Leaders of the American College of Surgeons (ACS) hosted a Stop the Bleed^® training program on Capitol Hill October 12 for members of Congress and their staffs. The congressional event focused on how early intervention from a Stop the Bleed-trained individual can save the life of someone suffering from a bleeding injury. Participants came to learn more about the ACS’ efforts with Stop the Bleed and engage in the hands-on training in how to control bleeding. The training was led by ACS Fellows, including Lenworth M. Jacobs, Jr., MD, MPH, FACS; Leonard J. Weireter, Jr., MD, FACS; Mark L. Gestring, MD, FACS; John H. Armstrong, MD, FACS; Joseph V. Sakran, MD, MPH, MPA, FACS; and Jack Sava, MD, FACS. Congressional guests included Reps. Ami Bera, MD (D-CA); Phil Roe, MD (R-TN); Raul Ruiz, MD (D-CA); and Brad Wenstrup, DPM (R-OH), who provided opening remarks.

Leaders of the American College of Surgeons (ACS) hosted a Stop the Bleed^® training program on Capitol Hill October 12 for members of Congress and their staffs. The congressional event focused on how early intervention from a Stop the Bleed-trained individual can save the life of someone suffering from a bleeding injury. Participants came to learn more about the ACS’ efforts with Stop the Bleed and engage in the hands-on training in how to control bleeding. The training was led by ACS Fellows, including Lenworth M. Jacobs, Jr., MD, MPH, FACS; Leonard J. Weireter, Jr., MD, FACS; Mark L. Gestring, MD, FACS; John H. Armstrong, MD, FACS; Joseph V. Sakran, MD, MPH, MPA, FACS; and Jack Sava, MD, FACS. Congressional guests included Reps. Ami Bera, MD (D-CA); Phil Roe, MD (R-TN); Raul Ruiz, MD (D-CA); and Brad Wenstrup, DPM (R-OH), who provided opening remarks.

Leaders of the American College of Surgeons (ACS) hosted a Stop the Bleed^® training program on Capitol Hill October 12 for members of Congress and their staffs. The congressional event focused on how early intervention from a Stop the Bleed-trained individual can save the life of someone suffering from a bleeding injury. Participants came to learn more about the ACS’ efforts with Stop the Bleed and engage in the hands-on training in how to control bleeding. The training was led by ACS Fellows, including Lenworth M. Jacobs, Jr., MD, MPH, FACS; Leonard J. Weireter, Jr., MD, FACS; Mark L. Gestring, MD, FACS; John H. Armstrong, MD, FACS; Joseph V. Sakran, MD, MPH, MPA, FACS; and Jack Sava, MD, FACS. Congressional guests included Reps. Ami Bera, MD (D-CA); Phil Roe, MD (R-TN); Raul Ruiz, MD (D-CA); and Brad Wenstrup, DPM (R-OH), who provided opening remarks.

The November issue of the Bulletin of the American College of Surgeons is now available online at bulletin.facs.org. This month’s Bulletin includes the following features, columns, and new stories, among others:

Features

The November issue of the Bulletin of the American College of Surgeons is now available online at bulletin.facs.org. This month’s Bulletin includes the following features, columns, and new stories, among others:

Features

The November issue of the Bulletin of the American College of Surgeons is now available online at bulletin.facs.org. This month’s Bulletin includes the following features, columns, and new stories, among others:

Features

GENEVA – Psoriasis patients are roughly two-thirds more likely to die of alcohol-related causes than their peers in the general population, Rosa Parisi, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Indeed, alcohol-related mortality appears to be an important contributor to the long-recognized elevated risk of premature mortality in patients who’ve been diagnosed with psoriasis, according to Dr. Parisi of the University of Manchester (England), who presented the results of a retrospective cohort study of alcohol-related deaths. The reasons for psoriasis patients’ increased risk of early mortality have been unclear, although it’s well established that psoriasis is associated with increased rates of unhealthy behaviors, including smoking and high alcohol consumption.

[email protected]
 

GENEVA – Psoriasis patients are roughly two-thirds more likely to die of alcohol-related causes than their peers in the general population, Rosa Parisi, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Indeed, alcohol-related mortality appears to be an important contributor to the long-recognized elevated risk of premature mortality in patients who’ve been diagnosed with psoriasis, according to Dr. Parisi of the University of Manchester (England), who presented the results of a retrospective cohort study of alcohol-related deaths. The reasons for psoriasis patients’ increased risk of early mortality have been unclear, although it’s well established that psoriasis is associated with increased rates of unhealthy behaviors, including smoking and high alcohol consumption.

[email protected]
 

GENEVA – Psoriasis patients are roughly two-thirds more likely to die of alcohol-related causes than their peers in the general population, Rosa Parisi, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Indeed, alcohol-related mortality appears to be an important contributor to the long-recognized elevated risk of premature mortality in patients who’ve been diagnosed with psoriasis, according to Dr. Parisi of the University of Manchester (England), who presented the results of a retrospective cohort study of alcohol-related deaths. The reasons for psoriasis patients’ increased risk of early mortality have been unclear, although it’s well established that psoriasis is associated with increased rates of unhealthy behaviors, including smoking and high alcohol consumption.

[email protected]
 

Given the recent rise in marijuana legalization efforts and an overall increase in the prevalence of marijuana use, it is becoming increasingly important to recognize conditions that are associated with its use. Data obtained from the National Survey on Drug Use and Health show the prevalence of marijuana use within the past month among those surveyed was 8.4% in 2014. This represents a 35% increase from the same study in 2002. Based on this survey, 2.5 million people (or ~7,000 per day) used marijuana for the first time.¹

Following the liberalization of marijuana in Colorado, the prevalence of presentation to the emergency department (ED) for cyclic vomiting nearly doubled.² During the 2016 election season, several states included legislation that increased access to marijuana on the ballot, most of which passed. There are now 28 states plus the District of Columbia that permit medical marijuana usage, and 8 of those states and the District of Columbia have laws allowing for recreational use of marijuana.³

First described in a case series by Allen and colleagues in 2004, cannabinoid hyperemesis syndrome (CHS) is indicated by recurrent episodes of nausea and vomiting with vague abdominal pain and compulsive hot bathing in the setting of chronic, often daily, cannabis use.⁴ A case of a middle-aged veteran with chronic marijuana use and recurrent, self-limited nausea and vomiting is presented here.

Case Presentation

A 45-year-old man presented to the ED with a 5-day history of persistent nausea and vomiting that began abruptly. The symptoms had been constant since onset, resulting in very little oral intake. The patient reported no hematemesis or coffee ground emesis. He noted a drop in his urine output over the previous 2 days. He also reported abdominal pain associated with the nausea. The patient characterized his pain as “dull and achy” diffuse pain that was partially relieved with emesis. His bowel movements had been regular, and he reported no diarrhea, fever, chills, or other constitutional symptoms. Additional 10-point review of systems was otherwise negative. The patient reported smoking marijuana multiple times daily for many years. The patient reported he had not used alcohol for several months.

A physical exam showed a pale and diaphoretic patient. Vital signs were significant for mild hypertension (150/75), but the patient was afebrile with a normal heart rate. An abdominal exam revealed a nontender, nondistended abdomen with no signs of rebound or guarding. The remainder of the examination was unremarkable. An initial workup showed a mild elevation of serum creatinine to 1.36 mg/dL (baseline is 1.10 mg/dL). Other workups, including complete blood count (CBC) with differential, complete metabolic panel, lipase, amylase, and urine analysis, were all unremarkable.

The patient’s urine drug screen (UDS) was positive for tetrahydrocannabinol (THC). A computed tomography (CT) scan of his abdomen and pelvis with contrast was unremarkable. The patient was admitted for his inability to tolerate oral intake and dehydration and treated supportively with IV fluids and antiemetics.

Overnight, the nursing staff reported that the patient took multiple, prolonged hot showers. Upon further questioning, he reported the hot showers significantly helped the nausea and abdominal pain. He had learned this behavior after experiencing previous episodes of self-limited nausea, vomiting, and abdominal pain.

Extensive review of his medical record revealed that the patient had, in fact, presented to the ED with similar symptoms 11 times in the prior 8 years. He was admitted on 8 occasions over that time frame. The typical hospital course included supportive care with antiemetics and IV fluids. The patient’s symptoms typically resolved within 24 to 72 hours of hospitalization. Previous evaluations included additional unremarkable CT imaging of the abdomen and pelvis. The patient also had received 2 esophagogastroduodenoscopies (EGDs), one 2 years prior and the other 5 years prior. Both EGDs showed only mild gastritis. On every check during the previous 8 years, the patient’s UDS was positive for THC.

Most of his previous admissions were attributed to viral gastroenteritis due to the self-limited nature of the symptoms. Other admissions were attributed to alcohol-induced gastritis. However, after abstaining from alcohol for long periods, the patient had continued recurrence of the symptoms and increased frequency of presentations to the ED.

The characteristics, signs, and symptoms of CHS were discussed with the patient. The patient strongly felt as though these symptoms aligned with his clinical course over the prior 8 years. At time of writing, the patient had gone 20 months without requiring hospitalization; however, he had a recent relapse of marijuana use and subsequently required hospitalization.

Discussion

As in this case, CHS often presents with refractory, self-limited nausea and vomiting with vague abdominal pain that is temporarily relieved by hot baths or showers. In the largest case series, it was noted the average age was 32 years, and the majority of subjects used marijuana at least weekly for > 2 years.⁵ Many studies categorize CHS into 3 phases: prodromal, hyperemetic, and recovery.

The prodromal, or preemetic phase, is characterized by early morning nausea without emesis and abdominal discomfort. The hyperemetic phase begins when the patient accesses the health care system via either the ED or primary care physician. This phase is characterized by intractable nausea and vomiting and may be associated with mild diffuse abdominal pain. The nausea and vomiting typically do not respond to antiemetic medications. Patients in this stage also develop a compulsive behavior of hot showers that temporarily relieve the symptoms. These behaviors are thought to be learned through their cyclical periods of emesis and may not be present during the first few hyperemetic phases. During the recovery phase, the patient returns to a baseline state of health and often ceases utilizing the hot shower. The recovery phase can last weeks to months despite continued cannabis use prior to returning to the hyperemetic phase (Figure).^6,7

Simonetto and colleagues proposed clinical criteria for the diagnosis of CHS based on their case series as well as on previously proposed criteria presented by Sontineni and colleagues.^5,8 Long-term cannabis use is required for the diagnosis. In the Simonetto and colleagues case series, the majority of patients developed symptoms within the first 5 years of cannabis use; however, Soriano and colleagues conducted a smaller case series that showed that the majority of subjects used marijuana for roughly 16 years prior to the onset of vomiting.^5,7

The major CHS features that suggest the diagnosis are severe cyclic nausea and vomiting, relief of symptoms with abstinence from cannabis, temporary symptom relief with hot bathing, abdominal pain, and at least weekly use of marijuana. Other supportive features include aged < 50 years, weight loss > 5 kg, symptoms that are worse in the morning, normal bowel habits, and negative evaluation, including laboratory, radiography, and endoscopy (Table).⁵

Treatment often is supportive with emphasis placed on marijuana cessation. Intravenous fluids often are used due to dehydration from the emesis. The use of antiemetics, such as 5-HT3 (eg, ondansetron), D2 (eg, prochlorperazine), H1 (eg, promethazine), or neurokinin-1 receptor antagonists (eg, aprepitant) can be tried, but these therapies often are ineffective. Diet can be advanced as the patient tolerates. Given that many patients are found to have a mild gastritis, H2 blockers or proton pump inhibitors may be used. Extensive counseling on marijuana cessation is needed as it is the only therapy shown to have prolonged relief of the hyperemetic phase.⁶ The length of cessation from marijuana for resolution of the cyclical hyperemesis varies from 1 to 3 months. Returning to marijuana use often results in the returning of CHS.⁵

The pathophysiology of CHS is largely unknown; however, there are several hypothesized mechanisms. Many theorize that due to the lipophilicity and long half-life of THC, a primary compound in marijuana, it accumulates in the body over time.^4,6 It is thought that this accumulation may cause toxicity in both the gastrointestinal tract as well as in the brain. Central effects on the hypothalamic-pituitary axis may play a major role, and the reason for the symptom relief of hot baths is due to a change in thermoregulation in the hypothalamus.⁵ One interesting mechanism relates to CB1 receptor activation and vasodilation within the gastrointestinal tract due to chronic THC accumulation. The relief of the abdominal pain, nausea, and vomiting with hot showers can be secondary to the vasodilation of the skin, causing a redistribution from the gut. This theorized mechanism has been referred to as “cutaneous steal.”⁹

Conclusion

With the increased prevalence of marijuana use in the U.S. over the past decade and reform in legislation taking place over the next couple of years, it is increasingly important to be able to recognize CHS to avoid frequent hospital utilization and repeated costly evaluations. Cannabinoid hyperemesis syndrome is recognized by the triad of chronic cannabis use, cyclical hyperemesis, and compulsive hot bathing.⁴

The syndrome has 3 phases. In the prodromal phase the patient has morning predominance of nausea, usually without emesis. This is followed by the hyperemesis phase, which is characterized by hyperemesis, vague abdominal pain, and learned compulsive hot bathing.

The third phase is the recovery phase, which is a return to normal behavior. During the recovery phase, if patients cease marijuana use, they remain asymptomatic; however, if patients continue to use marijuana, they often have recurrence of the hyperemesis phase.⁵ The diagnosis of cannabinoid hyperemesis syndrome is difficult as it is a diagnosis of exclusion. Patients may present to the ED many times prior to diagnosis. With the changing climate of marijuana laws, it is an important condition to consider when establishing a differential. More studies will be required to evaluate the overall prevalence of this condition as well as if there are any changes following the liberalization of marijuana laws in many states.

Given the recent rise in marijuana legalization efforts and an overall increase in the prevalence of marijuana use, it is becoming increasingly important to recognize conditions that are associated with its use. Data obtained from the National Survey on Drug Use and Health show the prevalence of marijuana use within the past month among those surveyed was 8.4% in 2014. This represents a 35% increase from the same study in 2002. Based on this survey, 2.5 million people (or ~7,000 per day) used marijuana for the first time.¹

Following the liberalization of marijuana in Colorado, the prevalence of presentation to the emergency department (ED) for cyclic vomiting nearly doubled.² During the 2016 election season, several states included legislation that increased access to marijuana on the ballot, most of which passed. There are now 28 states plus the District of Columbia that permit medical marijuana usage, and 8 of those states and the District of Columbia have laws allowing for recreational use of marijuana.³

First described in a case series by Allen and colleagues in 2004, cannabinoid hyperemesis syndrome (CHS) is indicated by recurrent episodes of nausea and vomiting with vague abdominal pain and compulsive hot bathing in the setting of chronic, often daily, cannabis use.⁴ A case of a middle-aged veteran with chronic marijuana use and recurrent, self-limited nausea and vomiting is presented here.

Case Presentation

A 45-year-old man presented to the ED with a 5-day history of persistent nausea and vomiting that began abruptly. The symptoms had been constant since onset, resulting in very little oral intake. The patient reported no hematemesis or coffee ground emesis. He noted a drop in his urine output over the previous 2 days. He also reported abdominal pain associated with the nausea. The patient characterized his pain as “dull and achy” diffuse pain that was partially relieved with emesis. His bowel movements had been regular, and he reported no diarrhea, fever, chills, or other constitutional symptoms. Additional 10-point review of systems was otherwise negative. The patient reported smoking marijuana multiple times daily for many years. The patient reported he had not used alcohol for several months.

A physical exam showed a pale and diaphoretic patient. Vital signs were significant for mild hypertension (150/75), but the patient was afebrile with a normal heart rate. An abdominal exam revealed a nontender, nondistended abdomen with no signs of rebound or guarding. The remainder of the examination was unremarkable. An initial workup showed a mild elevation of serum creatinine to 1.36 mg/dL (baseline is 1.10 mg/dL). Other workups, including complete blood count (CBC) with differential, complete metabolic panel, lipase, amylase, and urine analysis, were all unremarkable.

The patient’s urine drug screen (UDS) was positive for tetrahydrocannabinol (THC). A computed tomography (CT) scan of his abdomen and pelvis with contrast was unremarkable. The patient was admitted for his inability to tolerate oral intake and dehydration and treated supportively with IV fluids and antiemetics.

Overnight, the nursing staff reported that the patient took multiple, prolonged hot showers. Upon further questioning, he reported the hot showers significantly helped the nausea and abdominal pain. He had learned this behavior after experiencing previous episodes of self-limited nausea, vomiting, and abdominal pain.

Extensive review of his medical record revealed that the patient had, in fact, presented to the ED with similar symptoms 11 times in the prior 8 years. He was admitted on 8 occasions over that time frame. The typical hospital course included supportive care with antiemetics and IV fluids. The patient’s symptoms typically resolved within 24 to 72 hours of hospitalization. Previous evaluations included additional unremarkable CT imaging of the abdomen and pelvis. The patient also had received 2 esophagogastroduodenoscopies (EGDs), one 2 years prior and the other 5 years prior. Both EGDs showed only mild gastritis. On every check during the previous 8 years, the patient’s UDS was positive for THC.

Most of his previous admissions were attributed to viral gastroenteritis due to the self-limited nature of the symptoms. Other admissions were attributed to alcohol-induced gastritis. However, after abstaining from alcohol for long periods, the patient had continued recurrence of the symptoms and increased frequency of presentations to the ED.

The characteristics, signs, and symptoms of CHS were discussed with the patient. The patient strongly felt as though these symptoms aligned with his clinical course over the prior 8 years. At time of writing, the patient had gone 20 months without requiring hospitalization; however, he had a recent relapse of marijuana use and subsequently required hospitalization.

Discussion

As in this case, CHS often presents with refractory, self-limited nausea and vomiting with vague abdominal pain that is temporarily relieved by hot baths or showers. In the largest case series, it was noted the average age was 32 years, and the majority of subjects used marijuana at least weekly for > 2 years.⁵ Many studies categorize CHS into 3 phases: prodromal, hyperemetic, and recovery.

The prodromal, or preemetic phase, is characterized by early morning nausea without emesis and abdominal discomfort. The hyperemetic phase begins when the patient accesses the health care system via either the ED or primary care physician. This phase is characterized by intractable nausea and vomiting and may be associated with mild diffuse abdominal pain. The nausea and vomiting typically do not respond to antiemetic medications. Patients in this stage also develop a compulsive behavior of hot showers that temporarily relieve the symptoms. These behaviors are thought to be learned through their cyclical periods of emesis and may not be present during the first few hyperemetic phases. During the recovery phase, the patient returns to a baseline state of health and often ceases utilizing the hot shower. The recovery phase can last weeks to months despite continued cannabis use prior to returning to the hyperemetic phase (Figure).^6,7

Simonetto and colleagues proposed clinical criteria for the diagnosis of CHS based on their case series as well as on previously proposed criteria presented by Sontineni and colleagues.^5,8 Long-term cannabis use is required for the diagnosis. In the Simonetto and colleagues case series, the majority of patients developed symptoms within the first 5 years of cannabis use; however, Soriano and colleagues conducted a smaller case series that showed that the majority of subjects used marijuana for roughly 16 years prior to the onset of vomiting.^5,7

The major CHS features that suggest the diagnosis are severe cyclic nausea and vomiting, relief of symptoms with abstinence from cannabis, temporary symptom relief with hot bathing, abdominal pain, and at least weekly use of marijuana. Other supportive features include aged < 50 years, weight loss > 5 kg, symptoms that are worse in the morning, normal bowel habits, and negative evaluation, including laboratory, radiography, and endoscopy (Table).⁵

Treatment often is supportive with emphasis placed on marijuana cessation. Intravenous fluids often are used due to dehydration from the emesis. The use of antiemetics, such as 5-HT3 (eg, ondansetron), D2 (eg, prochlorperazine), H1 (eg, promethazine), or neurokinin-1 receptor antagonists (eg, aprepitant) can be tried, but these therapies often are ineffective. Diet can be advanced as the patient tolerates. Given that many patients are found to have a mild gastritis, H2 blockers or proton pump inhibitors may be used. Extensive counseling on marijuana cessation is needed as it is the only therapy shown to have prolonged relief of the hyperemetic phase.⁶ The length of cessation from marijuana for resolution of the cyclical hyperemesis varies from 1 to 3 months. Returning to marijuana use often results in the returning of CHS.⁵

The pathophysiology of CHS is largely unknown; however, there are several hypothesized mechanisms. Many theorize that due to the lipophilicity and long half-life of THC, a primary compound in marijuana, it accumulates in the body over time.^4,6 It is thought that this accumulation may cause toxicity in both the gastrointestinal tract as well as in the brain. Central effects on the hypothalamic-pituitary axis may play a major role, and the reason for the symptom relief of hot baths is due to a change in thermoregulation in the hypothalamus.⁵ One interesting mechanism relates to CB1 receptor activation and vasodilation within the gastrointestinal tract due to chronic THC accumulation. The relief of the abdominal pain, nausea, and vomiting with hot showers can be secondary to the vasodilation of the skin, causing a redistribution from the gut. This theorized mechanism has been referred to as “cutaneous steal.”⁹

Conclusion

With the increased prevalence of marijuana use in the U.S. over the past decade and reform in legislation taking place over the next couple of years, it is increasingly important to be able to recognize CHS to avoid frequent hospital utilization and repeated costly evaluations. Cannabinoid hyperemesis syndrome is recognized by the triad of chronic cannabis use, cyclical hyperemesis, and compulsive hot bathing.⁴

The syndrome has 3 phases. In the prodromal phase the patient has morning predominance of nausea, usually without emesis. This is followed by the hyperemesis phase, which is characterized by hyperemesis, vague abdominal pain, and learned compulsive hot bathing.

The third phase is the recovery phase, which is a return to normal behavior. During the recovery phase, if patients cease marijuana use, they remain asymptomatic; however, if patients continue to use marijuana, they often have recurrence of the hyperemesis phase.⁵ The diagnosis of cannabinoid hyperemesis syndrome is difficult as it is a diagnosis of exclusion. Patients may present to the ED many times prior to diagnosis. With the changing climate of marijuana laws, it is an important condition to consider when establishing a differential. More studies will be required to evaluate the overall prevalence of this condition as well as if there are any changes following the liberalization of marijuana laws in many states.

Given the recent rise in marijuana legalization efforts and an overall increase in the prevalence of marijuana use, it is becoming increasingly important to recognize conditions that are associated with its use. Data obtained from the National Survey on Drug Use and Health show the prevalence of marijuana use within the past month among those surveyed was 8.4% in 2014. This represents a 35% increase from the same study in 2002. Based on this survey, 2.5 million people (or ~7,000 per day) used marijuana for the first time.¹

Following the liberalization of marijuana in Colorado, the prevalence of presentation to the emergency department (ED) for cyclic vomiting nearly doubled.² During the 2016 election season, several states included legislation that increased access to marijuana on the ballot, most of which passed. There are now 28 states plus the District of Columbia that permit medical marijuana usage, and 8 of those states and the District of Columbia have laws allowing for recreational use of marijuana.³

First described in a case series by Allen and colleagues in 2004, cannabinoid hyperemesis syndrome (CHS) is indicated by recurrent episodes of nausea and vomiting with vague abdominal pain and compulsive hot bathing in the setting of chronic, often daily, cannabis use.⁴ A case of a middle-aged veteran with chronic marijuana use and recurrent, self-limited nausea and vomiting is presented here.

Case Presentation

A 45-year-old man presented to the ED with a 5-day history of persistent nausea and vomiting that began abruptly. The symptoms had been constant since onset, resulting in very little oral intake. The patient reported no hematemesis or coffee ground emesis. He noted a drop in his urine output over the previous 2 days. He also reported abdominal pain associated with the nausea. The patient characterized his pain as “dull and achy” diffuse pain that was partially relieved with emesis. His bowel movements had been regular, and he reported no diarrhea, fever, chills, or other constitutional symptoms. Additional 10-point review of systems was otherwise negative. The patient reported smoking marijuana multiple times daily for many years. The patient reported he had not used alcohol for several months.

A physical exam showed a pale and diaphoretic patient. Vital signs were significant for mild hypertension (150/75), but the patient was afebrile with a normal heart rate. An abdominal exam revealed a nontender, nondistended abdomen with no signs of rebound or guarding. The remainder of the examination was unremarkable. An initial workup showed a mild elevation of serum creatinine to 1.36 mg/dL (baseline is 1.10 mg/dL). Other workups, including complete blood count (CBC) with differential, complete metabolic panel, lipase, amylase, and urine analysis, were all unremarkable.

The patient’s urine drug screen (UDS) was positive for tetrahydrocannabinol (THC). A computed tomography (CT) scan of his abdomen and pelvis with contrast was unremarkable. The patient was admitted for his inability to tolerate oral intake and dehydration and treated supportively with IV fluids and antiemetics.

Overnight, the nursing staff reported that the patient took multiple, prolonged hot showers. Upon further questioning, he reported the hot showers significantly helped the nausea and abdominal pain. He had learned this behavior after experiencing previous episodes of self-limited nausea, vomiting, and abdominal pain.

Extensive review of his medical record revealed that the patient had, in fact, presented to the ED with similar symptoms 11 times in the prior 8 years. He was admitted on 8 occasions over that time frame. The typical hospital course included supportive care with antiemetics and IV fluids. The patient’s symptoms typically resolved within 24 to 72 hours of hospitalization. Previous evaluations included additional unremarkable CT imaging of the abdomen and pelvis. The patient also had received 2 esophagogastroduodenoscopies (EGDs), one 2 years prior and the other 5 years prior. Both EGDs showed only mild gastritis. On every check during the previous 8 years, the patient’s UDS was positive for THC.

Most of his previous admissions were attributed to viral gastroenteritis due to the self-limited nature of the symptoms. Other admissions were attributed to alcohol-induced gastritis. However, after abstaining from alcohol for long periods, the patient had continued recurrence of the symptoms and increased frequency of presentations to the ED.

The characteristics, signs, and symptoms of CHS were discussed with the patient. The patient strongly felt as though these symptoms aligned with his clinical course over the prior 8 years. At time of writing, the patient had gone 20 months without requiring hospitalization; however, he had a recent relapse of marijuana use and subsequently required hospitalization.

Discussion

As in this case, CHS often presents with refractory, self-limited nausea and vomiting with vague abdominal pain that is temporarily relieved by hot baths or showers. In the largest case series, it was noted the average age was 32 years, and the majority of subjects used marijuana at least weekly for > 2 years.⁵ Many studies categorize CHS into 3 phases: prodromal, hyperemetic, and recovery.

The prodromal, or preemetic phase, is characterized by early morning nausea without emesis and abdominal discomfort. The hyperemetic phase begins when the patient accesses the health care system via either the ED or primary care physician. This phase is characterized by intractable nausea and vomiting and may be associated with mild diffuse abdominal pain. The nausea and vomiting typically do not respond to antiemetic medications. Patients in this stage also develop a compulsive behavior of hot showers that temporarily relieve the symptoms. These behaviors are thought to be learned through their cyclical periods of emesis and may not be present during the first few hyperemetic phases. During the recovery phase, the patient returns to a baseline state of health and often ceases utilizing the hot shower. The recovery phase can last weeks to months despite continued cannabis use prior to returning to the hyperemetic phase (Figure).^6,7

Simonetto and colleagues proposed clinical criteria for the diagnosis of CHS based on their case series as well as on previously proposed criteria presented by Sontineni and colleagues.^5,8 Long-term cannabis use is required for the diagnosis. In the Simonetto and colleagues case series, the majority of patients developed symptoms within the first 5 years of cannabis use; however, Soriano and colleagues conducted a smaller case series that showed that the majority of subjects used marijuana for roughly 16 years prior to the onset of vomiting.^5,7

The major CHS features that suggest the diagnosis are severe cyclic nausea and vomiting, relief of symptoms with abstinence from cannabis, temporary symptom relief with hot bathing, abdominal pain, and at least weekly use of marijuana. Other supportive features include aged < 50 years, weight loss > 5 kg, symptoms that are worse in the morning, normal bowel habits, and negative evaluation, including laboratory, radiography, and endoscopy (Table).⁵

Treatment often is supportive with emphasis placed on marijuana cessation. Intravenous fluids often are used due to dehydration from the emesis. The use of antiemetics, such as 5-HT3 (eg, ondansetron), D2 (eg, prochlorperazine), H1 (eg, promethazine), or neurokinin-1 receptor antagonists (eg, aprepitant) can be tried, but these therapies often are ineffective. Diet can be advanced as the patient tolerates. Given that many patients are found to have a mild gastritis, H2 blockers or proton pump inhibitors may be used. Extensive counseling on marijuana cessation is needed as it is the only therapy shown to have prolonged relief of the hyperemetic phase.⁶ The length of cessation from marijuana for resolution of the cyclical hyperemesis varies from 1 to 3 months. Returning to marijuana use often results in the returning of CHS.⁵

The pathophysiology of CHS is largely unknown; however, there are several hypothesized mechanisms. Many theorize that due to the lipophilicity and long half-life of THC, a primary compound in marijuana, it accumulates in the body over time.^4,6 It is thought that this accumulation may cause toxicity in both the gastrointestinal tract as well as in the brain. Central effects on the hypothalamic-pituitary axis may play a major role, and the reason for the symptom relief of hot baths is due to a change in thermoregulation in the hypothalamus.⁵ One interesting mechanism relates to CB1 receptor activation and vasodilation within the gastrointestinal tract due to chronic THC accumulation. The relief of the abdominal pain, nausea, and vomiting with hot showers can be secondary to the vasodilation of the skin, causing a redistribution from the gut. This theorized mechanism has been referred to as “cutaneous steal.”⁹

Conclusion

With the increased prevalence of marijuana use in the U.S. over the past decade and reform in legislation taking place over the next couple of years, it is increasingly important to be able to recognize CHS to avoid frequent hospital utilization and repeated costly evaluations. Cannabinoid hyperemesis syndrome is recognized by the triad of chronic cannabis use, cyclical hyperemesis, and compulsive hot bathing.⁴

The syndrome has 3 phases. In the prodromal phase the patient has morning predominance of nausea, usually without emesis. This is followed by the hyperemesis phase, which is characterized by hyperemesis, vague abdominal pain, and learned compulsive hot bathing.

The third phase is the recovery phase, which is a return to normal behavior. During the recovery phase, if patients cease marijuana use, they remain asymptomatic; however, if patients continue to use marijuana, they often have recurrence of the hyperemesis phase.⁵ The diagnosis of cannabinoid hyperemesis syndrome is difficult as it is a diagnosis of exclusion. Patients may present to the ED many times prior to diagnosis. With the changing climate of marijuana laws, it is an important condition to consider when establishing a differential. More studies will be required to evaluate the overall prevalence of this condition as well as if there are any changes following the liberalization of marijuana laws in many states.

Photo by Aaron Logan

Targeting two pathways simultaneously—one critical for oncogenesis and one essential for cell survival—may be an effective strategy for treating acute myeloid leukemia (AML), according to researchers.

The team studied mouse models of FLT3-ITD AML and found an inhibitor targeting the FLT3 pathway was largely effective against the disease.

However, targeting the BCL-2 pathway as well proved even more effective, completely eliminating AML in most cases.

Fumihiko Ishikawa, MD, PhD, of RIKEN Center for Integrative Medical Sciences in Yokohama, Kanagawa, Japan, and his colleagues described this work in Science Translational Medicine.

The researchers noted that mutations observed in AML patients have also been observed in elderly people without AML. So the team set out to determine which mutations actually contribute to the disease.

The researchers obtained bone marrow or blood samples from patients with FLT3-ITD AML and transplanted different cellular populations from each individual into mice. The team then examined how the cells behaved.

They were surprised to find that cells with similar surface marker profiles behaved differently. Therefore, the team used single-cell genomic sequencing to correlate mutational profiles with malignant potential.

The researchers said their results suggest that FLT3-ITD is “a critical trigger for leukemia initiation,” and it cooperates with accumulated mutations in DNMT3A, TET2, NPM1, and/or WT1.

The team went on to treat the FLT3-ITD AML mice with RK-20449, a FLT3/HCK inhibitor, and they observed “significant responses.”

In fact, RK-20449 eradicated leukemia originating from 5 different patients. The recipient mice experienced complete elimination of AML cells, in spite of the fact that they also carried mutations not directly targeted by RK-20449.

However, the researchers also noted the presence of RK-20449-resistant AML cells in some mice. The team therefore theorized that co-inhibition of an antiapoptotic signal—BCL-2—might remedy this.

So they treated resistant mice with the BCL-2 inhibitor venetoclax as well as RK-20449. The combination produced responses in all mice treated and completely eliminated AML cells in 9 of 12 cases.

“This shows that determining which of the mutations in a diverse landscape are critical in leukemia onset and which of the pathways are critical for therapeutic resistance in leukemia, and simultaneously targeting those pathways, is an encouraging way to treat difficult cancers such as AML,” Dr Ishikawa said.

Photo by Aaron Logan

Targeting two pathways simultaneously—one critical for oncogenesis and one essential for cell survival—may be an effective strategy for treating acute myeloid leukemia (AML), according to researchers.

The team studied mouse models of FLT3-ITD AML and found an inhibitor targeting the FLT3 pathway was largely effective against the disease.

However, targeting the BCL-2 pathway as well proved even more effective, completely eliminating AML in most cases.

Fumihiko Ishikawa, MD, PhD, of RIKEN Center for Integrative Medical Sciences in Yokohama, Kanagawa, Japan, and his colleagues described this work in Science Translational Medicine.

The researchers noted that mutations observed in AML patients have also been observed in elderly people without AML. So the team set out to determine which mutations actually contribute to the disease.

The researchers obtained bone marrow or blood samples from patients with FLT3-ITD AML and transplanted different cellular populations from each individual into mice. The team then examined how the cells behaved.

They were surprised to find that cells with similar surface marker profiles behaved differently. Therefore, the team used single-cell genomic sequencing to correlate mutational profiles with malignant potential.

The researchers said their results suggest that FLT3-ITD is “a critical trigger for leukemia initiation,” and it cooperates with accumulated mutations in DNMT3A, TET2, NPM1, and/or WT1.

The team went on to treat the FLT3-ITD AML mice with RK-20449, a FLT3/HCK inhibitor, and they observed “significant responses.”

In fact, RK-20449 eradicated leukemia originating from 5 different patients. The recipient mice experienced complete elimination of AML cells, in spite of the fact that they also carried mutations not directly targeted by RK-20449.

However, the researchers also noted the presence of RK-20449-resistant AML cells in some mice. The team therefore theorized that co-inhibition of an antiapoptotic signal—BCL-2—might remedy this.

So they treated resistant mice with the BCL-2 inhibitor venetoclax as well as RK-20449. The combination produced responses in all mice treated and completely eliminated AML cells in 9 of 12 cases.

“This shows that determining which of the mutations in a diverse landscape are critical in leukemia onset and which of the pathways are critical for therapeutic resistance in leukemia, and simultaneously targeting those pathways, is an encouraging way to treat difficult cancers such as AML,” Dr Ishikawa said.

Photo by Aaron Logan

Targeting two pathways simultaneously—one critical for oncogenesis and one essential for cell survival—may be an effective strategy for treating acute myeloid leukemia (AML), according to researchers.

The team studied mouse models of FLT3-ITD AML and found an inhibitor targeting the FLT3 pathway was largely effective against the disease.

However, targeting the BCL-2 pathway as well proved even more effective, completely eliminating AML in most cases.

Fumihiko Ishikawa, MD, PhD, of RIKEN Center for Integrative Medical Sciences in Yokohama, Kanagawa, Japan, and his colleagues described this work in Science Translational Medicine.

The researchers noted that mutations observed in AML patients have also been observed in elderly people without AML. So the team set out to determine which mutations actually contribute to the disease.

The researchers obtained bone marrow or blood samples from patients with FLT3-ITD AML and transplanted different cellular populations from each individual into mice. The team then examined how the cells behaved.

They were surprised to find that cells with similar surface marker profiles behaved differently. Therefore, the team used single-cell genomic sequencing to correlate mutational profiles with malignant potential.

The researchers said their results suggest that FLT3-ITD is “a critical trigger for leukemia initiation,” and it cooperates with accumulated mutations in DNMT3A, TET2, NPM1, and/or WT1.

The team went on to treat the FLT3-ITD AML mice with RK-20449, a FLT3/HCK inhibitor, and they observed “significant responses.”

In fact, RK-20449 eradicated leukemia originating from 5 different patients. The recipient mice experienced complete elimination of AML cells, in spite of the fact that they also carried mutations not directly targeted by RK-20449.

However, the researchers also noted the presence of RK-20449-resistant AML cells in some mice. The team therefore theorized that co-inhibition of an antiapoptotic signal—BCL-2—might remedy this.

So they treated resistant mice with the BCL-2 inhibitor venetoclax as well as RK-20449. The combination produced responses in all mice treated and completely eliminated AML cells in 9 of 12 cases.

“This shows that determining which of the mutations in a diverse landscape are critical in leukemia onset and which of the pathways are critical for therapeutic resistance in leukemia, and simultaneously targeting those pathways, is an encouraging way to treat difficult cancers such as AML,” Dr Ishikawa said.

Photo from TESARO

The US Food and Drug Administration (FDA) has approved an intravenous (IV) formulation of rolapitant (VARUBI®) for the same indication as the oral formulation.

This means IV rolapitant is now FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy in adults with cancer.

TESARO Inc., makers of rolapitant, said the US commercial launch of IV rolapitant is planned for November.

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV).

IV rolapitant features a ready-to-use, single-dose vial for administration. It does not require refrigerated storage or mixing.

The recommended dose of IV rolapitant is 166.5 mg, administered over 30 minutes. The drug is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information for IV rolapitant is available at www.varubirx.com.

Bioequivalence trial

Results from a bioequivalence trial suggest the IV and oral formulations of rolapitant are comparable.

The study was conducted in healthy volunteers. Subjects were randomized to receive a single dose of IV rolapitant at 166.5 mg administered over 30 minutes (n=61) or oral rolapitant at 180 mg (n=62).

The primary endpoint was bioequivalence, and the 166.5 mg IV infusion of rolapitant met bioequivalence criteria.

Researchers said the safety profile of IV rolapitant was largely consistent with that of oral rolapitant, although infusion-site reactions were observed with the IV formulation. These included the sensation of warmth, abdominal pain, dizziness, and paresthesia.

These results were recently published in The Journal of Clinical Pharmacology.

Oral rolapitant trials

Two phase 3 trials showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after highly emetogenic chemotherapy.

Results from these trials (NCT01499849 and NCT01500213) were published in a single article in The Lancet Oncology.

A third phase 3 trial showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after moderately emetogenic chemotherapy.

Results from this trial (NCT01500226) were also published in The Lancet Oncology.

Photo from TESARO

The US Food and Drug Administration (FDA) has approved an intravenous (IV) formulation of rolapitant (VARUBI®) for the same indication as the oral formulation.

This means IV rolapitant is now FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy in adults with cancer.

TESARO Inc., makers of rolapitant, said the US commercial launch of IV rolapitant is planned for November.

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV).

IV rolapitant features a ready-to-use, single-dose vial for administration. It does not require refrigerated storage or mixing.

The recommended dose of IV rolapitant is 166.5 mg, administered over 30 minutes. The drug is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information for IV rolapitant is available at www.varubirx.com.

Bioequivalence trial

Results from a bioequivalence trial suggest the IV and oral formulations of rolapitant are comparable.

The study was conducted in healthy volunteers. Subjects were randomized to receive a single dose of IV rolapitant at 166.5 mg administered over 30 minutes (n=61) or oral rolapitant at 180 mg (n=62).

The primary endpoint was bioequivalence, and the 166.5 mg IV infusion of rolapitant met bioequivalence criteria.

Researchers said the safety profile of IV rolapitant was largely consistent with that of oral rolapitant, although infusion-site reactions were observed with the IV formulation. These included the sensation of warmth, abdominal pain, dizziness, and paresthesia.

These results were recently published in The Journal of Clinical Pharmacology.

Oral rolapitant trials

Two phase 3 trials showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after highly emetogenic chemotherapy.

Results from these trials (NCT01499849 and NCT01500213) were published in a single article in The Lancet Oncology.

A third phase 3 trial showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after moderately emetogenic chemotherapy.

Results from this trial (NCT01500226) were also published in The Lancet Oncology.

Photo from TESARO

The US Food and Drug Administration (FDA) has approved an intravenous (IV) formulation of rolapitant (VARUBI®) for the same indication as the oral formulation.

This means IV rolapitant is now FDA-approved for use in combination with other antiemetic agents to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy in adults with cancer.

TESARO Inc., makers of rolapitant, said the US commercial launch of IV rolapitant is planned for November.

Rolapitant is a selective and competitive antagonist of human substance P/neurokinin 1 receptors, which play an important role in the delayed phase of chemotherapy-induced nausea and vomiting (CINV).

IV rolapitant features a ready-to-use, single-dose vial for administration. It does not require refrigerated storage or mixing.

The recommended dose of IV rolapitant is 166.5 mg, administered over 30 minutes. The drug is to be administered up to 2 hours before chemotherapy administration in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information for IV rolapitant is available at www.varubirx.com.

Bioequivalence trial

Results from a bioequivalence trial suggest the IV and oral formulations of rolapitant are comparable.

The study was conducted in healthy volunteers. Subjects were randomized to receive a single dose of IV rolapitant at 166.5 mg administered over 30 minutes (n=61) or oral rolapitant at 180 mg (n=62).

The primary endpoint was bioequivalence, and the 166.5 mg IV infusion of rolapitant met bioequivalence criteria.

Researchers said the safety profile of IV rolapitant was largely consistent with that of oral rolapitant, although infusion-site reactions were observed with the IV formulation. These included the sensation of warmth, abdominal pain, dizziness, and paresthesia.

These results were recently published in The Journal of Clinical Pharmacology.

Oral rolapitant trials

Two phase 3 trials showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after highly emetogenic chemotherapy.

Results from these trials (NCT01499849 and NCT01500213) were published in a single article in The Lancet Oncology.

A third phase 3 trial showed that oral rolapitant, in combination with a 5-HT3 receptor antagonist and dexamethasone, was well tolerated and more effective than active control in preventing CINV after moderately emetogenic chemotherapy.

Results from this trial (NCT01500226) were also published in The Lancet Oncology.

multiple myeloma

Preclinical research has revealed a potential method of overcoming resistance to proteasome inhibitors.

By studying a rare genetic disease known as NGLY1 deficiency, researchers have gained new understanding of resistance to proteasome inhibitors.

The team found that treatment with a NGLY1 inhibitor can enhance the activity of the proteasome inhibitor carfilzomib against multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL).

Carolyn Bertozzi, PhD, of Stanford University in California, and her colleagues reported these findings in ACS Central Science.

Previous studies have suggested that proteasome inhibitor resistance could be linked to a protein called Nrf1. When proteasome inhibitors swing into action, Nrf1 is spurred into overdrive to restore cancer cells’ normal activities and keep them alive.

Researchers theorized that, if they could block Nrf1, they might be able to overcome proteasome inhibitor resistance.

Through studying NGLY1 deficiency, Dr Bertozzi and her colleagues may have hit upon an approach to do just that.

The researchers were investigating how lacking NGLY1 causes a host of debilitating symptoms, and they found that NGLY1 is responsible for activating Nrf1.

Further testing revealed that inhibiting NGLY1 eliminated interference from Nrf1 and enhanced the cytotoxicity of carfilzomib in MM and T-ALL cell lines.

The researchers treated the MM cell lines U266 and H929 with the NGLY1 inhibitor, known as WRR139, and carfilzomib and observed a significant decrease in cell survival when compared to treatment with carfilzomib alone. The team observed the same results when testing the T-ALL Jurkat cell line.

The addition of WRR139 resulted in a 2.6-fold reduction in carfilzomib’s LD50 for U266, a 2.0-fold reduction for H929, and a 1.5-fold reduction for Jurkat cells.

The researchers said these findings hold promise for the development of combination therapies for hematologic malignancies.

multiple myeloma

Preclinical research has revealed a potential method of overcoming resistance to proteasome inhibitors.

By studying a rare genetic disease known as NGLY1 deficiency, researchers have gained new understanding of resistance to proteasome inhibitors.

The team found that treatment with a NGLY1 inhibitor can enhance the activity of the proteasome inhibitor carfilzomib against multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL).

Carolyn Bertozzi, PhD, of Stanford University in California, and her colleagues reported these findings in ACS Central Science.

Previous studies have suggested that proteasome inhibitor resistance could be linked to a protein called Nrf1. When proteasome inhibitors swing into action, Nrf1 is spurred into overdrive to restore cancer cells’ normal activities and keep them alive.

Researchers theorized that, if they could block Nrf1, they might be able to overcome proteasome inhibitor resistance.

Through studying NGLY1 deficiency, Dr Bertozzi and her colleagues may have hit upon an approach to do just that.

The researchers were investigating how lacking NGLY1 causes a host of debilitating symptoms, and they found that NGLY1 is responsible for activating Nrf1.

Further testing revealed that inhibiting NGLY1 eliminated interference from Nrf1 and enhanced the cytotoxicity of carfilzomib in MM and T-ALL cell lines.

The researchers treated the MM cell lines U266 and H929 with the NGLY1 inhibitor, known as WRR139, and carfilzomib and observed a significant decrease in cell survival when compared to treatment with carfilzomib alone. The team observed the same results when testing the T-ALL Jurkat cell line.

The addition of WRR139 resulted in a 2.6-fold reduction in carfilzomib’s LD50 for U266, a 2.0-fold reduction for H929, and a 1.5-fold reduction for Jurkat cells.

The researchers said these findings hold promise for the development of combination therapies for hematologic malignancies.

multiple myeloma

Preclinical research has revealed a potential method of overcoming resistance to proteasome inhibitors.

By studying a rare genetic disease known as NGLY1 deficiency, researchers have gained new understanding of resistance to proteasome inhibitors.

The team found that treatment with a NGLY1 inhibitor can enhance the activity of the proteasome inhibitor carfilzomib against multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL).

Carolyn Bertozzi, PhD, of Stanford University in California, and her colleagues reported these findings in ACS Central Science.

Previous studies have suggested that proteasome inhibitor resistance could be linked to a protein called Nrf1. When proteasome inhibitors swing into action, Nrf1 is spurred into overdrive to restore cancer cells’ normal activities and keep them alive.

Researchers theorized that, if they could block Nrf1, they might be able to overcome proteasome inhibitor resistance.

Through studying NGLY1 deficiency, Dr Bertozzi and her colleagues may have hit upon an approach to do just that.

The researchers were investigating how lacking NGLY1 causes a host of debilitating symptoms, and they found that NGLY1 is responsible for activating Nrf1.

Further testing revealed that inhibiting NGLY1 eliminated interference from Nrf1 and enhanced the cytotoxicity of carfilzomib in MM and T-ALL cell lines.

The researchers treated the MM cell lines U266 and H929 with the NGLY1 inhibitor, known as WRR139, and carfilzomib and observed a significant decrease in cell survival when compared to treatment with carfilzomib alone. The team observed the same results when testing the T-ALL Jurkat cell line.

The addition of WRR139 resulted in a 2.6-fold reduction in carfilzomib’s LD50 for U266, a 2.0-fold reduction for H929, and a 1.5-fold reduction for Jurkat cells.

The researchers said these findings hold promise for the development of combination therapies for hematologic malignancies.

Photo courtesy of Biogen

The Saudi Food and Drug Authority has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B in the Kingdom of Saudi Arabia.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for on-demand treatment and prophylaxis in hemophilia B patients of all ages.

Eftrenonacog alfa is engineered by fusing factor IX to the Fc portion of immunoglobulin G subclass 1. This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is approved to treat hemophilia B in the European Union, Iceland, Liechtenstein, Kuwait, Norway, and Switzerland (where it is marketed by Sobi). The product is also approved in the US, Canada, Japan, Australia, New Zealand, and other countries (where it is marketed by Bioverativ).

The approvals of eftrenonacog alfa are based on results from a pair of phase 3 trials—the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 males with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

• Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
• Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
• On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
• Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced a bleeding episode while on study. In total, 90.4% of bleeding episodes were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated males younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. There were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

Photo courtesy of Biogen

The Saudi Food and Drug Authority has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B in the Kingdom of Saudi Arabia.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for on-demand treatment and prophylaxis in hemophilia B patients of all ages.

Eftrenonacog alfa is engineered by fusing factor IX to the Fc portion of immunoglobulin G subclass 1. This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is approved to treat hemophilia B in the European Union, Iceland, Liechtenstein, Kuwait, Norway, and Switzerland (where it is marketed by Sobi). The product is also approved in the US, Canada, Japan, Australia, New Zealand, and other countries (where it is marketed by Bioverativ).

The approvals of eftrenonacog alfa are based on results from a pair of phase 3 trials—the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 males with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

• Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
• Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
• On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
• Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced a bleeding episode while on study. In total, 90.4% of bleeding episodes were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated males younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. There were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

Photo courtesy of Biogen

The Saudi Food and Drug Authority has approved eftrenonacog alfa (Alprolix®) for the treatment of hemophilia B in the Kingdom of Saudi Arabia.

Eftrenonacog alfa is a recombinant factor IX Fc fusion protein indicated for on-demand treatment and prophylaxis in hemophilia B patients of all ages.

Eftrenonacog alfa is engineered by fusing factor IX to the Fc portion of immunoglobulin G subclass 1. This enables eftrenonacog alfa to use a naturally occurring pathway to prolong the time the therapy remains in the body.

Eftrenonacog alfa is approved to treat hemophilia B in the European Union, Iceland, Liechtenstein, Kuwait, Norway, and Switzerland (where it is marketed by Sobi). The product is also approved in the US, Canada, Japan, Australia, New Zealand, and other countries (where it is marketed by Bioverativ).

The approvals of eftrenonacog alfa are based on results from a pair of phase 3 trials—the B-LONG study and the Kids B-LONG study.

B-LONG study

The B-LONG study included 123 males with severe hemophilia B who were 12 years of age or older. They had no current or previous factor IX inhibitors and a history of 100 or more documented prior exposure days to factor IX products.

Patients received eftrenonacog alfa in 1 of 4 treatment arms:

• Weekly prophylaxis starting at 50 IU/kg, with pharmacokinetic (PK)-driven dose adjustments (n=63)
• Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
• On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
• Perioperative management (n=12, including 8 from arms 1-3).

Researchers assessed control of bleeding in all patients who experienced a bleeding episode while on study. In total, 90.4% of bleeding episodes were controlled by a single injection of eftrenonacog alfa.

The overall median annualized bleeding rates (ABRs)—including spontaneous and traumatic bleeds—were 2.95 in the weekly prophylaxis arm, 1.38 in the individualized interval prophylaxis arm, and 17.69 in the episodic treatment arm.

The perioperative management arm consisted of 12 patients undergoing 14 major surgical procedures. The treating physicians rated the hemostatic efficacy of eftrenonacog alfa as “excellent” or “good” in all surgeries.

Eftrenonacog alfa was considered generally well-tolerated. None of the patients developed inhibitors, and none reported anaphylaxis.

The most common adverse events—with an incidence of 5% or greater—occurring outside of the perioperative management arm were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.

One serious adverse event may have been drug-related. The patient experienced obstructive uropathy in the setting of hematuria. However, he continued to receive eftrenonacog alfa, and the event resolved with medical management.

Kids B-LONG

In Kids B-LONG, researchers tested eftrenonacog alfa in 30 previously treated males younger than 12 who had severe hemophilia B. Patients had at least 50 prior exposure days to factor IX therapies.

Children who received eftrenonacog alfa prophylactically had an overall median ABR of 1.97. The median ABR for spontaneous joint bleeds was 0.

Approximately 33% of patients did not experience any bleeding episodes. About 92% of bleeding episodes were controlled by 1 or 2 injections of eftrenonacog alfa.

None of the patients developed inhibitors. There were no treatment-related serious adverse events and no cases of serious allergic reactions or vascular thrombotic events.

None of the patients discontinued the study due to an adverse event. One adverse event—decreased appetite occurring in 1 patient—was considered related to eftrenonacog alfa.

The pattern of treatment-emergent adverse events in this study was generally consistent with results seen in adolescents and adults in the B-LONG study.

WASHINGTON – Low market competition among liver transplant centers may affect which patients are considered too sick to transplant, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.

With 20% of patients dying while on the transplant wait list, including those who were delisted, understanding the distribution of organs among donor service areas (DSAs) is crucial to lowering mortality during the current organ shortage, according to presenter Yanik Babekov, MD, of Massachusetts General Hospital, Boston.

Investigators studied 3,131 patients who were delisted after being classified as “too sick” from 116 centers in 51 DSAs, between 2002 and 2012.

Researchers used the Herfindahl-Hirschman Index (HHI), which analyzes the market share of each participant to determine the overall level of competition. Measurements on the HHI range between 0 and 1, with 0 being the most competitive and 1 being the least.

Mean delisting Model for End-Stage Liver Disease (MELD) scores considered to be “too sick to transplant” were 26.1, and average HHI among DSAs was 0.46, according to investigators. They found that, for every 1% increase in HHI, the delisting MELD score increased by 0.06, according to a risk-adjustment analysis.

“In other words, more competitive DSAs delist patients for [being] ‘too sick’ at lower MELD scores,” Dr. Babekov explained in a video interview. “Interestingly, race, education, citizenship, and other DSA factors also impacted delisting MELD for ‘too sick.’ ”

While market competition may not be the only factor to explain the phenomenon of patients delisted for being ‘too sick,’ it is important to identify how having more transplant centers in DSAs can help more patients be added to, and stay on, these wait lists, according to investigators.

Dr. Babekov had no relevant financial disclosures.

[email protected]
On Twitter @eaztweets

WASHINGTON – Low market competition among liver transplant centers may affect which patients are considered too sick to transplant, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.

With 20% of patients dying while on the transplant wait list, including those who were delisted, understanding the distribution of organs among donor service areas (DSAs) is crucial to lowering mortality during the current organ shortage, according to presenter Yanik Babekov, MD, of Massachusetts General Hospital, Boston.

Investigators studied 3,131 patients who were delisted after being classified as “too sick” from 116 centers in 51 DSAs, between 2002 and 2012.

Researchers used the Herfindahl-Hirschman Index (HHI), which analyzes the market share of each participant to determine the overall level of competition. Measurements on the HHI range between 0 and 1, with 0 being the most competitive and 1 being the least.

Mean delisting Model for End-Stage Liver Disease (MELD) scores considered to be “too sick to transplant” were 26.1, and average HHI among DSAs was 0.46, according to investigators. They found that, for every 1% increase in HHI, the delisting MELD score increased by 0.06, according to a risk-adjustment analysis.

“In other words, more competitive DSAs delist patients for [being] ‘too sick’ at lower MELD scores,” Dr. Babekov explained in a video interview. “Interestingly, race, education, citizenship, and other DSA factors also impacted delisting MELD for ‘too sick.’ ”

While market competition may not be the only factor to explain the phenomenon of patients delisted for being ‘too sick,’ it is important to identify how having more transplant centers in DSAs can help more patients be added to, and stay on, these wait lists, according to investigators.

Dr. Babekov had no relevant financial disclosures.

[email protected]
On Twitter @eaztweets

WASHINGTON – Low market competition among liver transplant centers may affect which patients are considered too sick to transplant, according to a study presented at the annual meeting of the American Association for the Study of Liver Diseases.

With 20% of patients dying while on the transplant wait list, including those who were delisted, understanding the distribution of organs among donor service areas (DSAs) is crucial to lowering mortality during the current organ shortage, according to presenter Yanik Babekov, MD, of Massachusetts General Hospital, Boston.

Investigators studied 3,131 patients who were delisted after being classified as “too sick” from 116 centers in 51 DSAs, between 2002 and 2012.

Researchers used the Herfindahl-Hirschman Index (HHI), which analyzes the market share of each participant to determine the overall level of competition. Measurements on the HHI range between 0 and 1, with 0 being the most competitive and 1 being the least.

Mean delisting Model for End-Stage Liver Disease (MELD) scores considered to be “too sick to transplant” were 26.1, and average HHI among DSAs was 0.46, according to investigators. They found that, for every 1% increase in HHI, the delisting MELD score increased by 0.06, according to a risk-adjustment analysis.

“In other words, more competitive DSAs delist patients for [being] ‘too sick’ at lower MELD scores,” Dr. Babekov explained in a video interview. “Interestingly, race, education, citizenship, and other DSA factors also impacted delisting MELD for ‘too sick.’ ”

While market competition may not be the only factor to explain the phenomenon of patients delisted for being ‘too sick,’ it is important to identify how having more transplant centers in DSAs can help more patients be added to, and stay on, these wait lists, according to investigators.

Dr. Babekov had no relevant financial disclosures.

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SAN FRANCISCO – After years of stagnation in the field of acute myeloid leukemia – with most standard therapies developed in the 1970s – times are changing, Bruno Medeiros, MD, said at the annual congress on hematologic malignancies held by the National Comprehensive Cancer Network.

“2017 is the year of AML,” he said. Four new therapies have been approved by the FDA since April. They include midostaurin for newly diagnosed, FLT-3–mutated patients; enasidenib, for relapsed/refractory IDH2-mutated patients; CPX-351, for high-risk AML patients; and gemtuzumab ozogamicin for newly diagnosed, CD-33–positive patients.

SAN FRANCISCO – After years of stagnation in the field of acute myeloid leukemia – with most standard therapies developed in the 1970s – times are changing, Bruno Medeiros, MD, said at the annual congress on hematologic malignancies held by the National Comprehensive Cancer Network.

“2017 is the year of AML,” he said. Four new therapies have been approved by the FDA since April. They include midostaurin for newly diagnosed, FLT-3–mutated patients; enasidenib, for relapsed/refractory IDH2-mutated patients; CPX-351, for high-risk AML patients; and gemtuzumab ozogamicin for newly diagnosed, CD-33–positive patients.

SAN FRANCISCO – After years of stagnation in the field of acute myeloid leukemia – with most standard therapies developed in the 1970s – times are changing, Bruno Medeiros, MD, said at the annual congress on hematologic malignancies held by the National Comprehensive Cancer Network.

“2017 is the year of AML,” he said. Four new therapies have been approved by the FDA since April. They include midostaurin for newly diagnosed, FLT-3–mutated patients; enasidenib, for relapsed/refractory IDH2-mutated patients; CPX-351, for high-risk AML patients; and gemtuzumab ozogamicin for newly diagnosed, CD-33–positive patients.