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VIDEO: No effect of donor on FMT outcomes in C. difficile patients
NEW ORLEANS – Fecal microbiota transplantation, or FMT, is a highly effective treatment for Clostridium difficile infection (CDI) and other digestive and autoimmune disorders, but little is known about the role of donor characteristics with respect to outcomes in patients with recurrent CDI.
A study of nearly 1,999 patients with an 83.9% cure rate showed no significant difference between 28 donors in terms of clinical outcomes at 8 weeks, according to Majdi Osman, MD, of OpenBiome, a not-for-profit stool bank in the Boston area.
Studies in inflammatory bowel diseases have suggested that donors do matter, but that does not appear to be the case when it comes to recurrent CDI, Dr. Osman said at an annual scientific meeting on infectious diseases.
“Broadly speaking, it seems like the efficacy rate is the same amongst all of our donors,” he said in a video interview at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Potential donors are subject to a rigorous screening process, and less than 3% are accepted, but given that donors were shown in previous studies to play a role in effectiveness in some other conditions, Dr. Osman said it was worth checking to see if outcomes in CDI could be further improved through donor selection.
In fact, it appears that “the donor doesn’t matter,” he said, noting that it may be that “we are selecting for a fairly narrow spectrum of the population, and actually the stool that we’re selecting is fairly similar in composition.”
Efforts are underway to look more closely at that possibility, and Dr. Osman said he hopes to see more standardized clinical trials and clinical follow-up. He also said he is excited about an FMT registry – a joint project of the American Gastroenterology Association and the Infectious Diseases Society of America – that will follow 4,000 patients for 10 years.
“We will be working closely with them to provide material and get some really good robust clinical data going forward,” he said.
Dr. Osman reported having no disclosures.
NEW ORLEANS – Fecal microbiota transplantation, or FMT, is a highly effective treatment for Clostridium difficile infection (CDI) and other digestive and autoimmune disorders, but little is known about the role of donor characteristics with respect to outcomes in patients with recurrent CDI.
A study of nearly 1,999 patients with an 83.9% cure rate showed no significant difference between 28 donors in terms of clinical outcomes at 8 weeks, according to Majdi Osman, MD, of OpenBiome, a not-for-profit stool bank in the Boston area.
Studies in inflammatory bowel diseases have suggested that donors do matter, but that does not appear to be the case when it comes to recurrent CDI, Dr. Osman said at an annual scientific meeting on infectious diseases.
“Broadly speaking, it seems like the efficacy rate is the same amongst all of our donors,” he said in a video interview at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Potential donors are subject to a rigorous screening process, and less than 3% are accepted, but given that donors were shown in previous studies to play a role in effectiveness in some other conditions, Dr. Osman said it was worth checking to see if outcomes in CDI could be further improved through donor selection.
In fact, it appears that “the donor doesn’t matter,” he said, noting that it may be that “we are selecting for a fairly narrow spectrum of the population, and actually the stool that we’re selecting is fairly similar in composition.”
Efforts are underway to look more closely at that possibility, and Dr. Osman said he hopes to see more standardized clinical trials and clinical follow-up. He also said he is excited about an FMT registry – a joint project of the American Gastroenterology Association and the Infectious Diseases Society of America – that will follow 4,000 patients for 10 years.
“We will be working closely with them to provide material and get some really good robust clinical data going forward,” he said.
Dr. Osman reported having no disclosures.
NEW ORLEANS – Fecal microbiota transplantation, or FMT, is a highly effective treatment for Clostridium difficile infection (CDI) and other digestive and autoimmune disorders, but little is known about the role of donor characteristics with respect to outcomes in patients with recurrent CDI.
A study of nearly 1,999 patients with an 83.9% cure rate showed no significant difference between 28 donors in terms of clinical outcomes at 8 weeks, according to Majdi Osman, MD, of OpenBiome, a not-for-profit stool bank in the Boston area.
Studies in inflammatory bowel diseases have suggested that donors do matter, but that does not appear to be the case when it comes to recurrent CDI, Dr. Osman said at an annual scientific meeting on infectious diseases.
“Broadly speaking, it seems like the efficacy rate is the same amongst all of our donors,” he said in a video interview at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Potential donors are subject to a rigorous screening process, and less than 3% are accepted, but given that donors were shown in previous studies to play a role in effectiveness in some other conditions, Dr. Osman said it was worth checking to see if outcomes in CDI could be further improved through donor selection.
In fact, it appears that “the donor doesn’t matter,” he said, noting that it may be that “we are selecting for a fairly narrow spectrum of the population, and actually the stool that we’re selecting is fairly similar in composition.”
Efforts are underway to look more closely at that possibility, and Dr. Osman said he hopes to see more standardized clinical trials and clinical follow-up. He also said he is excited about an FMT registry – a joint project of the American Gastroenterology Association and the Infectious Diseases Society of America – that will follow 4,000 patients for 10 years.
“We will be working closely with them to provide material and get some really good robust clinical data going forward,” he said.
Dr. Osman reported having no disclosures.
VIDEO: The surgical treatment of pelvic congestion
BY CHARLES E. MILLER, MD
Chronic pelvic pain is described as the presence of lower abdominal or pelvic pain for longer than 6 months. It is believed to affect approximately one in six women and 12%-15% of women of reproductive age. The diagnosis and treatment of chronic pelvic pain adds as much as a $2 billion burden to our health system annually.
It was first described clinically in the literature in 1857, while the existence of pelvic varicosities wasn’t documented for nearly another 100 years. Pelvic congestion syndrome (PCS) accounts for 30%-70% of cases presenting with chronic pelvic pain. PCS can be due to pelvic venous insufficiency, characterized by reflux into pelvic veins leading to pelvic varicosities or alternative venous pathways secondary to varicose veins of the leg.
Other etiologies of PCS include nutcracker syndrome (left renal vein compressed between the aorta and the superior mesenteric artery), May-Thurner syndrome (compression of the left common iliac vein by the right common iliac artery) or, less likely, tumor thrombosis of the inferior vena cava, portal vein thrombosis, renal cell carcinoma, left renal thrombosis, or left kidney arterial-venous fistula.
While there appears to be significant literature indicating a long-term success rate of greater than 80% in patients treated by percutaneous endovascular procedures (embolization, stenting), there is far less information on the postsurgical success of blocking the varicose gonadal vein. Nevertheless, our long-term results with gonadal vein clipping is virtually the same as that of our radiological colleagues.
It is a pleasure to welcome Courtney Steller, DO, to this edition of the Master Class in Gynecologic Surgery to discuss the diagnosis and treatment of PCS, with an emphasis on surgical correction.
Dr. Steller is a recent graduate of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill. She is currently in private practice and is an associate at the Family Health Centers of San Diego, Calif.
Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported having no financial disclosures relevant to this column. Email him at [email protected].
Pelvic congestion syndrome: A treatable cause of pain
BY COURTNEY STELLER, DO
Pelvic congestion syndrome is a poorly understood and underdiagnosed disease. Yet, over the last decade, the syndrome has become less controversial as the etiology has become better understood and as the diagnostic approach has become more specific. Through these advances, treatments have also become increasingly more successful.
This is an important shift, because the chronic pelvic pain experienced by patients with pelvic congestion significantly impacts their quality of life and well-being. As the pain persists, it can become exceedingly difficult to manage. Many patients we have ultimately treated for pelvic congestion syndrome have had years of various work-ups, significant diagnostic investigations, and trials of different treatments without having any cause of their pain identified or achieving any lasting symptom relief.
The pelvic pain in patients with pelvic congestion syndrome (PCS) can be noncyclical or cyclical. It is present most of the time but tends to get worse at the end of the day and after long periods of standing and/or sitting. The pain also may worsen with intercourse, largely afterward. The syndrome tends to occur in premenopausal and multiparous women, but it’s important to appreciate that this is not always the case; we have diagnosed and treated PCS in several young, nulliparous patients as well.
Features and diagnosis
PCS is a disorder of pelvic venous circulation that predominantly affects the ovarian veins. It is sometimes referred to as pelvic vein incompetence or pelvic vascular dysfunction. Just as veins in the legs can enlarge and become varicose, the ovarian veins – and sometimes the internal iliac veins – can become incompetent and unable to effectively return blood back to the heart.
Pregnancy may predispose patients to developing the abnormally dilated and refluxing veins that characterize PCS, as the increase in pelvic vein capacity and uterine compression can lead to significant stasis of blood in the pelvis and subsequent damage to the veins and the venous valves. There also is believed to be an estrogen component to the development of PCS, because estrogen is known to act as a vasodilator. Moreover, a congenital absence and incompetence of venous valves in some cases has been reported.
In a recent study looking at pelvic vein incompetence and symptoms of chronic pelvic pain, these women were reported to have a distinctive symptom profile, with the “most notable” features being the presence of dull pelvic pain that radiates to the upper thighs and is aggravated by prolonged standing and walking – symptoms that are similar to the leg symptoms experienced by patients with severe varicose veins (Eur J Obstet Gynecol Reprod Biol. 2016 Jan;196:21-5).
Other investigators have similarly described the pelvic pain related to PCS as a dull ache or heaviness sensation that is most severe at the end of the day and that is lessened with supine positioning (though not necessarily immediately) and often exacerbated with sexual intercourse, especially post coitus. These descriptions are in line with my experience with PCS. There is usually exquisite tenderness on pelvic exam, especially localized to the adnexa. Patients will often have varicose veins on their upper legs or labia.
Interestingly, it has been repeatedly shown that many women have dilated and incompetent pelvic veins without also having such pathognomonic pain. We therefore cannot treat women based solely on the finding of abnormal veins.
On the other hand we must determine which patients with chronic pelvic pain have PCS. The differential diagnosis for PCS includes endometriosis, adenomyosis chronic pelvic inflammatory disease, adhesive disease, adnexal masses, adnexal torsion, and several nongynecologic diseases including interstitial cystitis and irritable bowel syndrome.
Venography has become the gold standard for diagnosing pelvic congestion. The procedure involves catheterization of the ovarian veins through a femoral or jugular approach. In our experience, the common femoral vein is the more frequently used access point. Using a contrast injection, the interventional radiologist can assess the degree of venous dilation and reflux in the pelvis.
There currently is no consensus on a cutoff for vein diameter or on any validated measures for congestion. According to one report on PCS authored by interventional radiologists, the diagnosis of PCS is confirmed with the venographic findings of ovarian vein diameter greater than 6 mm, retrograde ovarian or pelvic venous flow, presence of several tortuous collateral pelvic venous pathways, and delayed or stagnant clearance on contrast (Semin Intervent Radiol. 2008 Dec;25[4]:361-8).
The criteria vary, however. A recent literature review on pelvic congestion syndrome by Chiara Borghi, MD, and Lucio Dell’Atti, MD, states that incompetent pelvic veins are defined as more than 5-10 mm in diameter (Arch Gynecol Obstet. 2016 Feb;293[2]:291-301).
To more accurately diagnose PCS, our patients undergo tilt-table venography. The patient is placed into a reverse-Trendelenburg upright or semi-upright position to potentially exacerbate any venous reflux or dilation.
Other methods of identifying and diagnosing pelvic congestion have included transabdominal and transvaginal ultrasound, CT, and MRI. While CT and MRI both offer an overview of the pelvic vasculature and are helpful for ruling out other causes of chronic pelvic pain, they have low specificity for pelvic varices, according to the Italian review.
Sonography performed in the supine position, on the other hand, appears to be increasingly viewed as an acceptable screening tool for determining which patients may ultimately benefit from venography. It is also important in evaluation to rule out other pathologies not yet excluded. However, it should not be used for diagnosis of PCS.
Treating PCS
There are two main approaches to treating PCS: venous ligation (a gynecologic surgical approach) and percutaneous transcatheter embolization (performed by interventional radiologists).
The literature and evidence base is still in its infancy, but is growing. In our experience, both approaches lead to good resolution of symptoms over time in the majority of patients, and appear superior to the medical therapies that have been proposed for treating PCS, such as progestins and gonadotropin-releasing hormone agonists. Success rates with medical therapy are more variable and appear to be more short lived.
A review published this year on the effectiveness of embolization of pelvic veins for reducing chronic pelvic pain showed that 75% of women undergoing embolization had symptomatic relief that generally increased over time and was sustained. The authors concluded that embolization appears to be effective for the majority of women, and is safe, although they also noted that the quality of the evidence is low (J Vasc Interv Radiol. 2016 Oct;27[10]:1478-86.e8). Their review was based almost entirely on prospective case series.
Dr. Borghi and Dr. Dell’Atti offered a similar assessment of embolization for PCS, stating in their review article that clinical success has been reported in 70%-85% of patients. They also report nearly equivalent success rates of up to 75% with treatment via surgical ligation of ovarian and/or pelvic vasculature. These findings are from mostly observational data and case series.
Decisions about which approach to take should be individualized. If there are no differences with respect to insurance coverage for the patient, then embolization may be the preferred approach because it is the most minimally invasive technique and can potentially be performed at the time of diagnostic venography, negating the need for a second procedure. A skilled interventional radiologist familiar with the disease and the treatment is necessary. Various embolic agents are utilized, including coils, glues, foams, and other agents that cause sclerosis of the abnormal veins.
In other cases, venous ligation is preferred, especially when an additional gynecologic surgery, such as a cystectomy or myomectomy, is required.
Surgical ligation of ovarian veins was initially performed via laparotomy using a traditional retroperitoneal approach. The surgical goal is to isolate the ovarian vein significantly above the pelvic brim and before the vein becomes substantially dilated. Laparotomy therefore requires a vertical mid-line incision to provide adequate access to the appropriate portion of the ovarian vessels, leading to potentially high morbidity and poor cosmesis.
More recently, gynecologic surgeons skilled in laparoscopy have successfully managed PCS transperitoneally. A few small series of bilateral laparoscopic transperitoneal ligation of ovarian veins have been reported, including one by Tigellio Gargiulo, MD, who clipped both veins in their upper third, near their distal ends at the inferior vena cava (right) and the renal vein (left) (J Am Assoc Gynecol Laparosc. 2003 Nov;10[4]:501-4).
We prefer a robot-assisted laparoscopic approach for most of our patients. Not only does the improved dexterity help while working with sensitive vasculature, but more importantly we are able to use Firefly fluorescence.
The procedure generally is as follows. The uterine adnexa on the affected side is grasped and placed on tension so that the infundibulopelvic (IP) ligament can be visualized as it courses up and above the pelvic brim. The peritoneum immediately over the IP ligament is gently grasped and tented upward, and a small incision is made into the peritoneum, providing access into the retroperitoneum. The ureter should be visualized medial to this dissection.
The peritoneal tissue is then gently dissected off the ovarian vessels. Once the vessels are freed from the peritoneal tissue, the dilated ovarian vein is often clearly visualized. It is important to note that if no venous dilation is seen during laparoscopy, the procedure should not be aborted. Due to the Trendelenburg position that is utilized in gynecologic – and especially laparoscopic – surgery, the venous system sometimes appears falsely “normal” at this time.
Once the ovarian vessels have been isolated, the arteries must be separated from the veins. The adventitial tissue is dissected until the vessels are separated. Great care should be taken to ensure that all movements run parallel to the vessels and not perpendicular, therefore decreasing the risk of bleeding.
This process can be challenging. The surgeon is working with delicate vasculature. Often there are several branches from the vein that have formed due to the abnormal venous system. The best way to approach it is to identify planes and separate those planes in order to isolate individual vessels. If difficulties are still encountered, the surgeon should restart the dissection higher.
Once the dilated ovarian vein is isolated, one to two clips are placed.
Usually the artery is clearly distinct from the vein as it is smaller, more elastic, and can be seen pulsing. However, occasionally it is difficult to distinguish. In these cases, assistance with the da Vinci surgical system is useful: Indocyanine green (ICG) dye can be injected intravenously and visualized with a near-infrared light on the da Vinci platform. The dye is then seen glowing green as it first courses through the artery and then the vein.
For patients who have been found on venography to have bilateral disease, we perform the ligation procedure bilaterally. Once ligation is complete, the more competent collateral veins in the pelvis will assume more of the venous circulation.
In our experience, patients have ultimately noted substantial pain relief after these procedures, both with the endoscopic embolization and the surgical ligation. Patients are counseled that it can take several months to notice a relief in the pain.
In rare cases, pelvic congestion is related to extrinsic compression. For instance, the left renal vein can become compressed between the aorta and the superior mesenteric artery (the nutcracker syndrome), or the left common iliac vein can be compressed between the overlying right internal iliac artery and the underlying vertebral body (May-Thurner syndrome). Both of these conditions can lead to secondary PCS.
Such complex conditions are usually treated by vascular surgeons. May-Thurner syndrome is treated via stenting, while nutcracker syndrome can be treated with stenting or transposition of the renal vein to the distal vena cava.
Dr. Steller is an associate at the Family Health Centers of San Diego. She reported having no relevant financial disclosures.
BY CHARLES E. MILLER, MD
Chronic pelvic pain is described as the presence of lower abdominal or pelvic pain for longer than 6 months. It is believed to affect approximately one in six women and 12%-15% of women of reproductive age. The diagnosis and treatment of chronic pelvic pain adds as much as a $2 billion burden to our health system annually.
It was first described clinically in the literature in 1857, while the existence of pelvic varicosities wasn’t documented for nearly another 100 years. Pelvic congestion syndrome (PCS) accounts for 30%-70% of cases presenting with chronic pelvic pain. PCS can be due to pelvic venous insufficiency, characterized by reflux into pelvic veins leading to pelvic varicosities or alternative venous pathways secondary to varicose veins of the leg.
Other etiologies of PCS include nutcracker syndrome (left renal vein compressed between the aorta and the superior mesenteric artery), May-Thurner syndrome (compression of the left common iliac vein by the right common iliac artery) or, less likely, tumor thrombosis of the inferior vena cava, portal vein thrombosis, renal cell carcinoma, left renal thrombosis, or left kidney arterial-venous fistula.
While there appears to be significant literature indicating a long-term success rate of greater than 80% in patients treated by percutaneous endovascular procedures (embolization, stenting), there is far less information on the postsurgical success of blocking the varicose gonadal vein. Nevertheless, our long-term results with gonadal vein clipping is virtually the same as that of our radiological colleagues.
It is a pleasure to welcome Courtney Steller, DO, to this edition of the Master Class in Gynecologic Surgery to discuss the diagnosis and treatment of PCS, with an emphasis on surgical correction.
Dr. Steller is a recent graduate of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill. She is currently in private practice and is an associate at the Family Health Centers of San Diego, Calif.
Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported having no financial disclosures relevant to this column. Email him at [email protected].
Pelvic congestion syndrome: A treatable cause of pain
BY COURTNEY STELLER, DO
Pelvic congestion syndrome is a poorly understood and underdiagnosed disease. Yet, over the last decade, the syndrome has become less controversial as the etiology has become better understood and as the diagnostic approach has become more specific. Through these advances, treatments have also become increasingly more successful.
This is an important shift, because the chronic pelvic pain experienced by patients with pelvic congestion significantly impacts their quality of life and well-being. As the pain persists, it can become exceedingly difficult to manage. Many patients we have ultimately treated for pelvic congestion syndrome have had years of various work-ups, significant diagnostic investigations, and trials of different treatments without having any cause of their pain identified or achieving any lasting symptom relief.
The pelvic pain in patients with pelvic congestion syndrome (PCS) can be noncyclical or cyclical. It is present most of the time but tends to get worse at the end of the day and after long periods of standing and/or sitting. The pain also may worsen with intercourse, largely afterward. The syndrome tends to occur in premenopausal and multiparous women, but it’s important to appreciate that this is not always the case; we have diagnosed and treated PCS in several young, nulliparous patients as well.
Features and diagnosis
PCS is a disorder of pelvic venous circulation that predominantly affects the ovarian veins. It is sometimes referred to as pelvic vein incompetence or pelvic vascular dysfunction. Just as veins in the legs can enlarge and become varicose, the ovarian veins – and sometimes the internal iliac veins – can become incompetent and unable to effectively return blood back to the heart.
Pregnancy may predispose patients to developing the abnormally dilated and refluxing veins that characterize PCS, as the increase in pelvic vein capacity and uterine compression can lead to significant stasis of blood in the pelvis and subsequent damage to the veins and the venous valves. There also is believed to be an estrogen component to the development of PCS, because estrogen is known to act as a vasodilator. Moreover, a congenital absence and incompetence of venous valves in some cases has been reported.
In a recent study looking at pelvic vein incompetence and symptoms of chronic pelvic pain, these women were reported to have a distinctive symptom profile, with the “most notable” features being the presence of dull pelvic pain that radiates to the upper thighs and is aggravated by prolonged standing and walking – symptoms that are similar to the leg symptoms experienced by patients with severe varicose veins (Eur J Obstet Gynecol Reprod Biol. 2016 Jan;196:21-5).
Other investigators have similarly described the pelvic pain related to PCS as a dull ache or heaviness sensation that is most severe at the end of the day and that is lessened with supine positioning (though not necessarily immediately) and often exacerbated with sexual intercourse, especially post coitus. These descriptions are in line with my experience with PCS. There is usually exquisite tenderness on pelvic exam, especially localized to the adnexa. Patients will often have varicose veins on their upper legs or labia.
Interestingly, it has been repeatedly shown that many women have dilated and incompetent pelvic veins without also having such pathognomonic pain. We therefore cannot treat women based solely on the finding of abnormal veins.
On the other hand we must determine which patients with chronic pelvic pain have PCS. The differential diagnosis for PCS includes endometriosis, adenomyosis chronic pelvic inflammatory disease, adhesive disease, adnexal masses, adnexal torsion, and several nongynecologic diseases including interstitial cystitis and irritable bowel syndrome.
Venography has become the gold standard for diagnosing pelvic congestion. The procedure involves catheterization of the ovarian veins through a femoral or jugular approach. In our experience, the common femoral vein is the more frequently used access point. Using a contrast injection, the interventional radiologist can assess the degree of venous dilation and reflux in the pelvis.
There currently is no consensus on a cutoff for vein diameter or on any validated measures for congestion. According to one report on PCS authored by interventional radiologists, the diagnosis of PCS is confirmed with the venographic findings of ovarian vein diameter greater than 6 mm, retrograde ovarian or pelvic venous flow, presence of several tortuous collateral pelvic venous pathways, and delayed or stagnant clearance on contrast (Semin Intervent Radiol. 2008 Dec;25[4]:361-8).
The criteria vary, however. A recent literature review on pelvic congestion syndrome by Chiara Borghi, MD, and Lucio Dell’Atti, MD, states that incompetent pelvic veins are defined as more than 5-10 mm in diameter (Arch Gynecol Obstet. 2016 Feb;293[2]:291-301).
To more accurately diagnose PCS, our patients undergo tilt-table venography. The patient is placed into a reverse-Trendelenburg upright or semi-upright position to potentially exacerbate any venous reflux or dilation.
Other methods of identifying and diagnosing pelvic congestion have included transabdominal and transvaginal ultrasound, CT, and MRI. While CT and MRI both offer an overview of the pelvic vasculature and are helpful for ruling out other causes of chronic pelvic pain, they have low specificity for pelvic varices, according to the Italian review.
Sonography performed in the supine position, on the other hand, appears to be increasingly viewed as an acceptable screening tool for determining which patients may ultimately benefit from venography. It is also important in evaluation to rule out other pathologies not yet excluded. However, it should not be used for diagnosis of PCS.
Treating PCS
There are two main approaches to treating PCS: venous ligation (a gynecologic surgical approach) and percutaneous transcatheter embolization (performed by interventional radiologists).
The literature and evidence base is still in its infancy, but is growing. In our experience, both approaches lead to good resolution of symptoms over time in the majority of patients, and appear superior to the medical therapies that have been proposed for treating PCS, such as progestins and gonadotropin-releasing hormone agonists. Success rates with medical therapy are more variable and appear to be more short lived.
A review published this year on the effectiveness of embolization of pelvic veins for reducing chronic pelvic pain showed that 75% of women undergoing embolization had symptomatic relief that generally increased over time and was sustained. The authors concluded that embolization appears to be effective for the majority of women, and is safe, although they also noted that the quality of the evidence is low (J Vasc Interv Radiol. 2016 Oct;27[10]:1478-86.e8). Their review was based almost entirely on prospective case series.
Dr. Borghi and Dr. Dell’Atti offered a similar assessment of embolization for PCS, stating in their review article that clinical success has been reported in 70%-85% of patients. They also report nearly equivalent success rates of up to 75% with treatment via surgical ligation of ovarian and/or pelvic vasculature. These findings are from mostly observational data and case series.
Decisions about which approach to take should be individualized. If there are no differences with respect to insurance coverage for the patient, then embolization may be the preferred approach because it is the most minimally invasive technique and can potentially be performed at the time of diagnostic venography, negating the need for a second procedure. A skilled interventional radiologist familiar with the disease and the treatment is necessary. Various embolic agents are utilized, including coils, glues, foams, and other agents that cause sclerosis of the abnormal veins.
In other cases, venous ligation is preferred, especially when an additional gynecologic surgery, such as a cystectomy or myomectomy, is required.
Surgical ligation of ovarian veins was initially performed via laparotomy using a traditional retroperitoneal approach. The surgical goal is to isolate the ovarian vein significantly above the pelvic brim and before the vein becomes substantially dilated. Laparotomy therefore requires a vertical mid-line incision to provide adequate access to the appropriate portion of the ovarian vessels, leading to potentially high morbidity and poor cosmesis.
More recently, gynecologic surgeons skilled in laparoscopy have successfully managed PCS transperitoneally. A few small series of bilateral laparoscopic transperitoneal ligation of ovarian veins have been reported, including one by Tigellio Gargiulo, MD, who clipped both veins in their upper third, near their distal ends at the inferior vena cava (right) and the renal vein (left) (J Am Assoc Gynecol Laparosc. 2003 Nov;10[4]:501-4).
We prefer a robot-assisted laparoscopic approach for most of our patients. Not only does the improved dexterity help while working with sensitive vasculature, but more importantly we are able to use Firefly fluorescence.
The procedure generally is as follows. The uterine adnexa on the affected side is grasped and placed on tension so that the infundibulopelvic (IP) ligament can be visualized as it courses up and above the pelvic brim. The peritoneum immediately over the IP ligament is gently grasped and tented upward, and a small incision is made into the peritoneum, providing access into the retroperitoneum. The ureter should be visualized medial to this dissection.
The peritoneal tissue is then gently dissected off the ovarian vessels. Once the vessels are freed from the peritoneal tissue, the dilated ovarian vein is often clearly visualized. It is important to note that if no venous dilation is seen during laparoscopy, the procedure should not be aborted. Due to the Trendelenburg position that is utilized in gynecologic – and especially laparoscopic – surgery, the venous system sometimes appears falsely “normal” at this time.
Once the ovarian vessels have been isolated, the arteries must be separated from the veins. The adventitial tissue is dissected until the vessels are separated. Great care should be taken to ensure that all movements run parallel to the vessels and not perpendicular, therefore decreasing the risk of bleeding.
This process can be challenging. The surgeon is working with delicate vasculature. Often there are several branches from the vein that have formed due to the abnormal venous system. The best way to approach it is to identify planes and separate those planes in order to isolate individual vessels. If difficulties are still encountered, the surgeon should restart the dissection higher.
Once the dilated ovarian vein is isolated, one to two clips are placed.
Usually the artery is clearly distinct from the vein as it is smaller, more elastic, and can be seen pulsing. However, occasionally it is difficult to distinguish. In these cases, assistance with the da Vinci surgical system is useful: Indocyanine green (ICG) dye can be injected intravenously and visualized with a near-infrared light on the da Vinci platform. The dye is then seen glowing green as it first courses through the artery and then the vein.
For patients who have been found on venography to have bilateral disease, we perform the ligation procedure bilaterally. Once ligation is complete, the more competent collateral veins in the pelvis will assume more of the venous circulation.
In our experience, patients have ultimately noted substantial pain relief after these procedures, both with the endoscopic embolization and the surgical ligation. Patients are counseled that it can take several months to notice a relief in the pain.
In rare cases, pelvic congestion is related to extrinsic compression. For instance, the left renal vein can become compressed between the aorta and the superior mesenteric artery (the nutcracker syndrome), or the left common iliac vein can be compressed between the overlying right internal iliac artery and the underlying vertebral body (May-Thurner syndrome). Both of these conditions can lead to secondary PCS.
Such complex conditions are usually treated by vascular surgeons. May-Thurner syndrome is treated via stenting, while nutcracker syndrome can be treated with stenting or transposition of the renal vein to the distal vena cava.
Dr. Steller is an associate at the Family Health Centers of San Diego. She reported having no relevant financial disclosures.
BY CHARLES E. MILLER, MD
Chronic pelvic pain is described as the presence of lower abdominal or pelvic pain for longer than 6 months. It is believed to affect approximately one in six women and 12%-15% of women of reproductive age. The diagnosis and treatment of chronic pelvic pain adds as much as a $2 billion burden to our health system annually.
It was first described clinically in the literature in 1857, while the existence of pelvic varicosities wasn’t documented for nearly another 100 years. Pelvic congestion syndrome (PCS) accounts for 30%-70% of cases presenting with chronic pelvic pain. PCS can be due to pelvic venous insufficiency, characterized by reflux into pelvic veins leading to pelvic varicosities or alternative venous pathways secondary to varicose veins of the leg.
Other etiologies of PCS include nutcracker syndrome (left renal vein compressed between the aorta and the superior mesenteric artery), May-Thurner syndrome (compression of the left common iliac vein by the right common iliac artery) or, less likely, tumor thrombosis of the inferior vena cava, portal vein thrombosis, renal cell carcinoma, left renal thrombosis, or left kidney arterial-venous fistula.
While there appears to be significant literature indicating a long-term success rate of greater than 80% in patients treated by percutaneous endovascular procedures (embolization, stenting), there is far less information on the postsurgical success of blocking the varicose gonadal vein. Nevertheless, our long-term results with gonadal vein clipping is virtually the same as that of our radiological colleagues.
It is a pleasure to welcome Courtney Steller, DO, to this edition of the Master Class in Gynecologic Surgery to discuss the diagnosis and treatment of PCS, with an emphasis on surgical correction.
Dr. Steller is a recent graduate of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill. She is currently in private practice and is an associate at the Family Health Centers of San Diego, Calif.
Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported having no financial disclosures relevant to this column. Email him at [email protected].
Pelvic congestion syndrome: A treatable cause of pain
BY COURTNEY STELLER, DO
Pelvic congestion syndrome is a poorly understood and underdiagnosed disease. Yet, over the last decade, the syndrome has become less controversial as the etiology has become better understood and as the diagnostic approach has become more specific. Through these advances, treatments have also become increasingly more successful.
This is an important shift, because the chronic pelvic pain experienced by patients with pelvic congestion significantly impacts their quality of life and well-being. As the pain persists, it can become exceedingly difficult to manage. Many patients we have ultimately treated for pelvic congestion syndrome have had years of various work-ups, significant diagnostic investigations, and trials of different treatments without having any cause of their pain identified or achieving any lasting symptom relief.
The pelvic pain in patients with pelvic congestion syndrome (PCS) can be noncyclical or cyclical. It is present most of the time but tends to get worse at the end of the day and after long periods of standing and/or sitting. The pain also may worsen with intercourse, largely afterward. The syndrome tends to occur in premenopausal and multiparous women, but it’s important to appreciate that this is not always the case; we have diagnosed and treated PCS in several young, nulliparous patients as well.
Features and diagnosis
PCS is a disorder of pelvic venous circulation that predominantly affects the ovarian veins. It is sometimes referred to as pelvic vein incompetence or pelvic vascular dysfunction. Just as veins in the legs can enlarge and become varicose, the ovarian veins – and sometimes the internal iliac veins – can become incompetent and unable to effectively return blood back to the heart.
Pregnancy may predispose patients to developing the abnormally dilated and refluxing veins that characterize PCS, as the increase in pelvic vein capacity and uterine compression can lead to significant stasis of blood in the pelvis and subsequent damage to the veins and the venous valves. There also is believed to be an estrogen component to the development of PCS, because estrogen is known to act as a vasodilator. Moreover, a congenital absence and incompetence of venous valves in some cases has been reported.
In a recent study looking at pelvic vein incompetence and symptoms of chronic pelvic pain, these women were reported to have a distinctive symptom profile, with the “most notable” features being the presence of dull pelvic pain that radiates to the upper thighs and is aggravated by prolonged standing and walking – symptoms that are similar to the leg symptoms experienced by patients with severe varicose veins (Eur J Obstet Gynecol Reprod Biol. 2016 Jan;196:21-5).
Other investigators have similarly described the pelvic pain related to PCS as a dull ache or heaviness sensation that is most severe at the end of the day and that is lessened with supine positioning (though not necessarily immediately) and often exacerbated with sexual intercourse, especially post coitus. These descriptions are in line with my experience with PCS. There is usually exquisite tenderness on pelvic exam, especially localized to the adnexa. Patients will often have varicose veins on their upper legs or labia.
Interestingly, it has been repeatedly shown that many women have dilated and incompetent pelvic veins without also having such pathognomonic pain. We therefore cannot treat women based solely on the finding of abnormal veins.
On the other hand we must determine which patients with chronic pelvic pain have PCS. The differential diagnosis for PCS includes endometriosis, adenomyosis chronic pelvic inflammatory disease, adhesive disease, adnexal masses, adnexal torsion, and several nongynecologic diseases including interstitial cystitis and irritable bowel syndrome.
Venography has become the gold standard for diagnosing pelvic congestion. The procedure involves catheterization of the ovarian veins through a femoral or jugular approach. In our experience, the common femoral vein is the more frequently used access point. Using a contrast injection, the interventional radiologist can assess the degree of venous dilation and reflux in the pelvis.
There currently is no consensus on a cutoff for vein diameter or on any validated measures for congestion. According to one report on PCS authored by interventional radiologists, the diagnosis of PCS is confirmed with the venographic findings of ovarian vein diameter greater than 6 mm, retrograde ovarian or pelvic venous flow, presence of several tortuous collateral pelvic venous pathways, and delayed or stagnant clearance on contrast (Semin Intervent Radiol. 2008 Dec;25[4]:361-8).
The criteria vary, however. A recent literature review on pelvic congestion syndrome by Chiara Borghi, MD, and Lucio Dell’Atti, MD, states that incompetent pelvic veins are defined as more than 5-10 mm in diameter (Arch Gynecol Obstet. 2016 Feb;293[2]:291-301).
To more accurately diagnose PCS, our patients undergo tilt-table venography. The patient is placed into a reverse-Trendelenburg upright or semi-upright position to potentially exacerbate any venous reflux or dilation.
Other methods of identifying and diagnosing pelvic congestion have included transabdominal and transvaginal ultrasound, CT, and MRI. While CT and MRI both offer an overview of the pelvic vasculature and are helpful for ruling out other causes of chronic pelvic pain, they have low specificity for pelvic varices, according to the Italian review.
Sonography performed in the supine position, on the other hand, appears to be increasingly viewed as an acceptable screening tool for determining which patients may ultimately benefit from venography. It is also important in evaluation to rule out other pathologies not yet excluded. However, it should not be used for diagnosis of PCS.
Treating PCS
There are two main approaches to treating PCS: venous ligation (a gynecologic surgical approach) and percutaneous transcatheter embolization (performed by interventional radiologists).
The literature and evidence base is still in its infancy, but is growing. In our experience, both approaches lead to good resolution of symptoms over time in the majority of patients, and appear superior to the medical therapies that have been proposed for treating PCS, such as progestins and gonadotropin-releasing hormone agonists. Success rates with medical therapy are more variable and appear to be more short lived.
A review published this year on the effectiveness of embolization of pelvic veins for reducing chronic pelvic pain showed that 75% of women undergoing embolization had symptomatic relief that generally increased over time and was sustained. The authors concluded that embolization appears to be effective for the majority of women, and is safe, although they also noted that the quality of the evidence is low (J Vasc Interv Radiol. 2016 Oct;27[10]:1478-86.e8). Their review was based almost entirely on prospective case series.
Dr. Borghi and Dr. Dell’Atti offered a similar assessment of embolization for PCS, stating in their review article that clinical success has been reported in 70%-85% of patients. They also report nearly equivalent success rates of up to 75% with treatment via surgical ligation of ovarian and/or pelvic vasculature. These findings are from mostly observational data and case series.
Decisions about which approach to take should be individualized. If there are no differences with respect to insurance coverage for the patient, then embolization may be the preferred approach because it is the most minimally invasive technique and can potentially be performed at the time of diagnostic venography, negating the need for a second procedure. A skilled interventional radiologist familiar with the disease and the treatment is necessary. Various embolic agents are utilized, including coils, glues, foams, and other agents that cause sclerosis of the abnormal veins.
In other cases, venous ligation is preferred, especially when an additional gynecologic surgery, such as a cystectomy or myomectomy, is required.
Surgical ligation of ovarian veins was initially performed via laparotomy using a traditional retroperitoneal approach. The surgical goal is to isolate the ovarian vein significantly above the pelvic brim and before the vein becomes substantially dilated. Laparotomy therefore requires a vertical mid-line incision to provide adequate access to the appropriate portion of the ovarian vessels, leading to potentially high morbidity and poor cosmesis.
More recently, gynecologic surgeons skilled in laparoscopy have successfully managed PCS transperitoneally. A few small series of bilateral laparoscopic transperitoneal ligation of ovarian veins have been reported, including one by Tigellio Gargiulo, MD, who clipped both veins in their upper third, near their distal ends at the inferior vena cava (right) and the renal vein (left) (J Am Assoc Gynecol Laparosc. 2003 Nov;10[4]:501-4).
We prefer a robot-assisted laparoscopic approach for most of our patients. Not only does the improved dexterity help while working with sensitive vasculature, but more importantly we are able to use Firefly fluorescence.
The procedure generally is as follows. The uterine adnexa on the affected side is grasped and placed on tension so that the infundibulopelvic (IP) ligament can be visualized as it courses up and above the pelvic brim. The peritoneum immediately over the IP ligament is gently grasped and tented upward, and a small incision is made into the peritoneum, providing access into the retroperitoneum. The ureter should be visualized medial to this dissection.
The peritoneal tissue is then gently dissected off the ovarian vessels. Once the vessels are freed from the peritoneal tissue, the dilated ovarian vein is often clearly visualized. It is important to note that if no venous dilation is seen during laparoscopy, the procedure should not be aborted. Due to the Trendelenburg position that is utilized in gynecologic – and especially laparoscopic – surgery, the venous system sometimes appears falsely “normal” at this time.
Once the ovarian vessels have been isolated, the arteries must be separated from the veins. The adventitial tissue is dissected until the vessels are separated. Great care should be taken to ensure that all movements run parallel to the vessels and not perpendicular, therefore decreasing the risk of bleeding.
This process can be challenging. The surgeon is working with delicate vasculature. Often there are several branches from the vein that have formed due to the abnormal venous system. The best way to approach it is to identify planes and separate those planes in order to isolate individual vessels. If difficulties are still encountered, the surgeon should restart the dissection higher.
Once the dilated ovarian vein is isolated, one to two clips are placed.
Usually the artery is clearly distinct from the vein as it is smaller, more elastic, and can be seen pulsing. However, occasionally it is difficult to distinguish. In these cases, assistance with the da Vinci surgical system is useful: Indocyanine green (ICG) dye can be injected intravenously and visualized with a near-infrared light on the da Vinci platform. The dye is then seen glowing green as it first courses through the artery and then the vein.
For patients who have been found on venography to have bilateral disease, we perform the ligation procedure bilaterally. Once ligation is complete, the more competent collateral veins in the pelvis will assume more of the venous circulation.
In our experience, patients have ultimately noted substantial pain relief after these procedures, both with the endoscopic embolization and the surgical ligation. Patients are counseled that it can take several months to notice a relief in the pain.
In rare cases, pelvic congestion is related to extrinsic compression. For instance, the left renal vein can become compressed between the aorta and the superior mesenteric artery (the nutcracker syndrome), or the left common iliac vein can be compressed between the overlying right internal iliac artery and the underlying vertebral body (May-Thurner syndrome). Both of these conditions can lead to secondary PCS.
Such complex conditions are usually treated by vascular surgeons. May-Thurner syndrome is treated via stenting, while nutcracker syndrome can be treated with stenting or transposition of the renal vein to the distal vena cava.
Dr. Steller is an associate at the Family Health Centers of San Diego. She reported having no relevant financial disclosures.
Treating agitation in schizophrenia
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The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
TBI scoring system predicts outcomes with only initial head CT findings
WASHINGTON – A simple 8-point scoring system based on head CT accurately predicts mortality, morbidity, and even discharge disposition among patients with a traumatic brain injury (TBI).
In its first clinical study, the Cranial CT Scoring Tool (CCTST) predictive power rivaled both the Glasgow Coma Score (GCS) and the Abbreviated Injury Scale (AIS), Ronnie Mubang, MD, said at the American College of Surgeons’ Clinical Congress.
In addition to adding valuable prognostic information, the CCTST is quick, easy, and completely objective, said Dr. Mubang, of St. Luke’s University Health Network, Bethlehem, Pa.
“The near-universal head CT makes this tool valuable in immediate prognostication and clinical risk assessment for physicians, patients and families. It can serve as a potential adjunct to the Glasgow score and Abbreviated Injury Score for risk assessment,” he said. Of note, the final AIS-Head may not be available until relatively late in the patient’s clinical course, and the GCS has important limitations in terms of outcome prognostication.
The CCTST is an 8-point assessment with one point assigned to each individual cranial CT finding: epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intraventricular hemorrhage, cerebral contusion/ intraparenchymal hemorrhage, skull fracture, brain edema/herniation, and midline shift. The ninth factor is the presence of an external injury to the head.
Dr. Mubang, a fourth-year surgical resident, and his colleagues retrospectively examined the CCTST in 620 patients included in an administrative database at the three-hospital St. Luke’s Regional Trauma Network. Patients were older than 45 years. Half of them underwent neurosurgical intervention within 24 hours of admission and were matched with 310 patients who did not require neurosurgery. The primary clinical endpoint was mortality from head injury. Secondary endpoints included morbidity, hospital and intensive care unit length of stay, and post-discharge destination.
The mean age of the cohort was 73 years. Almost all injuries (99%) were due to blunt force trauma. The mean GCS was 11; the mean Injury Severity Score (ISS) was 24; and the mean AIS – Head score was 4.6, indicating severe to critical level of TBI. Midline shift was significantly greater in the surgical group (0.74 cm vs. 0.29 cm).
Several CT findings were significantly more common in the surgical group, including subdural hematoma (96% vs. 7%); midline shift (74% vs. 29%); brain edema (39% vs. 23%); and epidural hematoma (10% vs. 3%).
As the total CCTST score increased, outcomes worsened accordingly, Dr. Mubang said. Patients with a score of 1-2 had a 20%-30% chance of complications and an approximately 10% chance of injury-related mortality. Patients with higher scores (7-8) had a 60%-75% chance of morbidity and a 55% chance of mortality.
Rising scores correlated well with both hospital and ICU length of stay, with a score of 1-2 associated with a 3-day average stay, and a score of 8 associated with stays exceeding 10 days. The same pattern occurred with overall hospital length of stay: the lowest scores were associated with a stay of about a week, while the highest scores with a stay exceeding 2 weeks.
CCTST was highly associated with discharge disposition. With every additional point, the chance of discharge to home fell. While the majority of patients with scores below 2 were discharged home, no patients with a score of 8 were discharged home.
Finally, the investigators performed a multivariate analysis that controlled for sex; GCS, ISS, and AIS-head scores; time in the trauma bay; and preinjury anticoagulation treatment. The CCTST score was strongly associated with patient mortality (OR 1.31), rivaling both GCS (OR, 1.14) and AIS-Head (OR, 2.68). Neither ISS nor pre-injury anticoagulation predicted mortality. CCTST was also the only variable independently associated with the need for neurosurgical intervention.
The team is planning a multicenter retrospective validation, followed by a prospective observational study in the next 2 years, according to Dr. Stan Stawicki, the senior investigator, also with St. Luke’s. “CCTST offers potential promise to add much needed granularity to our existing TBI clinical assessment paradigm that continues to rely heavily on AIS-Head and GCS,” he said.
Neither Dr. Mubang nor Dr. Stawicki had any financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_Gal
WASHINGTON – A simple 8-point scoring system based on head CT accurately predicts mortality, morbidity, and even discharge disposition among patients with a traumatic brain injury (TBI).
In its first clinical study, the Cranial CT Scoring Tool (CCTST) predictive power rivaled both the Glasgow Coma Score (GCS) and the Abbreviated Injury Scale (AIS), Ronnie Mubang, MD, said at the American College of Surgeons’ Clinical Congress.
In addition to adding valuable prognostic information, the CCTST is quick, easy, and completely objective, said Dr. Mubang, of St. Luke’s University Health Network, Bethlehem, Pa.
“The near-universal head CT makes this tool valuable in immediate prognostication and clinical risk assessment for physicians, patients and families. It can serve as a potential adjunct to the Glasgow score and Abbreviated Injury Score for risk assessment,” he said. Of note, the final AIS-Head may not be available until relatively late in the patient’s clinical course, and the GCS has important limitations in terms of outcome prognostication.
The CCTST is an 8-point assessment with one point assigned to each individual cranial CT finding: epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intraventricular hemorrhage, cerebral contusion/ intraparenchymal hemorrhage, skull fracture, brain edema/herniation, and midline shift. The ninth factor is the presence of an external injury to the head.
Dr. Mubang, a fourth-year surgical resident, and his colleagues retrospectively examined the CCTST in 620 patients included in an administrative database at the three-hospital St. Luke’s Regional Trauma Network. Patients were older than 45 years. Half of them underwent neurosurgical intervention within 24 hours of admission and were matched with 310 patients who did not require neurosurgery. The primary clinical endpoint was mortality from head injury. Secondary endpoints included morbidity, hospital and intensive care unit length of stay, and post-discharge destination.
The mean age of the cohort was 73 years. Almost all injuries (99%) were due to blunt force trauma. The mean GCS was 11; the mean Injury Severity Score (ISS) was 24; and the mean AIS – Head score was 4.6, indicating severe to critical level of TBI. Midline shift was significantly greater in the surgical group (0.74 cm vs. 0.29 cm).
Several CT findings were significantly more common in the surgical group, including subdural hematoma (96% vs. 7%); midline shift (74% vs. 29%); brain edema (39% vs. 23%); and epidural hematoma (10% vs. 3%).
As the total CCTST score increased, outcomes worsened accordingly, Dr. Mubang said. Patients with a score of 1-2 had a 20%-30% chance of complications and an approximately 10% chance of injury-related mortality. Patients with higher scores (7-8) had a 60%-75% chance of morbidity and a 55% chance of mortality.
Rising scores correlated well with both hospital and ICU length of stay, with a score of 1-2 associated with a 3-day average stay, and a score of 8 associated with stays exceeding 10 days. The same pattern occurred with overall hospital length of stay: the lowest scores were associated with a stay of about a week, while the highest scores with a stay exceeding 2 weeks.
CCTST was highly associated with discharge disposition. With every additional point, the chance of discharge to home fell. While the majority of patients with scores below 2 were discharged home, no patients with a score of 8 were discharged home.
Finally, the investigators performed a multivariate analysis that controlled for sex; GCS, ISS, and AIS-head scores; time in the trauma bay; and preinjury anticoagulation treatment. The CCTST score was strongly associated with patient mortality (OR 1.31), rivaling both GCS (OR, 1.14) and AIS-Head (OR, 2.68). Neither ISS nor pre-injury anticoagulation predicted mortality. CCTST was also the only variable independently associated with the need for neurosurgical intervention.
The team is planning a multicenter retrospective validation, followed by a prospective observational study in the next 2 years, according to Dr. Stan Stawicki, the senior investigator, also with St. Luke’s. “CCTST offers potential promise to add much needed granularity to our existing TBI clinical assessment paradigm that continues to rely heavily on AIS-Head and GCS,” he said.
Neither Dr. Mubang nor Dr. Stawicki had any financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_Gal
WASHINGTON – A simple 8-point scoring system based on head CT accurately predicts mortality, morbidity, and even discharge disposition among patients with a traumatic brain injury (TBI).
In its first clinical study, the Cranial CT Scoring Tool (CCTST) predictive power rivaled both the Glasgow Coma Score (GCS) and the Abbreviated Injury Scale (AIS), Ronnie Mubang, MD, said at the American College of Surgeons’ Clinical Congress.
In addition to adding valuable prognostic information, the CCTST is quick, easy, and completely objective, said Dr. Mubang, of St. Luke’s University Health Network, Bethlehem, Pa.
“The near-universal head CT makes this tool valuable in immediate prognostication and clinical risk assessment for physicians, patients and families. It can serve as a potential adjunct to the Glasgow score and Abbreviated Injury Score for risk assessment,” he said. Of note, the final AIS-Head may not be available until relatively late in the patient’s clinical course, and the GCS has important limitations in terms of outcome prognostication.
The CCTST is an 8-point assessment with one point assigned to each individual cranial CT finding: epidural hematoma, subdural hematoma, subarachnoid hemorrhage, intraventricular hemorrhage, cerebral contusion/ intraparenchymal hemorrhage, skull fracture, brain edema/herniation, and midline shift. The ninth factor is the presence of an external injury to the head.
Dr. Mubang, a fourth-year surgical resident, and his colleagues retrospectively examined the CCTST in 620 patients included in an administrative database at the three-hospital St. Luke’s Regional Trauma Network. Patients were older than 45 years. Half of them underwent neurosurgical intervention within 24 hours of admission and were matched with 310 patients who did not require neurosurgery. The primary clinical endpoint was mortality from head injury. Secondary endpoints included morbidity, hospital and intensive care unit length of stay, and post-discharge destination.
The mean age of the cohort was 73 years. Almost all injuries (99%) were due to blunt force trauma. The mean GCS was 11; the mean Injury Severity Score (ISS) was 24; and the mean AIS – Head score was 4.6, indicating severe to critical level of TBI. Midline shift was significantly greater in the surgical group (0.74 cm vs. 0.29 cm).
Several CT findings were significantly more common in the surgical group, including subdural hematoma (96% vs. 7%); midline shift (74% vs. 29%); brain edema (39% vs. 23%); and epidural hematoma (10% vs. 3%).
As the total CCTST score increased, outcomes worsened accordingly, Dr. Mubang said. Patients with a score of 1-2 had a 20%-30% chance of complications and an approximately 10% chance of injury-related mortality. Patients with higher scores (7-8) had a 60%-75% chance of morbidity and a 55% chance of mortality.
Rising scores correlated well with both hospital and ICU length of stay, with a score of 1-2 associated with a 3-day average stay, and a score of 8 associated with stays exceeding 10 days. The same pattern occurred with overall hospital length of stay: the lowest scores were associated with a stay of about a week, while the highest scores with a stay exceeding 2 weeks.
CCTST was highly associated with discharge disposition. With every additional point, the chance of discharge to home fell. While the majority of patients with scores below 2 were discharged home, no patients with a score of 8 were discharged home.
Finally, the investigators performed a multivariate analysis that controlled for sex; GCS, ISS, and AIS-head scores; time in the trauma bay; and preinjury anticoagulation treatment. The CCTST score was strongly associated with patient mortality (OR 1.31), rivaling both GCS (OR, 1.14) and AIS-Head (OR, 2.68). Neither ISS nor pre-injury anticoagulation predicted mortality. CCTST was also the only variable independently associated with the need for neurosurgical intervention.
The team is planning a multicenter retrospective validation, followed by a prospective observational study in the next 2 years, according to Dr. Stan Stawicki, the senior investigator, also with St. Luke’s. “CCTST offers potential promise to add much needed granularity to our existing TBI clinical assessment paradigm that continues to rely heavily on AIS-Head and GCS,” he said.
Neither Dr. Mubang nor Dr. Stawicki had any financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_Gal
AT ACS 2016
Key clinical point:
Major finding: CCTST score was strongly associated with patient mortality (Odds ratio, 1.31), rivaling both the Glasgow Coma Score (OR, 1.14) and the Abbreviated Injury Score – Head (OR, 2.68)Data source: The retrospective database study comprised 620 head trauma patients.
Disclosures: Neither Ronnie Mubang, MD, or Stan Stawicki, MD, had financial disclosures.
VIDEO: Pre–gastric bypass antibiotics alter gut microbiome
WASHINGTON – Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.
Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.
Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.
Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.
Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.
At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.
Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.
Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.
“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”
Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”
Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.
Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.
He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.
Dr. Jahansouz said that he had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_Gal
WASHINGTON – Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.
Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.
Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.
Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.
Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.
At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.
Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.
Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.
“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”
Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”
Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.
Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.
He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.
Dr. Jahansouz said that he had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_Gal
WASHINGTON – Antibiotics given in advance of gastric bypass surgery preferentially alter the microbiome, nudging it toward a more “lean” physiologic profile.
Given before a sleeve gastrectomy, vancomycin, which has little gut penetration, barely shifted the high ratio of Firmicutes to Bacteroidetes, a profile typically associated with obesity and insulin resistance. But cefazolin, which has much higher gut penetration, suppressed the presence of Firmicutes, which metabolize fat, and allowed the expansion of carbohydrate-loving Bacteroidetes – a profile generally seen in lean people.
Cyrus Jahansouz, MD, of the University of Minnesota, Minneapolis, and his colleagues wanted to examine whether a shift in preoperative antibiotics might affect the way the microbiome re-establishes itself in the wake of vertical sleeve gastrectomy. They enrolled 32 patients who were candidates for the procedure. None had undergone prior gastrointestinal surgery, and none had been exposed to antibiotics in the 3 months prior to bariatric surgery. They were similar in age, weight, body mass index, and fasting glucose. The mean HbA1c was about 6%.
Patients were randomized to three groups: maximal diet therapy (800 calories per day) without surgery; vertical sleeve gastrectomy with the usual preoperative antibiotic cefazolin and the postsurgical diet; and vertical sleeve gastrectomy with preoperative vancomycin and the postsurgical diet. All patients gave a fecal sample immediately before surgery and another one 6 days after surgery.
Preoperative cluster analysis of bacterial DNA showed that all of the samples had a similar composition, predominated by Firmicutes species (60%-70%). Bacteroidetes species made up about 20%-30%, with Proteobacteriae, Actinobacteriae, Verrucomicrobia, and other phyla comprising the remainder of the microbiome.
At the second sampling, the diet-only group showed no microbiome changes at all. The vancomycin group showed a very small but not significant expansion of Bacteroidetes and reduction of Firmicutes.
Patients in the cefazolin group showed a significant shift in the ratio – and it was quite striking, Dr. Jahansouz said. Among these patients, Firmicutes had decreased from 70% to 40% of the community. Bacteroidetes showed a corresponding shift, increasing from 20% of the community to 45%. The findings are quite surprising, he noted, considering that only one dose of antibiotic was associated with the changes and that they were evident within just a few days.
Although “a little hard to interpret” because of its small size and short follow-up, the study suggests that antibiotic choice might contribute to the success of weight-loss surgery, Dr. Jahansouz said at the annual clinical congress of the American College of Surgeons.
“There are still several factors in the perioperative period that we have to study to be able to identify what other things might have also influenced the shift,” he said in an interview. “But I do think that, in the future, these changes can be manipulated to benefit metabolic outcomes.”
Two phyla – Bacteroidetes and Firmicutes – dominate the human gut microbiome in a dynamic ratio that is highly associated with the way energy is extracted from food. Bacteroidetes species specialize in carbohydrate digestion and Firmicutes in fat digestion. “In a lean, insulin-sensitive state, Bacteroidetes dominates the human gut microbiome,” Dr. Jahansouz said. “With the progression of obesity and insulin resistance, there is a subsequent shift in the microbiome phenotype, favoring the growth of Firmicutes at the expense and reduction of Bacteroidetes. This is a significant change, because this obesity-associated phenotype has an increased capacity to harvest energy. It’s not the same for a lean person to consume 1,000 calories as it is for an obese person to consume them.”
Bariatric surgery has been shown to alter the gut microbiome, shifting it toward this more “lean” profile (Cell Metab. 2015 Aug 4;22[2]:228-38). This shift may be an important component of the still not fully elucidated mechanisms by which bariatric surgery causes weight loss and normalizes insulin signaling, Dr. Jahansouz said.
Dr. Jahansouz is following this group of patients to explore whether there are differences in weight loss and insulin signaling. He also will track whether the microbiome stabilizes at its early postsurgical profile, or continues to shift, either toward an even higher Bacteroidetes to Firmicutes ratio, or back to a more “obese” profile.
He and his colleagues are also investigating the effect of antibiotics and gastric bypass surgery in mouse models. “I can say that antibiotics seem to have a remarkable impact on the effect of mouse sleeve gastrectomy. We’re not quite there yet with humans,” but the data are compelling.
Dr. Jahansouz said that he had no financial disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @Alz_Gal
EXPERT ANALYSIS FROM THE ACS CLINICAL CONGRESS
Ultrasound-Guided Percutaneous Reconstruction of the Anterolateral Ligament: Surgical Technique
VIDEO: The Business of Hospital Medicine
The business of hospital medicine is an important factor in individual clinicians' careers and for the specialty as a whole. Dr. Jasen Gundersen of TeamHealth and James Levy of Indigo Health Partners talk about the importance of recognizing the personal, and the system-wide, impacts and opportunities of the business side of HM.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The business of hospital medicine is an important factor in individual clinicians' careers and for the specialty as a whole. Dr. Jasen Gundersen of TeamHealth and James Levy of Indigo Health Partners talk about the importance of recognizing the personal, and the system-wide, impacts and opportunities of the business side of HM.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The business of hospital medicine is an important factor in individual clinicians' careers and for the specialty as a whole. Dr. Jasen Gundersen of TeamHealth and James Levy of Indigo Health Partners talk about the importance of recognizing the personal, and the system-wide, impacts and opportunities of the business side of HM.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
VIDEO: DNA-derived Zika vaccine in humans holds promise
BALTIMORE – Hope is high right now for a genetically engineered Zika virus vaccine currently being tested in humans.
“If we saw something, even early on, that we were concerned about, we would stop the trial and re-evaluate it. And that hasn’t happened, so that’s good news,” said Kathleen M. Neuzil, MD, lead investigator of the trial and a professor at the University of Maryland in Baltimore, where she is also director of the Center for Vaccine Development.
Testing of the DNA-based Zika vaccine began in early August. Now that Congress has approved a $1.1 billion funding package, Dr. Neuzil said investigators can rest assured that there is enough funding for the duration of this trial, which ultimately could take 2 years or longer.
Sponsored by the National Institutes of Health, phase I of the trial is being conducted at three U.S. sites, including the University of Maryland’s Vaccine Development Center, the NIH Clinical Center in Bethesda, Md., and Emory University in Atlanta.
Safety and tolerability results from all three sites are expected by year’s end and will inform how to construct phase II, currently set to begin in early 2017. That phase is expected to include a much larger population than the 80 current participants, although the exact numbers are still to be determined, Dr. Neuzil said. Also still unknown is whether phase II will be conducted internationally.
If the vaccine proves effective, it will be a high point in the annals of maternal-fetal medicine, said Christopher Harman, MD, chair of obstetrics and gynecology and director of the division of maternal-fetal medicine at the University of Maryland. “It’s going to become a story where the power of modern medicine has defeated an epidemic that had enormous potential for harm.”
Dr. Harman also predicted that a viable vaccine, combined with infectious disease prevention services globally, will mitigate Zika’s threat to the population, particularly developing fetuses.
In the meantime, there needs to be continued public education about preventing the spread of Zika, as well as rigorous attention to family planning, Dr. Harman said.
“Planned pregnancy is essential,” he said. “This puts the burden on the couple or the woman. Don’t get pregnant if you’re in an endemic area.”
For more about the vaccine trial and how clinicians can counsel patients about the threat of Zika, watch this video recorded at the University of Maryland.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
BALTIMORE – Hope is high right now for a genetically engineered Zika virus vaccine currently being tested in humans.
“If we saw something, even early on, that we were concerned about, we would stop the trial and re-evaluate it. And that hasn’t happened, so that’s good news,” said Kathleen M. Neuzil, MD, lead investigator of the trial and a professor at the University of Maryland in Baltimore, where she is also director of the Center for Vaccine Development.
Testing of the DNA-based Zika vaccine began in early August. Now that Congress has approved a $1.1 billion funding package, Dr. Neuzil said investigators can rest assured that there is enough funding for the duration of this trial, which ultimately could take 2 years or longer.
Sponsored by the National Institutes of Health, phase I of the trial is being conducted at three U.S. sites, including the University of Maryland’s Vaccine Development Center, the NIH Clinical Center in Bethesda, Md., and Emory University in Atlanta.
Safety and tolerability results from all three sites are expected by year’s end and will inform how to construct phase II, currently set to begin in early 2017. That phase is expected to include a much larger population than the 80 current participants, although the exact numbers are still to be determined, Dr. Neuzil said. Also still unknown is whether phase II will be conducted internationally.
If the vaccine proves effective, it will be a high point in the annals of maternal-fetal medicine, said Christopher Harman, MD, chair of obstetrics and gynecology and director of the division of maternal-fetal medicine at the University of Maryland. “It’s going to become a story where the power of modern medicine has defeated an epidemic that had enormous potential for harm.”
Dr. Harman also predicted that a viable vaccine, combined with infectious disease prevention services globally, will mitigate Zika’s threat to the population, particularly developing fetuses.
In the meantime, there needs to be continued public education about preventing the spread of Zika, as well as rigorous attention to family planning, Dr. Harman said.
“Planned pregnancy is essential,” he said. “This puts the burden on the couple or the woman. Don’t get pregnant if you’re in an endemic area.”
For more about the vaccine trial and how clinicians can counsel patients about the threat of Zika, watch this video recorded at the University of Maryland.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
BALTIMORE – Hope is high right now for a genetically engineered Zika virus vaccine currently being tested in humans.
“If we saw something, even early on, that we were concerned about, we would stop the trial and re-evaluate it. And that hasn’t happened, so that’s good news,” said Kathleen M. Neuzil, MD, lead investigator of the trial and a professor at the University of Maryland in Baltimore, where she is also director of the Center for Vaccine Development.
Testing of the DNA-based Zika vaccine began in early August. Now that Congress has approved a $1.1 billion funding package, Dr. Neuzil said investigators can rest assured that there is enough funding for the duration of this trial, which ultimately could take 2 years or longer.
Sponsored by the National Institutes of Health, phase I of the trial is being conducted at three U.S. sites, including the University of Maryland’s Vaccine Development Center, the NIH Clinical Center in Bethesda, Md., and Emory University in Atlanta.
Safety and tolerability results from all three sites are expected by year’s end and will inform how to construct phase II, currently set to begin in early 2017. That phase is expected to include a much larger population than the 80 current participants, although the exact numbers are still to be determined, Dr. Neuzil said. Also still unknown is whether phase II will be conducted internationally.
If the vaccine proves effective, it will be a high point in the annals of maternal-fetal medicine, said Christopher Harman, MD, chair of obstetrics and gynecology and director of the division of maternal-fetal medicine at the University of Maryland. “It’s going to become a story where the power of modern medicine has defeated an epidemic that had enormous potential for harm.”
Dr. Harman also predicted that a viable vaccine, combined with infectious disease prevention services globally, will mitigate Zika’s threat to the population, particularly developing fetuses.
In the meantime, there needs to be continued public education about preventing the spread of Zika, as well as rigorous attention to family planning, Dr. Harman said.
“Planned pregnancy is essential,” he said. “This puts the burden on the couple or the woman. Don’t get pregnant if you’re in an endemic area.”
For more about the vaccine trial and how clinicians can counsel patients about the threat of Zika, watch this video recorded at the University of Maryland.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
VIDEO: Harvoni shows safety, efficacy in adolescents for hepatitis C
MONTREAL – One of the antiviral drug combinations that has revolutionized treatment of hepatitis C virus in adults has for the first time been shown safe and effective against genotype 1 infections in adolescents aged 12-17 years old, paving the way to new regulatory labeling followed by easier and more reliable payer coverage for definitive hepatitis C treatment in this age group.
“I think having clear data on safety and efficacy and FDA [Food and Drug Administration] approval will greatly help getting insurance coverage,” for the tested combination of ledipasvir/sofosbuvir (Harvoni) Karen F. Murray, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.
The results showed that in adolescents the ledipasvir/sofosbuvir formulation tested, at the same dosage approved for adults, was “very potent for genotype 1 hepatitis C, and was not only well tolerated but very easy” when given for 12 weeks, Dr. Murray said in an interview. The nearly perfect score for sustained virologic responses was “spectacular,” she added.
Ongoing studies that should finish soon are also looking at the safety and efficacy of ledipasvir/sofosbuvir in children aged 3-11 years old and in children and adolescents infected by other hepatitis C genotypes, specifically 4, 5, and 6. Taking on genotypes 2 and 3 will require additional treatment with ribavirin, she noted. Subsequent reports will also document patient outcomes 24 weeks from the start of treatment, after they’ve been off their completed regimen for 12 weeks. Gilead staffers have told Dr. Murray that they anticipate asking the FDA before the end of 2016 for approval to relabel the ledipasvir/sofosbuvir formulation they market to include adolescents, and possibly children too, depending on the outcome of studies still underway.
The result she reported came from 100 patients enrolled at 24 centers in the United States, Canada, and Europe. They averaged 15 years old, nearly two-thirds were girls, and 90% were white. One-fifth of the patients had been previously treated, and 81% were infected by genotype 1a hepatitis C with the remaining 19% infected with genotype 1b. Patients received the conventional, marketed formulation of ledipasvir/sofosbuvir, 90/400 mg, orally once daily.
Ninety-eight of the patients had no detectable hepatitis C virus in their blood at the end of 12 weeks of treatment. The other two patients were lost to follow-up and did not undergo virologic testing at the end of treatment and conservatively were tallied as nonresponders, she reported. A pharmacokinetic study done in a subgroup of patients showed plasma drug levels comparable with those seen in adults.
Although 71% of the patients reported having some adverse effect, no patient reported a serious or grade 3 or 4 adverse effect and no patient stopped treatment because of adverse effects. Nine patients had a grade 3 or 4 laboratory abnormality on treatment. The only lab abnormality to occur in more than one patient was a transient rise in amylase levels, which happened in three patients. The regimen’s overall performance in adolescents closely tracked what’s been seen in adults, Dr. Murray said.
“These data will lead to FDA approval” of the regimen for adolescents, she said confidently, and that will ease insurance coverage. “There will still be hoops to jump through, but with approval and once written into guidelines, insurers will be under pressure to reimburse for it,” she noted. “We find that, because of the cost, insurers resist or refuse to pay for these medications. The idea of treating only patients with advanced liver disease is morally inappropriate. These children must be treated before they develop significant or irreversible liver disease.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
MONTREAL – One of the antiviral drug combinations that has revolutionized treatment of hepatitis C virus in adults has for the first time been shown safe and effective against genotype 1 infections in adolescents aged 12-17 years old, paving the way to new regulatory labeling followed by easier and more reliable payer coverage for definitive hepatitis C treatment in this age group.
“I think having clear data on safety and efficacy and FDA [Food and Drug Administration] approval will greatly help getting insurance coverage,” for the tested combination of ledipasvir/sofosbuvir (Harvoni) Karen F. Murray, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.
The results showed that in adolescents the ledipasvir/sofosbuvir formulation tested, at the same dosage approved for adults, was “very potent for genotype 1 hepatitis C, and was not only well tolerated but very easy” when given for 12 weeks, Dr. Murray said in an interview. The nearly perfect score for sustained virologic responses was “spectacular,” she added.
Ongoing studies that should finish soon are also looking at the safety and efficacy of ledipasvir/sofosbuvir in children aged 3-11 years old and in children and adolescents infected by other hepatitis C genotypes, specifically 4, 5, and 6. Taking on genotypes 2 and 3 will require additional treatment with ribavirin, she noted. Subsequent reports will also document patient outcomes 24 weeks from the start of treatment, after they’ve been off their completed regimen for 12 weeks. Gilead staffers have told Dr. Murray that they anticipate asking the FDA before the end of 2016 for approval to relabel the ledipasvir/sofosbuvir formulation they market to include adolescents, and possibly children too, depending on the outcome of studies still underway.
The result she reported came from 100 patients enrolled at 24 centers in the United States, Canada, and Europe. They averaged 15 years old, nearly two-thirds were girls, and 90% were white. One-fifth of the patients had been previously treated, and 81% were infected by genotype 1a hepatitis C with the remaining 19% infected with genotype 1b. Patients received the conventional, marketed formulation of ledipasvir/sofosbuvir, 90/400 mg, orally once daily.
Ninety-eight of the patients had no detectable hepatitis C virus in their blood at the end of 12 weeks of treatment. The other two patients were lost to follow-up and did not undergo virologic testing at the end of treatment and conservatively were tallied as nonresponders, she reported. A pharmacokinetic study done in a subgroup of patients showed plasma drug levels comparable with those seen in adults.
Although 71% of the patients reported having some adverse effect, no patient reported a serious or grade 3 or 4 adverse effect and no patient stopped treatment because of adverse effects. Nine patients had a grade 3 or 4 laboratory abnormality on treatment. The only lab abnormality to occur in more than one patient was a transient rise in amylase levels, which happened in three patients. The regimen’s overall performance in adolescents closely tracked what’s been seen in adults, Dr. Murray said.
“These data will lead to FDA approval” of the regimen for adolescents, she said confidently, and that will ease insurance coverage. “There will still be hoops to jump through, but with approval and once written into guidelines, insurers will be under pressure to reimburse for it,” she noted. “We find that, because of the cost, insurers resist or refuse to pay for these medications. The idea of treating only patients with advanced liver disease is morally inappropriate. These children must be treated before they develop significant or irreversible liver disease.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
MONTREAL – One of the antiviral drug combinations that has revolutionized treatment of hepatitis C virus in adults has for the first time been shown safe and effective against genotype 1 infections in adolescents aged 12-17 years old, paving the way to new regulatory labeling followed by easier and more reliable payer coverage for definitive hepatitis C treatment in this age group.
“I think having clear data on safety and efficacy and FDA [Food and Drug Administration] approval will greatly help getting insurance coverage,” for the tested combination of ledipasvir/sofosbuvir (Harvoni) Karen F. Murray, MD, said at the World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.
The results showed that in adolescents the ledipasvir/sofosbuvir formulation tested, at the same dosage approved for adults, was “very potent for genotype 1 hepatitis C, and was not only well tolerated but very easy” when given for 12 weeks, Dr. Murray said in an interview. The nearly perfect score for sustained virologic responses was “spectacular,” she added.
Ongoing studies that should finish soon are also looking at the safety and efficacy of ledipasvir/sofosbuvir in children aged 3-11 years old and in children and adolescents infected by other hepatitis C genotypes, specifically 4, 5, and 6. Taking on genotypes 2 and 3 will require additional treatment with ribavirin, she noted. Subsequent reports will also document patient outcomes 24 weeks from the start of treatment, after they’ve been off their completed regimen for 12 weeks. Gilead staffers have told Dr. Murray that they anticipate asking the FDA before the end of 2016 for approval to relabel the ledipasvir/sofosbuvir formulation they market to include adolescents, and possibly children too, depending on the outcome of studies still underway.
The result she reported came from 100 patients enrolled at 24 centers in the United States, Canada, and Europe. They averaged 15 years old, nearly two-thirds were girls, and 90% were white. One-fifth of the patients had been previously treated, and 81% were infected by genotype 1a hepatitis C with the remaining 19% infected with genotype 1b. Patients received the conventional, marketed formulation of ledipasvir/sofosbuvir, 90/400 mg, orally once daily.
Ninety-eight of the patients had no detectable hepatitis C virus in their blood at the end of 12 weeks of treatment. The other two patients were lost to follow-up and did not undergo virologic testing at the end of treatment and conservatively were tallied as nonresponders, she reported. A pharmacokinetic study done in a subgroup of patients showed plasma drug levels comparable with those seen in adults.
Although 71% of the patients reported having some adverse effect, no patient reported a serious or grade 3 or 4 adverse effect and no patient stopped treatment because of adverse effects. Nine patients had a grade 3 or 4 laboratory abnormality on treatment. The only lab abnormality to occur in more than one patient was a transient rise in amylase levels, which happened in three patients. The regimen’s overall performance in adolescents closely tracked what’s been seen in adults, Dr. Murray said.
“These data will lead to FDA approval” of the regimen for adolescents, she said confidently, and that will ease insurance coverage. “There will still be hoops to jump through, but with approval and once written into guidelines, insurers will be under pressure to reimburse for it,” she noted. “We find that, because of the cost, insurers resist or refuse to pay for these medications. The idea of treating only patients with advanced liver disease is morally inappropriate. These children must be treated before they develop significant or irreversible liver disease.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @mitchelzoler
AT WCPGHAN 2016
Key clinical point:
Major finding: Hepatitis C virus was undetectable after 12 weeks of treatment in 98%; the remaining two patients were lost to follow-up.
Data source: A multicenter, open-label study with 100 patients, aged 12-17 years old, and chronically infected with hepatitis C genotype 1.
Disclosures: The study was sponsored by Gilead, the company that markets ledipasvir/sofosbuvir (Harvoni). Dr. Murray has received research support from Gilead and is a shareholder in Merck.
VIDEO: What will be the NIMH’s focus under Dr. Joshua Gordon?
NEW YORK – “Most clinicians probably don’t have problems identifying patients who are depressed and giving them a trial of an antidepressant or a second antidepressant, but where do they run into stumbling blocks?” That’s a question Joshua A. Gordon, MD, PhD, the new director of the National Institute of Mental Health, said he is pondering as he steps into his new role.
Both a practicing clinical psychiatrist and a neuroscientist with a lab chiefly dedicated to optogenetics, Dr. Gordon shared his thoughts about what the priorities of the world’s largest mental health research institute should be, and how to balance immediate patient needs with the development of future interventions.
Conducted in New York City, where Dr. Gordon saw patients, maintained a lab, and was an associate professor of psychiatry at Columbia University for nearly 2 decades, this is the last installment in a series of interviews.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
NEW YORK – “Most clinicians probably don’t have problems identifying patients who are depressed and giving them a trial of an antidepressant or a second antidepressant, but where do they run into stumbling blocks?” That’s a question Joshua A. Gordon, MD, PhD, the new director of the National Institute of Mental Health, said he is pondering as he steps into his new role.
Both a practicing clinical psychiatrist and a neuroscientist with a lab chiefly dedicated to optogenetics, Dr. Gordon shared his thoughts about what the priorities of the world’s largest mental health research institute should be, and how to balance immediate patient needs with the development of future interventions.
Conducted in New York City, where Dr. Gordon saw patients, maintained a lab, and was an associate professor of psychiatry at Columbia University for nearly 2 decades, this is the last installment in a series of interviews.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
NEW YORK – “Most clinicians probably don’t have problems identifying patients who are depressed and giving them a trial of an antidepressant or a second antidepressant, but where do they run into stumbling blocks?” That’s a question Joshua A. Gordon, MD, PhD, the new director of the National Institute of Mental Health, said he is pondering as he steps into his new role.
Both a practicing clinical psychiatrist and a neuroscientist with a lab chiefly dedicated to optogenetics, Dr. Gordon shared his thoughts about what the priorities of the world’s largest mental health research institute should be, and how to balance immediate patient needs with the development of future interventions.
Conducted in New York City, where Dr. Gordon saw patients, maintained a lab, and was an associate professor of psychiatry at Columbia University for nearly 2 decades, this is the last installment in a series of interviews.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
[email protected]
On Twitter @whitneymcknight
