Take-Home Points

• Physician fees, operating room costs, therapy costs, and missed work account for most (92%) of the costs in distal radius fractures.
• Indirect costs (especially missed work) contribute a significant amount to the total cost of injury.
• Patients continue to accrue costs up to 3-6 months post-injury.
• Implant costs make up only 6% of the total costs of operatively treated distal radius fractures.

Distal radius fractures (DRFs) account for 20% of all fractures seen in the emergency department, and are the most common fractures in all patients under age 75 years.^1,2 Apart from causing pain and disability, DRFs have a large associated economic burden.^3-6 In addition, over the past decade, the fixation technology used for DRF treatment has expanded rapidly and revolutionized operative management. With this expansion has come a growing body of high-level evidence guiding treatment decisions regarding patient outcomes.^7-11 As operative treatment of these injuries has evolved, researchers have begun to critically evaluate both health outcomes and the cost-effectiveness of treatment choices.^12,13

Determining the cost-effectiveness of any medical intervention requires an accurate and standardized method for measuring the total cost of a course of treatment. Although several studies have attempted to evaluate the treatment costs of DRFs,^14-18 none has rigorously examined exactly what needs to be measured, and for how long, to accurately describe the overall cost. Many studies have examined only direct costs (treatment-related costs incurred in the hospital or clinic itself) and neglected indirect costs (eg, missed work, time in treatment, additional care requirements). As patient-reported disability from these injuries can be high,^19-22 it is likely that the additional indirect costs, often borne by the patient, are correspondingly high. This relationship has been suggested by indirect data from large retrospective epidemiologic studies^3-6 but has never been evaluated with primary data obtained in a prospective study.

Given these questions, we conducted an in-depth study of the treatment costs of these injuries to identify which factors should be captured, and for how long, to accurately describe the overall cost without missing any of the major cost-drivers. We hypothesized that indirect costs (particularly missed work) would be significant and variable cost-drivers in the overall economic impact of these injuries, and that direct prospective measurement of these costs would be the most reliable method for accurately assessing them. In short, this was a prospective, observational study of all the direct and indirect costs associated with treating DRFs. Its 2 main goals were to determine how much of the overall cost was attributable to indirect costs, and which cost factors should be measured, and for how long, to capture the true economic cost of these injuries.

Patients and Methods

Study Design

This prospective, observational study was approved by our hospital’s Institutional Review Board, and patients gave informed consent to participate. Patients with an isolated DRF that was treated either operatively or nonoperatively and followed at our hospital were eligible for the study. Treatment decisions for each patient were made by the treating surgeon and were based on injury characteristics. Patients with multiple concomitant injuries (polytrauma) were excluded. The AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) classification system was used to grade all fractures.²³

Patients were seen 2 weeks, 1 month, 3 months, 6 months, and 1 year after injury. Each time, clinical data (strength, range of motion, patient-rated outcome forms) and economic data were collected. A patient’s economic data were considered complete if the patient had full follow-up in our clinic up to 1 year after injury or, if applicable, the patient returned to work and had all recurring direct and indirect costs resolved. Costs were measured and calculated from the broadest possible perspective (overall societal costs) rather than from payer-specific perspectives (eg, institution costs, insurance costs).

Treatment and Rehabilitation Protocol

Each patient who underwent nonoperative treatment was placed in a molded sugar-tong splint with hand motion encouraged and followed in clinic. At 4 to 6 weeks, the splint was removed, and the patient was placed in a removable cock-up wrist splint for another 2 to 4 weeks. Throughout this period, the patient worked on elbow and finger motion with an occupational therapist (OT). On discontinuation of the wrist splint, the patient returned to the OT for gentle wrist motion and continuation of elbow and finger motion.

For each patient who underwent operative treatment, implant and approach were based on fracture pattern. Implants used included isolated Kirschner wires (K-wires), volar locked plates, dorsal plates, radial column plates, and ulnar plates. After fixation, the patient was placed in a well-padded volar splint and encouraged to start immediate finger motion. Ten to 14 days after surgery, the splint was removed, and the patient was referred to an OT for gentle wrist, finger, and elbow motion. Therapy was continued until wrist, finger, and elbow motion was full.

Direct Costs

Direct costs were obtained from hospital billing and collections records. Cost items measured included physician fees, imaging fees, inpatient bed fees (when applicable), operating room (OR) facility fees, implant costs, and OT costs. Whenever possible, the final amount collected (vs charged) was used for the cost, as this was thought to be the most reliable indicator of the real cost of an item. Total cost was obtained from ultimate collection/reimbursement for all physician, imaging, and OT fees.

In a few cases, ultimate amount collected was not in our system and instead was calculated by normalizing the charges based on internal departmental cost-to-charge ratios. Cost-to-charge ratios were used for OR/emergency department facility fees, inpatient bed fees, and implant costs.

Indirect Costs

Indirect costs were calculated from questionnaires completed by patients at initial enrollment and at each follow-up visit. The initial enrollment form captured basic demographic information, employment status and work type, and annual income. The follow-up form included questions about current work status, physical/occupational therapy frequency, and extra recurring expenses related to transportation, household chores, and personal care, among other items. Total recurring expenses from transportation, chores, and personal care were calculated by multiplying the weekly expenses listed at a given visit by the time since the previous visit.

Costs for missed work were estimated as a function of preinjury wages multiplied by decreased level of productivity and period of work missed. For a patient who indicated part-time work status, decreased level of productivity was calculated by dividing the patient’s weekly hours by 40 (assumes 40-hour week is full-time), which yielded a percentage of full-time capacity. The patient was also asked to indicate any change in work status, which allowed for an accurate accounting of how long the patient was away from work and how much the patient’s capacity was decreased, ultimately providing an estimate of total amount of work missed. Multiplying that period by annual preinjury wages gave the value used for total cost of missed work.

Results

Of the 82 patients enrolled in the study, 36 were treated operatively and 46 nonoperatively. Table 1 lists additional demographic information about the study population.

Table 2 provides a full breakdown of costs. OT costs were similar between groups but proportionally made up 27% of the costs for the nonoperative group and 4.9% for the operative group.

Discussion

The drive to use evidence-based treatments in medicine has led to increased scrutiny of the benefits of novel treatments and technologies. However, in addition to carefully measuring clinical benefits, we must monitor costs. Implementation of new treatments based on small clinical advantages, without consideration of economic impact, will not be sustainable over the long term.

This study was not intended to report the “true” cost of treating these injuries, or to make direct comparisons between operative and nonoperative groups (regional and institutional costs and practices vary so much that no single-site study can report a meaningful number for cost). Furthermore, the observational (nonrandomized) nature of this study makes direct comparison of operative and nonoperative groups too confounded to draw conclusions. Simply, this study was conducted to help determine what needs to be measured, with the ultimate goal being to obtain a relatively reliable estimate of the total cost to society of a given injury and its treatment.

In this study, physician fees and facility fees were major direct expenses—not surprising given the value of physician time and OR time. In addition, OT was a fairly large direct-cost driver, particularly for nonoperative patients, for whom other costs were relatively low. This finding supports what has been reported in studies of the frequency and duration of therapy as potential targets for cost containment.²⁴ Surprisingly, OT costs were lower for operatively (vs nonoperatively) treated patients. This finding may be attributable to earlier wrist motion in operatively treated patients (10-14 days) relative to nonoperatively treated patients (6-8 weeks), as earlier wrist motion may reduce stiffness and total need for therapy. Alternatively, the finding may be attributable to sampling error caused by difficulty in obtaining accurate OT costs, as some patients received therapy at multiple private offices, with records unavailable.

Although significant attention is often focused on implant costs, these actually comprised a relatively small portion (6%) of the total treatment costs for these injuries. However, implant costs vary significantly between institutions.

Indirect costs were a major factor, accounting for about one-third of total cost. Missed work was the single largest cost item in this study, comprising 93% of the indirect cost and 27% of the total cost. These findings suggest that the cost of missed work is crucial and should be measured in any study that compares the cost-effectiveness of different treatment modalities.

In orthopedic trauma, earlier return to work is often cited as a potential benefit of surgical intervention. However, without defining the exact economic impact of missed work, it is difficult to decide if earlier return to work justifies the added cost of surgery. The situation is further muddled by conflicting priorities, as the entities that bear the cost of missed work (patient, disability insurance) are often different from the entity that bears the cost of surgery (medical insurance). In the light of this complex decision-making with multiple and sometimes conflicting stakeholders, accurate understanding of the economic impact of missed work is paramount. Our data showed return to work took slightly longer for operatively (vs nonoperatively) treated patients, though we think this is more likely a result of higher injury severity than treatment choice.

Patients in both groups were still not back working up to 6 months after injury, indicating that return of function after these injuries is not as rapid as we might hope or expect, and may play a role in setting expectations during initial discussions with patients.

The major strength of this study is that it was the first of its kind to prospectively measure these costs at a single institution in order to make direct comparisons of different cost factors. Whenever possible, rather than relying on cost-to-charge ratio estimates, we analyzed costs obtained directly from collections reports, which improved the validity of the results generated. Missed work was captured by directly asking patients about work capacity, not by retrospectively reviewing disability applications, which for a variety of reasons often inaccurately reflects true work productivity. In addition, our final follow-up rate was relatively high (91%), which helped minimize bias. Although this study focused on DRFs, the hope is that these data can serve as a template for the kinds of factors that need to be measured to accurately describe the cost of many different upper extremity injuries. This idea, however, needs to be formally tested.

This study had several limitations. First, some costs (OR time, facility fees) still had to be estimated with cost-to-charge ratios—a less precise method. Second, measuring the societal cost of missed work is controversial. We calculated this cost by using standard economic techniques, valuing the decreased productivity period according to baseline salary, though the true “loss” to society is less clear. Third, our data represent the costs at one hospital in one city and might be very different at other institutions with different cost structures. Fourth, this study was observational (vs randomized) and subject to the usual bias of such studies, so conclusions between treatment choices and cost or clinical outcomes could not be drawn (which was not our intent in this study). Although these issues limited our ability to calculate the exact “cost” of these injuries, the relative impact of the different cost factors could be measured (which was our intent).

DRFs are common injuries that can have significant associated expenses, many of which were not captured in previous cost analyses. In the present study, we found that measuring physician, OR, therapy, and missed work costs for at least 6 months after injury was generally sufficient for accurate capture of major costs. We hope these data can help in planning studies of the treatment costs of upper extremity injuries. Only through accurate and conscientious data gathering can we evaluate the clinical and economic effects of novel technologies and ensure delivery of high-quality care while containing costs and improving efficiency.

Am J Orthop. 2017;46(1):E54-E59. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Physician fees, operating room costs, therapy costs, and missed work account for most (92%) of the costs in distal radius fractures.
• Indirect costs (especially missed work) contribute a significant amount to the total cost of injury.
• Patients continue to accrue costs up to 3-6 months post-injury.
• Implant costs make up only 6% of the total costs of operatively treated distal radius fractures.

Distal radius fractures (DRFs) account for 20% of all fractures seen in the emergency department, and are the most common fractures in all patients under age 75 years.^1,2 Apart from causing pain and disability, DRFs have a large associated economic burden.^3-6 In addition, over the past decade, the fixation technology used for DRF treatment has expanded rapidly and revolutionized operative management. With this expansion has come a growing body of high-level evidence guiding treatment decisions regarding patient outcomes.^7-11 As operative treatment of these injuries has evolved, researchers have begun to critically evaluate both health outcomes and the cost-effectiveness of treatment choices.^12,13

Determining the cost-effectiveness of any medical intervention requires an accurate and standardized method for measuring the total cost of a course of treatment. Although several studies have attempted to evaluate the treatment costs of DRFs,^14-18 none has rigorously examined exactly what needs to be measured, and for how long, to accurately describe the overall cost. Many studies have examined only direct costs (treatment-related costs incurred in the hospital or clinic itself) and neglected indirect costs (eg, missed work, time in treatment, additional care requirements). As patient-reported disability from these injuries can be high,^19-22 it is likely that the additional indirect costs, often borne by the patient, are correspondingly high. This relationship has been suggested by indirect data from large retrospective epidemiologic studies^3-6 but has never been evaluated with primary data obtained in a prospective study.

Given these questions, we conducted an in-depth study of the treatment costs of these injuries to identify which factors should be captured, and for how long, to accurately describe the overall cost without missing any of the major cost-drivers. We hypothesized that indirect costs (particularly missed work) would be significant and variable cost-drivers in the overall economic impact of these injuries, and that direct prospective measurement of these costs would be the most reliable method for accurately assessing them. In short, this was a prospective, observational study of all the direct and indirect costs associated with treating DRFs. Its 2 main goals were to determine how much of the overall cost was attributable to indirect costs, and which cost factors should be measured, and for how long, to capture the true economic cost of these injuries.

Patients and Methods

Study Design

This prospective, observational study was approved by our hospital’s Institutional Review Board, and patients gave informed consent to participate. Patients with an isolated DRF that was treated either operatively or nonoperatively and followed at our hospital were eligible for the study. Treatment decisions for each patient were made by the treating surgeon and were based on injury characteristics. Patients with multiple concomitant injuries (polytrauma) were excluded. The AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) classification system was used to grade all fractures.²³

Patients were seen 2 weeks, 1 month, 3 months, 6 months, and 1 year after injury. Each time, clinical data (strength, range of motion, patient-rated outcome forms) and economic data were collected. A patient’s economic data were considered complete if the patient had full follow-up in our clinic up to 1 year after injury or, if applicable, the patient returned to work and had all recurring direct and indirect costs resolved. Costs were measured and calculated from the broadest possible perspective (overall societal costs) rather than from payer-specific perspectives (eg, institution costs, insurance costs).

Treatment and Rehabilitation Protocol

Each patient who underwent nonoperative treatment was placed in a molded sugar-tong splint with hand motion encouraged and followed in clinic. At 4 to 6 weeks, the splint was removed, and the patient was placed in a removable cock-up wrist splint for another 2 to 4 weeks. Throughout this period, the patient worked on elbow and finger motion with an occupational therapist (OT). On discontinuation of the wrist splint, the patient returned to the OT for gentle wrist motion and continuation of elbow and finger motion.

For each patient who underwent operative treatment, implant and approach were based on fracture pattern. Implants used included isolated Kirschner wires (K-wires), volar locked plates, dorsal plates, radial column plates, and ulnar plates. After fixation, the patient was placed in a well-padded volar splint and encouraged to start immediate finger motion. Ten to 14 days after surgery, the splint was removed, and the patient was referred to an OT for gentle wrist, finger, and elbow motion. Therapy was continued until wrist, finger, and elbow motion was full.

Direct Costs

Direct costs were obtained from hospital billing and collections records. Cost items measured included physician fees, imaging fees, inpatient bed fees (when applicable), operating room (OR) facility fees, implant costs, and OT costs. Whenever possible, the final amount collected (vs charged) was used for the cost, as this was thought to be the most reliable indicator of the real cost of an item. Total cost was obtained from ultimate collection/reimbursement for all physician, imaging, and OT fees.

In a few cases, ultimate amount collected was not in our system and instead was calculated by normalizing the charges based on internal departmental cost-to-charge ratios. Cost-to-charge ratios were used for OR/emergency department facility fees, inpatient bed fees, and implant costs.

Indirect Costs

Indirect costs were calculated from questionnaires completed by patients at initial enrollment and at each follow-up visit. The initial enrollment form captured basic demographic information, employment status and work type, and annual income. The follow-up form included questions about current work status, physical/occupational therapy frequency, and extra recurring expenses related to transportation, household chores, and personal care, among other items. Total recurring expenses from transportation, chores, and personal care were calculated by multiplying the weekly expenses listed at a given visit by the time since the previous visit.

Costs for missed work were estimated as a function of preinjury wages multiplied by decreased level of productivity and period of work missed. For a patient who indicated part-time work status, decreased level of productivity was calculated by dividing the patient’s weekly hours by 40 (assumes 40-hour week is full-time), which yielded a percentage of full-time capacity. The patient was also asked to indicate any change in work status, which allowed for an accurate accounting of how long the patient was away from work and how much the patient’s capacity was decreased, ultimately providing an estimate of total amount of work missed. Multiplying that period by annual preinjury wages gave the value used for total cost of missed work.

Results

Of the 82 patients enrolled in the study, 36 were treated operatively and 46 nonoperatively. Table 1 lists additional demographic information about the study population.

Table 2 provides a full breakdown of costs. OT costs were similar between groups but proportionally made up 27% of the costs for the nonoperative group and 4.9% for the operative group.

Discussion

The drive to use evidence-based treatments in medicine has led to increased scrutiny of the benefits of novel treatments and technologies. However, in addition to carefully measuring clinical benefits, we must monitor costs. Implementation of new treatments based on small clinical advantages, without consideration of economic impact, will not be sustainable over the long term.

This study was not intended to report the “true” cost of treating these injuries, or to make direct comparisons between operative and nonoperative groups (regional and institutional costs and practices vary so much that no single-site study can report a meaningful number for cost). Furthermore, the observational (nonrandomized) nature of this study makes direct comparison of operative and nonoperative groups too confounded to draw conclusions. Simply, this study was conducted to help determine what needs to be measured, with the ultimate goal being to obtain a relatively reliable estimate of the total cost to society of a given injury and its treatment.

In this study, physician fees and facility fees were major direct expenses—not surprising given the value of physician time and OR time. In addition, OT was a fairly large direct-cost driver, particularly for nonoperative patients, for whom other costs were relatively low. This finding supports what has been reported in studies of the frequency and duration of therapy as potential targets for cost containment.²⁴ Surprisingly, OT costs were lower for operatively (vs nonoperatively) treated patients. This finding may be attributable to earlier wrist motion in operatively treated patients (10-14 days) relative to nonoperatively treated patients (6-8 weeks), as earlier wrist motion may reduce stiffness and total need for therapy. Alternatively, the finding may be attributable to sampling error caused by difficulty in obtaining accurate OT costs, as some patients received therapy at multiple private offices, with records unavailable.

Although significant attention is often focused on implant costs, these actually comprised a relatively small portion (6%) of the total treatment costs for these injuries. However, implant costs vary significantly between institutions.

Indirect costs were a major factor, accounting for about one-third of total cost. Missed work was the single largest cost item in this study, comprising 93% of the indirect cost and 27% of the total cost. These findings suggest that the cost of missed work is crucial and should be measured in any study that compares the cost-effectiveness of different treatment modalities.

In orthopedic trauma, earlier return to work is often cited as a potential benefit of surgical intervention. However, without defining the exact economic impact of missed work, it is difficult to decide if earlier return to work justifies the added cost of surgery. The situation is further muddled by conflicting priorities, as the entities that bear the cost of missed work (patient, disability insurance) are often different from the entity that bears the cost of surgery (medical insurance). In the light of this complex decision-making with multiple and sometimes conflicting stakeholders, accurate understanding of the economic impact of missed work is paramount. Our data showed return to work took slightly longer for operatively (vs nonoperatively) treated patients, though we think this is more likely a result of higher injury severity than treatment choice.

Patients in both groups were still not back working up to 6 months after injury, indicating that return of function after these injuries is not as rapid as we might hope or expect, and may play a role in setting expectations during initial discussions with patients.

The major strength of this study is that it was the first of its kind to prospectively measure these costs at a single institution in order to make direct comparisons of different cost factors. Whenever possible, rather than relying on cost-to-charge ratio estimates, we analyzed costs obtained directly from collections reports, which improved the validity of the results generated. Missed work was captured by directly asking patients about work capacity, not by retrospectively reviewing disability applications, which for a variety of reasons often inaccurately reflects true work productivity. In addition, our final follow-up rate was relatively high (91%), which helped minimize bias. Although this study focused on DRFs, the hope is that these data can serve as a template for the kinds of factors that need to be measured to accurately describe the cost of many different upper extremity injuries. This idea, however, needs to be formally tested.

This study had several limitations. First, some costs (OR time, facility fees) still had to be estimated with cost-to-charge ratios—a less precise method. Second, measuring the societal cost of missed work is controversial. We calculated this cost by using standard economic techniques, valuing the decreased productivity period according to baseline salary, though the true “loss” to society is less clear. Third, our data represent the costs at one hospital in one city and might be very different at other institutions with different cost structures. Fourth, this study was observational (vs randomized) and subject to the usual bias of such studies, so conclusions between treatment choices and cost or clinical outcomes could not be drawn (which was not our intent in this study). Although these issues limited our ability to calculate the exact “cost” of these injuries, the relative impact of the different cost factors could be measured (which was our intent).

DRFs are common injuries that can have significant associated expenses, many of which were not captured in previous cost analyses. In the present study, we found that measuring physician, OR, therapy, and missed work costs for at least 6 months after injury was generally sufficient for accurate capture of major costs. We hope these data can help in planning studies of the treatment costs of upper extremity injuries. Only through accurate and conscientious data gathering can we evaluate the clinical and economic effects of novel technologies and ensure delivery of high-quality care while containing costs and improving efficiency.

Am J Orthop. 2017;46(1):E54-E59. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Physician fees, operating room costs, therapy costs, and missed work account for most (92%) of the costs in distal radius fractures.
• Indirect costs (especially missed work) contribute a significant amount to the total cost of injury.
• Patients continue to accrue costs up to 3-6 months post-injury.
• Implant costs make up only 6% of the total costs of operatively treated distal radius fractures.

Distal radius fractures (DRFs) account for 20% of all fractures seen in the emergency department, and are the most common fractures in all patients under age 75 years.^1,2 Apart from causing pain and disability, DRFs have a large associated economic burden.^3-6 In addition, over the past decade, the fixation technology used for DRF treatment has expanded rapidly and revolutionized operative management. With this expansion has come a growing body of high-level evidence guiding treatment decisions regarding patient outcomes.^7-11 As operative treatment of these injuries has evolved, researchers have begun to critically evaluate both health outcomes and the cost-effectiveness of treatment choices.^12,13

Determining the cost-effectiveness of any medical intervention requires an accurate and standardized method for measuring the total cost of a course of treatment. Although several studies have attempted to evaluate the treatment costs of DRFs,^14-18 none has rigorously examined exactly what needs to be measured, and for how long, to accurately describe the overall cost. Many studies have examined only direct costs (treatment-related costs incurred in the hospital or clinic itself) and neglected indirect costs (eg, missed work, time in treatment, additional care requirements). As patient-reported disability from these injuries can be high,^19-22 it is likely that the additional indirect costs, often borne by the patient, are correspondingly high. This relationship has been suggested by indirect data from large retrospective epidemiologic studies^3-6 but has never been evaluated with primary data obtained in a prospective study.

Given these questions, we conducted an in-depth study of the treatment costs of these injuries to identify which factors should be captured, and for how long, to accurately describe the overall cost without missing any of the major cost-drivers. We hypothesized that indirect costs (particularly missed work) would be significant and variable cost-drivers in the overall economic impact of these injuries, and that direct prospective measurement of these costs would be the most reliable method for accurately assessing them. In short, this was a prospective, observational study of all the direct and indirect costs associated with treating DRFs. Its 2 main goals were to determine how much of the overall cost was attributable to indirect costs, and which cost factors should be measured, and for how long, to capture the true economic cost of these injuries.

Patients and Methods

Study Design

This prospective, observational study was approved by our hospital’s Institutional Review Board, and patients gave informed consent to participate. Patients with an isolated DRF that was treated either operatively or nonoperatively and followed at our hospital were eligible for the study. Treatment decisions for each patient were made by the treating surgeon and were based on injury characteristics. Patients with multiple concomitant injuries (polytrauma) were excluded. The AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) classification system was used to grade all fractures.²³

Patients were seen 2 weeks, 1 month, 3 months, 6 months, and 1 year after injury. Each time, clinical data (strength, range of motion, patient-rated outcome forms) and economic data were collected. A patient’s economic data were considered complete if the patient had full follow-up in our clinic up to 1 year after injury or, if applicable, the patient returned to work and had all recurring direct and indirect costs resolved. Costs were measured and calculated from the broadest possible perspective (overall societal costs) rather than from payer-specific perspectives (eg, institution costs, insurance costs).

Treatment and Rehabilitation Protocol

Each patient who underwent nonoperative treatment was placed in a molded sugar-tong splint with hand motion encouraged and followed in clinic. At 4 to 6 weeks, the splint was removed, and the patient was placed in a removable cock-up wrist splint for another 2 to 4 weeks. Throughout this period, the patient worked on elbow and finger motion with an occupational therapist (OT). On discontinuation of the wrist splint, the patient returned to the OT for gentle wrist motion and continuation of elbow and finger motion.

For each patient who underwent operative treatment, implant and approach were based on fracture pattern. Implants used included isolated Kirschner wires (K-wires), volar locked plates, dorsal plates, radial column plates, and ulnar plates. After fixation, the patient was placed in a well-padded volar splint and encouraged to start immediate finger motion. Ten to 14 days after surgery, the splint was removed, and the patient was referred to an OT for gentle wrist, finger, and elbow motion. Therapy was continued until wrist, finger, and elbow motion was full.

Direct Costs

Direct costs were obtained from hospital billing and collections records. Cost items measured included physician fees, imaging fees, inpatient bed fees (when applicable), operating room (OR) facility fees, implant costs, and OT costs. Whenever possible, the final amount collected (vs charged) was used for the cost, as this was thought to be the most reliable indicator of the real cost of an item. Total cost was obtained from ultimate collection/reimbursement for all physician, imaging, and OT fees.

In a few cases, ultimate amount collected was not in our system and instead was calculated by normalizing the charges based on internal departmental cost-to-charge ratios. Cost-to-charge ratios were used for OR/emergency department facility fees, inpatient bed fees, and implant costs.

Indirect Costs

Indirect costs were calculated from questionnaires completed by patients at initial enrollment and at each follow-up visit. The initial enrollment form captured basic demographic information, employment status and work type, and annual income. The follow-up form included questions about current work status, physical/occupational therapy frequency, and extra recurring expenses related to transportation, household chores, and personal care, among other items. Total recurring expenses from transportation, chores, and personal care were calculated by multiplying the weekly expenses listed at a given visit by the time since the previous visit.

Costs for missed work were estimated as a function of preinjury wages multiplied by decreased level of productivity and period of work missed. For a patient who indicated part-time work status, decreased level of productivity was calculated by dividing the patient’s weekly hours by 40 (assumes 40-hour week is full-time), which yielded a percentage of full-time capacity. The patient was also asked to indicate any change in work status, which allowed for an accurate accounting of how long the patient was away from work and how much the patient’s capacity was decreased, ultimately providing an estimate of total amount of work missed. Multiplying that period by annual preinjury wages gave the value used for total cost of missed work.

Results

Of the 82 patients enrolled in the study, 36 were treated operatively and 46 nonoperatively. Table 1 lists additional demographic information about the study population.

Table 2 provides a full breakdown of costs. OT costs were similar between groups but proportionally made up 27% of the costs for the nonoperative group and 4.9% for the operative group.

Discussion

The drive to use evidence-based treatments in medicine has led to increased scrutiny of the benefits of novel treatments and technologies. However, in addition to carefully measuring clinical benefits, we must monitor costs. Implementation of new treatments based on small clinical advantages, without consideration of economic impact, will not be sustainable over the long term.

This study was not intended to report the “true” cost of treating these injuries, or to make direct comparisons between operative and nonoperative groups (regional and institutional costs and practices vary so much that no single-site study can report a meaningful number for cost). Furthermore, the observational (nonrandomized) nature of this study makes direct comparison of operative and nonoperative groups too confounded to draw conclusions. Simply, this study was conducted to help determine what needs to be measured, with the ultimate goal being to obtain a relatively reliable estimate of the total cost to society of a given injury and its treatment.

In this study, physician fees and facility fees were major direct expenses—not surprising given the value of physician time and OR time. In addition, OT was a fairly large direct-cost driver, particularly for nonoperative patients, for whom other costs were relatively low. This finding supports what has been reported in studies of the frequency and duration of therapy as potential targets for cost containment.²⁴ Surprisingly, OT costs were lower for operatively (vs nonoperatively) treated patients. This finding may be attributable to earlier wrist motion in operatively treated patients (10-14 days) relative to nonoperatively treated patients (6-8 weeks), as earlier wrist motion may reduce stiffness and total need for therapy. Alternatively, the finding may be attributable to sampling error caused by difficulty in obtaining accurate OT costs, as some patients received therapy at multiple private offices, with records unavailable.

Although significant attention is often focused on implant costs, these actually comprised a relatively small portion (6%) of the total treatment costs for these injuries. However, implant costs vary significantly between institutions.

Indirect costs were a major factor, accounting for about one-third of total cost. Missed work was the single largest cost item in this study, comprising 93% of the indirect cost and 27% of the total cost. These findings suggest that the cost of missed work is crucial and should be measured in any study that compares the cost-effectiveness of different treatment modalities.

In orthopedic trauma, earlier return to work is often cited as a potential benefit of surgical intervention. However, without defining the exact economic impact of missed work, it is difficult to decide if earlier return to work justifies the added cost of surgery. The situation is further muddled by conflicting priorities, as the entities that bear the cost of missed work (patient, disability insurance) are often different from the entity that bears the cost of surgery (medical insurance). In the light of this complex decision-making with multiple and sometimes conflicting stakeholders, accurate understanding of the economic impact of missed work is paramount. Our data showed return to work took slightly longer for operatively (vs nonoperatively) treated patients, though we think this is more likely a result of higher injury severity than treatment choice.

Patients in both groups were still not back working up to 6 months after injury, indicating that return of function after these injuries is not as rapid as we might hope or expect, and may play a role in setting expectations during initial discussions with patients.

The major strength of this study is that it was the first of its kind to prospectively measure these costs at a single institution in order to make direct comparisons of different cost factors. Whenever possible, rather than relying on cost-to-charge ratio estimates, we analyzed costs obtained directly from collections reports, which improved the validity of the results generated. Missed work was captured by directly asking patients about work capacity, not by retrospectively reviewing disability applications, which for a variety of reasons often inaccurately reflects true work productivity. In addition, our final follow-up rate was relatively high (91%), which helped minimize bias. Although this study focused on DRFs, the hope is that these data can serve as a template for the kinds of factors that need to be measured to accurately describe the cost of many different upper extremity injuries. This idea, however, needs to be formally tested.

This study had several limitations. First, some costs (OR time, facility fees) still had to be estimated with cost-to-charge ratios—a less precise method. Second, measuring the societal cost of missed work is controversial. We calculated this cost by using standard economic techniques, valuing the decreased productivity period according to baseline salary, though the true “loss” to society is less clear. Third, our data represent the costs at one hospital in one city and might be very different at other institutions with different cost structures. Fourth, this study was observational (vs randomized) and subject to the usual bias of such studies, so conclusions between treatment choices and cost or clinical outcomes could not be drawn (which was not our intent in this study). Although these issues limited our ability to calculate the exact “cost” of these injuries, the relative impact of the different cost factors could be measured (which was our intent).

DRFs are common injuries that can have significant associated expenses, many of which were not captured in previous cost analyses. In the present study, we found that measuring physician, OR, therapy, and missed work costs for at least 6 months after injury was generally sufficient for accurate capture of major costs. We hope these data can help in planning studies of the treatment costs of upper extremity injuries. Only through accurate and conscientious data gathering can we evaluate the clinical and economic effects of novel technologies and ensure delivery of high-quality care while containing costs and improving efficiency.

Am J Orthop. 2017;46(1):E54-E59. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor selective for both EGFR and T790M mutations that render cancers resistant to EGFR-TKIs, yielded a high overall response rate, “encouraging” progression-free survival, and a durable treatment response in advanced non–small cell lung cancer (NSCLC) that had progressed despite EGFR-TKI therapy, according to a report published online Feb. 21 in the Journal of Clinical Oncology.

In a manufacturer-sponsored, open-label phase II trial, 198 patients in 10 countries took 80 mg of oral osimertinib once daily for a median duration of 13.2 months (range, 1-18 months). The overall response rate was 62%, and the median duration of response was 15.2 months. The disease control rate was 90%, said James Chih-Hsin Yang, MD, PhD, of National Taiwan Hospital, Taipei, and his associates.

The median progression-free survival was 12.3 months, and the treatment benefit was generally consistent across all subgroups of patients regardless of age, smoking status, previous therapies, and duration of treatment. Questionnaire responses showed that patients “had consistent and sustained improvements in key lung cancer symptoms including dyspnea, cough, chest pain, and pain in the arm or shoulder,” as well as in global health status and physical functioning. This is particularly noteworthy because some patients had received “many (up to 11) lines of cancer therapy before osimertinib,” the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.70.3223).

“We also report encouraging systemic progression-free survival with osimertinib in patients with CNS metastases, and a high CNS response rate (64%) in those with measurable CNS lesions,” they wrote. This finding is particularly important “because new pharmacologic strategies are needed to treat brain metastases, given the long-term complications of brain radiation,” they added.

Osimertinib was generally well tolerated, with 21% of patients having adverse effects leading to dose interruptions and 5% to dose reductions. Nine patients (3%) discontinued the agent because of adverse effects, which included interstitial lung disease (3 fatal cases), QT prolongation, a reduced neutrophil count, and severe vomiting and diarrhea.

This trial was sponsored by AstraZeneca. Dr. Yang and his associates reported ties to numerous industry sources.

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor selective for both EGFR and T790M mutations that render cancers resistant to EGFR-TKIs, yielded a high overall response rate, “encouraging” progression-free survival, and a durable treatment response in advanced non–small cell lung cancer (NSCLC) that had progressed despite EGFR-TKI therapy, according to a report published online Feb. 21 in the Journal of Clinical Oncology.

In a manufacturer-sponsored, open-label phase II trial, 198 patients in 10 countries took 80 mg of oral osimertinib once daily for a median duration of 13.2 months (range, 1-18 months). The overall response rate was 62%, and the median duration of response was 15.2 months. The disease control rate was 90%, said James Chih-Hsin Yang, MD, PhD, of National Taiwan Hospital, Taipei, and his associates.

The median progression-free survival was 12.3 months, and the treatment benefit was generally consistent across all subgroups of patients regardless of age, smoking status, previous therapies, and duration of treatment. Questionnaire responses showed that patients “had consistent and sustained improvements in key lung cancer symptoms including dyspnea, cough, chest pain, and pain in the arm or shoulder,” as well as in global health status and physical functioning. This is particularly noteworthy because some patients had received “many (up to 11) lines of cancer therapy before osimertinib,” the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.70.3223).

“We also report encouraging systemic progression-free survival with osimertinib in patients with CNS metastases, and a high CNS response rate (64%) in those with measurable CNS lesions,” they wrote. This finding is particularly important “because new pharmacologic strategies are needed to treat brain metastases, given the long-term complications of brain radiation,” they added.

Osimertinib was generally well tolerated, with 21% of patients having adverse effects leading to dose interruptions and 5% to dose reductions. Nine patients (3%) discontinued the agent because of adverse effects, which included interstitial lung disease (3 fatal cases), QT prolongation, a reduced neutrophil count, and severe vomiting and diarrhea.

This trial was sponsored by AstraZeneca. Dr. Yang and his associates reported ties to numerous industry sources.

Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor selective for both EGFR and T790M mutations that render cancers resistant to EGFR-TKIs, yielded a high overall response rate, “encouraging” progression-free survival, and a durable treatment response in advanced non–small cell lung cancer (NSCLC) that had progressed despite EGFR-TKI therapy, according to a report published online Feb. 21 in the Journal of Clinical Oncology.

In a manufacturer-sponsored, open-label phase II trial, 198 patients in 10 countries took 80 mg of oral osimertinib once daily for a median duration of 13.2 months (range, 1-18 months). The overall response rate was 62%, and the median duration of response was 15.2 months. The disease control rate was 90%, said James Chih-Hsin Yang, MD, PhD, of National Taiwan Hospital, Taipei, and his associates.

The median progression-free survival was 12.3 months, and the treatment benefit was generally consistent across all subgroups of patients regardless of age, smoking status, previous therapies, and duration of treatment. Questionnaire responses showed that patients “had consistent and sustained improvements in key lung cancer symptoms including dyspnea, cough, chest pain, and pain in the arm or shoulder,” as well as in global health status and physical functioning. This is particularly noteworthy because some patients had received “many (up to 11) lines of cancer therapy before osimertinib,” the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.70.3223).

“We also report encouraging systemic progression-free survival with osimertinib in patients with CNS metastases, and a high CNS response rate (64%) in those with measurable CNS lesions,” they wrote. This finding is particularly important “because new pharmacologic strategies are needed to treat brain metastases, given the long-term complications of brain radiation,” they added.

Osimertinib was generally well tolerated, with 21% of patients having adverse effects leading to dose interruptions and 5% to dose reductions. Nine patients (3%) discontinued the agent because of adverse effects, which included interstitial lung disease (3 fatal cases), QT prolongation, a reduced neutrophil count, and severe vomiting and diarrhea.

This trial was sponsored by AstraZeneca. Dr. Yang and his associates reported ties to numerous industry sources.

Hormone maintenance therapy, when given after primary cytoreductive surgery and platinum-based chemotherapy, prolonged progression-free survival among women who had low-grade serous carcinoma of the ovary or peritoneum, a study showed.

Low-grade serous carcinoma (LGSC) is a rare histologic subtype that is somewhat resistant to conventional chemotherapy, so researchers have been searching for alternative or add-on treatments. To examine whether hormone maintenance therapy would be beneficial, the investigators analyzed information from a longitudinal database of patients with the malignancy who were treated at a single medical center.

They focused on 203 patients diagnosed as having stage II-IV disease of the ovary or peritoneum between 1981 and 2013, who underwent primary cytoreductive surgery followed by platinum-based chemotherapy. Seventy of these patients received hormone maintenance therapy for a median of 33 months (range, 1-223 months), taking letrozole, tamoxifen, leuprolide, anastrozole, medroxyprogesterone, or some combination of these agents. The remaining 133 patients took no hormone therapy and served as a control group, said David M. Gershenson, MD, and his associates at the University of Texas M.D. Anderson Cancer Center, Houston.

Women who took hormone maintenance therapy had a median progression-free survival of 64.9 months, compared with 26.4 months for the control group. This benefit was similar between women who had persistent disease after completing chemotherapy and those who were clinically disease free after completing chemotherapy, the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.71.0632).

“The findings of this hypothesis-generating study are potentially practice changing and warrant using a prospective trial design. A phase III randomized trial is currently under development” to compare hormone therapy against placebo in women with LGSC, Dr. Gersehnson and his associates noted.

They added that reports during the last decade showing that LGSC is resistant to platinum-based chemotherapy have led some clinicians to conclude that it is of no benefit at all and should be abandoned in this patient population. “In our view, that perspective is premature based on available data. Although LGSC is indolent and not as chemotherapy sensitive as high-grade serous carcinoma, it is not entirely chemotherapy resistant,” they wrote. Some women do respond, while “a high proportion … have stable disease for a period of time.”

Hormone maintenance therapy, when given after primary cytoreductive surgery and platinum-based chemotherapy, prolonged progression-free survival among women who had low-grade serous carcinoma of the ovary or peritoneum, a study showed.

Low-grade serous carcinoma (LGSC) is a rare histologic subtype that is somewhat resistant to conventional chemotherapy, so researchers have been searching for alternative or add-on treatments. To examine whether hormone maintenance therapy would be beneficial, the investigators analyzed information from a longitudinal database of patients with the malignancy who were treated at a single medical center.

They focused on 203 patients diagnosed as having stage II-IV disease of the ovary or peritoneum between 1981 and 2013, who underwent primary cytoreductive surgery followed by platinum-based chemotherapy. Seventy of these patients received hormone maintenance therapy for a median of 33 months (range, 1-223 months), taking letrozole, tamoxifen, leuprolide, anastrozole, medroxyprogesterone, or some combination of these agents. The remaining 133 patients took no hormone therapy and served as a control group, said David M. Gershenson, MD, and his associates at the University of Texas M.D. Anderson Cancer Center, Houston.

Women who took hormone maintenance therapy had a median progression-free survival of 64.9 months, compared with 26.4 months for the control group. This benefit was similar between women who had persistent disease after completing chemotherapy and those who were clinically disease free after completing chemotherapy, the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.71.0632).

“The findings of this hypothesis-generating study are potentially practice changing and warrant using a prospective trial design. A phase III randomized trial is currently under development” to compare hormone therapy against placebo in women with LGSC, Dr. Gersehnson and his associates noted.

They added that reports during the last decade showing that LGSC is resistant to platinum-based chemotherapy have led some clinicians to conclude that it is of no benefit at all and should be abandoned in this patient population. “In our view, that perspective is premature based on available data. Although LGSC is indolent and not as chemotherapy sensitive as high-grade serous carcinoma, it is not entirely chemotherapy resistant,” they wrote. Some women do respond, while “a high proportion … have stable disease for a period of time.”

Hormone maintenance therapy, when given after primary cytoreductive surgery and platinum-based chemotherapy, prolonged progression-free survival among women who had low-grade serous carcinoma of the ovary or peritoneum, a study showed.

Low-grade serous carcinoma (LGSC) is a rare histologic subtype that is somewhat resistant to conventional chemotherapy, so researchers have been searching for alternative or add-on treatments. To examine whether hormone maintenance therapy would be beneficial, the investigators analyzed information from a longitudinal database of patients with the malignancy who were treated at a single medical center.

They focused on 203 patients diagnosed as having stage II-IV disease of the ovary or peritoneum between 1981 and 2013, who underwent primary cytoreductive surgery followed by platinum-based chemotherapy. Seventy of these patients received hormone maintenance therapy for a median of 33 months (range, 1-223 months), taking letrozole, tamoxifen, leuprolide, anastrozole, medroxyprogesterone, or some combination of these agents. The remaining 133 patients took no hormone therapy and served as a control group, said David M. Gershenson, MD, and his associates at the University of Texas M.D. Anderson Cancer Center, Houston.

Women who took hormone maintenance therapy had a median progression-free survival of 64.9 months, compared with 26.4 months for the control group. This benefit was similar between women who had persistent disease after completing chemotherapy and those who were clinically disease free after completing chemotherapy, the investigators reported (J Clin Oncol. 2017 Feb 21. doi: 10.1200/jco.2016.71.0632).

“The findings of this hypothesis-generating study are potentially practice changing and warrant using a prospective trial design. A phase III randomized trial is currently under development” to compare hormone therapy against placebo in women with LGSC, Dr. Gersehnson and his associates noted.

They added that reports during the last decade showing that LGSC is resistant to platinum-based chemotherapy have led some clinicians to conclude that it is of no benefit at all and should be abandoned in this patient population. “In our view, that perspective is premature based on available data. Although LGSC is indolent and not as chemotherapy sensitive as high-grade serous carcinoma, it is not entirely chemotherapy resistant,” they wrote. Some women do respond, while “a high proportion … have stable disease for a period of time.”

LAS VEGAS – Patients with pheochromocytoma are likely to have preoperative comorbidities that predispose them to postoperative cardiopulmonary complications, leading to a longer length of stay and greater hospital charges.

A 5-year national database review found high rates of chronic lung disease and malignant hypertension among these patients, Punam P. Parikh, MD, said at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

“They are also at an increased risk for vascular injury during surgery, perhaps because these tumors are so vascular in nature, and associated intraoperative blood transfusion,” said Dr. Parikh of the University of Miami. Postoperatively, patients with pheochromocytoma are twice as likely to experience respiratory complications and almost eight times as likely to experience cardiac complications as patients with other hormonally active adrenal tumors.

Dr. Parikh queried the National Inpatient Sample to find patients who underwent adrenalectomy for the rare adrenal tumor from 2006 to 2011. Of 27,312 patients who had adrenalectomy during the 5-year period, 22% had hormonally active adrenal tumors. Of these, just 1.4% (85) were pheochromocytoma. Other hormonally active adrenal tumors were Conn’s syndrome (65%) and Cushing’s syndrome (33%).

A number of comorbidities were significantly more common among pheochromocytoma patients than among those with Conn’s and Cushing’s syndromes, including congestive heart failure (12% vs. 4% in the other syndromes) and malignant hypertension (5% vs. 3% and 0.3%, respectively). A third of pheochromocytoma patients also had diabetes.

The rate of intraoperative complications was significantly higher in these patients (22%) than in those with Conn’s and Cushing’s (11% and 17%). Vascular injury occurred in 6% vs. 2% and 4%, respectively. Almost a quarter of pheochromocytoma patients (21%) needed an intraoperative transfusion, compared with 2% of Conn’s patients and 3% of Cushing’s patients.

There were also more postoperative complications among pheochromocytoma patients than Conn’s or Cushing’s patients, including cardiac (6% vs. 0.4% and 0.6%) and pulmonary complications (17% vs. 6% and 9%).

Not surprisingly, Dr. Parikh said, pheochromocytoma patients had longer hospital stays (5 days), compared with patients with the other tumors (3 days). Hospital charges were also higher for those with pheochromocytoma ($50,000) than those with Conn’s or Cushing’s ($35,500 and $46,334, respectively).

A multivariate analysis concluded that pheochromocytoma was an independent risk factor for intraoperative blood transfusion (odds ratio, 4.2), postoperative cardiac complications (OR, 7.6), and postoperative respiratory complications (OR, 1.9).

Dr. Parikh suggested that patients with pheochromocytoma could benefit from some preoperative preparation.

“Because of these issues, these high-risk patients should undergo appropriate preoperative medical optimization in preparation for their adrenalectomy,” she noted.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

LAS VEGAS – Patients with pheochromocytoma are likely to have preoperative comorbidities that predispose them to postoperative cardiopulmonary complications, leading to a longer length of stay and greater hospital charges.

A 5-year national database review found high rates of chronic lung disease and malignant hypertension among these patients, Punam P. Parikh, MD, said at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

“They are also at an increased risk for vascular injury during surgery, perhaps because these tumors are so vascular in nature, and associated intraoperative blood transfusion,” said Dr. Parikh of the University of Miami. Postoperatively, patients with pheochromocytoma are twice as likely to experience respiratory complications and almost eight times as likely to experience cardiac complications as patients with other hormonally active adrenal tumors.

Dr. Parikh queried the National Inpatient Sample to find patients who underwent adrenalectomy for the rare adrenal tumor from 2006 to 2011. Of 27,312 patients who had adrenalectomy during the 5-year period, 22% had hormonally active adrenal tumors. Of these, just 1.4% (85) were pheochromocytoma. Other hormonally active adrenal tumors were Conn’s syndrome (65%) and Cushing’s syndrome (33%).

A number of comorbidities were significantly more common among pheochromocytoma patients than among those with Conn’s and Cushing’s syndromes, including congestive heart failure (12% vs. 4% in the other syndromes) and malignant hypertension (5% vs. 3% and 0.3%, respectively). A third of pheochromocytoma patients also had diabetes.

The rate of intraoperative complications was significantly higher in these patients (22%) than in those with Conn’s and Cushing’s (11% and 17%). Vascular injury occurred in 6% vs. 2% and 4%, respectively. Almost a quarter of pheochromocytoma patients (21%) needed an intraoperative transfusion, compared with 2% of Conn’s patients and 3% of Cushing’s patients.

There were also more postoperative complications among pheochromocytoma patients than Conn’s or Cushing’s patients, including cardiac (6% vs. 0.4% and 0.6%) and pulmonary complications (17% vs. 6% and 9%).

Not surprisingly, Dr. Parikh said, pheochromocytoma patients had longer hospital stays (5 days), compared with patients with the other tumors (3 days). Hospital charges were also higher for those with pheochromocytoma ($50,000) than those with Conn’s or Cushing’s ($35,500 and $46,334, respectively).

A multivariate analysis concluded that pheochromocytoma was an independent risk factor for intraoperative blood transfusion (odds ratio, 4.2), postoperative cardiac complications (OR, 7.6), and postoperative respiratory complications (OR, 1.9).

Dr. Parikh suggested that patients with pheochromocytoma could benefit from some preoperative preparation.

“Because of these issues, these high-risk patients should undergo appropriate preoperative medical optimization in preparation for their adrenalectomy,” she noted.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

LAS VEGAS – Patients with pheochromocytoma are likely to have preoperative comorbidities that predispose them to postoperative cardiopulmonary complications, leading to a longer length of stay and greater hospital charges.

A 5-year national database review found high rates of chronic lung disease and malignant hypertension among these patients, Punam P. Parikh, MD, said at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

“They are also at an increased risk for vascular injury during surgery, perhaps because these tumors are so vascular in nature, and associated intraoperative blood transfusion,” said Dr. Parikh of the University of Miami. Postoperatively, patients with pheochromocytoma are twice as likely to experience respiratory complications and almost eight times as likely to experience cardiac complications as patients with other hormonally active adrenal tumors.

Dr. Parikh queried the National Inpatient Sample to find patients who underwent adrenalectomy for the rare adrenal tumor from 2006 to 2011. Of 27,312 patients who had adrenalectomy during the 5-year period, 22% had hormonally active adrenal tumors. Of these, just 1.4% (85) were pheochromocytoma. Other hormonally active adrenal tumors were Conn’s syndrome (65%) and Cushing’s syndrome (33%).

A number of comorbidities were significantly more common among pheochromocytoma patients than among those with Conn’s and Cushing’s syndromes, including congestive heart failure (12% vs. 4% in the other syndromes) and malignant hypertension (5% vs. 3% and 0.3%, respectively). A third of pheochromocytoma patients also had diabetes.

The rate of intraoperative complications was significantly higher in these patients (22%) than in those with Conn’s and Cushing’s (11% and 17%). Vascular injury occurred in 6% vs. 2% and 4%, respectively. Almost a quarter of pheochromocytoma patients (21%) needed an intraoperative transfusion, compared with 2% of Conn’s patients and 3% of Cushing’s patients.

There were also more postoperative complications among pheochromocytoma patients than Conn’s or Cushing’s patients, including cardiac (6% vs. 0.4% and 0.6%) and pulmonary complications (17% vs. 6% and 9%).

Not surprisingly, Dr. Parikh said, pheochromocytoma patients had longer hospital stays (5 days), compared with patients with the other tumors (3 days). Hospital charges were also higher for those with pheochromocytoma ($50,000) than those with Conn’s or Cushing’s ($35,500 and $46,334, respectively).

A multivariate analysis concluded that pheochromocytoma was an independent risk factor for intraoperative blood transfusion (odds ratio, 4.2), postoperative cardiac complications (OR, 7.6), and postoperative respiratory complications (OR, 1.9).

Dr. Parikh suggested that patients with pheochromocytoma could benefit from some preoperative preparation.

“Because of these issues, these high-risk patients should undergo appropriate preoperative medical optimization in preparation for their adrenalectomy,” she noted.

She had no financial disclosures.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.

“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.

Primary MR

“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.

The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.

Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.

“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.

It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.

“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.

The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.

“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.

He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).

The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.

Secondary MR

Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.

“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.

In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).

“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.

He reported serving on a data safety monitoring board for Edwards Lifesciences.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.

“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.

Primary MR

“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.

The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.

Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.

“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.

It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.

“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.

The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.

“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.

He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).

The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.

Secondary MR

Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.

“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.

In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).

“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.

He reported serving on a data safety monitoring board for Edwards Lifesciences.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Primary mitral regurgitation and secondary mitral regurgitation may sound a lot alike, but they are in fact starkly different diseases, Blase A. Carabello, MD, said at the Annual Cardiovascular Conference at Snowmass.

“They are almost entirely different in their etiologies, in their pathophysiologies, and in their therapies,” according to Dr. Carabello, professor of medicine and chief of cardiology at East Carolina University in Greenville, N.C.

Primary MR

“Primary MR, unlike aortic regurgitation, is not well tolerated. Early repair is key,” the cardiologist stressed.

The ACC/AHA guidelines emphasize the importance of early referral for surgery for primary MR because of surgery’s proven survival benefit. The triggers for surgery, as described in the guidelines, are easy to remember, namely, “symptoms/60/50/40.” That is, it’s time to move on to surgery when any of the following occurs: The patient becomes even mildly symptomatic, the left ventricular ejection fraction (LVEF) drops to 60%, the pulmonary artery pressure climbs to 50 mm Hg, or the LV end-systolic dimension reaches 40 mm.

Dr. Carabello said he believes those surgical thresholds are conservative, and it’s best to make the surgical referral when a patient approaches one or more of those triggers, but before actually reaching them.

“That’s the way I practice: Don’t wait for any of those things. Just get it done. One advantage to early repair is the patient can’t get lost to follow-up. They’re repaired, and they can’t take it out,” he said.

It’s possible that the next iteration of the guidelines will utilize stricter thresholds for surgery. French investigators have shown that surgery for primary MR achieves a significantly higher rate of normal LV function if the operation occurs when patients have an LVEF of 64% or more and an LV end-systolic dimension of less than 37 mm (Eur J Echocardiogr. 2011 Sep;12[9]:702-10). So far, though, there hasn’t been a confirmatory study.

“I think the normal EF in primary MR is about 70%. By the time the EF in a patient with primary MR gets down into the 50s, you’re looking at an extraordinarily sick ventricle,” according to Dr. Carabello.

The impetus for including the “symptoms/60/50/40” surgical triggers in the guidelines is to encourage physicians to make the surgical referral earlier than has often been the case. Too frequently, the surgical referral is delayed until damage to the ventricle is irreversible, with a resultant worsened prognosis.

“The natural history is such that, from the time a patient with severe primary MR enters your office to the annual mortality risk reaching 50% is only about 5 years. So if you’re going to do watchful waiting, fine, but remember: You don’t have all that long to watch and wait before something bad happens to these folks,” the cardiologist cautioned.

He added that it’s possible that, in the future, cardiac biomarkers will be utilized to help predict the long-term mortality risk of patients under medical management of their primary MR. In a recent study of 1,331 patients with primary MR, the investigators showed that the ratio of B-type natriuretic peptide (BNP) to the upper limit of normal BNP, adjusted for age and sex, was a powerful independent predictor of this risk (J Am Coll Cardiol. 2016 Sep 20;68[12]:1297-307).

The guidelines state that mitral valve repair is preferable to replacement as long as the heart team determines there’s at least a 95% chance of a durable repair. That’s because the operative mortality associated with replacement is significantly higher than with repair.

Secondary MR

Unlike in primary MR, it’s unclear whether surgery prolongs life for patients with secondary MR, or if mitral repair is superior to replacement. Thus, the current guidelines recommend surgery only for patients who are still severely symptomatic despite maximal guideline-directed medical therapy for heart failure as well as cardiac resynchronization therapy, provided they have a conduction system abnormality and qualify for the device therapy.

“If you’ve done all that and they’re still sick, I think that surgery or the MitraClip may benefit them very much,” Dr. Carabello said.

In the United States, the MitraClip transcatheter device is approved only for the treatment of primary MR in inoperable patients. But in the rest of the world, roughly three-quarters of these devices are used for treatment of secondary MR. That potential indication is currently under study in the United States in the phase III COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation).

“In the acute setting, the changes in hemodynamic variables and left ventricular performance that occur with the MitraClip are quite dramatic, with a marked decrease in wedge pressure and a markedly increased stroke volume, which is what it’s supposed to do. So I’m encouraged. We’ll wait for the results of the COAPT trial, which I believe is likely to demonstrate a reduction in hospitalizations and certainly an improvement in patient symptoms. But I doubt very much that we’ll ever see a change in lifespan because the ventricle is still sick, and we in 2017 have not found a way yet to revive a sick ventricle. It’s unlikely that fixing the MR will do so,” according to Dr. Carabello.

He reported serving on a data safety monitoring board for Edwards Lifesciences.

bjancin@frontlinemedcom.com

Image by James Thomson

Researchers say they have created a model that shows the step-by-step progression from normal blood cells to acute myeloid leukemia (AML).

The team generated induced pluripotent stem cell (iPSC) lines capturing disease stages that included preleukemia, low-risk myelodysplastic syndrome (MDS), high-risk MDS, and AML.

The researchers then used CRISPR/Cas9 genome editing to induce disease progression and reversal.

And they used the iPSCs to uncover disease-stage-specific effects of 2 drugs.

Eirini P. Papapetrou, MD, PhD, of the Icahn School of Medicine at Mount Sinai in New York, New York, and her colleagues described this work in Cell Stem Cell.

The researchers first explained how they generated patient-derived iPSCs that represented familial predisposition to myeloid malignancy, low-risk and high-risk MDS, and AML.

By studying these iPSC lines, the team uncovered “a phenotypic road map of disease progression” that led to a “serially transplantable leukemia.”

“We are encouraged by the discovery that it was possible to generate potent, engraftable leukemia derived from AML induced pluripotent stem cells,” said study author Michael G. Kharas, PhD, of the Icahn School of Medicine at Mount Sinai.

The researchers also showed that they could revert a high-risk MDS iPSC line to a premalignant state by correcting a chromosome 7q deletion.

And they could force progression in a preleukemic iPSC line. The team induced progression to low-risk MDS by inactivating the second GATA2 allele and progression to high-risk MDS by deleting chromosome 7q.

“This work shows that integrated patient cell reprogramming and cancer genetics is a powerful way to dissect cancer progression,” Dr Kharas said.

The researchers reported that, ultimately, they were able to model the stepwise progression of normal cells to preleukemia and MDS by sequentially introducing genetic lesions associated with earlier and later disease stages (ASXL1 truncation and chromosome 7q deletion, respectively).

“The new model will empower investigation into the cellular and molecular events underlying the development of leukemia in ways that were not possible before,” Dr Papapetrou said.

She added that the group’s findings provide a framework to aid investigation into disease mechanisms, events driving progression, and drug responses.

In fact, the researchers did use hematopoietic progenitor cells (HPCs) derived from their iPSCs to analyze the disease-stage-specific effects of 2 drugs—5-azacytidine and rigosertib.

The team said they found evidence to suggest that 5-azacytidine may work in low-risk MDS by affecting differentiation, and the drug’s main therapeutic action in high-risk MDS might be mediated through selective inhibition of the MDS clone.

The researchers tested rigosertib in HPCs derived from 2 AML lines (from the same patient) that captured 2 different disease stages. One line was derived from the dominant clone (del 7q), and the other was derived from a KRAS-mutated subclone.

The team found that HPCs derived from the KRAS-mutated line demonstrated “marked sensitivity” to rigosertib, but the other HPCs were “marginally affected.”

Image by James Thomson

Researchers say they have created a model that shows the step-by-step progression from normal blood cells to acute myeloid leukemia (AML).

The team generated induced pluripotent stem cell (iPSC) lines capturing disease stages that included preleukemia, low-risk myelodysplastic syndrome (MDS), high-risk MDS, and AML.

The researchers then used CRISPR/Cas9 genome editing to induce disease progression and reversal.

And they used the iPSCs to uncover disease-stage-specific effects of 2 drugs.

Eirini P. Papapetrou, MD, PhD, of the Icahn School of Medicine at Mount Sinai in New York, New York, and her colleagues described this work in Cell Stem Cell.

The researchers first explained how they generated patient-derived iPSCs that represented familial predisposition to myeloid malignancy, low-risk and high-risk MDS, and AML.

By studying these iPSC lines, the team uncovered “a phenotypic road map of disease progression” that led to a “serially transplantable leukemia.”

“We are encouraged by the discovery that it was possible to generate potent, engraftable leukemia derived from AML induced pluripotent stem cells,” said study author Michael G. Kharas, PhD, of the Icahn School of Medicine at Mount Sinai.

The researchers also showed that they could revert a high-risk MDS iPSC line to a premalignant state by correcting a chromosome 7q deletion.

And they could force progression in a preleukemic iPSC line. The team induced progression to low-risk MDS by inactivating the second GATA2 allele and progression to high-risk MDS by deleting chromosome 7q.

“This work shows that integrated patient cell reprogramming and cancer genetics is a powerful way to dissect cancer progression,” Dr Kharas said.

The researchers reported that, ultimately, they were able to model the stepwise progression of normal cells to preleukemia and MDS by sequentially introducing genetic lesions associated with earlier and later disease stages (ASXL1 truncation and chromosome 7q deletion, respectively).

“The new model will empower investigation into the cellular and molecular events underlying the development of leukemia in ways that were not possible before,” Dr Papapetrou said.

She added that the group’s findings provide a framework to aid investigation into disease mechanisms, events driving progression, and drug responses.

In fact, the researchers did use hematopoietic progenitor cells (HPCs) derived from their iPSCs to analyze the disease-stage-specific effects of 2 drugs—5-azacytidine and rigosertib.

The team said they found evidence to suggest that 5-azacytidine may work in low-risk MDS by affecting differentiation, and the drug’s main therapeutic action in high-risk MDS might be mediated through selective inhibition of the MDS clone.

The researchers tested rigosertib in HPCs derived from 2 AML lines (from the same patient) that captured 2 different disease stages. One line was derived from the dominant clone (del 7q), and the other was derived from a KRAS-mutated subclone.

The team found that HPCs derived from the KRAS-mutated line demonstrated “marked sensitivity” to rigosertib, but the other HPCs were “marginally affected.”

Image by James Thomson

Researchers say they have created a model that shows the step-by-step progression from normal blood cells to acute myeloid leukemia (AML).

The team generated induced pluripotent stem cell (iPSC) lines capturing disease stages that included preleukemia, low-risk myelodysplastic syndrome (MDS), high-risk MDS, and AML.

The researchers then used CRISPR/Cas9 genome editing to induce disease progression and reversal.

And they used the iPSCs to uncover disease-stage-specific effects of 2 drugs.

Eirini P. Papapetrou, MD, PhD, of the Icahn School of Medicine at Mount Sinai in New York, New York, and her colleagues described this work in Cell Stem Cell.

The researchers first explained how they generated patient-derived iPSCs that represented familial predisposition to myeloid malignancy, low-risk and high-risk MDS, and AML.

By studying these iPSC lines, the team uncovered “a phenotypic road map of disease progression” that led to a “serially transplantable leukemia.”

“We are encouraged by the discovery that it was possible to generate potent, engraftable leukemia derived from AML induced pluripotent stem cells,” said study author Michael G. Kharas, PhD, of the Icahn School of Medicine at Mount Sinai.

The researchers also showed that they could revert a high-risk MDS iPSC line to a premalignant state by correcting a chromosome 7q deletion.

And they could force progression in a preleukemic iPSC line. The team induced progression to low-risk MDS by inactivating the second GATA2 allele and progression to high-risk MDS by deleting chromosome 7q.

“This work shows that integrated patient cell reprogramming and cancer genetics is a powerful way to dissect cancer progression,” Dr Kharas said.

The researchers reported that, ultimately, they were able to model the stepwise progression of normal cells to preleukemia and MDS by sequentially introducing genetic lesions associated with earlier and later disease stages (ASXL1 truncation and chromosome 7q deletion, respectively).

“The new model will empower investigation into the cellular and molecular events underlying the development of leukemia in ways that were not possible before,” Dr Papapetrou said.

She added that the group’s findings provide a framework to aid investigation into disease mechanisms, events driving progression, and drug responses.

In fact, the researchers did use hematopoietic progenitor cells (HPCs) derived from their iPSCs to analyze the disease-stage-specific effects of 2 drugs—5-azacytidine and rigosertib.

The team said they found evidence to suggest that 5-azacytidine may work in low-risk MDS by affecting differentiation, and the drug’s main therapeutic action in high-risk MDS might be mediated through selective inhibition of the MDS clone.

The researchers tested rigosertib in HPCs derived from 2 AML lines (from the same patient) that captured 2 different disease stages. One line was derived from the dominant clone (del 7q), and the other was derived from a KRAS-mutated subclone.

The team found that HPCs derived from the KRAS-mutated line demonstrated “marked sensitivity” to rigosertib, but the other HPCs were “marginally affected.”

Estimates of high pertussis susceptibility in infants suggest a need for greater public health efforts to increase DTaP vaccine coverage in children and Tdap coverage in pregnant women, according to results of research by Lana Childs and Robert A. Bednarczyk, PhD.

There were 32,971 pertussis cases reported in 2014, a 15% increase over 2013; most cases occurred in children who were too young to be fully vaccinated and in preadolescents with waning immunity from their vaccines. In the United States, vaccine coverage during childhood tends to be high overall, but DTaP coverage (84% in 2014) “remains lower than coverage for other childhood vaccinations,” they noted.

©michaeljung/Thinkstock

acruz@frontlinemedcom.com

Estimates of high pertussis susceptibility in infants suggest a need for greater public health efforts to increase DTaP vaccine coverage in children and Tdap coverage in pregnant women, according to results of research by Lana Childs and Robert A. Bednarczyk, PhD.

There were 32,971 pertussis cases reported in 2014, a 15% increase over 2013; most cases occurred in children who were too young to be fully vaccinated and in preadolescents with waning immunity from their vaccines. In the United States, vaccine coverage during childhood tends to be high overall, but DTaP coverage (84% in 2014) “remains lower than coverage for other childhood vaccinations,” they noted.

©michaeljung/Thinkstock

acruz@frontlinemedcom.com

Estimates of high pertussis susceptibility in infants suggest a need for greater public health efforts to increase DTaP vaccine coverage in children and Tdap coverage in pregnant women, according to results of research by Lana Childs and Robert A. Bednarczyk, PhD.

There were 32,971 pertussis cases reported in 2014, a 15% increase over 2013; most cases occurred in children who were too young to be fully vaccinated and in preadolescents with waning immunity from their vaccines. In the United States, vaccine coverage during childhood tends to be high overall, but DTaP coverage (84% in 2014) “remains lower than coverage for other childhood vaccinations,” they noted.

©michaeljung/Thinkstock

acruz@frontlinemedcom.com

LAS VEGAS – Micropapillary thyroid carcinoma may not be as indolent as generally thought, according to the findings of a retrospective study of thyroidectomy cases.

A review of 213 patients diagnosed with the cancer found that 34% of them had multifocal disease, and 14%, metastatic disease, Maggie Bosley reported at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

LAS VEGAS – Micropapillary thyroid carcinoma may not be as indolent as generally thought, according to the findings of a retrospective study of thyroidectomy cases.

A review of 213 patients diagnosed with the cancer found that 34% of them had multifocal disease, and 14%, metastatic disease, Maggie Bosley reported at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

LAS VEGAS – Micropapillary thyroid carcinoma may not be as indolent as generally thought, according to the findings of a retrospective study of thyroidectomy cases.

A review of 213 patients diagnosed with the cancer found that 34% of them had multifocal disease, and 14%, metastatic disease, Maggie Bosley reported at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

SNOWMASS, COLO. – Progress in the understanding and treatment of immunoglobulin G4–related disease is occurring “at lightning speed,” John H. Stone, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

Eight or nine years ago no one had heard of immunoglobulin G4–related disease (IgG4-RD). Today, because of the broad swath the disease cuts, it’s a hot research topic in every subspecialty of medicine as well as surgery, pathology, and radiology.

Bruce Jancin/Frontline Medical News

This new understanding of IgG4-RD, he added, is opening the door to novel treatments.

“This is not a new disease. It was there when we were all in medical school, and for hundreds of years before that. But it’s really only in the last decade that we have come to understand that the disease can affect literally every organ system in the body with syndromes that we once thought were isolated organ-specific syndromes but we now recognize are part of a multiorgan disease currently called IgG4-related disease,” the rheumatologist said.

IgG4-RD is an immune-mediated fibroinflammatory condition characterized histopathologically by three hallmark features in involved tissue: obliterative phlebitis, storiform fibrosis, and a dense lymphoplasmacytic infiltrate.

Clinically, IgG4-RD often presents as a mass lesion that can affect any organ.

“I have many patients who’ve undergone modified Whipple procedures because they were thought to have adenocarcinoma of the pancreas,” according to Dr. Stone.

Other common presentations include Riedel’s thyroiditis, autoimmune pancreatitis, sclerosing cholangitis, sialadenitis, dacryoadenitis, periaortitis, an eosinophilic rash, and pseudotumor of the lung, lymph nodes, or orbits.

“Retroperitoneal fibrosis is a common and underappreciated manifestation. It may be the most common subsyndrome associated with IgG4-related disease,” he observed.

Another common presentation involves atopic disease – asthma, allergic rhinitis, eczema, eosinophilia, nasal polyps – developing out of the blue in middle age or later life. This observation led some other investigators to posit that IgG4-RD is a T-helper type 2–driven disease, an assertion debunked by Dr. Stone and coworkers (Allergy. 2014 Feb;69[2]:269-72).

Dr. Stone and his coinvestigators have published the largest series of patients with biopsy-proven IgG4-RD reported to date (Arthritis Rheumatol. 2015 Sep; 67[9]:2466-75). The average age at disease onset was 50 years. Of note, multiorgan involvement was the norm: 24% of patients had two organs involved, and 38% had three or more.

Analysis of this large patient series has led Dr. Stone to a surprising conclusion about the nature of IgG4-RD: “We have greatly overemphasized the importance of IgG4 in this condition,” he asserted.

Indeed, a mere 51% of the patients with clinically active untreated IgG4-RD in his series had an elevated serum IgG level. Dr. Stone characterized IgG4 as “kind of a wimpy antibody” incapable of driving the disease process because it is a noninflammatory immunoglobulin. This has led to speculation that IgG4 functions as what he termed an “antigen sink,” attempting to bind antigen at sites of inflammation.

But while an elevated serum IgG4 is of limited utility for diagnostic purposes, Dr. Stone and coworkers have demonstrated that it is of value as a predictor of relapse. Among patients with a treatment-induced remission, those in the top quartile in terms of baseline pretreatment serum IgG4 were 6.2-fold more likely to relapse (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).

“This is a very useful marker for patients who are going to need chronic ongoing therapy. The notion of putting such patients on steroids for months and years is not appealing,” he said.

Levels of circulating plasmablasts as measured by peripheral blood flow cytometry, especially IgG4-positive plasmablasts, have proven much more helpful than serum IgG4 levels as a diagnostic tool, a reliable biomarker of disease activity, and a therapeutic target. Levels of these short-lived CD19+CD38+CD27+ plasmablasts are enormously elevated independent of serum IgG4 in patients with active IgG4-RD.

“One of the questions I’m most often asked is whether IgG4-related disease is a premalignant condition. My answer is no. The plasmablast expansion is oligoclonal, not polyclonal,” Dr. Stone continued.

He described IgG4-RD as “a continuous dance between T cells and B cells.” The latest thinking regarding pathogenesis is that type 2 T follicular helper cells activate B cells, which become memory B cells or plasmablasts. These activated B cells and plasmablasts present antigen to CD4+ cytotoxic T cells at sites of disease. Dr. Stone and his coinvestigators recently identified these CD4+ cytotoxic T cells as a novel population of clonally expanded T cells with SLAMF7 as a surface marker. The cells secrete interferon-gamma, interleukin-1, and transforming growth factor-beta, all of which are capable of driving the intense fibrosis characteristic of IgG4-RD. In addition, these CD4+ cytotoxic T cells secrete granzyme B and perforin, previously thought to be released mainly by natural killer T cells.

Joint American College of Rheumatology/European League Against Rheumatism classification criteria for the disease are expected to be finalized this winter at the Third International Symposium on IgG4-Related Diseases.

Treatment with rituxumab

Glucocorticoids remain the first-line therapy in IgG4-related disease, but it’s essential to bear in mind that their long-term efficacy in this immune-mediated fibroinflammatory disease is the exception rather than the rule, Dr. Stone said at the symposium.

Dr. Stone was a coauthor of an international expert consensus statement on the treatment of IgG4-related disease (IgG4-RD), which emphasized that point (Arthritis Rheumatol. 2015 Jul;67[7]:1688-99).

“I typically start with prednisone at 40 mg/day, and there’s a dramatic response in these patients. Then I taper them off after 2-3 months. If 2-3 months doesn’t put them into a long-term sustained remission, it’s time to go to something else,” said Dr. Stone.

So what’s the next move, then, after steroids fail? Dr. Stone was a pioneer in the strikingly successful use of B cell depletion via rituximab (Rituxan) in patients with IgG4-RD. First he and his coinvestigators demonstrated that this off-label use of rituximab led to rapid clinical and histologic improvement (Ann Rheum Dis. 2015 Jun; 74[6]:1171-7), then they showed it also causes levels of circulating plasmablasts, serum IgG4, and biomarkers of fibrosis to plunge, suggesting B cell depletion may halt the destructive process of collagen deposition that characterizes this immune-related disease (Ann Rheum Dis. 2015 Dec;74[12]:2236-43). They have also reported that patients with very elevated baseline serum IgG4 levels are at more than sixfold increased risk of relapse at a median of 244 days from their first rituximab infusion (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).

The success with rituximab is just one example of how improved understanding of the pathophysiology of IgG4-RD has opened the door to novel treatments. Dr. Stone is the lead investigator in an ongoing phase II, open-label study in which 15 patients with active IgG4-RD will receive intravenous XmAb5871 every 2 weeks for 6 months to evaluate the effect on the IgG4-RD Responder Index. XmAb5871 is a monoclonal antibody that binds to CD19 and FCgammaRIIb in order to downregulate activated B cells and plasmablasts. It is also being developed for treatment of systemic lupus erythematosus.

Dr. Stone and his coinvestigators are working on a therapeutic approach to IgG4-RD that targets antigen presentation by activated B cells to CD4+ cytotoxic T cells at sites of disease. These CD4+ cytotoxic T cells contain signaling lymphocyte activation molecule F7 (SLAMF7) as a surface marker. Elotuzumab (Empliciti), an immunostimulatory humanized monoclonal antibody targeting SLAMF7, is already on the market for treatment of multiple myeloma, he noted.

Dr. Stone reported receiving IgG4-RD-related research funding from and serving as a consultant to Genentech and Xencor, which is developing XmAb5871.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Progress in the understanding and treatment of immunoglobulin G4–related disease is occurring “at lightning speed,” John H. Stone, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

Eight or nine years ago no one had heard of immunoglobulin G4–related disease (IgG4-RD). Today, because of the broad swath the disease cuts, it’s a hot research topic in every subspecialty of medicine as well as surgery, pathology, and radiology.

Bruce Jancin/Frontline Medical News

This new understanding of IgG4-RD, he added, is opening the door to novel treatments.

“This is not a new disease. It was there when we were all in medical school, and for hundreds of years before that. But it’s really only in the last decade that we have come to understand that the disease can affect literally every organ system in the body with syndromes that we once thought were isolated organ-specific syndromes but we now recognize are part of a multiorgan disease currently called IgG4-related disease,” the rheumatologist said.

IgG4-RD is an immune-mediated fibroinflammatory condition characterized histopathologically by three hallmark features in involved tissue: obliterative phlebitis, storiform fibrosis, and a dense lymphoplasmacytic infiltrate.

Clinically, IgG4-RD often presents as a mass lesion that can affect any organ.

“I have many patients who’ve undergone modified Whipple procedures because they were thought to have adenocarcinoma of the pancreas,” according to Dr. Stone.

Other common presentations include Riedel’s thyroiditis, autoimmune pancreatitis, sclerosing cholangitis, sialadenitis, dacryoadenitis, periaortitis, an eosinophilic rash, and pseudotumor of the lung, lymph nodes, or orbits.

“Retroperitoneal fibrosis is a common and underappreciated manifestation. It may be the most common subsyndrome associated with IgG4-related disease,” he observed.

Another common presentation involves atopic disease – asthma, allergic rhinitis, eczema, eosinophilia, nasal polyps – developing out of the blue in middle age or later life. This observation led some other investigators to posit that IgG4-RD is a T-helper type 2–driven disease, an assertion debunked by Dr. Stone and coworkers (Allergy. 2014 Feb;69[2]:269-72).

Dr. Stone and his coinvestigators have published the largest series of patients with biopsy-proven IgG4-RD reported to date (Arthritis Rheumatol. 2015 Sep; 67[9]:2466-75). The average age at disease onset was 50 years. Of note, multiorgan involvement was the norm: 24% of patients had two organs involved, and 38% had three or more.

Analysis of this large patient series has led Dr. Stone to a surprising conclusion about the nature of IgG4-RD: “We have greatly overemphasized the importance of IgG4 in this condition,” he asserted.

Indeed, a mere 51% of the patients with clinically active untreated IgG4-RD in his series had an elevated serum IgG level. Dr. Stone characterized IgG4 as “kind of a wimpy antibody” incapable of driving the disease process because it is a noninflammatory immunoglobulin. This has led to speculation that IgG4 functions as what he termed an “antigen sink,” attempting to bind antigen at sites of inflammation.

But while an elevated serum IgG4 is of limited utility for diagnostic purposes, Dr. Stone and coworkers have demonstrated that it is of value as a predictor of relapse. Among patients with a treatment-induced remission, those in the top quartile in terms of baseline pretreatment serum IgG4 were 6.2-fold more likely to relapse (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).

“This is a very useful marker for patients who are going to need chronic ongoing therapy. The notion of putting such patients on steroids for months and years is not appealing,” he said.

Levels of circulating plasmablasts as measured by peripheral blood flow cytometry, especially IgG4-positive plasmablasts, have proven much more helpful than serum IgG4 levels as a diagnostic tool, a reliable biomarker of disease activity, and a therapeutic target. Levels of these short-lived CD19+CD38+CD27+ plasmablasts are enormously elevated independent of serum IgG4 in patients with active IgG4-RD.

“One of the questions I’m most often asked is whether IgG4-related disease is a premalignant condition. My answer is no. The plasmablast expansion is oligoclonal, not polyclonal,” Dr. Stone continued.

He described IgG4-RD as “a continuous dance between T cells and B cells.” The latest thinking regarding pathogenesis is that type 2 T follicular helper cells activate B cells, which become memory B cells or plasmablasts. These activated B cells and plasmablasts present antigen to CD4+ cytotoxic T cells at sites of disease. Dr. Stone and his coinvestigators recently identified these CD4+ cytotoxic T cells as a novel population of clonally expanded T cells with SLAMF7 as a surface marker. The cells secrete interferon-gamma, interleukin-1, and transforming growth factor-beta, all of which are capable of driving the intense fibrosis characteristic of IgG4-RD. In addition, these CD4+ cytotoxic T cells secrete granzyme B and perforin, previously thought to be released mainly by natural killer T cells.

Joint American College of Rheumatology/European League Against Rheumatism classification criteria for the disease are expected to be finalized this winter at the Third International Symposium on IgG4-Related Diseases.

Treatment with rituxumab

Glucocorticoids remain the first-line therapy in IgG4-related disease, but it’s essential to bear in mind that their long-term efficacy in this immune-mediated fibroinflammatory disease is the exception rather than the rule, Dr. Stone said at the symposium.

Dr. Stone was a coauthor of an international expert consensus statement on the treatment of IgG4-related disease (IgG4-RD), which emphasized that point (Arthritis Rheumatol. 2015 Jul;67[7]:1688-99).

“I typically start with prednisone at 40 mg/day, and there’s a dramatic response in these patients. Then I taper them off after 2-3 months. If 2-3 months doesn’t put them into a long-term sustained remission, it’s time to go to something else,” said Dr. Stone.

So what’s the next move, then, after steroids fail? Dr. Stone was a pioneer in the strikingly successful use of B cell depletion via rituximab (Rituxan) in patients with IgG4-RD. First he and his coinvestigators demonstrated that this off-label use of rituximab led to rapid clinical and histologic improvement (Ann Rheum Dis. 2015 Jun; 74[6]:1171-7), then they showed it also causes levels of circulating plasmablasts, serum IgG4, and biomarkers of fibrosis to plunge, suggesting B cell depletion may halt the destructive process of collagen deposition that characterizes this immune-related disease (Ann Rheum Dis. 2015 Dec;74[12]:2236-43). They have also reported that patients with very elevated baseline serum IgG4 levels are at more than sixfold increased risk of relapse at a median of 244 days from their first rituximab infusion (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).

The success with rituximab is just one example of how improved understanding of the pathophysiology of IgG4-RD has opened the door to novel treatments. Dr. Stone is the lead investigator in an ongoing phase II, open-label study in which 15 patients with active IgG4-RD will receive intravenous XmAb5871 every 2 weeks for 6 months to evaluate the effect on the IgG4-RD Responder Index. XmAb5871 is a monoclonal antibody that binds to CD19 and FCgammaRIIb in order to downregulate activated B cells and plasmablasts. It is also being developed for treatment of systemic lupus erythematosus.

Dr. Stone and his coinvestigators are working on a therapeutic approach to IgG4-RD that targets antigen presentation by activated B cells to CD4+ cytotoxic T cells at sites of disease. These CD4+ cytotoxic T cells contain signaling lymphocyte activation molecule F7 (SLAMF7) as a surface marker. Elotuzumab (Empliciti), an immunostimulatory humanized monoclonal antibody targeting SLAMF7, is already on the market for treatment of multiple myeloma, he noted.

Dr. Stone reported receiving IgG4-RD-related research funding from and serving as a consultant to Genentech and Xencor, which is developing XmAb5871.

bjancin@frontlinemedcom.com

SNOWMASS, COLO. – Progress in the understanding and treatment of immunoglobulin G4–related disease is occurring “at lightning speed,” John H. Stone, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.

Eight or nine years ago no one had heard of immunoglobulin G4–related disease (IgG4-RD). Today, because of the broad swath the disease cuts, it’s a hot research topic in every subspecialty of medicine as well as surgery, pathology, and radiology.

Bruce Jancin/Frontline Medical News

This new understanding of IgG4-RD, he added, is opening the door to novel treatments.

“This is not a new disease. It was there when we were all in medical school, and for hundreds of years before that. But it’s really only in the last decade that we have come to understand that the disease can affect literally every organ system in the body with syndromes that we once thought were isolated organ-specific syndromes but we now recognize are part of a multiorgan disease currently called IgG4-related disease,” the rheumatologist said.

IgG4-RD is an immune-mediated fibroinflammatory condition characterized histopathologically by three hallmark features in involved tissue: obliterative phlebitis, storiform fibrosis, and a dense lymphoplasmacytic infiltrate.

Clinically, IgG4-RD often presents as a mass lesion that can affect any organ.

“I have many patients who’ve undergone modified Whipple procedures because they were thought to have adenocarcinoma of the pancreas,” according to Dr. Stone.

Other common presentations include Riedel’s thyroiditis, autoimmune pancreatitis, sclerosing cholangitis, sialadenitis, dacryoadenitis, periaortitis, an eosinophilic rash, and pseudotumor of the lung, lymph nodes, or orbits.

“Retroperitoneal fibrosis is a common and underappreciated manifestation. It may be the most common subsyndrome associated with IgG4-related disease,” he observed.

Another common presentation involves atopic disease – asthma, allergic rhinitis, eczema, eosinophilia, nasal polyps – developing out of the blue in middle age or later life. This observation led some other investigators to posit that IgG4-RD is a T-helper type 2–driven disease, an assertion debunked by Dr. Stone and coworkers (Allergy. 2014 Feb;69[2]:269-72).

Dr. Stone and his coinvestigators have published the largest series of patients with biopsy-proven IgG4-RD reported to date (Arthritis Rheumatol. 2015 Sep; 67[9]:2466-75). The average age at disease onset was 50 years. Of note, multiorgan involvement was the norm: 24% of patients had two organs involved, and 38% had three or more.

Analysis of this large patient series has led Dr. Stone to a surprising conclusion about the nature of IgG4-RD: “We have greatly overemphasized the importance of IgG4 in this condition,” he asserted.

Indeed, a mere 51% of the patients with clinically active untreated IgG4-RD in his series had an elevated serum IgG level. Dr. Stone characterized IgG4 as “kind of a wimpy antibody” incapable of driving the disease process because it is a noninflammatory immunoglobulin. This has led to speculation that IgG4 functions as what he termed an “antigen sink,” attempting to bind antigen at sites of inflammation.

But while an elevated serum IgG4 is of limited utility for diagnostic purposes, Dr. Stone and coworkers have demonstrated that it is of value as a predictor of relapse. Among patients with a treatment-induced remission, those in the top quartile in terms of baseline pretreatment serum IgG4 were 6.2-fold more likely to relapse (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).

“This is a very useful marker for patients who are going to need chronic ongoing therapy. The notion of putting such patients on steroids for months and years is not appealing,” he said.

Levels of circulating plasmablasts as measured by peripheral blood flow cytometry, especially IgG4-positive plasmablasts, have proven much more helpful than serum IgG4 levels as a diagnostic tool, a reliable biomarker of disease activity, and a therapeutic target. Levels of these short-lived CD19+CD38+CD27+ plasmablasts are enormously elevated independent of serum IgG4 in patients with active IgG4-RD.

“One of the questions I’m most often asked is whether IgG4-related disease is a premalignant condition. My answer is no. The plasmablast expansion is oligoclonal, not polyclonal,” Dr. Stone continued.

He described IgG4-RD as “a continuous dance between T cells and B cells.” The latest thinking regarding pathogenesis is that type 2 T follicular helper cells activate B cells, which become memory B cells or plasmablasts. These activated B cells and plasmablasts present antigen to CD4+ cytotoxic T cells at sites of disease. Dr. Stone and his coinvestigators recently identified these CD4+ cytotoxic T cells as a novel population of clonally expanded T cells with SLAMF7 as a surface marker. The cells secrete interferon-gamma, interleukin-1, and transforming growth factor-beta, all of which are capable of driving the intense fibrosis characteristic of IgG4-RD. In addition, these CD4+ cytotoxic T cells secrete granzyme B and perforin, previously thought to be released mainly by natural killer T cells.

Joint American College of Rheumatology/European League Against Rheumatism classification criteria for the disease are expected to be finalized this winter at the Third International Symposium on IgG4-Related Diseases.

Treatment with rituxumab

Glucocorticoids remain the first-line therapy in IgG4-related disease, but it’s essential to bear in mind that their long-term efficacy in this immune-mediated fibroinflammatory disease is the exception rather than the rule, Dr. Stone said at the symposium.

Dr. Stone was a coauthor of an international expert consensus statement on the treatment of IgG4-related disease (IgG4-RD), which emphasized that point (Arthritis Rheumatol. 2015 Jul;67[7]:1688-99).

“I typically start with prednisone at 40 mg/day, and there’s a dramatic response in these patients. Then I taper them off after 2-3 months. If 2-3 months doesn’t put them into a long-term sustained remission, it’s time to go to something else,” said Dr. Stone.

So what’s the next move, then, after steroids fail? Dr. Stone was a pioneer in the strikingly successful use of B cell depletion via rituximab (Rituxan) in patients with IgG4-RD. First he and his coinvestigators demonstrated that this off-label use of rituximab led to rapid clinical and histologic improvement (Ann Rheum Dis. 2015 Jun; 74[6]:1171-7), then they showed it also causes levels of circulating plasmablasts, serum IgG4, and biomarkers of fibrosis to plunge, suggesting B cell depletion may halt the destructive process of collagen deposition that characterizes this immune-related disease (Ann Rheum Dis. 2015 Dec;74[12]:2236-43). They have also reported that patients with very elevated baseline serum IgG4 levels are at more than sixfold increased risk of relapse at a median of 244 days from their first rituximab infusion (Rheumatology [Oxford]. 2016 Jun;55[6]:1000-8).

The success with rituximab is just one example of how improved understanding of the pathophysiology of IgG4-RD has opened the door to novel treatments. Dr. Stone is the lead investigator in an ongoing phase II, open-label study in which 15 patients with active IgG4-RD will receive intravenous XmAb5871 every 2 weeks for 6 months to evaluate the effect on the IgG4-RD Responder Index. XmAb5871 is a monoclonal antibody that binds to CD19 and FCgammaRIIb in order to downregulate activated B cells and plasmablasts. It is also being developed for treatment of systemic lupus erythematosus.

Dr. Stone and his coinvestigators are working on a therapeutic approach to IgG4-RD that targets antigen presentation by activated B cells to CD4+ cytotoxic T cells at sites of disease. These CD4+ cytotoxic T cells contain signaling lymphocyte activation molecule F7 (SLAMF7) as a surface marker. Elotuzumab (Empliciti), an immunostimulatory humanized monoclonal antibody targeting SLAMF7, is already on the market for treatment of multiple myeloma, he noted.

Dr. Stone reported receiving IgG4-RD-related research funding from and serving as a consultant to Genentech and Xencor, which is developing XmAb5871.

bjancin@frontlinemedcom.com

Flu activity in the United States continued to increase as half of the states reached the highest level of influenza-like illness (ILI) activity in the week ending Feb. 11, according to the Centers for Disease Control and Prevention.

For the week, the 25 states at level 10 on the CDC’s 1-10 scale of ILI activity were joined in the high range by Illinois and Kentucky at level 9 and Iowa at level 8, the CDC reported. The previous week, there were 23 states in the high range.

rfranki@frontlinemedcom.com

Flu activity in the United States continued to increase as half of the states reached the highest level of influenza-like illness (ILI) activity in the week ending Feb. 11, according to the Centers for Disease Control and Prevention.

For the week, the 25 states at level 10 on the CDC’s 1-10 scale of ILI activity were joined in the high range by Illinois and Kentucky at level 9 and Iowa at level 8, the CDC reported. The previous week, there were 23 states in the high range.

rfranki@frontlinemedcom.com

Flu activity in the United States continued to increase as half of the states reached the highest level of influenza-like illness (ILI) activity in the week ending Feb. 11, according to the Centers for Disease Control and Prevention.

For the week, the 25 states at level 10 on the CDC’s 1-10 scale of ILI activity were joined in the high range by Illinois and Kentucky at level 9 and Iowa at level 8, the CDC reported. The previous week, there were 23 states in the high range.

rfranki@frontlinemedcom.com