Restoring native kinematics of the knee has been a primary goal of anterior cruciate ligament (ACL) procedures. Double-bundle ACL reconstruction, compared to single-bundle, has been hypothesized to more effectively re-establish rotational stability by re-creating the anatomic ACL, but has not yet proven to result in better clinical outcomes.¹

In 1879, Dr. Paul Segond described a “fibrous, pearly band” at the lateral aspect of the knee that avulsed off the anterolateral proximal tibia during many ACL injuries.² The role of the lateral tissues in knee stability and their relationship with ACL pathology has attracted noteworthy attention in recent time. There have been multiple studies presenting an anatomical description of a structure at the anterolateral portion of the knee with definitive femoral, meniscal, and tibial attachments, which helps control internal rotational forces.^3-7 Claes and colleagues⁴ later found that band of tissue to be the anterolateral ligament (ALL) and determined its injury to be pathognomonic with ACL ruptures.

The ALL is a vital static stabilizer of the tibio-femoral joint, especially during internal tibial rotation.^8-10 In their report on ALL and ACL reconstruction, Helito and colleagues¹¹ acknowledge the necessity of accurate assessment of the lateral structures through imaging to determine the presence of extra-articular injury. Musculoskeletal diagnostic ultrasound has been established as an appropriate means to identify the ALL.¹²

Ultrasound can accurately determine the exact anatomic location of the origin and insertion of the ALL. Reconstruction of the ALL could yield better patient outcomes for those who experience concurrent ACL/ALL injury. Here we present an innovative technique for an ultrasound-guided percutaneous method for reconstruction of the ALL and report on a patient who had underwent ALL reconstruction.

Surgical Indications

All patients undergo an ultrasound evaluation preoperatively to determine if the ALL is intact or injured. Our experience has shown that when ultrasound evaluation reveals an intact ALL, the pivot shift has never been a grade III.

Surgical Technique

For a demonstration of this technique, see the video that accompanies this article.

The pivot shift test is conducted under anesthesia to determine whether an ALL reconstruction is required. The patient is placed in a supine position with the knee flexed at 30^o, at neutral rotation, and without any varus or valgus stress.

Rehabilitation

Rehabilitation following an ALL procedure is similar to traditional ACL rehabilitation with an added emphasis on minimizing rotational torque of the tibia in the early stages.

Case Report

In January 2013, a 17-year-old male soccer player suffered an ACL rupture of his right knee. Later that spring, he had an ACL reconstruction with an allograft. Twelve months postoperatively, the patient returned, saying that he felt much better; however, anytime he tried to plant his foot and rotate over that fixed foot, his knee felt unstable. The physical examination revealed both negative Lachman and anterior drawer tests but a I+ pivot shift test. A magnetic resonance imaging (MRI) examination revealed an intact ACL graft. A diagnostic ultrasound evaluation revealed a distal ALL injury. After discussing the risks, benefits, and goals with the patient, we opted for a diagnostic arthroscopy and a percutaneous, ultrasound-guided reconstruction of the ALL.

Postoperatively, the patient did very well. One week after surgery, he returned, saying he felt completely stable and demonstrated by repeating the rotation of his knee. The patient continued to have no issues until he returned 13 months post-ALL surgery, complaining of a recent injury that had caused the return of his feelings of instability. An MRI evaluation showed an intact ACL graft and the possibility of a ruptured ALL. Fifteen months after the initial ALL reconstruction, we proceeded with surgery. At arthroscopy, the patient was found to have a pivot shift of I+ and an intact ACL graft. The ALL was reconstructed again using an allograft, internal brace, and bone marrow concentrate. At 13 months post-ALL reconstruction revision, the patient had no complaints.

Discussion

Reconstruction of the ALL is aimed to restore anatomic rotational kinematics. Sonnery-Cottet and colleagues¹⁴ have reported promising initial results in their 2-year follow-up study of combined ACL and ALL reconstruction outcomes. This surgical technique includes use of an internal brace, which negates the necessity for external support devices and allows for earlier mobilization of the joint. A reconstruction of the ALL, performed concurrently with the ACL, does not add recovery time, but could prevent postsurgical complications and improve rehabilitation by eliminating rotational instability that presents in some ACL-reconstructed patients.

Sonnery-Cottet and colleagues¹⁵ state that their arthroscopic identification of the ALL can help to cultivate a “less invasive and more anatomic” reconstruction. The use of musculoskeletal ultrasound allows our technique to utilize a completely noninvasive imaging tool that allows proper establishment of ALL anatomy prior to the procedure. The entirety of the ALL is easily identifiable,^4,12 which has proven to be shortcoming of MRI evaluation.^15-17 Accurate preoperative assessment of the lateral structures is necessary in ACL-deficient individuals.^11,15 Sonography also provides a means of accurate guidance and socket creation, without generating large incisions.

If the ALL is responsible for internal rotatory stability as asserted, the structure should exhibit biomechanical properties during movement. In their study on the function of the ligament, Parsons and colleagues⁹ established the inverse relationship between the ALL and ACL during internal rotation. As their cadaveric knees were subjected to an internal rotatory force through increasing angles of flexion, the contribution of the ALL towards stability significantly increased while the ACL declined. Helito and colleagues⁸ and Zens and colleagues¹⁰ have demonstrated length changes of the ligament through varying degrees of flexion and internal rotation. Their reports indicate greater tension during knee movements, coinciding with the description of increasing ALL stability contribution by Parsons and colleagues.⁹ Kennedy and colleagues⁷ conducted a pull-to-failure test on the ALL. The average failure load was 175 N with a stiffness of 20 N/mm, illustrating the structure is a candidate for most traditional soft tissue grafts. The biomechanical evidence of the structural properties of the ALL confirms its importance in knee function and the necessity for its reconstruction.

With the understanding that ACL contributes to rotatory stability to some extent, the notion begs the question of how a centrally located ligament is able to prevent excessive rotation in a structure with a large relative radius. Biomechanically, with such a small moment arm, the ACL would experience tremendous stress when a rotatory force is applied. The same torque applied to a more superficial structure, with a greater moment, would sustain a large reduction in the applied force. The concept of a wheel and an axle should be considered. The equation is F₁ × R₁ = F₂ × R₂. We measured on a cadaveric knee the distance from the center of rotation to the ACL and the ALL, finding the radii were 5 mm and 30 mm, respectively. Taking these measurements, we would then expect the force experienced on the axle (ACL) to be 6 times greater than what would be experienced on the periphery of the wheel (ALL). The ALL (wheel) has a significant biomechanical advantage over the ACL (axle) in controlling and enduring internal rotatory forces of the knee. This would imply that if the ALL were damaged and not re-established, the ACL would experience a 6 times greater force trying to control internal rotation, which would result in a significantly increased chance of failure and rupture.

While there is a degree of dissent on the presence of the ALL, a number of studies have classified the tissue as an independent ligamentous structure.^3-7 While there is disagreement on the precise location of the femoral attachment, there is a consensus on the location of the tibial and meniscal attachments. Claes and colleagues⁴ originally outlined the femoral attachment as anterior and distal to the origin of the fibular collateral ligament (FCL), which is the description this technique follows. Since Claes and colleagues’⁴ report, many have investigated the ligament’s femoral origin with delineations ranging from posterior and proximal^3,5,7 to anterior and distal.^6,16-18

The accurate, noninvasive nature of the musculoskeletal ultrasound prior to any incisions being made makes this technique innovative and superior to other open surgical techniques or those that require fluoroscopy.

Conclusion

The ALL has been determined to play an integral role in the rotational stability of the knee. In the setting of instability and insufficiency, reconstruction will lead to better patient outcomes for concurrent ACL/ALL injuries and postsurgical rotatory instability following ACL procedures. This innovative technique utilizes ultrasound to ascertain the precise anatomical attachments of the ALL prior to the operation. The novel nature of this ultrasound-guided reconstruction has the potential to be applicable in many other surgical procedures.

Restoring native kinematics of the knee has been a primary goal of anterior cruciate ligament (ACL) procedures. Double-bundle ACL reconstruction, compared to single-bundle, has been hypothesized to more effectively re-establish rotational stability by re-creating the anatomic ACL, but has not yet proven to result in better clinical outcomes.¹

In 1879, Dr. Paul Segond described a “fibrous, pearly band” at the lateral aspect of the knee that avulsed off the anterolateral proximal tibia during many ACL injuries.² The role of the lateral tissues in knee stability and their relationship with ACL pathology has attracted noteworthy attention in recent time. There have been multiple studies presenting an anatomical description of a structure at the anterolateral portion of the knee with definitive femoral, meniscal, and tibial attachments, which helps control internal rotational forces.^3-7 Claes and colleagues⁴ later found that band of tissue to be the anterolateral ligament (ALL) and determined its injury to be pathognomonic with ACL ruptures.

The ALL is a vital static stabilizer of the tibio-femoral joint, especially during internal tibial rotation.^8-10 In their report on ALL and ACL reconstruction, Helito and colleagues¹¹ acknowledge the necessity of accurate assessment of the lateral structures through imaging to determine the presence of extra-articular injury. Musculoskeletal diagnostic ultrasound has been established as an appropriate means to identify the ALL.¹²

Ultrasound can accurately determine the exact anatomic location of the origin and insertion of the ALL. Reconstruction of the ALL could yield better patient outcomes for those who experience concurrent ACL/ALL injury. Here we present an innovative technique for an ultrasound-guided percutaneous method for reconstruction of the ALL and report on a patient who had underwent ALL reconstruction.

Surgical Indications

All patients undergo an ultrasound evaluation preoperatively to determine if the ALL is intact or injured. Our experience has shown that when ultrasound evaluation reveals an intact ALL, the pivot shift has never been a grade III.

Surgical Technique

For a demonstration of this technique, see the video that accompanies this article.

The pivot shift test is conducted under anesthesia to determine whether an ALL reconstruction is required. The patient is placed in a supine position with the knee flexed at 30^o, at neutral rotation, and without any varus or valgus stress.

Rehabilitation

Rehabilitation following an ALL procedure is similar to traditional ACL rehabilitation with an added emphasis on minimizing rotational torque of the tibia in the early stages.

Case Report

In January 2013, a 17-year-old male soccer player suffered an ACL rupture of his right knee. Later that spring, he had an ACL reconstruction with an allograft. Twelve months postoperatively, the patient returned, saying that he felt much better; however, anytime he tried to plant his foot and rotate over that fixed foot, his knee felt unstable. The physical examination revealed both negative Lachman and anterior drawer tests but a I+ pivot shift test. A magnetic resonance imaging (MRI) examination revealed an intact ACL graft. A diagnostic ultrasound evaluation revealed a distal ALL injury. After discussing the risks, benefits, and goals with the patient, we opted for a diagnostic arthroscopy and a percutaneous, ultrasound-guided reconstruction of the ALL.

Postoperatively, the patient did very well. One week after surgery, he returned, saying he felt completely stable and demonstrated by repeating the rotation of his knee. The patient continued to have no issues until he returned 13 months post-ALL surgery, complaining of a recent injury that had caused the return of his feelings of instability. An MRI evaluation showed an intact ACL graft and the possibility of a ruptured ALL. Fifteen months after the initial ALL reconstruction, we proceeded with surgery. At arthroscopy, the patient was found to have a pivot shift of I+ and an intact ACL graft. The ALL was reconstructed again using an allograft, internal brace, and bone marrow concentrate. At 13 months post-ALL reconstruction revision, the patient had no complaints.

Discussion

Reconstruction of the ALL is aimed to restore anatomic rotational kinematics. Sonnery-Cottet and colleagues¹⁴ have reported promising initial results in their 2-year follow-up study of combined ACL and ALL reconstruction outcomes. This surgical technique includes use of an internal brace, which negates the necessity for external support devices and allows for earlier mobilization of the joint. A reconstruction of the ALL, performed concurrently with the ACL, does not add recovery time, but could prevent postsurgical complications and improve rehabilitation by eliminating rotational instability that presents in some ACL-reconstructed patients.

Sonnery-Cottet and colleagues¹⁵ state that their arthroscopic identification of the ALL can help to cultivate a “less invasive and more anatomic” reconstruction. The use of musculoskeletal ultrasound allows our technique to utilize a completely noninvasive imaging tool that allows proper establishment of ALL anatomy prior to the procedure. The entirety of the ALL is easily identifiable,^4,12 which has proven to be shortcoming of MRI evaluation.^15-17 Accurate preoperative assessment of the lateral structures is necessary in ACL-deficient individuals.^11,15 Sonography also provides a means of accurate guidance and socket creation, without generating large incisions.

If the ALL is responsible for internal rotatory stability as asserted, the structure should exhibit biomechanical properties during movement. In their study on the function of the ligament, Parsons and colleagues⁹ established the inverse relationship between the ALL and ACL during internal rotation. As their cadaveric knees were subjected to an internal rotatory force through increasing angles of flexion, the contribution of the ALL towards stability significantly increased while the ACL declined. Helito and colleagues⁸ and Zens and colleagues¹⁰ have demonstrated length changes of the ligament through varying degrees of flexion and internal rotation. Their reports indicate greater tension during knee movements, coinciding with the description of increasing ALL stability contribution by Parsons and colleagues.⁹ Kennedy and colleagues⁷ conducted a pull-to-failure test on the ALL. The average failure load was 175 N with a stiffness of 20 N/mm, illustrating the structure is a candidate for most traditional soft tissue grafts. The biomechanical evidence of the structural properties of the ALL confirms its importance in knee function and the necessity for its reconstruction.

With the understanding that ACL contributes to rotatory stability to some extent, the notion begs the question of how a centrally located ligament is able to prevent excessive rotation in a structure with a large relative radius. Biomechanically, with such a small moment arm, the ACL would experience tremendous stress when a rotatory force is applied. The same torque applied to a more superficial structure, with a greater moment, would sustain a large reduction in the applied force. The concept of a wheel and an axle should be considered. The equation is F₁ × R₁ = F₂ × R₂. We measured on a cadaveric knee the distance from the center of rotation to the ACL and the ALL, finding the radii were 5 mm and 30 mm, respectively. Taking these measurements, we would then expect the force experienced on the axle (ACL) to be 6 times greater than what would be experienced on the periphery of the wheel (ALL). The ALL (wheel) has a significant biomechanical advantage over the ACL (axle) in controlling and enduring internal rotatory forces of the knee. This would imply that if the ALL were damaged and not re-established, the ACL would experience a 6 times greater force trying to control internal rotation, which would result in a significantly increased chance of failure and rupture.

While there is a degree of dissent on the presence of the ALL, a number of studies have classified the tissue as an independent ligamentous structure.^3-7 While there is disagreement on the precise location of the femoral attachment, there is a consensus on the location of the tibial and meniscal attachments. Claes and colleagues⁴ originally outlined the femoral attachment as anterior and distal to the origin of the fibular collateral ligament (FCL), which is the description this technique follows. Since Claes and colleagues’⁴ report, many have investigated the ligament’s femoral origin with delineations ranging from posterior and proximal^3,5,7 to anterior and distal.^6,16-18

The accurate, noninvasive nature of the musculoskeletal ultrasound prior to any incisions being made makes this technique innovative and superior to other open surgical techniques or those that require fluoroscopy.

Conclusion

The ALL has been determined to play an integral role in the rotational stability of the knee. In the setting of instability and insufficiency, reconstruction will lead to better patient outcomes for concurrent ACL/ALL injuries and postsurgical rotatory instability following ACL procedures. This innovative technique utilizes ultrasound to ascertain the precise anatomical attachments of the ALL prior to the operation. The novel nature of this ultrasound-guided reconstruction has the potential to be applicable in many other surgical procedures.

Restoring native kinematics of the knee has been a primary goal of anterior cruciate ligament (ACL) procedures. Double-bundle ACL reconstruction, compared to single-bundle, has been hypothesized to more effectively re-establish rotational stability by re-creating the anatomic ACL, but has not yet proven to result in better clinical outcomes.¹

In 1879, Dr. Paul Segond described a “fibrous, pearly band” at the lateral aspect of the knee that avulsed off the anterolateral proximal tibia during many ACL injuries.² The role of the lateral tissues in knee stability and their relationship with ACL pathology has attracted noteworthy attention in recent time. There have been multiple studies presenting an anatomical description of a structure at the anterolateral portion of the knee with definitive femoral, meniscal, and tibial attachments, which helps control internal rotational forces.^3-7 Claes and colleagues⁴ later found that band of tissue to be the anterolateral ligament (ALL) and determined its injury to be pathognomonic with ACL ruptures.

The ALL is a vital static stabilizer of the tibio-femoral joint, especially during internal tibial rotation.^8-10 In their report on ALL and ACL reconstruction, Helito and colleagues¹¹ acknowledge the necessity of accurate assessment of the lateral structures through imaging to determine the presence of extra-articular injury. Musculoskeletal diagnostic ultrasound has been established as an appropriate means to identify the ALL.¹²

Ultrasound can accurately determine the exact anatomic location of the origin and insertion of the ALL. Reconstruction of the ALL could yield better patient outcomes for those who experience concurrent ACL/ALL injury. Here we present an innovative technique for an ultrasound-guided percutaneous method for reconstruction of the ALL and report on a patient who had underwent ALL reconstruction.

Surgical Indications

All patients undergo an ultrasound evaluation preoperatively to determine if the ALL is intact or injured. Our experience has shown that when ultrasound evaluation reveals an intact ALL, the pivot shift has never been a grade III.

Surgical Technique

For a demonstration of this technique, see the video that accompanies this article.

The pivot shift test is conducted under anesthesia to determine whether an ALL reconstruction is required. The patient is placed in a supine position with the knee flexed at 30^o, at neutral rotation, and without any varus or valgus stress.

Rehabilitation

Rehabilitation following an ALL procedure is similar to traditional ACL rehabilitation with an added emphasis on minimizing rotational torque of the tibia in the early stages.

Case Report

In January 2013, a 17-year-old male soccer player suffered an ACL rupture of his right knee. Later that spring, he had an ACL reconstruction with an allograft. Twelve months postoperatively, the patient returned, saying that he felt much better; however, anytime he tried to plant his foot and rotate over that fixed foot, his knee felt unstable. The physical examination revealed both negative Lachman and anterior drawer tests but a I+ pivot shift test. A magnetic resonance imaging (MRI) examination revealed an intact ACL graft. A diagnostic ultrasound evaluation revealed a distal ALL injury. After discussing the risks, benefits, and goals with the patient, we opted for a diagnostic arthroscopy and a percutaneous, ultrasound-guided reconstruction of the ALL.

Postoperatively, the patient did very well. One week after surgery, he returned, saying he felt completely stable and demonstrated by repeating the rotation of his knee. The patient continued to have no issues until he returned 13 months post-ALL surgery, complaining of a recent injury that had caused the return of his feelings of instability. An MRI evaluation showed an intact ACL graft and the possibility of a ruptured ALL. Fifteen months after the initial ALL reconstruction, we proceeded with surgery. At arthroscopy, the patient was found to have a pivot shift of I+ and an intact ACL graft. The ALL was reconstructed again using an allograft, internal brace, and bone marrow concentrate. At 13 months post-ALL reconstruction revision, the patient had no complaints.

Discussion

Reconstruction of the ALL is aimed to restore anatomic rotational kinematics. Sonnery-Cottet and colleagues¹⁴ have reported promising initial results in their 2-year follow-up study of combined ACL and ALL reconstruction outcomes. This surgical technique includes use of an internal brace, which negates the necessity for external support devices and allows for earlier mobilization of the joint. A reconstruction of the ALL, performed concurrently with the ACL, does not add recovery time, but could prevent postsurgical complications and improve rehabilitation by eliminating rotational instability that presents in some ACL-reconstructed patients.

Sonnery-Cottet and colleagues¹⁵ state that their arthroscopic identification of the ALL can help to cultivate a “less invasive and more anatomic” reconstruction. The use of musculoskeletal ultrasound allows our technique to utilize a completely noninvasive imaging tool that allows proper establishment of ALL anatomy prior to the procedure. The entirety of the ALL is easily identifiable,^4,12 which has proven to be shortcoming of MRI evaluation.^15-17 Accurate preoperative assessment of the lateral structures is necessary in ACL-deficient individuals.^11,15 Sonography also provides a means of accurate guidance and socket creation, without generating large incisions.

If the ALL is responsible for internal rotatory stability as asserted, the structure should exhibit biomechanical properties during movement. In their study on the function of the ligament, Parsons and colleagues⁹ established the inverse relationship between the ALL and ACL during internal rotation. As their cadaveric knees were subjected to an internal rotatory force through increasing angles of flexion, the contribution of the ALL towards stability significantly increased while the ACL declined. Helito and colleagues⁸ and Zens and colleagues¹⁰ have demonstrated length changes of the ligament through varying degrees of flexion and internal rotation. Their reports indicate greater tension during knee movements, coinciding with the description of increasing ALL stability contribution by Parsons and colleagues.⁹ Kennedy and colleagues⁷ conducted a pull-to-failure test on the ALL. The average failure load was 175 N with a stiffness of 20 N/mm, illustrating the structure is a candidate for most traditional soft tissue grafts. The biomechanical evidence of the structural properties of the ALL confirms its importance in knee function and the necessity for its reconstruction.

With the understanding that ACL contributes to rotatory stability to some extent, the notion begs the question of how a centrally located ligament is able to prevent excessive rotation in a structure with a large relative radius. Biomechanically, with such a small moment arm, the ACL would experience tremendous stress when a rotatory force is applied. The same torque applied to a more superficial structure, with a greater moment, would sustain a large reduction in the applied force. The concept of a wheel and an axle should be considered. The equation is F₁ × R₁ = F₂ × R₂. We measured on a cadaveric knee the distance from the center of rotation to the ACL and the ALL, finding the radii were 5 mm and 30 mm, respectively. Taking these measurements, we would then expect the force experienced on the axle (ACL) to be 6 times greater than what would be experienced on the periphery of the wheel (ALL). The ALL (wheel) has a significant biomechanical advantage over the ACL (axle) in controlling and enduring internal rotatory forces of the knee. This would imply that if the ALL were damaged and not re-established, the ACL would experience a 6 times greater force trying to control internal rotation, which would result in a significantly increased chance of failure and rupture.

While there is a degree of dissent on the presence of the ALL, a number of studies have classified the tissue as an independent ligamentous structure.^3-7 While there is disagreement on the precise location of the femoral attachment, there is a consensus on the location of the tibial and meniscal attachments. Claes and colleagues⁴ originally outlined the femoral attachment as anterior and distal to the origin of the fibular collateral ligament (FCL), which is the description this technique follows. Since Claes and colleagues’⁴ report, many have investigated the ligament’s femoral origin with delineations ranging from posterior and proximal^3,5,7 to anterior and distal.^6,16-18

The accurate, noninvasive nature of the musculoskeletal ultrasound prior to any incisions being made makes this technique innovative and superior to other open surgical techniques or those that require fluoroscopy.

Conclusion

The ALL has been determined to play an integral role in the rotational stability of the knee. In the setting of instability and insufficiency, reconstruction will lead to better patient outcomes for concurrent ACL/ALL injuries and postsurgical rotatory instability following ACL procedures. This innovative technique utilizes ultrasound to ascertain the precise anatomical attachments of the ALL prior to the operation. The novel nature of this ultrasound-guided reconstruction has the potential to be applicable in many other surgical procedures.

Those who cannot remember the past are condemned to repeat it.

—George Santayana (Life of Reason, 1905)

Zero. That’s the number I put on the screen when I start the lecture I give to residents about the future of orthopedics. It represents the number of cases I still do exactly the same way now as I did when I graduated from my residency program. It represents the commitment to lifelong learning that we’ve made as orthopedists. Surgical techniques innovate so rapidly that they often outpace our research, leaving us performing new techniques based solely on industry and key opinion leader recommendation, and not on randomized controlled studies. Sometimes we’re led down the wrong path (remember when the meniscus was thought to be vestigial?) and other times new techniques lead to disappointing long-term results (the transtibial anterior cruciate ligament’s (ACL’s) failure to prevent arthritis). Sometimes, the old way is just as good as the new (there is no evidence to suggest that results from arthroscopic cuff repair are better than open in the long term). If we’ve been in practice long enough, we see the same ideas come around again (meniscal spacers, ACL repair, anterolateral ligament [ALL]). Most often, these new variations offer a slightly different twist and supporting literature.

So it seems “everything old is new again.” That’s why this issue of AJO is called The Throwback Issue. In this issue, we revisit ideas whose time has come and gone and now come again.

Our lead article this month focuses on ACL repair. Once abandoned after a landmark paper by Feagin and Curl¹ showed poor mid-term results, new and innovative techniques and instrumentation for knee surgery have made this possible. Investigators such as Murray² and DiFelice³ have done outstanding work showing the feasibility of ACL repair. In this issue we offer a comprehensive review and surgical technique for adding ACL repair to your portfolio of surgical offerings (see pages 408 and 454). Expanded versions of both of these articles are available at amjorthopedics.com.

Our second feature article discusses the reemergence of the ALL, an idea so hot in the public domain that it has been featured as a Jeopardy question. Described originally by Müller⁴ as the missing link in persistent rotational instability, the ALL might offer the key to improved long-term outcomes for patients undergoing ACL surgery. Read the article on page 418 and learn how to identify which patients are candidates for ALL reconstruction, and a simple surgical technique you can apply to your practice. Scan the provided QR code to watch the accompanying surgical technique video.

The Throwback Issue marks the fifth edition of the “new AJO.” It’s time to let us know how we are doing. Please email us at [email protected] to suggest future themes, articles you’d like to read, or suggestions for improvement.

Recently, based on the work of the authors mentioned above, I’ve begun offering ACL repair to select patients in my practice. I wouldn’t be able to do this if we as orthopedists weren’t constantly looking to improve, and weren’t willing to revisit old ideas to do it. Our goal at AJO is to present something in every article that can be immediately applied to your practice. Take a look at the articles presented this month, as we go “Back to the Future” to see what discarded ideas from our recent past can be applied to improve outcomes for your patients in the future.

Those who cannot remember the past are condemned to repeat it.

—George Santayana (Life of Reason, 1905)

Zero. That’s the number I put on the screen when I start the lecture I give to residents about the future of orthopedics. It represents the number of cases I still do exactly the same way now as I did when I graduated from my residency program. It represents the commitment to lifelong learning that we’ve made as orthopedists. Surgical techniques innovate so rapidly that they often outpace our research, leaving us performing new techniques based solely on industry and key opinion leader recommendation, and not on randomized controlled studies. Sometimes we’re led down the wrong path (remember when the meniscus was thought to be vestigial?) and other times new techniques lead to disappointing long-term results (the transtibial anterior cruciate ligament’s (ACL’s) failure to prevent arthritis). Sometimes, the old way is just as good as the new (there is no evidence to suggest that results from arthroscopic cuff repair are better than open in the long term). If we’ve been in practice long enough, we see the same ideas come around again (meniscal spacers, ACL repair, anterolateral ligament [ALL]). Most often, these new variations offer a slightly different twist and supporting literature.

So it seems “everything old is new again.” That’s why this issue of AJO is called The Throwback Issue. In this issue, we revisit ideas whose time has come and gone and now come again.

Our lead article this month focuses on ACL repair. Once abandoned after a landmark paper by Feagin and Curl¹ showed poor mid-term results, new and innovative techniques and instrumentation for knee surgery have made this possible. Investigators such as Murray² and DiFelice³ have done outstanding work showing the feasibility of ACL repair. In this issue we offer a comprehensive review and surgical technique for adding ACL repair to your portfolio of surgical offerings (see pages 408 and 454). Expanded versions of both of these articles are available at amjorthopedics.com.

Our second feature article discusses the reemergence of the ALL, an idea so hot in the public domain that it has been featured as a Jeopardy question. Described originally by Müller⁴ as the missing link in persistent rotational instability, the ALL might offer the key to improved long-term outcomes for patients undergoing ACL surgery. Read the article on page 418 and learn how to identify which patients are candidates for ALL reconstruction, and a simple surgical technique you can apply to your practice. Scan the provided QR code to watch the accompanying surgical technique video.

The Throwback Issue marks the fifth edition of the “new AJO.” It’s time to let us know how we are doing. Please email us at [email protected] to suggest future themes, articles you’d like to read, or suggestions for improvement.

Recently, based on the work of the authors mentioned above, I’ve begun offering ACL repair to select patients in my practice. I wouldn’t be able to do this if we as orthopedists weren’t constantly looking to improve, and weren’t willing to revisit old ideas to do it. Our goal at AJO is to present something in every article that can be immediately applied to your practice. Take a look at the articles presented this month, as we go “Back to the Future” to see what discarded ideas from our recent past can be applied to improve outcomes for your patients in the future.

Those who cannot remember the past are condemned to repeat it.

—George Santayana (Life of Reason, 1905)

Zero. That’s the number I put on the screen when I start the lecture I give to residents about the future of orthopedics. It represents the number of cases I still do exactly the same way now as I did when I graduated from my residency program. It represents the commitment to lifelong learning that we’ve made as orthopedists. Surgical techniques innovate so rapidly that they often outpace our research, leaving us performing new techniques based solely on industry and key opinion leader recommendation, and not on randomized controlled studies. Sometimes we’re led down the wrong path (remember when the meniscus was thought to be vestigial?) and other times new techniques lead to disappointing long-term results (the transtibial anterior cruciate ligament’s (ACL’s) failure to prevent arthritis). Sometimes, the old way is just as good as the new (there is no evidence to suggest that results from arthroscopic cuff repair are better than open in the long term). If we’ve been in practice long enough, we see the same ideas come around again (meniscal spacers, ACL repair, anterolateral ligament [ALL]). Most often, these new variations offer a slightly different twist and supporting literature.

So it seems “everything old is new again.” That’s why this issue of AJO is called The Throwback Issue. In this issue, we revisit ideas whose time has come and gone and now come again.

Our lead article this month focuses on ACL repair. Once abandoned after a landmark paper by Feagin and Curl¹ showed poor mid-term results, new and innovative techniques and instrumentation for knee surgery have made this possible. Investigators such as Murray² and DiFelice³ have done outstanding work showing the feasibility of ACL repair. In this issue we offer a comprehensive review and surgical technique for adding ACL repair to your portfolio of surgical offerings (see pages 408 and 454). Expanded versions of both of these articles are available at amjorthopedics.com.

Our second feature article discusses the reemergence of the ALL, an idea so hot in the public domain that it has been featured as a Jeopardy question. Described originally by Müller⁴ as the missing link in persistent rotational instability, the ALL might offer the key to improved long-term outcomes for patients undergoing ACL surgery. Read the article on page 418 and learn how to identify which patients are candidates for ALL reconstruction, and a simple surgical technique you can apply to your practice. Scan the provided QR code to watch the accompanying surgical technique video.

The Throwback Issue marks the fifth edition of the “new AJO.” It’s time to let us know how we are doing. Please email us at [email protected] to suggest future themes, articles you’d like to read, or suggestions for improvement.

Recently, based on the work of the authors mentioned above, I’ve begun offering ACL repair to select patients in my practice. I wouldn’t be able to do this if we as orthopedists weren’t constantly looking to improve, and weren’t willing to revisit old ideas to do it. Our goal at AJO is to present something in every article that can be immediately applied to your practice. Take a look at the articles presented this month, as we go “Back to the Future” to see what discarded ideas from our recent past can be applied to improve outcomes for your patients in the future.

Research flock at US

Sheep Experiment Station

Research conducted in sheep indicates that pretreating red blood cells (RBCs) with nitric oxide (NO) may make it safer to transfuse blood nearing its expiration date.

Past studies have suggested that RBCs stored for more than 30 days are less likely than “fresher” RBCs to survive after transfusion, and receiving a transfusion of RBCs nearing their expiration date of 42 days may increase the risk of pulmonary hypertension.

However, a new study published in Anesthesiology suggests that pretreating older RBCs with NO may increase their likelihood of survival after transfusion and reduce the risk of pulmonary hypertension in the recipient.

“Extended storage of RBCs makes them rigid and decreases their ability to change shape, which is necessary as they travel through small blood vessels,” said study author Warren M. Zapol, MD, of Massachusetts General Hospital in Boston.

“We found that pretreatment with nitric oxide actually rejuvenates RBCs, making them more flexible so they can more easily travel through blood vessels. This can further reduce the risk of pulmonary hypertension.”

Dr Zapol and his colleagues performed their experiments on RBCs derived from lambs. The team treated RBCs with NO gas, a short-lived NO donor, or gas without NO (control).

The RBCs were then stored for either 2 days (hereafter referred to as “fresh” RBCs) or 40 days (referred to as “stored” RBCs) and transfused back into the original lambs.

RBC survival

The researchers found that treatment with NO gas improved the early post-transfusion survival of stored RBCs.

At 1 hour after transfusion, 75.3 ± 5.8% of the control-treated stored RBCs remained in the circulation, compared to 86.8 ± 8.1% of the NO-treated stored RBCs and 94.2 ± 4.6% of the fresh RBCs.

At 24 hours after transfusion, 73.4 ± 3.8% of the control-treated stored RBCs remained in the circulation, compared to 78.3 ± 6.3% of the NO-treated stored RBCs, 90.8 ± 4.1% of control-treated fresh RBCs, and 91.4 ± 1.4% of NO-treated fresh RBCs.

The differences between stored RBCs that were treated with NO gas and stored control RBCs was statistically significant at both 1 hour and 24 hours, with P values of 0.002 and 0.046, respectively.

Seven days after transfusion, there was no significant difference in the percentage of NO-treated and control-treated RBCs in the circulation.

Pulmonary hypertension

The researchers found that pretreating RBCs with NO prevented transfusion-associated pulmonary hypertension in the lambs.

Lambs that received control-treated stored RBCs had an increase in pulmonary arterial pressure (PAP) during and after transfusion—from 13.4 ± 0.8 mmHg at baseline to a maximum of 22.7 ± 2.2 mmHg.

However, lambs that received stored RBCs treated with NO gas did not have an increase in PAP when compared to lambs that received fresh RBCs.

At 20 minutes, PAP was 14.5 ± 1.4 mmHg for NO-treated stored RBCs, 13.9 ± 0.6 mmHg for control-treated fresh RBCs, and 14 ± 1.2 mmHg for NO-treated fresh RBCs.

The researchers also found that transfusion of stored RBCs caused a transient increase in the pulmonary vascular resistance index (PVRI) from 10 minutes to 30 minutes after transfusion, but pretreatment with NO gas prevented this increase.

At 20 minutes, the PVRI was 211.1 ± 44.4 dyn·sec·cm⁻⁵·m⁻² for control-treated stored RBCs and 114.6 ± 18.9 dyn·sec·cm⁻⁵·m⁻² for NO-treated stored RBCs (P<0.0001).

Transfusion of fresh RBCs, with or without prior NO exposure, did not alter the PVRI.

Finally, the researchers found that treating stored RBCs with the NO donor compound MAHMA NONOate prevented transfusion-associated pulmonary hypertension and pulmonary vasoconstriction in awake lambs.

The team said studies with human RBCs are required to confirm the beneficial effects of NO exposure observed in this study.

Research flock at US

Sheep Experiment Station

Research conducted in sheep indicates that pretreating red blood cells (RBCs) with nitric oxide (NO) may make it safer to transfuse blood nearing its expiration date.

Past studies have suggested that RBCs stored for more than 30 days are less likely than “fresher” RBCs to survive after transfusion, and receiving a transfusion of RBCs nearing their expiration date of 42 days may increase the risk of pulmonary hypertension.

However, a new study published in Anesthesiology suggests that pretreating older RBCs with NO may increase their likelihood of survival after transfusion and reduce the risk of pulmonary hypertension in the recipient.

“Extended storage of RBCs makes them rigid and decreases their ability to change shape, which is necessary as they travel through small blood vessels,” said study author Warren M. Zapol, MD, of Massachusetts General Hospital in Boston.

“We found that pretreatment with nitric oxide actually rejuvenates RBCs, making them more flexible so they can more easily travel through blood vessels. This can further reduce the risk of pulmonary hypertension.”

Dr Zapol and his colleagues performed their experiments on RBCs derived from lambs. The team treated RBCs with NO gas, a short-lived NO donor, or gas without NO (control).

The RBCs were then stored for either 2 days (hereafter referred to as “fresh” RBCs) or 40 days (referred to as “stored” RBCs) and transfused back into the original lambs.

RBC survival

The researchers found that treatment with NO gas improved the early post-transfusion survival of stored RBCs.

At 1 hour after transfusion, 75.3 ± 5.8% of the control-treated stored RBCs remained in the circulation, compared to 86.8 ± 8.1% of the NO-treated stored RBCs and 94.2 ± 4.6% of the fresh RBCs.

At 24 hours after transfusion, 73.4 ± 3.8% of the control-treated stored RBCs remained in the circulation, compared to 78.3 ± 6.3% of the NO-treated stored RBCs, 90.8 ± 4.1% of control-treated fresh RBCs, and 91.4 ± 1.4% of NO-treated fresh RBCs.

The differences between stored RBCs that were treated with NO gas and stored control RBCs was statistically significant at both 1 hour and 24 hours, with P values of 0.002 and 0.046, respectively.

Seven days after transfusion, there was no significant difference in the percentage of NO-treated and control-treated RBCs in the circulation.

Pulmonary hypertension

The researchers found that pretreating RBCs with NO prevented transfusion-associated pulmonary hypertension in the lambs.

Lambs that received control-treated stored RBCs had an increase in pulmonary arterial pressure (PAP) during and after transfusion—from 13.4 ± 0.8 mmHg at baseline to a maximum of 22.7 ± 2.2 mmHg.

However, lambs that received stored RBCs treated with NO gas did not have an increase in PAP when compared to lambs that received fresh RBCs.

At 20 minutes, PAP was 14.5 ± 1.4 mmHg for NO-treated stored RBCs, 13.9 ± 0.6 mmHg for control-treated fresh RBCs, and 14 ± 1.2 mmHg for NO-treated fresh RBCs.

The researchers also found that transfusion of stored RBCs caused a transient increase in the pulmonary vascular resistance index (PVRI) from 10 minutes to 30 minutes after transfusion, but pretreatment with NO gas prevented this increase.

At 20 minutes, the PVRI was 211.1 ± 44.4 dyn·sec·cm⁻⁵·m⁻² for control-treated stored RBCs and 114.6 ± 18.9 dyn·sec·cm⁻⁵·m⁻² for NO-treated stored RBCs (P<0.0001).

Transfusion of fresh RBCs, with or without prior NO exposure, did not alter the PVRI.

Finally, the researchers found that treating stored RBCs with the NO donor compound MAHMA NONOate prevented transfusion-associated pulmonary hypertension and pulmonary vasoconstriction in awake lambs.

The team said studies with human RBCs are required to confirm the beneficial effects of NO exposure observed in this study.

Research flock at US

Sheep Experiment Station

Research conducted in sheep indicates that pretreating red blood cells (RBCs) with nitric oxide (NO) may make it safer to transfuse blood nearing its expiration date.

Past studies have suggested that RBCs stored for more than 30 days are less likely than “fresher” RBCs to survive after transfusion, and receiving a transfusion of RBCs nearing their expiration date of 42 days may increase the risk of pulmonary hypertension.

However, a new study published in Anesthesiology suggests that pretreating older RBCs with NO may increase their likelihood of survival after transfusion and reduce the risk of pulmonary hypertension in the recipient.

“Extended storage of RBCs makes them rigid and decreases their ability to change shape, which is necessary as they travel through small blood vessels,” said study author Warren M. Zapol, MD, of Massachusetts General Hospital in Boston.

“We found that pretreatment with nitric oxide actually rejuvenates RBCs, making them more flexible so they can more easily travel through blood vessels. This can further reduce the risk of pulmonary hypertension.”

Dr Zapol and his colleagues performed their experiments on RBCs derived from lambs. The team treated RBCs with NO gas, a short-lived NO donor, or gas without NO (control).

The RBCs were then stored for either 2 days (hereafter referred to as “fresh” RBCs) or 40 days (referred to as “stored” RBCs) and transfused back into the original lambs.

RBC survival

The researchers found that treatment with NO gas improved the early post-transfusion survival of stored RBCs.

At 1 hour after transfusion, 75.3 ± 5.8% of the control-treated stored RBCs remained in the circulation, compared to 86.8 ± 8.1% of the NO-treated stored RBCs and 94.2 ± 4.6% of the fresh RBCs.

At 24 hours after transfusion, 73.4 ± 3.8% of the control-treated stored RBCs remained in the circulation, compared to 78.3 ± 6.3% of the NO-treated stored RBCs, 90.8 ± 4.1% of control-treated fresh RBCs, and 91.4 ± 1.4% of NO-treated fresh RBCs.

The differences between stored RBCs that were treated with NO gas and stored control RBCs was statistically significant at both 1 hour and 24 hours, with P values of 0.002 and 0.046, respectively.

Seven days after transfusion, there was no significant difference in the percentage of NO-treated and control-treated RBCs in the circulation.

Pulmonary hypertension

The researchers found that pretreating RBCs with NO prevented transfusion-associated pulmonary hypertension in the lambs.

Lambs that received control-treated stored RBCs had an increase in pulmonary arterial pressure (PAP) during and after transfusion—from 13.4 ± 0.8 mmHg at baseline to a maximum of 22.7 ± 2.2 mmHg.

However, lambs that received stored RBCs treated with NO gas did not have an increase in PAP when compared to lambs that received fresh RBCs.

At 20 minutes, PAP was 14.5 ± 1.4 mmHg for NO-treated stored RBCs, 13.9 ± 0.6 mmHg for control-treated fresh RBCs, and 14 ± 1.2 mmHg for NO-treated fresh RBCs.

The researchers also found that transfusion of stored RBCs caused a transient increase in the pulmonary vascular resistance index (PVRI) from 10 minutes to 30 minutes after transfusion, but pretreatment with NO gas prevented this increase.

At 20 minutes, the PVRI was 211.1 ± 44.4 dyn·sec·cm⁻⁵·m⁻² for control-treated stored RBCs and 114.6 ± 18.9 dyn·sec·cm⁻⁵·m⁻² for NO-treated stored RBCs (P<0.0001).

Transfusion of fresh RBCs, with or without prior NO exposure, did not alter the PVRI.

Finally, the researchers found that treating stored RBCs with the NO donor compound MAHMA NONOate prevented transfusion-associated pulmonary hypertension and pulmonary vasoconstriction in awake lambs.

The team said studies with human RBCs are required to confirm the beneficial effects of NO exposure observed in this study.

Cancer patient

receiving treatment

Photo by Rhoda Baer

The American Cancer Society and National Cancer Institute have launched an online tool for cancer patients and survivors.

The tool, Springboard Beyond Cancer, was designed to help these individuals address medical, psychosocial, and wellness needs during and after treatment.

Springboard Beyond Cancer provides information to help cancer patients and survivors manage ongoing cancer-related symptoms, deal with stress, ensure healthy behavior, communicate better with healthcare teams, and seek support from friends and family.

“With Springboard Beyond Cancer, we want to empower cancer survivors by giving them the information they need to help identify issues, set goals, and create a plan to more smoothly navigate the cancer journey and take control of their health,” said Corinne Leach, PhD, a behavioral scientist and strategic director in the Behavioral Research Center at the American Cancer Society.

“We hope that Springboard Beyond Cancer, along with the close collaboration of their medical team, can help cancer survivors reduce their disease burden and improve their overall wellbeing,” added Erik Augustson, PhD, program director at the National Cancer Institute.

Cancer patient

receiving treatment

Photo by Rhoda Baer

The American Cancer Society and National Cancer Institute have launched an online tool for cancer patients and survivors.

The tool, Springboard Beyond Cancer, was designed to help these individuals address medical, psychosocial, and wellness needs during and after treatment.

Springboard Beyond Cancer provides information to help cancer patients and survivors manage ongoing cancer-related symptoms, deal with stress, ensure healthy behavior, communicate better with healthcare teams, and seek support from friends and family.

“With Springboard Beyond Cancer, we want to empower cancer survivors by giving them the information they need to help identify issues, set goals, and create a plan to more smoothly navigate the cancer journey and take control of their health,” said Corinne Leach, PhD, a behavioral scientist and strategic director in the Behavioral Research Center at the American Cancer Society.

“We hope that Springboard Beyond Cancer, along with the close collaboration of their medical team, can help cancer survivors reduce their disease burden and improve their overall wellbeing,” added Erik Augustson, PhD, program director at the National Cancer Institute.

Cancer patient

receiving treatment

Photo by Rhoda Baer

The American Cancer Society and National Cancer Institute have launched an online tool for cancer patients and survivors.

The tool, Springboard Beyond Cancer, was designed to help these individuals address medical, psychosocial, and wellness needs during and after treatment.

Springboard Beyond Cancer provides information to help cancer patients and survivors manage ongoing cancer-related symptoms, deal with stress, ensure healthy behavior, communicate better with healthcare teams, and seek support from friends and family.

“With Springboard Beyond Cancer, we want to empower cancer survivors by giving them the information they need to help identify issues, set goals, and create a plan to more smoothly navigate the cancer journey and take control of their health,” said Corinne Leach, PhD, a behavioral scientist and strategic director in the Behavioral Research Center at the American Cancer Society.

“We hope that Springboard Beyond Cancer, along with the close collaboration of their medical team, can help cancer survivors reduce their disease burden and improve their overall wellbeing,” added Erik Augustson, PhD, program director at the National Cancer Institute.

 

 

Blood sample collection

Photo by Juan D. Alfonso

 

A blood test can reveal genetic features linked to outcomes in patients with diffuse large B-cell lymphoma (DLBCL), according to research published in Science Translational Medicine.

Investigators used targeted sequencing to analyze circulating tumor DNA (ctDNA) in blood samples from DLBCL patients.

This allowed the team to identify the cell of origin, detect minimal residual disease (MRD), and predict progression-free survival (PFS) in these patients.

Florian Scherer, MD, of Stanford University in California, and his colleagues conducted this research.

They used cancer personalized profiling by deep sequencing (CAPP-Seq) to analyze tumor biopsies and cell-free DNA samples from 92 patients with DLBCL and 24 healthy controls.

The investigators found that CAPP-Seq could effectively detect somatic mutations in DLBCL plasma samples as well as tumor biopsies. They said their results suggest ctDNA is a “robust surrogate for direct assessment of primary tumor genotypes” in most DLBCL patients.

In addition, ctDNA profiling with CAPP-Seq revealed mutations associated with resistance to the BTK inhibitor ibrutinib.

The investigators also said their results suggest ctDNA profiling can be used to classify DLBCL subtypes. The overall concordance in cell of origin predictions between tumor tissue and plasma genotyping was 88%.

Another key finding of this study is that the amount of ctDNA at DLBCL diagnosis was predictive of PFS. The investigators said higher ctDNA levels at diagnosis were “continuously and independently” correlated with inferior PFS.

Dr Scherer and his colleagues also discovered that ctDNA profiling could detect MRD with greater accuracy than immunoglobulin sequencing and radiographic imaging. And patients with ctDNA in their plasma had significantly worse PFS than patients with undetectable ctDNA.

Finally, the investigators found evidence to suggest that ctDNA profiling could provide early detection of disease transformation. They identified “distinct patterns of clonal evolution” by which they could distinguish indolent follicular lymphomas from follicular lymphomas that transformed into DLBCL.

 

 

Blood sample collection

Photo by Juan D. Alfonso

 

A blood test can reveal genetic features linked to outcomes in patients with diffuse large B-cell lymphoma (DLBCL), according to research published in Science Translational Medicine.

Investigators used targeted sequencing to analyze circulating tumor DNA (ctDNA) in blood samples from DLBCL patients.

This allowed the team to identify the cell of origin, detect minimal residual disease (MRD), and predict progression-free survival (PFS) in these patients.

Florian Scherer, MD, of Stanford University in California, and his colleagues conducted this research.

They used cancer personalized profiling by deep sequencing (CAPP-Seq) to analyze tumor biopsies and cell-free DNA samples from 92 patients with DLBCL and 24 healthy controls.

The investigators found that CAPP-Seq could effectively detect somatic mutations in DLBCL plasma samples as well as tumor biopsies. They said their results suggest ctDNA is a “robust surrogate for direct assessment of primary tumor genotypes” in most DLBCL patients.

In addition, ctDNA profiling with CAPP-Seq revealed mutations associated with resistance to the BTK inhibitor ibrutinib.

The investigators also said their results suggest ctDNA profiling can be used to classify DLBCL subtypes. The overall concordance in cell of origin predictions between tumor tissue and plasma genotyping was 88%.

Another key finding of this study is that the amount of ctDNA at DLBCL diagnosis was predictive of PFS. The investigators said higher ctDNA levels at diagnosis were “continuously and independently” correlated with inferior PFS.

Dr Scherer and his colleagues also discovered that ctDNA profiling could detect MRD with greater accuracy than immunoglobulin sequencing and radiographic imaging. And patients with ctDNA in their plasma had significantly worse PFS than patients with undetectable ctDNA.

Finally, the investigators found evidence to suggest that ctDNA profiling could provide early detection of disease transformation. They identified “distinct patterns of clonal evolution” by which they could distinguish indolent follicular lymphomas from follicular lymphomas that transformed into DLBCL.

 

 

Blood sample collection

Photo by Juan D. Alfonso

 

A blood test can reveal genetic features linked to outcomes in patients with diffuse large B-cell lymphoma (DLBCL), according to research published in Science Translational Medicine.

Investigators used targeted sequencing to analyze circulating tumor DNA (ctDNA) in blood samples from DLBCL patients.

This allowed the team to identify the cell of origin, detect minimal residual disease (MRD), and predict progression-free survival (PFS) in these patients.

Florian Scherer, MD, of Stanford University in California, and his colleagues conducted this research.

They used cancer personalized profiling by deep sequencing (CAPP-Seq) to analyze tumor biopsies and cell-free DNA samples from 92 patients with DLBCL and 24 healthy controls.

The investigators found that CAPP-Seq could effectively detect somatic mutations in DLBCL plasma samples as well as tumor biopsies. They said their results suggest ctDNA is a “robust surrogate for direct assessment of primary tumor genotypes” in most DLBCL patients.

In addition, ctDNA profiling with CAPP-Seq revealed mutations associated with resistance to the BTK inhibitor ibrutinib.

The investigators also said their results suggest ctDNA profiling can be used to classify DLBCL subtypes. The overall concordance in cell of origin predictions between tumor tissue and plasma genotyping was 88%.

Another key finding of this study is that the amount of ctDNA at DLBCL diagnosis was predictive of PFS. The investigators said higher ctDNA levels at diagnosis were “continuously and independently” correlated with inferior PFS.

Dr Scherer and his colleagues also discovered that ctDNA profiling could detect MRD with greater accuracy than immunoglobulin sequencing and radiographic imaging. And patients with ctDNA in their plasma had significantly worse PFS than patients with undetectable ctDNA.

Finally, the investigators found evidence to suggest that ctDNA profiling could provide early detection of disease transformation. They identified “distinct patterns of clonal evolution” by which they could distinguish indolent follicular lymphomas from follicular lymphomas that transformed into DLBCL.

The experimental Ebola treatment ZMapp, which is composed of 3 different monoclonal antibodies, prevents progression of Ebola virus disease by targeting the main surface protein of the virus. According to findings from the clinical trial PREVAIL II, ZMapp is safe and well tolerated. But because the Ebola epidemic is “waning,” NIH says, the study enrolled too few people to determine definitively whether it is a better treatment than the best available standard of care.

Related: Novel Treatment for Ebola Virus

The study involved 72 men and women with confirmed infection. However, the researchers closed the study early because they could not enroll the target number of 200 participants due to the decline in cases. All patients received the optimized standard of care—IV fluids, electrolyte balance, maintaining oxygen and blood pressure levels—and half also received 3 IV infusions of ZMapp 3 days apart.

At 28 days, 13 of the 35 patients (37%) in the standard care group had died, compared with 8 of 36 (22%) in the ZMapp group. That difference, a 40% lower risk of death with ZMapp, still did not reach statistical significance.

Related: Ebola Virus Persists in Semen Long Term

The findings are “promising and provide valuable scientific data,” says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases. Moreover, he adds, “Importantly, the study establishes that it is feasible to conduct a randomized, controlled trial during a major public health emergency in a scientifically and ethically sound manner.”

The experimental Ebola treatment ZMapp, which is composed of 3 different monoclonal antibodies, prevents progression of Ebola virus disease by targeting the main surface protein of the virus. According to findings from the clinical trial PREVAIL II, ZMapp is safe and well tolerated. But because the Ebola epidemic is “waning,” NIH says, the study enrolled too few people to determine definitively whether it is a better treatment than the best available standard of care.

Related: Novel Treatment for Ebola Virus

The study involved 72 men and women with confirmed infection. However, the researchers closed the study early because they could not enroll the target number of 200 participants due to the decline in cases. All patients received the optimized standard of care—IV fluids, electrolyte balance, maintaining oxygen and blood pressure levels—and half also received 3 IV infusions of ZMapp 3 days apart.

At 28 days, 13 of the 35 patients (37%) in the standard care group had died, compared with 8 of 36 (22%) in the ZMapp group. That difference, a 40% lower risk of death with ZMapp, still did not reach statistical significance.

Related: Ebola Virus Persists in Semen Long Term

The findings are “promising and provide valuable scientific data,” says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases. Moreover, he adds, “Importantly, the study establishes that it is feasible to conduct a randomized, controlled trial during a major public health emergency in a scientifically and ethically sound manner.”

The experimental Ebola treatment ZMapp, which is composed of 3 different monoclonal antibodies, prevents progression of Ebola virus disease by targeting the main surface protein of the virus. According to findings from the clinical trial PREVAIL II, ZMapp is safe and well tolerated. But because the Ebola epidemic is “waning,” NIH says, the study enrolled too few people to determine definitively whether it is a better treatment than the best available standard of care.

Related: Novel Treatment for Ebola Virus

The study involved 72 men and women with confirmed infection. However, the researchers closed the study early because they could not enroll the target number of 200 participants due to the decline in cases. All patients received the optimized standard of care—IV fluids, electrolyte balance, maintaining oxygen and blood pressure levels—and half also received 3 IV infusions of ZMapp 3 days apart.

At 28 days, 13 of the 35 patients (37%) in the standard care group had died, compared with 8 of 36 (22%) in the ZMapp group. That difference, a 40% lower risk of death with ZMapp, still did not reach statistical significance.

Related: Ebola Virus Persists in Semen Long Term

The findings are “promising and provide valuable scientific data,” says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases. Moreover, he adds, “Importantly, the study establishes that it is feasible to conduct a randomized, controlled trial during a major public health emergency in a scientifically and ethically sound manner.”

Based on the pattern of the rash and the patient’s history, the family physician (FP) considered tinea corporis and cruris, but the history of failing treatment seemed unusual. The FP also considered a diagnosis of pityriasis rubra pilaris because he observed a “skip” area on the left thigh.

The FP performed a potassium hydroxide (KOH) preparation using a fungal stain and found branching septate hyphae. (See video on how to perform a KOH preparation here.) He also wondered if the failed treatment was secondary to inadequate dosing or duration of the oral medicines previously used, given that the patient was 6 feet, 5 inches tall and weighed more than 250 pounds. The patient didn’t have liver disease and rarely drank alcohol. Baseline liver function tests (LFTs) were within normal limits.

The FP told the patient to use oral terbinafine for one month rather than the recommended 2 weeks. One month later, there was less erythema and scaling, but the rash had not completely resolved. At that time, the FP and patient decided together to do a punch biopsy to make sure the diagnosis was correct. The punch biopsy supported the diagnosis of tinea with a positive periodic acid–Schiff stain for fungal elements; no other pathology was noted.

Since the LFTs were still normal, the FP and patient discussed a second month of treatment. The FP also performed a fungal culture and requested that the lab test the fungus for identification and sensitivities. Two weeks later, the results showed Trichophyton rubrum that was sensitive to all oral antifungal medications tested, including terbinafine.

At this point, the FP became concerned about the patient’s immune system, so he ordered a complete blood count (CBC) and human immunodeficiency virus (HIV) test. The CBC came back normal and the HIV test was negative. At the end of the second month, the fungal infection was still present clinically and the KOH preparation was still positive.

The FP offered oral itraconazole 100 mg/d and the patient was happy to try another therapy. The LFTs remained normal and after one month of itraconazole, the tinea was still present. At this point, the patient decided that he could live with the condition and would use a topical antifungal when the rash was itchy.

This case demonstrates a situation in which the patient’s immune system is “blind” to the foreign fungus. This has been known to happen with human papillomavirus, when patients have warts that do not resolve even with the most aggressive therapies.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Smith M. Tinea cruris. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:795-798.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Based on the pattern of the rash and the patient’s history, the family physician (FP) considered tinea corporis and cruris, but the history of failing treatment seemed unusual. The FP also considered a diagnosis of pityriasis rubra pilaris because he observed a “skip” area on the left thigh.

The FP performed a potassium hydroxide (KOH) preparation using a fungal stain and found branching septate hyphae. (See video on how to perform a KOH preparation here.) He also wondered if the failed treatment was secondary to inadequate dosing or duration of the oral medicines previously used, given that the patient was 6 feet, 5 inches tall and weighed more than 250 pounds. The patient didn’t have liver disease and rarely drank alcohol. Baseline liver function tests (LFTs) were within normal limits.

The FP told the patient to use oral terbinafine for one month rather than the recommended 2 weeks. One month later, there was less erythema and scaling, but the rash had not completely resolved. At that time, the FP and patient decided together to do a punch biopsy to make sure the diagnosis was correct. The punch biopsy supported the diagnosis of tinea with a positive periodic acid–Schiff stain for fungal elements; no other pathology was noted.

Since the LFTs were still normal, the FP and patient discussed a second month of treatment. The FP also performed a fungal culture and requested that the lab test the fungus for identification and sensitivities. Two weeks later, the results showed Trichophyton rubrum that was sensitive to all oral antifungal medications tested, including terbinafine.

At this point, the FP became concerned about the patient’s immune system, so he ordered a complete blood count (CBC) and human immunodeficiency virus (HIV) test. The CBC came back normal and the HIV test was negative. At the end of the second month, the fungal infection was still present clinically and the KOH preparation was still positive.

The FP offered oral itraconazole 100 mg/d and the patient was happy to try another therapy. The LFTs remained normal and after one month of itraconazole, the tinea was still present. At this point, the patient decided that he could live with the condition and would use a topical antifungal when the rash was itchy.

This case demonstrates a situation in which the patient’s immune system is “blind” to the foreign fungus. This has been known to happen with human papillomavirus, when patients have warts that do not resolve even with the most aggressive therapies.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Smith M. Tinea cruris. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:795-798.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Based on the pattern of the rash and the patient’s history, the family physician (FP) considered tinea corporis and cruris, but the history of failing treatment seemed unusual. The FP also considered a diagnosis of pityriasis rubra pilaris because he observed a “skip” area on the left thigh.

The FP performed a potassium hydroxide (KOH) preparation using a fungal stain and found branching septate hyphae. (See video on how to perform a KOH preparation here.) He also wondered if the failed treatment was secondary to inadequate dosing or duration of the oral medicines previously used, given that the patient was 6 feet, 5 inches tall and weighed more than 250 pounds. The patient didn’t have liver disease and rarely drank alcohol. Baseline liver function tests (LFTs) were within normal limits.

The FP told the patient to use oral terbinafine for one month rather than the recommended 2 weeks. One month later, there was less erythema and scaling, but the rash had not completely resolved. At that time, the FP and patient decided together to do a punch biopsy to make sure the diagnosis was correct. The punch biopsy supported the diagnosis of tinea with a positive periodic acid–Schiff stain for fungal elements; no other pathology was noted.

Since the LFTs were still normal, the FP and patient discussed a second month of treatment. The FP also performed a fungal culture and requested that the lab test the fungus for identification and sensitivities. Two weeks later, the results showed Trichophyton rubrum that was sensitive to all oral antifungal medications tested, including terbinafine.

At this point, the FP became concerned about the patient’s immune system, so he ordered a complete blood count (CBC) and human immunodeficiency virus (HIV) test. The CBC came back normal and the HIV test was negative. At the end of the second month, the fungal infection was still present clinically and the KOH preparation was still positive.

The FP offered oral itraconazole 100 mg/d and the patient was happy to try another therapy. The LFTs remained normal and after one month of itraconazole, the tinea was still present. At this point, the patient decided that he could live with the condition and would use a topical antifungal when the rash was itchy.

This case demonstrates a situation in which the patient’s immune system is “blind” to the foreign fungus. This has been known to happen with human papillomavirus, when patients have warts that do not resolve even with the most aggressive therapies.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Smith M. Tinea cruris. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:795-798.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

ANSWER

The correct diagnosis in this case is juvenile xanthogranuloma (JXG; choice “d”).

Anderson-Fabry disease (choice “a”) is a rare inherited disorder characterized by widespread red papules; these lesions, however, are much smaller and far more widespread than those of JXG.

Considered a possibility at initial presentation, molluscum contagiosum (choice “b”) was quickly ruled out upon further inspection. This patient’s condition lacked the typical features of molluscum: umbilicated, white, firm papules caused by a pox virus. 

Eruptive xanthomata (choice “c”) is a collection of lipid-laden macrophages caused by hypertriglyceridemia. They present as papules and nodules under, rather than on, the skin.

DISCUSSION

Solitary JXG lesions are fairly common, developing on the trunk, face, or extremities as smooth, reddish brown to cream papules. Typically, they cause no problems—but when multiple lesions manifest at birth, the condition can affect the eye (especially the iris, as in this case).

JXG is considered a form of histiocytosis, specifically classified as a type II non-Langerhans cell-mediated lesion. It is believed to result from a disordered macrophage response to a nonspecific tissue injury, which leads to a distinct variety of granulomatous change. These lesions are part of a spectrum of related conditions that also includes Langerhans cell histiocytosis.

No perfect treatment exists for this patient’s multitudinous skin lesions, because her darker skin could easily be permanently changed by burning, freezing, laser, or other destructive modality. Fair or not, in many cases, insurance coverage (or lack thereof) ultimately dictates what treatment is used.

Once the biopsy confirmed the diagnosis and effectively ruled out the other items in the differential, she was referred to ophthalmology for ongoing care of her eyes. Beyond that, she’ll need an annual physical with labs, because JXG is known to affect internal organs as well.

ANSWER

The correct diagnosis in this case is juvenile xanthogranuloma (JXG; choice “d”).

Anderson-Fabry disease (choice “a”) is a rare inherited disorder characterized by widespread red papules; these lesions, however, are much smaller and far more widespread than those of JXG.

Considered a possibility at initial presentation, molluscum contagiosum (choice “b”) was quickly ruled out upon further inspection. This patient’s condition lacked the typical features of molluscum: umbilicated, white, firm papules caused by a pox virus. 

Eruptive xanthomata (choice “c”) is a collection of lipid-laden macrophages caused by hypertriglyceridemia. They present as papules and nodules under, rather than on, the skin.

DISCUSSION

Solitary JXG lesions are fairly common, developing on the trunk, face, or extremities as smooth, reddish brown to cream papules. Typically, they cause no problems—but when multiple lesions manifest at birth, the condition can affect the eye (especially the iris, as in this case).

JXG is considered a form of histiocytosis, specifically classified as a type II non-Langerhans cell-mediated lesion. It is believed to result from a disordered macrophage response to a nonspecific tissue injury, which leads to a distinct variety of granulomatous change. These lesions are part of a spectrum of related conditions that also includes Langerhans cell histiocytosis.

No perfect treatment exists for this patient’s multitudinous skin lesions, because her darker skin could easily be permanently changed by burning, freezing, laser, or other destructive modality. Fair or not, in many cases, insurance coverage (or lack thereof) ultimately dictates what treatment is used.

Once the biopsy confirmed the diagnosis and effectively ruled out the other items in the differential, she was referred to ophthalmology for ongoing care of her eyes. Beyond that, she’ll need an annual physical with labs, because JXG is known to affect internal organs as well.

ANSWER

The correct diagnosis in this case is juvenile xanthogranuloma (JXG; choice “d”).

Anderson-Fabry disease (choice “a”) is a rare inherited disorder characterized by widespread red papules; these lesions, however, are much smaller and far more widespread than those of JXG.

Considered a possibility at initial presentation, molluscum contagiosum (choice “b”) was quickly ruled out upon further inspection. This patient’s condition lacked the typical features of molluscum: umbilicated, white, firm papules caused by a pox virus. 

Eruptive xanthomata (choice “c”) is a collection of lipid-laden macrophages caused by hypertriglyceridemia. They present as papules and nodules under, rather than on, the skin.

DISCUSSION

Solitary JXG lesions are fairly common, developing on the trunk, face, or extremities as smooth, reddish brown to cream papules. Typically, they cause no problems—but when multiple lesions manifest at birth, the condition can affect the eye (especially the iris, as in this case).

JXG is considered a form of histiocytosis, specifically classified as a type II non-Langerhans cell-mediated lesion. It is believed to result from a disordered macrophage response to a nonspecific tissue injury, which leads to a distinct variety of granulomatous change. These lesions are part of a spectrum of related conditions that also includes Langerhans cell histiocytosis.

No perfect treatment exists for this patient’s multitudinous skin lesions, because her darker skin could easily be permanently changed by burning, freezing, laser, or other destructive modality. Fair or not, in many cases, insurance coverage (or lack thereof) ultimately dictates what treatment is used.

Once the biopsy confirmed the diagnosis and effectively ruled out the other items in the differential, she was referred to ophthalmology for ongoing care of her eyes. Beyond that, she’ll need an annual physical with labs, because JXG is known to affect internal organs as well.

Passive immunization against HIV using the broadly neutralizing antibody VRC01 is associated with a delay in plasma viral rebound in individuals undergoing interruption of antiretroviral therapy, according to a new study, but the viral suppression is not sustained.

Two open-label trials investigated the impact of different dosing regiments of VRC01 in a total of 24 patients who were taking a break from antiretroviral therapy, according to a paper published Nov. 9 in the New England Journal of Medicine.

©grandeduc/Thinkstock

Passive immunization against HIV using the broadly neutralizing antibody VRC01 is associated with a delay in plasma viral rebound in individuals undergoing interruption of antiretroviral therapy, according to a new study, but the viral suppression is not sustained.

Two open-label trials investigated the impact of different dosing regiments of VRC01 in a total of 24 patients who were taking a break from antiretroviral therapy, according to a paper published Nov. 9 in the New England Journal of Medicine.

©grandeduc/Thinkstock

Passive immunization against HIV using the broadly neutralizing antibody VRC01 is associated with a delay in plasma viral rebound in individuals undergoing interruption of antiretroviral therapy, according to a new study, but the viral suppression is not sustained.

Two open-label trials investigated the impact of different dosing regiments of VRC01 in a total of 24 patients who were taking a break from antiretroviral therapy, according to a paper published Nov. 9 in the New England Journal of Medicine.

©grandeduc/Thinkstock

The emphasis on this year’s American Heart Association Scientific Sessions in New Orleans is bigness: “Big science, big technology, and big networking opportunities,” the AHA 16 website says.

And so the 19 abstracts out of thousands submitted that got the biggest score from program committee for AHA 2016, led by Frank Sellke, MD, were chosen for presentation at four Late-Breaking Clinical Trials session previewed the late-breaking science.

CrackerClips/Thinkstock

Big trials for big questions

The first late-breaker session, on Sunday, Nov. 13, at 3:45 p.m., CT, is titled will, as its title says present the long-awaited results of four trials with large enrollment and long-term outcomes.

EUCLID (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease) randomized an estimated 16,000 patients with symptomatic PAD to long-term antiplatelet monotherapy with either ticagrelor or clopidogrel to see which one would be superior in preventing the composite of cardiovascular death, myocardial infarction and ischemic stroke up to 40 months. Secondarily, it looked at acute limb ischemia, need for revascularization, and disease progression. “This could have tremendous implications for patients treat for pad trying to prevent CV disease,” Dr. Sellke said.

PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) harks back to 2005, when the Food and Drug Administration, wrestling with the growing evidence that NSAIDs were linked with cardiovascular events, asked for a large, cardiovascular outcomes trial. PRECISION, sponsored by Pfizer but run by an academic-led steering committee led by Steven Nissen, MD, now chief of cardiovascular medicine at the Cleveland Clinic, randomized some 20,000 arthritis patients with or at risk for cardiovascular disease to long-term pain treatment with celecoxib, naproxen, or ibuprofen for a planned follow-up of 2 years. The primary endpoint is a composite of cardiovascular death, nonfatal MI, and nonfatal stroke. Dr. Sellke noted that the results will be important for many physicians and patients wanting to minimize the risks associated with NSAIDs.

HOPE 3 (Heart Outcomes Evaluation 3), presented in April this year at the American College of Cardiology meeting in Chicago, showed the combination of rosuvastatin plus candesartan and hydrochlorothiazide reduced cardiovascular events in intermediate-risk patients with hypertension, regardless of their baseline LDL cholesterol and inflammatory biomarker levels. The analysis to be presented at AHA will show whether the combination has any effect on cognitive function. As evidence builds of the cardiovascular benefit of aggressive treatment of hypertension, as in the SPRINT trial, the results could be tremendously important, Dr. Sellke said.

TRUE AHF (Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure) randomized about 2,150 patients with acute decompensated heart failure to receive a 48-hour intravenous infusion of the natriuretic peptide ularitide or placebo. The primary outcome is a composite of 48-hour improved in-hospital worsening or unchanged clinical conditions, as well as long-term cardiovascular mortality with a median follow-up of 7 months. Because there are no effective treatments for acute systolic heart failure, the results of TRUE AHF could be of tremendous benefit, Dr. Sellke said.

Pioneering the Future of HeART Interventions

The trials with the greatest impact for practice to be presented at AHA 2015, according to the Dr. Sellke’s admitted bias as a cardiothoracic surgeon, will all be presented in this second of the late-breaker sessions, on Monday, Nov. 14, at 10:45 a.m., CT.

ART (Arterial Revascularization Trial) was a comparison of single vs. bilateral internal mammary artery grafting in more than 3,000 randomized patients undergoing coronary artery bypass surgery (CABG). The outcomes of mortality, stroke, MI, and repeat revascularization were published in 2010, showing no differences between groups. The 5-year results to be presented on Monday may resolve some of the controversy surrounding the two methods, as surgeons and cardiologists are strongly divided on the benefits and risks of single, compared with double, internal mammary artery grafting.

FUTURE (Functional Testing Underlying Coronary Revascularization) compared fractional flow reserve–guided management with conventional management in roughly 900 patients undergoing revascularization with multivessel coronary artery disease. The primary outcome is a composite of death, MI, coronary revascularization, and stroke. FFR has received a lot of attention recently, Dr. Sellke said, because it looks at the physiologic, rather than the anatomic, effects of lesion on catheterization. The results will show whether there’s clinical benefit to adding FFR to angiography that will offset the additional time it takes to perform before PCI or CABG.

PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) addressed the conundrum of treating anticoagulated patients with atrial fibrillation who are undergoing PCI with adequate dual-antiplatelet therapy – and avoiding bleeding events. About 2,000 patients were randomized to varying combinations of rivaroxaban or warfarin plus aspirin, ticagrelor prasugrel, and/or clopidogrel for 1 year. The primary outcome is significant bleeding. Dr. Sellke said that because drug-eluting stents require at least a year of DAPT, the PIONEER AF-PCI results will add knowledge in an important and controversial area.

GERMANY is a report from the German Aortic Valve Registry (GARY) on the 1-year outcomes of patients with intermediate-risk severe aortic stenosis who underwent either transcatheter or surgical aortic replacement on the efficacy and outcomes of the two approaches. Dr. Sellke noted that these results will be important because the patients in this registry were not at high risk or ineligible for surgical aortic replacement.

Insights from New Therapeutic Trials for Lipids

Of the five trials presented in this session on Tuesday, Nov. 15, at 10:45 a.m., CT, only one is in an approved treatment for lowering lipids. That is GLAGOV (Global Assessment of Plaque Regression With a PCSK9 Antibody as Measured by Intravascular Ultrasound), is looking at whether LDL lowering with the PCSK9 inhibitor evolocumab reduces atheroma volume in almost 1,000 patients.

Guiding the Momentum to Effect HF Outcomes – Ironing Out the Wrinkles

Two of the six heart failure trials presented in this session on Wednesday, Nov. 16, at 10:45 a.m., CT, study cardiorespiratory effects of iron, thus the title, Dr. Sellke said.

REDUCE LAP HF (A Study to Evaluate the DC Devices, Inc. IASD System II to REDUCE Elevated Left Atrial Pressure in Patients With Heart Failure). The primary outcome is a composite of death, stroke, MI, or a systemic embolic event at 6 months. The trial evaluated a transcatheter interatrial shunt device to left atrial pressure in patients with heart failure with preserved ejection fraction (HFpEF). In this type of diastolic heart failure in which patients’ hearts cannot relax, there is really no treatment, Dr. Sellke said. So although this treatment seems “hokey,” a positive result could be important.

ATHENA HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) tested the diuretic spironolactone in heart failure. The investigators randomized 360 patients to high-dose spironolactone or usual care to see whether they could provide greater reductions of n-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels within 96 hours. There’s evidence that spironolactone can provide symptomatic relief for patients with heart failure, so these results could be important, Dr. Sellke said.

IRONOUT HF (Oral Iron Repletion Effects on Oxygen Up Take in Heart Failure) randomized heart failure patients with iron deficiency to oral iron supplementation or placebo and measured peak oxygen uptake at 16 weeks.

EFFECT-HF (Effect of Ferric Carboxymaltose on Exercise Capacity in Patients with Iron Deficiency and Chronic Heart Failure) also studied the effect of iron supplementation, intravenous in this case, on exercise capacity in heart failure patients at 24 weeks. Iron depletion is a hallmark of heart failure, Dr. Sellke pointed out, so iron repletion could be a simple way to improve functional capacity.

MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HM3) evaluated the safety and effectiveness of the Thoratec HeartMate 3 left-ventricular assist device employing MagLev technology, which is said to facilitate the free flow of blood through the device. Roughly 1,000 patients with advanced, refractory heart failure were randomized to receive either the investigational HeartMate 3 or the HeartMate 2. The primary outcomes included short- and long-term survival and freedom from debilitating stroke. Trials such as this are very important, Dr. Sellke said, because the need for donor hearts far exceeds demand and better, cheaper LVADs that last longer could extend the lives of many thousands of patients every year.

MultiSENSE (Evaluation of Multisensor Data in Heart Failure Patients With Implanted Devices) collected information taken from sensors in an implanted cardiac synchronization therapy device in 1,000 patients to develop algorithms that would detect worsening heart failure. Multiple readmissions for heart failure are frequent and ineffective, and detecting the onset of worsening heart failure has the potential to bring those admissions way down, Dr. Sellke said.

[email protected]

The emphasis on this year’s American Heart Association Scientific Sessions in New Orleans is bigness: “Big science, big technology, and big networking opportunities,” the AHA 16 website says.

And so the 19 abstracts out of thousands submitted that got the biggest score from program committee for AHA 2016, led by Frank Sellke, MD, were chosen for presentation at four Late-Breaking Clinical Trials session previewed the late-breaking science.

CrackerClips/Thinkstock

Big trials for big questions

The first late-breaker session, on Sunday, Nov. 13, at 3:45 p.m., CT, is titled will, as its title says present the long-awaited results of four trials with large enrollment and long-term outcomes.

EUCLID (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease) randomized an estimated 16,000 patients with symptomatic PAD to long-term antiplatelet monotherapy with either ticagrelor or clopidogrel to see which one would be superior in preventing the composite of cardiovascular death, myocardial infarction and ischemic stroke up to 40 months. Secondarily, it looked at acute limb ischemia, need for revascularization, and disease progression. “This could have tremendous implications for patients treat for pad trying to prevent CV disease,” Dr. Sellke said.

PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) harks back to 2005, when the Food and Drug Administration, wrestling with the growing evidence that NSAIDs were linked with cardiovascular events, asked for a large, cardiovascular outcomes trial. PRECISION, sponsored by Pfizer but run by an academic-led steering committee led by Steven Nissen, MD, now chief of cardiovascular medicine at the Cleveland Clinic, randomized some 20,000 arthritis patients with or at risk for cardiovascular disease to long-term pain treatment with celecoxib, naproxen, or ibuprofen for a planned follow-up of 2 years. The primary endpoint is a composite of cardiovascular death, nonfatal MI, and nonfatal stroke. Dr. Sellke noted that the results will be important for many physicians and patients wanting to minimize the risks associated with NSAIDs.

HOPE 3 (Heart Outcomes Evaluation 3), presented in April this year at the American College of Cardiology meeting in Chicago, showed the combination of rosuvastatin plus candesartan and hydrochlorothiazide reduced cardiovascular events in intermediate-risk patients with hypertension, regardless of their baseline LDL cholesterol and inflammatory biomarker levels. The analysis to be presented at AHA will show whether the combination has any effect on cognitive function. As evidence builds of the cardiovascular benefit of aggressive treatment of hypertension, as in the SPRINT trial, the results could be tremendously important, Dr. Sellke said.

TRUE AHF (Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure) randomized about 2,150 patients with acute decompensated heart failure to receive a 48-hour intravenous infusion of the natriuretic peptide ularitide or placebo. The primary outcome is a composite of 48-hour improved in-hospital worsening or unchanged clinical conditions, as well as long-term cardiovascular mortality with a median follow-up of 7 months. Because there are no effective treatments for acute systolic heart failure, the results of TRUE AHF could be of tremendous benefit, Dr. Sellke said.

Pioneering the Future of HeART Interventions

The trials with the greatest impact for practice to be presented at AHA 2015, according to the Dr. Sellke’s admitted bias as a cardiothoracic surgeon, will all be presented in this second of the late-breaker sessions, on Monday, Nov. 14, at 10:45 a.m., CT.

ART (Arterial Revascularization Trial) was a comparison of single vs. bilateral internal mammary artery grafting in more than 3,000 randomized patients undergoing coronary artery bypass surgery (CABG). The outcomes of mortality, stroke, MI, and repeat revascularization were published in 2010, showing no differences between groups. The 5-year results to be presented on Monday may resolve some of the controversy surrounding the two methods, as surgeons and cardiologists are strongly divided on the benefits and risks of single, compared with double, internal mammary artery grafting.

FUTURE (Functional Testing Underlying Coronary Revascularization) compared fractional flow reserve–guided management with conventional management in roughly 900 patients undergoing revascularization with multivessel coronary artery disease. The primary outcome is a composite of death, MI, coronary revascularization, and stroke. FFR has received a lot of attention recently, Dr. Sellke said, because it looks at the physiologic, rather than the anatomic, effects of lesion on catheterization. The results will show whether there’s clinical benefit to adding FFR to angiography that will offset the additional time it takes to perform before PCI or CABG.

PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) addressed the conundrum of treating anticoagulated patients with atrial fibrillation who are undergoing PCI with adequate dual-antiplatelet therapy – and avoiding bleeding events. About 2,000 patients were randomized to varying combinations of rivaroxaban or warfarin plus aspirin, ticagrelor prasugrel, and/or clopidogrel for 1 year. The primary outcome is significant bleeding. Dr. Sellke said that because drug-eluting stents require at least a year of DAPT, the PIONEER AF-PCI results will add knowledge in an important and controversial area.

GERMANY is a report from the German Aortic Valve Registry (GARY) on the 1-year outcomes of patients with intermediate-risk severe aortic stenosis who underwent either transcatheter or surgical aortic replacement on the efficacy and outcomes of the two approaches. Dr. Sellke noted that these results will be important because the patients in this registry were not at high risk or ineligible for surgical aortic replacement.

Insights from New Therapeutic Trials for Lipids

Of the five trials presented in this session on Tuesday, Nov. 15, at 10:45 a.m., CT, only one is in an approved treatment for lowering lipids. That is GLAGOV (Global Assessment of Plaque Regression With a PCSK9 Antibody as Measured by Intravascular Ultrasound), is looking at whether LDL lowering with the PCSK9 inhibitor evolocumab reduces atheroma volume in almost 1,000 patients.

Guiding the Momentum to Effect HF Outcomes – Ironing Out the Wrinkles

Two of the six heart failure trials presented in this session on Wednesday, Nov. 16, at 10:45 a.m., CT, study cardiorespiratory effects of iron, thus the title, Dr. Sellke said.

REDUCE LAP HF (A Study to Evaluate the DC Devices, Inc. IASD System II to REDUCE Elevated Left Atrial Pressure in Patients With Heart Failure). The primary outcome is a composite of death, stroke, MI, or a systemic embolic event at 6 months. The trial evaluated a transcatheter interatrial shunt device to left atrial pressure in patients with heart failure with preserved ejection fraction (HFpEF). In this type of diastolic heart failure in which patients’ hearts cannot relax, there is really no treatment, Dr. Sellke said. So although this treatment seems “hokey,” a positive result could be important.

ATHENA HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) tested the diuretic spironolactone in heart failure. The investigators randomized 360 patients to high-dose spironolactone or usual care to see whether they could provide greater reductions of n-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels within 96 hours. There’s evidence that spironolactone can provide symptomatic relief for patients with heart failure, so these results could be important, Dr. Sellke said.

IRONOUT HF (Oral Iron Repletion Effects on Oxygen Up Take in Heart Failure) randomized heart failure patients with iron deficiency to oral iron supplementation or placebo and measured peak oxygen uptake at 16 weeks.

EFFECT-HF (Effect of Ferric Carboxymaltose on Exercise Capacity in Patients with Iron Deficiency and Chronic Heart Failure) also studied the effect of iron supplementation, intravenous in this case, on exercise capacity in heart failure patients at 24 weeks. Iron depletion is a hallmark of heart failure, Dr. Sellke pointed out, so iron repletion could be a simple way to improve functional capacity.

MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HM3) evaluated the safety and effectiveness of the Thoratec HeartMate 3 left-ventricular assist device employing MagLev technology, which is said to facilitate the free flow of blood through the device. Roughly 1,000 patients with advanced, refractory heart failure were randomized to receive either the investigational HeartMate 3 or the HeartMate 2. The primary outcomes included short- and long-term survival and freedom from debilitating stroke. Trials such as this are very important, Dr. Sellke said, because the need for donor hearts far exceeds demand and better, cheaper LVADs that last longer could extend the lives of many thousands of patients every year.

MultiSENSE (Evaluation of Multisensor Data in Heart Failure Patients With Implanted Devices) collected information taken from sensors in an implanted cardiac synchronization therapy device in 1,000 patients to develop algorithms that would detect worsening heart failure. Multiple readmissions for heart failure are frequent and ineffective, and detecting the onset of worsening heart failure has the potential to bring those admissions way down, Dr. Sellke said.

[email protected]

The emphasis on this year’s American Heart Association Scientific Sessions in New Orleans is bigness: “Big science, big technology, and big networking opportunities,” the AHA 16 website says.

And so the 19 abstracts out of thousands submitted that got the biggest score from program committee for AHA 2016, led by Frank Sellke, MD, were chosen for presentation at four Late-Breaking Clinical Trials session previewed the late-breaking science.

CrackerClips/Thinkstock

Big trials for big questions

The first late-breaker session, on Sunday, Nov. 13, at 3:45 p.m., CT, is titled will, as its title says present the long-awaited results of four trials with large enrollment and long-term outcomes.

EUCLID (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease) randomized an estimated 16,000 patients with symptomatic PAD to long-term antiplatelet monotherapy with either ticagrelor or clopidogrel to see which one would be superior in preventing the composite of cardiovascular death, myocardial infarction and ischemic stroke up to 40 months. Secondarily, it looked at acute limb ischemia, need for revascularization, and disease progression. “This could have tremendous implications for patients treat for pad trying to prevent CV disease,” Dr. Sellke said.

PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) harks back to 2005, when the Food and Drug Administration, wrestling with the growing evidence that NSAIDs were linked with cardiovascular events, asked for a large, cardiovascular outcomes trial. PRECISION, sponsored by Pfizer but run by an academic-led steering committee led by Steven Nissen, MD, now chief of cardiovascular medicine at the Cleveland Clinic, randomized some 20,000 arthritis patients with or at risk for cardiovascular disease to long-term pain treatment with celecoxib, naproxen, or ibuprofen for a planned follow-up of 2 years. The primary endpoint is a composite of cardiovascular death, nonfatal MI, and nonfatal stroke. Dr. Sellke noted that the results will be important for many physicians and patients wanting to minimize the risks associated with NSAIDs.

HOPE 3 (Heart Outcomes Evaluation 3), presented in April this year at the American College of Cardiology meeting in Chicago, showed the combination of rosuvastatin plus candesartan and hydrochlorothiazide reduced cardiovascular events in intermediate-risk patients with hypertension, regardless of their baseline LDL cholesterol and inflammatory biomarker levels. The analysis to be presented at AHA will show whether the combination has any effect on cognitive function. As evidence builds of the cardiovascular benefit of aggressive treatment of hypertension, as in the SPRINT trial, the results could be tremendously important, Dr. Sellke said.

TRUE AHF (Efficacy and Safety of Ularitide for the Treatment of Acute Decompensated Heart Failure) randomized about 2,150 patients with acute decompensated heart failure to receive a 48-hour intravenous infusion of the natriuretic peptide ularitide or placebo. The primary outcome is a composite of 48-hour improved in-hospital worsening or unchanged clinical conditions, as well as long-term cardiovascular mortality with a median follow-up of 7 months. Because there are no effective treatments for acute systolic heart failure, the results of TRUE AHF could be of tremendous benefit, Dr. Sellke said.

Pioneering the Future of HeART Interventions

The trials with the greatest impact for practice to be presented at AHA 2015, according to the Dr. Sellke’s admitted bias as a cardiothoracic surgeon, will all be presented in this second of the late-breaker sessions, on Monday, Nov. 14, at 10:45 a.m., CT.

ART (Arterial Revascularization Trial) was a comparison of single vs. bilateral internal mammary artery grafting in more than 3,000 randomized patients undergoing coronary artery bypass surgery (CABG). The outcomes of mortality, stroke, MI, and repeat revascularization were published in 2010, showing no differences between groups. The 5-year results to be presented on Monday may resolve some of the controversy surrounding the two methods, as surgeons and cardiologists are strongly divided on the benefits and risks of single, compared with double, internal mammary artery grafting.

FUTURE (Functional Testing Underlying Coronary Revascularization) compared fractional flow reserve–guided management with conventional management in roughly 900 patients undergoing revascularization with multivessel coronary artery disease. The primary outcome is a composite of death, MI, coronary revascularization, and stroke. FFR has received a lot of attention recently, Dr. Sellke said, because it looks at the physiologic, rather than the anatomic, effects of lesion on catheterization. The results will show whether there’s clinical benefit to adding FFR to angiography that will offset the additional time it takes to perform before PCI or CABG.

PIONEER AF-PCI (An Open-label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention) addressed the conundrum of treating anticoagulated patients with atrial fibrillation who are undergoing PCI with adequate dual-antiplatelet therapy – and avoiding bleeding events. About 2,000 patients were randomized to varying combinations of rivaroxaban or warfarin plus aspirin, ticagrelor prasugrel, and/or clopidogrel for 1 year. The primary outcome is significant bleeding. Dr. Sellke said that because drug-eluting stents require at least a year of DAPT, the PIONEER AF-PCI results will add knowledge in an important and controversial area.

GERMANY is a report from the German Aortic Valve Registry (GARY) on the 1-year outcomes of patients with intermediate-risk severe aortic stenosis who underwent either transcatheter or surgical aortic replacement on the efficacy and outcomes of the two approaches. Dr. Sellke noted that these results will be important because the patients in this registry were not at high risk or ineligible for surgical aortic replacement.

Insights from New Therapeutic Trials for Lipids

Of the five trials presented in this session on Tuesday, Nov. 15, at 10:45 a.m., CT, only one is in an approved treatment for lowering lipids. That is GLAGOV (Global Assessment of Plaque Regression With a PCSK9 Antibody as Measured by Intravascular Ultrasound), is looking at whether LDL lowering with the PCSK9 inhibitor evolocumab reduces atheroma volume in almost 1,000 patients.

Guiding the Momentum to Effect HF Outcomes – Ironing Out the Wrinkles

Two of the six heart failure trials presented in this session on Wednesday, Nov. 16, at 10:45 a.m., CT, study cardiorespiratory effects of iron, thus the title, Dr. Sellke said.

REDUCE LAP HF (A Study to Evaluate the DC Devices, Inc. IASD System II to REDUCE Elevated Left Atrial Pressure in Patients With Heart Failure). The primary outcome is a composite of death, stroke, MI, or a systemic embolic event at 6 months. The trial evaluated a transcatheter interatrial shunt device to left atrial pressure in patients with heart failure with preserved ejection fraction (HFpEF). In this type of diastolic heart failure in which patients’ hearts cannot relax, there is really no treatment, Dr. Sellke said. So although this treatment seems “hokey,” a positive result could be important.

ATHENA HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) tested the diuretic spironolactone in heart failure. The investigators randomized 360 patients to high-dose spironolactone or usual care to see whether they could provide greater reductions of n-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels within 96 hours. There’s evidence that spironolactone can provide symptomatic relief for patients with heart failure, so these results could be important, Dr. Sellke said.

IRONOUT HF (Oral Iron Repletion Effects on Oxygen Up Take in Heart Failure) randomized heart failure patients with iron deficiency to oral iron supplementation or placebo and measured peak oxygen uptake at 16 weeks.

EFFECT-HF (Effect of Ferric Carboxymaltose on Exercise Capacity in Patients with Iron Deficiency and Chronic Heart Failure) also studied the effect of iron supplementation, intravenous in this case, on exercise capacity in heart failure patients at 24 weeks. Iron depletion is a hallmark of heart failure, Dr. Sellke pointed out, so iron repletion could be a simple way to improve functional capacity.

MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HM3) evaluated the safety and effectiveness of the Thoratec HeartMate 3 left-ventricular assist device employing MagLev technology, which is said to facilitate the free flow of blood through the device. Roughly 1,000 patients with advanced, refractory heart failure were randomized to receive either the investigational HeartMate 3 or the HeartMate 2. The primary outcomes included short- and long-term survival and freedom from debilitating stroke. Trials such as this are very important, Dr. Sellke said, because the need for donor hearts far exceeds demand and better, cheaper LVADs that last longer could extend the lives of many thousands of patients every year.

MultiSENSE (Evaluation of Multisensor Data in Heart Failure Patients With Implanted Devices) collected information taken from sensors in an implanted cardiac synchronization therapy device in 1,000 patients to develop algorithms that would detect worsening heart failure. Multiple readmissions for heart failure are frequent and ineffective, and detecting the onset of worsening heart failure has the potential to bring those admissions way down, Dr. Sellke said.

[email protected]