Throughout antiquity, physicians and surgeons have concerned themselves with maladies of the foot and ankle. The literature is rife with articles describing management of clubfoot deformities and traumatic amputations of feet and legs. Authors have described tenotomies and manipulation for clubfeet as well as optimal techniques and levels for amputations to promote healing and functional outcomes. In progressive and aggressive surgical centers in Austria and Germany, techniques for correction of the deformities created by disease and trauma formed the basis for today’s reconstructive methodologies.

During my orthopedic residency in the 1960s, we managed pediatric versions of clubfoot, vertical talus, and neuromuscular conditions of the lower extremity (myelomeningocele, muscular dystrophy, cerebral palsy); adolescent bunions and pathologic flat feet; and, in adults, residual polio, arthritis, bunions, lesser toe deformities, ankle disorders, and trauma. Then along came the excitement of total joint arthroplasty, with its spectacular results, and the thrill in devoting careers to athletes and their myriad problems. Other interesting subspecialties emerged, and the orthopedic focus on a significant part of our heritage, the issues of foot and ankle, was lost for decades. Care for these problems was left to a small cadre of pediatric doctors, and soon-to-retire orthopedists who tended to view the field as
less demanding. Dynamic young practitioners showed little or no interest in caring for foot and ankle patients, and no progress was made in clinical care, research, and development of orthopedic technology and devices.

In the late 1960s, a small group of middle-aged and senior devotees of the specialty met in New York to form the American Orthopaedic Foot Society (AOFS), later to become the American Orthopaedic Foot and Ankle Society (AOFAS). The group’s goal was to renew interest in the foot and ankle specialty among orthopedic surgeons. As everyone knows, AOFAS has flourished and become one of the most progressive, innovative, and dynamic of all the orthopedic subspecialty
groups. In 1985, John Gartland, president of the American Academy of Orthopaedic Surgeons, called together the leaders in the foot and ankle field to formulate a long-range plan to reclaim foot and ankle from the morass of substandard care
and to advance the subspecialty in every quarter. As AOFS (and later AOFAS) president, I was part of Gartland’s team. I recall we aimed to convince orthopedic chairs, the Residency Review Committee for Orthopaedic Surgery, and the Board
of Orthopaedic Surgery to increase training requirements, to develop foot and ankle educators, and to promote the area in training programs. Orthopedic educators developed fellowships (essentially nonexistent up until then) and organized and taught beginner and advanced continuing education courses at annual meetings and throughout the year.

There were other needs to be addressed. One was to educate nonorthopedic doctors to appreciate that foot and ankle problems had good nonoperative and surgical solutions, that there was an orthopedic subspecialty for these conditions, and that foot and ankle patients should be referred to its practitioners. Second, these patients’ public advocacy groups needed to know what knowledgeable orthopedists could provide and needed to be encouraged to seek care from these physicians rather than from less qualified providers and nonspecialists.

To an extraordinary degree, the goal of educating orthopedists has been achieved, and the field is now populated with young, energetic leaders, teachers, and practitioners. We have been less successful in educating potential referring physicians, the public, public advocacy groups, and third-party payers, including the US government. Progress has been made with private insurers and, as advisors, with the Centers for Medicare and Medicaid Services and state government health committees.

Driven by emerging market opportunities, the orthopedic device industry has made unanticipated and enormous advances in the distal lower extremity realm. Small
companies have been founded, and larger companies have dedicated entire divisions to making fixation devices and prosthetic implants for every procedure involving the foot or the ankle. Biomedical engineers, metallurgists, orthopedic
consultant researchers, and well-funded projects have led the surge to develop the best foot and ankle technology. In addition, industry courses and scholarships for residents, fellows, teaching programs, and young physicians have been generating interest in these advances. Although it may be argued that entrepreneurship brings enormous bias, it must be conceded that interest in the foot and ankle field has increased tremendously. Outreach programs for foot and ankle care in the Third World have emerged as an additional humanitarian benefit of the expansion of the field.

From its strong start as a medical specialty to its fall into ignorance and neglect, the foot and ankle field, the unwanted stepchild of medicine and orthopedics, has made a dramatic recovery and has become a premier example of what medicine can achieve through focused effort. As leaders in orthopedic medicine in North America, we must also acknowledge the huge contributions made by a sterling array of international researchers, educators, and practitioners.

Some journals in the United States and other countries now concentrate solely on foot and ankle. Nevertheless, it is appropriate that The American Journal of Orthopedics and other general orthopedic surgery publications focus on foot and
ankle (and other specialties) in an annual issue. As each orthopedist tends mainly to his or her own area of interest, it is essential that we all stay current on the field as a whole. The basic science, innovations, and concepts of one specialty are often applicable to the entire field, and a casual notation of an idea from such a focused issue may have unimagined benefits for the readership and their patients. ◾

Throughout antiquity, physicians and surgeons have concerned themselves with maladies of the foot and ankle. The literature is rife with articles describing management of clubfoot deformities and traumatic amputations of feet and legs. Authors have described tenotomies and manipulation for clubfeet as well as optimal techniques and levels for amputations to promote healing and functional outcomes. In progressive and aggressive surgical centers in Austria and Germany, techniques for correction of the deformities created by disease and trauma formed the basis for today’s reconstructive methodologies.

During my orthopedic residency in the 1960s, we managed pediatric versions of clubfoot, vertical talus, and neuromuscular conditions of the lower extremity (myelomeningocele, muscular dystrophy, cerebral palsy); adolescent bunions and pathologic flat feet; and, in adults, residual polio, arthritis, bunions, lesser toe deformities, ankle disorders, and trauma. Then along came the excitement of total joint arthroplasty, with its spectacular results, and the thrill in devoting careers to athletes and their myriad problems. Other interesting subspecialties emerged, and the orthopedic focus on a significant part of our heritage, the issues of foot and ankle, was lost for decades. Care for these problems was left to a small cadre of pediatric doctors, and soon-to-retire orthopedists who tended to view the field as
less demanding. Dynamic young practitioners showed little or no interest in caring for foot and ankle patients, and no progress was made in clinical care, research, and development of orthopedic technology and devices.

In the late 1960s, a small group of middle-aged and senior devotees of the specialty met in New York to form the American Orthopaedic Foot Society (AOFS), later to become the American Orthopaedic Foot and Ankle Society (AOFAS). The group’s goal was to renew interest in the foot and ankle specialty among orthopedic surgeons. As everyone knows, AOFAS has flourished and become one of the most progressive, innovative, and dynamic of all the orthopedic subspecialty
groups. In 1985, John Gartland, president of the American Academy of Orthopaedic Surgeons, called together the leaders in the foot and ankle field to formulate a long-range plan to reclaim foot and ankle from the morass of substandard care
and to advance the subspecialty in every quarter. As AOFS (and later AOFAS) president, I was part of Gartland’s team. I recall we aimed to convince orthopedic chairs, the Residency Review Committee for Orthopaedic Surgery, and the Board
of Orthopaedic Surgery to increase training requirements, to develop foot and ankle educators, and to promote the area in training programs. Orthopedic educators developed fellowships (essentially nonexistent up until then) and organized and taught beginner and advanced continuing education courses at annual meetings and throughout the year.

There were other needs to be addressed. One was to educate nonorthopedic doctors to appreciate that foot and ankle problems had good nonoperative and surgical solutions, that there was an orthopedic subspecialty for these conditions, and that foot and ankle patients should be referred to its practitioners. Second, these patients’ public advocacy groups needed to know what knowledgeable orthopedists could provide and needed to be encouraged to seek care from these physicians rather than from less qualified providers and nonspecialists.

To an extraordinary degree, the goal of educating orthopedists has been achieved, and the field is now populated with young, energetic leaders, teachers, and practitioners. We have been less successful in educating potential referring physicians, the public, public advocacy groups, and third-party payers, including the US government. Progress has been made with private insurers and, as advisors, with the Centers for Medicare and Medicaid Services and state government health committees.

Driven by emerging market opportunities, the orthopedic device industry has made unanticipated and enormous advances in the distal lower extremity realm. Small
companies have been founded, and larger companies have dedicated entire divisions to making fixation devices and prosthetic implants for every procedure involving the foot or the ankle. Biomedical engineers, metallurgists, orthopedic
consultant researchers, and well-funded projects have led the surge to develop the best foot and ankle technology. In addition, industry courses and scholarships for residents, fellows, teaching programs, and young physicians have been generating interest in these advances. Although it may be argued that entrepreneurship brings enormous bias, it must be conceded that interest in the foot and ankle field has increased tremendously. Outreach programs for foot and ankle care in the Third World have emerged as an additional humanitarian benefit of the expansion of the field.

From its strong start as a medical specialty to its fall into ignorance and neglect, the foot and ankle field, the unwanted stepchild of medicine and orthopedics, has made a dramatic recovery and has become a premier example of what medicine can achieve through focused effort. As leaders in orthopedic medicine in North America, we must also acknowledge the huge contributions made by a sterling array of international researchers, educators, and practitioners.

Some journals in the United States and other countries now concentrate solely on foot and ankle. Nevertheless, it is appropriate that The American Journal of Orthopedics and other general orthopedic surgery publications focus on foot and
ankle (and other specialties) in an annual issue. As each orthopedist tends mainly to his or her own area of interest, it is essential that we all stay current on the field as a whole. The basic science, innovations, and concepts of one specialty are often applicable to the entire field, and a casual notation of an idea from such a focused issue may have unimagined benefits for the readership and their patients. ◾

Throughout antiquity, physicians and surgeons have concerned themselves with maladies of the foot and ankle. The literature is rife with articles describing management of clubfoot deformities and traumatic amputations of feet and legs. Authors have described tenotomies and manipulation for clubfeet as well as optimal techniques and levels for amputations to promote healing and functional outcomes. In progressive and aggressive surgical centers in Austria and Germany, techniques for correction of the deformities created by disease and trauma formed the basis for today’s reconstructive methodologies.

During my orthopedic residency in the 1960s, we managed pediatric versions of clubfoot, vertical talus, and neuromuscular conditions of the lower extremity (myelomeningocele, muscular dystrophy, cerebral palsy); adolescent bunions and pathologic flat feet; and, in adults, residual polio, arthritis, bunions, lesser toe deformities, ankle disorders, and trauma. Then along came the excitement of total joint arthroplasty, with its spectacular results, and the thrill in devoting careers to athletes and their myriad problems. Other interesting subspecialties emerged, and the orthopedic focus on a significant part of our heritage, the issues of foot and ankle, was lost for decades. Care for these problems was left to a small cadre of pediatric doctors, and soon-to-retire orthopedists who tended to view the field as
less demanding. Dynamic young practitioners showed little or no interest in caring for foot and ankle patients, and no progress was made in clinical care, research, and development of orthopedic technology and devices.

In the late 1960s, a small group of middle-aged and senior devotees of the specialty met in New York to form the American Orthopaedic Foot Society (AOFS), later to become the American Orthopaedic Foot and Ankle Society (AOFAS). The group’s goal was to renew interest in the foot and ankle specialty among orthopedic surgeons. As everyone knows, AOFAS has flourished and become one of the most progressive, innovative, and dynamic of all the orthopedic subspecialty
groups. In 1985, John Gartland, president of the American Academy of Orthopaedic Surgeons, called together the leaders in the foot and ankle field to formulate a long-range plan to reclaim foot and ankle from the morass of substandard care
and to advance the subspecialty in every quarter. As AOFS (and later AOFAS) president, I was part of Gartland’s team. I recall we aimed to convince orthopedic chairs, the Residency Review Committee for Orthopaedic Surgery, and the Board
of Orthopaedic Surgery to increase training requirements, to develop foot and ankle educators, and to promote the area in training programs. Orthopedic educators developed fellowships (essentially nonexistent up until then) and organized and taught beginner and advanced continuing education courses at annual meetings and throughout the year.

There were other needs to be addressed. One was to educate nonorthopedic doctors to appreciate that foot and ankle problems had good nonoperative and surgical solutions, that there was an orthopedic subspecialty for these conditions, and that foot and ankle patients should be referred to its practitioners. Second, these patients’ public advocacy groups needed to know what knowledgeable orthopedists could provide and needed to be encouraged to seek care from these physicians rather than from less qualified providers and nonspecialists.

To an extraordinary degree, the goal of educating orthopedists has been achieved, and the field is now populated with young, energetic leaders, teachers, and practitioners. We have been less successful in educating potential referring physicians, the public, public advocacy groups, and third-party payers, including the US government. Progress has been made with private insurers and, as advisors, with the Centers for Medicare and Medicaid Services and state government health committees.

Driven by emerging market opportunities, the orthopedic device industry has made unanticipated and enormous advances in the distal lower extremity realm. Small
companies have been founded, and larger companies have dedicated entire divisions to making fixation devices and prosthetic implants for every procedure involving the foot or the ankle. Biomedical engineers, metallurgists, orthopedic
consultant researchers, and well-funded projects have led the surge to develop the best foot and ankle technology. In addition, industry courses and scholarships for residents, fellows, teaching programs, and young physicians have been generating interest in these advances. Although it may be argued that entrepreneurship brings enormous bias, it must be conceded that interest in the foot and ankle field has increased tremendously. Outreach programs for foot and ankle care in the Third World have emerged as an additional humanitarian benefit of the expansion of the field.

From its strong start as a medical specialty to its fall into ignorance and neglect, the foot and ankle field, the unwanted stepchild of medicine and orthopedics, has made a dramatic recovery and has become a premier example of what medicine can achieve through focused effort. As leaders in orthopedic medicine in North America, we must also acknowledge the huge contributions made by a sterling array of international researchers, educators, and practitioners.

Some journals in the United States and other countries now concentrate solely on foot and ankle. Nevertheless, it is appropriate that The American Journal of Orthopedics and other general orthopedic surgery publications focus on foot and
ankle (and other specialties) in an annual issue. As each orthopedist tends mainly to his or her own area of interest, it is essential that we all stay current on the field as a whole. The basic science, innovations, and concepts of one specialty are often applicable to the entire field, and a casual notation of an idea from such a focused issue may have unimagined benefits for the readership and their patients. ◾

MILAN – Many U.S. patients with gastrointestinal stromal tumors today start on the wrong adjuvant treatment because their physicians don’t order genetic assessment of the cancer, said two American oncologists.

"Initial treatment for GIST [gastrointestinal stromal tumors] is enhanced by molecular decision making," Dr. Jonathan C. Trent said at Sarcoma and GIST 2014, hosted by the European Society for Medical Oncology.

"I’ve had patients referred to me from academic centers where the patient was treated with imatinib [Gleevec], which didn’t work, sunitinib [Sutent], which didn’t work, and regorafenib [Stivarga], which didn’t work. We did genetic testing, and it was a D842V mutation [in the PDGFRA gene]. This patient should never have been treated with these drugs," because GIST that carry this PDGFRA mutation are resistant to all three of these tyrosine kinase inhibitor [TKI] drugs, said Dr. Trent, professor of medicine and director of the bone and soft tissue program at the University of Miami.

"If you’re thinking of giving adjuvant therapy, you absolutely need molecular profiling because in the primary, resected-disease setting, a full 20% of patients will have a mutation that makes imatinib useless, the D842V mutation," said Dr. George D. Demetri, professor of medicine at Harvard University and director of the Center for Sarcoma and Bone Oncology at Dana Farber Cancer Institute, Boston. The potential consequence of not performing a genetic analysis is "you could overtreat 20% of patients with what is a still moderately expensive drug that will give them side effects for 3 years when they don’t need it. That is bad medicine," Dr. Demetri said in an interview. "I’m flabbergasted that more people are not getting molecular profiling for GIST patients being considered for adjuvant therapy. We have not communicated this well. Genetic testing is easily accessible at reference labs."

Dr. Demetri highlighted that identifying a D842V mutation in the PDGFRA gene of a GIST is good news for patients, because when this mutation appears in a primary tumor it flags a very indolent form of GIST. "The physician can tell patients that they don’t need to take this drug because it won’t do them any good, plus most patients with your mutation don’t have their tumor recur for many years and sometimes never."

In its most recent guidelines for GIST management, the National Comprehensive Cancer Network (NCCN) said: "If tyrosine kinase inhibitors are considered as part of the treatment plan, genetic analysis of the tumor should be considered since the presence of mutations (or absence of mutations) in specific regions of the KIT and PDGFRA tyrosine kinase genes are correlated with response (or lack of a response) to specific tyrosine kinase inhibitors."

Similar language exists in the posted GIST management recommendations of the National Cancer Institute (NCI), which date from 2012: "KIT- and PDGFRA-mutational analysis may be of help in predicting responses to kinase inhibitors for patients with unresectable, metastatic, or recurrent GIST who are undergoing therapy with selective TKIs. However, the data are preliminary and mutational analysis for treatment decisions is not routine. There is currently no evidence that basing treatment decisions on mutational analysis improves OS [overall survival]."

Dr. Trent took issue with these positions and said that the NCCN and NCI need to call genetic assessment of primary GIST necessary, especially for patients considered for adjuvant treatment. But others saw reason for equivocation.

"Since the mutational status of GIST can impact your use of adjuvant therapy or even therapy for metastatic disease, most sarcoma physicians prefer to see it done," noted Dr. Robert G. Maki, professor of medicine and director of the sarcoma program at Mount Sinai Medical Center in New York. "That said, we often do not have clinical trial data to support" this approach to management. For example, no trial results clearly show that GIST that carry a PDGFRA D842V mutation do not respond well to imatinib and have better outcomes when treated with some other drug. "I would like to have these data to discuss the options" with patients, Dr. Maki said in an interview. The relatively well-described patterns of genetic mutation and drug sensitivity seen in GIST make this tumor different from other adult sarcomas, he added.

"We had a patient with the PDGFRA D842V mutation who clearly responded to imatinib," said Dr. Robert S. Benjamin, professor and chairman of sarcoma medical oncology at M.D. Anderson Cancer Center in Houston.

"You use imatinib empirically because it is the most benign drug, especially at the 400-mg/day level," Dr. Benjamin said in an interview. "It’s well tolerated, and it usually works." But Dr. Benjamin acknowledged the added value of learning a tumor’s genetic profile. "It’s analogous to infectious disease," where you might start a patient on an empiric antibiotic but then reconsider once you receive antibiotic-sensitivity results. Genotyping complements the clinical findings made after starting a patient on imatinib, he said.

Based on current data for GIST sensitivity to TKIs, Dr. Trent and Dr. Demetri summarized the current GIST mutation and treatment landscape this way:

• About 60% of GIST have the most common tyrosine kinase mutation, in exon 11 of the KIT gene, and are sensitive to 400 mg/day of imatinib.

• About 7% of GIST have the exon 9 mutation of KIT and are sensitive to a higher dosage of imatinib, ideally 800 mg/day if that is tolerated.

• About 20% of GIST have the D842V mutation in the PDGFRA tyrosine kinase gene, and these patients are candidates for enrollment in a trial, as no regimens are known effective for these tumors.

• About 12% of GIST have a mutation in the SDF gene, which appears to make them resistant to imatinib and sunitinib but which may be sensitive to another TKI, regorafenib.

• The remaining GIST have other, rare mutations.

Dr. Trent said that he had no disclosures. Dr. Demetri said that he has been a consultant to Bayer, Novartis, and other companies. Dr. Maki said that he has been a consultant to Eisai/Morphotek, Bayer, and other companies, and has received research support from Eisai/Morphotek, Tracon, and Bayer. Dr. Benjamin said that he has been a consultant to Johnson & Johnson, Merck, and Pfizer.

[email protected]

On Twitter @mitchelzoler

MILAN – Many U.S. patients with gastrointestinal stromal tumors today start on the wrong adjuvant treatment because their physicians don’t order genetic assessment of the cancer, said two American oncologists.

"Initial treatment for GIST [gastrointestinal stromal tumors] is enhanced by molecular decision making," Dr. Jonathan C. Trent said at Sarcoma and GIST 2014, hosted by the European Society for Medical Oncology.

"I’ve had patients referred to me from academic centers where the patient was treated with imatinib [Gleevec], which didn’t work, sunitinib [Sutent], which didn’t work, and regorafenib [Stivarga], which didn’t work. We did genetic testing, and it was a D842V mutation [in the PDGFRA gene]. This patient should never have been treated with these drugs," because GIST that carry this PDGFRA mutation are resistant to all three of these tyrosine kinase inhibitor [TKI] drugs, said Dr. Trent, professor of medicine and director of the bone and soft tissue program at the University of Miami.

"If you’re thinking of giving adjuvant therapy, you absolutely need molecular profiling because in the primary, resected-disease setting, a full 20% of patients will have a mutation that makes imatinib useless, the D842V mutation," said Dr. George D. Demetri, professor of medicine at Harvard University and director of the Center for Sarcoma and Bone Oncology at Dana Farber Cancer Institute, Boston. The potential consequence of not performing a genetic analysis is "you could overtreat 20% of patients with what is a still moderately expensive drug that will give them side effects for 3 years when they don’t need it. That is bad medicine," Dr. Demetri said in an interview. "I’m flabbergasted that more people are not getting molecular profiling for GIST patients being considered for adjuvant therapy. We have not communicated this well. Genetic testing is easily accessible at reference labs."

Dr. Demetri highlighted that identifying a D842V mutation in the PDGFRA gene of a GIST is good news for patients, because when this mutation appears in a primary tumor it flags a very indolent form of GIST. "The physician can tell patients that they don’t need to take this drug because it won’t do them any good, plus most patients with your mutation don’t have their tumor recur for many years and sometimes never."

In its most recent guidelines for GIST management, the National Comprehensive Cancer Network (NCCN) said: "If tyrosine kinase inhibitors are considered as part of the treatment plan, genetic analysis of the tumor should be considered since the presence of mutations (or absence of mutations) in specific regions of the KIT and PDGFRA tyrosine kinase genes are correlated with response (or lack of a response) to specific tyrosine kinase inhibitors."

Similar language exists in the posted GIST management recommendations of the National Cancer Institute (NCI), which date from 2012: "KIT- and PDGFRA-mutational analysis may be of help in predicting responses to kinase inhibitors for patients with unresectable, metastatic, or recurrent GIST who are undergoing therapy with selective TKIs. However, the data are preliminary and mutational analysis for treatment decisions is not routine. There is currently no evidence that basing treatment decisions on mutational analysis improves OS [overall survival]."

Dr. Trent took issue with these positions and said that the NCCN and NCI need to call genetic assessment of primary GIST necessary, especially for patients considered for adjuvant treatment. But others saw reason for equivocation.

"Since the mutational status of GIST can impact your use of adjuvant therapy or even therapy for metastatic disease, most sarcoma physicians prefer to see it done," noted Dr. Robert G. Maki, professor of medicine and director of the sarcoma program at Mount Sinai Medical Center in New York. "That said, we often do not have clinical trial data to support" this approach to management. For example, no trial results clearly show that GIST that carry a PDGFRA D842V mutation do not respond well to imatinib and have better outcomes when treated with some other drug. "I would like to have these data to discuss the options" with patients, Dr. Maki said in an interview. The relatively well-described patterns of genetic mutation and drug sensitivity seen in GIST make this tumor different from other adult sarcomas, he added.

"We had a patient with the PDGFRA D842V mutation who clearly responded to imatinib," said Dr. Robert S. Benjamin, professor and chairman of sarcoma medical oncology at M.D. Anderson Cancer Center in Houston.

"You use imatinib empirically because it is the most benign drug, especially at the 400-mg/day level," Dr. Benjamin said in an interview. "It’s well tolerated, and it usually works." But Dr. Benjamin acknowledged the added value of learning a tumor’s genetic profile. "It’s analogous to infectious disease," where you might start a patient on an empiric antibiotic but then reconsider once you receive antibiotic-sensitivity results. Genotyping complements the clinical findings made after starting a patient on imatinib, he said.

Based on current data for GIST sensitivity to TKIs, Dr. Trent and Dr. Demetri summarized the current GIST mutation and treatment landscape this way:

• About 60% of GIST have the most common tyrosine kinase mutation, in exon 11 of the KIT gene, and are sensitive to 400 mg/day of imatinib.

• About 7% of GIST have the exon 9 mutation of KIT and are sensitive to a higher dosage of imatinib, ideally 800 mg/day if that is tolerated.

• About 20% of GIST have the D842V mutation in the PDGFRA tyrosine kinase gene, and these patients are candidates for enrollment in a trial, as no regimens are known effective for these tumors.

• About 12% of GIST have a mutation in the SDF gene, which appears to make them resistant to imatinib and sunitinib but which may be sensitive to another TKI, regorafenib.

• The remaining GIST have other, rare mutations.

Dr. Trent said that he had no disclosures. Dr. Demetri said that he has been a consultant to Bayer, Novartis, and other companies. Dr. Maki said that he has been a consultant to Eisai/Morphotek, Bayer, and other companies, and has received research support from Eisai/Morphotek, Tracon, and Bayer. Dr. Benjamin said that he has been a consultant to Johnson & Johnson, Merck, and Pfizer.

[email protected]

On Twitter @mitchelzoler

MILAN – Many U.S. patients with gastrointestinal stromal tumors today start on the wrong adjuvant treatment because their physicians don’t order genetic assessment of the cancer, said two American oncologists.

"Initial treatment for GIST [gastrointestinal stromal tumors] is enhanced by molecular decision making," Dr. Jonathan C. Trent said at Sarcoma and GIST 2014, hosted by the European Society for Medical Oncology.

"I’ve had patients referred to me from academic centers where the patient was treated with imatinib [Gleevec], which didn’t work, sunitinib [Sutent], which didn’t work, and regorafenib [Stivarga], which didn’t work. We did genetic testing, and it was a D842V mutation [in the PDGFRA gene]. This patient should never have been treated with these drugs," because GIST that carry this PDGFRA mutation are resistant to all three of these tyrosine kinase inhibitor [TKI] drugs, said Dr. Trent, professor of medicine and director of the bone and soft tissue program at the University of Miami.

"If you’re thinking of giving adjuvant therapy, you absolutely need molecular profiling because in the primary, resected-disease setting, a full 20% of patients will have a mutation that makes imatinib useless, the D842V mutation," said Dr. George D. Demetri, professor of medicine at Harvard University and director of the Center for Sarcoma and Bone Oncology at Dana Farber Cancer Institute, Boston. The potential consequence of not performing a genetic analysis is "you could overtreat 20% of patients with what is a still moderately expensive drug that will give them side effects for 3 years when they don’t need it. That is bad medicine," Dr. Demetri said in an interview. "I’m flabbergasted that more people are not getting molecular profiling for GIST patients being considered for adjuvant therapy. We have not communicated this well. Genetic testing is easily accessible at reference labs."

Dr. Demetri highlighted that identifying a D842V mutation in the PDGFRA gene of a GIST is good news for patients, because when this mutation appears in a primary tumor it flags a very indolent form of GIST. "The physician can tell patients that they don’t need to take this drug because it won’t do them any good, plus most patients with your mutation don’t have their tumor recur for many years and sometimes never."

In its most recent guidelines for GIST management, the National Comprehensive Cancer Network (NCCN) said: "If tyrosine kinase inhibitors are considered as part of the treatment plan, genetic analysis of the tumor should be considered since the presence of mutations (or absence of mutations) in specific regions of the KIT and PDGFRA tyrosine kinase genes are correlated with response (or lack of a response) to specific tyrosine kinase inhibitors."

Similar language exists in the posted GIST management recommendations of the National Cancer Institute (NCI), which date from 2012: "KIT- and PDGFRA-mutational analysis may be of help in predicting responses to kinase inhibitors for patients with unresectable, metastatic, or recurrent GIST who are undergoing therapy with selective TKIs. However, the data are preliminary and mutational analysis for treatment decisions is not routine. There is currently no evidence that basing treatment decisions on mutational analysis improves OS [overall survival]."

Dr. Trent took issue with these positions and said that the NCCN and NCI need to call genetic assessment of primary GIST necessary, especially for patients considered for adjuvant treatment. But others saw reason for equivocation.

"Since the mutational status of GIST can impact your use of adjuvant therapy or even therapy for metastatic disease, most sarcoma physicians prefer to see it done," noted Dr. Robert G. Maki, professor of medicine and director of the sarcoma program at Mount Sinai Medical Center in New York. "That said, we often do not have clinical trial data to support" this approach to management. For example, no trial results clearly show that GIST that carry a PDGFRA D842V mutation do not respond well to imatinib and have better outcomes when treated with some other drug. "I would like to have these data to discuss the options" with patients, Dr. Maki said in an interview. The relatively well-described patterns of genetic mutation and drug sensitivity seen in GIST make this tumor different from other adult sarcomas, he added.

"We had a patient with the PDGFRA D842V mutation who clearly responded to imatinib," said Dr. Robert S. Benjamin, professor and chairman of sarcoma medical oncology at M.D. Anderson Cancer Center in Houston.

"You use imatinib empirically because it is the most benign drug, especially at the 400-mg/day level," Dr. Benjamin said in an interview. "It’s well tolerated, and it usually works." But Dr. Benjamin acknowledged the added value of learning a tumor’s genetic profile. "It’s analogous to infectious disease," where you might start a patient on an empiric antibiotic but then reconsider once you receive antibiotic-sensitivity results. Genotyping complements the clinical findings made after starting a patient on imatinib, he said.

Based on current data for GIST sensitivity to TKIs, Dr. Trent and Dr. Demetri summarized the current GIST mutation and treatment landscape this way:

• About 60% of GIST have the most common tyrosine kinase mutation, in exon 11 of the KIT gene, and are sensitive to 400 mg/day of imatinib.

• About 7% of GIST have the exon 9 mutation of KIT and are sensitive to a higher dosage of imatinib, ideally 800 mg/day if that is tolerated.

• About 20% of GIST have the D842V mutation in the PDGFRA tyrosine kinase gene, and these patients are candidates for enrollment in a trial, as no regimens are known effective for these tumors.

• About 12% of GIST have a mutation in the SDF gene, which appears to make them resistant to imatinib and sunitinib but which may be sensitive to another TKI, regorafenib.

• The remaining GIST have other, rare mutations.

Dr. Trent said that he had no disclosures. Dr. Demetri said that he has been a consultant to Bayer, Novartis, and other companies. Dr. Maki said that he has been a consultant to Eisai/Morphotek, Bayer, and other companies, and has received research support from Eisai/Morphotek, Tracon, and Bayer. Dr. Benjamin said that he has been a consultant to Johnson & Johnson, Merck, and Pfizer.

[email protected]

On Twitter @mitchelzoler

MILAN – Although genetic analysis has become a key part of gastrointestinal-stromal tumor assessment before treating a primary tumor, its use at the time of recurrence remains problematic because of the heterogeneity of recurrent clones at the time of relapse, according to Dr. George D. Demetri.

"Liquid biopsy" is a new genetic assessment method with the potential to address the heterogeneity by sampling the complete spectrum of a patient’s tumor using free circulating tumor DNA in the patient’s plasma, rather than biopsying specific pieces of the tumor.

"The challenge from multiple, progressing tumors in a patient with GIST who is failing tyrosine-kinase inhibitor treatment is how to get around the limitation of tumor biopsy. How useful are biopsies when each corner of the tumor tells you something different" when a patient has recurrent GIST? said Dr. Demetri at Sarcoma and GIST 2014, hosted by the European Society for Medical Oncology. "Do you think you get a comprehensive look by biopsying the tumor? How many biopsies do you take?" asked Dr. Demetri, professor of medicine at Harvard Medical School and director of the center for sarcoma and bone oncology at Dana Farber Cancer Institute, both in Boston.

Dr. Demetri called for continued research to prove the efficacy and utility of liquid biopsies. "We need to develop liquid biopsies to get around the issue of tumor biopsies," he said.

The approach relies on the concept that tumor cells are constantly dying and releasing their DNA into a patient’s blood, and hence the free DNA circulating reflects the genetic profile, including all mutations and clones the patient’s tumor has at the time; this approach was pioneered by researchers at Johns Hopkins University (Sci. Transl. Med. 2012;4:162ra154).

Last year, researchers in Germany reported good correlations when assessing mutations in free circulating DNA in multiple plasma samples drawn from 38 patients with recurrent GIST and matching the results with the patients’ clinical state (Clin. Cancer Res. 2013;19:4854-67).

Dr. Demetri said his own laboratory recently compared mutational analyses in 32 patients with primary GIST and found that in 29 of 32 cases (91%), the mutational profile seen in the free circulating DNA matched that seen in biopsy specimens from each patient.

Currently, genetic assessment of free circulating DNA relies on looking for known mutations using specific amplification primers for those mutations, but next-generation sequencing could be used instead to search for any type of mutation, Dr. Demetri said.

Genetic analysis of GIST at the time of relapse is important, given today’s treatment options and the need to match the right treatment to the right genetic profile, but the challenge is how to perform this analysis in a meaningful way, commented Dr. Robert S. Benjamin, professor and chairman of sarcoma medical oncology at M.D. Anderson Cancer Center in Houston. "The idea of using free DNA in blood is very exciting," he said in an interview.

Dr. Demetri said he has been a consultant to Bayer, Novartis, Pfizer, Sanofi Oncology, Merck, GlaxoSmithKline, and Ariad. Dr. Benjamin said he has been a consultant to Johnson & Johnson, Merck, and Pfizer.

[email protected]

On Twitter @mitchelzoler

MILAN – Although genetic analysis has become a key part of gastrointestinal-stromal tumor assessment before treating a primary tumor, its use at the time of recurrence remains problematic because of the heterogeneity of recurrent clones at the time of relapse, according to Dr. George D. Demetri.

"Liquid biopsy" is a new genetic assessment method with the potential to address the heterogeneity by sampling the complete spectrum of a patient’s tumor using free circulating tumor DNA in the patient’s plasma, rather than biopsying specific pieces of the tumor.

"The challenge from multiple, progressing tumors in a patient with GIST who is failing tyrosine-kinase inhibitor treatment is how to get around the limitation of tumor biopsy. How useful are biopsies when each corner of the tumor tells you something different" when a patient has recurrent GIST? said Dr. Demetri at Sarcoma and GIST 2014, hosted by the European Society for Medical Oncology. "Do you think you get a comprehensive look by biopsying the tumor? How many biopsies do you take?" asked Dr. Demetri, professor of medicine at Harvard Medical School and director of the center for sarcoma and bone oncology at Dana Farber Cancer Institute, both in Boston.

Dr. Demetri called for continued research to prove the efficacy and utility of liquid biopsies. "We need to develop liquid biopsies to get around the issue of tumor biopsies," he said.

The approach relies on the concept that tumor cells are constantly dying and releasing their DNA into a patient’s blood, and hence the free DNA circulating reflects the genetic profile, including all mutations and clones the patient’s tumor has at the time; this approach was pioneered by researchers at Johns Hopkins University (Sci. Transl. Med. 2012;4:162ra154).

Last year, researchers in Germany reported good correlations when assessing mutations in free circulating DNA in multiple plasma samples drawn from 38 patients with recurrent GIST and matching the results with the patients’ clinical state (Clin. Cancer Res. 2013;19:4854-67).

Dr. Demetri said his own laboratory recently compared mutational analyses in 32 patients with primary GIST and found that in 29 of 32 cases (91%), the mutational profile seen in the free circulating DNA matched that seen in biopsy specimens from each patient.

Currently, genetic assessment of free circulating DNA relies on looking for known mutations using specific amplification primers for those mutations, but next-generation sequencing could be used instead to search for any type of mutation, Dr. Demetri said.

Genetic analysis of GIST at the time of relapse is important, given today’s treatment options and the need to match the right treatment to the right genetic profile, but the challenge is how to perform this analysis in a meaningful way, commented Dr. Robert S. Benjamin, professor and chairman of sarcoma medical oncology at M.D. Anderson Cancer Center in Houston. "The idea of using free DNA in blood is very exciting," he said in an interview.

Dr. Demetri said he has been a consultant to Bayer, Novartis, Pfizer, Sanofi Oncology, Merck, GlaxoSmithKline, and Ariad. Dr. Benjamin said he has been a consultant to Johnson & Johnson, Merck, and Pfizer.

[email protected]

On Twitter @mitchelzoler

MILAN – Although genetic analysis has become a key part of gastrointestinal-stromal tumor assessment before treating a primary tumor, its use at the time of recurrence remains problematic because of the heterogeneity of recurrent clones at the time of relapse, according to Dr. George D. Demetri.

"Liquid biopsy" is a new genetic assessment method with the potential to address the heterogeneity by sampling the complete spectrum of a patient’s tumor using free circulating tumor DNA in the patient’s plasma, rather than biopsying specific pieces of the tumor.

"The challenge from multiple, progressing tumors in a patient with GIST who is failing tyrosine-kinase inhibitor treatment is how to get around the limitation of tumor biopsy. How useful are biopsies when each corner of the tumor tells you something different" when a patient has recurrent GIST? said Dr. Demetri at Sarcoma and GIST 2014, hosted by the European Society for Medical Oncology. "Do you think you get a comprehensive look by biopsying the tumor? How many biopsies do you take?" asked Dr. Demetri, professor of medicine at Harvard Medical School and director of the center for sarcoma and bone oncology at Dana Farber Cancer Institute, both in Boston.

Dr. Demetri called for continued research to prove the efficacy and utility of liquid biopsies. "We need to develop liquid biopsies to get around the issue of tumor biopsies," he said.

The approach relies on the concept that tumor cells are constantly dying and releasing their DNA into a patient’s blood, and hence the free DNA circulating reflects the genetic profile, including all mutations and clones the patient’s tumor has at the time; this approach was pioneered by researchers at Johns Hopkins University (Sci. Transl. Med. 2012;4:162ra154).

Last year, researchers in Germany reported good correlations when assessing mutations in free circulating DNA in multiple plasma samples drawn from 38 patients with recurrent GIST and matching the results with the patients’ clinical state (Clin. Cancer Res. 2013;19:4854-67).

Dr. Demetri said his own laboratory recently compared mutational analyses in 32 patients with primary GIST and found that in 29 of 32 cases (91%), the mutational profile seen in the free circulating DNA matched that seen in biopsy specimens from each patient.

Currently, genetic assessment of free circulating DNA relies on looking for known mutations using specific amplification primers for those mutations, but next-generation sequencing could be used instead to search for any type of mutation, Dr. Demetri said.

Genetic analysis of GIST at the time of relapse is important, given today’s treatment options and the need to match the right treatment to the right genetic profile, but the challenge is how to perform this analysis in a meaningful way, commented Dr. Robert S. Benjamin, professor and chairman of sarcoma medical oncology at M.D. Anderson Cancer Center in Houston. "The idea of using free DNA in blood is very exciting," he said in an interview.

Dr. Demetri said he has been a consultant to Bayer, Novartis, Pfizer, Sanofi Oncology, Merck, GlaxoSmithKline, and Ariad. Dr. Benjamin said he has been a consultant to Johnson & Johnson, Merck, and Pfizer.

[email protected]

On Twitter @mitchelzoler

Recently, the Senate Judiciary Committee heard testimony regarding the use of solitary confinement in the Federal Bureau of Prisons. This was the second hearing on this issue, which featured testimony from the director of the federal system, from several human rights organizations, from state prison officials, and from former inmates themselves. Although one of the main concerns of the hearing was the psychological effects of solitary confinement, only one of the 11 speakers was a mental health professional. Psychology professor Craig Haney, Ph.D., has spent 30 years studying the effects of solitary confinement; however, by his own testimony, he did this primarily as an expert witness retained in the context of correctional litigation. None of those offering testimony was a mental health professional actively involved in the treatment of segregated prisoners. In fact, according to the curriculum vitae that Dr. Haney filed in his capacity as an expert in the California prison overcrowding case, Dr. Haney has never worked in a jail or a prison.

During the hearing, Sen. Al Franken (D-Minn.) made a reference to the risks some inmates posed to prison "guards." For those readers who have never worked in corrections, this is a tremendous faux pas. A "guard" is a generic term for a civilian hired by a private company or business who is given minimal training, slapped into a uniform, and told to stand watch over something. A correctional officer is a law enforcement professional who is trained, regulated, and monitored by the state. A correctional officer is a professional with a code of ethics and who is granted police powers, including the right to use deadly force. Confusing a correctional officer with a "guard" is like mistaking a Navy Seal for a Boy Scout.

So we have a hearing about the psychological effects of confinement in which a psychologist with no correctional experience is testifying before a senator who is not familiar with even basic correctional training standards. What could possibly go wrong?

This topic is close to my heart lately, because there is a bill currently before the Maryland General Assembly to study the use of solitary confinement in our prison system. I’ve read the bill, I’ve listened to the testimony, and I have a few opinions on the issue myself.

First, a few stipulations and clarifications. People involved in this issue tend to confuse terminology related to restricted housing within a correctional facility. The term "solitary confinement" traditionally means a housing situation in which the inmate is placed alone in a cell. The term "administrative segregation" or "ad seg" is sometimes used interchangeably with "disciplinary segregation," although this is not accurate. Disciplinary segregation means that the inmate is removed from the general population because of a rule violation. Inmates on disciplinary segregation are often barred from owning certain property like a television or radio. Visiting privileges and phone calls may also be restricted as a punishment.

In contrast, an inmate could be placed on administrative segregation for nondisciplinary reasons if the prisoner requires medical isolation temporarily, if the inmate voluntarily requests special housing, or if there is a need for protective custody. In this case, the inmate is still allowed to own property, and he retains basic visiting and telephone privileges. In all cases, there is time allowed out of the cell for exercise and recreation. There is also still access to medical and mental health services.

Regarding the stipulations, I don’t question that the prevalence of mental illness among prisoners will be high in a facility that is designated as maximum security or in a control unit prison. I also agree that solitary confinement, or housing without a cellmate, is a bad idea for a prisoner who is deemed a high suicide risk. I agree that boredom and lack of activity are generally a very bad thing for anyone, prisoner or not, and that we shouldn’t keep prisoners on segregation status longer than is necessary to accomplish the intended purpose of the housing.

Here’s where the agreement ends: I don’t think restricted housing is automatically and consistently bad for everyone, and I certainly don’t agree that the segregated housing itself causes whatever mental disturbance may be present. Association does not prove cause and effect, and the number of well-designed, controlled studies of this issue are too few and far between to allow a causal link to be drawn. I realize that this goes against the grain of most court findings on this issue, but that’s the state of the science. I was not surprised to see that the proponents of the solitary confinement bill didn’t mention contradictory evidence. Few journalists in the traditional media have, either.

I think when it comes to dictating prison policy, our legislators need to realize how dangerous our prison systems have become. According to the Bureau of Justice Statistics, between 2001 and 2011, the number of murders in American prisons increased by 79%. During that time my own state ranked second in the country in per capita prison murders. According to the testimony by the federal prison director, 47% of the inmates confined in the Florence SuperMax facility – the institution at the heart of the latest class action suit over solitary confinement – are there for killing another prisoner or staff member while incarcerated. Some of them have killed more than once. If one of my patients tells me that he feels safer in segregated housing and wants to be there, I’m not going to question that, and I hope no outside politician or advocacy group is going to criticize that intervention.

Dr. Hanson is a forensic psychiatrist and coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011). The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

Recently, the Senate Judiciary Committee heard testimony regarding the use of solitary confinement in the Federal Bureau of Prisons. This was the second hearing on this issue, which featured testimony from the director of the federal system, from several human rights organizations, from state prison officials, and from former inmates themselves. Although one of the main concerns of the hearing was the psychological effects of solitary confinement, only one of the 11 speakers was a mental health professional. Psychology professor Craig Haney, Ph.D., has spent 30 years studying the effects of solitary confinement; however, by his own testimony, he did this primarily as an expert witness retained in the context of correctional litigation. None of those offering testimony was a mental health professional actively involved in the treatment of segregated prisoners. In fact, according to the curriculum vitae that Dr. Haney filed in his capacity as an expert in the California prison overcrowding case, Dr. Haney has never worked in a jail or a prison.

During the hearing, Sen. Al Franken (D-Minn.) made a reference to the risks some inmates posed to prison "guards." For those readers who have never worked in corrections, this is a tremendous faux pas. A "guard" is a generic term for a civilian hired by a private company or business who is given minimal training, slapped into a uniform, and told to stand watch over something. A correctional officer is a law enforcement professional who is trained, regulated, and monitored by the state. A correctional officer is a professional with a code of ethics and who is granted police powers, including the right to use deadly force. Confusing a correctional officer with a "guard" is like mistaking a Navy Seal for a Boy Scout.

So we have a hearing about the psychological effects of confinement in which a psychologist with no correctional experience is testifying before a senator who is not familiar with even basic correctional training standards. What could possibly go wrong?

This topic is close to my heart lately, because there is a bill currently before the Maryland General Assembly to study the use of solitary confinement in our prison system. I’ve read the bill, I’ve listened to the testimony, and I have a few opinions on the issue myself.

First, a few stipulations and clarifications. People involved in this issue tend to confuse terminology related to restricted housing within a correctional facility. The term "solitary confinement" traditionally means a housing situation in which the inmate is placed alone in a cell. The term "administrative segregation" or "ad seg" is sometimes used interchangeably with "disciplinary segregation," although this is not accurate. Disciplinary segregation means that the inmate is removed from the general population because of a rule violation. Inmates on disciplinary segregation are often barred from owning certain property like a television or radio. Visiting privileges and phone calls may also be restricted as a punishment.

In contrast, an inmate could be placed on administrative segregation for nondisciplinary reasons if the prisoner requires medical isolation temporarily, if the inmate voluntarily requests special housing, or if there is a need for protective custody. In this case, the inmate is still allowed to own property, and he retains basic visiting and telephone privileges. In all cases, there is time allowed out of the cell for exercise and recreation. There is also still access to medical and mental health services.

Regarding the stipulations, I don’t question that the prevalence of mental illness among prisoners will be high in a facility that is designated as maximum security or in a control unit prison. I also agree that solitary confinement, or housing without a cellmate, is a bad idea for a prisoner who is deemed a high suicide risk. I agree that boredom and lack of activity are generally a very bad thing for anyone, prisoner or not, and that we shouldn’t keep prisoners on segregation status longer than is necessary to accomplish the intended purpose of the housing.

Here’s where the agreement ends: I don’t think restricted housing is automatically and consistently bad for everyone, and I certainly don’t agree that the segregated housing itself causes whatever mental disturbance may be present. Association does not prove cause and effect, and the number of well-designed, controlled studies of this issue are too few and far between to allow a causal link to be drawn. I realize that this goes against the grain of most court findings on this issue, but that’s the state of the science. I was not surprised to see that the proponents of the solitary confinement bill didn’t mention contradictory evidence. Few journalists in the traditional media have, either.

I think when it comes to dictating prison policy, our legislators need to realize how dangerous our prison systems have become. According to the Bureau of Justice Statistics, between 2001 and 2011, the number of murders in American prisons increased by 79%. During that time my own state ranked second in the country in per capita prison murders. According to the testimony by the federal prison director, 47% of the inmates confined in the Florence SuperMax facility – the institution at the heart of the latest class action suit over solitary confinement – are there for killing another prisoner or staff member while incarcerated. Some of them have killed more than once. If one of my patients tells me that he feels safer in segregated housing and wants to be there, I’m not going to question that, and I hope no outside politician or advocacy group is going to criticize that intervention.

Dr. Hanson is a forensic psychiatrist and coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011). The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

Recently, the Senate Judiciary Committee heard testimony regarding the use of solitary confinement in the Federal Bureau of Prisons. This was the second hearing on this issue, which featured testimony from the director of the federal system, from several human rights organizations, from state prison officials, and from former inmates themselves. Although one of the main concerns of the hearing was the psychological effects of solitary confinement, only one of the 11 speakers was a mental health professional. Psychology professor Craig Haney, Ph.D., has spent 30 years studying the effects of solitary confinement; however, by his own testimony, he did this primarily as an expert witness retained in the context of correctional litigation. None of those offering testimony was a mental health professional actively involved in the treatment of segregated prisoners. In fact, according to the curriculum vitae that Dr. Haney filed in his capacity as an expert in the California prison overcrowding case, Dr. Haney has never worked in a jail or a prison.

During the hearing, Sen. Al Franken (D-Minn.) made a reference to the risks some inmates posed to prison "guards." For those readers who have never worked in corrections, this is a tremendous faux pas. A "guard" is a generic term for a civilian hired by a private company or business who is given minimal training, slapped into a uniform, and told to stand watch over something. A correctional officer is a law enforcement professional who is trained, regulated, and monitored by the state. A correctional officer is a professional with a code of ethics and who is granted police powers, including the right to use deadly force. Confusing a correctional officer with a "guard" is like mistaking a Navy Seal for a Boy Scout.

So we have a hearing about the psychological effects of confinement in which a psychologist with no correctional experience is testifying before a senator who is not familiar with even basic correctional training standards. What could possibly go wrong?

This topic is close to my heart lately, because there is a bill currently before the Maryland General Assembly to study the use of solitary confinement in our prison system. I’ve read the bill, I’ve listened to the testimony, and I have a few opinions on the issue myself.

First, a few stipulations and clarifications. People involved in this issue tend to confuse terminology related to restricted housing within a correctional facility. The term "solitary confinement" traditionally means a housing situation in which the inmate is placed alone in a cell. The term "administrative segregation" or "ad seg" is sometimes used interchangeably with "disciplinary segregation," although this is not accurate. Disciplinary segregation means that the inmate is removed from the general population because of a rule violation. Inmates on disciplinary segregation are often barred from owning certain property like a television or radio. Visiting privileges and phone calls may also be restricted as a punishment.

In contrast, an inmate could be placed on administrative segregation for nondisciplinary reasons if the prisoner requires medical isolation temporarily, if the inmate voluntarily requests special housing, or if there is a need for protective custody. In this case, the inmate is still allowed to own property, and he retains basic visiting and telephone privileges. In all cases, there is time allowed out of the cell for exercise and recreation. There is also still access to medical and mental health services.

Regarding the stipulations, I don’t question that the prevalence of mental illness among prisoners will be high in a facility that is designated as maximum security or in a control unit prison. I also agree that solitary confinement, or housing without a cellmate, is a bad idea for a prisoner who is deemed a high suicide risk. I agree that boredom and lack of activity are generally a very bad thing for anyone, prisoner or not, and that we shouldn’t keep prisoners on segregation status longer than is necessary to accomplish the intended purpose of the housing.

Here’s where the agreement ends: I don’t think restricted housing is automatically and consistently bad for everyone, and I certainly don’t agree that the segregated housing itself causes whatever mental disturbance may be present. Association does not prove cause and effect, and the number of well-designed, controlled studies of this issue are too few and far between to allow a causal link to be drawn. I realize that this goes against the grain of most court findings on this issue, but that’s the state of the science. I was not surprised to see that the proponents of the solitary confinement bill didn’t mention contradictory evidence. Few journalists in the traditional media have, either.

I think when it comes to dictating prison policy, our legislators need to realize how dangerous our prison systems have become. According to the Bureau of Justice Statistics, between 2001 and 2011, the number of murders in American prisons increased by 79%. During that time my own state ranked second in the country in per capita prison murders. According to the testimony by the federal prison director, 47% of the inmates confined in the Florence SuperMax facility – the institution at the heart of the latest class action suit over solitary confinement – are there for killing another prisoner or staff member while incarcerated. Some of them have killed more than once. If one of my patients tells me that he feels safer in segregated housing and wants to be there, I’m not going to question that, and I hope no outside politician or advocacy group is going to criticize that intervention.

Dr. Hanson is a forensic psychiatrist and coauthor of "Shrink Rap: Three Psychiatrists Explain Their Work" (Baltimore: The Johns Hopkins University Press, 2011). The opinions expressed are those of the author only, and do not represent those of any of Dr. Hanson’s employers or consultees, including the Maryland Department of Health and Mental Hygiene or the Maryland Division of Correction.

GRAPEVINE, TEXAS—The total nucleated cell (TNC) dose delivered in an allogeneic peripheral blood stem cell transplant (allo-PBSCT) can affect outcomes in certain patients, according to a study presented at the 2014 BMT Tandem Meetings.

Researchers found that a higher TNC dose was associated with better progression-free survival (PFS) and overall survival (OS) among patients who received allo-PBSCT with reduced-intensity conditioning (RIC) and total-body irradiation (TBI).

On the other hand, the dose of CD3+, CD4+, CD8+, or CD34+ cells did not have a significant impact on survival rates in these patients.

And none of the cell doses studied had a significant impact in patients who did not receive TBI or in those who received TBI with myeloablative conditioning.

Michael Burns, of Roswell Park Cancer Institute in Buffalo, New York, presented these findings at the meeting as abstract 12.*

Burns noted that studies have produced conflicting results regarding the correlation between patient outcomes and the dose of CD34+, CD3+, CD4+, or CD8+ cells given in allo-PBSCT. In addition, TNC dose has not been analyzed much in the context of PBSCTs.

Therefore, he and his colleagues retrospectively analyzed graft cell composition in 254 patients who received their first allo-PBSCT from January 2001 to September 2012.

Fifty-eight percent of the patients were male, and the median age was 50 (range, 19-73 years). Forty-four percent of patients had acute myeloid leukemia, 18% had myelodysplastic syndromes or myeloproliferative neoplasms, 13% had acute lymphoblastic leukemia, 13% had non-Hodgkin lymphoma, and 12% had other diseases.

Of the 254 patients studied, 93 had received TBI. Among these, 53 received myeloablative conditioning (91% cyclophosphamide, 120 cGy), and 40 received RIC (100% fludarabine and melphalan, 400 cGy).

Of the 161 patients who did not receive TBI, 41 received myeloablative conditioning (88% busulfan and cyclophosphamide), and 120 received RIC (87% fludarabine and melphalan).

Patients received T-cell-replete, G-CSF mobilized, PB allografts. Fifty-six percent had a 6/6 HLA matched related donor, and 44% had an 8/8 HLA matched unrelated donor. Forty-nine percent of patients were in complete remission at the time of transplant.

The researchers analyzed cell doses according to the median dose (above vs below). But they also analyzed CD34+ dose as < 4 x 10⁶ cells/kg vs ≥ 4 x 10⁶ cells/kg and as < 4 x 10⁶ cells/kg vs 4 to 8 x 10⁶ cells/kg vs > 8 x 10⁶ cells/kg. They analyzed TNC as < 8 x 10⁸ cells/kg vs ≥ to 8 x 10⁸ cells/kg.

The team found that a CD34+ cell dose greater than 4 x 10⁶ cells/kg was significantly associated with time to platelet engraftment in all patients. It was also associated with time to neutrophil engraftment in the TBI group, but this was predominantly among patients who received RIC.

On the other hand, CD3+, CD4+, CD8+, and TNC doses were not significantly associated with platelet or neutrophil engraftment in any patients.

CD34+, CD3+, CD4+, and CD8+ cell dose were not associated with OS, PFS, or acute graft-vs-host disease (GVHD). And TNC had no significant effect on acute GVHD.

“However, we did find that the TNC dose did show some pretty interesting survival outcomes,” Burns said.

A higher TNC dose (≥ 8 x10⁸ cells/kg) was associated with significantly better PFS (P=0.027) and OS (P=0.018) in the TBI patients but not in patients who did not receive TBI (P>0.1 for PFS and OS).

When they analyzed patients according to conditioning regimen, the researchers found the association retained significance among patients who received RIC (P=0.01 for PFS and P=0.007 for OS) but not among patients who received myeloablative conditioning (P>0.1 for PFS and OS).

Burns and his colleagues also conducted a multivariate analysis to see if any other factors affected the relationship between TNC and survival. They controlled for patient age, Karnofsky performance status, and body mass index. And they stratified patients into 4 groups according to TBI and conditioning regimen.

The results showed that patients who received TBI and RIC, as well as a TNC dose less than 8 x 10⁸ cells/kg, had a relative risk of 3.3 for PFS (P=0.026) and a relative risk of 3.4 for OS (P=0.021).

“The association of higher TNC dose with better progression-free and overall survival implies there is a population of nucleated cells which mitigate GVHD but enhance the [graft-vs-leukemia] effect after reduced-intensity TBI conditioning,” Burns said.

“Myeloablative conditioning regimens result in more direct tumor killing. Thus, they rely less on the graft-vs-leukemia effect than the RIC regimens.”

He also noted that the lack of an association between TNC dose and survival rates with non-TBI-based regimens implies there are different mechanisms of tumor kill with TBI and non-TBI-containing regimens.

And a more detailed analysis of cell population subsets in apheresis product may allow researchers to identify cell populations that could improve patient outcomes.

*Some data in the abstract differ from data presented at the meeting.

GRAPEVINE, TEXAS—The total nucleated cell (TNC) dose delivered in an allogeneic peripheral blood stem cell transplant (allo-PBSCT) can affect outcomes in certain patients, according to a study presented at the 2014 BMT Tandem Meetings.

Researchers found that a higher TNC dose was associated with better progression-free survival (PFS) and overall survival (OS) among patients who received allo-PBSCT with reduced-intensity conditioning (RIC) and total-body irradiation (TBI).

On the other hand, the dose of CD3+, CD4+, CD8+, or CD34+ cells did not have a significant impact on survival rates in these patients.

And none of the cell doses studied had a significant impact in patients who did not receive TBI or in those who received TBI with myeloablative conditioning.

Michael Burns, of Roswell Park Cancer Institute in Buffalo, New York, presented these findings at the meeting as abstract 12.*

Burns noted that studies have produced conflicting results regarding the correlation between patient outcomes and the dose of CD34+, CD3+, CD4+, or CD8+ cells given in allo-PBSCT. In addition, TNC dose has not been analyzed much in the context of PBSCTs.

Therefore, he and his colleagues retrospectively analyzed graft cell composition in 254 patients who received their first allo-PBSCT from January 2001 to September 2012.

Fifty-eight percent of the patients were male, and the median age was 50 (range, 19-73 years). Forty-four percent of patients had acute myeloid leukemia, 18% had myelodysplastic syndromes or myeloproliferative neoplasms, 13% had acute lymphoblastic leukemia, 13% had non-Hodgkin lymphoma, and 12% had other diseases.

Of the 254 patients studied, 93 had received TBI. Among these, 53 received myeloablative conditioning (91% cyclophosphamide, 120 cGy), and 40 received RIC (100% fludarabine and melphalan, 400 cGy).

Of the 161 patients who did not receive TBI, 41 received myeloablative conditioning (88% busulfan and cyclophosphamide), and 120 received RIC (87% fludarabine and melphalan).

Patients received T-cell-replete, G-CSF mobilized, PB allografts. Fifty-six percent had a 6/6 HLA matched related donor, and 44% had an 8/8 HLA matched unrelated donor. Forty-nine percent of patients were in complete remission at the time of transplant.

The researchers analyzed cell doses according to the median dose (above vs below). But they also analyzed CD34+ dose as < 4 x 10⁶ cells/kg vs ≥ 4 x 10⁶ cells/kg and as < 4 x 10⁶ cells/kg vs 4 to 8 x 10⁶ cells/kg vs > 8 x 10⁶ cells/kg. They analyzed TNC as < 8 x 10⁸ cells/kg vs ≥ to 8 x 10⁸ cells/kg.

The team found that a CD34+ cell dose greater than 4 x 10⁶ cells/kg was significantly associated with time to platelet engraftment in all patients. It was also associated with time to neutrophil engraftment in the TBI group, but this was predominantly among patients who received RIC.

On the other hand, CD3+, CD4+, CD8+, and TNC doses were not significantly associated with platelet or neutrophil engraftment in any patients.

CD34+, CD3+, CD4+, and CD8+ cell dose were not associated with OS, PFS, or acute graft-vs-host disease (GVHD). And TNC had no significant effect on acute GVHD.

“However, we did find that the TNC dose did show some pretty interesting survival outcomes,” Burns said.

A higher TNC dose (≥ 8 x10⁸ cells/kg) was associated with significantly better PFS (P=0.027) and OS (P=0.018) in the TBI patients but not in patients who did not receive TBI (P>0.1 for PFS and OS).

When they analyzed patients according to conditioning regimen, the researchers found the association retained significance among patients who received RIC (P=0.01 for PFS and P=0.007 for OS) but not among patients who received myeloablative conditioning (P>0.1 for PFS and OS).

Burns and his colleagues also conducted a multivariate analysis to see if any other factors affected the relationship between TNC and survival. They controlled for patient age, Karnofsky performance status, and body mass index. And they stratified patients into 4 groups according to TBI and conditioning regimen.

The results showed that patients who received TBI and RIC, as well as a TNC dose less than 8 x 10⁸ cells/kg, had a relative risk of 3.3 for PFS (P=0.026) and a relative risk of 3.4 for OS (P=0.021).

“The association of higher TNC dose with better progression-free and overall survival implies there is a population of nucleated cells which mitigate GVHD but enhance the [graft-vs-leukemia] effect after reduced-intensity TBI conditioning,” Burns said.

“Myeloablative conditioning regimens result in more direct tumor killing. Thus, they rely less on the graft-vs-leukemia effect than the RIC regimens.”

He also noted that the lack of an association between TNC dose and survival rates with non-TBI-based regimens implies there are different mechanisms of tumor kill with TBI and non-TBI-containing regimens.

And a more detailed analysis of cell population subsets in apheresis product may allow researchers to identify cell populations that could improve patient outcomes.

*Some data in the abstract differ from data presented at the meeting.

GRAPEVINE, TEXAS—The total nucleated cell (TNC) dose delivered in an allogeneic peripheral blood stem cell transplant (allo-PBSCT) can affect outcomes in certain patients, according to a study presented at the 2014 BMT Tandem Meetings.

Researchers found that a higher TNC dose was associated with better progression-free survival (PFS) and overall survival (OS) among patients who received allo-PBSCT with reduced-intensity conditioning (RIC) and total-body irradiation (TBI).

On the other hand, the dose of CD3+, CD4+, CD8+, or CD34+ cells did not have a significant impact on survival rates in these patients.

And none of the cell doses studied had a significant impact in patients who did not receive TBI or in those who received TBI with myeloablative conditioning.

Michael Burns, of Roswell Park Cancer Institute in Buffalo, New York, presented these findings at the meeting as abstract 12.*

Burns noted that studies have produced conflicting results regarding the correlation between patient outcomes and the dose of CD34+, CD3+, CD4+, or CD8+ cells given in allo-PBSCT. In addition, TNC dose has not been analyzed much in the context of PBSCTs.

Therefore, he and his colleagues retrospectively analyzed graft cell composition in 254 patients who received their first allo-PBSCT from January 2001 to September 2012.

Fifty-eight percent of the patients were male, and the median age was 50 (range, 19-73 years). Forty-four percent of patients had acute myeloid leukemia, 18% had myelodysplastic syndromes or myeloproliferative neoplasms, 13% had acute lymphoblastic leukemia, 13% had non-Hodgkin lymphoma, and 12% had other diseases.

Of the 254 patients studied, 93 had received TBI. Among these, 53 received myeloablative conditioning (91% cyclophosphamide, 120 cGy), and 40 received RIC (100% fludarabine and melphalan, 400 cGy).

Of the 161 patients who did not receive TBI, 41 received myeloablative conditioning (88% busulfan and cyclophosphamide), and 120 received RIC (87% fludarabine and melphalan).

Patients received T-cell-replete, G-CSF mobilized, PB allografts. Fifty-six percent had a 6/6 HLA matched related donor, and 44% had an 8/8 HLA matched unrelated donor. Forty-nine percent of patients were in complete remission at the time of transplant.

The researchers analyzed cell doses according to the median dose (above vs below). But they also analyzed CD34+ dose as < 4 x 10⁶ cells/kg vs ≥ 4 x 10⁶ cells/kg and as < 4 x 10⁶ cells/kg vs 4 to 8 x 10⁶ cells/kg vs > 8 x 10⁶ cells/kg. They analyzed TNC as < 8 x 10⁸ cells/kg vs ≥ to 8 x 10⁸ cells/kg.

The team found that a CD34+ cell dose greater than 4 x 10⁶ cells/kg was significantly associated with time to platelet engraftment in all patients. It was also associated with time to neutrophil engraftment in the TBI group, but this was predominantly among patients who received RIC.

On the other hand, CD3+, CD4+, CD8+, and TNC doses were not significantly associated with platelet or neutrophil engraftment in any patients.

CD34+, CD3+, CD4+, and CD8+ cell dose were not associated with OS, PFS, or acute graft-vs-host disease (GVHD). And TNC had no significant effect on acute GVHD.

“However, we did find that the TNC dose did show some pretty interesting survival outcomes,” Burns said.

A higher TNC dose (≥ 8 x10⁸ cells/kg) was associated with significantly better PFS (P=0.027) and OS (P=0.018) in the TBI patients but not in patients who did not receive TBI (P>0.1 for PFS and OS).

When they analyzed patients according to conditioning regimen, the researchers found the association retained significance among patients who received RIC (P=0.01 for PFS and P=0.007 for OS) but not among patients who received myeloablative conditioning (P>0.1 for PFS and OS).

Burns and his colleagues also conducted a multivariate analysis to see if any other factors affected the relationship between TNC and survival. They controlled for patient age, Karnofsky performance status, and body mass index. And they stratified patients into 4 groups according to TBI and conditioning regimen.

The results showed that patients who received TBI and RIC, as well as a TNC dose less than 8 x 10⁸ cells/kg, had a relative risk of 3.3 for PFS (P=0.026) and a relative risk of 3.4 for OS (P=0.021).

“The association of higher TNC dose with better progression-free and overall survival implies there is a population of nucleated cells which mitigate GVHD but enhance the [graft-vs-leukemia] effect after reduced-intensity TBI conditioning,” Burns said.

“Myeloablative conditioning regimens result in more direct tumor killing. Thus, they rely less on the graft-vs-leukemia effect than the RIC regimens.”

He also noted that the lack of an association between TNC dose and survival rates with non-TBI-based regimens implies there are different mechanisms of tumor kill with TBI and non-TBI-containing regimens.

And a more detailed analysis of cell population subsets in apheresis product may allow researchers to identify cell populations that could improve patient outcomes.

*Some data in the abstract differ from data presented at the meeting.

Red blood cells

Investigators have identified a novel strategy for treating paroxysmal nocturnal hemoglobinuria (PNH), according to a paper published in Blood.

In patients with PNH, defective expression of regulatory proteins on the surface of red blood cells leaves the cells vulnerable to attack by the complement immune system.

This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.

Eculizumab is the only approved therapeutic for PNH. The drug reduces hemolysis and can provide patients with relief from blood transfusions.

However, eculizumab is costly (currently more than $400,000 per year per patient), and one third of PNH patients who receive eculizumab continue to require blood transfusions to manage their anemia.

Investigators previously discovered that this non-response is due to fragments of complement C3 proteins on the surface of red blood cells, which are eventually attacked by immune cells.

Therefore, John Lambris, PhD, of the University of Pennsylvania, and his colleagues hypothesized that using small molecules to inhibit the complement cascade at the level of C3 proteins might be an effective strategy for treating PNH.

The team thought this method would prevent both hemolysis and immune cell recognition, and it might be more cost-effective than the current antibody-based treatment.

So they investigated the effect of a C3 inhibitor called Cp40 and its long-acting form, PEG-Cp40, on self-attack and resulting hemolysis using human PNH cells. Both compounds effectively inhibited hemolysis and efficiently prevented deposition of C3 fragments on PNH red blood cells.

In non-human primates, a single injection of PEG-Cp40 had an elimination half-life of more than 5 days. However, the investigators found evidence to suggest the drug may affect plasma levels of C3.

“We think these 2 compounds are excellent and potentially cost-effective candidates for further clinical investigation,” Dr Lambris said.

He hopes the compounds will be tested in clinical trials by 2015. Dr Lambris and his colleague, Daniel Ricklin, PhD, are the inventors of patents and patent applications owned by the University of Pennsylvania that describe the use of complement inhibitors for therapeutic purposes.

And Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals, which has exclusively licensed the Cp40 and PEG-Cp40 technologies from the university and is developing complement inhibitors for clinical applications.

Red blood cells

Investigators have identified a novel strategy for treating paroxysmal nocturnal hemoglobinuria (PNH), according to a paper published in Blood.

In patients with PNH, defective expression of regulatory proteins on the surface of red blood cells leaves the cells vulnerable to attack by the complement immune system.

This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.

Eculizumab is the only approved therapeutic for PNH. The drug reduces hemolysis and can provide patients with relief from blood transfusions.

However, eculizumab is costly (currently more than $400,000 per year per patient), and one third of PNH patients who receive eculizumab continue to require blood transfusions to manage their anemia.

Investigators previously discovered that this non-response is due to fragments of complement C3 proteins on the surface of red blood cells, which are eventually attacked by immune cells.

Therefore, John Lambris, PhD, of the University of Pennsylvania, and his colleagues hypothesized that using small molecules to inhibit the complement cascade at the level of C3 proteins might be an effective strategy for treating PNH.

The team thought this method would prevent both hemolysis and immune cell recognition, and it might be more cost-effective than the current antibody-based treatment.

So they investigated the effect of a C3 inhibitor called Cp40 and its long-acting form, PEG-Cp40, on self-attack and resulting hemolysis using human PNH cells. Both compounds effectively inhibited hemolysis and efficiently prevented deposition of C3 fragments on PNH red blood cells.

In non-human primates, a single injection of PEG-Cp40 had an elimination half-life of more than 5 days. However, the investigators found evidence to suggest the drug may affect plasma levels of C3.

“We think these 2 compounds are excellent and potentially cost-effective candidates for further clinical investigation,” Dr Lambris said.

He hopes the compounds will be tested in clinical trials by 2015. Dr Lambris and his colleague, Daniel Ricklin, PhD, are the inventors of patents and patent applications owned by the University of Pennsylvania that describe the use of complement inhibitors for therapeutic purposes.

And Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals, which has exclusively licensed the Cp40 and PEG-Cp40 technologies from the university and is developing complement inhibitors for clinical applications.

Red blood cells

Investigators have identified a novel strategy for treating paroxysmal nocturnal hemoglobinuria (PNH), according to a paper published in Blood.

In patients with PNH, defective expression of regulatory proteins on the surface of red blood cells leaves the cells vulnerable to attack by the complement immune system.

This can lead to hemolysis, which results in severe anemia and contributes to a high risk of thrombosis.

Eculizumab is the only approved therapeutic for PNH. The drug reduces hemolysis and can provide patients with relief from blood transfusions.

However, eculizumab is costly (currently more than $400,000 per year per patient), and one third of PNH patients who receive eculizumab continue to require blood transfusions to manage their anemia.

Investigators previously discovered that this non-response is due to fragments of complement C3 proteins on the surface of red blood cells, which are eventually attacked by immune cells.

Therefore, John Lambris, PhD, of the University of Pennsylvania, and his colleagues hypothesized that using small molecules to inhibit the complement cascade at the level of C3 proteins might be an effective strategy for treating PNH.

The team thought this method would prevent both hemolysis and immune cell recognition, and it might be more cost-effective than the current antibody-based treatment.

So they investigated the effect of a C3 inhibitor called Cp40 and its long-acting form, PEG-Cp40, on self-attack and resulting hemolysis using human PNH cells. Both compounds effectively inhibited hemolysis and efficiently prevented deposition of C3 fragments on PNH red blood cells.

In non-human primates, a single injection of PEG-Cp40 had an elimination half-life of more than 5 days. However, the investigators found evidence to suggest the drug may affect plasma levels of C3.

“We think these 2 compounds are excellent and potentially cost-effective candidates for further clinical investigation,” Dr Lambris said.

He hopes the compounds will be tested in clinical trials by 2015. Dr Lambris and his colleague, Daniel Ricklin, PhD, are the inventors of patents and patent applications owned by the University of Pennsylvania that describe the use of complement inhibitors for therapeutic purposes.

And Dr Lambris is a founder and equity holder of Amyndas Pharmaceuticals, which has exclusively licensed the Cp40 and PEG-Cp40 technologies from the university and is developing complement inhibitors for clinical applications.

Dr. Morse

Global health hospitalists are passionate about their work. The Hospitalist asked them to expand on the reasons they choose this work.

“Working in Haiti has been the most compelling work in my life,” says Michelle Morse, MD, MPH, an instructor in medicine at Harvard Medical School and deputy chief medical officer for Partners in Health (PIH) in Boston. She has worked with the Navajo Nation in conjunction with PIH’s Community Outreach and Patient Empowerment (COPE) program. The sharing of information is “bi-directional,” Dr. Morse says.

Dr. Morse

Her Haitian colleagues, she says, have developed “transformative” systems improvements, and she’s found that her own diagnostic and physical exam skills have strengthened because of her work abroad.

“You really have to think bigger than your group of patients and bigger than your community, and think about the whole system to make things better around the world,” she says. “I think that is a fundamental part of becoming a physician.”

UCSF clinical fellow Varun Verma, MD, says he was tired of working in “fragmented volunteer assignments” with relief organizations. Three-month clinical rotations, in which he essentially functions as a teaching attending, have solved the “filling in” feeling he’d grown weary of.

“Here at St. Thérèse Hospital [in Hinche, Haiti], they do not need us to take care of patients on a moment-to-moment basis. There are Haitian clinicians for that,” he says. “Part of our job is to do medical teaching of residents and try to involve everyone in quality improvement projects. It’s sometimes challenging discussing best practices of managing conditions, given the resources at hand, but I find that the Haitian doctors are always interested in learning how we do things in the U.S.”

Evan Lyon, MD, assistant professor of medicine in the section of hospital medicine, supervises clinical fellows in the department of medicine at the University of Chicago. He believes hospitalists who take on global health assignments gain a deeper appreciation for assessing patients’ social histories.

“There’s no better way to deepen your learning of physical exam and history-taking skills than to be out here on the edge and have to rely on those skills,” he says. “Back in the states, you might order an echocardiogram before you listen to the patient’s heart. I think all of us have a different relationship to labs, testing, and X-rays when we return. But the deepest influence for me has been around understanding patients’ social histories and their social context, which is a neglected piece of American medicine.”

Dr. Shoeb

Sharing resources and knowledge is what drives Marwa Shoeb MD, MS, assistant professor in the division of hospital medicine at UCSF. “I see this as an extension of our daily work,” she says. “We are just taking it to a different context.”

Gretchen Henkel is a freelance writer in southern California.

Dr. Morse

Global health hospitalists are passionate about their work. The Hospitalist asked them to expand on the reasons they choose this work.

“Working in Haiti has been the most compelling work in my life,” says Michelle Morse, MD, MPH, an instructor in medicine at Harvard Medical School and deputy chief medical officer for Partners in Health (PIH) in Boston. She has worked with the Navajo Nation in conjunction with PIH’s Community Outreach and Patient Empowerment (COPE) program. The sharing of information is “bi-directional,” Dr. Morse says.

Dr. Morse

Her Haitian colleagues, she says, have developed “transformative” systems improvements, and she’s found that her own diagnostic and physical exam skills have strengthened because of her work abroad.

“You really have to think bigger than your group of patients and bigger than your community, and think about the whole system to make things better around the world,” she says. “I think that is a fundamental part of becoming a physician.”

UCSF clinical fellow Varun Verma, MD, says he was tired of working in “fragmented volunteer assignments” with relief organizations. Three-month clinical rotations, in which he essentially functions as a teaching attending, have solved the “filling in” feeling he’d grown weary of.

“Here at St. Thérèse Hospital [in Hinche, Haiti], they do not need us to take care of patients on a moment-to-moment basis. There are Haitian clinicians for that,” he says. “Part of our job is to do medical teaching of residents and try to involve everyone in quality improvement projects. It’s sometimes challenging discussing best practices of managing conditions, given the resources at hand, but I find that the Haitian doctors are always interested in learning how we do things in the U.S.”

Evan Lyon, MD, assistant professor of medicine in the section of hospital medicine, supervises clinical fellows in the department of medicine at the University of Chicago. He believes hospitalists who take on global health assignments gain a deeper appreciation for assessing patients’ social histories.

“There’s no better way to deepen your learning of physical exam and history-taking skills than to be out here on the edge and have to rely on those skills,” he says. “Back in the states, you might order an echocardiogram before you listen to the patient’s heart. I think all of us have a different relationship to labs, testing, and X-rays when we return. But the deepest influence for me has been around understanding patients’ social histories and their social context, which is a neglected piece of American medicine.”

Dr. Shoeb

Sharing resources and knowledge is what drives Marwa Shoeb MD, MS, assistant professor in the division of hospital medicine at UCSF. “I see this as an extension of our daily work,” she says. “We are just taking it to a different context.”

Gretchen Henkel is a freelance writer in southern California.

Dr. Morse

Global health hospitalists are passionate about their work. The Hospitalist asked them to expand on the reasons they choose this work.

“Working in Haiti has been the most compelling work in my life,” says Michelle Morse, MD, MPH, an instructor in medicine at Harvard Medical School and deputy chief medical officer for Partners in Health (PIH) in Boston. She has worked with the Navajo Nation in conjunction with PIH’s Community Outreach and Patient Empowerment (COPE) program. The sharing of information is “bi-directional,” Dr. Morse says.

Dr. Morse

Her Haitian colleagues, she says, have developed “transformative” systems improvements, and she’s found that her own diagnostic and physical exam skills have strengthened because of her work abroad.

“You really have to think bigger than your group of patients and bigger than your community, and think about the whole system to make things better around the world,” she says. “I think that is a fundamental part of becoming a physician.”

UCSF clinical fellow Varun Verma, MD, says he was tired of working in “fragmented volunteer assignments” with relief organizations. Three-month clinical rotations, in which he essentially functions as a teaching attending, have solved the “filling in” feeling he’d grown weary of.

“Here at St. Thérèse Hospital [in Hinche, Haiti], they do not need us to take care of patients on a moment-to-moment basis. There are Haitian clinicians for that,” he says. “Part of our job is to do medical teaching of residents and try to involve everyone in quality improvement projects. It’s sometimes challenging discussing best practices of managing conditions, given the resources at hand, but I find that the Haitian doctors are always interested in learning how we do things in the U.S.”

Evan Lyon, MD, assistant professor of medicine in the section of hospital medicine, supervises clinical fellows in the department of medicine at the University of Chicago. He believes hospitalists who take on global health assignments gain a deeper appreciation for assessing patients’ social histories.

“There’s no better way to deepen your learning of physical exam and history-taking skills than to be out here on the edge and have to rely on those skills,” he says. “Back in the states, you might order an echocardiogram before you listen to the patient’s heart. I think all of us have a different relationship to labs, testing, and X-rays when we return. But the deepest influence for me has been around understanding patients’ social histories and their social context, which is a neglected piece of American medicine.”

Dr. Shoeb

Sharing resources and knowledge is what drives Marwa Shoeb MD, MS, assistant professor in the division of hospital medicine at UCSF. “I see this as an extension of our daily work,” she says. “We are just taking it to a different context.”

Gretchen Henkel is a freelance writer in southern California.