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Implementing enhanced recovery protocols for gynecologic surgery
“Enhanced Recovery After Surgery” (ERAS) practices and protocols have been increasingly refined and adopted for the field of gynecology, and there is hope among gynecologic surgeons – and some recent evidence – that, with the ERAS movement, we are improving patient recoveries and outcomes and minimizing the need for opioids.
This applies not only to open surgeries but also to the minimally invasive procedures that already are prized for significant reductions in morbidity and length of stay. The overarching and guiding principle of ERAS is that any surgery – whether open or minimally invasive, major or minor – places stress on the body and is associated with risks and morbidity.
Enhanced recovery protocols are multidisciplinary, perioperative approaches designed to lessen the body’s stress response to surgery. The protocols and pathways offer us a menu of small changes that, in the aggregate, can lead to large and demonstrable benefits – especially when these small changes are chosen across the preoperative, intraoperative, and postoperative arenas and then standardized in one’s practice. Among the major components of ERAS practices and protocols are limiting preoperative fasting, employing multimodal analgesia, encouraging early ambulation and early postsurgical feeding, and creating culture shift that includes greater emphasis on patient expectations.
In our practice, we are incorporating ERAS practices not only in hopes of reducing the stress of all surgeries before, during, and after, but also with the goal of achieving a postoperative opioid-free hysterectomy, myomectomy, and extensive endometriosis surgery. (All of our advanced procedures are performed laparoscopically or robotically.)
Over the past 7 or so years, we have adopted a multimodal approach to pain control that includes a bundle of preoperative analgesics – acetaminophen, pregabalin, and celecoxib (we call it “TLC” for Tylenol, Lyrica, and Celebrex) – and the use of liposomal bupivacaine in our robotic surgeries. We are now turning toward ERAS nutritional changes, most of which run counter to traditional paradigms for surgical care. And in other areas, such as dedicated preoperative counseling, we continue to refine and improve our practices.
Improved Outcomes
The ERAS mindset notably intersected gynecology with the publication in 2016 of a two-part series of guidelines for gynecology/oncology surgery from the ERAS Society. The 8-year-old society has its roots in a study group of European surgeons and others who decided to examine surgical practices and the concept of multimodal surgical care put forth in the 1990s by Henrik Kehlet, MD, PhD, then a professor at the University of Copenhagen.
The first set of recommendations addressed pre- and intraoperative care (Gynecol Oncol. 2016 Feb;140[2]:313-22), and the second set addressed postoperative care (Gynecol Oncol. 2016 Feb;140[2]:323-32). Similar evidence-based recommendations were previously written for colonic resections, rectal and pelvic surgery, and other surgical specialties.
Most of the published outcomes of enhanced recovery protocols come from colorectal surgery. As noted in the ERAS Society gynecology/oncology guidelines, the benefits include an average reduction in length of stay of 2.5 days and a decrease in complications by as much as 50%.
There is growing evidence, however, that ERAS programs are also beneficial for patients undergoing laparoscopic surgery, and outcomes from gynecology – including minimally invasive surgery – are also being reported.
For instance, a retrospective case-control study of 55 consecutive gynecologic oncology patients treated at the University of California, San Francisco, with laparoscopic or robotic surgery and an enhanced recovery pathway – and 110 historical control patients matched on the basis of age and surgery type – found significant improvements in recovery time, decreased pain despite reduced opioid use, and overall lower hospital costs (Obstet Gynecol. 2016 Jul;128[1]:138-44).
The enhanced recovery pathway included patient education, multimodal antiemetics, multimodal analgesia, and balanced fluid administration. Early catheter removal, ambulation, and feeding were also components. Analgesia included routine preoperative gabapentin, diclofenac, and acetaminophen; routine postoperative gabapentin, NSAIDs, and acetaminophen; and transversus abdominis plane blocks in 32 of the ERAS patients.
ERAS patients were significantly more likely to be discharged on day 1 (91%, compared with 60% in the control group). Opioid use decreased by 30%, and pain scores on postoperative day 1 were significantly lower.
Another study looking at the effect of enhanced recovery implementation in gynecologic surgeries at the University of Virginia, Charlottesville, (gynecologic oncology, urogynecology, and general gynecology) similarly reported benefits for vaginal and minimally invasive procedures, as well as for open procedures (Obstet Gynecol. 2016 Sep;128[3]:457-66).
In the minimally invasive group, investigators compared 324 patients before ERAS implementation with 249 patients afterward and found that the median length of stay was unchanged (1 day). However, intraoperative and postoperative opioid consumption decreased significantly and – even though actual pain scores improved only slightly – patient satisfaction scores improved markedly among post-ERAS patients. Patients gave higher marks, for instance, to questions regarding pain control (“how well your pain was controlled”) and teamwork (“staff worked together to care for you”).
Reducing Opioids
New opioid use that persists after a surgical procedure is a postsurgical complication that we all should be working to prevent. It has been estimated that 6% of surgical patients – even those who’ve had relatively minor surgical procedures – will become long-term opioid users, developing a dependence on the drugs prescribed to them for postsurgical pain.
This was shown last year in a national study of insurance claims data from between 2013 and 2014; investigators identified adults without opioid use in the year prior to surgery (including hysterectomy) and found that 5.9%-6.5% were filling opioid prescriptions 90-180 days after their surgical procedure. The incidence in a nonoperative control cohort was 0.4% (JAMA Surg. 2017 Jun 21;152[6]:e170504). Notably, this prolonged use was greatest in patients with prior pain conditions, substance abuse, and mental health disorders – a finding that may have implications for the counseling we provide prior to surgery.
It’s not clear what the optimal analgesic regimen is for minimally invasive or other gynecologic surgeries. What is clearly recommended, however, is that the approach be multifaceted. In our practice, we believe that the preoperative use of acetaminophen, pregabalin, and celecoxib plays an important role in reducing postoperative pain and opioid use. But we also have striven to create a practice-wide culture shift (throughout the operating and recovery rooms), for instance, that encourages using the least amounts of narcotics possible and using the shortest-acting formulations possible.
Transversus abdominis plane (TAP) blocks are also often part of ERAS protocols; they have been shown in at least two randomized controlled trials of abdominal hysterectomy to reduce intraoperative fentanyl requirements and to reduce immediate postoperative pain scores and postoperative morphine requirements (Anesth Analg. 2008 Dec;107[6]:2056-60; J Anaesthesiol Clin Pharmacol. 2014 Jul-Sep;30[3]:391-6).
More recently, liposomal bupivacaine, which is slowly released over several days, has gained traction as a substitute for standard bupivacaine and other agents in TAP blocks. In one recent retrospective study, abdominal incision infiltration with liposomal bupivacaine was associated with less opioid use (with no change in pain scores), compared with bupivacaine hydrochloride after laparotomy for gynecologic malignancies (Obstet Gynecol. 2016 Nov;128[5]:1009-17). It’s significantly more expensive, however, making it likely that the formulation is being used more judiciously in minimally invasive gynecologic surgery than in open surgeries.
Because of costs, we currently are restricted to using liposomal bupivacaine in our robotic surgeries only. In our practice, the single 20 mL vial (266 mg of liposomal bupivacaine) is diluted with 20 mL of normal saline, but it can be further diluted without loss of efficacy. With a 16-gauge needle, the liposomal bupivacaine is distributed across the incisions (usually 20 mL in the umbilicus with a larger incision and 10 mL in each of the two lateral incisions). Patients are counseled that they may have more discomfort after 3 days, but by this point most are mobile and feeling relatively well with a combination of NSAIDs and acetaminophen.
With growing visibility of the problem of narcotic dependence in the United States, patients seem increasingly receptive and even eager to limit or avoid the use of opioids. Patients should be counseled that minimizing or avoiding opioids may also speed recovery. Narcotics cause gut motility to slow down, which may hinder mobilization. Early mobilization (within 24 hours) is among the enhanced recovery elements that the ERAS Society guidelines say is “of particular value” for minimally invasive surgery, along with maintenance of normothermia and normovolemia with maintenance of adequate cardiac output.
Selecting Steps
Our practice is also trying to reduce preoperative bowel preparation and preoperative fasting, both of which have been found to be stressful for the body without evidence of benefit. These practices can lead to insulin resistance and hyperglycemia, which are associated with increased morbidity and length of stay.
It is now recommended that clear fluids be allowed up to 2 hours before surgery and solids up to 6 hours before. Some health systems and practices also recommend presurgical carbohydrate loading (for example, 10 ounces of apple juice 2 hours before surgery) – another small change on the ERAS menu – to further reduce postoperative insulin resistance and help the body cope with its stress response to surgery.
Along with nutritional changes are also various measures aimed at optimizing the body’s functionality before surgery (“prehabilitation”), from walking 30 minutes a day to abstaining from alcohol for patients who drink heavily.
Throughout the country, enhanced recovery protocols are taking shape in gynecologic surgery. ERAS was featured in an aptly titled panel session at the 2017 annual meeting of the American Association of Gynecologic Laparoscopists: “Outpatient Hysterectomy, ERAS, and Same-Day Discharge: The Next Big Thing in Gyn Surgery.” Others are applying ERAS to scheduled cesarean sections. And in our practice, I believe that if we continue making small changes, we will reach our goal of opioid-free recoveries and a better surgical experience for our patients.
Kirsten Sasaki, MD, is an associate of the Advanced Gynecologic Surgery Institute. She reported that she has no disclosures relevant to this Master Class.
“Enhanced Recovery After Surgery” (ERAS) practices and protocols have been increasingly refined and adopted for the field of gynecology, and there is hope among gynecologic surgeons – and some recent evidence – that, with the ERAS movement, we are improving patient recoveries and outcomes and minimizing the need for opioids.
This applies not only to open surgeries but also to the minimally invasive procedures that already are prized for significant reductions in morbidity and length of stay. The overarching and guiding principle of ERAS is that any surgery – whether open or minimally invasive, major or minor – places stress on the body and is associated with risks and morbidity.
Enhanced recovery protocols are multidisciplinary, perioperative approaches designed to lessen the body’s stress response to surgery. The protocols and pathways offer us a menu of small changes that, in the aggregate, can lead to large and demonstrable benefits – especially when these small changes are chosen across the preoperative, intraoperative, and postoperative arenas and then standardized in one’s practice. Among the major components of ERAS practices and protocols are limiting preoperative fasting, employing multimodal analgesia, encouraging early ambulation and early postsurgical feeding, and creating culture shift that includes greater emphasis on patient expectations.
In our practice, we are incorporating ERAS practices not only in hopes of reducing the stress of all surgeries before, during, and after, but also with the goal of achieving a postoperative opioid-free hysterectomy, myomectomy, and extensive endometriosis surgery. (All of our advanced procedures are performed laparoscopically or robotically.)
Over the past 7 or so years, we have adopted a multimodal approach to pain control that includes a bundle of preoperative analgesics – acetaminophen, pregabalin, and celecoxib (we call it “TLC” for Tylenol, Lyrica, and Celebrex) – and the use of liposomal bupivacaine in our robotic surgeries. We are now turning toward ERAS nutritional changes, most of which run counter to traditional paradigms for surgical care. And in other areas, such as dedicated preoperative counseling, we continue to refine and improve our practices.
Improved Outcomes
The ERAS mindset notably intersected gynecology with the publication in 2016 of a two-part series of guidelines for gynecology/oncology surgery from the ERAS Society. The 8-year-old society has its roots in a study group of European surgeons and others who decided to examine surgical practices and the concept of multimodal surgical care put forth in the 1990s by Henrik Kehlet, MD, PhD, then a professor at the University of Copenhagen.
The first set of recommendations addressed pre- and intraoperative care (Gynecol Oncol. 2016 Feb;140[2]:313-22), and the second set addressed postoperative care (Gynecol Oncol. 2016 Feb;140[2]:323-32). Similar evidence-based recommendations were previously written for colonic resections, rectal and pelvic surgery, and other surgical specialties.
Most of the published outcomes of enhanced recovery protocols come from colorectal surgery. As noted in the ERAS Society gynecology/oncology guidelines, the benefits include an average reduction in length of stay of 2.5 days and a decrease in complications by as much as 50%.
There is growing evidence, however, that ERAS programs are also beneficial for patients undergoing laparoscopic surgery, and outcomes from gynecology – including minimally invasive surgery – are also being reported.
For instance, a retrospective case-control study of 55 consecutive gynecologic oncology patients treated at the University of California, San Francisco, with laparoscopic or robotic surgery and an enhanced recovery pathway – and 110 historical control patients matched on the basis of age and surgery type – found significant improvements in recovery time, decreased pain despite reduced opioid use, and overall lower hospital costs (Obstet Gynecol. 2016 Jul;128[1]:138-44).
The enhanced recovery pathway included patient education, multimodal antiemetics, multimodal analgesia, and balanced fluid administration. Early catheter removal, ambulation, and feeding were also components. Analgesia included routine preoperative gabapentin, diclofenac, and acetaminophen; routine postoperative gabapentin, NSAIDs, and acetaminophen; and transversus abdominis plane blocks in 32 of the ERAS patients.
ERAS patients were significantly more likely to be discharged on day 1 (91%, compared with 60% in the control group). Opioid use decreased by 30%, and pain scores on postoperative day 1 were significantly lower.
Another study looking at the effect of enhanced recovery implementation in gynecologic surgeries at the University of Virginia, Charlottesville, (gynecologic oncology, urogynecology, and general gynecology) similarly reported benefits for vaginal and minimally invasive procedures, as well as for open procedures (Obstet Gynecol. 2016 Sep;128[3]:457-66).
In the minimally invasive group, investigators compared 324 patients before ERAS implementation with 249 patients afterward and found that the median length of stay was unchanged (1 day). However, intraoperative and postoperative opioid consumption decreased significantly and – even though actual pain scores improved only slightly – patient satisfaction scores improved markedly among post-ERAS patients. Patients gave higher marks, for instance, to questions regarding pain control (“how well your pain was controlled”) and teamwork (“staff worked together to care for you”).
Reducing Opioids
New opioid use that persists after a surgical procedure is a postsurgical complication that we all should be working to prevent. It has been estimated that 6% of surgical patients – even those who’ve had relatively minor surgical procedures – will become long-term opioid users, developing a dependence on the drugs prescribed to them for postsurgical pain.
This was shown last year in a national study of insurance claims data from between 2013 and 2014; investigators identified adults without opioid use in the year prior to surgery (including hysterectomy) and found that 5.9%-6.5% were filling opioid prescriptions 90-180 days after their surgical procedure. The incidence in a nonoperative control cohort was 0.4% (JAMA Surg. 2017 Jun 21;152[6]:e170504). Notably, this prolonged use was greatest in patients with prior pain conditions, substance abuse, and mental health disorders – a finding that may have implications for the counseling we provide prior to surgery.
It’s not clear what the optimal analgesic regimen is for minimally invasive or other gynecologic surgeries. What is clearly recommended, however, is that the approach be multifaceted. In our practice, we believe that the preoperative use of acetaminophen, pregabalin, and celecoxib plays an important role in reducing postoperative pain and opioid use. But we also have striven to create a practice-wide culture shift (throughout the operating and recovery rooms), for instance, that encourages using the least amounts of narcotics possible and using the shortest-acting formulations possible.
Transversus abdominis plane (TAP) blocks are also often part of ERAS protocols; they have been shown in at least two randomized controlled trials of abdominal hysterectomy to reduce intraoperative fentanyl requirements and to reduce immediate postoperative pain scores and postoperative morphine requirements (Anesth Analg. 2008 Dec;107[6]:2056-60; J Anaesthesiol Clin Pharmacol. 2014 Jul-Sep;30[3]:391-6).
More recently, liposomal bupivacaine, which is slowly released over several days, has gained traction as a substitute for standard bupivacaine and other agents in TAP blocks. In one recent retrospective study, abdominal incision infiltration with liposomal bupivacaine was associated with less opioid use (with no change in pain scores), compared with bupivacaine hydrochloride after laparotomy for gynecologic malignancies (Obstet Gynecol. 2016 Nov;128[5]:1009-17). It’s significantly more expensive, however, making it likely that the formulation is being used more judiciously in minimally invasive gynecologic surgery than in open surgeries.
Because of costs, we currently are restricted to using liposomal bupivacaine in our robotic surgeries only. In our practice, the single 20 mL vial (266 mg of liposomal bupivacaine) is diluted with 20 mL of normal saline, but it can be further diluted without loss of efficacy. With a 16-gauge needle, the liposomal bupivacaine is distributed across the incisions (usually 20 mL in the umbilicus with a larger incision and 10 mL in each of the two lateral incisions). Patients are counseled that they may have more discomfort after 3 days, but by this point most are mobile and feeling relatively well with a combination of NSAIDs and acetaminophen.
With growing visibility of the problem of narcotic dependence in the United States, patients seem increasingly receptive and even eager to limit or avoid the use of opioids. Patients should be counseled that minimizing or avoiding opioids may also speed recovery. Narcotics cause gut motility to slow down, which may hinder mobilization. Early mobilization (within 24 hours) is among the enhanced recovery elements that the ERAS Society guidelines say is “of particular value” for minimally invasive surgery, along with maintenance of normothermia and normovolemia with maintenance of adequate cardiac output.
Selecting Steps
Our practice is also trying to reduce preoperative bowel preparation and preoperative fasting, both of which have been found to be stressful for the body without evidence of benefit. These practices can lead to insulin resistance and hyperglycemia, which are associated with increased morbidity and length of stay.
It is now recommended that clear fluids be allowed up to 2 hours before surgery and solids up to 6 hours before. Some health systems and practices also recommend presurgical carbohydrate loading (for example, 10 ounces of apple juice 2 hours before surgery) – another small change on the ERAS menu – to further reduce postoperative insulin resistance and help the body cope with its stress response to surgery.
Along with nutritional changes are also various measures aimed at optimizing the body’s functionality before surgery (“prehabilitation”), from walking 30 minutes a day to abstaining from alcohol for patients who drink heavily.
Throughout the country, enhanced recovery protocols are taking shape in gynecologic surgery. ERAS was featured in an aptly titled panel session at the 2017 annual meeting of the American Association of Gynecologic Laparoscopists: “Outpatient Hysterectomy, ERAS, and Same-Day Discharge: The Next Big Thing in Gyn Surgery.” Others are applying ERAS to scheduled cesarean sections. And in our practice, I believe that if we continue making small changes, we will reach our goal of opioid-free recoveries and a better surgical experience for our patients.
Kirsten Sasaki, MD, is an associate of the Advanced Gynecologic Surgery Institute. She reported that she has no disclosures relevant to this Master Class.
“Enhanced Recovery After Surgery” (ERAS) practices and protocols have been increasingly refined and adopted for the field of gynecology, and there is hope among gynecologic surgeons – and some recent evidence – that, with the ERAS movement, we are improving patient recoveries and outcomes and minimizing the need for opioids.
This applies not only to open surgeries but also to the minimally invasive procedures that already are prized for significant reductions in morbidity and length of stay. The overarching and guiding principle of ERAS is that any surgery – whether open or minimally invasive, major or minor – places stress on the body and is associated with risks and morbidity.
Enhanced recovery protocols are multidisciplinary, perioperative approaches designed to lessen the body’s stress response to surgery. The protocols and pathways offer us a menu of small changes that, in the aggregate, can lead to large and demonstrable benefits – especially when these small changes are chosen across the preoperative, intraoperative, and postoperative arenas and then standardized in one’s practice. Among the major components of ERAS practices and protocols are limiting preoperative fasting, employing multimodal analgesia, encouraging early ambulation and early postsurgical feeding, and creating culture shift that includes greater emphasis on patient expectations.
In our practice, we are incorporating ERAS practices not only in hopes of reducing the stress of all surgeries before, during, and after, but also with the goal of achieving a postoperative opioid-free hysterectomy, myomectomy, and extensive endometriosis surgery. (All of our advanced procedures are performed laparoscopically or robotically.)
Over the past 7 or so years, we have adopted a multimodal approach to pain control that includes a bundle of preoperative analgesics – acetaminophen, pregabalin, and celecoxib (we call it “TLC” for Tylenol, Lyrica, and Celebrex) – and the use of liposomal bupivacaine in our robotic surgeries. We are now turning toward ERAS nutritional changes, most of which run counter to traditional paradigms for surgical care. And in other areas, such as dedicated preoperative counseling, we continue to refine and improve our practices.
Improved Outcomes
The ERAS mindset notably intersected gynecology with the publication in 2016 of a two-part series of guidelines for gynecology/oncology surgery from the ERAS Society. The 8-year-old society has its roots in a study group of European surgeons and others who decided to examine surgical practices and the concept of multimodal surgical care put forth in the 1990s by Henrik Kehlet, MD, PhD, then a professor at the University of Copenhagen.
The first set of recommendations addressed pre- and intraoperative care (Gynecol Oncol. 2016 Feb;140[2]:313-22), and the second set addressed postoperative care (Gynecol Oncol. 2016 Feb;140[2]:323-32). Similar evidence-based recommendations were previously written for colonic resections, rectal and pelvic surgery, and other surgical specialties.
Most of the published outcomes of enhanced recovery protocols come from colorectal surgery. As noted in the ERAS Society gynecology/oncology guidelines, the benefits include an average reduction in length of stay of 2.5 days and a decrease in complications by as much as 50%.
There is growing evidence, however, that ERAS programs are also beneficial for patients undergoing laparoscopic surgery, and outcomes from gynecology – including minimally invasive surgery – are also being reported.
For instance, a retrospective case-control study of 55 consecutive gynecologic oncology patients treated at the University of California, San Francisco, with laparoscopic or robotic surgery and an enhanced recovery pathway – and 110 historical control patients matched on the basis of age and surgery type – found significant improvements in recovery time, decreased pain despite reduced opioid use, and overall lower hospital costs (Obstet Gynecol. 2016 Jul;128[1]:138-44).
The enhanced recovery pathway included patient education, multimodal antiemetics, multimodal analgesia, and balanced fluid administration. Early catheter removal, ambulation, and feeding were also components. Analgesia included routine preoperative gabapentin, diclofenac, and acetaminophen; routine postoperative gabapentin, NSAIDs, and acetaminophen; and transversus abdominis plane blocks in 32 of the ERAS patients.
ERAS patients were significantly more likely to be discharged on day 1 (91%, compared with 60% in the control group). Opioid use decreased by 30%, and pain scores on postoperative day 1 were significantly lower.
Another study looking at the effect of enhanced recovery implementation in gynecologic surgeries at the University of Virginia, Charlottesville, (gynecologic oncology, urogynecology, and general gynecology) similarly reported benefits for vaginal and minimally invasive procedures, as well as for open procedures (Obstet Gynecol. 2016 Sep;128[3]:457-66).
In the minimally invasive group, investigators compared 324 patients before ERAS implementation with 249 patients afterward and found that the median length of stay was unchanged (1 day). However, intraoperative and postoperative opioid consumption decreased significantly and – even though actual pain scores improved only slightly – patient satisfaction scores improved markedly among post-ERAS patients. Patients gave higher marks, for instance, to questions regarding pain control (“how well your pain was controlled”) and teamwork (“staff worked together to care for you”).
Reducing Opioids
New opioid use that persists after a surgical procedure is a postsurgical complication that we all should be working to prevent. It has been estimated that 6% of surgical patients – even those who’ve had relatively minor surgical procedures – will become long-term opioid users, developing a dependence on the drugs prescribed to them for postsurgical pain.
This was shown last year in a national study of insurance claims data from between 2013 and 2014; investigators identified adults without opioid use in the year prior to surgery (including hysterectomy) and found that 5.9%-6.5% were filling opioid prescriptions 90-180 days after their surgical procedure. The incidence in a nonoperative control cohort was 0.4% (JAMA Surg. 2017 Jun 21;152[6]:e170504). Notably, this prolonged use was greatest in patients with prior pain conditions, substance abuse, and mental health disorders – a finding that may have implications for the counseling we provide prior to surgery.
It’s not clear what the optimal analgesic regimen is for minimally invasive or other gynecologic surgeries. What is clearly recommended, however, is that the approach be multifaceted. In our practice, we believe that the preoperative use of acetaminophen, pregabalin, and celecoxib plays an important role in reducing postoperative pain and opioid use. But we also have striven to create a practice-wide culture shift (throughout the operating and recovery rooms), for instance, that encourages using the least amounts of narcotics possible and using the shortest-acting formulations possible.
Transversus abdominis plane (TAP) blocks are also often part of ERAS protocols; they have been shown in at least two randomized controlled trials of abdominal hysterectomy to reduce intraoperative fentanyl requirements and to reduce immediate postoperative pain scores and postoperative morphine requirements (Anesth Analg. 2008 Dec;107[6]:2056-60; J Anaesthesiol Clin Pharmacol. 2014 Jul-Sep;30[3]:391-6).
More recently, liposomal bupivacaine, which is slowly released over several days, has gained traction as a substitute for standard bupivacaine and other agents in TAP blocks. In one recent retrospective study, abdominal incision infiltration with liposomal bupivacaine was associated with less opioid use (with no change in pain scores), compared with bupivacaine hydrochloride after laparotomy for gynecologic malignancies (Obstet Gynecol. 2016 Nov;128[5]:1009-17). It’s significantly more expensive, however, making it likely that the formulation is being used more judiciously in minimally invasive gynecologic surgery than in open surgeries.
Because of costs, we currently are restricted to using liposomal bupivacaine in our robotic surgeries only. In our practice, the single 20 mL vial (266 mg of liposomal bupivacaine) is diluted with 20 mL of normal saline, but it can be further diluted without loss of efficacy. With a 16-gauge needle, the liposomal bupivacaine is distributed across the incisions (usually 20 mL in the umbilicus with a larger incision and 10 mL in each of the two lateral incisions). Patients are counseled that they may have more discomfort after 3 days, but by this point most are mobile and feeling relatively well with a combination of NSAIDs and acetaminophen.
With growing visibility of the problem of narcotic dependence in the United States, patients seem increasingly receptive and even eager to limit or avoid the use of opioids. Patients should be counseled that minimizing or avoiding opioids may also speed recovery. Narcotics cause gut motility to slow down, which may hinder mobilization. Early mobilization (within 24 hours) is among the enhanced recovery elements that the ERAS Society guidelines say is “of particular value” for minimally invasive surgery, along with maintenance of normothermia and normovolemia with maintenance of adequate cardiac output.
Selecting Steps
Our practice is also trying to reduce preoperative bowel preparation and preoperative fasting, both of which have been found to be stressful for the body without evidence of benefit. These practices can lead to insulin resistance and hyperglycemia, which are associated with increased morbidity and length of stay.
It is now recommended that clear fluids be allowed up to 2 hours before surgery and solids up to 6 hours before. Some health systems and practices also recommend presurgical carbohydrate loading (for example, 10 ounces of apple juice 2 hours before surgery) – another small change on the ERAS menu – to further reduce postoperative insulin resistance and help the body cope with its stress response to surgery.
Along with nutritional changes are also various measures aimed at optimizing the body’s functionality before surgery (“prehabilitation”), from walking 30 minutes a day to abstaining from alcohol for patients who drink heavily.
Throughout the country, enhanced recovery protocols are taking shape in gynecologic surgery. ERAS was featured in an aptly titled panel session at the 2017 annual meeting of the American Association of Gynecologic Laparoscopists: “Outpatient Hysterectomy, ERAS, and Same-Day Discharge: The Next Big Thing in Gyn Surgery.” Others are applying ERAS to scheduled cesarean sections. And in our practice, I believe that if we continue making small changes, we will reach our goal of opioid-free recoveries and a better surgical experience for our patients.
Kirsten Sasaki, MD, is an associate of the Advanced Gynecologic Surgery Institute. She reported that she has no disclosures relevant to this Master Class.
In the Evolving Mystery of BV, an Innovative Oral Treatment Emerges
Click Here to Read the Supplement
Topics include:
- BV terminology and treatment over time
- Current understanding of BV etiology
- BV consequences
- BV treatments
- Future research needs in BV
Author:
Steven E. Chavoustie, MD, FACOG, CCRP
University of Miami
Miller School of Medicine
Miami, Florida
Click Here to Read the Supplement
Topics include:
- BV terminology and treatment over time
- Current understanding of BV etiology
- BV consequences
- BV treatments
- Future research needs in BV
Author:
Steven E. Chavoustie, MD, FACOG, CCRP
University of Miami
Miller School of Medicine
Miami, Florida
Click Here to Read the Supplement
Topics include:
- BV terminology and treatment over time
- Current understanding of BV etiology
- BV consequences
- BV treatments
- Future research needs in BV
Author:
Steven E. Chavoustie, MD, FACOG, CCRP
University of Miami
Miller School of Medicine
Miami, Florida
Best practices address latest trends in PDT, skin cancer treatment
MIAMI – Pearls for providers of photodynamic therapy (PDT) include tips on skin preparation, eye protection, and use of three new codes to maximize reimbursement. Also trending in medical dermatology are best practices for intralesional injections of 5-FU to treat the often challenging isomorphic squamous cell carcinomas (SCCs) or keratoacanthomas on the lower leg, as well as use of neoadjuvant hedgehog inhibitors to shrink large skin cancer lesions, according to Glenn David Goldman, MD.
“This talk is about what you can do medically as a dermatologic surgeon,” Dr. Goldman said at the Orlando Dermatology Aesthetic and Clinical Conference.
Use new billing codes for photodynamic therapy
There are now three new PDT billing codes. “Make sure your coders are using these properly. They are active now, and if you don’t use them, you won’t get paid properly,” said Dr. Goldman, professor and medical director of dermatology at the University of Vermont, Burlington. Specifically, 96567 is for standard PDT applied by staff; 96573 is for PDT applied by a physician; and 96574 is for PDT and curettage performed by a physician.
“Be involved, don’t delegate,” Dr. Goldman added. “If you do, you will get paid half as much as you used to, which means you will lose money on every single patient you treat.”
What type of PDT physicians choose to use in their practice remains controversial. “Do you do short-contact PDT, do you do daylight PDT? We’ve gone back and forth in our practice,” Dr. Goldman said. “I’m not impressed with daylight PDT. I know this is at odds with some of the people here, but at least in Vermont, it doesn’t work very well.”
The way PDT was described in the original trials (a photosensitizer applied in the office followed by PDT) “works the best, with one caveat,” Dr. Goldman said. The caveat is that dermatologists should aim for a PDT clearance that approaches the efficacy of 5-fluorouracil (5-FU). “If you can get to that – which is difficult by the way – I think your patients will really appreciate this.”
An additional PDT pearl Dr. Goldman shared involves skin preparation: the use of acetone to defat the skin, even in patients with very thick lesions. Apply acetone with gauze to the site for 5 minutes and “all of that hyperkeratosis just wipes away,” curette off any residual hyperkeratosis – and consider a ring anesthetic block to control pain for the patient with severe disease, he advised.
Another tip is to forgo the goggles that come with most PDT kits. Instead, purchase smaller, disposable laser eye shields for PDT patients, Dr. Goldman said. “They work better. You can get closer to the eye … and they are more comfortable for the patient.”
Dr. Goldman’s practice is providing more PDT and much less 5-FU for patient convenience. “I believe if someone is willing to go through 3 weeks of 5-FU or 12-16 weeks of imiquimod, they get the best results. However, most people don’t want to do that if they can sit in front of a light for 15 minutes.”
Consider intralesional injections for SCCs and KAs on the legs
An ongoing challenge in medical dermatology is preventing rapid recurrence of SCCs and/or keratoacanthomas (KAs) near sites of previous excision on the legs. “We all see this quite a bit. Often you get lesions on the leg, you cut them out, and they come right back” close to the excision site, Dr. Goldman said.
He does not recommend methotrexate injections for these lesions. “Methotrexate does not work. It doesn’t hurt, but I’ve injected methotrexate into squamous cell carcinomas many times and they’ve never gone away.” In contrast, 5-FU “works incredibly well. They go away, I’ve had tremendous success. This has changed the way we treat these lesions.” 5-FU is inexpensive and can be obtained from oncology pharmacies. One caveat is 5-FU injections can be painful and patients require anesthesia prior to injection.
Using a 25-gauge or 27-gauge needle, Dr. Goldman injects 5-FU “exactly as I would a hypertrophic scar. I inject a squamous cell carcinoma carefully and ‘expand’ the tumor.” He typically injects a lesion every 2 weeks until it resolves completely, which typically takes two or three sessions.
“I want to emphasize that that’s really true about intralesional 5-FU for those KAs and scars on the legs,” said session moderator James Spencer, MD, a dermatologist in private practice in St. Petersburg, Florida. “Otherwise, you’re just chasing your tail trying to cut them out. You’ll do much better with the intralesional 5-FU; it’s easy to get, it’s affordable, it comes as 50 mg/mL … just keep it in the office.”
A recommended role for hedgehog inhibitors
Hedgehog inhibitors work best as neoadjuvant therapy to shrink large skin cancer tumors prior to excision, Dr. Goldman said. “Hedgehog inhibitors don’t cure anything … except for rare cases of small basal cell carcinomas.” For most lesions, however, the strategy is not curative.
“I don’t believe in hedgehog inhibitors for things that are readily resectable. We use them to shrink things down,” he added.
Dr. Goldman recommended treating patients with neoadjuvant hedgehog inhibitors to achieve the maximum tumor shrinking effect. Adverse effects tend to develop slowly over time, typically after a 6-week “grace period.” Nighttime leg muscle cramps, loss of taste, hair loss, and weight loss can occur. Also, electrolyte imbalances can occur, particularly in older patients with renal clearance issues. When the patient can no longer reasonably tolerate the adverse effects, which is usually the case, “then you do the surgery,” Dr. Goldman said.
“The benefits of neoadjuvant hedgehog inhibitors include predictable shrinkage of tumors,” and manufacturers have been helpful with financial issues, he noted.
Dr. Goldman had no relevant financial disclosures. Dr. Spencer has served on the speakers bureau for Genentech and Leo Pharma.
MIAMI – Pearls for providers of photodynamic therapy (PDT) include tips on skin preparation, eye protection, and use of three new codes to maximize reimbursement. Also trending in medical dermatology are best practices for intralesional injections of 5-FU to treat the often challenging isomorphic squamous cell carcinomas (SCCs) or keratoacanthomas on the lower leg, as well as use of neoadjuvant hedgehog inhibitors to shrink large skin cancer lesions, according to Glenn David Goldman, MD.
“This talk is about what you can do medically as a dermatologic surgeon,” Dr. Goldman said at the Orlando Dermatology Aesthetic and Clinical Conference.
Use new billing codes for photodynamic therapy
There are now three new PDT billing codes. “Make sure your coders are using these properly. They are active now, and if you don’t use them, you won’t get paid properly,” said Dr. Goldman, professor and medical director of dermatology at the University of Vermont, Burlington. Specifically, 96567 is for standard PDT applied by staff; 96573 is for PDT applied by a physician; and 96574 is for PDT and curettage performed by a physician.
“Be involved, don’t delegate,” Dr. Goldman added. “If you do, you will get paid half as much as you used to, which means you will lose money on every single patient you treat.”
What type of PDT physicians choose to use in their practice remains controversial. “Do you do short-contact PDT, do you do daylight PDT? We’ve gone back and forth in our practice,” Dr. Goldman said. “I’m not impressed with daylight PDT. I know this is at odds with some of the people here, but at least in Vermont, it doesn’t work very well.”
The way PDT was described in the original trials (a photosensitizer applied in the office followed by PDT) “works the best, with one caveat,” Dr. Goldman said. The caveat is that dermatologists should aim for a PDT clearance that approaches the efficacy of 5-fluorouracil (5-FU). “If you can get to that – which is difficult by the way – I think your patients will really appreciate this.”
An additional PDT pearl Dr. Goldman shared involves skin preparation: the use of acetone to defat the skin, even in patients with very thick lesions. Apply acetone with gauze to the site for 5 minutes and “all of that hyperkeratosis just wipes away,” curette off any residual hyperkeratosis – and consider a ring anesthetic block to control pain for the patient with severe disease, he advised.
Another tip is to forgo the goggles that come with most PDT kits. Instead, purchase smaller, disposable laser eye shields for PDT patients, Dr. Goldman said. “They work better. You can get closer to the eye … and they are more comfortable for the patient.”
Dr. Goldman’s practice is providing more PDT and much less 5-FU for patient convenience. “I believe if someone is willing to go through 3 weeks of 5-FU or 12-16 weeks of imiquimod, they get the best results. However, most people don’t want to do that if they can sit in front of a light for 15 minutes.”
Consider intralesional injections for SCCs and KAs on the legs
An ongoing challenge in medical dermatology is preventing rapid recurrence of SCCs and/or keratoacanthomas (KAs) near sites of previous excision on the legs. “We all see this quite a bit. Often you get lesions on the leg, you cut them out, and they come right back” close to the excision site, Dr. Goldman said.
He does not recommend methotrexate injections for these lesions. “Methotrexate does not work. It doesn’t hurt, but I’ve injected methotrexate into squamous cell carcinomas many times and they’ve never gone away.” In contrast, 5-FU “works incredibly well. They go away, I’ve had tremendous success. This has changed the way we treat these lesions.” 5-FU is inexpensive and can be obtained from oncology pharmacies. One caveat is 5-FU injections can be painful and patients require anesthesia prior to injection.
Using a 25-gauge or 27-gauge needle, Dr. Goldman injects 5-FU “exactly as I would a hypertrophic scar. I inject a squamous cell carcinoma carefully and ‘expand’ the tumor.” He typically injects a lesion every 2 weeks until it resolves completely, which typically takes two or three sessions.
“I want to emphasize that that’s really true about intralesional 5-FU for those KAs and scars on the legs,” said session moderator James Spencer, MD, a dermatologist in private practice in St. Petersburg, Florida. “Otherwise, you’re just chasing your tail trying to cut them out. You’ll do much better with the intralesional 5-FU; it’s easy to get, it’s affordable, it comes as 50 mg/mL … just keep it in the office.”
A recommended role for hedgehog inhibitors
Hedgehog inhibitors work best as neoadjuvant therapy to shrink large skin cancer tumors prior to excision, Dr. Goldman said. “Hedgehog inhibitors don’t cure anything … except for rare cases of small basal cell carcinomas.” For most lesions, however, the strategy is not curative.
“I don’t believe in hedgehog inhibitors for things that are readily resectable. We use them to shrink things down,” he added.
Dr. Goldman recommended treating patients with neoadjuvant hedgehog inhibitors to achieve the maximum tumor shrinking effect. Adverse effects tend to develop slowly over time, typically after a 6-week “grace period.” Nighttime leg muscle cramps, loss of taste, hair loss, and weight loss can occur. Also, electrolyte imbalances can occur, particularly in older patients with renal clearance issues. When the patient can no longer reasonably tolerate the adverse effects, which is usually the case, “then you do the surgery,” Dr. Goldman said.
“The benefits of neoadjuvant hedgehog inhibitors include predictable shrinkage of tumors,” and manufacturers have been helpful with financial issues, he noted.
Dr. Goldman had no relevant financial disclosures. Dr. Spencer has served on the speakers bureau for Genentech and Leo Pharma.
MIAMI – Pearls for providers of photodynamic therapy (PDT) include tips on skin preparation, eye protection, and use of three new codes to maximize reimbursement. Also trending in medical dermatology are best practices for intralesional injections of 5-FU to treat the often challenging isomorphic squamous cell carcinomas (SCCs) or keratoacanthomas on the lower leg, as well as use of neoadjuvant hedgehog inhibitors to shrink large skin cancer lesions, according to Glenn David Goldman, MD.
“This talk is about what you can do medically as a dermatologic surgeon,” Dr. Goldman said at the Orlando Dermatology Aesthetic and Clinical Conference.
Use new billing codes for photodynamic therapy
There are now three new PDT billing codes. “Make sure your coders are using these properly. They are active now, and if you don’t use them, you won’t get paid properly,” said Dr. Goldman, professor and medical director of dermatology at the University of Vermont, Burlington. Specifically, 96567 is for standard PDT applied by staff; 96573 is for PDT applied by a physician; and 96574 is for PDT and curettage performed by a physician.
“Be involved, don’t delegate,” Dr. Goldman added. “If you do, you will get paid half as much as you used to, which means you will lose money on every single patient you treat.”
What type of PDT physicians choose to use in their practice remains controversial. “Do you do short-contact PDT, do you do daylight PDT? We’ve gone back and forth in our practice,” Dr. Goldman said. “I’m not impressed with daylight PDT. I know this is at odds with some of the people here, but at least in Vermont, it doesn’t work very well.”
The way PDT was described in the original trials (a photosensitizer applied in the office followed by PDT) “works the best, with one caveat,” Dr. Goldman said. The caveat is that dermatologists should aim for a PDT clearance that approaches the efficacy of 5-fluorouracil (5-FU). “If you can get to that – which is difficult by the way – I think your patients will really appreciate this.”
An additional PDT pearl Dr. Goldman shared involves skin preparation: the use of acetone to defat the skin, even in patients with very thick lesions. Apply acetone with gauze to the site for 5 minutes and “all of that hyperkeratosis just wipes away,” curette off any residual hyperkeratosis – and consider a ring anesthetic block to control pain for the patient with severe disease, he advised.
Another tip is to forgo the goggles that come with most PDT kits. Instead, purchase smaller, disposable laser eye shields for PDT patients, Dr. Goldman said. “They work better. You can get closer to the eye … and they are more comfortable for the patient.”
Dr. Goldman’s practice is providing more PDT and much less 5-FU for patient convenience. “I believe if someone is willing to go through 3 weeks of 5-FU or 12-16 weeks of imiquimod, they get the best results. However, most people don’t want to do that if they can sit in front of a light for 15 minutes.”
Consider intralesional injections for SCCs and KAs on the legs
An ongoing challenge in medical dermatology is preventing rapid recurrence of SCCs and/or keratoacanthomas (KAs) near sites of previous excision on the legs. “We all see this quite a bit. Often you get lesions on the leg, you cut them out, and they come right back” close to the excision site, Dr. Goldman said.
He does not recommend methotrexate injections for these lesions. “Methotrexate does not work. It doesn’t hurt, but I’ve injected methotrexate into squamous cell carcinomas many times and they’ve never gone away.” In contrast, 5-FU “works incredibly well. They go away, I’ve had tremendous success. This has changed the way we treat these lesions.” 5-FU is inexpensive and can be obtained from oncology pharmacies. One caveat is 5-FU injections can be painful and patients require anesthesia prior to injection.
Using a 25-gauge or 27-gauge needle, Dr. Goldman injects 5-FU “exactly as I would a hypertrophic scar. I inject a squamous cell carcinoma carefully and ‘expand’ the tumor.” He typically injects a lesion every 2 weeks until it resolves completely, which typically takes two or three sessions.
“I want to emphasize that that’s really true about intralesional 5-FU for those KAs and scars on the legs,” said session moderator James Spencer, MD, a dermatologist in private practice in St. Petersburg, Florida. “Otherwise, you’re just chasing your tail trying to cut them out. You’ll do much better with the intralesional 5-FU; it’s easy to get, it’s affordable, it comes as 50 mg/mL … just keep it in the office.”
A recommended role for hedgehog inhibitors
Hedgehog inhibitors work best as neoadjuvant therapy to shrink large skin cancer tumors prior to excision, Dr. Goldman said. “Hedgehog inhibitors don’t cure anything … except for rare cases of small basal cell carcinomas.” For most lesions, however, the strategy is not curative.
“I don’t believe in hedgehog inhibitors for things that are readily resectable. We use them to shrink things down,” he added.
Dr. Goldman recommended treating patients with neoadjuvant hedgehog inhibitors to achieve the maximum tumor shrinking effect. Adverse effects tend to develop slowly over time, typically after a 6-week “grace period.” Nighttime leg muscle cramps, loss of taste, hair loss, and weight loss can occur. Also, electrolyte imbalances can occur, particularly in older patients with renal clearance issues. When the patient can no longer reasonably tolerate the adverse effects, which is usually the case, “then you do the surgery,” Dr. Goldman said.
“The benefits of neoadjuvant hedgehog inhibitors include predictable shrinkage of tumors,” and manufacturers have been helpful with financial issues, he noted.
Dr. Goldman had no relevant financial disclosures. Dr. Spencer has served on the speakers bureau for Genentech and Leo Pharma.
REPORTING FROM ODAC 2018
Clinical trial: Telescopic vs. balloon dissection for hernia
A randomized clinical trial will compare two techniques for achieving extraperitoneal space during hernia surgery.
The in operative times, early postoperative pain scores, surgical complications, and rate of hernia recurrence. The Spacemaker Balloon Dissector will be used for the trial.
The techniques will be timed and measured in minutes from incision to end of procedure. Pain outcomes will be measured using the Numeric Pain Rating Scale (NRS-11) at postoperative days 1, 7, and 30. Intraoperative complications, 30-day infections, and 1-year recurrence will be reported in numbers and percent as appropriate.
The study is sponsored by The Cleveland Clinic.
For more details about the trial, go to www.clinicaltrials.gov.
SOURCE: Clinical Trial NCT03276871.
A randomized clinical trial will compare two techniques for achieving extraperitoneal space during hernia surgery.
The in operative times, early postoperative pain scores, surgical complications, and rate of hernia recurrence. The Spacemaker Balloon Dissector will be used for the trial.
The techniques will be timed and measured in minutes from incision to end of procedure. Pain outcomes will be measured using the Numeric Pain Rating Scale (NRS-11) at postoperative days 1, 7, and 30. Intraoperative complications, 30-day infections, and 1-year recurrence will be reported in numbers and percent as appropriate.
The study is sponsored by The Cleveland Clinic.
For more details about the trial, go to www.clinicaltrials.gov.
SOURCE: Clinical Trial NCT03276871.
A randomized clinical trial will compare two techniques for achieving extraperitoneal space during hernia surgery.
The in operative times, early postoperative pain scores, surgical complications, and rate of hernia recurrence. The Spacemaker Balloon Dissector will be used for the trial.
The techniques will be timed and measured in minutes from incision to end of procedure. Pain outcomes will be measured using the Numeric Pain Rating Scale (NRS-11) at postoperative days 1, 7, and 30. Intraoperative complications, 30-day infections, and 1-year recurrence will be reported in numbers and percent as appropriate.
The study is sponsored by The Cleveland Clinic.
For more details about the trial, go to www.clinicaltrials.gov.
SOURCE: Clinical Trial NCT03276871.
FROM CLINICALTRIALS.GOV
New hematologic, cardiovascular system link may have therapeutic implications
ATLANTA – An intriguing link between the sex steroid hormonal milieu and platelet mitochondria has potential implications for reducing thrombosis risk.
The link, which involves a mitochondrial protein known as optic atrophy 1 (OPA1), appears to play a role in the regulation of thrombosis, and provides a possible explanation for the marked differences in cardiovascular risks between men and women, according to E. Dale Abel, MD, chair of the department of internal medicine, and director of the Fraternal Order of Eagles Diabetes Research Center at the University of Iowa, Iowa City.
The findings could lead to risk-stratification strategies and the identification of therapeutic targets, Dr. Abel said in an interview.
OPA1 is an inner mitochondrial membrane protein involved in mitochondrial fusion, he explained.
“My laboratory, for a very long time, has been interested in the cardiovascular complications of diabetes, and a lot of our work has focused on the heart and on the relationship between changes in metabolism and mitochondrial biology in those complications. We got interested in platelets because of a collaboration that actually started with Dr. [Andrew] Weyrich when my lab was at the University of Utah. There was a request for proposals from the National Heart, Lung, and Blood Institute for projects that would seek to understand the increased risk of thrombosis that occurs in people with diabetes,” he said.
Specifically, Dr. Weyrich had some preliminary data showing a backup of intermediates of glucose metabolism occurring in the platelets of diabetics.
“This suggested either that there was increased import of glucose into those cells or a decreased ability of those cells to metabolize glucose,” Dr. Abel said, adding that a closer look at the expression of certain genes in platelets as they related to the risk of thrombosis showed that a number of mitochondrial genes were involved, including OPA1.
Since Dr. Abel’s lab was already involved with studying glucose metabolism and mitochondrial metabolism, and had created a number of tools for modifying alleles, which would enable the targeting of expression of some of these genes, he and his colleagues began to look closer at the role of OPA1.
“The relationship between OPA1 and platelet biology, at least based on epidemiological studies from Dr. [Jane] Freedman’s analysis of platelet RNA expression in the Framingham cohort, really seemed to suggest that this had more to do with events in females rather than males,” Dr. Abel said.
He and his colleagues then generated a mouse model in which OPA1 levels in platelets could be manipulated. The goal was to determine if such manipulation would affect platelet function or platelet biology, and also to see if the effects differed between males and females.
“Initially, we didn’t have an expectation that we would see a difference between males and females, but in retrospect, it actually fits very nicely with what the epidemiological data in humans would suggest,” he said, referring to the differences in thrombosis risk between men and women.
Mitochondria go through a process of fusion and fission; OPA1 is involved in the fusion of the inner mitochondrial membrane, which has many folds known as cristae.
“These cristae are very important in the ability of mitochondria to generate energy, and OPA1 plays a very important role in maintaining the structure of these cristae,” he explained.
He and his colleagues generated mice that lacked OPA1 specifically in platelets. They then characterized the mitochondria and platelet function in these knockout mice.
“We saw that there was a difference between males and females in terms of how they responded to OPA1 deletion. Specifically, the males appeared to get more overt mitochondrial damage in terms of their structure and function, whereas the mitochondria appeared remarkably normal in females,” he said.
A look at platelet function showed that platelets in males were somewhat hyperactive, while in females they were somewhat underactive.
When the researchers used a model of deep venous thrombosis (DVT), more than 90% of male knockout mice developed a DVT versus 50% of wild-type controls. In contrast, there was no increase in DVT in female knockout mice relative to wild-type controls.
“So they were really opposite phenotypes in terms of platelet activity, and whenever one sees a difference between sexes in any biological variable or phenotype, you wonder if this is because of sex hormones,” he said.
This question led to a number of additional experiments.
In one of those experiments, Dr. Abel and his colleagues used a mouse model in which platelets were depleted and replaced via transfusion with platelets from another animal.
“We took male mice that were wild type and we depleted their platelets, and then we took platelets from an OPA1 deficient female and transfused these back into male mice, and took OPA1 deficient platelets from males and transfused them back into platelet-depleted female hosts. The really interesting thing in those experiments was that the phenotype switched,” he said.
That is, platelets in male mice with OPA1 deficiency, which had increased platelet activation in the male mice, became hypoactive when they were transfused into female mice. Similarly, hypoactive platelets from female mice became hyperactive when transfused into platelet-depleted male mice.
“What this told us then, is that the hormonal milieu interacts with OPA1 deficiency to modulate the function of the platelets,” he said.
Additional hormonal manipulations, involving orchiectomy in male mice to lower testosterone levels and increase estrogen levels, and ovariectomy in female mice to lower estrogen levels, showed that this could also modify platelet response.
“So we have discovered that somehow the amount of OPA1 in platelets interacts with circulating estrogens to modify the activity of platelets. This is not a trivial issue, because, as in the epidemiological study, the relationship is something that seems to be particularly true in females, and it also turned out that the OPA1 tended to track with increased cardiovascular events,” he said.
Preliminary studies involving pregnant women, looking at both the first and third trimester (when estrogen levels spike), also showed a correlation between increased platelet activity in the third trimester and higher levels of OPA1 in their platelets.
“It seems there is a relationship between OPA1 and platelets in women and estrogen levels that may then increase the risk of thrombosis. Maybe our mouse model phenotype is explained by the fact that we did the opposite: We reduced OPA1 in the platelets of females, and we actually saw that this was protective,” he said.
The findings are generating excitement, according to Dr. Weyrich, professor of internal medicine and vice president for research at the University of Utah, Salt Lake City, who was involved in the earlier studies that led Dr. Abel and his team to delve into the OPA1 research.
During a presentation of Dr. Abel’s findings at the annual meeting of the American Society of Hematology, Dr. Weyrich called the work “really, really striking,” and said the gender-specific findings are of particular importance.
“It’s something we often overlook and don’t think about, but I think it’s something that’s probably going to be more and more important as we begin to understand all types of diseases both in benign and malignant hematology,” he said.
Dr. Abel and his team plan to do their part to further that understanding. They are awaiting word on a new National Institutes of Health grant that will allow for expansion of their mouse studies into humans. Specifically, those studies will look at correlations between levels of OPA1 expression in platelets in women and history of/risk for developing a thrombotic event.
“Thrombosis is a significant problem in women who are exposed to estrogens ... and with the exception of a small number of specific genetic disorders of platelets, very little is known about what the risk factors are for this estrogen dependent increase in thrombotic risk,” he said.
What needs to be uncovered, Dr. Abel said, is whether women with the highest levels of OPA1 carry the highest risk of thrombosis.
“If we understand that, we may be in a position to stratify these women based on thrombosis risk in the setting of estrogen exposure. I think the other thing that will come out of the work, as we begin to understand the mechanisms for this relationship, is the identification of targets that we could therapeutically modulate to reduce this risk,” he added.
Eventually, as more is learned about the mechanisms that underlie the relationship between OPA1 and platelet activation, the findings might also lead to new approaches for reducing the risk of thrombosis in men, he noted.
Dr. Abel and Dr. Weyrich reported having no relevant financial disclosures.
ATLANTA – An intriguing link between the sex steroid hormonal milieu and platelet mitochondria has potential implications for reducing thrombosis risk.
The link, which involves a mitochondrial protein known as optic atrophy 1 (OPA1), appears to play a role in the regulation of thrombosis, and provides a possible explanation for the marked differences in cardiovascular risks between men and women, according to E. Dale Abel, MD, chair of the department of internal medicine, and director of the Fraternal Order of Eagles Diabetes Research Center at the University of Iowa, Iowa City.
The findings could lead to risk-stratification strategies and the identification of therapeutic targets, Dr. Abel said in an interview.
OPA1 is an inner mitochondrial membrane protein involved in mitochondrial fusion, he explained.
“My laboratory, for a very long time, has been interested in the cardiovascular complications of diabetes, and a lot of our work has focused on the heart and on the relationship between changes in metabolism and mitochondrial biology in those complications. We got interested in platelets because of a collaboration that actually started with Dr. [Andrew] Weyrich when my lab was at the University of Utah. There was a request for proposals from the National Heart, Lung, and Blood Institute for projects that would seek to understand the increased risk of thrombosis that occurs in people with diabetes,” he said.
Specifically, Dr. Weyrich had some preliminary data showing a backup of intermediates of glucose metabolism occurring in the platelets of diabetics.
“This suggested either that there was increased import of glucose into those cells or a decreased ability of those cells to metabolize glucose,” Dr. Abel said, adding that a closer look at the expression of certain genes in platelets as they related to the risk of thrombosis showed that a number of mitochondrial genes were involved, including OPA1.
Since Dr. Abel’s lab was already involved with studying glucose metabolism and mitochondrial metabolism, and had created a number of tools for modifying alleles, which would enable the targeting of expression of some of these genes, he and his colleagues began to look closer at the role of OPA1.
“The relationship between OPA1 and platelet biology, at least based on epidemiological studies from Dr. [Jane] Freedman’s analysis of platelet RNA expression in the Framingham cohort, really seemed to suggest that this had more to do with events in females rather than males,” Dr. Abel said.
He and his colleagues then generated a mouse model in which OPA1 levels in platelets could be manipulated. The goal was to determine if such manipulation would affect platelet function or platelet biology, and also to see if the effects differed between males and females.
“Initially, we didn’t have an expectation that we would see a difference between males and females, but in retrospect, it actually fits very nicely with what the epidemiological data in humans would suggest,” he said, referring to the differences in thrombosis risk between men and women.
Mitochondria go through a process of fusion and fission; OPA1 is involved in the fusion of the inner mitochondrial membrane, which has many folds known as cristae.
“These cristae are very important in the ability of mitochondria to generate energy, and OPA1 plays a very important role in maintaining the structure of these cristae,” he explained.
He and his colleagues generated mice that lacked OPA1 specifically in platelets. They then characterized the mitochondria and platelet function in these knockout mice.
“We saw that there was a difference between males and females in terms of how they responded to OPA1 deletion. Specifically, the males appeared to get more overt mitochondrial damage in terms of their structure and function, whereas the mitochondria appeared remarkably normal in females,” he said.
A look at platelet function showed that platelets in males were somewhat hyperactive, while in females they were somewhat underactive.
When the researchers used a model of deep venous thrombosis (DVT), more than 90% of male knockout mice developed a DVT versus 50% of wild-type controls. In contrast, there was no increase in DVT in female knockout mice relative to wild-type controls.
“So they were really opposite phenotypes in terms of platelet activity, and whenever one sees a difference between sexes in any biological variable or phenotype, you wonder if this is because of sex hormones,” he said.
This question led to a number of additional experiments.
In one of those experiments, Dr. Abel and his colleagues used a mouse model in which platelets were depleted and replaced via transfusion with platelets from another animal.
“We took male mice that were wild type and we depleted their platelets, and then we took platelets from an OPA1 deficient female and transfused these back into male mice, and took OPA1 deficient platelets from males and transfused them back into platelet-depleted female hosts. The really interesting thing in those experiments was that the phenotype switched,” he said.
That is, platelets in male mice with OPA1 deficiency, which had increased platelet activation in the male mice, became hypoactive when they were transfused into female mice. Similarly, hypoactive platelets from female mice became hyperactive when transfused into platelet-depleted male mice.
“What this told us then, is that the hormonal milieu interacts with OPA1 deficiency to modulate the function of the platelets,” he said.
Additional hormonal manipulations, involving orchiectomy in male mice to lower testosterone levels and increase estrogen levels, and ovariectomy in female mice to lower estrogen levels, showed that this could also modify platelet response.
“So we have discovered that somehow the amount of OPA1 in platelets interacts with circulating estrogens to modify the activity of platelets. This is not a trivial issue, because, as in the epidemiological study, the relationship is something that seems to be particularly true in females, and it also turned out that the OPA1 tended to track with increased cardiovascular events,” he said.
Preliminary studies involving pregnant women, looking at both the first and third trimester (when estrogen levels spike), also showed a correlation between increased platelet activity in the third trimester and higher levels of OPA1 in their platelets.
“It seems there is a relationship between OPA1 and platelets in women and estrogen levels that may then increase the risk of thrombosis. Maybe our mouse model phenotype is explained by the fact that we did the opposite: We reduced OPA1 in the platelets of females, and we actually saw that this was protective,” he said.
The findings are generating excitement, according to Dr. Weyrich, professor of internal medicine and vice president for research at the University of Utah, Salt Lake City, who was involved in the earlier studies that led Dr. Abel and his team to delve into the OPA1 research.
During a presentation of Dr. Abel’s findings at the annual meeting of the American Society of Hematology, Dr. Weyrich called the work “really, really striking,” and said the gender-specific findings are of particular importance.
“It’s something we often overlook and don’t think about, but I think it’s something that’s probably going to be more and more important as we begin to understand all types of diseases both in benign and malignant hematology,” he said.
Dr. Abel and his team plan to do their part to further that understanding. They are awaiting word on a new National Institutes of Health grant that will allow for expansion of their mouse studies into humans. Specifically, those studies will look at correlations between levels of OPA1 expression in platelets in women and history of/risk for developing a thrombotic event.
“Thrombosis is a significant problem in women who are exposed to estrogens ... and with the exception of a small number of specific genetic disorders of platelets, very little is known about what the risk factors are for this estrogen dependent increase in thrombotic risk,” he said.
What needs to be uncovered, Dr. Abel said, is whether women with the highest levels of OPA1 carry the highest risk of thrombosis.
“If we understand that, we may be in a position to stratify these women based on thrombosis risk in the setting of estrogen exposure. I think the other thing that will come out of the work, as we begin to understand the mechanisms for this relationship, is the identification of targets that we could therapeutically modulate to reduce this risk,” he added.
Eventually, as more is learned about the mechanisms that underlie the relationship between OPA1 and platelet activation, the findings might also lead to new approaches for reducing the risk of thrombosis in men, he noted.
Dr. Abel and Dr. Weyrich reported having no relevant financial disclosures.
ATLANTA – An intriguing link between the sex steroid hormonal milieu and platelet mitochondria has potential implications for reducing thrombosis risk.
The link, which involves a mitochondrial protein known as optic atrophy 1 (OPA1), appears to play a role in the regulation of thrombosis, and provides a possible explanation for the marked differences in cardiovascular risks between men and women, according to E. Dale Abel, MD, chair of the department of internal medicine, and director of the Fraternal Order of Eagles Diabetes Research Center at the University of Iowa, Iowa City.
The findings could lead to risk-stratification strategies and the identification of therapeutic targets, Dr. Abel said in an interview.
OPA1 is an inner mitochondrial membrane protein involved in mitochondrial fusion, he explained.
“My laboratory, for a very long time, has been interested in the cardiovascular complications of diabetes, and a lot of our work has focused on the heart and on the relationship between changes in metabolism and mitochondrial biology in those complications. We got interested in platelets because of a collaboration that actually started with Dr. [Andrew] Weyrich when my lab was at the University of Utah. There was a request for proposals from the National Heart, Lung, and Blood Institute for projects that would seek to understand the increased risk of thrombosis that occurs in people with diabetes,” he said.
Specifically, Dr. Weyrich had some preliminary data showing a backup of intermediates of glucose metabolism occurring in the platelets of diabetics.
“This suggested either that there was increased import of glucose into those cells or a decreased ability of those cells to metabolize glucose,” Dr. Abel said, adding that a closer look at the expression of certain genes in platelets as they related to the risk of thrombosis showed that a number of mitochondrial genes were involved, including OPA1.
Since Dr. Abel’s lab was already involved with studying glucose metabolism and mitochondrial metabolism, and had created a number of tools for modifying alleles, which would enable the targeting of expression of some of these genes, he and his colleagues began to look closer at the role of OPA1.
“The relationship between OPA1 and platelet biology, at least based on epidemiological studies from Dr. [Jane] Freedman’s analysis of platelet RNA expression in the Framingham cohort, really seemed to suggest that this had more to do with events in females rather than males,” Dr. Abel said.
He and his colleagues then generated a mouse model in which OPA1 levels in platelets could be manipulated. The goal was to determine if such manipulation would affect platelet function or platelet biology, and also to see if the effects differed between males and females.
“Initially, we didn’t have an expectation that we would see a difference between males and females, but in retrospect, it actually fits very nicely with what the epidemiological data in humans would suggest,” he said, referring to the differences in thrombosis risk between men and women.
Mitochondria go through a process of fusion and fission; OPA1 is involved in the fusion of the inner mitochondrial membrane, which has many folds known as cristae.
“These cristae are very important in the ability of mitochondria to generate energy, and OPA1 plays a very important role in maintaining the structure of these cristae,” he explained.
He and his colleagues generated mice that lacked OPA1 specifically in platelets. They then characterized the mitochondria and platelet function in these knockout mice.
“We saw that there was a difference between males and females in terms of how they responded to OPA1 deletion. Specifically, the males appeared to get more overt mitochondrial damage in terms of their structure and function, whereas the mitochondria appeared remarkably normal in females,” he said.
A look at platelet function showed that platelets in males were somewhat hyperactive, while in females they were somewhat underactive.
When the researchers used a model of deep venous thrombosis (DVT), more than 90% of male knockout mice developed a DVT versus 50% of wild-type controls. In contrast, there was no increase in DVT in female knockout mice relative to wild-type controls.
“So they were really opposite phenotypes in terms of platelet activity, and whenever one sees a difference between sexes in any biological variable or phenotype, you wonder if this is because of sex hormones,” he said.
This question led to a number of additional experiments.
In one of those experiments, Dr. Abel and his colleagues used a mouse model in which platelets were depleted and replaced via transfusion with platelets from another animal.
“We took male mice that were wild type and we depleted their platelets, and then we took platelets from an OPA1 deficient female and transfused these back into male mice, and took OPA1 deficient platelets from males and transfused them back into platelet-depleted female hosts. The really interesting thing in those experiments was that the phenotype switched,” he said.
That is, platelets in male mice with OPA1 deficiency, which had increased platelet activation in the male mice, became hypoactive when they were transfused into female mice. Similarly, hypoactive platelets from female mice became hyperactive when transfused into platelet-depleted male mice.
“What this told us then, is that the hormonal milieu interacts with OPA1 deficiency to modulate the function of the platelets,” he said.
Additional hormonal manipulations, involving orchiectomy in male mice to lower testosterone levels and increase estrogen levels, and ovariectomy in female mice to lower estrogen levels, showed that this could also modify platelet response.
“So we have discovered that somehow the amount of OPA1 in platelets interacts with circulating estrogens to modify the activity of platelets. This is not a trivial issue, because, as in the epidemiological study, the relationship is something that seems to be particularly true in females, and it also turned out that the OPA1 tended to track with increased cardiovascular events,” he said.
Preliminary studies involving pregnant women, looking at both the first and third trimester (when estrogen levels spike), also showed a correlation between increased platelet activity in the third trimester and higher levels of OPA1 in their platelets.
“It seems there is a relationship between OPA1 and platelets in women and estrogen levels that may then increase the risk of thrombosis. Maybe our mouse model phenotype is explained by the fact that we did the opposite: We reduced OPA1 in the platelets of females, and we actually saw that this was protective,” he said.
The findings are generating excitement, according to Dr. Weyrich, professor of internal medicine and vice president for research at the University of Utah, Salt Lake City, who was involved in the earlier studies that led Dr. Abel and his team to delve into the OPA1 research.
During a presentation of Dr. Abel’s findings at the annual meeting of the American Society of Hematology, Dr. Weyrich called the work “really, really striking,” and said the gender-specific findings are of particular importance.
“It’s something we often overlook and don’t think about, but I think it’s something that’s probably going to be more and more important as we begin to understand all types of diseases both in benign and malignant hematology,” he said.
Dr. Abel and his team plan to do their part to further that understanding. They are awaiting word on a new National Institutes of Health grant that will allow for expansion of their mouse studies into humans. Specifically, those studies will look at correlations between levels of OPA1 expression in platelets in women and history of/risk for developing a thrombotic event.
“Thrombosis is a significant problem in women who are exposed to estrogens ... and with the exception of a small number of specific genetic disorders of platelets, very little is known about what the risk factors are for this estrogen dependent increase in thrombotic risk,” he said.
What needs to be uncovered, Dr. Abel said, is whether women with the highest levels of OPA1 carry the highest risk of thrombosis.
“If we understand that, we may be in a position to stratify these women based on thrombosis risk in the setting of estrogen exposure. I think the other thing that will come out of the work, as we begin to understand the mechanisms for this relationship, is the identification of targets that we could therapeutically modulate to reduce this risk,” he added.
Eventually, as more is learned about the mechanisms that underlie the relationship between OPA1 and platelet activation, the findings might also lead to new approaches for reducing the risk of thrombosis in men, he noted.
Dr. Abel and Dr. Weyrich reported having no relevant financial disclosures.
EXPERT ANALYSIS FROM ASH 2017
Study IDs predictors of nonmelanoma skin cancer in IBD
LAS VEGAS – , a large national analysis showed.
“Some studies have shown that patients with IBD may be at increased risk for nonmelanoma skin cancer (NMSC) because of the immunomodulators that they take for the management of their disease,” Zubair Khan, MD, said in an interview at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “But these are mostly small, single-center studies.” In an effort to determine the epidemiology of NMSC in patients hospitalized with IBD, Dr. Khan, associate chief resident in the internal medicine department at the University of Toledo (Ohio) Medical Center and his associates analyzed the National Inpatient Sample (NIS) database for all subjects who had a primary or secondary discharge diagnosis of IBD during 2002-2014. Next, they used ICD-9 codes to identify the rate of NMSC in this population.
Compared with IBD patients without NMSC, most of the IBD patients with NMSC were males (54% vs. 42%; P less than 0.001), covered by Medicare (65% vs. 37%), were white (96% vs. 81%; P less than .001), lived in the Midwest or Western United States (27% and 26% vs. 22% and 17%), were admitted to urban teaching hospitals (57% vs. 51%; P less than .001), were discharged to skilled nursing facilities (16% vs. 10%; P less than .001), required home health care (17% vs. 11%), and were admitted electively (27% vs. 20%). The researchers observed no significant difference in mortality among IBD patients with and without NMSC (1.61% vs. 1.53%; P = .22).
Multivariate analysis revealed that the following factors were predictive of NMSC in IBD: comorbid diagnosis of rheumatoid arthritis, collagen vasculature diseases, male sex, and white race. “Patients with those risk factors should be made more aware of their risk for developing NMSC,” Dr. Khan said. “They shouldn’t be taken lightly.”
Dr. Khan reported having no financial disclosures.
*This story was updated on 3/26.
SOURCE: Khan Z et al. Crohn’s & Colitis Congress, Poster 209.
LAS VEGAS – , a large national analysis showed.
“Some studies have shown that patients with IBD may be at increased risk for nonmelanoma skin cancer (NMSC) because of the immunomodulators that they take for the management of their disease,” Zubair Khan, MD, said in an interview at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “But these are mostly small, single-center studies.” In an effort to determine the epidemiology of NMSC in patients hospitalized with IBD, Dr. Khan, associate chief resident in the internal medicine department at the University of Toledo (Ohio) Medical Center and his associates analyzed the National Inpatient Sample (NIS) database for all subjects who had a primary or secondary discharge diagnosis of IBD during 2002-2014. Next, they used ICD-9 codes to identify the rate of NMSC in this population.
Compared with IBD patients without NMSC, most of the IBD patients with NMSC were males (54% vs. 42%; P less than 0.001), covered by Medicare (65% vs. 37%), were white (96% vs. 81%; P less than .001), lived in the Midwest or Western United States (27% and 26% vs. 22% and 17%), were admitted to urban teaching hospitals (57% vs. 51%; P less than .001), were discharged to skilled nursing facilities (16% vs. 10%; P less than .001), required home health care (17% vs. 11%), and were admitted electively (27% vs. 20%). The researchers observed no significant difference in mortality among IBD patients with and without NMSC (1.61% vs. 1.53%; P = .22).
Multivariate analysis revealed that the following factors were predictive of NMSC in IBD: comorbid diagnosis of rheumatoid arthritis, collagen vasculature diseases, male sex, and white race. “Patients with those risk factors should be made more aware of their risk for developing NMSC,” Dr. Khan said. “They shouldn’t be taken lightly.”
Dr. Khan reported having no financial disclosures.
*This story was updated on 3/26.
SOURCE: Khan Z et al. Crohn’s & Colitis Congress, Poster 209.
LAS VEGAS – , a large national analysis showed.
“Some studies have shown that patients with IBD may be at increased risk for nonmelanoma skin cancer (NMSC) because of the immunomodulators that they take for the management of their disease,” Zubair Khan, MD, said in an interview at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “But these are mostly small, single-center studies.” In an effort to determine the epidemiology of NMSC in patients hospitalized with IBD, Dr. Khan, associate chief resident in the internal medicine department at the University of Toledo (Ohio) Medical Center and his associates analyzed the National Inpatient Sample (NIS) database for all subjects who had a primary or secondary discharge diagnosis of IBD during 2002-2014. Next, they used ICD-9 codes to identify the rate of NMSC in this population.
Compared with IBD patients without NMSC, most of the IBD patients with NMSC were males (54% vs. 42%; P less than 0.001), covered by Medicare (65% vs. 37%), were white (96% vs. 81%; P less than .001), lived in the Midwest or Western United States (27% and 26% vs. 22% and 17%), were admitted to urban teaching hospitals (57% vs. 51%; P less than .001), were discharged to skilled nursing facilities (16% vs. 10%; P less than .001), required home health care (17% vs. 11%), and were admitted electively (27% vs. 20%). The researchers observed no significant difference in mortality among IBD patients with and without NMSC (1.61% vs. 1.53%; P = .22).
Multivariate analysis revealed that the following factors were predictive of NMSC in IBD: comorbid diagnosis of rheumatoid arthritis, collagen vasculature diseases, male sex, and white race. “Patients with those risk factors should be made more aware of their risk for developing NMSC,” Dr. Khan said. “They shouldn’t be taken lightly.”
Dr. Khan reported having no financial disclosures.
*This story was updated on 3/26.
SOURCE: Khan Z et al. Crohn’s & Colitis Congress, Poster 209.
REPORTING FROM THE CROHN’S & COLITIS CONGRESS
Key clinical point: Many factors predict which IBD patients are at risk for developing nonmelanoma skin cancer.
Major finding: Compared with IBD patients without NMSC, most of the IBD patients with NMSC were males (54% vs. 42%; P less than .001) and white (96% vs. 81%; P less than .001).
Study details: An analysis of 22,620 patients who had a primary or secondary discharge diagnosis of IBD during 2002-2014.
Disclosures: Dr. Khan reported having no financial disclosures.
Source: Khan Z et al. Crohn’s & Colitis Congress, Poster 209.
Three in 10 of your diabetic patients may have liver fibrosis
LOS ANGELES – For every 10 of your adult patients with type 2 diabetes, three are likely to have moderate to severe liver fibrosis, according to Kenneth Cusi, MD, FACP, FACE.
“If in the last 10 patients, you didn’t diagnose anybody with fibrosis, you probably missed it,” he said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The question is, How are we going to tackle this problem? My academic goal is that we incorporate screening for NASH [nonalcoholic steatohepatitis], or for fibrosis more specifically, in the same way we do for retinopathy or nephropathy, because we do have a way to treat it.”
As part of the large population-based Rotterdam study of individuals aged 45 years and older, researchers found that liver stiffness of 8 kPa or more by transient elastography was present in 5.6% of the study participants and was strongly associated with steatosis and diabetes (Hepatology. 2016;63:138-47). According to Dr. Cusi, individuals who have steatosis without diabetes face a 5%-10% risk of fibrosis, while those with steatosis and diabetes face a 15%-20% risk.
“It’s well established in a number of studies that if you have fibrosis, you’re at high risk not only of cirrhosis, but also of hepatocellular carcinoma,” he said. “The key thing is not detecting fat, which is not really the target. The target is if there’s fibrosis or not.” Three ways to assess for fibrosis include MR elastography, transient elastography (which is the most commonly used), and fibrosis marker panels.
Liver fibrosis likely starts with adipose tissue dysfunction, said Dr. Cusi, who authored a review on the pathophysiology of interactions between adipose tissue and target organs in obesity and the resulting clinical implications for the management of nonalcoholic steatohepatitis (Gastroenterology. 2012;142[4]:711-25.e6).
“When you have insulin-resistant, sick adipose tissue, that leads to the accumulation of fat in the liver,” he said. “. Even if you get people who are matched for BMIs [body mass indexes] between 30 and 35 kg/m2, there is a spectrum in which some individuals have very insulin-resistant adipose tissue and others less so. I would say that 1 out of 10 are metabolically healthy, and we don’t understand exactly why.”
In a recent cross-sectional analysis of 352 healthy individuals, Dr. Cusi and his associates found that intrahepatic triglyceride (IHTG) accumulation is strongly associated with adipose tissue insulin resistance, supporting the current theory of lipotoxicity as a driver of IHTG accumulation (Hepatology. 2017;65[4]:1132-44). The researchers observed that once IHTG accumulation reaches about 6%, skeletal muscle insulin resistance, hypertriglyceridemia, and low HDL cholesterol become fully established.
“The next question is, How does this correlate with NASH?” Dr. Cusi said. “Our take is that there is a threshold effect. Once you have a critical amount of triglycerides in your liver, some individuals are going to activate pathways that are harmful. NASH is not something exclusive to individuals who are obese. Lean people can also develop NASH. The key feature is insulin resistance, not metabolic syndrome. Once you develop a fatty liver, your chances of NASH are comparable to that of an obese individual. The paradox is that lean individuals get a fatty liver, but when they get a fatty liver, they are at risk for NASH and for fibrosis.”
Why lean individuals develop NASH is not fully understood, but Dr. Cusi said he suspects that the problem develops at the mitochondrial level.
Results from an unpublished animal model in which mice were fed a high–trans-fat diet for 24 weeks showed that the mice developed steatosis by week 8 and NASH by week 24. The mice had an increase in the tricarboxylic acid (TCA) cycle, which is typical of the NASH period, as well as an increase in ceramides.
“Perhaps a unifying hypothesis would be that the development of NASH is linked to inflammation and to insulin signaling,” Dr. Cusi said. “Not surprisingly, it had a number of effects on the mitochondria, and in this animal model it decreases the TCA.” He noted that the biology of fibrosis remains unknown in humans. “What we have been familiar with is the high-triglyceride, low-HDL pattern,” he said. “If you look at how that correlates with the amount of liver fat, it is basically a threshold effect. Once you have steatosis, you don’t see much worse dyslipidemia, which is typical of these patients.”
Recently published guidance from the American Association for the Study of Liver Diseases on the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) suggests that patients require a weight loss of 3%-5% to improve steatosis, but a loss of 7%-10% to improve most histologic features of NASH, including fibrosis (Hepatology. 2018;67[1]:328-57). Exercise alone may prevent or reduce steatosis, but its ability to improve other aspects of liver histology remains unknown. Bariatric surgery can be considered in otherwise eligible obese individuals with NAFLD or NASH. The procedure’s impact on fibrosis is unknown.
The AASLD practice guideline notes that metformin is not recommended for treating NASH in adult patients, but pioglitazone improves liver histology in patients with and without type 2 diabetes with biopsy-proven NASH.
“Pioglitazone has had the greatest benefit in terms of treatment effect, compared to placebo,” Dr. Cusi said. “It’s a generic drug; at the VA [Veterans Affairs], it costs 8 cents per tablet. I think that pioglitazone will be to NASH what metformin has been to type 2 diabetes. The most common side effect is weight gain, typically between 4 and 9 lb. Risks and benefits should be discussed with each patient. It should not be used for NAFLD without biopsy-proven NASH.”
The guideline goes on to say that it’s currently premature to consider GLP-1 (glucagonlike peptide–1) agonists for treating liver disease in patients with NAFLD or NASH. Meanwhile, vitamin E at 800 IU has been shown to improve liver histology in nondiabetic adults with NASH, but the risks and benefits should be discussed with each patient. Vitamin E is not recommended for NASH in diabetic patients, NAFLD without a liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis.
The AASLD practice guideline also states that the best evidence for using SGLT2 (sodium-glucose cotransporter–2) inhibitors in NAFLD comes from animal studies, which report a reduction in steatosis with and without weight loss. Clinical studies reporting a reduction in steatosis are limited. There are positive observational studies with a reduction in alanine aminotransferase and some studies that have shown a reduction in liver fat. “For me, the best option is to tailor treatment to the pathophysiology of the disease,” Dr. Cusi said. “You reduce fat by weight loss in some way, or you change the biology of fat with a thiazolidinedione.”
Dr. Cusi reported that he has received grant support from the Burroughs Wellcome Fund, the American Diabetes Association, and the National Institutes of Health.
LOS ANGELES – For every 10 of your adult patients with type 2 diabetes, three are likely to have moderate to severe liver fibrosis, according to Kenneth Cusi, MD, FACP, FACE.
“If in the last 10 patients, you didn’t diagnose anybody with fibrosis, you probably missed it,” he said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The question is, How are we going to tackle this problem? My academic goal is that we incorporate screening for NASH [nonalcoholic steatohepatitis], or for fibrosis more specifically, in the same way we do for retinopathy or nephropathy, because we do have a way to treat it.”
As part of the large population-based Rotterdam study of individuals aged 45 years and older, researchers found that liver stiffness of 8 kPa or more by transient elastography was present in 5.6% of the study participants and was strongly associated with steatosis and diabetes (Hepatology. 2016;63:138-47). According to Dr. Cusi, individuals who have steatosis without diabetes face a 5%-10% risk of fibrosis, while those with steatosis and diabetes face a 15%-20% risk.
“It’s well established in a number of studies that if you have fibrosis, you’re at high risk not only of cirrhosis, but also of hepatocellular carcinoma,” he said. “The key thing is not detecting fat, which is not really the target. The target is if there’s fibrosis or not.” Three ways to assess for fibrosis include MR elastography, transient elastography (which is the most commonly used), and fibrosis marker panels.
Liver fibrosis likely starts with adipose tissue dysfunction, said Dr. Cusi, who authored a review on the pathophysiology of interactions between adipose tissue and target organs in obesity and the resulting clinical implications for the management of nonalcoholic steatohepatitis (Gastroenterology. 2012;142[4]:711-25.e6).
“When you have insulin-resistant, sick adipose tissue, that leads to the accumulation of fat in the liver,” he said. “. Even if you get people who are matched for BMIs [body mass indexes] between 30 and 35 kg/m2, there is a spectrum in which some individuals have very insulin-resistant adipose tissue and others less so. I would say that 1 out of 10 are metabolically healthy, and we don’t understand exactly why.”
In a recent cross-sectional analysis of 352 healthy individuals, Dr. Cusi and his associates found that intrahepatic triglyceride (IHTG) accumulation is strongly associated with adipose tissue insulin resistance, supporting the current theory of lipotoxicity as a driver of IHTG accumulation (Hepatology. 2017;65[4]:1132-44). The researchers observed that once IHTG accumulation reaches about 6%, skeletal muscle insulin resistance, hypertriglyceridemia, and low HDL cholesterol become fully established.
“The next question is, How does this correlate with NASH?” Dr. Cusi said. “Our take is that there is a threshold effect. Once you have a critical amount of triglycerides in your liver, some individuals are going to activate pathways that are harmful. NASH is not something exclusive to individuals who are obese. Lean people can also develop NASH. The key feature is insulin resistance, not metabolic syndrome. Once you develop a fatty liver, your chances of NASH are comparable to that of an obese individual. The paradox is that lean individuals get a fatty liver, but when they get a fatty liver, they are at risk for NASH and for fibrosis.”
Why lean individuals develop NASH is not fully understood, but Dr. Cusi said he suspects that the problem develops at the mitochondrial level.
Results from an unpublished animal model in which mice were fed a high–trans-fat diet for 24 weeks showed that the mice developed steatosis by week 8 and NASH by week 24. The mice had an increase in the tricarboxylic acid (TCA) cycle, which is typical of the NASH period, as well as an increase in ceramides.
“Perhaps a unifying hypothesis would be that the development of NASH is linked to inflammation and to insulin signaling,” Dr. Cusi said. “Not surprisingly, it had a number of effects on the mitochondria, and in this animal model it decreases the TCA.” He noted that the biology of fibrosis remains unknown in humans. “What we have been familiar with is the high-triglyceride, low-HDL pattern,” he said. “If you look at how that correlates with the amount of liver fat, it is basically a threshold effect. Once you have steatosis, you don’t see much worse dyslipidemia, which is typical of these patients.”
Recently published guidance from the American Association for the Study of Liver Diseases on the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) suggests that patients require a weight loss of 3%-5% to improve steatosis, but a loss of 7%-10% to improve most histologic features of NASH, including fibrosis (Hepatology. 2018;67[1]:328-57). Exercise alone may prevent or reduce steatosis, but its ability to improve other aspects of liver histology remains unknown. Bariatric surgery can be considered in otherwise eligible obese individuals with NAFLD or NASH. The procedure’s impact on fibrosis is unknown.
The AASLD practice guideline notes that metformin is not recommended for treating NASH in adult patients, but pioglitazone improves liver histology in patients with and without type 2 diabetes with biopsy-proven NASH.
“Pioglitazone has had the greatest benefit in terms of treatment effect, compared to placebo,” Dr. Cusi said. “It’s a generic drug; at the VA [Veterans Affairs], it costs 8 cents per tablet. I think that pioglitazone will be to NASH what metformin has been to type 2 diabetes. The most common side effect is weight gain, typically between 4 and 9 lb. Risks and benefits should be discussed with each patient. It should not be used for NAFLD without biopsy-proven NASH.”
The guideline goes on to say that it’s currently premature to consider GLP-1 (glucagonlike peptide–1) agonists for treating liver disease in patients with NAFLD or NASH. Meanwhile, vitamin E at 800 IU has been shown to improve liver histology in nondiabetic adults with NASH, but the risks and benefits should be discussed with each patient. Vitamin E is not recommended for NASH in diabetic patients, NAFLD without a liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis.
The AASLD practice guideline also states that the best evidence for using SGLT2 (sodium-glucose cotransporter–2) inhibitors in NAFLD comes from animal studies, which report a reduction in steatosis with and without weight loss. Clinical studies reporting a reduction in steatosis are limited. There are positive observational studies with a reduction in alanine aminotransferase and some studies that have shown a reduction in liver fat. “For me, the best option is to tailor treatment to the pathophysiology of the disease,” Dr. Cusi said. “You reduce fat by weight loss in some way, or you change the biology of fat with a thiazolidinedione.”
Dr. Cusi reported that he has received grant support from the Burroughs Wellcome Fund, the American Diabetes Association, and the National Institutes of Health.
LOS ANGELES – For every 10 of your adult patients with type 2 diabetes, three are likely to have moderate to severe liver fibrosis, according to Kenneth Cusi, MD, FACP, FACE.
“If in the last 10 patients, you didn’t diagnose anybody with fibrosis, you probably missed it,” he said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The question is, How are we going to tackle this problem? My academic goal is that we incorporate screening for NASH [nonalcoholic steatohepatitis], or for fibrosis more specifically, in the same way we do for retinopathy or nephropathy, because we do have a way to treat it.”
As part of the large population-based Rotterdam study of individuals aged 45 years and older, researchers found that liver stiffness of 8 kPa or more by transient elastography was present in 5.6% of the study participants and was strongly associated with steatosis and diabetes (Hepatology. 2016;63:138-47). According to Dr. Cusi, individuals who have steatosis without diabetes face a 5%-10% risk of fibrosis, while those with steatosis and diabetes face a 15%-20% risk.
“It’s well established in a number of studies that if you have fibrosis, you’re at high risk not only of cirrhosis, but also of hepatocellular carcinoma,” he said. “The key thing is not detecting fat, which is not really the target. The target is if there’s fibrosis or not.” Three ways to assess for fibrosis include MR elastography, transient elastography (which is the most commonly used), and fibrosis marker panels.
Liver fibrosis likely starts with adipose tissue dysfunction, said Dr. Cusi, who authored a review on the pathophysiology of interactions between adipose tissue and target organs in obesity and the resulting clinical implications for the management of nonalcoholic steatohepatitis (Gastroenterology. 2012;142[4]:711-25.e6).
“When you have insulin-resistant, sick adipose tissue, that leads to the accumulation of fat in the liver,” he said. “. Even if you get people who are matched for BMIs [body mass indexes] between 30 and 35 kg/m2, there is a spectrum in which some individuals have very insulin-resistant adipose tissue and others less so. I would say that 1 out of 10 are metabolically healthy, and we don’t understand exactly why.”
In a recent cross-sectional analysis of 352 healthy individuals, Dr. Cusi and his associates found that intrahepatic triglyceride (IHTG) accumulation is strongly associated with adipose tissue insulin resistance, supporting the current theory of lipotoxicity as a driver of IHTG accumulation (Hepatology. 2017;65[4]:1132-44). The researchers observed that once IHTG accumulation reaches about 6%, skeletal muscle insulin resistance, hypertriglyceridemia, and low HDL cholesterol become fully established.
“The next question is, How does this correlate with NASH?” Dr. Cusi said. “Our take is that there is a threshold effect. Once you have a critical amount of triglycerides in your liver, some individuals are going to activate pathways that are harmful. NASH is not something exclusive to individuals who are obese. Lean people can also develop NASH. The key feature is insulin resistance, not metabolic syndrome. Once you develop a fatty liver, your chances of NASH are comparable to that of an obese individual. The paradox is that lean individuals get a fatty liver, but when they get a fatty liver, they are at risk for NASH and for fibrosis.”
Why lean individuals develop NASH is not fully understood, but Dr. Cusi said he suspects that the problem develops at the mitochondrial level.
Results from an unpublished animal model in which mice were fed a high–trans-fat diet for 24 weeks showed that the mice developed steatosis by week 8 and NASH by week 24. The mice had an increase in the tricarboxylic acid (TCA) cycle, which is typical of the NASH period, as well as an increase in ceramides.
“Perhaps a unifying hypothesis would be that the development of NASH is linked to inflammation and to insulin signaling,” Dr. Cusi said. “Not surprisingly, it had a number of effects on the mitochondria, and in this animal model it decreases the TCA.” He noted that the biology of fibrosis remains unknown in humans. “What we have been familiar with is the high-triglyceride, low-HDL pattern,” he said. “If you look at how that correlates with the amount of liver fat, it is basically a threshold effect. Once you have steatosis, you don’t see much worse dyslipidemia, which is typical of these patients.”
Recently published guidance from the American Association for the Study of Liver Diseases on the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) suggests that patients require a weight loss of 3%-5% to improve steatosis, but a loss of 7%-10% to improve most histologic features of NASH, including fibrosis (Hepatology. 2018;67[1]:328-57). Exercise alone may prevent or reduce steatosis, but its ability to improve other aspects of liver histology remains unknown. Bariatric surgery can be considered in otherwise eligible obese individuals with NAFLD or NASH. The procedure’s impact on fibrosis is unknown.
The AASLD practice guideline notes that metformin is not recommended for treating NASH in adult patients, but pioglitazone improves liver histology in patients with and without type 2 diabetes with biopsy-proven NASH.
“Pioglitazone has had the greatest benefit in terms of treatment effect, compared to placebo,” Dr. Cusi said. “It’s a generic drug; at the VA [Veterans Affairs], it costs 8 cents per tablet. I think that pioglitazone will be to NASH what metformin has been to type 2 diabetes. The most common side effect is weight gain, typically between 4 and 9 lb. Risks and benefits should be discussed with each patient. It should not be used for NAFLD without biopsy-proven NASH.”
The guideline goes on to say that it’s currently premature to consider GLP-1 (glucagonlike peptide–1) agonists for treating liver disease in patients with NAFLD or NASH. Meanwhile, vitamin E at 800 IU has been shown to improve liver histology in nondiabetic adults with NASH, but the risks and benefits should be discussed with each patient. Vitamin E is not recommended for NASH in diabetic patients, NAFLD without a liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis.
The AASLD practice guideline also states that the best evidence for using SGLT2 (sodium-glucose cotransporter–2) inhibitors in NAFLD comes from animal studies, which report a reduction in steatosis with and without weight loss. Clinical studies reporting a reduction in steatosis are limited. There are positive observational studies with a reduction in alanine aminotransferase and some studies that have shown a reduction in liver fat. “For me, the best option is to tailor treatment to the pathophysiology of the disease,” Dr. Cusi said. “You reduce fat by weight loss in some way, or you change the biology of fat with a thiazolidinedione.”
Dr. Cusi reported that he has received grant support from the Burroughs Wellcome Fund, the American Diabetes Association, and the National Institutes of Health.
EXPERT ANALYSIS FROM WCIRDC 2017
Daily update: An emerging cardiac disease, CHIP, and more
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“This is an emerging disease that you’re all going to see in your practices this year. You’ve got to know what to do with these patients. Get to them early,” one expert warns.
To learn about this important development and more, click on the link above for today's four-minute medical news update.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“This is an emerging disease that you’re all going to see in your practices this year. You’ve got to know what to do with these patients. Get to them early,” one expert warns.
To learn about this important development and more, click on the link above for today's four-minute medical news update.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
“This is an emerging disease that you’re all going to see in your practices this year. You’ve got to know what to do with these patients. Get to them early,” one expert warns.
To learn about this important development and more, click on the link above for today's four-minute medical news update.
Sex disparities seen in surgical professorships
Female surgeons were less likely than were male surgeons to be full professors in 2014, according to an analysis that adjusted for a number of “factors known to influence academic rank independently of sex.”
The overall , after adjustment for such factors as age, years since residency, subspecialty, total publications, and clinical trial participation. “This methodological rigor is a central and unique strength of this analysis and bolsters the validity of the study findings,” wrote Daniel M. Blumenthal, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his associates. The report was published in Annals of Surgery (2018 Jan 12. doi: 10.1097/SLA.0000000000002662).
Differences favoring men were seen in eight of the nine subspecialties included in the study, with vascular surgery being the exception (adjusted odds ratio, 1.63). Of the other eight, however, only in general surgery (adjusted odds ratio, 0.68) was the difference significant, the investigators said.
Another factor included in the analysis was the research ranking of the medical schools. There was no significant sex disparity for faculty members at medical schools ranked in the top 20 by U.S. News & World Report (adjusted odds ratio, 1.03), but schools outside the top 20 had an adjusted odds ratio (AOR) of 0.65 for women, compared with men. Geographically speaking, the largest disadvantage for female surgeons among the four main census divisions was in the Northeast (AOR, 0.52), with the West generating relative equality (AOR, 1.02) and the South (AOR, 0.83) and the Midwest (AOR, 0.87) in between, they reported.
Dr. Blumenthal and his associates used a cross-sectional database maintained by Doximity, an online networking company. The analysis included data for 11,549 surgeons with faculty appointments in 2014: 3,080 were full professors (7% were women), 2,931 were associate professors (13.8% were women), and 5,538 were assistant professors (19.4% were women).
Dr. Blumenthal reported research funding from a fellowship at Harvard. The investigators declared no conflict of interests.
SOURCE: Blumenthal DM et al. Ann Surg. 2018 Jan 12. doi: 10.1097/SLA.0000000000002662.
Female surgeons were less likely than were male surgeons to be full professors in 2014, according to an analysis that adjusted for a number of “factors known to influence academic rank independently of sex.”
The overall , after adjustment for such factors as age, years since residency, subspecialty, total publications, and clinical trial participation. “This methodological rigor is a central and unique strength of this analysis and bolsters the validity of the study findings,” wrote Daniel M. Blumenthal, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his associates. The report was published in Annals of Surgery (2018 Jan 12. doi: 10.1097/SLA.0000000000002662).
Differences favoring men were seen in eight of the nine subspecialties included in the study, with vascular surgery being the exception (adjusted odds ratio, 1.63). Of the other eight, however, only in general surgery (adjusted odds ratio, 0.68) was the difference significant, the investigators said.
Another factor included in the analysis was the research ranking of the medical schools. There was no significant sex disparity for faculty members at medical schools ranked in the top 20 by U.S. News & World Report (adjusted odds ratio, 1.03), but schools outside the top 20 had an adjusted odds ratio (AOR) of 0.65 for women, compared with men. Geographically speaking, the largest disadvantage for female surgeons among the four main census divisions was in the Northeast (AOR, 0.52), with the West generating relative equality (AOR, 1.02) and the South (AOR, 0.83) and the Midwest (AOR, 0.87) in between, they reported.
Dr. Blumenthal and his associates used a cross-sectional database maintained by Doximity, an online networking company. The analysis included data for 11,549 surgeons with faculty appointments in 2014: 3,080 were full professors (7% were women), 2,931 were associate professors (13.8% were women), and 5,538 were assistant professors (19.4% were women).
Dr. Blumenthal reported research funding from a fellowship at Harvard. The investigators declared no conflict of interests.
SOURCE: Blumenthal DM et al. Ann Surg. 2018 Jan 12. doi: 10.1097/SLA.0000000000002662.
Female surgeons were less likely than were male surgeons to be full professors in 2014, according to an analysis that adjusted for a number of “factors known to influence academic rank independently of sex.”
The overall , after adjustment for such factors as age, years since residency, subspecialty, total publications, and clinical trial participation. “This methodological rigor is a central and unique strength of this analysis and bolsters the validity of the study findings,” wrote Daniel M. Blumenthal, MD, of Massachusetts General Hospital and Harvard Medical School, Boston, and his associates. The report was published in Annals of Surgery (2018 Jan 12. doi: 10.1097/SLA.0000000000002662).
Differences favoring men were seen in eight of the nine subspecialties included in the study, with vascular surgery being the exception (adjusted odds ratio, 1.63). Of the other eight, however, only in general surgery (adjusted odds ratio, 0.68) was the difference significant, the investigators said.
Another factor included in the analysis was the research ranking of the medical schools. There was no significant sex disparity for faculty members at medical schools ranked in the top 20 by U.S. News & World Report (adjusted odds ratio, 1.03), but schools outside the top 20 had an adjusted odds ratio (AOR) of 0.65 for women, compared with men. Geographically speaking, the largest disadvantage for female surgeons among the four main census divisions was in the Northeast (AOR, 0.52), with the West generating relative equality (AOR, 1.02) and the South (AOR, 0.83) and the Midwest (AOR, 0.87) in between, they reported.
Dr. Blumenthal and his associates used a cross-sectional database maintained by Doximity, an online networking company. The analysis included data for 11,549 surgeons with faculty appointments in 2014: 3,080 were full professors (7% were women), 2,931 were associate professors (13.8% were women), and 5,538 were assistant professors (19.4% were women).
Dr. Blumenthal reported research funding from a fellowship at Harvard. The investigators declared no conflict of interests.
SOURCE: Blumenthal DM et al. Ann Surg. 2018 Jan 12. doi: 10.1097/SLA.0000000000002662.
FROM ANNALS OF SURGERY
FDA Pledges Faster Updates for Antibiotics
The FDA is launching a new website to get critical updates about antibiotics and antifungals out faster to health care professionals to help them make more informed prescribing decisions. The site will provide “direct and timely access” to information about when bacterial or fungal infections are likely to respond to a specific drug.
“When you are treating critically ill patients, you want as much information as possible about the pathogen…and the susceptibility of that pathogen to various treatment,” said FDA Commissioner Scott Gottlieb, MD. Under the old approach, he said, updating each drug’s individual labeling took too long. Only after the revised drug labeling was approved could a drug or device manufacturer update testing criteria and labeling for the latest antimicrobial susceptibility test results. Each drug and device labeling had to be updated whenever criteria changed.
The new tool will allow the FDA to simultaneously provide updates multiple drugs that have the same active ingredient and share that information transparently via a dedicated web page.
The FDA is launching a new website to get critical updates about antibiotics and antifungals out faster to health care professionals to help them make more informed prescribing decisions. The site will provide “direct and timely access” to information about when bacterial or fungal infections are likely to respond to a specific drug.
“When you are treating critically ill patients, you want as much information as possible about the pathogen…and the susceptibility of that pathogen to various treatment,” said FDA Commissioner Scott Gottlieb, MD. Under the old approach, he said, updating each drug’s individual labeling took too long. Only after the revised drug labeling was approved could a drug or device manufacturer update testing criteria and labeling for the latest antimicrobial susceptibility test results. Each drug and device labeling had to be updated whenever criteria changed.
The new tool will allow the FDA to simultaneously provide updates multiple drugs that have the same active ingredient and share that information transparently via a dedicated web page.
The FDA is launching a new website to get critical updates about antibiotics and antifungals out faster to health care professionals to help them make more informed prescribing decisions. The site will provide “direct and timely access” to information about when bacterial or fungal infections are likely to respond to a specific drug.
“When you are treating critically ill patients, you want as much information as possible about the pathogen…and the susceptibility of that pathogen to various treatment,” said FDA Commissioner Scott Gottlieb, MD. Under the old approach, he said, updating each drug’s individual labeling took too long. Only after the revised drug labeling was approved could a drug or device manufacturer update testing criteria and labeling for the latest antimicrobial susceptibility test results. Each drug and device labeling had to be updated whenever criteria changed.
The new tool will allow the FDA to simultaneously provide updates multiple drugs that have the same active ingredient and share that information transparently via a dedicated web page.