and other specialists with the latest scientific achievements in the field of headache and to provide guidance about diagnosing and treating various headache types. During the opening ceremony, Mansoureh Togha, MD, Chair of the IHA, and Hossein Pakdaman, MD, President of the Iranian Neurological Association and Professor of Neurology at Beheshtee University School of Medicine in Tehran, welcomed attendees.

Alan M. Rapoport, MD, Clinical Professor of Neurology at David Geffen School of Medicine at the University of California, Los Angeles, was an honorary guest speaker. During his term as president of IHS, Dr. Rapoport helped IHA to become an affiliate of IHS. He briefly reviewed the benefits of IHA’s new affiliation and the services now available to IHA members. He welcomed the IHA into the international community of the IHS and discussed ways that Iranians could join the IHS and access Cephalalgia. In addition, Dr. Rapoport discussed the various travel grants, scholarships, and fellowships that the IHS makes available to its members. He expressed regret that several young Iranians had received travel grants to attend the IHS Congress in Valencia, Spain, in May 2015, but could not attend because they were unable to obtain visas. He expressed hope that the neurologists would be able to attend the next IHS Congress in Vancouver in 2017.

Abstracts and most full texts of presented lectures at the Iranian International Headache Congress were available online on the IHA website on the first day of the congress. In addition, printed copies of the abstracts were offered to all participants upon registration.

Main Lectures

Headache specialists and physicians who were considered experts in a specific field related to primary or secondary headaches presented a total of 35 lectures. Some of the highlights included Dr. Bolay’s lecture on how neurologists can use animal models and Dr. Rapoport’s lecture on the pathophysiology of migraine, which emphasized the role of calcitonin gene-related peptide (CGRP).

In addition, various lectures presenting updates in the diagnosis and treatment of primary headaches were presented, including Dr. Cowan’s talk about noncephalic migraine equivalents, Dr. Maniyar’s presentation about optimizing the treatment of acute migraine attacks, and Dr. Ansari’s review of cluster headache.

Several neurologists gave presentations about migraine variants, secondary headaches, and related subjects, such as metabolic headache and ictal epileptic headache. Dr. Togha spoke about migraine and vertigo, and Dr. Ansari provided an overview of cervicogenic headache. In addition, Leila Kuti, PhD, talked about drug interactions in headache treatment.

In his first lecture, Dr. Rapoport discussed the importance of an organized, widely used hierarchical classification for headache. He described the new International Classification of Headache Disorders III beta and indicated its changes from the previous version, as well as its potentially problematic areas.

In his final talk, Dr. Cowan used case presentations to discuss how technology can help neurologists bring expert diagnosis and treatment to patients with headache. He reviewed recent advances in technology that promise to make headache diagnosis and treatment more accurate and shorten the time that physicians spend collecting detailed histories.

In one of her three presentations, Dr. Bolay discussed the challenges in pediatric headache. She used case presentations to illustrate key points and clarify diagnostic and management challenges.

Case Presentations

Seyed Masood Nabavi, MD, Professor of Neurology at Beheshtee University School of Medicine, moderated a session dedicated to case presentations, which was one of the most popular portions of the congress. During this time, neurologists presented five challenging cases and invited responses from the audience. Attendees discussed differential diagnoses and management strategies for each case.

Workshops

Another part of the congress was devoted to workshops. Dr. Ansari moderated two workshops, the first of which was intended for younger neurologists and provided training on techniques of onabotulinumtoxinA injection for chronic migraine. The second workshop focused on peripheral nerve block techniques for headache, including sphenopalatine ganglion blocks. All participants had the opportunity to acquire hands-on experience in injection techniques and were given time to ask questions.

Panel Discussions

The congress also included two panel discussions. The first discussion examined various aspects of headache in idiopathic intracranial hypertension and idiopathic intracranial hypotension (ie, low CSF pressure headache). The panel spoke about challenging aspects of the diagnosis and management of these two secondary headache disorders. Drs. Rapoport, Cowan, and Bolay oversaw the panel and answered attendees’ questions.

The second panel, presented by Dr. Ansari and colleagues, reviewed several unapproved but potentially effective treatment modalities for headache, including migraine surgery (ie, trigger-point deactivation), nutritional treatments, exercise, and the techniques of Iranian traditional medicine.

Residents Scientific Competition

Neurology residents from 13 Iranian universities participated in a competition. First-, second-, and third-place winners were awarded valuable prizes.

In addition, 21 exhibitors presented their products and books in the exhibit hall.

The Future of Iranian 
Headache Medicine

The Fourth Iranian International Headache Congress was intended to advance the status of headache medicine in Iran. Positive feedback from attendees suggested that the congress had achieved its primary goal, which was to present high-quality programs and inspire neurologists and headache doctors to continue their already advanced headache work and care.

The attendance of distinguished international headache specialists, the cooperation of the International Headache Association, the participation of esteemed Iranian neurologists as lecturers, and the attendance of participants from various parts of Iran have all contributed to the establishment of a positive working relationship between the Iranian Headache Association and IHS.

The next step in the advancement of headache medicine in Iran could be a regional headache congress with the participation of the country’s neighbors. The conference’s organizers hope to replicate their successful planning, organization, and execution by hosting such a regional event in the future.

—Hossein Ansari, MD, and Mansoureh Togha, MD

COPENHAGEN – Patients with venous leg ulcers have an increased risk of occult cancer – especially hematologic and immune-related malignancies, according to a Danish nationwide cohort study.

The risk of newly detected cancer was greatest during the first 89 days after diagnosis of a venous leg ulcer. Indeed, during that initial period the risk of being diagnosed with a hematologic cancer was 3.48-fold greater than expected based upon Danish Cancer Registry data, Dr. Sigrun Alba Johannesdottir Schmidt reported at the annual congress of the European Academy of Dermatology and Venereology.

It’s reasonable to assume that the vast majority of cancers identified within a year following diagnosis of a venous leg ulcer were probably present at the time when the ulcer was first diagnosed, meaning venous leg ulcers can serve as a red flag for occult cancer.

However, it’s also worth noting that the increased risk of hematologic malignancies persisted, albeit to a lesser degree, for up to 10 years. This suggests that venous ulceration could also have a carcinogenic effect. It’s biologically plausible that a venous leg ulcer could promote development of cancer through a variety of mechanisms, including inflammation, alteration of plasma viscosity and the adhesive properties of blood cells, and disruptions of venous pressure that encourage direct neoplastic invasion, according to Dr. Schmidt of Aarhus (Denmark) University.

She presented a Danish national patient registry study, which included all 29,705 patients with a first-time inpatient, outpatient, or emergency department diagnosis of a venous leg ulcer during 1982-2010. Fifty-five percent of them were age 70 years or older at the time of ulcer diagnosis. And 42% had moderate to very severe comorbid conditions based upon their Charlson Comorbidity Index score. During a median of 5.1 years of follow-up, or a total of 203,453 person-years, their overall risk of a first-time cancer diagnosis was significantly increased by 11%,compared with the general Danish population.

The malignancy risk was strongly time-dependent . However, the absolute risk of cancer was relatively low: less than 1% within the first 90 days after diagnosis of a venous leg ulcer. The number of patients who would need to be examined for a possible malignancy at the time of diagnosis of a venous leg ulcer in order to diagnosis one excess cancer was 146.

Dr. Schmidt indicated she would defer to experts in cost-benefit analysis as to whether an extensive work-up for occult malignancy is worthwhile in patients with a newly diagnosed venous leg ulcer, given the low absolute risk of cancer.

She reported having no financial conflicts of interest regarding her study, which was conducted with Danish institutional research funds.

[email protected]

COPENHAGEN – Patients with venous leg ulcers have an increased risk of occult cancer – especially hematologic and immune-related malignancies, according to a Danish nationwide cohort study.

The risk of newly detected cancer was greatest during the first 89 days after diagnosis of a venous leg ulcer. Indeed, during that initial period the risk of being diagnosed with a hematologic cancer was 3.48-fold greater than expected based upon Danish Cancer Registry data, Dr. Sigrun Alba Johannesdottir Schmidt reported at the annual congress of the European Academy of Dermatology and Venereology.

It’s reasonable to assume that the vast majority of cancers identified within a year following diagnosis of a venous leg ulcer were probably present at the time when the ulcer was first diagnosed, meaning venous leg ulcers can serve as a red flag for occult cancer.

However, it’s also worth noting that the increased risk of hematologic malignancies persisted, albeit to a lesser degree, for up to 10 years. This suggests that venous ulceration could also have a carcinogenic effect. It’s biologically plausible that a venous leg ulcer could promote development of cancer through a variety of mechanisms, including inflammation, alteration of plasma viscosity and the adhesive properties of blood cells, and disruptions of venous pressure that encourage direct neoplastic invasion, according to Dr. Schmidt of Aarhus (Denmark) University.

She presented a Danish national patient registry study, which included all 29,705 patients with a first-time inpatient, outpatient, or emergency department diagnosis of a venous leg ulcer during 1982-2010. Fifty-five percent of them were age 70 years or older at the time of ulcer diagnosis. And 42% had moderate to very severe comorbid conditions based upon their Charlson Comorbidity Index score. During a median of 5.1 years of follow-up, or a total of 203,453 person-years, their overall risk of a first-time cancer diagnosis was significantly increased by 11%,compared with the general Danish population.

The malignancy risk was strongly time-dependent . However, the absolute risk of cancer was relatively low: less than 1% within the first 90 days after diagnosis of a venous leg ulcer. The number of patients who would need to be examined for a possible malignancy at the time of diagnosis of a venous leg ulcer in order to diagnosis one excess cancer was 146.

Dr. Schmidt indicated she would defer to experts in cost-benefit analysis as to whether an extensive work-up for occult malignancy is worthwhile in patients with a newly diagnosed venous leg ulcer, given the low absolute risk of cancer.

She reported having no financial conflicts of interest regarding her study, which was conducted with Danish institutional research funds.

[email protected]

COPENHAGEN – Patients with venous leg ulcers have an increased risk of occult cancer – especially hematologic and immune-related malignancies, according to a Danish nationwide cohort study.

The risk of newly detected cancer was greatest during the first 89 days after diagnosis of a venous leg ulcer. Indeed, during that initial period the risk of being diagnosed with a hematologic cancer was 3.48-fold greater than expected based upon Danish Cancer Registry data, Dr. Sigrun Alba Johannesdottir Schmidt reported at the annual congress of the European Academy of Dermatology and Venereology.

It’s reasonable to assume that the vast majority of cancers identified within a year following diagnosis of a venous leg ulcer were probably present at the time when the ulcer was first diagnosed, meaning venous leg ulcers can serve as a red flag for occult cancer.

However, it’s also worth noting that the increased risk of hematologic malignancies persisted, albeit to a lesser degree, for up to 10 years. This suggests that venous ulceration could also have a carcinogenic effect. It’s biologically plausible that a venous leg ulcer could promote development of cancer through a variety of mechanisms, including inflammation, alteration of plasma viscosity and the adhesive properties of blood cells, and disruptions of venous pressure that encourage direct neoplastic invasion, according to Dr. Schmidt of Aarhus (Denmark) University.

She presented a Danish national patient registry study, which included all 29,705 patients with a first-time inpatient, outpatient, or emergency department diagnosis of a venous leg ulcer during 1982-2010. Fifty-five percent of them were age 70 years or older at the time of ulcer diagnosis. And 42% had moderate to very severe comorbid conditions based upon their Charlson Comorbidity Index score. During a median of 5.1 years of follow-up, or a total of 203,453 person-years, their overall risk of a first-time cancer diagnosis was significantly increased by 11%,compared with the general Danish population.

The malignancy risk was strongly time-dependent . However, the absolute risk of cancer was relatively low: less than 1% within the first 90 days after diagnosis of a venous leg ulcer. The number of patients who would need to be examined for a possible malignancy at the time of diagnosis of a venous leg ulcer in order to diagnosis one excess cancer was 146.

Dr. Schmidt indicated she would defer to experts in cost-benefit analysis as to whether an extensive work-up for occult malignancy is worthwhile in patients with a newly diagnosed venous leg ulcer, given the low absolute risk of cancer.

She reported having no financial conflicts of interest regarding her study, which was conducted with Danish institutional research funds.

[email protected]

Hospitalists care for patients with the most serious, chronic, and complex illnesses. As a result, they are often faced with the daunting task of counseling their patients to help them clearly define their end-of-life wishes. The mere subject of death is met with apprehension and avoidance, but its inevitability warrants an early discussion.

End-of-life care, also known as Advance Care Planning (ACP), enables patients to formulate advanced directives: a living will, the designation of a healthcare proxy, Medical Orders for Life-Sustaining Treatment (MOLST), and the preparation for hospice care, among others. Patients should start thinking about their healthcare options and share such important decisions with their physicians and family before the need for hospitalization.

On October 30, 2015, the Centers for Medicare and Medicaid Services (CMS) released the final payment rules for Medicare reimbursement of physicians who consult with their patients on advance care planning. This separate payment system under the 2016 Physician Fee Schedule will impact the almost 55 million Medicare beneficiaries and their healthcare providers.

Effective January 1, 2016, Medicare will pay $86 for 30 minutes of ACP in a physician’s office and will pay $80 for the same service in a hospital (CPT billing code 99497). In both settings, Medicare will pay up to $75 for 30 additional minutes of consultation (add-on CPT billing code 99498). Such counseling can take place during a senior’s annual wellness visit or during a routine office visit and at various stages of health, always “at the discretion of the beneficiary.”

Six years ago, proposed legislation on Medicare reimbursement for ACP under the Accountable Care Act (ACA) sparked political debate over fears that the implementation of so-called “death panels” could influence decisions to avoid medical care. The goal was to reduce healthcare costs, but these controversial provisions were dropped with the passage of the ACA. This time, there was less resistance.

Proponents of this new legislation, such as the American Medical Association and the American Academy of Palliative and Hospice Medicine, say that this rule will encourage physicians to make time for these lengthy discussions and facilitate patient choices while improving quality of care for seniors. Opponents, including the Association of American Physicians and Surgeons, contend that such payments will “create financial incentives to persuade patients to consent to the denial of care.”

Patrick Conway, MD, CMS' chief medical officer, told the New York Times, "We received overwhelmingly positive comments about the importance of these conversations between physicians and patients. We know that many patients and families want to have these discussions."

Future endeavors should focus on efforts to improve the quality of delivering end-of-life care that honors and upholds a patient’s wishes. Strengthening the clinical training of physicians in palliative care, developing quality metrics and standards, and educating the public should remain a top priority.

Will tying a financial incentive to these services have an impact on the cost and quality of care delivered? Hospitalists can begin billing for valuable services they are already providing on a daily basis, and can better coordinate inpatient medical care when more seniors have clear advanced directives. TH

Dr. Zeitoun is a member of Team Hospitalist.

Hospitalists care for patients with the most serious, chronic, and complex illnesses. As a result, they are often faced with the daunting task of counseling their patients to help them clearly define their end-of-life wishes. The mere subject of death is met with apprehension and avoidance, but its inevitability warrants an early discussion.

End-of-life care, also known as Advance Care Planning (ACP), enables patients to formulate advanced directives: a living will, the designation of a healthcare proxy, Medical Orders for Life-Sustaining Treatment (MOLST), and the preparation for hospice care, among others. Patients should start thinking about their healthcare options and share such important decisions with their physicians and family before the need for hospitalization.

On October 30, 2015, the Centers for Medicare and Medicaid Services (CMS) released the final payment rules for Medicare reimbursement of physicians who consult with their patients on advance care planning. This separate payment system under the 2016 Physician Fee Schedule will impact the almost 55 million Medicare beneficiaries and their healthcare providers.

Effective January 1, 2016, Medicare will pay $86 for 30 minutes of ACP in a physician’s office and will pay $80 for the same service in a hospital (CPT billing code 99497). In both settings, Medicare will pay up to $75 for 30 additional minutes of consultation (add-on CPT billing code 99498). Such counseling can take place during a senior’s annual wellness visit or during a routine office visit and at various stages of health, always “at the discretion of the beneficiary.”

Six years ago, proposed legislation on Medicare reimbursement for ACP under the Accountable Care Act (ACA) sparked political debate over fears that the implementation of so-called “death panels” could influence decisions to avoid medical care. The goal was to reduce healthcare costs, but these controversial provisions were dropped with the passage of the ACA. This time, there was less resistance.

Proponents of this new legislation, such as the American Medical Association and the American Academy of Palliative and Hospice Medicine, say that this rule will encourage physicians to make time for these lengthy discussions and facilitate patient choices while improving quality of care for seniors. Opponents, including the Association of American Physicians and Surgeons, contend that such payments will “create financial incentives to persuade patients to consent to the denial of care.”

Patrick Conway, MD, CMS' chief medical officer, told the New York Times, "We received overwhelmingly positive comments about the importance of these conversations between physicians and patients. We know that many patients and families want to have these discussions."

Future endeavors should focus on efforts to improve the quality of delivering end-of-life care that honors and upholds a patient’s wishes. Strengthening the clinical training of physicians in palliative care, developing quality metrics and standards, and educating the public should remain a top priority.

Will tying a financial incentive to these services have an impact on the cost and quality of care delivered? Hospitalists can begin billing for valuable services they are already providing on a daily basis, and can better coordinate inpatient medical care when more seniors have clear advanced directives. TH

Dr. Zeitoun is a member of Team Hospitalist.

Hospitalists care for patients with the most serious, chronic, and complex illnesses. As a result, they are often faced with the daunting task of counseling their patients to help them clearly define their end-of-life wishes. The mere subject of death is met with apprehension and avoidance, but its inevitability warrants an early discussion.

End-of-life care, also known as Advance Care Planning (ACP), enables patients to formulate advanced directives: a living will, the designation of a healthcare proxy, Medical Orders for Life-Sustaining Treatment (MOLST), and the preparation for hospice care, among others. Patients should start thinking about their healthcare options and share such important decisions with their physicians and family before the need for hospitalization.

On October 30, 2015, the Centers for Medicare and Medicaid Services (CMS) released the final payment rules for Medicare reimbursement of physicians who consult with their patients on advance care planning. This separate payment system under the 2016 Physician Fee Schedule will impact the almost 55 million Medicare beneficiaries and their healthcare providers.

Effective January 1, 2016, Medicare will pay $86 for 30 minutes of ACP in a physician’s office and will pay $80 for the same service in a hospital (CPT billing code 99497). In both settings, Medicare will pay up to $75 for 30 additional minutes of consultation (add-on CPT billing code 99498). Such counseling can take place during a senior’s annual wellness visit or during a routine office visit and at various stages of health, always “at the discretion of the beneficiary.”

Six years ago, proposed legislation on Medicare reimbursement for ACP under the Accountable Care Act (ACA) sparked political debate over fears that the implementation of so-called “death panels” could influence decisions to avoid medical care. The goal was to reduce healthcare costs, but these controversial provisions were dropped with the passage of the ACA. This time, there was less resistance.

Proponents of this new legislation, such as the American Medical Association and the American Academy of Palliative and Hospice Medicine, say that this rule will encourage physicians to make time for these lengthy discussions and facilitate patient choices while improving quality of care for seniors. Opponents, including the Association of American Physicians and Surgeons, contend that such payments will “create financial incentives to persuade patients to consent to the denial of care.”

Patrick Conway, MD, CMS' chief medical officer, told the New York Times, "We received overwhelmingly positive comments about the importance of these conversations between physicians and patients. We know that many patients and families want to have these discussions."

Future endeavors should focus on efforts to improve the quality of delivering end-of-life care that honors and upholds a patient’s wishes. Strengthening the clinical training of physicians in palliative care, developing quality metrics and standards, and educating the public should remain a top priority.

Will tying a financial incentive to these services have an impact on the cost and quality of care delivered? Hospitalists can begin billing for valuable services they are already providing on a daily basis, and can better coordinate inpatient medical care when more seniors have clear advanced directives. TH

Dr. Zeitoun is a member of Team Hospitalist.

WASHINGTON – Maintaining safety and helping to ensure caregiver well-being are critical interventions for children with posttraumatic stress disorder (PTSD) and other trauma syndromes, Dr. Mary Margaret Gleason said at the annual meeting of the American Academy of Pediatrics.

“Talk a lot [with caregivers] about safety, meaning the [importance of a] lack of violence in the home and the lack of corporal punishment,” said Dr. Gleason, a pediatrician and child and adolescent psychiatrist at Tulane University in New Orleans. “And equally important, make sure that parents are taking care of themselves and are getting treatment [if they’ve also experienced trauma].”

Skyak/iStock.com

PTSD must be treated with evidence-based therapy or it will become more entrenched with time, she said. Both child-parent psychotherapy in toddlers and preschool-aged children, and cognitive behavioral therapy (CBT) in children of preschool age and up, lead to short-term and sustained reductions in children’s symptoms.

In communities without treatment specialists and resources, stressing safety becomes even more important. Help children with PTSD and other trauma disorders to learn to recognize and label their feelings, manage emotional dysregulation, learn the principles of CBT, and achieve deep relaxation. “You can put a pulse oximeter on a child and teach them how to do deep relaxation,” she said. “You can challenge them to bring down the numbers.”

Books on CBT for general anxiety – and, increasingly, online CBT tools – can be helpful for some families, as can the National Child Traumatic Stress Network’s online resources (www.nctsn.org).

Dr. Gleason advised looking for a broad range of disorders in children who have experienced trauma – whether the trauma is acute or chronic, and whether it involves personal or community events. “You need to be thinking about PTSD, certainly, but also attention-deficit/hyperactivity disorder (ADHD), disruptive behaviors, mood disorders, separation anxiety disorders, and sleep disorders,” she said. Conversely, “if a child develops another disorder after a traumatic event, look for signs of PTSD.”

A study of children living in and around New Orleans when Hurricane Katrina struck in 2005 found a wide range of disorders as well as high prevalence of PTSD. “There were [few] children who developed new diagnoses who didn’t also have some symptoms of PTSD,” Dr. Gleason said.

The Diagnostic and Statistical Manual of Mental Disorders–5 placed PTSD in the diagnostic category of trauma- and stressor-related disorders and included separate criteria for PTSD in preschool children. PTSD broadly involves symptoms of at least 1-month duration from four symptom clusters: Intrusive thoughts (e.g. distressing dreams), avoidance, negative alterations in cognition and mood, and changed arousal and reactivity.

Preschool PTSD applies to children ages 6 years and younger, and requires fewer symptoms to be present. The arousal/reactivity symptoms cluster includes irritability and extreme tantrums, she noted.

For children of any age, it is important to note that distressing dreams do not have to involve content specific to the traumatic event to meet diagnostic criteria, Dr. Gleason said.

Compared with PTSD, less is known about the presentation in school-age children and adolescents of reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) – two other trauma-related disorders in DSM-5. Both are related to the attachment system and require a developmental age of at least 9 months, and both involve “pathogenic care,” which can mean emotional neglect and/or persistent disregard of the child’s basic physical needs.

The child with RAD “rarely seeks comfort” when distressed, has a limited response to comfort, and has limited positive affect, Dr. Gleason explained.

“When they fall and hurt their knee, or when they build a tower and it falls over, they don’t look for anyone to help them organize their feelings. And when someone tries to help them, this doesn’t reduce their distress,” she said.

There is some overlap with the clinical presentation of autism spectrum disorder, so it is important to rule out ASD in diagnosing RAD.

Treatment, she said, entails placement in an adequate caregiving environment. “What’s really important to know about RAD is that it’s really a reflection of the current caregiving environment,” Dr. Gleason said. “It’s not about the history. It’s about the [trauma] of what’s happening now.”

DSED is quite different in its clinical construct and course. “These children are indiscriminately social,” she said. “They’ll go off with a stranger … off into new situations without ever looking back to see if their caregiver is there.”

Unlike RAD, this disorder is not associated with current caregiving quality. “It’s important for caregivers to know that this syndrome is a reflection of what happened earlier and not what’s happening now,” Dr. Gleason said. “And it does respond to quality caregiving, but very, very slowly. It can take years.”

Dr. Gleason reported that she has no relevant financial disclosures.

WASHINGTON – Maintaining safety and helping to ensure caregiver well-being are critical interventions for children with posttraumatic stress disorder (PTSD) and other trauma syndromes, Dr. Mary Margaret Gleason said at the annual meeting of the American Academy of Pediatrics.

“Talk a lot [with caregivers] about safety, meaning the [importance of a] lack of violence in the home and the lack of corporal punishment,” said Dr. Gleason, a pediatrician and child and adolescent psychiatrist at Tulane University in New Orleans. “And equally important, make sure that parents are taking care of themselves and are getting treatment [if they’ve also experienced trauma].”

Skyak/iStock.com

PTSD must be treated with evidence-based therapy or it will become more entrenched with time, she said. Both child-parent psychotherapy in toddlers and preschool-aged children, and cognitive behavioral therapy (CBT) in children of preschool age and up, lead to short-term and sustained reductions in children’s symptoms.

In communities without treatment specialists and resources, stressing safety becomes even more important. Help children with PTSD and other trauma disorders to learn to recognize and label their feelings, manage emotional dysregulation, learn the principles of CBT, and achieve deep relaxation. “You can put a pulse oximeter on a child and teach them how to do deep relaxation,” she said. “You can challenge them to bring down the numbers.”

Books on CBT for general anxiety – and, increasingly, online CBT tools – can be helpful for some families, as can the National Child Traumatic Stress Network’s online resources (www.nctsn.org).

Dr. Gleason advised looking for a broad range of disorders in children who have experienced trauma – whether the trauma is acute or chronic, and whether it involves personal or community events. “You need to be thinking about PTSD, certainly, but also attention-deficit/hyperactivity disorder (ADHD), disruptive behaviors, mood disorders, separation anxiety disorders, and sleep disorders,” she said. Conversely, “if a child develops another disorder after a traumatic event, look for signs of PTSD.”

A study of children living in and around New Orleans when Hurricane Katrina struck in 2005 found a wide range of disorders as well as high prevalence of PTSD. “There were [few] children who developed new diagnoses who didn’t also have some symptoms of PTSD,” Dr. Gleason said.

The Diagnostic and Statistical Manual of Mental Disorders–5 placed PTSD in the diagnostic category of trauma- and stressor-related disorders and included separate criteria for PTSD in preschool children. PTSD broadly involves symptoms of at least 1-month duration from four symptom clusters: Intrusive thoughts (e.g. distressing dreams), avoidance, negative alterations in cognition and mood, and changed arousal and reactivity.

Preschool PTSD applies to children ages 6 years and younger, and requires fewer symptoms to be present. The arousal/reactivity symptoms cluster includes irritability and extreme tantrums, she noted.

For children of any age, it is important to note that distressing dreams do not have to involve content specific to the traumatic event to meet diagnostic criteria, Dr. Gleason said.

Compared with PTSD, less is known about the presentation in school-age children and adolescents of reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) – two other trauma-related disorders in DSM-5. Both are related to the attachment system and require a developmental age of at least 9 months, and both involve “pathogenic care,” which can mean emotional neglect and/or persistent disregard of the child’s basic physical needs.

The child with RAD “rarely seeks comfort” when distressed, has a limited response to comfort, and has limited positive affect, Dr. Gleason explained.

“When they fall and hurt their knee, or when they build a tower and it falls over, they don’t look for anyone to help them organize their feelings. And when someone tries to help them, this doesn’t reduce their distress,” she said.

There is some overlap with the clinical presentation of autism spectrum disorder, so it is important to rule out ASD in diagnosing RAD.

Treatment, she said, entails placement in an adequate caregiving environment. “What’s really important to know about RAD is that it’s really a reflection of the current caregiving environment,” Dr. Gleason said. “It’s not about the history. It’s about the [trauma] of what’s happening now.”

DSED is quite different in its clinical construct and course. “These children are indiscriminately social,” she said. “They’ll go off with a stranger … off into new situations without ever looking back to see if their caregiver is there.”

Unlike RAD, this disorder is not associated with current caregiving quality. “It’s important for caregivers to know that this syndrome is a reflection of what happened earlier and not what’s happening now,” Dr. Gleason said. “And it does respond to quality caregiving, but very, very slowly. It can take years.”

Dr. Gleason reported that she has no relevant financial disclosures.

WASHINGTON – Maintaining safety and helping to ensure caregiver well-being are critical interventions for children with posttraumatic stress disorder (PTSD) and other trauma syndromes, Dr. Mary Margaret Gleason said at the annual meeting of the American Academy of Pediatrics.

“Talk a lot [with caregivers] about safety, meaning the [importance of a] lack of violence in the home and the lack of corporal punishment,” said Dr. Gleason, a pediatrician and child and adolescent psychiatrist at Tulane University in New Orleans. “And equally important, make sure that parents are taking care of themselves and are getting treatment [if they’ve also experienced trauma].”

Skyak/iStock.com

PTSD must be treated with evidence-based therapy or it will become more entrenched with time, she said. Both child-parent psychotherapy in toddlers and preschool-aged children, and cognitive behavioral therapy (CBT) in children of preschool age and up, lead to short-term and sustained reductions in children’s symptoms.

In communities without treatment specialists and resources, stressing safety becomes even more important. Help children with PTSD and other trauma disorders to learn to recognize and label their feelings, manage emotional dysregulation, learn the principles of CBT, and achieve deep relaxation. “You can put a pulse oximeter on a child and teach them how to do deep relaxation,” she said. “You can challenge them to bring down the numbers.”

Books on CBT for general anxiety – and, increasingly, online CBT tools – can be helpful for some families, as can the National Child Traumatic Stress Network’s online resources (www.nctsn.org).

Dr. Gleason advised looking for a broad range of disorders in children who have experienced trauma – whether the trauma is acute or chronic, and whether it involves personal or community events. “You need to be thinking about PTSD, certainly, but also attention-deficit/hyperactivity disorder (ADHD), disruptive behaviors, mood disorders, separation anxiety disorders, and sleep disorders,” she said. Conversely, “if a child develops another disorder after a traumatic event, look for signs of PTSD.”

A study of children living in and around New Orleans when Hurricane Katrina struck in 2005 found a wide range of disorders as well as high prevalence of PTSD. “There were [few] children who developed new diagnoses who didn’t also have some symptoms of PTSD,” Dr. Gleason said.

The Diagnostic and Statistical Manual of Mental Disorders–5 placed PTSD in the diagnostic category of trauma- and stressor-related disorders and included separate criteria for PTSD in preschool children. PTSD broadly involves symptoms of at least 1-month duration from four symptom clusters: Intrusive thoughts (e.g. distressing dreams), avoidance, negative alterations in cognition and mood, and changed arousal and reactivity.

Preschool PTSD applies to children ages 6 years and younger, and requires fewer symptoms to be present. The arousal/reactivity symptoms cluster includes irritability and extreme tantrums, she noted.

For children of any age, it is important to note that distressing dreams do not have to involve content specific to the traumatic event to meet diagnostic criteria, Dr. Gleason said.

Compared with PTSD, less is known about the presentation in school-age children and adolescents of reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED) – two other trauma-related disorders in DSM-5. Both are related to the attachment system and require a developmental age of at least 9 months, and both involve “pathogenic care,” which can mean emotional neglect and/or persistent disregard of the child’s basic physical needs.

The child with RAD “rarely seeks comfort” when distressed, has a limited response to comfort, and has limited positive affect, Dr. Gleason explained.

“When they fall and hurt their knee, or when they build a tower and it falls over, they don’t look for anyone to help them organize their feelings. And when someone tries to help them, this doesn’t reduce their distress,” she said.

There is some overlap with the clinical presentation of autism spectrum disorder, so it is important to rule out ASD in diagnosing RAD.

Treatment, she said, entails placement in an adequate caregiving environment. “What’s really important to know about RAD is that it’s really a reflection of the current caregiving environment,” Dr. Gleason said. “It’s not about the history. It’s about the [trauma] of what’s happening now.”

DSED is quite different in its clinical construct and course. “These children are indiscriminately social,” she said. “They’ll go off with a stranger … off into new situations without ever looking back to see if their caregiver is there.”

Unlike RAD, this disorder is not associated with current caregiving quality. “It’s important for caregivers to know that this syndrome is a reflection of what happened earlier and not what’s happening now,” Dr. Gleason said. “And it does respond to quality caregiving, but very, very slowly. It can take years.”

Dr. Gleason reported that she has no relevant financial disclosures.

Hematopoietic stem cells

in the bone marrow

Scientists say that, using a model of the hematopoietic system, they have determined which signaling pathways play an essential role in the self-renewal of hematopoietic stem cells (HSCs).

They found that a particularly important role in this process is the interactive communication with surrounding tissue cells in the bone marrow.

Robert Oostendorp, PhD, of Klinikum Rechts der Isar der Technischen Universität München in Munich, Germany, and his colleagues described these findings in Stem Cell Reports.

The team noted that, in steady-state conditions, HSCs are maintained as slow-dividing clones of quiescent cells. However, when stress occurs, such as an accident that leads to substantial blood loss or the defense against a pathogen requires more blood cells in the course of an infection, HSCs are activated.

In response, the entire hematopoietic system switches from “standby” mode into a state of alert. The activated HSCs generate new blood cells to counteract the blood loss or combat the pathogen. At the same time, self-renewal keeps the stem cell pool replenished.

This switch is accompanied by a complex communication process between the HSCs and tissue cells—an area that had not previously been examined in depth.

“In our study, we set out to establish which tissue signals are important to stem cell maintenance and functionality, and which HSC signals influence the microenvironment,” Dr Oostendorp said.

He and his colleagues used mixed cultures of tissue cells and HSCs to investigate how these cell types interact.

The scientists analyzed factors that are upregulated or downregulated in the interplay between tissue cells and HSCs. And they linked these findings with the signaling pathways described in existing literature.

The team then consolidated this information in a bioinformatics computer model. And they conducted extensive cell experiments to confirm the computer-generated signaling pathway model.

“The outcome was very interesting indeed,” Dr Oostendorp said. “The entire system operates in a feedback loop. In ‘alert’ mode, the stem cells first influence the behavior of the tissue cells, which, in turn, impact on the stem cells, triggering the self-renewal step.”

In alert mode, HSCs emit signaling substances, which induce tissue cells to release the connective tissue growth factor (CTGF) messenger. This is essential to maintain the HSCs through self-renewal. In the absence of CTGF, HSCs age and cannot replenish the stem cell pool.

“Our findings could prove significant in treating leukemia,” Dr Oostendorp noted. “In this condition, the stem cells are hyperactive, and their division is unchecked. Leukemic blood cells are in a constant state of alert, so we would expect a similar interplay with the tissue cells.”

To date, however, the focus here has been limited to stem cells as the actual source of the defect.

“Given what we know now about feedback loops, it would be important to integrate the surrounding cells in therapeutic approaches too, since they exert a strong influence on stem cell division,” Dr Oostendorp concluded.

Hematopoietic stem cells

in the bone marrow

Scientists say that, using a model of the hematopoietic system, they have determined which signaling pathways play an essential role in the self-renewal of hematopoietic stem cells (HSCs).

They found that a particularly important role in this process is the interactive communication with surrounding tissue cells in the bone marrow.

Robert Oostendorp, PhD, of Klinikum Rechts der Isar der Technischen Universität München in Munich, Germany, and his colleagues described these findings in Stem Cell Reports.

The team noted that, in steady-state conditions, HSCs are maintained as slow-dividing clones of quiescent cells. However, when stress occurs, such as an accident that leads to substantial blood loss or the defense against a pathogen requires more blood cells in the course of an infection, HSCs are activated.

In response, the entire hematopoietic system switches from “standby” mode into a state of alert. The activated HSCs generate new blood cells to counteract the blood loss or combat the pathogen. At the same time, self-renewal keeps the stem cell pool replenished.

This switch is accompanied by a complex communication process between the HSCs and tissue cells—an area that had not previously been examined in depth.

“In our study, we set out to establish which tissue signals are important to stem cell maintenance and functionality, and which HSC signals influence the microenvironment,” Dr Oostendorp said.

He and his colleagues used mixed cultures of tissue cells and HSCs to investigate how these cell types interact.

The scientists analyzed factors that are upregulated or downregulated in the interplay between tissue cells and HSCs. And they linked these findings with the signaling pathways described in existing literature.

The team then consolidated this information in a bioinformatics computer model. And they conducted extensive cell experiments to confirm the computer-generated signaling pathway model.

“The outcome was very interesting indeed,” Dr Oostendorp said. “The entire system operates in a feedback loop. In ‘alert’ mode, the stem cells first influence the behavior of the tissue cells, which, in turn, impact on the stem cells, triggering the self-renewal step.”

In alert mode, HSCs emit signaling substances, which induce tissue cells to release the connective tissue growth factor (CTGF) messenger. This is essential to maintain the HSCs through self-renewal. In the absence of CTGF, HSCs age and cannot replenish the stem cell pool.

“Our findings could prove significant in treating leukemia,” Dr Oostendorp noted. “In this condition, the stem cells are hyperactive, and their division is unchecked. Leukemic blood cells are in a constant state of alert, so we would expect a similar interplay with the tissue cells.”

To date, however, the focus here has been limited to stem cells as the actual source of the defect.

“Given what we know now about feedback loops, it would be important to integrate the surrounding cells in therapeutic approaches too, since they exert a strong influence on stem cell division,” Dr Oostendorp concluded.

Hematopoietic stem cells

in the bone marrow

Scientists say that, using a model of the hematopoietic system, they have determined which signaling pathways play an essential role in the self-renewal of hematopoietic stem cells (HSCs).

They found that a particularly important role in this process is the interactive communication with surrounding tissue cells in the bone marrow.

Robert Oostendorp, PhD, of Klinikum Rechts der Isar der Technischen Universität München in Munich, Germany, and his colleagues described these findings in Stem Cell Reports.

The team noted that, in steady-state conditions, HSCs are maintained as slow-dividing clones of quiescent cells. However, when stress occurs, such as an accident that leads to substantial blood loss or the defense against a pathogen requires more blood cells in the course of an infection, HSCs are activated.

In response, the entire hematopoietic system switches from “standby” mode into a state of alert. The activated HSCs generate new blood cells to counteract the blood loss or combat the pathogen. At the same time, self-renewal keeps the stem cell pool replenished.

This switch is accompanied by a complex communication process between the HSCs and tissue cells—an area that had not previously been examined in depth.

“In our study, we set out to establish which tissue signals are important to stem cell maintenance and functionality, and which HSC signals influence the microenvironment,” Dr Oostendorp said.

He and his colleagues used mixed cultures of tissue cells and HSCs to investigate how these cell types interact.

The scientists analyzed factors that are upregulated or downregulated in the interplay between tissue cells and HSCs. And they linked these findings with the signaling pathways described in existing literature.

The team then consolidated this information in a bioinformatics computer model. And they conducted extensive cell experiments to confirm the computer-generated signaling pathway model.

“The outcome was very interesting indeed,” Dr Oostendorp said. “The entire system operates in a feedback loop. In ‘alert’ mode, the stem cells first influence the behavior of the tissue cells, which, in turn, impact on the stem cells, triggering the self-renewal step.”

In alert mode, HSCs emit signaling substances, which induce tissue cells to release the connective tissue growth factor (CTGF) messenger. This is essential to maintain the HSCs through self-renewal. In the absence of CTGF, HSCs age and cannot replenish the stem cell pool.

“Our findings could prove significant in treating leukemia,” Dr Oostendorp noted. “In this condition, the stem cells are hyperactive, and their division is unchecked. Leukemic blood cells are in a constant state of alert, so we would expect a similar interplay with the tissue cells.”

To date, however, the focus here has been limited to stem cells as the actual source of the defect.

“Given what we know now about feedback loops, it would be important to integrate the surrounding cells in therapeutic approaches too, since they exert a strong influence on stem cell division,” Dr Oostendorp concluded.

Thomas J. Braciale, MD, PhD

Photo courtesy of

Josh Barney/University of

Virginia Health System

An unexpected result of a lab experiment has led researchers to a new way to trigger red blood cell (RBC) production.

They found that engaging a stress receptor on type 1 conventional dendritic cells can induce stress erythropoiesis in mice.

The team believes that, eventually, this method could be used to turn on RBC production in humans when necessary, perhaps to replace a blood transfusion or as a stop-gap measure when a transfusion is delayed.

Thomas J. Braciale, MD, PhD, of the University of Virginia in Charlottesville, and his colleagues conducted this research and reported the results in The Journal of Clinical Investigation.

The team was not investigating RBC production when they made their discovery. They were looking into the role of dendritic cells in the lungs.

Dendritic cells have traditionally been thought to be sensors of infection and inflammation, but a lab test involving the flu virus produced an unexpected effect in mice that ultimately revealed a new aspect to the cells’ function.

The researchers injected mice with the flu virus and an αCD24 monoclonal antibody, which resulted in splenomegaly. The team was baffled at this outcome, so they repeated the experiment, only to get the same results.

“We did it again, and I didn’t believe it, and we did it again, and I didn’t believe it,” Dr Braciale recalled. “I asked whether you needed flu to infect the mice when you injected this antibody. So the postdoc did the experiment, and he just injected the antibody without flu-injecting the mice—giant spleens. After much consultation, after talking with my colleagues in pathology, we decided we were inducing stress erythropoiesis.”

Specifically, the researchers found that engaging CD24 on type 1 conventional dendritic cells upregulates expression of the Kit ligand stem cell factor, which results in Kit-mediated proliferative expansion of early erythroid progenitors and transient reticulocytosis.

“In a very basic way, what we’ve discovered is that the process of regulating stress in the body is mediated—certainly in part, at least—by these dendritic cells,” Dr Braciale explained. “And stress can be a variety of different stresses.”

“It doesn’t have to be infection. It doesn’t have to be inflammation. It can be anemia. It can be hemorrhage. And these cells act to initiate this response that, until this report, there’s been really no evidence that [dendritic] cells ever participate in making red blood cells.”

More work is needed before this approach to RBC production can be tested in humans. However, Dr Braciale is optimistic, based on the findings so far.

“We’re very excited to see where this goes,” he said. “We know that the same things can be done in humans in the following sense. There are mice called humanized mice. These are mice that are engineered so they have a human blood system. And if you inject these mice with this antibody, they’ll make red blood cells.”

Thomas J. Braciale, MD, PhD

Photo courtesy of

Josh Barney/University of

Virginia Health System

An unexpected result of a lab experiment has led researchers to a new way to trigger red blood cell (RBC) production.

They found that engaging a stress receptor on type 1 conventional dendritic cells can induce stress erythropoiesis in mice.

The team believes that, eventually, this method could be used to turn on RBC production in humans when necessary, perhaps to replace a blood transfusion or as a stop-gap measure when a transfusion is delayed.

Thomas J. Braciale, MD, PhD, of the University of Virginia in Charlottesville, and his colleagues conducted this research and reported the results in The Journal of Clinical Investigation.

The team was not investigating RBC production when they made their discovery. They were looking into the role of dendritic cells in the lungs.

Dendritic cells have traditionally been thought to be sensors of infection and inflammation, but a lab test involving the flu virus produced an unexpected effect in mice that ultimately revealed a new aspect to the cells’ function.

The researchers injected mice with the flu virus and an αCD24 monoclonal antibody, which resulted in splenomegaly. The team was baffled at this outcome, so they repeated the experiment, only to get the same results.

“We did it again, and I didn’t believe it, and we did it again, and I didn’t believe it,” Dr Braciale recalled. “I asked whether you needed flu to infect the mice when you injected this antibody. So the postdoc did the experiment, and he just injected the antibody without flu-injecting the mice—giant spleens. After much consultation, after talking with my colleagues in pathology, we decided we were inducing stress erythropoiesis.”

Specifically, the researchers found that engaging CD24 on type 1 conventional dendritic cells upregulates expression of the Kit ligand stem cell factor, which results in Kit-mediated proliferative expansion of early erythroid progenitors and transient reticulocytosis.

“In a very basic way, what we’ve discovered is that the process of regulating stress in the body is mediated—certainly in part, at least—by these dendritic cells,” Dr Braciale explained. “And stress can be a variety of different stresses.”

“It doesn’t have to be infection. It doesn’t have to be inflammation. It can be anemia. It can be hemorrhage. And these cells act to initiate this response that, until this report, there’s been really no evidence that [dendritic] cells ever participate in making red blood cells.”

More work is needed before this approach to RBC production can be tested in humans. However, Dr Braciale is optimistic, based on the findings so far.

“We’re very excited to see where this goes,” he said. “We know that the same things can be done in humans in the following sense. There are mice called humanized mice. These are mice that are engineered so they have a human blood system. And if you inject these mice with this antibody, they’ll make red blood cells.”

Thomas J. Braciale, MD, PhD

Photo courtesy of

Josh Barney/University of

Virginia Health System

An unexpected result of a lab experiment has led researchers to a new way to trigger red blood cell (RBC) production.

They found that engaging a stress receptor on type 1 conventional dendritic cells can induce stress erythropoiesis in mice.

The team believes that, eventually, this method could be used to turn on RBC production in humans when necessary, perhaps to replace a blood transfusion or as a stop-gap measure when a transfusion is delayed.

Thomas J. Braciale, MD, PhD, of the University of Virginia in Charlottesville, and his colleagues conducted this research and reported the results in The Journal of Clinical Investigation.

The team was not investigating RBC production when they made their discovery. They were looking into the role of dendritic cells in the lungs.

Dendritic cells have traditionally been thought to be sensors of infection and inflammation, but a lab test involving the flu virus produced an unexpected effect in mice that ultimately revealed a new aspect to the cells’ function.

The researchers injected mice with the flu virus and an αCD24 monoclonal antibody, which resulted in splenomegaly. The team was baffled at this outcome, so they repeated the experiment, only to get the same results.

“We did it again, and I didn’t believe it, and we did it again, and I didn’t believe it,” Dr Braciale recalled. “I asked whether you needed flu to infect the mice when you injected this antibody. So the postdoc did the experiment, and he just injected the antibody without flu-injecting the mice—giant spleens. After much consultation, after talking with my colleagues in pathology, we decided we were inducing stress erythropoiesis.”

Specifically, the researchers found that engaging CD24 on type 1 conventional dendritic cells upregulates expression of the Kit ligand stem cell factor, which results in Kit-mediated proliferative expansion of early erythroid progenitors and transient reticulocytosis.

“In a very basic way, what we’ve discovered is that the process of regulating stress in the body is mediated—certainly in part, at least—by these dendritic cells,” Dr Braciale explained. “And stress can be a variety of different stresses.”

“It doesn’t have to be infection. It doesn’t have to be inflammation. It can be anemia. It can be hemorrhage. And these cells act to initiate this response that, until this report, there’s been really no evidence that [dendritic] cells ever participate in making red blood cells.”

More work is needed before this approach to RBC production can be tested in humans. However, Dr Braciale is optimistic, based on the findings so far.

“We’re very excited to see where this goes,” he said. “We know that the same things can be done in humans in the following sense. There are mice called humanized mice. These are mice that are engineered so they have a human blood system. And if you inject these mice with this antibody, they’ll make red blood cells.”