Take-Home Points

• TSTC-PLFD is a rare hyperextension wrist injury characterized by fracture of both the scaphoid and the capitate and rotation of the proximal bone fragment of the capitate.
• TSTC-PLFD is associated by a complex ligamentous injury of the wrist.
• Impaction of the wrist in extension seems to be the most important predictor of this injury.
• Optimal treatment for TSTC-PLFD is open reduction, anatomical alignment, and ligamentous and osseous stabilization.
• The most important complications of scaphoid and capitate fractures and PLFD are osteonecrosis and nonunion.

Trans-scaphoid transcapitate (TSTC) perilunate fracture-dislocation (PLFD) is a rare hyperextension wrist injury characterized by fracture of both the scaphoid and the capitate and rotation of the proximal bone fragment of the capitate.¹ Isolated capitate fractures with or without rotation of its proximal fragment have been well described.^2,3 Obviously, this specific type of injury represents just the osseous part of a more complex ligamentous wrist injury.^2,3

TSTC-PLFD was first described by Nicholson⁴ in 1940. In 1956, Fenton⁵ coined the term scaphocapitate syndrome, which became widely known. With PLFD, accurate diagnosis may be delayed. Usually, only the scaphoid fracture is identified by radiologic examination, and thus the severity of the injury is underestimated and appropriate treatment delayed.^3,6,7 The English literature includes only case reports and small series on this rare perilunate injury.^6-9 In this article, we report the case of an adult with TSTC-PLFD. We describe the radiographic and intraoperative findings, review the current surgical principles for reduction and stabilization of this injury, and assess the clinical and radiologic outcomes. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 32-year-old man sustained an isolated injury of his right (dominant) hand after falling from a height of 6 feet and landing on his outstretched right arm with the wrist in extension.

With the patient under general anesthesia and a humerus tourniquet applied, an external fixator was placed for spanning of the wrist joint. The dorsal aspect of the wrist joint was approached through a midline longitudinal 5-cm incision, centered over the Lister tubercle. For adequate exposure of the dorsal wrist, a flap of the dorsal capsule was raised with the apex at the triquetrum and a radial broad base, as previously described.⁹ An avulsion fracture at the insertion of the dorsal capsule to the triquetrum was observed. The dorsal surface of the hamate and lunate showed a small area of bone contusion with hemorrhagic infiltration. The scapholunate and lunotriquetral ligaments were intact. The proximal fragment of the capitate was identified deep into the space between the lunate and distal capitate fragment; the articular surface of the bone fragment was rotated 180° distally (Figure 3).

Discussion

The exact biomechanism of TSTC-PLFD is unclear. Impaction of the wrist in extension seems to be the most important predictor of this injury.^5,7,9-11 According to Stein and Siegel,¹⁰ scaphoid fractures first allow hyperextension of the wrist; the lunate and the capitate rotate dorsally, and the dorsal surface of the capitate impacts the dorsal edge of the distal radius, causing a fracture of the neck of the capitate. If the wrist continues to rotate into further hyperextension, the unsupported, proximal part of the capitate rotates 90° around itself.^9,10 When the carpus returns to neutral position, the bone fragment of the capitate rotates further, reaching a position of 180°, with its proximal articular surface facing distally. In this type of injury, the axis of rotation is transverse (radioulnar), in contrast to the perpendicular (anteroposterior) axis of rotation suggested by the initial report by Fenton.⁵ The scaphoid is fractured by impaction of the radial styloid process. Monahan and Galasko¹¹ reported a case of capitate fracture with palmar displacement and 90° rotation of the proximal bone fragment; the fragmented surface was facing dorsally. A transverse axis of rotation, as in our patient’s case, could explain this type of displacement supporting the mechanism of injury proposed by Stein and Siegel.¹⁰ Vance and colleagues⁷ described various patterns of scaphocapitate fractures and concluded that no single mechanism of injury accounts for these types of injuries. Other authors have considered scaphocapitate syndrome as a specific type of TSTC-PLFD, one that reduces either spontaneously or with manipulation.^1,3,12 Detailed evaluation of standard anteroposterior and lateral wrist radiographs can provide enough evidence for the diagnosis of this injury. Computed tomography may define further the type and extent of injury.⁷ In our patient’s case, wrist impaction caused the scaphoid and capitate fractures and the avulsion of the capsule attachment to the triquetrum. The distal fragment of the capitate subluxated dorsally in relation to the lunate. The lateral radiograph of the wrist showed its position in the lunate fossa. According to the classification of Herzberg and colleagues¹² and Mayfield and colleagues,¹³ this represents a dorsal PLFD of the greater carpal bones arc.

Conservative treatment is not recommended for PLFD because closed reduction usually is not possible, and poor functional outcomes are common. Instead, optimal treatment is open reduction, anatomical alignment, and ligamentous and osseous stabilization.^7,12,14,15 Dorsal, palmar, and combined approaches have been used in surgery for perilunate injuries. A dorsal approach through a radius-based capsular flap allows excellent exposure of the dorsal wrist and facilitates reduction of fractures.⁹ Capitate reduction should precede scaphoid reduction because scaphoid reduction cannot be easily maintained, especially when the fracture interface is comminuted.⁷ In addition, scaphoid reduction may be guided from the radial surface of the capitate. Moreover, when the scaphoid is fixated first, reduction of the rotated head of the capitate usually is difficult. In our patient’s case, traction applied through the external fixator facilitated reduction and K-wire fixation of the capitate fracture. After scaphoid fixation, the K-wires were advanced through the capitate to the lunate to stabilize the capitolunate joint. The wrist must be immobilized for 6 to 8 weeks after surgical repair of PLFD. A cast can be used, but, as with our patient, an external fixator facilitates fracture reduction and wrist stability during osteosynthesis. During immobilization, the wrist should be maintained in neutral position to avoid stretching the dorsal and palmar wrist capsule and ligaments.¹⁶The most important complications of scaphoid and capitate fractures and PLFD are osteonecrosis and nonunion.^17-20 Similar to scaphoid fractures, capitate fractures proximal to the waist of the capitate are associated with increased risk of osteonecrosis. Therefore, anatomical reduction and stabilization favor revascularization of the proximal bone fragment. Moreover, any osteonecrosis that occurs in the proximal part of the capitate is not an indication for further surgery as long as wrist height is maintained. Nonunion is not common after open reduction and internal fixation of PLFD (eg, our patient’s fractures healed completely).¹⁷ Radiographically, nonunion is characterized by bone absorption and sclerosis of the ends of the bone. Treatment of capitate nonunion depends on symptom severity, bone fragment size, and radiographic evidence of arthritic changes.^3,7,21-23 Treatment options include resection of sclerotic edges, bone grafting, and stabilization²¹ and removal of the proximal capitate fragment and limited arthrodesis,²² as arthritic changes likely are inevitable.^22,23TSTC-PLFD is a rare wrist injury. Careful radiographic evaluation of the carpal bones and their relationships on both anteroposterior and lateral views is mandatory in making the correct diagnosis. Open reduction (preferably with use of an external fixator) and internal fixation are recommended for optimal healing and functional outcomes.

Am J Orthop. 2017;46(4):E230-E234. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• TSTC-PLFD is a rare hyperextension wrist injury characterized by fracture of both the scaphoid and the capitate and rotation of the proximal bone fragment of the capitate.
• TSTC-PLFD is associated by a complex ligamentous injury of the wrist.
• Impaction of the wrist in extension seems to be the most important predictor of this injury.
• Optimal treatment for TSTC-PLFD is open reduction, anatomical alignment, and ligamentous and osseous stabilization.
• The most important complications of scaphoid and capitate fractures and PLFD are osteonecrosis and nonunion.

Trans-scaphoid transcapitate (TSTC) perilunate fracture-dislocation (PLFD) is a rare hyperextension wrist injury characterized by fracture of both the scaphoid and the capitate and rotation of the proximal bone fragment of the capitate.¹ Isolated capitate fractures with or without rotation of its proximal fragment have been well described.^2,3 Obviously, this specific type of injury represents just the osseous part of a more complex ligamentous wrist injury.^2,3

TSTC-PLFD was first described by Nicholson⁴ in 1940. In 1956, Fenton⁵ coined the term scaphocapitate syndrome, which became widely known. With PLFD, accurate diagnosis may be delayed. Usually, only the scaphoid fracture is identified by radiologic examination, and thus the severity of the injury is underestimated and appropriate treatment delayed.^3,6,7 The English literature includes only case reports and small series on this rare perilunate injury.^6-9 In this article, we report the case of an adult with TSTC-PLFD. We describe the radiographic and intraoperative findings, review the current surgical principles for reduction and stabilization of this injury, and assess the clinical and radiologic outcomes. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 32-year-old man sustained an isolated injury of his right (dominant) hand after falling from a height of 6 feet and landing on his outstretched right arm with the wrist in extension.

With the patient under general anesthesia and a humerus tourniquet applied, an external fixator was placed for spanning of the wrist joint. The dorsal aspect of the wrist joint was approached through a midline longitudinal 5-cm incision, centered over the Lister tubercle. For adequate exposure of the dorsal wrist, a flap of the dorsal capsule was raised with the apex at the triquetrum and a radial broad base, as previously described.⁹ An avulsion fracture at the insertion of the dorsal capsule to the triquetrum was observed. The dorsal surface of the hamate and lunate showed a small area of bone contusion with hemorrhagic infiltration. The scapholunate and lunotriquetral ligaments were intact. The proximal fragment of the capitate was identified deep into the space between the lunate and distal capitate fragment; the articular surface of the bone fragment was rotated 180° distally (Figure 3).

Discussion

The exact biomechanism of TSTC-PLFD is unclear. Impaction of the wrist in extension seems to be the most important predictor of this injury.^5,7,9-11 According to Stein and Siegel,¹⁰ scaphoid fractures first allow hyperextension of the wrist; the lunate and the capitate rotate dorsally, and the dorsal surface of the capitate impacts the dorsal edge of the distal radius, causing a fracture of the neck of the capitate. If the wrist continues to rotate into further hyperextension, the unsupported, proximal part of the capitate rotates 90° around itself.^9,10 When the carpus returns to neutral position, the bone fragment of the capitate rotates further, reaching a position of 180°, with its proximal articular surface facing distally. In this type of injury, the axis of rotation is transverse (radioulnar), in contrast to the perpendicular (anteroposterior) axis of rotation suggested by the initial report by Fenton.⁵ The scaphoid is fractured by impaction of the radial styloid process. Monahan and Galasko¹¹ reported a case of capitate fracture with palmar displacement and 90° rotation of the proximal bone fragment; the fragmented surface was facing dorsally. A transverse axis of rotation, as in our patient’s case, could explain this type of displacement supporting the mechanism of injury proposed by Stein and Siegel.¹⁰ Vance and colleagues⁷ described various patterns of scaphocapitate fractures and concluded that no single mechanism of injury accounts for these types of injuries. Other authors have considered scaphocapitate syndrome as a specific type of TSTC-PLFD, one that reduces either spontaneously or with manipulation.^1,3,12 Detailed evaluation of standard anteroposterior and lateral wrist radiographs can provide enough evidence for the diagnosis of this injury. Computed tomography may define further the type and extent of injury.⁷ In our patient’s case, wrist impaction caused the scaphoid and capitate fractures and the avulsion of the capsule attachment to the triquetrum. The distal fragment of the capitate subluxated dorsally in relation to the lunate. The lateral radiograph of the wrist showed its position in the lunate fossa. According to the classification of Herzberg and colleagues¹² and Mayfield and colleagues,¹³ this represents a dorsal PLFD of the greater carpal bones arc.

Conservative treatment is not recommended for PLFD because closed reduction usually is not possible, and poor functional outcomes are common. Instead, optimal treatment is open reduction, anatomical alignment, and ligamentous and osseous stabilization.^7,12,14,15 Dorsal, palmar, and combined approaches have been used in surgery for perilunate injuries. A dorsal approach through a radius-based capsular flap allows excellent exposure of the dorsal wrist and facilitates reduction of fractures.⁹ Capitate reduction should precede scaphoid reduction because scaphoid reduction cannot be easily maintained, especially when the fracture interface is comminuted.⁷ In addition, scaphoid reduction may be guided from the radial surface of the capitate. Moreover, when the scaphoid is fixated first, reduction of the rotated head of the capitate usually is difficult. In our patient’s case, traction applied through the external fixator facilitated reduction and K-wire fixation of the capitate fracture. After scaphoid fixation, the K-wires were advanced through the capitate to the lunate to stabilize the capitolunate joint. The wrist must be immobilized for 6 to 8 weeks after surgical repair of PLFD. A cast can be used, but, as with our patient, an external fixator facilitates fracture reduction and wrist stability during osteosynthesis. During immobilization, the wrist should be maintained in neutral position to avoid stretching the dorsal and palmar wrist capsule and ligaments.¹⁶The most important complications of scaphoid and capitate fractures and PLFD are osteonecrosis and nonunion.^17-20 Similar to scaphoid fractures, capitate fractures proximal to the waist of the capitate are associated with increased risk of osteonecrosis. Therefore, anatomical reduction and stabilization favor revascularization of the proximal bone fragment. Moreover, any osteonecrosis that occurs in the proximal part of the capitate is not an indication for further surgery as long as wrist height is maintained. Nonunion is not common after open reduction and internal fixation of PLFD (eg, our patient’s fractures healed completely).¹⁷ Radiographically, nonunion is characterized by bone absorption and sclerosis of the ends of the bone. Treatment of capitate nonunion depends on symptom severity, bone fragment size, and radiographic evidence of arthritic changes.^3,7,21-23 Treatment options include resection of sclerotic edges, bone grafting, and stabilization²¹ and removal of the proximal capitate fragment and limited arthrodesis,²² as arthritic changes likely are inevitable.^22,23TSTC-PLFD is a rare wrist injury. Careful radiographic evaluation of the carpal bones and their relationships on both anteroposterior and lateral views is mandatory in making the correct diagnosis. Open reduction (preferably with use of an external fixator) and internal fixation are recommended for optimal healing and functional outcomes.

Am J Orthop. 2017;46(4):E230-E234. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• TSTC-PLFD is a rare hyperextension wrist injury characterized by fracture of both the scaphoid and the capitate and rotation of the proximal bone fragment of the capitate.
• TSTC-PLFD is associated by a complex ligamentous injury of the wrist.
• Impaction of the wrist in extension seems to be the most important predictor of this injury.
• Optimal treatment for TSTC-PLFD is open reduction, anatomical alignment, and ligamentous and osseous stabilization.
• The most important complications of scaphoid and capitate fractures and PLFD are osteonecrosis and nonunion.

Trans-scaphoid transcapitate (TSTC) perilunate fracture-dislocation (PLFD) is a rare hyperextension wrist injury characterized by fracture of both the scaphoid and the capitate and rotation of the proximal bone fragment of the capitate.¹ Isolated capitate fractures with or without rotation of its proximal fragment have been well described.^2,3 Obviously, this specific type of injury represents just the osseous part of a more complex ligamentous wrist injury.^2,3

TSTC-PLFD was first described by Nicholson⁴ in 1940. In 1956, Fenton⁵ coined the term scaphocapitate syndrome, which became widely known. With PLFD, accurate diagnosis may be delayed. Usually, only the scaphoid fracture is identified by radiologic examination, and thus the severity of the injury is underestimated and appropriate treatment delayed.^3,6,7 The English literature includes only case reports and small series on this rare perilunate injury.^6-9 In this article, we report the case of an adult with TSTC-PLFD. We describe the radiographic and intraoperative findings, review the current surgical principles for reduction and stabilization of this injury, and assess the clinical and radiologic outcomes. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 32-year-old man sustained an isolated injury of his right (dominant) hand after falling from a height of 6 feet and landing on his outstretched right arm with the wrist in extension.

With the patient under general anesthesia and a humerus tourniquet applied, an external fixator was placed for spanning of the wrist joint. The dorsal aspect of the wrist joint was approached through a midline longitudinal 5-cm incision, centered over the Lister tubercle. For adequate exposure of the dorsal wrist, a flap of the dorsal capsule was raised with the apex at the triquetrum and a radial broad base, as previously described.⁹ An avulsion fracture at the insertion of the dorsal capsule to the triquetrum was observed. The dorsal surface of the hamate and lunate showed a small area of bone contusion with hemorrhagic infiltration. The scapholunate and lunotriquetral ligaments were intact. The proximal fragment of the capitate was identified deep into the space between the lunate and distal capitate fragment; the articular surface of the bone fragment was rotated 180° distally (Figure 3).

Discussion

The exact biomechanism of TSTC-PLFD is unclear. Impaction of the wrist in extension seems to be the most important predictor of this injury.^5,7,9-11 According to Stein and Siegel,¹⁰ scaphoid fractures first allow hyperextension of the wrist; the lunate and the capitate rotate dorsally, and the dorsal surface of the capitate impacts the dorsal edge of the distal radius, causing a fracture of the neck of the capitate. If the wrist continues to rotate into further hyperextension, the unsupported, proximal part of the capitate rotates 90° around itself.^9,10 When the carpus returns to neutral position, the bone fragment of the capitate rotates further, reaching a position of 180°, with its proximal articular surface facing distally. In this type of injury, the axis of rotation is transverse (radioulnar), in contrast to the perpendicular (anteroposterior) axis of rotation suggested by the initial report by Fenton.⁵ The scaphoid is fractured by impaction of the radial styloid process. Monahan and Galasko¹¹ reported a case of capitate fracture with palmar displacement and 90° rotation of the proximal bone fragment; the fragmented surface was facing dorsally. A transverse axis of rotation, as in our patient’s case, could explain this type of displacement supporting the mechanism of injury proposed by Stein and Siegel.¹⁰ Vance and colleagues⁷ described various patterns of scaphocapitate fractures and concluded that no single mechanism of injury accounts for these types of injuries. Other authors have considered scaphocapitate syndrome as a specific type of TSTC-PLFD, one that reduces either spontaneously or with manipulation.^1,3,12 Detailed evaluation of standard anteroposterior and lateral wrist radiographs can provide enough evidence for the diagnosis of this injury. Computed tomography may define further the type and extent of injury.⁷ In our patient’s case, wrist impaction caused the scaphoid and capitate fractures and the avulsion of the capsule attachment to the triquetrum. The distal fragment of the capitate subluxated dorsally in relation to the lunate. The lateral radiograph of the wrist showed its position in the lunate fossa. According to the classification of Herzberg and colleagues¹² and Mayfield and colleagues,¹³ this represents a dorsal PLFD of the greater carpal bones arc.

Conservative treatment is not recommended for PLFD because closed reduction usually is not possible, and poor functional outcomes are common. Instead, optimal treatment is open reduction, anatomical alignment, and ligamentous and osseous stabilization.^7,12,14,15 Dorsal, palmar, and combined approaches have been used in surgery for perilunate injuries. A dorsal approach through a radius-based capsular flap allows excellent exposure of the dorsal wrist and facilitates reduction of fractures.⁹ Capitate reduction should precede scaphoid reduction because scaphoid reduction cannot be easily maintained, especially when the fracture interface is comminuted.⁷ In addition, scaphoid reduction may be guided from the radial surface of the capitate. Moreover, when the scaphoid is fixated first, reduction of the rotated head of the capitate usually is difficult. In our patient’s case, traction applied through the external fixator facilitated reduction and K-wire fixation of the capitate fracture. After scaphoid fixation, the K-wires were advanced through the capitate to the lunate to stabilize the capitolunate joint. The wrist must be immobilized for 6 to 8 weeks after surgical repair of PLFD. A cast can be used, but, as with our patient, an external fixator facilitates fracture reduction and wrist stability during osteosynthesis. During immobilization, the wrist should be maintained in neutral position to avoid stretching the dorsal and palmar wrist capsule and ligaments.¹⁶The most important complications of scaphoid and capitate fractures and PLFD are osteonecrosis and nonunion.^17-20 Similar to scaphoid fractures, capitate fractures proximal to the waist of the capitate are associated with increased risk of osteonecrosis. Therefore, anatomical reduction and stabilization favor revascularization of the proximal bone fragment. Moreover, any osteonecrosis that occurs in the proximal part of the capitate is not an indication for further surgery as long as wrist height is maintained. Nonunion is not common after open reduction and internal fixation of PLFD (eg, our patient’s fractures healed completely).¹⁷ Radiographically, nonunion is characterized by bone absorption and sclerosis of the ends of the bone. Treatment of capitate nonunion depends on symptom severity, bone fragment size, and radiographic evidence of arthritic changes.^3,7,21-23 Treatment options include resection of sclerotic edges, bone grafting, and stabilization²¹ and removal of the proximal capitate fragment and limited arthrodesis,²² as arthritic changes likely are inevitable.^22,23TSTC-PLFD is a rare wrist injury. Careful radiographic evaluation of the carpal bones and their relationships on both anteroposterior and lateral views is mandatory in making the correct diagnosis. Open reduction (preferably with use of an external fixator) and internal fixation are recommended for optimal healing and functional outcomes.

Am J Orthop. 2017;46(4):E230-E234. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Image by Dr Graham Beards

Computer models have revealed new details of what happens inside a red blood cell affected by sickle cell disease (SCD), according to research published in Biophysical Journal.

In patients with SCD, mutated hemoglobin can polymerize, assembling into long fibers that push against the membranes of red blood cells and force them out of shape.

“The goal of our work is to model both how these sickle hemoglobin fibers form as well as the mechanical properties of those fibers,” said study author Lu Lu, a PhD student at Brown University in Providence, Rhode Island.

“There had been separate models for each of these things individually developed by us, but this brings those together into one comprehensive model.”

The model uses detailed biomechanical data on how sickle hemoglobin molecules behave and bind with each other to simulate the assembly of a polymer fiber.

Prior to this work, the problem had been that, as the fiber grows, so does the amount of data the model must crunch. Modeling an entire polymer fiber at a cellular scale using the details of each molecule was simply too computationally expensive.

“Even the world’s fastest supercomputers wouldn’t be able to handle it,” said study author George Karniadakis, PhD, of Brown University.

“There’s just too much happening and no way to capture it all computationally. That’s what we were able to overcome with this work.”

The researchers’ solution was to apply what they call a mesoscopic adaptive resolution scheme (MARS).

The MARS model calculates the detailed dynamics of each individual hemoglobin molecule only at the end of polymer fibers, where new molecules are being recruited into the fiber.

Once 4 layers of a fiber have been established, the model automatically dials back the resolution at which it represents that section. The model retains the important information about how the fiber behaves mechanically but glosses over the fine details of each constituent molecule.

“By eliminating the fine details where we don’t need them, we develop a model that can simulate this whole process and its effects on a red blood cell,” Dr Karniadakis said.

Using the new MARS simulations, the researchers were able to show how different configurations of growing polymer fibers are able to produce cells with different shapes.

“We are able to produce a polymerization profile for each of the cell types associated with the disease,” Dr Karniadakis said. “Now, the goal is to use these models to look for ways of preventing the disease onset.”

Using these new models, Dr Karniadakis and his colleagues can run simulations that include fetal hemoglobin. Those simulations could be used to confirm the theory that fetal hemoglobin disrupts polymerization, as well as determine how much fetal hemoglobin is necessary.

That could help in establishing better dosage guidelines for hydroxyurea or in developing new and more effective drugs for SCD, according to the researchers.

“The models give us a way to do preliminary testing on new approaches to stopping this disease,” Dr Karniadakis said. “Now that we can simulate the entire polymerization process, we think the models will be much more useful.”

Image by Dr Graham Beards

Computer models have revealed new details of what happens inside a red blood cell affected by sickle cell disease (SCD), according to research published in Biophysical Journal.

In patients with SCD, mutated hemoglobin can polymerize, assembling into long fibers that push against the membranes of red blood cells and force them out of shape.

“The goal of our work is to model both how these sickle hemoglobin fibers form as well as the mechanical properties of those fibers,” said study author Lu Lu, a PhD student at Brown University in Providence, Rhode Island.

“There had been separate models for each of these things individually developed by us, but this brings those together into one comprehensive model.”

The model uses detailed biomechanical data on how sickle hemoglobin molecules behave and bind with each other to simulate the assembly of a polymer fiber.

Prior to this work, the problem had been that, as the fiber grows, so does the amount of data the model must crunch. Modeling an entire polymer fiber at a cellular scale using the details of each molecule was simply too computationally expensive.

“Even the world’s fastest supercomputers wouldn’t be able to handle it,” said study author George Karniadakis, PhD, of Brown University.

“There’s just too much happening and no way to capture it all computationally. That’s what we were able to overcome with this work.”

The researchers’ solution was to apply what they call a mesoscopic adaptive resolution scheme (MARS).

The MARS model calculates the detailed dynamics of each individual hemoglobin molecule only at the end of polymer fibers, where new molecules are being recruited into the fiber.

Once 4 layers of a fiber have been established, the model automatically dials back the resolution at which it represents that section. The model retains the important information about how the fiber behaves mechanically but glosses over the fine details of each constituent molecule.

“By eliminating the fine details where we don’t need them, we develop a model that can simulate this whole process and its effects on a red blood cell,” Dr Karniadakis said.

Using the new MARS simulations, the researchers were able to show how different configurations of growing polymer fibers are able to produce cells with different shapes.

“We are able to produce a polymerization profile for each of the cell types associated with the disease,” Dr Karniadakis said. “Now, the goal is to use these models to look for ways of preventing the disease onset.”

Using these new models, Dr Karniadakis and his colleagues can run simulations that include fetal hemoglobin. Those simulations could be used to confirm the theory that fetal hemoglobin disrupts polymerization, as well as determine how much fetal hemoglobin is necessary.

That could help in establishing better dosage guidelines for hydroxyurea or in developing new and more effective drugs for SCD, according to the researchers.

“The models give us a way to do preliminary testing on new approaches to stopping this disease,” Dr Karniadakis said. “Now that we can simulate the entire polymerization process, we think the models will be much more useful.”

Image by Dr Graham Beards

Computer models have revealed new details of what happens inside a red blood cell affected by sickle cell disease (SCD), according to research published in Biophysical Journal.

In patients with SCD, mutated hemoglobin can polymerize, assembling into long fibers that push against the membranes of red blood cells and force them out of shape.

“The goal of our work is to model both how these sickle hemoglobin fibers form as well as the mechanical properties of those fibers,” said study author Lu Lu, a PhD student at Brown University in Providence, Rhode Island.

“There had been separate models for each of these things individually developed by us, but this brings those together into one comprehensive model.”

The model uses detailed biomechanical data on how sickle hemoglobin molecules behave and bind with each other to simulate the assembly of a polymer fiber.

Prior to this work, the problem had been that, as the fiber grows, so does the amount of data the model must crunch. Modeling an entire polymer fiber at a cellular scale using the details of each molecule was simply too computationally expensive.

“Even the world’s fastest supercomputers wouldn’t be able to handle it,” said study author George Karniadakis, PhD, of Brown University.

“There’s just too much happening and no way to capture it all computationally. That’s what we were able to overcome with this work.”

The researchers’ solution was to apply what they call a mesoscopic adaptive resolution scheme (MARS).

The MARS model calculates the detailed dynamics of each individual hemoglobin molecule only at the end of polymer fibers, where new molecules are being recruited into the fiber.

Once 4 layers of a fiber have been established, the model automatically dials back the resolution at which it represents that section. The model retains the important information about how the fiber behaves mechanically but glosses over the fine details of each constituent molecule.

“By eliminating the fine details where we don’t need them, we develop a model that can simulate this whole process and its effects on a red blood cell,” Dr Karniadakis said.

Using the new MARS simulations, the researchers were able to show how different configurations of growing polymer fibers are able to produce cells with different shapes.

“We are able to produce a polymerization profile for each of the cell types associated with the disease,” Dr Karniadakis said. “Now, the goal is to use these models to look for ways of preventing the disease onset.”

Using these new models, Dr Karniadakis and his colleagues can run simulations that include fetal hemoglobin. Those simulations could be used to confirm the theory that fetal hemoglobin disrupts polymerization, as well as determine how much fetal hemoglobin is necessary.

That could help in establishing better dosage guidelines for hydroxyurea or in developing new and more effective drugs for SCD, according to the researchers.

“The models give us a way to do preliminary testing on new approaches to stopping this disease,” Dr Karniadakis said. “Now that we can simulate the entire polymerization process, we think the models will be much more useful.”

Photo courtesy of Abbvie

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to venetoclax (Venclexta®).

The designation is for venetoclax in combination with low-dose cytarabine to treat elderly patients with previously untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.

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

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

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

About venetoclax

Venetoclax is a small molecule designed to selectively bind and inhibit the BCL-2 protein. The drug is being developed by AbbVie and Roche.

Last year, the FDA granted venetoclax accelerated approval to treat patients with chronic lymphocytic leukemia who have 17p deletion and have received at least one prior therapy. Continued approval of venetoclax for this indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA granted venetoclax breakthrough therapy designation for the AML indication based on data from an ongoing phase 1/2 study. Preliminary data from the study were presented at the 22nd European Hematology Association (EHA) Annual Congress.

The presentation included data on 61 elderly patients (older than 65) with previously untreated AML who were ineligible for intensive chemotherapy.

They received venetoclax in combination with low-dose cytarabine (as well as prophylaxis for tumor lysis syndrome). The patients’ median time on treatment was 6 months (range, <1 to 19 months), and 72% of patients discontinued treatment.

The overall response rate was 65%. Twenty-five percent of patients achieved a complete response, 38% had a complete response with incomplete blood count recovery, and 2% had a partial response.

The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.

The most common adverse events of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).

Grade 3/4 adverse events (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), anemia (28%), hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).

Photo courtesy of Abbvie

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to venetoclax (Venclexta®).

The designation is for venetoclax in combination with low-dose cytarabine to treat elderly patients with previously untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.

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

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

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

About venetoclax

Venetoclax is a small molecule designed to selectively bind and inhibit the BCL-2 protein. The drug is being developed by AbbVie and Roche.

Last year, the FDA granted venetoclax accelerated approval to treat patients with chronic lymphocytic leukemia who have 17p deletion and have received at least one prior therapy. Continued approval of venetoclax for this indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA granted venetoclax breakthrough therapy designation for the AML indication based on data from an ongoing phase 1/2 study. Preliminary data from the study were presented at the 22nd European Hematology Association (EHA) Annual Congress.

The presentation included data on 61 elderly patients (older than 65) with previously untreated AML who were ineligible for intensive chemotherapy.

They received venetoclax in combination with low-dose cytarabine (as well as prophylaxis for tumor lysis syndrome). The patients’ median time on treatment was 6 months (range, <1 to 19 months), and 72% of patients discontinued treatment.

The overall response rate was 65%. Twenty-five percent of patients achieved a complete response, 38% had a complete response with incomplete blood count recovery, and 2% had a partial response.

The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.

The most common adverse events of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).

Grade 3/4 adverse events (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), anemia (28%), hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).

Photo courtesy of Abbvie

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to venetoclax (Venclexta®).

The designation is for venetoclax in combination with low-dose cytarabine to treat elderly patients with previously untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.

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

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

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

About venetoclax

Venetoclax is a small molecule designed to selectively bind and inhibit the BCL-2 protein. The drug is being developed by AbbVie and Roche.

Last year, the FDA granted venetoclax accelerated approval to treat patients with chronic lymphocytic leukemia who have 17p deletion and have received at least one prior therapy. Continued approval of venetoclax for this indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA granted venetoclax breakthrough therapy designation for the AML indication based on data from an ongoing phase 1/2 study. Preliminary data from the study were presented at the 22nd European Hematology Association (EHA) Annual Congress.

The presentation included data on 61 elderly patients (older than 65) with previously untreated AML who were ineligible for intensive chemotherapy.

They received venetoclax in combination with low-dose cytarabine (as well as prophylaxis for tumor lysis syndrome). The patients’ median time on treatment was 6 months (range, <1 to 19 months), and 72% of patients discontinued treatment.

The overall response rate was 65%. Twenty-five percent of patients achieved a complete response, 38% had a complete response with incomplete blood count recovery, and 2% had a partial response.

The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.

The most common adverse events of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).

Grade 3/4 adverse events (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), anemia (28%), hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).

Haemonetics Corporation

The US Food and Drug Administration (FDA) has granted 510(k) clearance for Haemonetics Corporation’s NexSys PCS™ plasmapheresis system.

The open architecture of NexSys PCS facilitates bi-directional connectivity to donor management systems, enabling automated collection procedure programming and automated end-of-procedure documentation.

The guided operation, large touch screen, and on-screen troubleshooting assistance on NexSys PCS are designed to improve plasma center efficiency. The goal is to reduce donors’ time in centers and improve the centers’ collection capacity.

“NexSys PCS is designed to increase productivity and improve quality and compliance in plasma collection centers,” said Christopher Simon, CEO of Haemonetics.

“Each of these benefits is noteworthy and, when combined, we believe will unlock meaningful value for our customers.”

Haemonetics plans to begin limited production of NexSys PCS devices immediately and to pursue further regulatory clearances for additional enhancements to the overall product offering.

NexSys PCS was previously referred to as PCS 300. 

Haemonetics Corporation

The US Food and Drug Administration (FDA) has granted 510(k) clearance for Haemonetics Corporation’s NexSys PCS™ plasmapheresis system.

The open architecture of NexSys PCS facilitates bi-directional connectivity to donor management systems, enabling automated collection procedure programming and automated end-of-procedure documentation.

The guided operation, large touch screen, and on-screen troubleshooting assistance on NexSys PCS are designed to improve plasma center efficiency. The goal is to reduce donors’ time in centers and improve the centers’ collection capacity.

“NexSys PCS is designed to increase productivity and improve quality and compliance in plasma collection centers,” said Christopher Simon, CEO of Haemonetics.

“Each of these benefits is noteworthy and, when combined, we believe will unlock meaningful value for our customers.”

Haemonetics plans to begin limited production of NexSys PCS devices immediately and to pursue further regulatory clearances for additional enhancements to the overall product offering.

NexSys PCS was previously referred to as PCS 300. 

Haemonetics Corporation

The US Food and Drug Administration (FDA) has granted 510(k) clearance for Haemonetics Corporation’s NexSys PCS™ plasmapheresis system.

The open architecture of NexSys PCS facilitates bi-directional connectivity to donor management systems, enabling automated collection procedure programming and automated end-of-procedure documentation.

The guided operation, large touch screen, and on-screen troubleshooting assistance on NexSys PCS are designed to improve plasma center efficiency. The goal is to reduce donors’ time in centers and improve the centers’ collection capacity.

“NexSys PCS is designed to increase productivity and improve quality and compliance in plasma collection centers,” said Christopher Simon, CEO of Haemonetics.

“Each of these benefits is noteworthy and, when combined, we believe will unlock meaningful value for our customers.”

Haemonetics plans to begin limited production of NexSys PCS devices immediately and to pursue further regulatory clearances for additional enhancements to the overall product offering.

NexSys PCS was previously referred to as PCS 300. 

The questioning of former FBI director James B. Comey by Sen. John McCain (R-Ariz.) during a June 8 Senate Intelligence Committee hearing raised more than a few eyebrows; Sen. McCain seemed confused and disoriented, at one point referring to Mr. Comey as “President Comey,” but a possible medical explanation emerged soon after.

On July 14, Sen. McCain, 80, underwent surgery to remove a 5-cm blood clot that had been discovered above his left eye during a physical, and on July 19, the Mayo Clinic in Phoenix, where he had undergone the procedure, announced at his request that, “subsequent tissue pathology revealed that a primary brain tumor known as a glioblastoma was associated with the blood clot.”
 

Glioblastoma features

While Sen. McCain’s symptoms can’t necessarily be attributed to the glioblastoma, it is not unusual for glioblastoma patients to present with some sort of neurologic deficit, such as speech issues, unilateral weakness, or confusion, according to Eudocia Quant Lee, MD, a neuro-oncologist at Dana-Farber Cancer Institute, Boston.

Prognosis and age

“We know, in general – as with most cancers – that the older you’re diagnosed with your cancer, the poorer your prognosis is,” she said, adding that other health issues and the ability to tolerate treatment can affect outcomes.

Outcomes also can be affected by type of surgery, functional status, extent of treatment, and molecular subtypes of the glioblastoma, Dr. Ahluwalia said.

Survival generally ranges about 14-18 months, although about 10% of patients live 5 years or longer.

Standard treatment approaches

The first step in the treatment of glioblastomas is maximal safe therapy, Dr. Lee said.

“You want to achieve as much of a resection as possible without leaving the patient with some sort of permanent neurologic deficit that could severely compromise the quality of their life,” she explained.

Sen. McCain’s tumor was “completely resected by imaging criteria,” according to the Mayo Clinic statement, which also noted that treatment options might include a combination of chemotherapy and radiation.

Indeed, the standard of care for glioblastomas after surgery is combined chemotherapy and radiation – typically given as approximately 6 weeks of radiation combined with oral temozolomide chemotherapy – followed by 6 monthly cycles of temozolomide, she explained.

Radiation is sometimes given for only 3 weeks, but this option is mainly reserved for elderly patients, she said, adding that trials in patients aged 65-70 years have shown that this shorter course of radiation can be equally effective but potentially less toxic.
 

Emerging treatment approaches

Another treatment that has shown promise involves the use of tumor-treating fields (TTFields) – a locoregionally delivered antimitotic treatment that disrupts cell division and organelle assembly.

A 2015 phase 3 trial showed that adding TTFields to maintenance temozolomide significantly prolonged progression-free and overall survival, Dr. Ahluwalia said.

Other studies, including two presented during poster sessions at the ASCO annual meeting, have shown a progression-free survival benefit with the addition of bevacizumab to the treatment regimen. One open-label phase 2 study showed that hypofractionated radiotherapy in combination with IV bevacizumab every 2 weeks vs. radiotherapy alone in newly diagnosed patients over age 65 years improved progression-free survival (median, 7.6 vs. 4.8 months), but not overall survival (median, 12.1 vs. 12.2 months).

Another phase 2 study presented by Phioanh (Leia) Nghiemphu, MD, of the University of California, Los Angeles, showed that in newly diagnosed patients aged 70 years and older, upfront treatment with bevacizumab and temozolomide was associated with promising survival benefits (overall survival, 12.3 months; progression-free survival, 5.1 months) and tolerable side effects. The best survival in multivariate analysis was in patients who received radiotherapy at progression; it was unclear whether the addition of bevacizumab led to a survival advantage, but it may have allowed delay of radiotherapy treatment, she noted.

“Although we have no cure for glioblastoma, treatments can control tumor growth for a period of time, and there are additional promising therapies emerging every day to treat this deadly cancer, she said in an interview. “There has been increasing interest in developing better therapies for the older patients with glioblastoma with less toxicity and still-robust survival, such as the addition of bevacizumab or a short course of radiotherapy with temozolomide chemotherapy.”

Dr. Ahluwalia encourages clinical trial participation for patients diagnosed with glioblastoma and noted that he is particularly excited about immunotherapy and targeted therapy trials.

Dr. Lee has served as consultant to Eli Lilly. Dr. Ahluwalia disclosed a financial relationship with multiple companies, including Novocure, which markets a TTFields device. Dr. Weller disclosed a financial relationships with multiple companies, including Novocure; Merck Sharp & Dohme, which markets temozolomide; and Roche, which markets bevacizumab. Dr. Nghiemphu has received research funding from Genentech/Roche and Novartis. Dr. Mohapatra reporting having no disclosures.

[email protected]

The questioning of former FBI director James B. Comey by Sen. John McCain (R-Ariz.) during a June 8 Senate Intelligence Committee hearing raised more than a few eyebrows; Sen. McCain seemed confused and disoriented, at one point referring to Mr. Comey as “President Comey,” but a possible medical explanation emerged soon after.

On July 14, Sen. McCain, 80, underwent surgery to remove a 5-cm blood clot that had been discovered above his left eye during a physical, and on July 19, the Mayo Clinic in Phoenix, where he had undergone the procedure, announced at his request that, “subsequent tissue pathology revealed that a primary brain tumor known as a glioblastoma was associated with the blood clot.”
 

Glioblastoma features

While Sen. McCain’s symptoms can’t necessarily be attributed to the glioblastoma, it is not unusual for glioblastoma patients to present with some sort of neurologic deficit, such as speech issues, unilateral weakness, or confusion, according to Eudocia Quant Lee, MD, a neuro-oncologist at Dana-Farber Cancer Institute, Boston.

Prognosis and age

“We know, in general – as with most cancers – that the older you’re diagnosed with your cancer, the poorer your prognosis is,” she said, adding that other health issues and the ability to tolerate treatment can affect outcomes.

Outcomes also can be affected by type of surgery, functional status, extent of treatment, and molecular subtypes of the glioblastoma, Dr. Ahluwalia said.

Survival generally ranges about 14-18 months, although about 10% of patients live 5 years or longer.

Standard treatment approaches

The first step in the treatment of glioblastomas is maximal safe therapy, Dr. Lee said.

“You want to achieve as much of a resection as possible without leaving the patient with some sort of permanent neurologic deficit that could severely compromise the quality of their life,” she explained.

Sen. McCain’s tumor was “completely resected by imaging criteria,” according to the Mayo Clinic statement, which also noted that treatment options might include a combination of chemotherapy and radiation.

Indeed, the standard of care for glioblastomas after surgery is combined chemotherapy and radiation – typically given as approximately 6 weeks of radiation combined with oral temozolomide chemotherapy – followed by 6 monthly cycles of temozolomide, she explained.

Radiation is sometimes given for only 3 weeks, but this option is mainly reserved for elderly patients, she said, adding that trials in patients aged 65-70 years have shown that this shorter course of radiation can be equally effective but potentially less toxic.
 

Emerging treatment approaches

Another treatment that has shown promise involves the use of tumor-treating fields (TTFields) – a locoregionally delivered antimitotic treatment that disrupts cell division and organelle assembly.

A 2015 phase 3 trial showed that adding TTFields to maintenance temozolomide significantly prolonged progression-free and overall survival, Dr. Ahluwalia said.

Other studies, including two presented during poster sessions at the ASCO annual meeting, have shown a progression-free survival benefit with the addition of bevacizumab to the treatment regimen. One open-label phase 2 study showed that hypofractionated radiotherapy in combination with IV bevacizumab every 2 weeks vs. radiotherapy alone in newly diagnosed patients over age 65 years improved progression-free survival (median, 7.6 vs. 4.8 months), but not overall survival (median, 12.1 vs. 12.2 months).

Another phase 2 study presented by Phioanh (Leia) Nghiemphu, MD, of the University of California, Los Angeles, showed that in newly diagnosed patients aged 70 years and older, upfront treatment with bevacizumab and temozolomide was associated with promising survival benefits (overall survival, 12.3 months; progression-free survival, 5.1 months) and tolerable side effects. The best survival in multivariate analysis was in patients who received radiotherapy at progression; it was unclear whether the addition of bevacizumab led to a survival advantage, but it may have allowed delay of radiotherapy treatment, she noted.

“Although we have no cure for glioblastoma, treatments can control tumor growth for a period of time, and there are additional promising therapies emerging every day to treat this deadly cancer, she said in an interview. “There has been increasing interest in developing better therapies for the older patients with glioblastoma with less toxicity and still-robust survival, such as the addition of bevacizumab or a short course of radiotherapy with temozolomide chemotherapy.”

Dr. Ahluwalia encourages clinical trial participation for patients diagnosed with glioblastoma and noted that he is particularly excited about immunotherapy and targeted therapy trials.

Dr. Lee has served as consultant to Eli Lilly. Dr. Ahluwalia disclosed a financial relationship with multiple companies, including Novocure, which markets a TTFields device. Dr. Weller disclosed a financial relationships with multiple companies, including Novocure; Merck Sharp & Dohme, which markets temozolomide; and Roche, which markets bevacizumab. Dr. Nghiemphu has received research funding from Genentech/Roche and Novartis. Dr. Mohapatra reporting having no disclosures.

[email protected]

The questioning of former FBI director James B. Comey by Sen. John McCain (R-Ariz.) during a June 8 Senate Intelligence Committee hearing raised more than a few eyebrows; Sen. McCain seemed confused and disoriented, at one point referring to Mr. Comey as “President Comey,” but a possible medical explanation emerged soon after.

On July 14, Sen. McCain, 80, underwent surgery to remove a 5-cm blood clot that had been discovered above his left eye during a physical, and on July 19, the Mayo Clinic in Phoenix, where he had undergone the procedure, announced at his request that, “subsequent tissue pathology revealed that a primary brain tumor known as a glioblastoma was associated with the blood clot.”
 

Glioblastoma features

While Sen. McCain’s symptoms can’t necessarily be attributed to the glioblastoma, it is not unusual for glioblastoma patients to present with some sort of neurologic deficit, such as speech issues, unilateral weakness, or confusion, according to Eudocia Quant Lee, MD, a neuro-oncologist at Dana-Farber Cancer Institute, Boston.

Prognosis and age

“We know, in general – as with most cancers – that the older you’re diagnosed with your cancer, the poorer your prognosis is,” she said, adding that other health issues and the ability to tolerate treatment can affect outcomes.

Outcomes also can be affected by type of surgery, functional status, extent of treatment, and molecular subtypes of the glioblastoma, Dr. Ahluwalia said.

Survival generally ranges about 14-18 months, although about 10% of patients live 5 years or longer.

Standard treatment approaches

The first step in the treatment of glioblastomas is maximal safe therapy, Dr. Lee said.

“You want to achieve as much of a resection as possible without leaving the patient with some sort of permanent neurologic deficit that could severely compromise the quality of their life,” she explained.

Sen. McCain’s tumor was “completely resected by imaging criteria,” according to the Mayo Clinic statement, which also noted that treatment options might include a combination of chemotherapy and radiation.

Indeed, the standard of care for glioblastomas after surgery is combined chemotherapy and radiation – typically given as approximately 6 weeks of radiation combined with oral temozolomide chemotherapy – followed by 6 monthly cycles of temozolomide, she explained.

Radiation is sometimes given for only 3 weeks, but this option is mainly reserved for elderly patients, she said, adding that trials in patients aged 65-70 years have shown that this shorter course of radiation can be equally effective but potentially less toxic.
 

Emerging treatment approaches

Another treatment that has shown promise involves the use of tumor-treating fields (TTFields) – a locoregionally delivered antimitotic treatment that disrupts cell division and organelle assembly.

A 2015 phase 3 trial showed that adding TTFields to maintenance temozolomide significantly prolonged progression-free and overall survival, Dr. Ahluwalia said.

Other studies, including two presented during poster sessions at the ASCO annual meeting, have shown a progression-free survival benefit with the addition of bevacizumab to the treatment regimen. One open-label phase 2 study showed that hypofractionated radiotherapy in combination with IV bevacizumab every 2 weeks vs. radiotherapy alone in newly diagnosed patients over age 65 years improved progression-free survival (median, 7.6 vs. 4.8 months), but not overall survival (median, 12.1 vs. 12.2 months).

Another phase 2 study presented by Phioanh (Leia) Nghiemphu, MD, of the University of California, Los Angeles, showed that in newly diagnosed patients aged 70 years and older, upfront treatment with bevacizumab and temozolomide was associated with promising survival benefits (overall survival, 12.3 months; progression-free survival, 5.1 months) and tolerable side effects. The best survival in multivariate analysis was in patients who received radiotherapy at progression; it was unclear whether the addition of bevacizumab led to a survival advantage, but it may have allowed delay of radiotherapy treatment, she noted.

“Although we have no cure for glioblastoma, treatments can control tumor growth for a period of time, and there are additional promising therapies emerging every day to treat this deadly cancer, she said in an interview. “There has been increasing interest in developing better therapies for the older patients with glioblastoma with less toxicity and still-robust survival, such as the addition of bevacizumab or a short course of radiotherapy with temozolomide chemotherapy.”

Dr. Ahluwalia encourages clinical trial participation for patients diagnosed with glioblastoma and noted that he is particularly excited about immunotherapy and targeted therapy trials.

Dr. Lee has served as consultant to Eli Lilly. Dr. Ahluwalia disclosed a financial relationship with multiple companies, including Novocure, which markets a TTFields device. Dr. Weller disclosed a financial relationships with multiple companies, including Novocure; Merck Sharp & Dohme, which markets temozolomide; and Roche, which markets bevacizumab. Dr. Nghiemphu has received research funding from Genentech/Roche and Novartis. Dr. Mohapatra reporting having no disclosures.

[email protected]

EXPERT ANALYSIS FROM THE 2017 AAD SUMMER MEETING

NEW YORK – When patients come to the office with painful “bumps” on the legs or elsewhere, panniculitis should be in the differential. And for some patients, said Alina Bridges, DO, the panniculitis may come with the dire diagnosis of calciphylaxis.

Calciphylaxis is an underrecognized crystal deposition disease that’s associated with panniculitis, said Dr. Bridges, speaking at the American Academy of Dermatology summer meeting. When calcium accumulates in small subcutaneous vessels, an occlusive vasculopathy is created within the dermis.

Niels Olson/Wikimedia Commons/CC BY-SA 3.0

Courtesy RegionalDerm.com

[email protected]

On Twitter @karioakes

EXPERT ANALYSIS FROM THE 2017 AAD SUMMER MEETING

NEW YORK – When patients come to the office with painful “bumps” on the legs or elsewhere, panniculitis should be in the differential. And for some patients, said Alina Bridges, DO, the panniculitis may come with the dire diagnosis of calciphylaxis.

Calciphylaxis is an underrecognized crystal deposition disease that’s associated with panniculitis, said Dr. Bridges, speaking at the American Academy of Dermatology summer meeting. When calcium accumulates in small subcutaneous vessels, an occlusive vasculopathy is created within the dermis.

Niels Olson/Wikimedia Commons/CC BY-SA 3.0

Courtesy RegionalDerm.com

[email protected]

On Twitter @karioakes

EXPERT ANALYSIS FROM THE 2017 AAD SUMMER MEETING

NEW YORK – When patients come to the office with painful “bumps” on the legs or elsewhere, panniculitis should be in the differential. And for some patients, said Alina Bridges, DO, the panniculitis may come with the dire diagnosis of calciphylaxis.

Calciphylaxis is an underrecognized crystal deposition disease that’s associated with panniculitis, said Dr. Bridges, speaking at the American Academy of Dermatology summer meeting. When calcium accumulates in small subcutaneous vessels, an occlusive vasculopathy is created within the dermis.

Niels Olson/Wikimedia Commons/CC BY-SA 3.0

Courtesy RegionalDerm.com

[email protected]

On Twitter @karioakes

Orthopedic physicians in the highest income tax brackets may have been presented with an unpleasant surprise in recent years when they learned of their investment tax liability. A prolonged period of strong domestic stock performance from 2009 to 2016, combined with the implementation of The American Taxpayer Relief Act of 2012, may have resulted in significantly higher taxes for many of you.

The top ordinary income tax rates increased by 24% when including the Net Investment Income surtax, while the top capital gains rate was increased by more than 58%. Writing a large check to the Internal Revenue Service serves as a harsh reminder that tax planning requires attention throughout the year, and is not a technique you can properly manage a few weeks before an April 15 deadline.

Proper tax planning became more critical as we moved into an era of higher taxes. A multi-year bull market for domestic stocks has caused many traditional investment vehicles to hold large amounts of unrealized gains, which can become realized gains if you are not careful. Most major equity indices took a breath in 2015 and finished the year in the red, which created a planning opportunity for astute investors and their advisors. Stocks in the US and emerging market countries quickly bounced back in 2016; however, European stocks struggled and continue to trade well below peak levels reached nearly a decade ago. Investors who missed the opportunity to offset gains of the prior 2 years may have an opportunity to reduce their tax bill in 2017.

In this article, we will provide you with 6 suggestions that could save you thousands of dollars in investment taxes over the next several years.

1. Account Registration Matters: A common mistake investors make is the failure to implement a tax diversification strategy. Brokerage accounts, Roth IRAs, and qualified plans are subject to various forms of taxation. It is important to utilize the tax advantages of these tools to ensure they work for you in the most productive manner possible. A properly integrated approach is critical during your accumulation phase. Further, it is just as important when you enter the distribution period of your investment life cycle (ie, retirement).

Master Limited Partnerships offer a potentially advantageous income stream for a brokerage account, while it is generally preferable for qualified accounts to own high yield bonds and corporate debt, as they are taxed at ordinary income rates. There are countless additional examples we could discuss, but the lesson is simple: it is important to review the pieces of your plan with an advisor who will consider both tax diversification and security diversification as they relate to your specific circumstances.

2. Consider Owning Municipal Bonds in Taxable Accounts: Most municipal bonds are exempt from federal taxation. Certain issues may also be exempt from state and local taxes. If you are in the highest federal tax bracket, you may be paying tax on investment income at a rate of 43.4%. Under these circumstances, a municipal bond yielding 3% will provide a superior after tax return in comparison to a corporate bond yielding 5% in an individual or joint registration, a pass-through LLC, or in many trust accounts. Therefore, it is important in many circumstances to make certain your long-term plan utilizes the advantages of owning certain municipal bonds in taxable accounts.

3. Be Cognizant of Holding Periods: Long-term capital gains rates are much more favorable than short-term rates. Holding a security for a period of 12 months presents an opportunity to save nearly 20% on the taxation of your appreciated position. For example, an initial investment of $50,000 which grows to $100,000 represents a $50,000 unrealized gain. If an investor in the highest tax bracket simply delays liquidation of the position (assuming the security price does not change) the tax savings in this scenario would be $9,800. Although an awareness of the holding period of a security would appear to be a basic principal of investing, many mutual funds and managed accounts are not designed for tax sensitivity. High income investors should be aware that the average client of most advisors is not in the highest federal tax bracket. Therefore, it is generally advantageous to seek the advice of a financial professional with experience executing an appropriate exit strategy that is aware of holding periods.

4. Proactively Realize Losses to Offset Gains: As mentioned in the opening paragraphs of the article, 2015 presented investors with an opportunity to realize losses in domestic stocks for the first time in 4 years. Clients with a diversified portfolio may still have an opportunity to offset gains in domestic stocks by selling foreign equities. One benefit of diversifying across asset classes is that if the portfolio is structured properly, the securities typically will not move in tandem. This divergence of returns among asset classes not only reduces portfolio volatility, but it creates a tax planning opportunity. Domestic equities experienced tremendous appreciation over a 5-year period through 2014; however, international stocks, commodities, and multiple fixed income investments experienced down years. Astute advisors were presented with the opportunity to save clients thousands of dollars in taxes by performing strategic tax swaps prior to year-end. It is important to understand the rules relating to wash sales when executing such tactics. The laws are confusing, and if a mistake is made your loss could be disallowed. Make certain your advisor is well-versed in utilizing tax offsets.

5. Think Twice About Gifting Cash: This is not to discourage your charitable intentions. Quite the opposite is true. However, a successful investor can occasionally find themselves in a precarious position. You may have allocated 5% of your portfolio to a growth stock with significant upside. Several years have passed, the security has experienced explosive growth, and it now represents 15% of your investable assets. Suddenly your portfolio has a concentrated position with significant gains, and the level of risk is no longer consistent with your long-term objectives. The sound practice of rebalancing your portfolio then becomes very costly, because liquidation of the stock could create a taxable event that may negatively impact your net return.

By planning ahead of time, you may be able to gift a portion of the appreciated security to a charitable organization able to accept this type of donation. The value of your gift can be replaced with the cash you originally intended to donate to the charitable organization and, in this scenario, your cash will create a new cost basis. The charity can liquidate the stock without paying tax, and you have removed a future tax liability from your portfolio. Implementing the aforementioned gifting strategy offers the potential to save thousands of dollars in taxes over the life of your portfolio.

6. Understand your Mutual Fund’s Tax Cost Ratio: The technical detail behind a mutual fund’s tax cost ratio is beyond the scope of this article. Our intent is to simply bring this topic to your attention. Tax cost ratio represents the percentage of an investor’s assets that are lost to taxes. Mutual funds avoid double taxation, provided they pay at least 90% of net investment income and realized capital gains to shareholders at the end of the calendar year. But all mutual funds are not created equally, and proper research will allow you to identify funds that are tax efficient.

A well-managed mutual fund will add diversification to a portfolio while creating the opportunity to outperform asset classes with inefficient markets. You do need to be aware of funds with excessive turnover. An understanding of when a fund pays its capital gains distributions is a critical component of successful investing. A poorly timed fund purchase can result in acquiring another investor’s tax liability. It is not unusual for an investor to experience a negative return in a calendar year, yet find himself on the receiving end of a capital gains distribution. Understanding the tax cost ratios of the funds that make up portions of your investment plan will enable you to take advantage of the many benefits of owning mutual funds.

The above steps are by no means the only tax strategies experienced advisors can execute on behalf of their clients. This article highlights several strategies you should discuss with your advisor to determine if implementation is appropriate for your unique portfolio and overall financial situation. Successful investing requires discipline that extends beyond proper security selection. While gross returns are important and should not be ignored, the percentage return you see on your statements does not tell the full story.

In today’s tax environment, successful investors must choose an advisor who will help them look beyond portfolio earnings and focus on strategic after-tax asset growth.

To receive a free hardcopy of Wealth Protection Planning for Orthopaedic Surgeons, please call 877-656-4362. Visit www.ojmbookstore.com and enter promotional code AJO30 for a free ebook download of Wealth Protection Planning or one of our other ebooks for your Kindle or iPad.

Orthopedic physicians in the highest income tax brackets may have been presented with an unpleasant surprise in recent years when they learned of their investment tax liability. A prolonged period of strong domestic stock performance from 2009 to 2016, combined with the implementation of The American Taxpayer Relief Act of 2012, may have resulted in significantly higher taxes for many of you.

The top ordinary income tax rates increased by 24% when including the Net Investment Income surtax, while the top capital gains rate was increased by more than 58%. Writing a large check to the Internal Revenue Service serves as a harsh reminder that tax planning requires attention throughout the year, and is not a technique you can properly manage a few weeks before an April 15 deadline.

Proper tax planning became more critical as we moved into an era of higher taxes. A multi-year bull market for domestic stocks has caused many traditional investment vehicles to hold large amounts of unrealized gains, which can become realized gains if you are not careful. Most major equity indices took a breath in 2015 and finished the year in the red, which created a planning opportunity for astute investors and their advisors. Stocks in the US and emerging market countries quickly bounced back in 2016; however, European stocks struggled and continue to trade well below peak levels reached nearly a decade ago. Investors who missed the opportunity to offset gains of the prior 2 years may have an opportunity to reduce their tax bill in 2017.

In this article, we will provide you with 6 suggestions that could save you thousands of dollars in investment taxes over the next several years.

1. Account Registration Matters: A common mistake investors make is the failure to implement a tax diversification strategy. Brokerage accounts, Roth IRAs, and qualified plans are subject to various forms of taxation. It is important to utilize the tax advantages of these tools to ensure they work for you in the most productive manner possible. A properly integrated approach is critical during your accumulation phase. Further, it is just as important when you enter the distribution period of your investment life cycle (ie, retirement).

Master Limited Partnerships offer a potentially advantageous income stream for a brokerage account, while it is generally preferable for qualified accounts to own high yield bonds and corporate debt, as they are taxed at ordinary income rates. There are countless additional examples we could discuss, but the lesson is simple: it is important to review the pieces of your plan with an advisor who will consider both tax diversification and security diversification as they relate to your specific circumstances.

2. Consider Owning Municipal Bonds in Taxable Accounts: Most municipal bonds are exempt from federal taxation. Certain issues may also be exempt from state and local taxes. If you are in the highest federal tax bracket, you may be paying tax on investment income at a rate of 43.4%. Under these circumstances, a municipal bond yielding 3% will provide a superior after tax return in comparison to a corporate bond yielding 5% in an individual or joint registration, a pass-through LLC, or in many trust accounts. Therefore, it is important in many circumstances to make certain your long-term plan utilizes the advantages of owning certain municipal bonds in taxable accounts.

3. Be Cognizant of Holding Periods: Long-term capital gains rates are much more favorable than short-term rates. Holding a security for a period of 12 months presents an opportunity to save nearly 20% on the taxation of your appreciated position. For example, an initial investment of $50,000 which grows to $100,000 represents a $50,000 unrealized gain. If an investor in the highest tax bracket simply delays liquidation of the position (assuming the security price does not change) the tax savings in this scenario would be $9,800. Although an awareness of the holding period of a security would appear to be a basic principal of investing, many mutual funds and managed accounts are not designed for tax sensitivity. High income investors should be aware that the average client of most advisors is not in the highest federal tax bracket. Therefore, it is generally advantageous to seek the advice of a financial professional with experience executing an appropriate exit strategy that is aware of holding periods.

4. Proactively Realize Losses to Offset Gains: As mentioned in the opening paragraphs of the article, 2015 presented investors with an opportunity to realize losses in domestic stocks for the first time in 4 years. Clients with a diversified portfolio may still have an opportunity to offset gains in domestic stocks by selling foreign equities. One benefit of diversifying across asset classes is that if the portfolio is structured properly, the securities typically will not move in tandem. This divergence of returns among asset classes not only reduces portfolio volatility, but it creates a tax planning opportunity. Domestic equities experienced tremendous appreciation over a 5-year period through 2014; however, international stocks, commodities, and multiple fixed income investments experienced down years. Astute advisors were presented with the opportunity to save clients thousands of dollars in taxes by performing strategic tax swaps prior to year-end. It is important to understand the rules relating to wash sales when executing such tactics. The laws are confusing, and if a mistake is made your loss could be disallowed. Make certain your advisor is well-versed in utilizing tax offsets.

5. Think Twice About Gifting Cash: This is not to discourage your charitable intentions. Quite the opposite is true. However, a successful investor can occasionally find themselves in a precarious position. You may have allocated 5% of your portfolio to a growth stock with significant upside. Several years have passed, the security has experienced explosive growth, and it now represents 15% of your investable assets. Suddenly your portfolio has a concentrated position with significant gains, and the level of risk is no longer consistent with your long-term objectives. The sound practice of rebalancing your portfolio then becomes very costly, because liquidation of the stock could create a taxable event that may negatively impact your net return.

By planning ahead of time, you may be able to gift a portion of the appreciated security to a charitable organization able to accept this type of donation. The value of your gift can be replaced with the cash you originally intended to donate to the charitable organization and, in this scenario, your cash will create a new cost basis. The charity can liquidate the stock without paying tax, and you have removed a future tax liability from your portfolio. Implementing the aforementioned gifting strategy offers the potential to save thousands of dollars in taxes over the life of your portfolio.

6. Understand your Mutual Fund’s Tax Cost Ratio: The technical detail behind a mutual fund’s tax cost ratio is beyond the scope of this article. Our intent is to simply bring this topic to your attention. Tax cost ratio represents the percentage of an investor’s assets that are lost to taxes. Mutual funds avoid double taxation, provided they pay at least 90% of net investment income and realized capital gains to shareholders at the end of the calendar year. But all mutual funds are not created equally, and proper research will allow you to identify funds that are tax efficient.

A well-managed mutual fund will add diversification to a portfolio while creating the opportunity to outperform asset classes with inefficient markets. You do need to be aware of funds with excessive turnover. An understanding of when a fund pays its capital gains distributions is a critical component of successful investing. A poorly timed fund purchase can result in acquiring another investor’s tax liability. It is not unusual for an investor to experience a negative return in a calendar year, yet find himself on the receiving end of a capital gains distribution. Understanding the tax cost ratios of the funds that make up portions of your investment plan will enable you to take advantage of the many benefits of owning mutual funds.

The above steps are by no means the only tax strategies experienced advisors can execute on behalf of their clients. This article highlights several strategies you should discuss with your advisor to determine if implementation is appropriate for your unique portfolio and overall financial situation. Successful investing requires discipline that extends beyond proper security selection. While gross returns are important and should not be ignored, the percentage return you see on your statements does not tell the full story.

In today’s tax environment, successful investors must choose an advisor who will help them look beyond portfolio earnings and focus on strategic after-tax asset growth.

To receive a free hardcopy of Wealth Protection Planning for Orthopaedic Surgeons, please call 877-656-4362. Visit www.ojmbookstore.com and enter promotional code AJO30 for a free ebook download of Wealth Protection Planning or one of our other ebooks for your Kindle or iPad.

Orthopedic physicians in the highest income tax brackets may have been presented with an unpleasant surprise in recent years when they learned of their investment tax liability. A prolonged period of strong domestic stock performance from 2009 to 2016, combined with the implementation of The American Taxpayer Relief Act of 2012, may have resulted in significantly higher taxes for many of you.

The top ordinary income tax rates increased by 24% when including the Net Investment Income surtax, while the top capital gains rate was increased by more than 58%. Writing a large check to the Internal Revenue Service serves as a harsh reminder that tax planning requires attention throughout the year, and is not a technique you can properly manage a few weeks before an April 15 deadline.

Proper tax planning became more critical as we moved into an era of higher taxes. A multi-year bull market for domestic stocks has caused many traditional investment vehicles to hold large amounts of unrealized gains, which can become realized gains if you are not careful. Most major equity indices took a breath in 2015 and finished the year in the red, which created a planning opportunity for astute investors and their advisors. Stocks in the US and emerging market countries quickly bounced back in 2016; however, European stocks struggled and continue to trade well below peak levels reached nearly a decade ago. Investors who missed the opportunity to offset gains of the prior 2 years may have an opportunity to reduce their tax bill in 2017.

In this article, we will provide you with 6 suggestions that could save you thousands of dollars in investment taxes over the next several years.

1. Account Registration Matters: A common mistake investors make is the failure to implement a tax diversification strategy. Brokerage accounts, Roth IRAs, and qualified plans are subject to various forms of taxation. It is important to utilize the tax advantages of these tools to ensure they work for you in the most productive manner possible. A properly integrated approach is critical during your accumulation phase. Further, it is just as important when you enter the distribution period of your investment life cycle (ie, retirement).

Master Limited Partnerships offer a potentially advantageous income stream for a brokerage account, while it is generally preferable for qualified accounts to own high yield bonds and corporate debt, as they are taxed at ordinary income rates. There are countless additional examples we could discuss, but the lesson is simple: it is important to review the pieces of your plan with an advisor who will consider both tax diversification and security diversification as they relate to your specific circumstances.

2. Consider Owning Municipal Bonds in Taxable Accounts: Most municipal bonds are exempt from federal taxation. Certain issues may also be exempt from state and local taxes. If you are in the highest federal tax bracket, you may be paying tax on investment income at a rate of 43.4%. Under these circumstances, a municipal bond yielding 3% will provide a superior after tax return in comparison to a corporate bond yielding 5% in an individual or joint registration, a pass-through LLC, or in many trust accounts. Therefore, it is important in many circumstances to make certain your long-term plan utilizes the advantages of owning certain municipal bonds in taxable accounts.

3. Be Cognizant of Holding Periods: Long-term capital gains rates are much more favorable than short-term rates. Holding a security for a period of 12 months presents an opportunity to save nearly 20% on the taxation of your appreciated position. For example, an initial investment of $50,000 which grows to $100,000 represents a $50,000 unrealized gain. If an investor in the highest tax bracket simply delays liquidation of the position (assuming the security price does not change) the tax savings in this scenario would be $9,800. Although an awareness of the holding period of a security would appear to be a basic principal of investing, many mutual funds and managed accounts are not designed for tax sensitivity. High income investors should be aware that the average client of most advisors is not in the highest federal tax bracket. Therefore, it is generally advantageous to seek the advice of a financial professional with experience executing an appropriate exit strategy that is aware of holding periods.

4. Proactively Realize Losses to Offset Gains: As mentioned in the opening paragraphs of the article, 2015 presented investors with an opportunity to realize losses in domestic stocks for the first time in 4 years. Clients with a diversified portfolio may still have an opportunity to offset gains in domestic stocks by selling foreign equities. One benefit of diversifying across asset classes is that if the portfolio is structured properly, the securities typically will not move in tandem. This divergence of returns among asset classes not only reduces portfolio volatility, but it creates a tax planning opportunity. Domestic equities experienced tremendous appreciation over a 5-year period through 2014; however, international stocks, commodities, and multiple fixed income investments experienced down years. Astute advisors were presented with the opportunity to save clients thousands of dollars in taxes by performing strategic tax swaps prior to year-end. It is important to understand the rules relating to wash sales when executing such tactics. The laws are confusing, and if a mistake is made your loss could be disallowed. Make certain your advisor is well-versed in utilizing tax offsets.

5. Think Twice About Gifting Cash: This is not to discourage your charitable intentions. Quite the opposite is true. However, a successful investor can occasionally find themselves in a precarious position. You may have allocated 5% of your portfolio to a growth stock with significant upside. Several years have passed, the security has experienced explosive growth, and it now represents 15% of your investable assets. Suddenly your portfolio has a concentrated position with significant gains, and the level of risk is no longer consistent with your long-term objectives. The sound practice of rebalancing your portfolio then becomes very costly, because liquidation of the stock could create a taxable event that may negatively impact your net return.

By planning ahead of time, you may be able to gift a portion of the appreciated security to a charitable organization able to accept this type of donation. The value of your gift can be replaced with the cash you originally intended to donate to the charitable organization and, in this scenario, your cash will create a new cost basis. The charity can liquidate the stock without paying tax, and you have removed a future tax liability from your portfolio. Implementing the aforementioned gifting strategy offers the potential to save thousands of dollars in taxes over the life of your portfolio.

6. Understand your Mutual Fund’s Tax Cost Ratio: The technical detail behind a mutual fund’s tax cost ratio is beyond the scope of this article. Our intent is to simply bring this topic to your attention. Tax cost ratio represents the percentage of an investor’s assets that are lost to taxes. Mutual funds avoid double taxation, provided they pay at least 90% of net investment income and realized capital gains to shareholders at the end of the calendar year. But all mutual funds are not created equally, and proper research will allow you to identify funds that are tax efficient.

A well-managed mutual fund will add diversification to a portfolio while creating the opportunity to outperform asset classes with inefficient markets. You do need to be aware of funds with excessive turnover. An understanding of when a fund pays its capital gains distributions is a critical component of successful investing. A poorly timed fund purchase can result in acquiring another investor’s tax liability. It is not unusual for an investor to experience a negative return in a calendar year, yet find himself on the receiving end of a capital gains distribution. Understanding the tax cost ratios of the funds that make up portions of your investment plan will enable you to take advantage of the many benefits of owning mutual funds.

The above steps are by no means the only tax strategies experienced advisors can execute on behalf of their clients. This article highlights several strategies you should discuss with your advisor to determine if implementation is appropriate for your unique portfolio and overall financial situation. Successful investing requires discipline that extends beyond proper security selection. While gross returns are important and should not be ignored, the percentage return you see on your statements does not tell the full story.

In today’s tax environment, successful investors must choose an advisor who will help them look beyond portfolio earnings and focus on strategic after-tax asset growth.

To receive a free hardcopy of Wealth Protection Planning for Orthopaedic Surgeons, please call 877-656-4362. Visit www.ojmbookstore.com and enter promotional code AJO30 for a free ebook download of Wealth Protection Planning or one of our other ebooks for your Kindle or iPad.

CHICAGO – Bone marrow transplantation is evolving as a promising treatment for patients with the most severe forms of epidermolysis bullosa.

“Is this a cure? It’s not,” Dr. Jakub Tolar, MD, PhD, said at the World Congress of Pediatric Dermatology. “It is, however, a path toward understanding how we can treat this grave disorder in a systemic way.”

Courtesy Gabriella McCann

[email protected]

CHICAGO – Bone marrow transplantation is evolving as a promising treatment for patients with the most severe forms of epidermolysis bullosa.

“Is this a cure? It’s not,” Dr. Jakub Tolar, MD, PhD, said at the World Congress of Pediatric Dermatology. “It is, however, a path toward understanding how we can treat this grave disorder in a systemic way.”

Courtesy Gabriella McCann

[email protected]

CHICAGO – Bone marrow transplantation is evolving as a promising treatment for patients with the most severe forms of epidermolysis bullosa.

“Is this a cure? It’s not,” Dr. Jakub Tolar, MD, PhD, said at the World Congress of Pediatric Dermatology. “It is, however, a path toward understanding how we can treat this grave disorder in a systemic way.”

Courtesy Gabriella McCann

[email protected]

Take-Home Points

• Complication rates did not statistically significantly differ between simultaneous and staged TKA.
• Length of stay of 2 TKA admissions was greater than 1 BTKA admission.
• Transfusion requirements were greater in BTKA.
• Avoid bilateral procedures in ASA 3 patients.
• Develop institutional protocols for BTKA with multidisciplinary input.

In the United States, osteoarthritis is the most common cause of knee pain and one of the leading causes of disability.¹ Total knee arthroplasty (TKA) is an effective treatment for end-stage osteoarthritis of the knee.² Whether patients with severe, debilitating bilateral disease should undergo simultaneous bilateral TKA (BTKA) or staged BTKA (2 separate procedures during separate hospital admissions) continues to be debated. The relative risks and benefits of simultaneous BTKA relative to staged BTKA or unilateral TKA are controversial.^3-6 Proponents of simultaneous BTKA have argued that this surgery results in shorter hospital length of stay (LOS) and higher patient satisfaction without increased risk of perioperative complications,^7-9 and opponents have argued that it leads to increased perioperative mortality and complications and should not be performed routinely.^10,11

The safety of simultaneous BTKA cannot necessarily be extrapolated from data on unilateral TKA. Authors have argued that the complication rate for simultaneous BTKA is not comparable to the rate for unilateral TKA but instead is double the rate.¹² Although a doubled rate may more closely approximate the true risk of simultaneous BTKA, it still does not account for the increased surgical impact of 2 procedures (vs 1 procedure) on a patient. In this regard, comparing simultaneous and staged BTKA provides a more accurate assessment of risk, as long as the interval between surgeries is not excessive. The major stress experienced during TKA affects the cardiovascular, pulmonary, and musculoskeletal systems, and full recovery may take up to 6 months.^13-15 Outcome studies have found significant improvement in validated measures of function and pain up to but not past 6 months.^13,15 Furthermore, a large study comparing American Society of Anesthesiologists (ASA) scores with morbidity and mortality rates recorded in the New Zealand Total Joint Database established 6 months as a best approximation of postoperative mortality and morbidity risk.¹⁴ Given these data, we propose that the most accurate analysis of postoperative morbidity and mortality would be a comparison of simultaneous BTKA with BTKA staged <6 months apart. The staged procedures fall within the crucial postoperative period when increased morbidity and mortality would more likely be present. A between-surgeries interval >6 months would effectively separate the 2 procedures, rendering their risks not truly representative.

We retrospectively analyzed all simultaneous BTKA and staged BTKA (<6 months apart) surgeries performed at our orthopedic specialty hospital between 2005 and 2009. We hypothesized there would be no significant difference in perioperative morbidity or mortality between the groups.

Methods and Materials

Our institution’s Institutional Review Board approved this study. All patients who underwent either simultaneous BTKA or staged BTKA (<6 months apart) at a single orthopedic specialty hospital between 2005 and 2009 were retrospectively identified. Twenty-five surgeons performed the procedures. Which procedure to perform (simultaneous or staged) was decided by the attending surgeon in consultation with an anesthesiologist. Preoperative medical diagnostic testing was determined by the internist, who provided medical clearance, and was subject to review by the anesthesiologist. A patient was excluded from simultaneous BTKA only if the medical or anesthesiology consultant deemed the patient too high risk for bilateral procedures. Revision TKAs were excluded from the study.

Implant, approach, tourniquet use, and TKA technique were selected by the individual surgeons. Strategies for the simultaneous procedures were (1) single surgeon, single team, sequential, start second knee after closure of first, and (2) single surgeon, single team, sequential, start second knee after implantation of first but before closure. The decision to proceed with the second knee was confirmed in consultation with the anesthesiologist after implantation and deflation of the tourniquet on the first knee.

Individual electronic patient charts were reviewed for information on demographics, comorbidities, anesthesia type, antibiotics, and postoperative venous thromboembolism prophylaxis. Demographic variables included age, sex, height, weight, and body mass index (BMI). Comorbidities recorded were diabetes mellitus, coronary artery disease, prior myocardial infarction, stroke, and endocrinopathies. In addition, available ASA scores were recorded. The primary outcome was perioperative complications, defined as any complications that occurred within 6 months after surgery. These included death, pulmonary embolism (PE), and deep surgical-site infections (SSIs). Secondary outcome measures were LOS, discharge location (rehabilitation or home), and blood transfusion requirements.

The 2 groups (simultaneous BTKA, staged BTKA) were compared using Student t test for continuous variables and χ² test for categorical variables. Subgroup analysis was performed to compare healthier patients (ASA score 1 or 2) with patients who had more severe comorbidities (ASA score 3). Statistical significance was set at P < .05.

Results

Between 2005 and 2009, 371 patients had simultaneous BTKA, and 67 had staged BTKA (134 procedures) <6 months apart (Table 1).

Most surgeries (84.4% simultaneous, 90.3% staged) were performed with the patient under spinal anesthesia, and there was a trend (P = .167) toward more frequent use of general anesthesia in the simultaneous group relative to the staged group (Table 2).

Discussion

Although there was no significant difference in postoperative complication rates within 6 months after surgery between the simultaneous and staged BTKA groups, the incidence of complications in the simultaneous group was notable. The disproportionate size of the 2 comparison groups limited the power of our study to analyze individual perioperative complications. This study may be underpowered to detect differences in complications occurring relatively infrequently, which may explain why the difference in number of complications (13 in simultaneous group, 1 in staged group) did not achieve statistical significance (β = 0.89). Post hoc power analysis showed 956 patients would be needed in each group to adequately power for such small complication rates. However, our results are consistent with those of other studies.^13-15 The 1.9% PE rate in our simultaneous BTKA group does not vary from the average PE rate for TKA in the literature and is actually lower than the PE rate in a previous study at our institution.¹⁶ Fat embolism traditionally is considered more of a concern in bilateral cases than in unilateral cases. Although fat embolism surely is inherent to the physiologic alterations caused by TKA, we did not find clinically significant fat embolism in either cohort.

Similarly, the 1.08% rate of deep SSIs is within the range for postoperative TKA infections at our institution and others.¹⁷ Our staged BTKA group’s complication rate, 0.75% (1 SSI), was slightly lower than expected. However, 0.75% is in keeping with institutional norms (typical rate, ~1%). We would have expected a nonzero rate for venous thromboembolism, and perhaps such a rate would have come with an inclusion period longer than 6 months. Last, the death in the simultaneous BTKA group was not an outlier, given the published rate of mortality after elective total joint surgery.¹⁸The characteristics of our simultaneous and staged BTKA groups were very similar (Table 1), though the larger number of staged-group patients with diabetes mellitus and coronary artery disease may represent selection bias. Nevertheless, the proportions of patients with each of 3 ASA scores were similar. It is also important to note that, in this context, a high percentage of patients in each group (33.6% simultaneous, 37.5% staged) received ASA score 3 from the anesthesiologist (P > .05). This may be an important factor in explaining the larger though not statistically significant number of complications in the simultaneous group (13) relative to the staged group (1).

Conclusion

In this study, the incidence of postoperative complications was higher for simultaneous BTKA than for staged BTKA performed <6 months apart, but the difference was not significantly different. There were significant differences in LOS and blood transfusion rates between the groups, as expected. At present, only patients with ASA score 1 or 2 are considered for simultaneous BTKA at our institution. Patients with ASA score 3 or higher are not eligible.

Am J Orthop. 2017;46(4):E224-E229. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Complication rates did not statistically significantly differ between simultaneous and staged TKA.
• Length of stay of 2 TKA admissions was greater than 1 BTKA admission.
• Transfusion requirements were greater in BTKA.
• Avoid bilateral procedures in ASA 3 patients.
• Develop institutional protocols for BTKA with multidisciplinary input.

In the United States, osteoarthritis is the most common cause of knee pain and one of the leading causes of disability.¹ Total knee arthroplasty (TKA) is an effective treatment for end-stage osteoarthritis of the knee.² Whether patients with severe, debilitating bilateral disease should undergo simultaneous bilateral TKA (BTKA) or staged BTKA (2 separate procedures during separate hospital admissions) continues to be debated. The relative risks and benefits of simultaneous BTKA relative to staged BTKA or unilateral TKA are controversial.^3-6 Proponents of simultaneous BTKA have argued that this surgery results in shorter hospital length of stay (LOS) and higher patient satisfaction without increased risk of perioperative complications,^7-9 and opponents have argued that it leads to increased perioperative mortality and complications and should not be performed routinely.^10,11

The safety of simultaneous BTKA cannot necessarily be extrapolated from data on unilateral TKA. Authors have argued that the complication rate for simultaneous BTKA is not comparable to the rate for unilateral TKA but instead is double the rate.¹² Although a doubled rate may more closely approximate the true risk of simultaneous BTKA, it still does not account for the increased surgical impact of 2 procedures (vs 1 procedure) on a patient. In this regard, comparing simultaneous and staged BTKA provides a more accurate assessment of risk, as long as the interval between surgeries is not excessive. The major stress experienced during TKA affects the cardiovascular, pulmonary, and musculoskeletal systems, and full recovery may take up to 6 months.^13-15 Outcome studies have found significant improvement in validated measures of function and pain up to but not past 6 months.^13,15 Furthermore, a large study comparing American Society of Anesthesiologists (ASA) scores with morbidity and mortality rates recorded in the New Zealand Total Joint Database established 6 months as a best approximation of postoperative mortality and morbidity risk.¹⁴ Given these data, we propose that the most accurate analysis of postoperative morbidity and mortality would be a comparison of simultaneous BTKA with BTKA staged <6 months apart. The staged procedures fall within the crucial postoperative period when increased morbidity and mortality would more likely be present. A between-surgeries interval >6 months would effectively separate the 2 procedures, rendering their risks not truly representative.

We retrospectively analyzed all simultaneous BTKA and staged BTKA (<6 months apart) surgeries performed at our orthopedic specialty hospital between 2005 and 2009. We hypothesized there would be no significant difference in perioperative morbidity or mortality between the groups.

Methods and Materials

Our institution’s Institutional Review Board approved this study. All patients who underwent either simultaneous BTKA or staged BTKA (<6 months apart) at a single orthopedic specialty hospital between 2005 and 2009 were retrospectively identified. Twenty-five surgeons performed the procedures. Which procedure to perform (simultaneous or staged) was decided by the attending surgeon in consultation with an anesthesiologist. Preoperative medical diagnostic testing was determined by the internist, who provided medical clearance, and was subject to review by the anesthesiologist. A patient was excluded from simultaneous BTKA only if the medical or anesthesiology consultant deemed the patient too high risk for bilateral procedures. Revision TKAs were excluded from the study.

Implant, approach, tourniquet use, and TKA technique were selected by the individual surgeons. Strategies for the simultaneous procedures were (1) single surgeon, single team, sequential, start second knee after closure of first, and (2) single surgeon, single team, sequential, start second knee after implantation of first but before closure. The decision to proceed with the second knee was confirmed in consultation with the anesthesiologist after implantation and deflation of the tourniquet on the first knee.

Individual electronic patient charts were reviewed for information on demographics, comorbidities, anesthesia type, antibiotics, and postoperative venous thromboembolism prophylaxis. Demographic variables included age, sex, height, weight, and body mass index (BMI). Comorbidities recorded were diabetes mellitus, coronary artery disease, prior myocardial infarction, stroke, and endocrinopathies. In addition, available ASA scores were recorded. The primary outcome was perioperative complications, defined as any complications that occurred within 6 months after surgery. These included death, pulmonary embolism (PE), and deep surgical-site infections (SSIs). Secondary outcome measures were LOS, discharge location (rehabilitation or home), and blood transfusion requirements.

The 2 groups (simultaneous BTKA, staged BTKA) were compared using Student t test for continuous variables and χ² test for categorical variables. Subgroup analysis was performed to compare healthier patients (ASA score 1 or 2) with patients who had more severe comorbidities (ASA score 3). Statistical significance was set at P < .05.

Results

Between 2005 and 2009, 371 patients had simultaneous BTKA, and 67 had staged BTKA (134 procedures) <6 months apart (Table 1).

Most surgeries (84.4% simultaneous, 90.3% staged) were performed with the patient under spinal anesthesia, and there was a trend (P = .167) toward more frequent use of general anesthesia in the simultaneous group relative to the staged group (Table 2).

Discussion

Although there was no significant difference in postoperative complication rates within 6 months after surgery between the simultaneous and staged BTKA groups, the incidence of complications in the simultaneous group was notable. The disproportionate size of the 2 comparison groups limited the power of our study to analyze individual perioperative complications. This study may be underpowered to detect differences in complications occurring relatively infrequently, which may explain why the difference in number of complications (13 in simultaneous group, 1 in staged group) did not achieve statistical significance (β = 0.89). Post hoc power analysis showed 956 patients would be needed in each group to adequately power for such small complication rates. However, our results are consistent with those of other studies.^13-15 The 1.9% PE rate in our simultaneous BTKA group does not vary from the average PE rate for TKA in the literature and is actually lower than the PE rate in a previous study at our institution.¹⁶ Fat embolism traditionally is considered more of a concern in bilateral cases than in unilateral cases. Although fat embolism surely is inherent to the physiologic alterations caused by TKA, we did not find clinically significant fat embolism in either cohort.

Similarly, the 1.08% rate of deep SSIs is within the range for postoperative TKA infections at our institution and others.¹⁷ Our staged BTKA group’s complication rate, 0.75% (1 SSI), was slightly lower than expected. However, 0.75% is in keeping with institutional norms (typical rate, ~1%). We would have expected a nonzero rate for venous thromboembolism, and perhaps such a rate would have come with an inclusion period longer than 6 months. Last, the death in the simultaneous BTKA group was not an outlier, given the published rate of mortality after elective total joint surgery.¹⁸The characteristics of our simultaneous and staged BTKA groups were very similar (Table 1), though the larger number of staged-group patients with diabetes mellitus and coronary artery disease may represent selection bias. Nevertheless, the proportions of patients with each of 3 ASA scores were similar. It is also important to note that, in this context, a high percentage of patients in each group (33.6% simultaneous, 37.5% staged) received ASA score 3 from the anesthesiologist (P > .05). This may be an important factor in explaining the larger though not statistically significant number of complications in the simultaneous group (13) relative to the staged group (1).

Conclusion

In this study, the incidence of postoperative complications was higher for simultaneous BTKA than for staged BTKA performed <6 months apart, but the difference was not significantly different. There were significant differences in LOS and blood transfusion rates between the groups, as expected. At present, only patients with ASA score 1 or 2 are considered for simultaneous BTKA at our institution. Patients with ASA score 3 or higher are not eligible.

Am J Orthop. 2017;46(4):E224-E229. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• Complication rates did not statistically significantly differ between simultaneous and staged TKA.
• Length of stay of 2 TKA admissions was greater than 1 BTKA admission.
• Transfusion requirements were greater in BTKA.
• Avoid bilateral procedures in ASA 3 patients.
• Develop institutional protocols for BTKA with multidisciplinary input.

In the United States, osteoarthritis is the most common cause of knee pain and one of the leading causes of disability.¹ Total knee arthroplasty (TKA) is an effective treatment for end-stage osteoarthritis of the knee.² Whether patients with severe, debilitating bilateral disease should undergo simultaneous bilateral TKA (BTKA) or staged BTKA (2 separate procedures during separate hospital admissions) continues to be debated. The relative risks and benefits of simultaneous BTKA relative to staged BTKA or unilateral TKA are controversial.^3-6 Proponents of simultaneous BTKA have argued that this surgery results in shorter hospital length of stay (LOS) and higher patient satisfaction without increased risk of perioperative complications,^7-9 and opponents have argued that it leads to increased perioperative mortality and complications and should not be performed routinely.^10,11

The safety of simultaneous BTKA cannot necessarily be extrapolated from data on unilateral TKA. Authors have argued that the complication rate for simultaneous BTKA is not comparable to the rate for unilateral TKA but instead is double the rate.¹² Although a doubled rate may more closely approximate the true risk of simultaneous BTKA, it still does not account for the increased surgical impact of 2 procedures (vs 1 procedure) on a patient. In this regard, comparing simultaneous and staged BTKA provides a more accurate assessment of risk, as long as the interval between surgeries is not excessive. The major stress experienced during TKA affects the cardiovascular, pulmonary, and musculoskeletal systems, and full recovery may take up to 6 months.^13-15 Outcome studies have found significant improvement in validated measures of function and pain up to but not past 6 months.^13,15 Furthermore, a large study comparing American Society of Anesthesiologists (ASA) scores with morbidity and mortality rates recorded in the New Zealand Total Joint Database established 6 months as a best approximation of postoperative mortality and morbidity risk.¹⁴ Given these data, we propose that the most accurate analysis of postoperative morbidity and mortality would be a comparison of simultaneous BTKA with BTKA staged <6 months apart. The staged procedures fall within the crucial postoperative period when increased morbidity and mortality would more likely be present. A between-surgeries interval >6 months would effectively separate the 2 procedures, rendering their risks not truly representative.

We retrospectively analyzed all simultaneous BTKA and staged BTKA (<6 months apart) surgeries performed at our orthopedic specialty hospital between 2005 and 2009. We hypothesized there would be no significant difference in perioperative morbidity or mortality between the groups.

Methods and Materials

Our institution’s Institutional Review Board approved this study. All patients who underwent either simultaneous BTKA or staged BTKA (<6 months apart) at a single orthopedic specialty hospital between 2005 and 2009 were retrospectively identified. Twenty-five surgeons performed the procedures. Which procedure to perform (simultaneous or staged) was decided by the attending surgeon in consultation with an anesthesiologist. Preoperative medical diagnostic testing was determined by the internist, who provided medical clearance, and was subject to review by the anesthesiologist. A patient was excluded from simultaneous BTKA only if the medical or anesthesiology consultant deemed the patient too high risk for bilateral procedures. Revision TKAs were excluded from the study.

Implant, approach, tourniquet use, and TKA technique were selected by the individual surgeons. Strategies for the simultaneous procedures were (1) single surgeon, single team, sequential, start second knee after closure of first, and (2) single surgeon, single team, sequential, start second knee after implantation of first but before closure. The decision to proceed with the second knee was confirmed in consultation with the anesthesiologist after implantation and deflation of the tourniquet on the first knee.

Individual electronic patient charts were reviewed for information on demographics, comorbidities, anesthesia type, antibiotics, and postoperative venous thromboembolism prophylaxis. Demographic variables included age, sex, height, weight, and body mass index (BMI). Comorbidities recorded were diabetes mellitus, coronary artery disease, prior myocardial infarction, stroke, and endocrinopathies. In addition, available ASA scores were recorded. The primary outcome was perioperative complications, defined as any complications that occurred within 6 months after surgery. These included death, pulmonary embolism (PE), and deep surgical-site infections (SSIs). Secondary outcome measures were LOS, discharge location (rehabilitation or home), and blood transfusion requirements.

The 2 groups (simultaneous BTKA, staged BTKA) were compared using Student t test for continuous variables and χ² test for categorical variables. Subgroup analysis was performed to compare healthier patients (ASA score 1 or 2) with patients who had more severe comorbidities (ASA score 3). Statistical significance was set at P < .05.

Results

Between 2005 and 2009, 371 patients had simultaneous BTKA, and 67 had staged BTKA (134 procedures) <6 months apart (Table 1).

Most surgeries (84.4% simultaneous, 90.3% staged) were performed with the patient under spinal anesthesia, and there was a trend (P = .167) toward more frequent use of general anesthesia in the simultaneous group relative to the staged group (Table 2).

Discussion

Although there was no significant difference in postoperative complication rates within 6 months after surgery between the simultaneous and staged BTKA groups, the incidence of complications in the simultaneous group was notable. The disproportionate size of the 2 comparison groups limited the power of our study to analyze individual perioperative complications. This study may be underpowered to detect differences in complications occurring relatively infrequently, which may explain why the difference in number of complications (13 in simultaneous group, 1 in staged group) did not achieve statistical significance (β = 0.89). Post hoc power analysis showed 956 patients would be needed in each group to adequately power for such small complication rates. However, our results are consistent with those of other studies.^13-15 The 1.9% PE rate in our simultaneous BTKA group does not vary from the average PE rate for TKA in the literature and is actually lower than the PE rate in a previous study at our institution.¹⁶ Fat embolism traditionally is considered more of a concern in bilateral cases than in unilateral cases. Although fat embolism surely is inherent to the physiologic alterations caused by TKA, we did not find clinically significant fat embolism in either cohort.

Similarly, the 1.08% rate of deep SSIs is within the range for postoperative TKA infections at our institution and others.¹⁷ Our staged BTKA group’s complication rate, 0.75% (1 SSI), was slightly lower than expected. However, 0.75% is in keeping with institutional norms (typical rate, ~1%). We would have expected a nonzero rate for venous thromboembolism, and perhaps such a rate would have come with an inclusion period longer than 6 months. Last, the death in the simultaneous BTKA group was not an outlier, given the published rate of mortality after elective total joint surgery.¹⁸The characteristics of our simultaneous and staged BTKA groups were very similar (Table 1), though the larger number of staged-group patients with diabetes mellitus and coronary artery disease may represent selection bias. Nevertheless, the proportions of patients with each of 3 ASA scores were similar. It is also important to note that, in this context, a high percentage of patients in each group (33.6% simultaneous, 37.5% staged) received ASA score 3 from the anesthesiologist (P > .05). This may be an important factor in explaining the larger though not statistically significant number of complications in the simultaneous group (13) relative to the staged group (1).

Conclusion

In this study, the incidence of postoperative complications was higher for simultaneous BTKA than for staged BTKA performed <6 months apart, but the difference was not significantly different. There were significant differences in LOS and blood transfusion rates between the groups, as expected. At present, only patients with ASA score 1 or 2 are considered for simultaneous BTKA at our institution. Patients with ASA score 3 or higher are not eligible.

Am J Orthop. 2017;46(4):E224-E229. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Severity of depression may be associated with epilepsy risk and outcomes, according to a study published in the May issue of JAMA Neurology. “Treated depression is associated with worse epilepsy outcomes, suggesting that this [factor] may be a surrogate for more severe depression and that severity of depression is associated with severity of epilepsy,” said Colin B. Josephson, MD, Assistant Professor of Neurology at the University of Calgary in Alberta, and colleagues.

“If one assumes that depression treatment is a surrogate marker for depression severity, then there … appears to be a biological gradient,” the investigators said. “This assertion is corroborated by the incremental hazard of epilepsy among those receiving counseling alone (lowest hazard), antidepressants alone (intermediate hazard), and a combination of counseling and antidepressants (highest hazard).”

Prior research has found that the incidence and prevalence of depression are significantly elevated before and after an epilepsy diagnosis. Studies have not assessed, however, the risk of epilepsy after an incident diagnosis of depression or whether depression severity affects the level of risk or seizure outcomes, the authors said.

Two Data Sources

Dr. Josephson and colleagues examined two independent sources of data to explore the relationship between depression and epilepsy further. First, they conducted an observational study using The Health Improvement Network (THIN) database, a population-based primary care cohort. The THIN database contains prospective data that are broadly representative of the general population of the United Kingdom. All patients included in the study were free of prevalent depression and epilepsy and between the ages of 18 and 90. Separately, they analyzed prospective data from the Calgary Comprehensive Epilepsy Programme, a registry of adult outpatient encounters.

Of the more than 10.5 million eligible patients in the THIN database, 229,164 (2.2%) developed depression and 97,177 (0.9%) developed epilepsy. The median age was 44 among patients with depression and 56 among patients with epilepsy. Sixty-three percent of the patients with depression and 56% of the patients with epilepsy were women.

Incident epilepsy was associated with an increased hazard of developing depression (hazard ratio [HR], 2.04), and incident depression was associated with an increased hazard of developing epilepsy (HR, 2.55). “The association with incident epilepsy was even stronger for those with treated depression (HR, 3.42), compared with a combination of those who did not develop depression and those who developed depression not requiring therapy.”

In a sensitivity analysis controlling for age, sex, socioeconomic status, and Charlson Comorbidity Index, “there was an incremental hazard according to depression treatment type, with lowest risk for those receiving counselling alone (HR, 1.84), an intermediate risk for those receiving antidepressants alone (HR, 3.43), and the highest risk for those receiving both (HR, 9.85).”

Likelihood of Seizure Freedom

To assess the effect of depression on seizure outcomes, the researchers analyzed data from 2,573 patients in the Calgary Comprehensive Epilepsy Programme cohort. Data were derived from patients’ first-visit evaluation forms. A total of 504 (20%) of the patients had achieved one-year seizure freedom during the year prior to their first clinic visit. Patients with past or current depression had higher odds of failing to achieve seizure freedom during the previous year, compared with patients without depression (odds ratio, 1.41). When considering only patients with current or past depression (n = 738), current depression treatment (ie, antidepressants, counseling, or both) was associated with significantly higher odds of failing to achieve one-year seizure freedom (odds ratio, 1.75) after controlling for age at onset of epilepsy, sex, lesional epilepsy detected by MRI, history of generalized tonic-clonic seizures, and current antiepileptic drug use.

Overall, the results “indicate a shared relationship between depression and epilepsy, with each appearing to act as a risk factor for the other, and, therefore, should have a direct effect on counseling and management,” Dr. Josephson and colleagues said.

Limitations

The researchers noted that they were unable to control for etiology, epilepsy subtype, or conditions that could cause epilepsy and depression, and they did not have information about the duration, dose, or frequency of depression treatments. Although depression severity may not necessarily determine treatment type, primary care guidelines recommend counseling as first-line treatment for mild depression and combination therapy for severe depression, the researchers said.

Other possible interpretations of the results, such as the idea that antidepressant treatment augments the risk of epilepsy or that patients are more severely depressed because they have not achieved one-year seizure freedom, are less likely. “Counseling interacted with antidepressant exposure and resulted in a threefold increase in the hazard of epilepsy over that of medications alone,” which suggests that “treatment is acting as a proxy for depression severity and is thus consistent with the existence of a biological dose-response relationship,” the researchers said. In addition, “a recent review has indicated that virtually all antidepressants are safe for patients with epilepsy, thereby debunking the notion that these medications increase the risk of seizures.”

—Jake Remaly

Suggested Reading

Josephson CB, Lowerison M, Vallerand I, et al. Association of depression and treated depression with epilepsy and seizure outcomes: A multicohort analysis. JAMA Neurol. 2017;74(5):533-539.

Kanner AM. Most antidepressant drugs are safe for patients with epilepsy at therapeutic doses: A review of the evidence. Epilepsy Behav. 2016;61:282-286.

Severity of depression may be associated with epilepsy risk and outcomes, according to a study published in the May issue of JAMA Neurology. “Treated depression is associated with worse epilepsy outcomes, suggesting that this [factor] may be a surrogate for more severe depression and that severity of depression is associated with severity of epilepsy,” said Colin B. Josephson, MD, Assistant Professor of Neurology at the University of Calgary in Alberta, and colleagues.

“If one assumes that depression treatment is a surrogate marker for depression severity, then there … appears to be a biological gradient,” the investigators said. “This assertion is corroborated by the incremental hazard of epilepsy among those receiving counseling alone (lowest hazard), antidepressants alone (intermediate hazard), and a combination of counseling and antidepressants (highest hazard).”

Prior research has found that the incidence and prevalence of depression are significantly elevated before and after an epilepsy diagnosis. Studies have not assessed, however, the risk of epilepsy after an incident diagnosis of depression or whether depression severity affects the level of risk or seizure outcomes, the authors said.

Two Data Sources

Dr. Josephson and colleagues examined two independent sources of data to explore the relationship between depression and epilepsy further. First, they conducted an observational study using The Health Improvement Network (THIN) database, a population-based primary care cohort. The THIN database contains prospective data that are broadly representative of the general population of the United Kingdom. All patients included in the study were free of prevalent depression and epilepsy and between the ages of 18 and 90. Separately, they analyzed prospective data from the Calgary Comprehensive Epilepsy Programme, a registry of adult outpatient encounters.

Of the more than 10.5 million eligible patients in the THIN database, 229,164 (2.2%) developed depression and 97,177 (0.9%) developed epilepsy. The median age was 44 among patients with depression and 56 among patients with epilepsy. Sixty-three percent of the patients with depression and 56% of the patients with epilepsy were women.

Incident epilepsy was associated with an increased hazard of developing depression (hazard ratio [HR], 2.04), and incident depression was associated with an increased hazard of developing epilepsy (HR, 2.55). “The association with incident epilepsy was even stronger for those with treated depression (HR, 3.42), compared with a combination of those who did not develop depression and those who developed depression not requiring therapy.”

In a sensitivity analysis controlling for age, sex, socioeconomic status, and Charlson Comorbidity Index, “there was an incremental hazard according to depression treatment type, with lowest risk for those receiving counselling alone (HR, 1.84), an intermediate risk for those receiving antidepressants alone (HR, 3.43), and the highest risk for those receiving both (HR, 9.85).”

Likelihood of Seizure Freedom

To assess the effect of depression on seizure outcomes, the researchers analyzed data from 2,573 patients in the Calgary Comprehensive Epilepsy Programme cohort. Data were derived from patients’ first-visit evaluation forms. A total of 504 (20%) of the patients had achieved one-year seizure freedom during the year prior to their first clinic visit. Patients with past or current depression had higher odds of failing to achieve seizure freedom during the previous year, compared with patients without depression (odds ratio, 1.41). When considering only patients with current or past depression (n = 738), current depression treatment (ie, antidepressants, counseling, or both) was associated with significantly higher odds of failing to achieve one-year seizure freedom (odds ratio, 1.75) after controlling for age at onset of epilepsy, sex, lesional epilepsy detected by MRI, history of generalized tonic-clonic seizures, and current antiepileptic drug use.

Overall, the results “indicate a shared relationship between depression and epilepsy, with each appearing to act as a risk factor for the other, and, therefore, should have a direct effect on counseling and management,” Dr. Josephson and colleagues said.

Limitations

The researchers noted that they were unable to control for etiology, epilepsy subtype, or conditions that could cause epilepsy and depression, and they did not have information about the duration, dose, or frequency of depression treatments. Although depression severity may not necessarily determine treatment type, primary care guidelines recommend counseling as first-line treatment for mild depression and combination therapy for severe depression, the researchers said.

Other possible interpretations of the results, such as the idea that antidepressant treatment augments the risk of epilepsy or that patients are more severely depressed because they have not achieved one-year seizure freedom, are less likely. “Counseling interacted with antidepressant exposure and resulted in a threefold increase in the hazard of epilepsy over that of medications alone,” which suggests that “treatment is acting as a proxy for depression severity and is thus consistent with the existence of a biological dose-response relationship,” the researchers said. In addition, “a recent review has indicated that virtually all antidepressants are safe for patients with epilepsy, thereby debunking the notion that these medications increase the risk of seizures.”

—Jake Remaly

Suggested Reading

Josephson CB, Lowerison M, Vallerand I, et al. Association of depression and treated depression with epilepsy and seizure outcomes: A multicohort analysis. JAMA Neurol. 2017;74(5):533-539.

Kanner AM. Most antidepressant drugs are safe for patients with epilepsy at therapeutic doses: A review of the evidence. Epilepsy Behav. 2016;61:282-286.

Severity of depression may be associated with epilepsy risk and outcomes, according to a study published in the May issue of JAMA Neurology. “Treated depression is associated with worse epilepsy outcomes, suggesting that this [factor] may be a surrogate for more severe depression and that severity of depression is associated with severity of epilepsy,” said Colin B. Josephson, MD, Assistant Professor of Neurology at the University of Calgary in Alberta, and colleagues.

“If one assumes that depression treatment is a surrogate marker for depression severity, then there … appears to be a biological gradient,” the investigators said. “This assertion is corroborated by the incremental hazard of epilepsy among those receiving counseling alone (lowest hazard), antidepressants alone (intermediate hazard), and a combination of counseling and antidepressants (highest hazard).”

Prior research has found that the incidence and prevalence of depression are significantly elevated before and after an epilepsy diagnosis. Studies have not assessed, however, the risk of epilepsy after an incident diagnosis of depression or whether depression severity affects the level of risk or seizure outcomes, the authors said.

Two Data Sources

Dr. Josephson and colleagues examined two independent sources of data to explore the relationship between depression and epilepsy further. First, they conducted an observational study using The Health Improvement Network (THIN) database, a population-based primary care cohort. The THIN database contains prospective data that are broadly representative of the general population of the United Kingdom. All patients included in the study were free of prevalent depression and epilepsy and between the ages of 18 and 90. Separately, they analyzed prospective data from the Calgary Comprehensive Epilepsy Programme, a registry of adult outpatient encounters.

Of the more than 10.5 million eligible patients in the THIN database, 229,164 (2.2%) developed depression and 97,177 (0.9%) developed epilepsy. The median age was 44 among patients with depression and 56 among patients with epilepsy. Sixty-three percent of the patients with depression and 56% of the patients with epilepsy were women.

Incident epilepsy was associated with an increased hazard of developing depression (hazard ratio [HR], 2.04), and incident depression was associated with an increased hazard of developing epilepsy (HR, 2.55). “The association with incident epilepsy was even stronger for those with treated depression (HR, 3.42), compared with a combination of those who did not develop depression and those who developed depression not requiring therapy.”

In a sensitivity analysis controlling for age, sex, socioeconomic status, and Charlson Comorbidity Index, “there was an incremental hazard according to depression treatment type, with lowest risk for those receiving counselling alone (HR, 1.84), an intermediate risk for those receiving antidepressants alone (HR, 3.43), and the highest risk for those receiving both (HR, 9.85).”

Likelihood of Seizure Freedom

To assess the effect of depression on seizure outcomes, the researchers analyzed data from 2,573 patients in the Calgary Comprehensive Epilepsy Programme cohort. Data were derived from patients’ first-visit evaluation forms. A total of 504 (20%) of the patients had achieved one-year seizure freedom during the year prior to their first clinic visit. Patients with past or current depression had higher odds of failing to achieve seizure freedom during the previous year, compared with patients without depression (odds ratio, 1.41). When considering only patients with current or past depression (n = 738), current depression treatment (ie, antidepressants, counseling, or both) was associated with significantly higher odds of failing to achieve one-year seizure freedom (odds ratio, 1.75) after controlling for age at onset of epilepsy, sex, lesional epilepsy detected by MRI, history of generalized tonic-clonic seizures, and current antiepileptic drug use.

Overall, the results “indicate a shared relationship between depression and epilepsy, with each appearing to act as a risk factor for the other, and, therefore, should have a direct effect on counseling and management,” Dr. Josephson and colleagues said.

Limitations

The researchers noted that they were unable to control for etiology, epilepsy subtype, or conditions that could cause epilepsy and depression, and they did not have information about the duration, dose, or frequency of depression treatments. Although depression severity may not necessarily determine treatment type, primary care guidelines recommend counseling as first-line treatment for mild depression and combination therapy for severe depression, the researchers said.

Other possible interpretations of the results, such as the idea that antidepressant treatment augments the risk of epilepsy or that patients are more severely depressed because they have not achieved one-year seizure freedom, are less likely. “Counseling interacted with antidepressant exposure and resulted in a threefold increase in the hazard of epilepsy over that of medications alone,” which suggests that “treatment is acting as a proxy for depression severity and is thus consistent with the existence of a biological dose-response relationship,” the researchers said. In addition, “a recent review has indicated that virtually all antidepressants are safe for patients with epilepsy, thereby debunking the notion that these medications increase the risk of seizures.”

—Jake Remaly

Suggested Reading

Josephson CB, Lowerison M, Vallerand I, et al. Association of depression and treated depression with epilepsy and seizure outcomes: A multicohort analysis. JAMA Neurol. 2017;74(5):533-539.

Kanner AM. Most antidepressant drugs are safe for patients with epilepsy at therapeutic doses: A review of the evidence. Epilepsy Behav. 2016;61:282-286.