Steven Pantilat, MD, MHM, has been named the first chief of the newly established division of palliative medicine at University of California, San Francisco Health. Dr. Pantilat’s new role commenced on May 1st, with the division launch anticipated for July 1st.

Gary J. Carver, MD, recently was named the chief medical officer at Coshocton (Ohio) Regional Medical Center. Dr. Carver has been the hospital’s director of hospital medicine since 2013 and will continue in that role in addition to his duties as CMO.

In his new position, Dr. Carver joins Coshocton Medical Center’s senior leadership team, providing medical oversight, as well as clinical direction and leadership as the facility seeks accreditation, quality improvement, and service line development.
 

Lisa Shah, MD, has been hired by Sound Physicians as the group’s chief innovation officer. Dr. Shah had been working as senior vice president of Evolent Health’s clinical operations and network. With Sound Physicians, Dr. Shah will lead clinical innovation and transformation for the nationwide organization of physicians providing emergency medical, critical care, and hospital medicine services at more than 180 hospitals.

Dr. Shah will be tasked with developing innovative care models, tech-centered clinical workflows, and telemedicine strategies. She brings a robust hospital medicine background, having served in a 2-year Hospitalist Scholars Fellowship at the University of Chicago, while simultaneously earning a master’s degree in public health.
 

BUSINESS MOVES

The University of Mississippi Medical Center Children’s of Mississippi, Hattiesburg, branch is joining forces with Memorial Hospital at Gulfport (Miss.) to provide care throughout southern Mississippi.

The highlight of the merger is the acquisition of six pediatric clinics into the UMMC family, with UMMC assuming control of the pediatric hospitalist program at each of the locations. The acquired clinics all have been branded as Children’s of Mississippi as of March 26th.
 

Sound Physicians’ parent company Fresenius Medical Care, which has held a controlling interest in Sound since 2014, has sold that interest to Germany-based Summit Partners for a reported $2.15 billion. The acquisition is expected to be finalized later this calendar year.

Sound, which reported revenues of approximately $1.5 billion in 2017, is optimistic that it can tap into new markets while under the Summit umbrella.
 

The Ob Hospitalist Group, Greenville, S.C., the nation’s largest Ob/Gyn hospitalist organization, recently announced the rollout of its CARE (Clinician Assistance, Recovery, and Encourage) program. CARE uses peer support to assist clinicians facing psychological and emotional impacts from adverse Ob events.

CARE peer counseling focuses on confidentiality, empathy, trust, and respect for colleagues suffering from a negative patient-care event. The program is available to more than 600 Ob hospitalist clinicians at more than 120 hospitals nationwide.

Steven Pantilat, MD, MHM, has been named the first chief of the newly established division of palliative medicine at University of California, San Francisco Health. Dr. Pantilat’s new role commenced on May 1st, with the division launch anticipated for July 1st.

Gary J. Carver, MD, recently was named the chief medical officer at Coshocton (Ohio) Regional Medical Center. Dr. Carver has been the hospital’s director of hospital medicine since 2013 and will continue in that role in addition to his duties as CMO.

In his new position, Dr. Carver joins Coshocton Medical Center’s senior leadership team, providing medical oversight, as well as clinical direction and leadership as the facility seeks accreditation, quality improvement, and service line development.
 

Lisa Shah, MD, has been hired by Sound Physicians as the group’s chief innovation officer. Dr. Shah had been working as senior vice president of Evolent Health’s clinical operations and network. With Sound Physicians, Dr. Shah will lead clinical innovation and transformation for the nationwide organization of physicians providing emergency medical, critical care, and hospital medicine services at more than 180 hospitals.

Dr. Shah will be tasked with developing innovative care models, tech-centered clinical workflows, and telemedicine strategies. She brings a robust hospital medicine background, having served in a 2-year Hospitalist Scholars Fellowship at the University of Chicago, while simultaneously earning a master’s degree in public health.
 

BUSINESS MOVES

The University of Mississippi Medical Center Children’s of Mississippi, Hattiesburg, branch is joining forces with Memorial Hospital at Gulfport (Miss.) to provide care throughout southern Mississippi.

The highlight of the merger is the acquisition of six pediatric clinics into the UMMC family, with UMMC assuming control of the pediatric hospitalist program at each of the locations. The acquired clinics all have been branded as Children’s of Mississippi as of March 26th.
 

Sound Physicians’ parent company Fresenius Medical Care, which has held a controlling interest in Sound since 2014, has sold that interest to Germany-based Summit Partners for a reported $2.15 billion. The acquisition is expected to be finalized later this calendar year.

Sound, which reported revenues of approximately $1.5 billion in 2017, is optimistic that it can tap into new markets while under the Summit umbrella.
 

The Ob Hospitalist Group, Greenville, S.C., the nation’s largest Ob/Gyn hospitalist organization, recently announced the rollout of its CARE (Clinician Assistance, Recovery, and Encourage) program. CARE uses peer support to assist clinicians facing psychological and emotional impacts from adverse Ob events.

CARE peer counseling focuses on confidentiality, empathy, trust, and respect for colleagues suffering from a negative patient-care event. The program is available to more than 600 Ob hospitalist clinicians at more than 120 hospitals nationwide.

Steven Pantilat, MD, MHM, has been named the first chief of the newly established division of palliative medicine at University of California, San Francisco Health. Dr. Pantilat’s new role commenced on May 1st, with the division launch anticipated for July 1st.

Gary J. Carver, MD, recently was named the chief medical officer at Coshocton (Ohio) Regional Medical Center. Dr. Carver has been the hospital’s director of hospital medicine since 2013 and will continue in that role in addition to his duties as CMO.

In his new position, Dr. Carver joins Coshocton Medical Center’s senior leadership team, providing medical oversight, as well as clinical direction and leadership as the facility seeks accreditation, quality improvement, and service line development.
 

Lisa Shah, MD, has been hired by Sound Physicians as the group’s chief innovation officer. Dr. Shah had been working as senior vice president of Evolent Health’s clinical operations and network. With Sound Physicians, Dr. Shah will lead clinical innovation and transformation for the nationwide organization of physicians providing emergency medical, critical care, and hospital medicine services at more than 180 hospitals.

Dr. Shah will be tasked with developing innovative care models, tech-centered clinical workflows, and telemedicine strategies. She brings a robust hospital medicine background, having served in a 2-year Hospitalist Scholars Fellowship at the University of Chicago, while simultaneously earning a master’s degree in public health.
 

BUSINESS MOVES

The University of Mississippi Medical Center Children’s of Mississippi, Hattiesburg, branch is joining forces with Memorial Hospital at Gulfport (Miss.) to provide care throughout southern Mississippi.

The highlight of the merger is the acquisition of six pediatric clinics into the UMMC family, with UMMC assuming control of the pediatric hospitalist program at each of the locations. The acquired clinics all have been branded as Children’s of Mississippi as of March 26th.
 

Sound Physicians’ parent company Fresenius Medical Care, which has held a controlling interest in Sound since 2014, has sold that interest to Germany-based Summit Partners for a reported $2.15 billion. The acquisition is expected to be finalized later this calendar year.

Sound, which reported revenues of approximately $1.5 billion in 2017, is optimistic that it can tap into new markets while under the Summit umbrella.
 

The Ob Hospitalist Group, Greenville, S.C., the nation’s largest Ob/Gyn hospitalist organization, recently announced the rollout of its CARE (Clinician Assistance, Recovery, and Encourage) program. CARE uses peer support to assist clinicians facing psychological and emotional impacts from adverse Ob events.

CARE peer counseling focuses on confidentiality, empathy, trust, and respect for colleagues suffering from a negative patient-care event. The program is available to more than 600 Ob hospitalist clinicians at more than 120 hospitals nationwide.

Preoperative opioid use was prevalent in nearly one-quarter of patients undergoing surgery at a large academic medical center, a cross-sectional observational study has determined.

Prescription or illegal opioid use can have profound implications for surgical outcomes and continued postoperative medication abuse. “Preoperative opioid use was associated with a greater burden of comorbid disease and multiple risk factors for poor recovery. ... Opioid-tolerant patients are at risk for opioid-associated adverse events and are less likely to discontinue opioid-based therapy after their surgery,” wrote Paul E. Hilliard, MD, and a team of researchers at the University of Michigan Health System. Although the question of preoperative opioid use has been examined and the Michigan findings are consistent with earlier estimates of prevalence (Ann Surg. 2017;265[4]:695-701), this study sought a more detailed profile of both the characteristics of these patients and the types of procedures correlated with opioid use.

Patient data were derived primarily from two ongoing institutional registries, the Michigan Genomics Initiative and the Analgesic Outcomes Study. Each of these projects involved recruiting nonemergency surgery patients to participate and self-report on pain and affect issues. Opioid use data were extracted from the preop anesthesia history and from physical examination. A total of 34,186 patients were recruited for this study; 54.2% were women, 89.1% were white, and the mean age was 53.1 years. Overall, 23.1% of these patients were taking opioids of various kinds, mostly by prescription along with nonprescription opioids and illegal drugs of other kinds.

The most common opioids found in this patient sample were hydrocodone bitartrate (59.4%), tramadol hydrochloride (21.2%) and oxycodone hydrochloride (18.5%), although the duration or frequency of use was not determined.

“In our experience, in surveys like this patients are pretty honest. [The data do not] track to their medical record, but was done privately for research. That having been said, I am sure there is significant underreporting,” study coauthor Michael J. Englesbe, MD, FACS, said in an interview. In addition to some nondisclosure by study participants, the exclusion of patients admitted to surgery from the ED could mean that 23.1% is a conservative estimate, he noted.

Patient characteristics included in the study (tobacco use, alcohol use, sleep apnea, pain, life satisfaction, depression, anxiety) were self-reported and validated using tools such as the Brief Pain Inventory, the Fibromyalgia Survey, and the Hospital Anxiety and Depression Scale. Procedural data were derived from patient records and ICD-10 data and rated via the ASA score and Charlson Comorbidity Index.

A multivariate analysis of patient characteristics found that age between 31 and 40, tobacco use, heavy alcohol use, pain score, depression, comorbidities reflected in a higher ASA score, and Charlson Comorbidity Score were all significant risk factors for presurgical opiate use.

Patients who were scheduled for surgical procedures involving lower extremities (adjusted odds ratio 3.61, 95% confidence interval, 2.81-4.64) were at the highest risk for opioid use, followed by pelvis surgery, excluding hip (aOR, 3.09, 95% CI, 1.88-5.08), upper arm or elbow (aOR, 3.07, 95% CI, 2.12-4.45), and spine surgery (aOR, 2.68, 95% CI, 2.15-3.32).

“All surgeons should take a preop pain history. They should ask about current pain and previous pain experiences. They should also ask about a history of substance use disorder. This should lead into a discussion of the pain expectations from the procedure. Patients should expect to be in pain, that is normal. Pain-free surgery is rare. If a patient has a complex pain history or takes chronic opioids, the surgeon should consider referring them to anesthesia for formal preop pain management planning and potentially weaning of opioid dose prior to elective surgery,” noted Dr. Englesbe, the Cyrenus G. Darling Sr., MD and Cyrenus G Darling Jr., MD Professor of Surgery, and faculty at the Center for Healthcare Outcomes & Policy, University of Michigan, Ann Arbor.

Surgeons are likely to see patients with a past history of opioid dependence or who are recovering from substance abuse. “Every effort should be made to avoid opioids in these patients. We have developed a Pain Optimization Pathway which facilitates no postoperative opioids for these and other patients. These patients are at high risk to relapse and surgeons must know who these patients are so they can provide optimal care,” Dr. Englesbe added.The limitations of this study as reported by the authors include the single-center design, the nondiverse racial makeup of the sample, and the difficulty of ascertaining the dosing and duration of opioid use, both prescription and illegal.

The investigators reported no disclosures relevant to this study. This study was supported by the National Institute on Drug Abuse, National Institutes of Health, the American College of Surgeons, and other noncommercial sources.

tborden@mdedge.com

SOURCE: Hilliard PE et al. JAMA Surg. 2018 Jul 11. doi: 10.1001/jamasurg.2018.2102.

Preoperative opioid use was prevalent in nearly one-quarter of patients undergoing surgery at a large academic medical center, a cross-sectional observational study has determined.

Prescription or illegal opioid use can have profound implications for surgical outcomes and continued postoperative medication abuse. “Preoperative opioid use was associated with a greater burden of comorbid disease and multiple risk factors for poor recovery. ... Opioid-tolerant patients are at risk for opioid-associated adverse events and are less likely to discontinue opioid-based therapy after their surgery,” wrote Paul E. Hilliard, MD, and a team of researchers at the University of Michigan Health System. Although the question of preoperative opioid use has been examined and the Michigan findings are consistent with earlier estimates of prevalence (Ann Surg. 2017;265[4]:695-701), this study sought a more detailed profile of both the characteristics of these patients and the types of procedures correlated with opioid use.

Patient data were derived primarily from two ongoing institutional registries, the Michigan Genomics Initiative and the Analgesic Outcomes Study. Each of these projects involved recruiting nonemergency surgery patients to participate and self-report on pain and affect issues. Opioid use data were extracted from the preop anesthesia history and from physical examination. A total of 34,186 patients were recruited for this study; 54.2% were women, 89.1% were white, and the mean age was 53.1 years. Overall, 23.1% of these patients were taking opioids of various kinds, mostly by prescription along with nonprescription opioids and illegal drugs of other kinds.

The most common opioids found in this patient sample were hydrocodone bitartrate (59.4%), tramadol hydrochloride (21.2%) and oxycodone hydrochloride (18.5%), although the duration or frequency of use was not determined.

“In our experience, in surveys like this patients are pretty honest. [The data do not] track to their medical record, but was done privately for research. That having been said, I am sure there is significant underreporting,” study coauthor Michael J. Englesbe, MD, FACS, said in an interview. In addition to some nondisclosure by study participants, the exclusion of patients admitted to surgery from the ED could mean that 23.1% is a conservative estimate, he noted.

Patient characteristics included in the study (tobacco use, alcohol use, sleep apnea, pain, life satisfaction, depression, anxiety) were self-reported and validated using tools such as the Brief Pain Inventory, the Fibromyalgia Survey, and the Hospital Anxiety and Depression Scale. Procedural data were derived from patient records and ICD-10 data and rated via the ASA score and Charlson Comorbidity Index.

A multivariate analysis of patient characteristics found that age between 31 and 40, tobacco use, heavy alcohol use, pain score, depression, comorbidities reflected in a higher ASA score, and Charlson Comorbidity Score were all significant risk factors for presurgical opiate use.

Patients who were scheduled for surgical procedures involving lower extremities (adjusted odds ratio 3.61, 95% confidence interval, 2.81-4.64) were at the highest risk for opioid use, followed by pelvis surgery, excluding hip (aOR, 3.09, 95% CI, 1.88-5.08), upper arm or elbow (aOR, 3.07, 95% CI, 2.12-4.45), and spine surgery (aOR, 2.68, 95% CI, 2.15-3.32).

“All surgeons should take a preop pain history. They should ask about current pain and previous pain experiences. They should also ask about a history of substance use disorder. This should lead into a discussion of the pain expectations from the procedure. Patients should expect to be in pain, that is normal. Pain-free surgery is rare. If a patient has a complex pain history or takes chronic opioids, the surgeon should consider referring them to anesthesia for formal preop pain management planning and potentially weaning of opioid dose prior to elective surgery,” noted Dr. Englesbe, the Cyrenus G. Darling Sr., MD and Cyrenus G Darling Jr., MD Professor of Surgery, and faculty at the Center for Healthcare Outcomes & Policy, University of Michigan, Ann Arbor.

Surgeons are likely to see patients with a past history of opioid dependence or who are recovering from substance abuse. “Every effort should be made to avoid opioids in these patients. We have developed a Pain Optimization Pathway which facilitates no postoperative opioids for these and other patients. These patients are at high risk to relapse and surgeons must know who these patients are so they can provide optimal care,” Dr. Englesbe added.The limitations of this study as reported by the authors include the single-center design, the nondiverse racial makeup of the sample, and the difficulty of ascertaining the dosing and duration of opioid use, both prescription and illegal.

The investigators reported no disclosures relevant to this study. This study was supported by the National Institute on Drug Abuse, National Institutes of Health, the American College of Surgeons, and other noncommercial sources.

tborden@mdedge.com

SOURCE: Hilliard PE et al. JAMA Surg. 2018 Jul 11. doi: 10.1001/jamasurg.2018.2102.

Preoperative opioid use was prevalent in nearly one-quarter of patients undergoing surgery at a large academic medical center, a cross-sectional observational study has determined.

Prescription or illegal opioid use can have profound implications for surgical outcomes and continued postoperative medication abuse. “Preoperative opioid use was associated with a greater burden of comorbid disease and multiple risk factors for poor recovery. ... Opioid-tolerant patients are at risk for opioid-associated adverse events and are less likely to discontinue opioid-based therapy after their surgery,” wrote Paul E. Hilliard, MD, and a team of researchers at the University of Michigan Health System. Although the question of preoperative opioid use has been examined and the Michigan findings are consistent with earlier estimates of prevalence (Ann Surg. 2017;265[4]:695-701), this study sought a more detailed profile of both the characteristics of these patients and the types of procedures correlated with opioid use.

Patient data were derived primarily from two ongoing institutional registries, the Michigan Genomics Initiative and the Analgesic Outcomes Study. Each of these projects involved recruiting nonemergency surgery patients to participate and self-report on pain and affect issues. Opioid use data were extracted from the preop anesthesia history and from physical examination. A total of 34,186 patients were recruited for this study; 54.2% were women, 89.1% were white, and the mean age was 53.1 years. Overall, 23.1% of these patients were taking opioids of various kinds, mostly by prescription along with nonprescription opioids and illegal drugs of other kinds.

The most common opioids found in this patient sample were hydrocodone bitartrate (59.4%), tramadol hydrochloride (21.2%) and oxycodone hydrochloride (18.5%), although the duration or frequency of use was not determined.

“In our experience, in surveys like this patients are pretty honest. [The data do not] track to their medical record, but was done privately for research. That having been said, I am sure there is significant underreporting,” study coauthor Michael J. Englesbe, MD, FACS, said in an interview. In addition to some nondisclosure by study participants, the exclusion of patients admitted to surgery from the ED could mean that 23.1% is a conservative estimate, he noted.

Patient characteristics included in the study (tobacco use, alcohol use, sleep apnea, pain, life satisfaction, depression, anxiety) were self-reported and validated using tools such as the Brief Pain Inventory, the Fibromyalgia Survey, and the Hospital Anxiety and Depression Scale. Procedural data were derived from patient records and ICD-10 data and rated via the ASA score and Charlson Comorbidity Index.

A multivariate analysis of patient characteristics found that age between 31 and 40, tobacco use, heavy alcohol use, pain score, depression, comorbidities reflected in a higher ASA score, and Charlson Comorbidity Score were all significant risk factors for presurgical opiate use.

Patients who were scheduled for surgical procedures involving lower extremities (adjusted odds ratio 3.61, 95% confidence interval, 2.81-4.64) were at the highest risk for opioid use, followed by pelvis surgery, excluding hip (aOR, 3.09, 95% CI, 1.88-5.08), upper arm or elbow (aOR, 3.07, 95% CI, 2.12-4.45), and spine surgery (aOR, 2.68, 95% CI, 2.15-3.32).

“All surgeons should take a preop pain history. They should ask about current pain and previous pain experiences. They should also ask about a history of substance use disorder. This should lead into a discussion of the pain expectations from the procedure. Patients should expect to be in pain, that is normal. Pain-free surgery is rare. If a patient has a complex pain history or takes chronic opioids, the surgeon should consider referring them to anesthesia for formal preop pain management planning and potentially weaning of opioid dose prior to elective surgery,” noted Dr. Englesbe, the Cyrenus G. Darling Sr., MD and Cyrenus G Darling Jr., MD Professor of Surgery, and faculty at the Center for Healthcare Outcomes & Policy, University of Michigan, Ann Arbor.

Surgeons are likely to see patients with a past history of opioid dependence or who are recovering from substance abuse. “Every effort should be made to avoid opioids in these patients. We have developed a Pain Optimization Pathway which facilitates no postoperative opioids for these and other patients. These patients are at high risk to relapse and surgeons must know who these patients are so they can provide optimal care,” Dr. Englesbe added.The limitations of this study as reported by the authors include the single-center design, the nondiverse racial makeup of the sample, and the difficulty of ascertaining the dosing and duration of opioid use, both prescription and illegal.

The investigators reported no disclosures relevant to this study. This study was supported by the National Institute on Drug Abuse, National Institutes of Health, the American College of Surgeons, and other noncommercial sources.

tborden@mdedge.com

SOURCE: Hilliard PE et al. JAMA Surg. 2018 Jul 11. doi: 10.1001/jamasurg.2018.2102.

MALMO, SWEDEN – Early identification of deep vein thrombosis in children with acute hematogenous osteomyelitis is critical given the need to plan anticoagulation management around the high likelihood that such patients will undergo multiple surgeries, Lawson A.B. Copley, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

He and his coinvestigators have identified a handful of risk factors helpful in expediting recognition of deep vein thrombosis (DVT) in children with suspected invasive infection of the musculoskeletal system.

“To improve the rate and timing of identification of DVT, we recommend performing early screening ultrasound on all children with these risk factors who are suspected of having acute hematogenous osteomyelitis,” declared Dr. Copley, professor of orthopaedic surgery and pediatrics at the University of Texas, Dallas.

Delayed diagnosis of DVT in the setting of acute hematogenous osteomyelitis (AHO) is common. Indeed, in a review of the experience at Children’s Medical Center Dallas during 2012-2014, the average time delay from ICU admission in patients suspected of having AHO to identification of DVT by ultrasound was 6.3 days.

“We’ve changed some things on the basis of that study in order to accelerate that timeline,” he explained.

Their major change was to identify actionable risk factors for DVT. This was accomplished by conducting a retrospective study of the EHR of nearly 902,000 Texas children during 2008-2016.

The study demonstrated that children with AHO complicated by DVT are, from the get-go, very different from AHO patients without DVT. They have higher illness severity of illness, are more likely to be admitted to the ICU, are prone to methicillin-resistant Staphylococcus aureus infection with prolonged bacteremia, and are much more likely to undergo multiple surgeries. Moreover, children with AHO and DVT differed substantially from other children with DVT: The dual diagnosis children lacked comorbid conditions, were prone to septic pulmonary emboli, didn’t develop postthrombotic syndrome marked by chronic venous stasis and ulcerations, and had invariably negative coagulopathy workups.

“There is no need, we feel, to perform a hypercoagulopathy workup in children with AHO complicated by DVT,” Dr. Copley said.

Drilling deeper into the data, he and his coinvestigators identified 224 new cases of DVT in the study population, for a prevalence of 2.5 per 10,000 children, along with 466 children with AHO. A total of 6% of children with AHO had DVT, and 12.1% of all children with DVT had AHO. The researchers then compared the demographics, laboratory parameters, and treatment in three cohorts: the 196 children with DVT without AHO, 28 with both AHO and DVT, and 438 with AHO without DVT.

Through this analysis, they came up with a list of risk factors warranting early screening ultrasound in children suspected of having AHO:

• An initial C-reactive protein level above 8 mg/dL, which was present in all 28 dual diagnosis children.
• ICU admission, which occurred in 19 of 28 (68%) children.
• A severity of illness score of at least 7 on a 10-point scale during the first several days in the hospital, present in 27 of the 28 children. The severity of illness scale was developed and validated by Dr. Copley and coworkers (J Pediatr Orthop. 2016 Oct 12. doi: 10.1097/BPO.0000000000000879).
• Bacteremia in the initial blood culture, present in 23 of 28 patients (82%).
• Just under 90% of the children with AHO and DVT had methicillin-resistant S. aureus, compared with 20% of those with AHO without DVT.
• Septic pulmonary emboli visualized on chest x-ray, a complication that occurred in 64% of the dual diagnosis group versus just 1% of patients with DVT without AHO.
• A band percentage of white blood cells greater than 1.5%, present in 86% of children with AHO and DVT.

More than 90% of children with AHO and DVT underwent surgery, with a mean of 2.7 surgeries per child, in contrast to the group with AHO without DVT, 55% of whom had surgery, with a mean of 0.7 surgeries per child.

Of note, there was no significant difference in the occurrence of pulmonary embolism between children with DVT without AHO versus those with DVT and AHO, with a rate of about 10% in both groups.

Dr. Copley reported having no relevant financial conflicts.

bjancin@mdedge.com

MALMO, SWEDEN – Early identification of deep vein thrombosis in children with acute hematogenous osteomyelitis is critical given the need to plan anticoagulation management around the high likelihood that such patients will undergo multiple surgeries, Lawson A.B. Copley, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

He and his coinvestigators have identified a handful of risk factors helpful in expediting recognition of deep vein thrombosis (DVT) in children with suspected invasive infection of the musculoskeletal system.

“To improve the rate and timing of identification of DVT, we recommend performing early screening ultrasound on all children with these risk factors who are suspected of having acute hematogenous osteomyelitis,” declared Dr. Copley, professor of orthopaedic surgery and pediatrics at the University of Texas, Dallas.

Delayed diagnosis of DVT in the setting of acute hematogenous osteomyelitis (AHO) is common. Indeed, in a review of the experience at Children’s Medical Center Dallas during 2012-2014, the average time delay from ICU admission in patients suspected of having AHO to identification of DVT by ultrasound was 6.3 days.

“We’ve changed some things on the basis of that study in order to accelerate that timeline,” he explained.

Their major change was to identify actionable risk factors for DVT. This was accomplished by conducting a retrospective study of the EHR of nearly 902,000 Texas children during 2008-2016.

The study demonstrated that children with AHO complicated by DVT are, from the get-go, very different from AHO patients without DVT. They have higher illness severity of illness, are more likely to be admitted to the ICU, are prone to methicillin-resistant Staphylococcus aureus infection with prolonged bacteremia, and are much more likely to undergo multiple surgeries. Moreover, children with AHO and DVT differed substantially from other children with DVT: The dual diagnosis children lacked comorbid conditions, were prone to septic pulmonary emboli, didn’t develop postthrombotic syndrome marked by chronic venous stasis and ulcerations, and had invariably negative coagulopathy workups.

“There is no need, we feel, to perform a hypercoagulopathy workup in children with AHO complicated by DVT,” Dr. Copley said.

Drilling deeper into the data, he and his coinvestigators identified 224 new cases of DVT in the study population, for a prevalence of 2.5 per 10,000 children, along with 466 children with AHO. A total of 6% of children with AHO had DVT, and 12.1% of all children with DVT had AHO. The researchers then compared the demographics, laboratory parameters, and treatment in three cohorts: the 196 children with DVT without AHO, 28 with both AHO and DVT, and 438 with AHO without DVT.

Through this analysis, they came up with a list of risk factors warranting early screening ultrasound in children suspected of having AHO:

• An initial C-reactive protein level above 8 mg/dL, which was present in all 28 dual diagnosis children.
• ICU admission, which occurred in 19 of 28 (68%) children.
• A severity of illness score of at least 7 on a 10-point scale during the first several days in the hospital, present in 27 of the 28 children. The severity of illness scale was developed and validated by Dr. Copley and coworkers (J Pediatr Orthop. 2016 Oct 12. doi: 10.1097/BPO.0000000000000879).
• Bacteremia in the initial blood culture, present in 23 of 28 patients (82%).
• Just under 90% of the children with AHO and DVT had methicillin-resistant S. aureus, compared with 20% of those with AHO without DVT.
• Septic pulmonary emboli visualized on chest x-ray, a complication that occurred in 64% of the dual diagnosis group versus just 1% of patients with DVT without AHO.
• A band percentage of white blood cells greater than 1.5%, present in 86% of children with AHO and DVT.

More than 90% of children with AHO and DVT underwent surgery, with a mean of 2.7 surgeries per child, in contrast to the group with AHO without DVT, 55% of whom had surgery, with a mean of 0.7 surgeries per child.

Of note, there was no significant difference in the occurrence of pulmonary embolism between children with DVT without AHO versus those with DVT and AHO, with a rate of about 10% in both groups.

Dr. Copley reported having no relevant financial conflicts.

bjancin@mdedge.com

MALMO, SWEDEN – Early identification of deep vein thrombosis in children with acute hematogenous osteomyelitis is critical given the need to plan anticoagulation management around the high likelihood that such patients will undergo multiple surgeries, Lawson A.B. Copley, MD, said at the annual meeting of the European Society for Paediatric Infectious Diseases.

Bruce Jancin/MDedge News

He and his coinvestigators have identified a handful of risk factors helpful in expediting recognition of deep vein thrombosis (DVT) in children with suspected invasive infection of the musculoskeletal system.

“To improve the rate and timing of identification of DVT, we recommend performing early screening ultrasound on all children with these risk factors who are suspected of having acute hematogenous osteomyelitis,” declared Dr. Copley, professor of orthopaedic surgery and pediatrics at the University of Texas, Dallas.

Delayed diagnosis of DVT in the setting of acute hematogenous osteomyelitis (AHO) is common. Indeed, in a review of the experience at Children’s Medical Center Dallas during 2012-2014, the average time delay from ICU admission in patients suspected of having AHO to identification of DVT by ultrasound was 6.3 days.

“We’ve changed some things on the basis of that study in order to accelerate that timeline,” he explained.

Their major change was to identify actionable risk factors for DVT. This was accomplished by conducting a retrospective study of the EHR of nearly 902,000 Texas children during 2008-2016.

The study demonstrated that children with AHO complicated by DVT are, from the get-go, very different from AHO patients without DVT. They have higher illness severity of illness, are more likely to be admitted to the ICU, are prone to methicillin-resistant Staphylococcus aureus infection with prolonged bacteremia, and are much more likely to undergo multiple surgeries. Moreover, children with AHO and DVT differed substantially from other children with DVT: The dual diagnosis children lacked comorbid conditions, were prone to septic pulmonary emboli, didn’t develop postthrombotic syndrome marked by chronic venous stasis and ulcerations, and had invariably negative coagulopathy workups.

“There is no need, we feel, to perform a hypercoagulopathy workup in children with AHO complicated by DVT,” Dr. Copley said.

Drilling deeper into the data, he and his coinvestigators identified 224 new cases of DVT in the study population, for a prevalence of 2.5 per 10,000 children, along with 466 children with AHO. A total of 6% of children with AHO had DVT, and 12.1% of all children with DVT had AHO. The researchers then compared the demographics, laboratory parameters, and treatment in three cohorts: the 196 children with DVT without AHO, 28 with both AHO and DVT, and 438 with AHO without DVT.

Through this analysis, they came up with a list of risk factors warranting early screening ultrasound in children suspected of having AHO:

• An initial C-reactive protein level above 8 mg/dL, which was present in all 28 dual diagnosis children.
• ICU admission, which occurred in 19 of 28 (68%) children.
• A severity of illness score of at least 7 on a 10-point scale during the first several days in the hospital, present in 27 of the 28 children. The severity of illness scale was developed and validated by Dr. Copley and coworkers (J Pediatr Orthop. 2016 Oct 12. doi: 10.1097/BPO.0000000000000879).
• Bacteremia in the initial blood culture, present in 23 of 28 patients (82%).
• Just under 90% of the children with AHO and DVT had methicillin-resistant S. aureus, compared with 20% of those with AHO without DVT.
• Septic pulmonary emboli visualized on chest x-ray, a complication that occurred in 64% of the dual diagnosis group versus just 1% of patients with DVT without AHO.
• A band percentage of white blood cells greater than 1.5%, present in 86% of children with AHO and DVT.

More than 90% of children with AHO and DVT underwent surgery, with a mean of 2.7 surgeries per child, in contrast to the group with AHO without DVT, 55% of whom had surgery, with a mean of 0.7 surgeries per child.

Of note, there was no significant difference in the occurrence of pulmonary embolism between children with DVT without AHO versus those with DVT and AHO, with a rate of about 10% in both groups.

Dr. Copley reported having no relevant financial conflicts.

bjancin@mdedge.com

“I can’t believe you’re drinking that.”

The young woman across the desk from me seemed perplexed, and I didn’t know why.

I’m one of those people who always has something to drink in front of me while working. A bottle of Costco green tea, Diet Coke, coffee. I also have a SodaStream gadget at my office, and that bottle is what I had on my desk at the moment.

I naively said “Why? I doubt it’s any worse for me than any other soda.”

That sure set her off, and I got a lecture about SodaStream being an Israeli company and her opinions on the Middle East, Israel, Palestine, etc. I listened politely for a moment, then redirected her back to the reason for her visit.

Not being someone who follows the news in detail, I‘d been unaware there was any controversy behind the soda bottle on my desk that morning. To me, it was just my choice of beverage.

The trouble here is that it’s possible to politicize pretty much anything in a divided world. I try to stay, for better or worse, ignorant of such things. My soft drink choice reflects nothing more than what I felt like drinking when I went back to my office’s tiny break room between appointments.

If you dig far enough into any company’s – or person’s – background, you’ll find something you disagree with. Just like any drug I prescribe will have side effects.

It’s for this reason that I keep politics out of my office. Patients, such as this lady, may express theirs, but I’ll never express mine. Too many in this world see each other in an “us vs. them” frame, quick to declare someone with different views as the enemy, rather than another decent person with an honest difference of opinion.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

“I can’t believe you’re drinking that.”

The young woman across the desk from me seemed perplexed, and I didn’t know why.

I’m one of those people who always has something to drink in front of me while working. A bottle of Costco green tea, Diet Coke, coffee. I also have a SodaStream gadget at my office, and that bottle is what I had on my desk at the moment.

I naively said “Why? I doubt it’s any worse for me than any other soda.”

That sure set her off, and I got a lecture about SodaStream being an Israeli company and her opinions on the Middle East, Israel, Palestine, etc. I listened politely for a moment, then redirected her back to the reason for her visit.

Not being someone who follows the news in detail, I‘d been unaware there was any controversy behind the soda bottle on my desk that morning. To me, it was just my choice of beverage.

The trouble here is that it’s possible to politicize pretty much anything in a divided world. I try to stay, for better or worse, ignorant of such things. My soft drink choice reflects nothing more than what I felt like drinking when I went back to my office’s tiny break room between appointments.

If you dig far enough into any company’s – or person’s – background, you’ll find something you disagree with. Just like any drug I prescribe will have side effects.

It’s for this reason that I keep politics out of my office. Patients, such as this lady, may express theirs, but I’ll never express mine. Too many in this world see each other in an “us vs. them” frame, quick to declare someone with different views as the enemy, rather than another decent person with an honest difference of opinion.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

“I can’t believe you’re drinking that.”

The young woman across the desk from me seemed perplexed, and I didn’t know why.

I’m one of those people who always has something to drink in front of me while working. A bottle of Costco green tea, Diet Coke, coffee. I also have a SodaStream gadget at my office, and that bottle is what I had on my desk at the moment.

I naively said “Why? I doubt it’s any worse for me than any other soda.”

That sure set her off, and I got a lecture about SodaStream being an Israeli company and her opinions on the Middle East, Israel, Palestine, etc. I listened politely for a moment, then redirected her back to the reason for her visit.

Not being someone who follows the news in detail, I‘d been unaware there was any controversy behind the soda bottle on my desk that morning. To me, it was just my choice of beverage.

The trouble here is that it’s possible to politicize pretty much anything in a divided world. I try to stay, for better or worse, ignorant of such things. My soft drink choice reflects nothing more than what I felt like drinking when I went back to my office’s tiny break room between appointments.

If you dig far enough into any company’s – or person’s – background, you’ll find something you disagree with. Just like any drug I prescribe will have side effects.

It’s for this reason that I keep politics out of my office. Patients, such as this lady, may express theirs, but I’ll never express mine. Too many in this world see each other in an “us vs. them” frame, quick to declare someone with different views as the enemy, rather than another decent person with an honest difference of opinion.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Melanoma patients who took high doses of glucocorticoids for hypophysitis induced by the checkpoint-inhibitor ipilimumab had a lower overall survival time and a shorter time to treatment failure than did patients taking low-dose steroids for the adverse event, according to a new retrospective analysis in Cancer.

“Treatment with high-dose glucocorticoids does not appear to confer any obvious advantage to patients with IH (ipilimumab-induced hypophysitis) and may negatively affect tumor response to CPI (checkpoint-inhibitor therapy),” wrote Alexander Faje, MD, a neuroendocrinologist at Massachusetts General Hospital, Boston. “We recommend against the routine use of higher doses in these patients and that such treatment should be reserved for clinical indications like visual compromise or perhaps for intractable headache.”

Hypophysitis after treatment with a CTLA-4 inhibitor, such as ipilimumab, can approach 12%, though it is much less common with the checkpoint inhibitors that target PD-1 and PD-L1. Past studies examining the effects of glucocorticoids for immune-related adverse events have compared patients with severe events to those with minimal or no events. Since emergence of hypophysitis correlates with better overall survival, this is a flawed approach, the researchers said.

For their study, the researchers compared groups of patients with the same immune-related adverse events who received treatment with varying amounts of glucocorticoids.

They reviewed outcomes for 64 melanoma patients who had received ipilimumab monotherapy and were diagnosed with ipilimumab-induced hypophysitis treated in the Partners Healthcare system. Fourteen patients had received low-dose glucocorticoids, defined as a maximum average daily dose of 7.5 mg of prednisone or the equivalent. Fifty patients received high-dose glucocorticoids, defined as anything above that amount.

Overall survival and time to treatment failure were significantly higher in the low-dose group than the high-dose group (P = .002 for OS and P = .001 for TTF). Median overall survival was 23.3 months and time to treatment failure was 11.4 months in those given high-dose steroids. Median overall survival had not been reached in those given low-dose steroids.

While the findings are preliminary, the authors noted they may have implications for managing other immune-related adverse events. “Although the use of lower doses of immunosuppressive medications may be less of an option in many circumstances for other (immune-related adverse events), therapeutic parsimony would seem desirable with more tailored regimens as the biologic mechanisms underpinning these processes are further elucidated.”

SOURCE: Faje AT et al. Cancer. 2018 Jul 5.

Melanoma patients who took high doses of glucocorticoids for hypophysitis induced by the checkpoint-inhibitor ipilimumab had a lower overall survival time and a shorter time to treatment failure than did patients taking low-dose steroids for the adverse event, according to a new retrospective analysis in Cancer.

“Treatment with high-dose glucocorticoids does not appear to confer any obvious advantage to patients with IH (ipilimumab-induced hypophysitis) and may negatively affect tumor response to CPI (checkpoint-inhibitor therapy),” wrote Alexander Faje, MD, a neuroendocrinologist at Massachusetts General Hospital, Boston. “We recommend against the routine use of higher doses in these patients and that such treatment should be reserved for clinical indications like visual compromise or perhaps for intractable headache.”

Hypophysitis after treatment with a CTLA-4 inhibitor, such as ipilimumab, can approach 12%, though it is much less common with the checkpoint inhibitors that target PD-1 and PD-L1. Past studies examining the effects of glucocorticoids for immune-related adverse events have compared patients with severe events to those with minimal or no events. Since emergence of hypophysitis correlates with better overall survival, this is a flawed approach, the researchers said.

For their study, the researchers compared groups of patients with the same immune-related adverse events who received treatment with varying amounts of glucocorticoids.

They reviewed outcomes for 64 melanoma patients who had received ipilimumab monotherapy and were diagnosed with ipilimumab-induced hypophysitis treated in the Partners Healthcare system. Fourteen patients had received low-dose glucocorticoids, defined as a maximum average daily dose of 7.5 mg of prednisone or the equivalent. Fifty patients received high-dose glucocorticoids, defined as anything above that amount.

Overall survival and time to treatment failure were significantly higher in the low-dose group than the high-dose group (P = .002 for OS and P = .001 for TTF). Median overall survival was 23.3 months and time to treatment failure was 11.4 months in those given high-dose steroids. Median overall survival had not been reached in those given low-dose steroids.

While the findings are preliminary, the authors noted they may have implications for managing other immune-related adverse events. “Although the use of lower doses of immunosuppressive medications may be less of an option in many circumstances for other (immune-related adverse events), therapeutic parsimony would seem desirable with more tailored regimens as the biologic mechanisms underpinning these processes are further elucidated.”

SOURCE: Faje AT et al. Cancer. 2018 Jul 5.

Melanoma patients who took high doses of glucocorticoids for hypophysitis induced by the checkpoint-inhibitor ipilimumab had a lower overall survival time and a shorter time to treatment failure than did patients taking low-dose steroids for the adverse event, according to a new retrospective analysis in Cancer.

“Treatment with high-dose glucocorticoids does not appear to confer any obvious advantage to patients with IH (ipilimumab-induced hypophysitis) and may negatively affect tumor response to CPI (checkpoint-inhibitor therapy),” wrote Alexander Faje, MD, a neuroendocrinologist at Massachusetts General Hospital, Boston. “We recommend against the routine use of higher doses in these patients and that such treatment should be reserved for clinical indications like visual compromise or perhaps for intractable headache.”

Hypophysitis after treatment with a CTLA-4 inhibitor, such as ipilimumab, can approach 12%, though it is much less common with the checkpoint inhibitors that target PD-1 and PD-L1. Past studies examining the effects of glucocorticoids for immune-related adverse events have compared patients with severe events to those with minimal or no events. Since emergence of hypophysitis correlates with better overall survival, this is a flawed approach, the researchers said.

For their study, the researchers compared groups of patients with the same immune-related adverse events who received treatment with varying amounts of glucocorticoids.

They reviewed outcomes for 64 melanoma patients who had received ipilimumab monotherapy and were diagnosed with ipilimumab-induced hypophysitis treated in the Partners Healthcare system. Fourteen patients had received low-dose glucocorticoids, defined as a maximum average daily dose of 7.5 mg of prednisone or the equivalent. Fifty patients received high-dose glucocorticoids, defined as anything above that amount.

Overall survival and time to treatment failure were significantly higher in the low-dose group than the high-dose group (P = .002 for OS and P = .001 for TTF). Median overall survival was 23.3 months and time to treatment failure was 11.4 months in those given high-dose steroids. Median overall survival had not been reached in those given low-dose steroids.

While the findings are preliminary, the authors noted they may have implications for managing other immune-related adverse events. “Although the use of lower doses of immunosuppressive medications may be less of an option in many circumstances for other (immune-related adverse events), therapeutic parsimony would seem desirable with more tailored regimens as the biologic mechanisms underpinning these processes are further elucidated.”

SOURCE: Faje AT et al. Cancer. 2018 Jul 5.

In this edition of the MDedge Psychast, Lorenzo Norris, MD, welcomes Leslie Citrome, MD, of New York Medical College in Valhalla, NY, for a conversation on the challenges of TD.

Sanjay Gupta, MD, of the University of Buffalo, spoke in an MDedge video earlier this year on the importance of using the Abnormal Involuntary Movement Scale to screen for TD and treating the disorder with vesicular monoamine transporter-2 inhibitors.

In the episode, Dr. Citrome notes that despite recent advances in pharmacological options, clinicians can be challenged by TD.

In this edition of the MDedge Psychast, Lorenzo Norris, MD, welcomes Leslie Citrome, MD, of New York Medical College in Valhalla, NY, for a conversation on the challenges of TD.

Sanjay Gupta, MD, of the University of Buffalo, spoke in an MDedge video earlier this year on the importance of using the Abnormal Involuntary Movement Scale to screen for TD and treating the disorder with vesicular monoamine transporter-2 inhibitors.

In the episode, Dr. Citrome notes that despite recent advances in pharmacological options, clinicians can be challenged by TD.

In this edition of the MDedge Psychast, Lorenzo Norris, MD, welcomes Leslie Citrome, MD, of New York Medical College in Valhalla, NY, for a conversation on the challenges of TD.

Sanjay Gupta, MD, of the University of Buffalo, spoke in an MDedge video earlier this year on the importance of using the Abnormal Involuntary Movement Scale to screen for TD and treating the disorder with vesicular monoamine transporter-2 inhibitors.

In the episode, Dr. Citrome notes that despite recent advances in pharmacological options, clinicians can be challenged by TD.

As if it were not bad enough that illnesses from mosquito, tick, and flea bites tripled between 2004 and 2016, 9 new germs spread by mosquitoes and ticks were discovered or introduced into the US in the same 13 years.

According to the CDC’s first summary collectively examining data trends for all nationally notifiable diseases caused by the bite of an infected mosquito, tick, or flea, the most common tickborne diseases in 2016 were Lyme disease and ehrlichiosis/anaplasmosis. The most common mosquito-borne viruses were West Nile, dengue, and Zika.

The increase is due to many factors, the CDC says, but 1 issue is that mosquitoes and ticks are moving into new areas, putting more people at risk. The US is “not fully prepared” to meet the public health threat, the CDC warns: About 80% of vector control organizations lack critical prevention and control capacities. Reducing the spread of the diseases and responding effectively to outbreaks will require additional capacity at the state and local levels for tracking, diagnosing, and reporting cases.

As if it were not bad enough that illnesses from mosquito, tick, and flea bites tripled between 2004 and 2016, 9 new germs spread by mosquitoes and ticks were discovered or introduced into the US in the same 13 years.

According to the CDC’s first summary collectively examining data trends for all nationally notifiable diseases caused by the bite of an infected mosquito, tick, or flea, the most common tickborne diseases in 2016 were Lyme disease and ehrlichiosis/anaplasmosis. The most common mosquito-borne viruses were West Nile, dengue, and Zika.

The increase is due to many factors, the CDC says, but 1 issue is that mosquitoes and ticks are moving into new areas, putting more people at risk. The US is “not fully prepared” to meet the public health threat, the CDC warns: About 80% of vector control organizations lack critical prevention and control capacities. Reducing the spread of the diseases and responding effectively to outbreaks will require additional capacity at the state and local levels for tracking, diagnosing, and reporting cases.

As if it were not bad enough that illnesses from mosquito, tick, and flea bites tripled between 2004 and 2016, 9 new germs spread by mosquitoes and ticks were discovered or introduced into the US in the same 13 years.

According to the CDC’s first summary collectively examining data trends for all nationally notifiable diseases caused by the bite of an infected mosquito, tick, or flea, the most common tickborne diseases in 2016 were Lyme disease and ehrlichiosis/anaplasmosis. The most common mosquito-borne viruses were West Nile, dengue, and Zika.

The increase is due to many factors, the CDC says, but 1 issue is that mosquitoes and ticks are moving into new areas, putting more people at risk. The US is “not fully prepared” to meet the public health threat, the CDC warns: About 80% of vector control organizations lack critical prevention and control capacities. Reducing the spread of the diseases and responding effectively to outbreaks will require additional capacity at the state and local levels for tracking, diagnosing, and reporting cases.

Data seem to indicate that service members and veterans may be at an increased risk of acquiring multiple neurologic diseases or injuries. The very nature of a career in the military often comes with a higher risk of sustaining a traumatic brain injury (TBI) either through combat or physical training, but other serious neurologic disorders seem to affect veterans disproportionally compared with those who did not serve in the Armed Forces.

Click here to continue reading.

Data seem to indicate that service members and veterans may be at an increased risk of acquiring multiple neurologic diseases or injuries. The very nature of a career in the military often comes with a higher risk of sustaining a traumatic brain injury (TBI) either through combat or physical training, but other serious neurologic disorders seem to affect veterans disproportionally compared with those who did not serve in the Armed Forces.

Click here to continue reading.

Data seem to indicate that service members and veterans may be at an increased risk of acquiring multiple neurologic diseases or injuries. The very nature of a career in the military often comes with a higher risk of sustaining a traumatic brain injury (TBI) either through combat or physical training, but other serious neurologic disorders seem to affect veterans disproportionally compared with those who did not serve in the Armed Forces.

Click here to continue reading.

© Universitätsklinikum Freiburg

New research suggests dasatinib could treat certain patients with juvenile myelomonocytic leukemia (JMML) or acute myeloid leukemia (AML).

The study showed that TNK2 inhibition has a negative effect on PTPN11-mutant leukemias.

PTPN11-mutant JMML and AML cells were sensitive to treatment with dasatinib, which inhibits TNK2.

Dasatinib also induced hematologic remission in a patient with PTPN11-mutant JMML.

Investigators reported these results in Science Signaling.

Past research showed that mutations in PTPN11 result in excessive cell proliferation and drive tumor growth in some cases of JMML and AML.

In the current study, investigators analyzed PTPN11-mutated leukemia cells and found that PTPN11 is activated by TNK2.

The investigators said TNK2 phosphorylates PTPN11, which then dephosphorylates TNK2 in a negative feedback loop. They also found that coexpression of TNK2 and mutant PTPN11 results in “robust” MAPK pathway activation.

Inhibiting TNK2 with dasatinib blocked MAPK signaling and colony formation in vitro.

Additional experiments showed that PTPN11-mutant AML samples were significantly more sensitive to dasatinib than wild-type AML samples.

Investigators also tested dasatinib in a sample from a JMML patient carrying a PTPN11 G60R mutation.

This patient’s cells were 10 times more sensitive to dasatinib than the average sample from a cohort of 151 patients who had AML, acute lymphoblastic leukemia, myeloproliferative neoplasms, or chronic lymphocytic leukemia.

Because the JMML patient’s cells were so responsive to dasatinib, the investigators decided to administer the drug to the patient.

The patient achieved sustained hematologic remission with dasatinib, and this allowed him to receive a stem cell transplant using an unrelated cord blood donor. The patient had previously failed 2 transplants (with myeloablative conditioning) from a matched sibling donor.

The third transplant prolonged the patient’s life by a year, but he eventually died of relapsed disease.

The investigators said this case study and the in vitro results support further investigation into the efficacy of dasatinib and other TNK2 inhibitors in PTPN11-mutant leukemias.

© Universitätsklinikum Freiburg

New research suggests dasatinib could treat certain patients with juvenile myelomonocytic leukemia (JMML) or acute myeloid leukemia (AML).

The study showed that TNK2 inhibition has a negative effect on PTPN11-mutant leukemias.

PTPN11-mutant JMML and AML cells were sensitive to treatment with dasatinib, which inhibits TNK2.

Dasatinib also induced hematologic remission in a patient with PTPN11-mutant JMML.

Investigators reported these results in Science Signaling.

Past research showed that mutations in PTPN11 result in excessive cell proliferation and drive tumor growth in some cases of JMML and AML.

In the current study, investigators analyzed PTPN11-mutated leukemia cells and found that PTPN11 is activated by TNK2.

The investigators said TNK2 phosphorylates PTPN11, which then dephosphorylates TNK2 in a negative feedback loop. They also found that coexpression of TNK2 and mutant PTPN11 results in “robust” MAPK pathway activation.

Inhibiting TNK2 with dasatinib blocked MAPK signaling and colony formation in vitro.

Additional experiments showed that PTPN11-mutant AML samples were significantly more sensitive to dasatinib than wild-type AML samples.

Investigators also tested dasatinib in a sample from a JMML patient carrying a PTPN11 G60R mutation.

This patient’s cells were 10 times more sensitive to dasatinib than the average sample from a cohort of 151 patients who had AML, acute lymphoblastic leukemia, myeloproliferative neoplasms, or chronic lymphocytic leukemia.

Because the JMML patient’s cells were so responsive to dasatinib, the investigators decided to administer the drug to the patient.

The patient achieved sustained hematologic remission with dasatinib, and this allowed him to receive a stem cell transplant using an unrelated cord blood donor. The patient had previously failed 2 transplants (with myeloablative conditioning) from a matched sibling donor.

The third transplant prolonged the patient’s life by a year, but he eventually died of relapsed disease.

The investigators said this case study and the in vitro results support further investigation into the efficacy of dasatinib and other TNK2 inhibitors in PTPN11-mutant leukemias.

© Universitätsklinikum Freiburg

New research suggests dasatinib could treat certain patients with juvenile myelomonocytic leukemia (JMML) or acute myeloid leukemia (AML).

The study showed that TNK2 inhibition has a negative effect on PTPN11-mutant leukemias.

PTPN11-mutant JMML and AML cells were sensitive to treatment with dasatinib, which inhibits TNK2.

Dasatinib also induced hematologic remission in a patient with PTPN11-mutant JMML.

Investigators reported these results in Science Signaling.

Past research showed that mutations in PTPN11 result in excessive cell proliferation and drive tumor growth in some cases of JMML and AML.

In the current study, investigators analyzed PTPN11-mutated leukemia cells and found that PTPN11 is activated by TNK2.

The investigators said TNK2 phosphorylates PTPN11, which then dephosphorylates TNK2 in a negative feedback loop. They also found that coexpression of TNK2 and mutant PTPN11 results in “robust” MAPK pathway activation.

Inhibiting TNK2 with dasatinib blocked MAPK signaling and colony formation in vitro.

Additional experiments showed that PTPN11-mutant AML samples were significantly more sensitive to dasatinib than wild-type AML samples.

Investigators also tested dasatinib in a sample from a JMML patient carrying a PTPN11 G60R mutation.

This patient’s cells were 10 times more sensitive to dasatinib than the average sample from a cohort of 151 patients who had AML, acute lymphoblastic leukemia, myeloproliferative neoplasms, or chronic lymphocytic leukemia.

Because the JMML patient’s cells were so responsive to dasatinib, the investigators decided to administer the drug to the patient.

The patient achieved sustained hematologic remission with dasatinib, and this allowed him to receive a stem cell transplant using an unrelated cord blood donor. The patient had previously failed 2 transplants (with myeloablative conditioning) from a matched sibling donor.

The third transplant prolonged the patient’s life by a year, but he eventually died of relapsed disease.

The investigators said this case study and the in vitro results support further investigation into the efficacy of dasatinib and other TNK2 inhibitors in PTPN11-mutant leukemias.

Photo courtesy of NHS

The US Food and Drug Administration (FDA) has granted orphan drug designation to NiCord for hematopoietic stem cell transplant.

NiCord is created by expanding and enriching a unit of umbilical cord blood (UCB).

The product consists of a CD133-positive fraction—which is cultured for 21 days with nicotinamide, thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor—and a CD133-negative fraction that is provided at the time of transplant.

NiCord already has orphan drug designation from the FDA as a treatment for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma, and myelodysplastic syndromes (MDS).

The product also has breakthrough therapy designation from the FDA.

NiCord trials

Final results from a phase 1/2 study suggested that NiCord can be used as a stand-alone graft in patients with high-risk hematologic malignancies. The results were presented at the 2018 BMT Tandem Meetings in February.

The trial included 36 adolescents and adults with AML (n=17), ALL (n=9), MDS (n=7), chronic myeloid leukemia (CML, n=2), and Hodgkin lymphoma (n=1).

All patients received a single NiCord unit. Researchers compared engraftment results in the NiCord recipients to results in a cohort of 148 patients from the CIBMTR registry.

The registry patients underwent standard UCB transplants and had similar characteristics as the NiCord recipients. However, only 20% of the CIBMTR patients received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

There was 1 case of primary graft failure among the NiCord recipients and 2 cases of secondary graft failure.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%. The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the 2-year rate of moderate to severe chronic GVHD was 9.8%.

These results prompted a phase 3 study of NiCord in patients with AML, ALL, CML, MDS, and lymphoma (NCT02730299). In this trial, researchers are comparing NiCord to standard single or double UCB transplant.

About orphan and breakthrough designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough designation entitles sponsors to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Photo courtesy of NHS

The US Food and Drug Administration (FDA) has granted orphan drug designation to NiCord for hematopoietic stem cell transplant.

NiCord is created by expanding and enriching a unit of umbilical cord blood (UCB).

The product consists of a CD133-positive fraction—which is cultured for 21 days with nicotinamide, thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor—and a CD133-negative fraction that is provided at the time of transplant.

NiCord already has orphan drug designation from the FDA as a treatment for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma, and myelodysplastic syndromes (MDS).

The product also has breakthrough therapy designation from the FDA.

NiCord trials

Final results from a phase 1/2 study suggested that NiCord can be used as a stand-alone graft in patients with high-risk hematologic malignancies. The results were presented at the 2018 BMT Tandem Meetings in February.

The trial included 36 adolescents and adults with AML (n=17), ALL (n=9), MDS (n=7), chronic myeloid leukemia (CML, n=2), and Hodgkin lymphoma (n=1).

All patients received a single NiCord unit. Researchers compared engraftment results in the NiCord recipients to results in a cohort of 148 patients from the CIBMTR registry.

The registry patients underwent standard UCB transplants and had similar characteristics as the NiCord recipients. However, only 20% of the CIBMTR patients received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

There was 1 case of primary graft failure among the NiCord recipients and 2 cases of secondary graft failure.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%. The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the 2-year rate of moderate to severe chronic GVHD was 9.8%.

These results prompted a phase 3 study of NiCord in patients with AML, ALL, CML, MDS, and lymphoma (NCT02730299). In this trial, researchers are comparing NiCord to standard single or double UCB transplant.

About orphan and breakthrough designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough designation entitles sponsors to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Photo courtesy of NHS

The US Food and Drug Administration (FDA) has granted orphan drug designation to NiCord for hematopoietic stem cell transplant.

NiCord is created by expanding and enriching a unit of umbilical cord blood (UCB).

The product consists of a CD133-positive fraction—which is cultured for 21 days with nicotinamide, thrombopoietin, IL-6, FLT-3 ligand, and stem cell factor—and a CD133-negative fraction that is provided at the time of transplant.

NiCord already has orphan drug designation from the FDA as a treatment for acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma, and myelodysplastic syndromes (MDS).

The product also has breakthrough therapy designation from the FDA.

NiCord trials

Final results from a phase 1/2 study suggested that NiCord can be used as a stand-alone graft in patients with high-risk hematologic malignancies. The results were presented at the 2018 BMT Tandem Meetings in February.

The trial included 36 adolescents and adults with AML (n=17), ALL (n=9), MDS (n=7), chronic myeloid leukemia (CML, n=2), and Hodgkin lymphoma (n=1).

All patients received a single NiCord unit. Researchers compared engraftment results in the NiCord recipients to results in a cohort of 148 patients from the CIBMTR registry.

The registry patients underwent standard UCB transplants and had similar characteristics as the NiCord recipients. However, only 20% of the CIBMTR patients received a single UCB unit.

The median time to neutrophil engraftment was 11.5 days (range, 6-26) with NiCord and 21 days in the control cohort (P<0.001). The cumulative incidence of neutrophil engraftment was 94.4% and 89.7%, respectively.

The median time to platelet engraftment was 34 days (range, 25-96) with NiCord and 46 days in the controls (P<0.001). The cumulative incidence of platelet engraftment was 80.6% and 67.1%, respectively.

There was 1 case of primary graft failure among the NiCord recipients and 2 cases of secondary graft failure.

The estimated 2-year rate of non-relapse mortality in NiCord recipients was 23.8%, and the 2-year incidence of relapse was 33.2%.

The estimated disease-free survival was 49.1% at 1 year and 43.0% at 2 years. The overall survival was 51.2% at 1 year and 2 years.

At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 44.0%, and the rate of grade 3-4 acute GVHD was 11.1%. The estimated 1-year rate of mild to severe chronic GVHD was 40.5%, and the 2-year rate of moderate to severe chronic GVHD was 9.8%.

These results prompted a phase 3 study of NiCord in patients with AML, ALL, CML, MDS, and lymphoma (NCT02730299). In this trial, researchers are comparing NiCord to standard single or double UCB transplant.

About orphan and breakthrough designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

Orphan designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

Breakthrough designation entitles sponsors to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.