In recent years, uterine isthmocele has increasingly been included as part of the differential in women with a history of a cesarean section who present with postmenstrual bleeding, pelvic pain, or secondary infertility.

The defect appears as a fluid-filled, pouch-like abnormality in the anterior uterine wall at the site of a prior cesarean section. The best method for diagnosis is usually a saline-infused sonogram. It can be treated in various ways, depending on the patient’s symptoms and desire for future fertility. Although we have treated isthmoceles with hysteroscopic desiccation, or resection, our best success has occurred with laparoscopic resection and reapproximation of normal tissue in a small series of patients.

There is no standard definition of the defect that fully describes its size, depth, and other characteristics. Many words and phrases have been used to describe the defect: It is commonly referred to as an isthmocele, because of its usual location at the uterine isthmus, but others have referred to it as a cesarean scar defect or niche, as the defect may be found at the endocervical canal or in the lower uterine segment. In any case, while diagnoses appear to be increasing, the incidence of the defect is unknown.

More research on risk factors and treatment is needed, but the literature, as well as our own experience, has demonstrated that this treatable defect should be considered in the differential diagnosis for women who have undergone cesarean section and subsequently have abnormal bleeding or staining, pelvic pain, or secondary infertility, especially when fluid is clearly visible in the cesarean section defect.

Diagnosis, symptoms

An isthmocele forms in the first place, it is thought, after an incision scar forms and causes retraction and dilation in the thinner, lower segment of the anterior wall and a thickening in the upper portion. There is a deficient scar, in other words, with disparate wound healing on the sides of the incision site.

The defect and its consequences were described in 1995 by Dr. Hugh Morris, who studied hysterectomy specimens in 51 women with a history of cesarean section (in most cases, more than one). Dr. Morris concluded that scar tissue in these patients contributed to significant pathological changes and anatomical abnormalities that, in turn, gave rise to a variety of clinical symptoms including menorrhagia, dysmenorrhea, dyspareunia, and lower abdominal pain refractory to medical management.

Distortion and widening of the lower uterine segment and “free” red blood cells in endometrial stroma of the scar were the most frequently identified pathological changes, followed by fragmentation and breakdown of the endometrium of the scar, and iatrogenic adenomyosis (Int. J. Gynecol. Pathol.1995;14:16-20).

Several small reports and case series published in the late 1990s offered additional support for a cause-and-effect correlation between cesarean scar defects and abnormal vaginal bleeding. Several years later, the link was strengthened as more investigators reported connections between the defects and various symptoms. These reports were followed by published comparisons of imaging techniques for the diagnosis of isthmoceles.

Diagnosis of the defects can be made with transvaginal ultrasound (TVUS), saline infused sonohysterogram (SIS), hysterosalpingogram, hysteroscopy, and magnetic resonance imaging (MRI). With any modality, imaging is best performed in the early proliferative phase, right after the menstrual cycle has ended.

Courtesy of Dr. Kirsten Sasaki

Comparisons of unenhanced TVUS and SIS – both of which may be easily performed in the office and at a much lower cost than MRI – have shown the latter technique to be superior for evaluating isthmoceles. Distension of the endometrial cavity makes the borders of the defects easier to delineate, which enables detection of more subtle defects and improves our ability to measure the size of defects.

This advantage was described by in 2010 by Dr. O. Vikhareva Osser and colleagues, who performed both TVUS and SIS in 108 women with a history of one or more cesarean sections. They identified more scar defects with SIS than with TVUS (Ultrasound Obstet. Gynecol. 2010;35:75-83).

Another benefit of SIS over TVUS and hysterosalpingogram is that one can measure the thickness of the remaining myometrium overlying the isthmocele, which is especially important knowledge for patients considering another pregnancy. As a result, we have relied on this technique to diagnose every case within our practice. I will perform SIS in a patient who has a history of one or multiple cesarean sections and symptoms of abnormal bleeding, pelvic pain, or secondary infertility as part of the basic work-up.

Similarly, an observational prospective cohort study of 225 women who had undergone a cesarean section 6-12 months prior compared TVUS and gel-infused sonohysterogram (GIS), and found that the prevalence of a niche – defined as an anechoic area at the site of the cesarean scar, with a depth of at least 1 mm on GIS – was 24% with TVUS and 56% with GIS (Ultrasound Obstet. Gynecol. 2011;37:93-9).

The abnormal bleeding is often described by patients as spotting or bleeding that continues for days or weeks after menstrual flow has ended; it is believed to result from an accumulation of blood in the defect and a lack of coordinated muscle contractions, which leads to continued accumulation of blood and menstrual debris. Dysmenorrhea and chronic pelvic pain are thought to be associated with iatrogenic adenomyosis and/or a chronic inflammatory state created when accumulated blood and mucus are intermittently expelled. Secondary infertility can occur, it is believed, as accumulated fluid and blood interfere with the endocervical and even the endometrial environment and disrupt sperm transport, sperm quality, and embryo implantation. Difficulty in embryo transfer may also occur because of the distortion caused to the endometrial cavity. Many of the isthmoceles that we and others have diagnosed have been in patients undergoing invitro fertilization. The patients are often found to have an accumulation of fluid in the endometrial canal and isthmocele during stimulation for either a fresh or frozen embryo transfer, thus necessitating the cancellation of their cycle.

Treatment

The choice of treatment depends upon the patient’s symptoms and desire for future fertility, but it can include hormonal treatment, hysteroscopic resection, transvaginal repair, a laparoscopic or robot-assisted approach, and hysterectomy.

Little has been published on nonsurgical treatment, but this may be considered for patients whose primary symptoms are bleeding or pain and who desire the least invasive option. In a small observational study of women with an isthmocele and bleeding, symptoms were eliminated with several cycles of oral contraceptive pills (Fertil. Steril. 2006;86: 477-9).

Courtesy of Dr. Kirsten Sasaki

Hysteroscopic isthmocele correction or resection are the surgical techniques most frequently described in the literature, but, as with other surgical approaches, studies are small. Hysteroscopic repair has typically involved the use of electrical energy to desiccate or cauterize abnormal tissue and eliminate the outpouching in which blood and fluid accumulate. Hysteroscopic resection is another technique that has also been championed.

However, for patients who desire future pregnancy, we do not recommend a hysteroscopic approach because it does not reinforce the often-thinning myometrium covering the defect. We are concerned that if this area is simply desiccated or resected, and not reapproximated, the patient will be at greater risk of pregnancy-related complications, including cesarean scar ectopic pregnancy with potential uterine dehiscence.

Laparoscopic repair was first described by Dr. Olivier Donnez, who rightly pointed out that the laparoscopic approach offers an optimal view from above during dissection of the vesico-vaginal space. Dr. Donnez used a CO₂ laser to excise fibrotic tissue, followed by laparoscopic closure (Fertil. Steril. 2008;89:974-80).

We have had success with a laparoscopic approach that uses concomitant hysteroscopy. The vesico-uterine peritoneum is incised over the anterior uterine wall, and the bladder is backfilled so that its boundaries may be identified prior to further dissection. With the area exposed, we perform a hysteroscopy to determine the exact location of the isthmocele. As the hysteroscope enters the thinned out isthmocele, the light will be more visible via laparoscopic visualization.

When performing conventional laparoscopy, the isthmocele is excised with an ultrasonic curved blade. We use this instrument because it has no opposing arm and because it enables precise tissue dissection in multiple planes. With harmonic energy, we can limit tissue dessication and destruction, lowering the risk of future pregnancy-related complications. Monopolar scissors are best when a robotic approach is used.

Once the isthmocele is resected, the clean edges are sutured together in two layers. The first layer is sutured in an interrupted mattress-style fashion, to prevent tissue strangulation and necrosis. We use a monofilament nonbarbed delayed-absorbable 3-0 PDS suture on a CT-1 needle – a choice that limits tissue trauma and postoperative inflammation.

Courtesy of Dr. Kirsten Sasaki

Sutures are initially placed at each angle with one or two sutures placed between. These sutures must be placed deep to close the bottom of the defect. A second layer of suture is then placed to imbricate over the initial layer of closure. We utilize 3-0 PDS in a running or mattress style, or a running 3-0 V-Loc suture. Our patients return after 1-3 months for a postoperative image, and are instructed to wait at least 3 months after surgery before attempting conception.

In our experience, of more than 10 patients, symptoms ceased in all patients whose surgery was performed for the indication of abnormal uterine bleeding. The follow-up on our series of patients who underwent the procedure for secondary infertility is ongoing, but the preliminary results are very positive, with resolution of intrauterine fluid in all of the patients, as well as several successful pregnancy outcomes.

A recent systematic review of minimally invasive therapy for symptoms related to an isthmocele shows good outcomes across the 12 included studies but does not offer evidence to favor one treatment over another. The studies show significant reductions in abnormal uterine bleeding and pain, as well as a high rate of satisfaction in most patients after hysteroscopic niche resection or vaginal or laparoscopic niche repair, with a low complication rate (BJOG 2014;121:145-6).

Pregnancies were reported after treatment, but sample sizes and follow-up were insufficient to draw conclusions on pregnancy and delivery outcomes, according to the review. As the reviewers wrote, following patients through their next delivery in larger, higher-quality studies will help provide more guidance for selecting the best isthmocele treatments and implementing these treatments into practice.

Dr. Sasaki reported having no financial disclosures relevant to this Master Class.

In recent years, uterine isthmocele has increasingly been included as part of the differential in women with a history of a cesarean section who present with postmenstrual bleeding, pelvic pain, or secondary infertility.

The defect appears as a fluid-filled, pouch-like abnormality in the anterior uterine wall at the site of a prior cesarean section. The best method for diagnosis is usually a saline-infused sonogram. It can be treated in various ways, depending on the patient’s symptoms and desire for future fertility. Although we have treated isthmoceles with hysteroscopic desiccation, or resection, our best success has occurred with laparoscopic resection and reapproximation of normal tissue in a small series of patients.

There is no standard definition of the defect that fully describes its size, depth, and other characteristics. Many words and phrases have been used to describe the defect: It is commonly referred to as an isthmocele, because of its usual location at the uterine isthmus, but others have referred to it as a cesarean scar defect or niche, as the defect may be found at the endocervical canal or in the lower uterine segment. In any case, while diagnoses appear to be increasing, the incidence of the defect is unknown.

More research on risk factors and treatment is needed, but the literature, as well as our own experience, has demonstrated that this treatable defect should be considered in the differential diagnosis for women who have undergone cesarean section and subsequently have abnormal bleeding or staining, pelvic pain, or secondary infertility, especially when fluid is clearly visible in the cesarean section defect.

Diagnosis, symptoms

An isthmocele forms in the first place, it is thought, after an incision scar forms and causes retraction and dilation in the thinner, lower segment of the anterior wall and a thickening in the upper portion. There is a deficient scar, in other words, with disparate wound healing on the sides of the incision site.

The defect and its consequences were described in 1995 by Dr. Hugh Morris, who studied hysterectomy specimens in 51 women with a history of cesarean section (in most cases, more than one). Dr. Morris concluded that scar tissue in these patients contributed to significant pathological changes and anatomical abnormalities that, in turn, gave rise to a variety of clinical symptoms including menorrhagia, dysmenorrhea, dyspareunia, and lower abdominal pain refractory to medical management.

Distortion and widening of the lower uterine segment and “free” red blood cells in endometrial stroma of the scar were the most frequently identified pathological changes, followed by fragmentation and breakdown of the endometrium of the scar, and iatrogenic adenomyosis (Int. J. Gynecol. Pathol.1995;14:16-20).

Several small reports and case series published in the late 1990s offered additional support for a cause-and-effect correlation between cesarean scar defects and abnormal vaginal bleeding. Several years later, the link was strengthened as more investigators reported connections between the defects and various symptoms. These reports were followed by published comparisons of imaging techniques for the diagnosis of isthmoceles.

Diagnosis of the defects can be made with transvaginal ultrasound (TVUS), saline infused sonohysterogram (SIS), hysterosalpingogram, hysteroscopy, and magnetic resonance imaging (MRI). With any modality, imaging is best performed in the early proliferative phase, right after the menstrual cycle has ended.

Courtesy of Dr. Kirsten Sasaki

Comparisons of unenhanced TVUS and SIS – both of which may be easily performed in the office and at a much lower cost than MRI – have shown the latter technique to be superior for evaluating isthmoceles. Distension of the endometrial cavity makes the borders of the defects easier to delineate, which enables detection of more subtle defects and improves our ability to measure the size of defects.

This advantage was described by in 2010 by Dr. O. Vikhareva Osser and colleagues, who performed both TVUS and SIS in 108 women with a history of one or more cesarean sections. They identified more scar defects with SIS than with TVUS (Ultrasound Obstet. Gynecol. 2010;35:75-83).

Another benefit of SIS over TVUS and hysterosalpingogram is that one can measure the thickness of the remaining myometrium overlying the isthmocele, which is especially important knowledge for patients considering another pregnancy. As a result, we have relied on this technique to diagnose every case within our practice. I will perform SIS in a patient who has a history of one or multiple cesarean sections and symptoms of abnormal bleeding, pelvic pain, or secondary infertility as part of the basic work-up.

Similarly, an observational prospective cohort study of 225 women who had undergone a cesarean section 6-12 months prior compared TVUS and gel-infused sonohysterogram (GIS), and found that the prevalence of a niche – defined as an anechoic area at the site of the cesarean scar, with a depth of at least 1 mm on GIS – was 24% with TVUS and 56% with GIS (Ultrasound Obstet. Gynecol. 2011;37:93-9).

The abnormal bleeding is often described by patients as spotting or bleeding that continues for days or weeks after menstrual flow has ended; it is believed to result from an accumulation of blood in the defect and a lack of coordinated muscle contractions, which leads to continued accumulation of blood and menstrual debris. Dysmenorrhea and chronic pelvic pain are thought to be associated with iatrogenic adenomyosis and/or a chronic inflammatory state created when accumulated blood and mucus are intermittently expelled. Secondary infertility can occur, it is believed, as accumulated fluid and blood interfere with the endocervical and even the endometrial environment and disrupt sperm transport, sperm quality, and embryo implantation. Difficulty in embryo transfer may also occur because of the distortion caused to the endometrial cavity. Many of the isthmoceles that we and others have diagnosed have been in patients undergoing invitro fertilization. The patients are often found to have an accumulation of fluid in the endometrial canal and isthmocele during stimulation for either a fresh or frozen embryo transfer, thus necessitating the cancellation of their cycle.

Treatment

The choice of treatment depends upon the patient’s symptoms and desire for future fertility, but it can include hormonal treatment, hysteroscopic resection, transvaginal repair, a laparoscopic or robot-assisted approach, and hysterectomy.

Little has been published on nonsurgical treatment, but this may be considered for patients whose primary symptoms are bleeding or pain and who desire the least invasive option. In a small observational study of women with an isthmocele and bleeding, symptoms were eliminated with several cycles of oral contraceptive pills (Fertil. Steril. 2006;86: 477-9).

Courtesy of Dr. Kirsten Sasaki

Hysteroscopic isthmocele correction or resection are the surgical techniques most frequently described in the literature, but, as with other surgical approaches, studies are small. Hysteroscopic repair has typically involved the use of electrical energy to desiccate or cauterize abnormal tissue and eliminate the outpouching in which blood and fluid accumulate. Hysteroscopic resection is another technique that has also been championed.

However, for patients who desire future pregnancy, we do not recommend a hysteroscopic approach because it does not reinforce the often-thinning myometrium covering the defect. We are concerned that if this area is simply desiccated or resected, and not reapproximated, the patient will be at greater risk of pregnancy-related complications, including cesarean scar ectopic pregnancy with potential uterine dehiscence.

Laparoscopic repair was first described by Dr. Olivier Donnez, who rightly pointed out that the laparoscopic approach offers an optimal view from above during dissection of the vesico-vaginal space. Dr. Donnez used a CO₂ laser to excise fibrotic tissue, followed by laparoscopic closure (Fertil. Steril. 2008;89:974-80).

We have had success with a laparoscopic approach that uses concomitant hysteroscopy. The vesico-uterine peritoneum is incised over the anterior uterine wall, and the bladder is backfilled so that its boundaries may be identified prior to further dissection. With the area exposed, we perform a hysteroscopy to determine the exact location of the isthmocele. As the hysteroscope enters the thinned out isthmocele, the light will be more visible via laparoscopic visualization.

When performing conventional laparoscopy, the isthmocele is excised with an ultrasonic curved blade. We use this instrument because it has no opposing arm and because it enables precise tissue dissection in multiple planes. With harmonic energy, we can limit tissue dessication and destruction, lowering the risk of future pregnancy-related complications. Monopolar scissors are best when a robotic approach is used.

Once the isthmocele is resected, the clean edges are sutured together in two layers. The first layer is sutured in an interrupted mattress-style fashion, to prevent tissue strangulation and necrosis. We use a monofilament nonbarbed delayed-absorbable 3-0 PDS suture on a CT-1 needle – a choice that limits tissue trauma and postoperative inflammation.

Courtesy of Dr. Kirsten Sasaki

Sutures are initially placed at each angle with one or two sutures placed between. These sutures must be placed deep to close the bottom of the defect. A second layer of suture is then placed to imbricate over the initial layer of closure. We utilize 3-0 PDS in a running or mattress style, or a running 3-0 V-Loc suture. Our patients return after 1-3 months for a postoperative image, and are instructed to wait at least 3 months after surgery before attempting conception.

In our experience, of more than 10 patients, symptoms ceased in all patients whose surgery was performed for the indication of abnormal uterine bleeding. The follow-up on our series of patients who underwent the procedure for secondary infertility is ongoing, but the preliminary results are very positive, with resolution of intrauterine fluid in all of the patients, as well as several successful pregnancy outcomes.

A recent systematic review of minimally invasive therapy for symptoms related to an isthmocele shows good outcomes across the 12 included studies but does not offer evidence to favor one treatment over another. The studies show significant reductions in abnormal uterine bleeding and pain, as well as a high rate of satisfaction in most patients after hysteroscopic niche resection or vaginal or laparoscopic niche repair, with a low complication rate (BJOG 2014;121:145-6).

Pregnancies were reported after treatment, but sample sizes and follow-up were insufficient to draw conclusions on pregnancy and delivery outcomes, according to the review. As the reviewers wrote, following patients through their next delivery in larger, higher-quality studies will help provide more guidance for selecting the best isthmocele treatments and implementing these treatments into practice.

Dr. Sasaki reported having no financial disclosures relevant to this Master Class.

In recent years, uterine isthmocele has increasingly been included as part of the differential in women with a history of a cesarean section who present with postmenstrual bleeding, pelvic pain, or secondary infertility.

The defect appears as a fluid-filled, pouch-like abnormality in the anterior uterine wall at the site of a prior cesarean section. The best method for diagnosis is usually a saline-infused sonogram. It can be treated in various ways, depending on the patient’s symptoms and desire for future fertility. Although we have treated isthmoceles with hysteroscopic desiccation, or resection, our best success has occurred with laparoscopic resection and reapproximation of normal tissue in a small series of patients.

There is no standard definition of the defect that fully describes its size, depth, and other characteristics. Many words and phrases have been used to describe the defect: It is commonly referred to as an isthmocele, because of its usual location at the uterine isthmus, but others have referred to it as a cesarean scar defect or niche, as the defect may be found at the endocervical canal or in the lower uterine segment. In any case, while diagnoses appear to be increasing, the incidence of the defect is unknown.

More research on risk factors and treatment is needed, but the literature, as well as our own experience, has demonstrated that this treatable defect should be considered in the differential diagnosis for women who have undergone cesarean section and subsequently have abnormal bleeding or staining, pelvic pain, or secondary infertility, especially when fluid is clearly visible in the cesarean section defect.

Diagnosis, symptoms

An isthmocele forms in the first place, it is thought, after an incision scar forms and causes retraction and dilation in the thinner, lower segment of the anterior wall and a thickening in the upper portion. There is a deficient scar, in other words, with disparate wound healing on the sides of the incision site.

The defect and its consequences were described in 1995 by Dr. Hugh Morris, who studied hysterectomy specimens in 51 women with a history of cesarean section (in most cases, more than one). Dr. Morris concluded that scar tissue in these patients contributed to significant pathological changes and anatomical abnormalities that, in turn, gave rise to a variety of clinical symptoms including menorrhagia, dysmenorrhea, dyspareunia, and lower abdominal pain refractory to medical management.

Distortion and widening of the lower uterine segment and “free” red blood cells in endometrial stroma of the scar were the most frequently identified pathological changes, followed by fragmentation and breakdown of the endometrium of the scar, and iatrogenic adenomyosis (Int. J. Gynecol. Pathol.1995;14:16-20).

Several small reports and case series published in the late 1990s offered additional support for a cause-and-effect correlation between cesarean scar defects and abnormal vaginal bleeding. Several years later, the link was strengthened as more investigators reported connections between the defects and various symptoms. These reports were followed by published comparisons of imaging techniques for the diagnosis of isthmoceles.

Diagnosis of the defects can be made with transvaginal ultrasound (TVUS), saline infused sonohysterogram (SIS), hysterosalpingogram, hysteroscopy, and magnetic resonance imaging (MRI). With any modality, imaging is best performed in the early proliferative phase, right after the menstrual cycle has ended.

Courtesy of Dr. Kirsten Sasaki

Comparisons of unenhanced TVUS and SIS – both of which may be easily performed in the office and at a much lower cost than MRI – have shown the latter technique to be superior for evaluating isthmoceles. Distension of the endometrial cavity makes the borders of the defects easier to delineate, which enables detection of more subtle defects and improves our ability to measure the size of defects.

This advantage was described by in 2010 by Dr. O. Vikhareva Osser and colleagues, who performed both TVUS and SIS in 108 women with a history of one or more cesarean sections. They identified more scar defects with SIS than with TVUS (Ultrasound Obstet. Gynecol. 2010;35:75-83).

Another benefit of SIS over TVUS and hysterosalpingogram is that one can measure the thickness of the remaining myometrium overlying the isthmocele, which is especially important knowledge for patients considering another pregnancy. As a result, we have relied on this technique to diagnose every case within our practice. I will perform SIS in a patient who has a history of one or multiple cesarean sections and symptoms of abnormal bleeding, pelvic pain, or secondary infertility as part of the basic work-up.

Similarly, an observational prospective cohort study of 225 women who had undergone a cesarean section 6-12 months prior compared TVUS and gel-infused sonohysterogram (GIS), and found that the prevalence of a niche – defined as an anechoic area at the site of the cesarean scar, with a depth of at least 1 mm on GIS – was 24% with TVUS and 56% with GIS (Ultrasound Obstet. Gynecol. 2011;37:93-9).

The abnormal bleeding is often described by patients as spotting or bleeding that continues for days or weeks after menstrual flow has ended; it is believed to result from an accumulation of blood in the defect and a lack of coordinated muscle contractions, which leads to continued accumulation of blood and menstrual debris. Dysmenorrhea and chronic pelvic pain are thought to be associated with iatrogenic adenomyosis and/or a chronic inflammatory state created when accumulated blood and mucus are intermittently expelled. Secondary infertility can occur, it is believed, as accumulated fluid and blood interfere with the endocervical and even the endometrial environment and disrupt sperm transport, sperm quality, and embryo implantation. Difficulty in embryo transfer may also occur because of the distortion caused to the endometrial cavity. Many of the isthmoceles that we and others have diagnosed have been in patients undergoing invitro fertilization. The patients are often found to have an accumulation of fluid in the endometrial canal and isthmocele during stimulation for either a fresh or frozen embryo transfer, thus necessitating the cancellation of their cycle.

Treatment

The choice of treatment depends upon the patient’s symptoms and desire for future fertility, but it can include hormonal treatment, hysteroscopic resection, transvaginal repair, a laparoscopic or robot-assisted approach, and hysterectomy.

Little has been published on nonsurgical treatment, but this may be considered for patients whose primary symptoms are bleeding or pain and who desire the least invasive option. In a small observational study of women with an isthmocele and bleeding, symptoms were eliminated with several cycles of oral contraceptive pills (Fertil. Steril. 2006;86: 477-9).

Courtesy of Dr. Kirsten Sasaki

Hysteroscopic isthmocele correction or resection are the surgical techniques most frequently described in the literature, but, as with other surgical approaches, studies are small. Hysteroscopic repair has typically involved the use of electrical energy to desiccate or cauterize abnormal tissue and eliminate the outpouching in which blood and fluid accumulate. Hysteroscopic resection is another technique that has also been championed.

However, for patients who desire future pregnancy, we do not recommend a hysteroscopic approach because it does not reinforce the often-thinning myometrium covering the defect. We are concerned that if this area is simply desiccated or resected, and not reapproximated, the patient will be at greater risk of pregnancy-related complications, including cesarean scar ectopic pregnancy with potential uterine dehiscence.

Laparoscopic repair was first described by Dr. Olivier Donnez, who rightly pointed out that the laparoscopic approach offers an optimal view from above during dissection of the vesico-vaginal space. Dr. Donnez used a CO₂ laser to excise fibrotic tissue, followed by laparoscopic closure (Fertil. Steril. 2008;89:974-80).

We have had success with a laparoscopic approach that uses concomitant hysteroscopy. The vesico-uterine peritoneum is incised over the anterior uterine wall, and the bladder is backfilled so that its boundaries may be identified prior to further dissection. With the area exposed, we perform a hysteroscopy to determine the exact location of the isthmocele. As the hysteroscope enters the thinned out isthmocele, the light will be more visible via laparoscopic visualization.

When performing conventional laparoscopy, the isthmocele is excised with an ultrasonic curved blade. We use this instrument because it has no opposing arm and because it enables precise tissue dissection in multiple planes. With harmonic energy, we can limit tissue dessication and destruction, lowering the risk of future pregnancy-related complications. Monopolar scissors are best when a robotic approach is used.

Once the isthmocele is resected, the clean edges are sutured together in two layers. The first layer is sutured in an interrupted mattress-style fashion, to prevent tissue strangulation and necrosis. We use a monofilament nonbarbed delayed-absorbable 3-0 PDS suture on a CT-1 needle – a choice that limits tissue trauma and postoperative inflammation.

Courtesy of Dr. Kirsten Sasaki

Sutures are initially placed at each angle with one or two sutures placed between. These sutures must be placed deep to close the bottom of the defect. A second layer of suture is then placed to imbricate over the initial layer of closure. We utilize 3-0 PDS in a running or mattress style, or a running 3-0 V-Loc suture. Our patients return after 1-3 months for a postoperative image, and are instructed to wait at least 3 months after surgery before attempting conception.

In our experience, of more than 10 patients, symptoms ceased in all patients whose surgery was performed for the indication of abnormal uterine bleeding. The follow-up on our series of patients who underwent the procedure for secondary infertility is ongoing, but the preliminary results are very positive, with resolution of intrauterine fluid in all of the patients, as well as several successful pregnancy outcomes.

A recent systematic review of minimally invasive therapy for symptoms related to an isthmocele shows good outcomes across the 12 included studies but does not offer evidence to favor one treatment over another. The studies show significant reductions in abnormal uterine bleeding and pain, as well as a high rate of satisfaction in most patients after hysteroscopic niche resection or vaginal or laparoscopic niche repair, with a low complication rate (BJOG 2014;121:145-6).

Pregnancies were reported after treatment, but sample sizes and follow-up were insufficient to draw conclusions on pregnancy and delivery outcomes, according to the review. As the reviewers wrote, following patients through their next delivery in larger, higher-quality studies will help provide more guidance for selecting the best isthmocele treatments and implementing these treatments into practice.

Dr. Sasaki reported having no financial disclosures relevant to this Master Class.

Dual-energy x-ray absorptiometry to screen for osteoporosis is both underused in women who meet the U.S. Preventive Services Task Force criteria for screening, and overused in low-risk younger women, new data suggest.

A retrospective, longitudinal cohort study of 50,995 women attending 13 primary care clinics found that among previously unscreened women who met the criteria for screening, the 7-year cumulative incidence of DXA screening ranged from 58.8% in women aged 60-64 years with at least one risk factor, to 42.7% in women aged 75 years and older.

©iStock / ThinkStockPhotos.com

But among women who didn’t meet screening criteria, the 7-year cumulative incidence was 45.5% in women aged 50-59 years and 58.6% in women aged 60-64 years without risk factors, according to a paper published May 19 in the Journal of General Internal Medicine (doi:10.1007/s11606-015-3349-8).

The U.S. Preventive Services Task Force currently recommends screening for osteoporosis with DXA for women aged 65 and older, as well as young women at increased risk for fracture. The American Academy of Family Physicians also advised against DXA screening in women younger than age 65 without osteoporosis risk factors as part of the “Choosing Wisely” campaign.

“Additional research is needed to elucidate patient, physician, and health system barriers to evidence-based screening so that interventions can maximize the value of population screening for osteoporosis,” wrote Dr. Anna Lee D. Amarnath of the University of California, Davis Health System, and her coauthors.

The study was supported by the National Institutes of Health and the Agency for Healthcare Research and Quality. The researchers reported having no financial disclosures.

Dual-energy x-ray absorptiometry to screen for osteoporosis is both underused in women who meet the U.S. Preventive Services Task Force criteria for screening, and overused in low-risk younger women, new data suggest.

A retrospective, longitudinal cohort study of 50,995 women attending 13 primary care clinics found that among previously unscreened women who met the criteria for screening, the 7-year cumulative incidence of DXA screening ranged from 58.8% in women aged 60-64 years with at least one risk factor, to 42.7% in women aged 75 years and older.

©iStock / ThinkStockPhotos.com

But among women who didn’t meet screening criteria, the 7-year cumulative incidence was 45.5% in women aged 50-59 years and 58.6% in women aged 60-64 years without risk factors, according to a paper published May 19 in the Journal of General Internal Medicine (doi:10.1007/s11606-015-3349-8).

The U.S. Preventive Services Task Force currently recommends screening for osteoporosis with DXA for women aged 65 and older, as well as young women at increased risk for fracture. The American Academy of Family Physicians also advised against DXA screening in women younger than age 65 without osteoporosis risk factors as part of the “Choosing Wisely” campaign.

“Additional research is needed to elucidate patient, physician, and health system barriers to evidence-based screening so that interventions can maximize the value of population screening for osteoporosis,” wrote Dr. Anna Lee D. Amarnath of the University of California, Davis Health System, and her coauthors.

The study was supported by the National Institutes of Health and the Agency for Healthcare Research and Quality. The researchers reported having no financial disclosures.

Dual-energy x-ray absorptiometry to screen for osteoporosis is both underused in women who meet the U.S. Preventive Services Task Force criteria for screening, and overused in low-risk younger women, new data suggest.

A retrospective, longitudinal cohort study of 50,995 women attending 13 primary care clinics found that among previously unscreened women who met the criteria for screening, the 7-year cumulative incidence of DXA screening ranged from 58.8% in women aged 60-64 years with at least one risk factor, to 42.7% in women aged 75 years and older.

©iStock / ThinkStockPhotos.com

But among women who didn’t meet screening criteria, the 7-year cumulative incidence was 45.5% in women aged 50-59 years and 58.6% in women aged 60-64 years without risk factors, according to a paper published May 19 in the Journal of General Internal Medicine (doi:10.1007/s11606-015-3349-8).

The U.S. Preventive Services Task Force currently recommends screening for osteoporosis with DXA for women aged 65 and older, as well as young women at increased risk for fracture. The American Academy of Family Physicians also advised against DXA screening in women younger than age 65 without osteoporosis risk factors as part of the “Choosing Wisely” campaign.

“Additional research is needed to elucidate patient, physician, and health system barriers to evidence-based screening so that interventions can maximize the value of population screening for osteoporosis,” wrote Dr. Anna Lee D. Amarnath of the University of California, Davis Health System, and her coauthors.

The study was supported by the National Institutes of Health and the Agency for Healthcare Research and Quality. The researchers reported having no financial disclosures.

After more than 20 years, this 60-year-old woman has had enough of her persistent leg condition, finally taking a friend’s advice to consult dermatology. When asked if she has ever scratched or rubbed the area, her response is, “Of course! It itches something awful! If it didn’t itch, I would leave it alone.”

She goes on to describe how she spends her work day fantasizing about getting home and scratching the spot. Sometimes she uses a hairbrush, sometimes a rag; but she always obtains exquisite, if temporary, pleasure from attacking the problem.

Some of her innumerable treatment attempts—with products topical and oral, OTC and prescription—have offered brief relief but no true resolution. Among the methods tried are moisturizers, antifungal creams and pills, and topical steroids.

The patient has long since forgotten precisely when or how the problem started. However, she denies having any other problems with her skin.

EXAMINATION
The condition is confined to the right anterior tibial area. The skin on the upper one-third of the leg is darkened and rough, with a leathery texture. No erythema is seen in or around the lesion, and no abnormalities are noted elsewhere.

What is the diagnosis?

DISCUSSION
This is an archetypical case of lichen simplex chronicus (LSC), previously known as neurodermatitis. LSC is, by definition, a secondary condition, starting with a bit of eczema, dry skin, or even a bug bite that draws the patient’s attention to the area.

For some, once the itching and scratching start, it becomes hard to stop, although the original insult is long gone. Scratched or rubbed long enough, the affected skin reacts by becoming thick and leathery. In patients with darker skin, postinflammatory hyperpigmentation will also be seen.

But the worst effect is that, in response to chronic scratching, the nerves in the affected area become more numerous and even more sensitive. It’s the classic “itch­-scratch-itch” cycle that takes on a life of its own until broken. Even then, many patients resume scratching at some point, purely out of habit.

Effective treatment has three components: First, the patient has to apply a relatively strong topical steroid, usually twice a day, to reduce the itching. This paves the way for the second phase of treatment: cessation of scratching. Within a fairly short period of time, the skin will begin to lose its rough feel and hyperpigmentation and look more normal. Then the third part of successful treatment: The patient must stop looking for the cause and begin to understand his/her role in the perpetuation of the problem.

The differential for LSC includes psoriasis, eczema, lichen planus, and xerosis (dry skin). But the key features of LSC, illustrated nicely by this case, are: easily accessible area, chronicity (sometimes extreme), and lichenification and postinflammatory hyperpigmentation. This patient’s history of chronic excoriation of the site was an extremely helpful diagnostic clue.

TAKE-HOME LEARNING POINTS
• Lichen simplex chronicus (LSC) is always secondary to another trigger, such as dry skin, eczema, bug bite, or minor skin injury that itches as it heals.

• LSC is characterized by localized thickening of the skin in an accessible area.

• Legs (especially the anterior tibial area) are common sites, but so is the nuchal scalp—particularly in women.

• LSC is treated with a potent topical steroid cream (eg, clobetasol 0.05%) and education of the patient as to his/her role in the creation and perpetuation of the problem. 

After more than 20 years, this 60-year-old woman has had enough of her persistent leg condition, finally taking a friend’s advice to consult dermatology. When asked if she has ever scratched or rubbed the area, her response is, “Of course! It itches something awful! If it didn’t itch, I would leave it alone.”

She goes on to describe how she spends her work day fantasizing about getting home and scratching the spot. Sometimes she uses a hairbrush, sometimes a rag; but she always obtains exquisite, if temporary, pleasure from attacking the problem.

Some of her innumerable treatment attempts—with products topical and oral, OTC and prescription—have offered brief relief but no true resolution. Among the methods tried are moisturizers, antifungal creams and pills, and topical steroids.

The patient has long since forgotten precisely when or how the problem started. However, she denies having any other problems with her skin.

EXAMINATION
The condition is confined to the right anterior tibial area. The skin on the upper one-third of the leg is darkened and rough, with a leathery texture. No erythema is seen in or around the lesion, and no abnormalities are noted elsewhere.

What is the diagnosis?

DISCUSSION
This is an archetypical case of lichen simplex chronicus (LSC), previously known as neurodermatitis. LSC is, by definition, a secondary condition, starting with a bit of eczema, dry skin, or even a bug bite that draws the patient’s attention to the area.

For some, once the itching and scratching start, it becomes hard to stop, although the original insult is long gone. Scratched or rubbed long enough, the affected skin reacts by becoming thick and leathery. In patients with darker skin, postinflammatory hyperpigmentation will also be seen.

But the worst effect is that, in response to chronic scratching, the nerves in the affected area become more numerous and even more sensitive. It’s the classic “itch­-scratch-itch” cycle that takes on a life of its own until broken. Even then, many patients resume scratching at some point, purely out of habit.

Effective treatment has three components: First, the patient has to apply a relatively strong topical steroid, usually twice a day, to reduce the itching. This paves the way for the second phase of treatment: cessation of scratching. Within a fairly short period of time, the skin will begin to lose its rough feel and hyperpigmentation and look more normal. Then the third part of successful treatment: The patient must stop looking for the cause and begin to understand his/her role in the perpetuation of the problem.

The differential for LSC includes psoriasis, eczema, lichen planus, and xerosis (dry skin). But the key features of LSC, illustrated nicely by this case, are: easily accessible area, chronicity (sometimes extreme), and lichenification and postinflammatory hyperpigmentation. This patient’s history of chronic excoriation of the site was an extremely helpful diagnostic clue.

TAKE-HOME LEARNING POINTS
• Lichen simplex chronicus (LSC) is always secondary to another trigger, such as dry skin, eczema, bug bite, or minor skin injury that itches as it heals.

• LSC is characterized by localized thickening of the skin in an accessible area.

• Legs (especially the anterior tibial area) are common sites, but so is the nuchal scalp—particularly in women.

• LSC is treated with a potent topical steroid cream (eg, clobetasol 0.05%) and education of the patient as to his/her role in the creation and perpetuation of the problem. 

After more than 20 years, this 60-year-old woman has had enough of her persistent leg condition, finally taking a friend’s advice to consult dermatology. When asked if she has ever scratched or rubbed the area, her response is, “Of course! It itches something awful! If it didn’t itch, I would leave it alone.”

She goes on to describe how she spends her work day fantasizing about getting home and scratching the spot. Sometimes she uses a hairbrush, sometimes a rag; but she always obtains exquisite, if temporary, pleasure from attacking the problem.

Some of her innumerable treatment attempts—with products topical and oral, OTC and prescription—have offered brief relief but no true resolution. Among the methods tried are moisturizers, antifungal creams and pills, and topical steroids.

The patient has long since forgotten precisely when or how the problem started. However, she denies having any other problems with her skin.

EXAMINATION
The condition is confined to the right anterior tibial area. The skin on the upper one-third of the leg is darkened and rough, with a leathery texture. No erythema is seen in or around the lesion, and no abnormalities are noted elsewhere.

What is the diagnosis?

DISCUSSION
This is an archetypical case of lichen simplex chronicus (LSC), previously known as neurodermatitis. LSC is, by definition, a secondary condition, starting with a bit of eczema, dry skin, or even a bug bite that draws the patient’s attention to the area.

For some, once the itching and scratching start, it becomes hard to stop, although the original insult is long gone. Scratched or rubbed long enough, the affected skin reacts by becoming thick and leathery. In patients with darker skin, postinflammatory hyperpigmentation will also be seen.

But the worst effect is that, in response to chronic scratching, the nerves in the affected area become more numerous and even more sensitive. It’s the classic “itch­-scratch-itch” cycle that takes on a life of its own until broken. Even then, many patients resume scratching at some point, purely out of habit.

Effective treatment has three components: First, the patient has to apply a relatively strong topical steroid, usually twice a day, to reduce the itching. This paves the way for the second phase of treatment: cessation of scratching. Within a fairly short period of time, the skin will begin to lose its rough feel and hyperpigmentation and look more normal. Then the third part of successful treatment: The patient must stop looking for the cause and begin to understand his/her role in the perpetuation of the problem.

The differential for LSC includes psoriasis, eczema, lichen planus, and xerosis (dry skin). But the key features of LSC, illustrated nicely by this case, are: easily accessible area, chronicity (sometimes extreme), and lichenification and postinflammatory hyperpigmentation. This patient’s history of chronic excoriation of the site was an extremely helpful diagnostic clue.

TAKE-HOME LEARNING POINTS
• Lichen simplex chronicus (LSC) is always secondary to another trigger, such as dry skin, eczema, bug bite, or minor skin injury that itches as it heals.

• LSC is characterized by localized thickening of the skin in an accessible area.

• Legs (especially the anterior tibial area) are common sites, but so is the nuchal scalp—particularly in women.

• LSC is treated with a potent topical steroid cream (eg, clobetasol 0.05%) and education of the patient as to his/her role in the creation and perpetuation of the problem. 

Researchers in the lab

Photo by Rhoda Baer

Researchers say they have created interleukin-2 (IL-2) variants that function as IL-2-receptor signaling “clamps” and allow for “fine tuning” of the signaling amplitude.

One variant, known as H9-RETR, was able to inhibit the actions of endogenous IL-2 and IL-15, prolong survival in a mouse model of graft-vs-host disease (GVHD), and inhibit the proliferation of cells derived from a patient with smoldering adult T-cell

leukemia (ATL).

The researchers reported these results in Immunity.

Warren J. Leonard, MD, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland, and his colleagues developed IL-2 variants in which activity can be tuned to either boost or block immune responses, depending on the desired therapeutic application.

The researchers said these variants had high affinity for IL-2Rβ and inhibited binding of endogenous IL-2, but their interaction with γc was weakened, thereby weakening IL-2Rβ-γc heterodimerization.

The team found that IL-2 signaling strength was inversely correlated with the degree of mutation at the γc interface. And differential effects on cell proliferation were dependent upon the cells’ state of activation.

One of the IL-2 variants, H9-RETR, inhibited IL-2- and IL-15-mediated proliferation and cytotoxicity. H9-RETR inhibited cytokine signaling and natural killer cell activity as well or better than blocking antibodies to IL-2Rα and IL-2Rβ.

In experiments with cells isolated from a patient with smoldering ATL, H9-RETR blocked IL-2 signaling and inhibited the spontaneous proliferation of ATL cells. In this regard, H9-RETR was at least as effective as the anti-IL-2Rα antibody daclizumab and much more effective than the anti-IL-2Rβ antibody Mikβ1.

In a mouse model of GVHD, animals that received a stabilized, Fc-fusion version of H9-RETR (H9-RETR-Fc4) had significantly longer survival than control mice (which received only Fc4 protein).

All of the control mice had died by 40 days post-injection, but it took 60 days for all of the H9-RETR-Fc4-treated mice to die (P=0.0001).

The researchers believe their receptor-clamping approach could potentially be used to engineer other immune-system cytokines with therapeutic potential.

Researchers in the lab

Photo by Rhoda Baer

Researchers say they have created interleukin-2 (IL-2) variants that function as IL-2-receptor signaling “clamps” and allow for “fine tuning” of the signaling amplitude.

One variant, known as H9-RETR, was able to inhibit the actions of endogenous IL-2 and IL-15, prolong survival in a mouse model of graft-vs-host disease (GVHD), and inhibit the proliferation of cells derived from a patient with smoldering adult T-cell

leukemia (ATL).

The researchers reported these results in Immunity.

Warren J. Leonard, MD, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland, and his colleagues developed IL-2 variants in which activity can be tuned to either boost or block immune responses, depending on the desired therapeutic application.

The researchers said these variants had high affinity for IL-2Rβ and inhibited binding of endogenous IL-2, but their interaction with γc was weakened, thereby weakening IL-2Rβ-γc heterodimerization.

The team found that IL-2 signaling strength was inversely correlated with the degree of mutation at the γc interface. And differential effects on cell proliferation were dependent upon the cells’ state of activation.

One of the IL-2 variants, H9-RETR, inhibited IL-2- and IL-15-mediated proliferation and cytotoxicity. H9-RETR inhibited cytokine signaling and natural killer cell activity as well or better than blocking antibodies to IL-2Rα and IL-2Rβ.

In experiments with cells isolated from a patient with smoldering ATL, H9-RETR blocked IL-2 signaling and inhibited the spontaneous proliferation of ATL cells. In this regard, H9-RETR was at least as effective as the anti-IL-2Rα antibody daclizumab and much more effective than the anti-IL-2Rβ antibody Mikβ1.

In a mouse model of GVHD, animals that received a stabilized, Fc-fusion version of H9-RETR (H9-RETR-Fc4) had significantly longer survival than control mice (which received only Fc4 protein).

All of the control mice had died by 40 days post-injection, but it took 60 days for all of the H9-RETR-Fc4-treated mice to die (P=0.0001).

The researchers believe their receptor-clamping approach could potentially be used to engineer other immune-system cytokines with therapeutic potential.

Researchers in the lab

Photo by Rhoda Baer

Researchers say they have created interleukin-2 (IL-2) variants that function as IL-2-receptor signaling “clamps” and allow for “fine tuning” of the signaling amplitude.

One variant, known as H9-RETR, was able to inhibit the actions of endogenous IL-2 and IL-15, prolong survival in a mouse model of graft-vs-host disease (GVHD), and inhibit the proliferation of cells derived from a patient with smoldering adult T-cell

leukemia (ATL).

The researchers reported these results in Immunity.

Warren J. Leonard, MD, of the National Heart, Lung, and Blood Institute in Bethesda, Maryland, and his colleagues developed IL-2 variants in which activity can be tuned to either boost or block immune responses, depending on the desired therapeutic application.

The researchers said these variants had high affinity for IL-2Rβ and inhibited binding of endogenous IL-2, but their interaction with γc was weakened, thereby weakening IL-2Rβ-γc heterodimerization.

The team found that IL-2 signaling strength was inversely correlated with the degree of mutation at the γc interface. And differential effects on cell proliferation were dependent upon the cells’ state of activation.

One of the IL-2 variants, H9-RETR, inhibited IL-2- and IL-15-mediated proliferation and cytotoxicity. H9-RETR inhibited cytokine signaling and natural killer cell activity as well or better than blocking antibodies to IL-2Rα and IL-2Rβ.

In experiments with cells isolated from a patient with smoldering ATL, H9-RETR blocked IL-2 signaling and inhibited the spontaneous proliferation of ATL cells. In this regard, H9-RETR was at least as effective as the anti-IL-2Rα antibody daclizumab and much more effective than the anti-IL-2Rβ antibody Mikβ1.

In a mouse model of GVHD, animals that received a stabilized, Fc-fusion version of H9-RETR (H9-RETR-Fc4) had significantly longer survival than control mice (which received only Fc4 protein).

All of the control mice had died by 40 days post-injection, but it took 60 days for all of the H9-RETR-Fc4-treated mice to die (P=0.0001).

The researchers believe their receptor-clamping approach could potentially be used to engineer other immune-system cytokines with therapeutic potential.

Anopheles gambiae mosquito

Photo courtesy of the CDC

Recent progress in halting the spread of malaria has hinged, in part, on the use of insecticide-treated bed nets and spraying programs that target Anopheles gambiae mosquitoes.

Unfortunately, the mosquitoes are developing resistance to insecticides such as pyrethroid.

Wondering if they could defeat the mosquitoes by developing a new insecticide,a group of researchers set out to make blood meals toxic for Anopheles gambiae.

The team described their method in The Journal of Experimental Biology.

The researchers decided to target the mosquito glutamate gated chloride channel (AgGluCl), which is an essential component of the insect’s nervous system.

They generated antibodies that specifically targeted a portion of the protein exposed on the surface of nerves, a strategy they acknowledged was somewhat risky.

“Antibodies against a single mosquito antigen have never been shown to have mosquitocidal properties before, and the majority of previous research had focused on midgut antigens, while we were targeting a neuronal antigen expressed only in tissues found outside of the midgut,” said study author Jacob Meyers, a graduate student at Colorado State University in Fort Collins.

After injecting rabbits with a tiny portion of the surface of the AgGluCl protein channel, the researchers waited for the rabbits’ immune systems to begin producing antibodies tailored to the channel.

Then, the team collected the antibodies, mixed them with fresh blood, and fed the mixture to malaria-carrying mosquitoes (Anopheles gambiae), yellow fever-carrying mosquitoes (Aedes aegypti), and mosquitoes that carry the West Nile virus (Culex tarsalis).

Neither the yellow fever nor West Nile virus mosquitoes responded to the spiked blood. However, significant numbers of Anopheles gambiae mosquitoes died after consuming the blood/antibody cocktail. The highest antibody doses killed more than 90% of the insects within a day.

The researchers looked into why the yellow fever and West Nile virus mosquitoes had been immune to the antibodies and found the antibodies could not pass across the mosquitoes’ guts into the hemolymph. But the antibodies passed into the hemolymph of Anopheles gambiae mosquitoes with ease.

Intrigued by the antibodies’ mode of action, the researchers fed the insects a blood meal laced with the antibodies and a lethal dose of ivermectin, an insecticide that also targets the AgGluCl protein channel.

Then, the team monitored the mosquitoes’ survival to find out more about how the antibodies may destroy the insects. Mosquitoes that received ivermectin with the antibodies were more likely to survive than insects that received ivermectin alone.

“We believe that ivermectin is able to bind to AgGluCl,” Meyers said, “but the antibody keeps the channel from opening and becoming active.”

Having shown that antibodies targeted to the glutamate gated chloride channel in blood meals can be effective insecticides, the researchers are interested to find out if antibody-laced blood meals are equally deadly outside the lab.

First, though, the team plans to immunize cattle against the AgGluCl antigen and feed Anopheles gambiae on the immunized cattle in the lab. If the strategy proves successful, Meyers envisages a large-scale cattle immunization program as part of a combined attack on the malaria parasite.

Anopheles gambiae mosquito

Photo courtesy of the CDC

Recent progress in halting the spread of malaria has hinged, in part, on the use of insecticide-treated bed nets and spraying programs that target Anopheles gambiae mosquitoes.

Unfortunately, the mosquitoes are developing resistance to insecticides such as pyrethroid.

Wondering if they could defeat the mosquitoes by developing a new insecticide,a group of researchers set out to make blood meals toxic for Anopheles gambiae.

The team described their method in The Journal of Experimental Biology.

The researchers decided to target the mosquito glutamate gated chloride channel (AgGluCl), which is an essential component of the insect’s nervous system.

They generated antibodies that specifically targeted a portion of the protein exposed on the surface of nerves, a strategy they acknowledged was somewhat risky.

“Antibodies against a single mosquito antigen have never been shown to have mosquitocidal properties before, and the majority of previous research had focused on midgut antigens, while we were targeting a neuronal antigen expressed only in tissues found outside of the midgut,” said study author Jacob Meyers, a graduate student at Colorado State University in Fort Collins.

After injecting rabbits with a tiny portion of the surface of the AgGluCl protein channel, the researchers waited for the rabbits’ immune systems to begin producing antibodies tailored to the channel.

Then, the team collected the antibodies, mixed them with fresh blood, and fed the mixture to malaria-carrying mosquitoes (Anopheles gambiae), yellow fever-carrying mosquitoes (Aedes aegypti), and mosquitoes that carry the West Nile virus (Culex tarsalis).

Neither the yellow fever nor West Nile virus mosquitoes responded to the spiked blood. However, significant numbers of Anopheles gambiae mosquitoes died after consuming the blood/antibody cocktail. The highest antibody doses killed more than 90% of the insects within a day.

The researchers looked into why the yellow fever and West Nile virus mosquitoes had been immune to the antibodies and found the antibodies could not pass across the mosquitoes’ guts into the hemolymph. But the antibodies passed into the hemolymph of Anopheles gambiae mosquitoes with ease.

Intrigued by the antibodies’ mode of action, the researchers fed the insects a blood meal laced with the antibodies and a lethal dose of ivermectin, an insecticide that also targets the AgGluCl protein channel.

Then, the team monitored the mosquitoes’ survival to find out more about how the antibodies may destroy the insects. Mosquitoes that received ivermectin with the antibodies were more likely to survive than insects that received ivermectin alone.

“We believe that ivermectin is able to bind to AgGluCl,” Meyers said, “but the antibody keeps the channel from opening and becoming active.”

Having shown that antibodies targeted to the glutamate gated chloride channel in blood meals can be effective insecticides, the researchers are interested to find out if antibody-laced blood meals are equally deadly outside the lab.

First, though, the team plans to immunize cattle against the AgGluCl antigen and feed Anopheles gambiae on the immunized cattle in the lab. If the strategy proves successful, Meyers envisages a large-scale cattle immunization program as part of a combined attack on the malaria parasite.

Anopheles gambiae mosquito

Photo courtesy of the CDC

Recent progress in halting the spread of malaria has hinged, in part, on the use of insecticide-treated bed nets and spraying programs that target Anopheles gambiae mosquitoes.

Unfortunately, the mosquitoes are developing resistance to insecticides such as pyrethroid.

Wondering if they could defeat the mosquitoes by developing a new insecticide,a group of researchers set out to make blood meals toxic for Anopheles gambiae.

The team described their method in The Journal of Experimental Biology.

The researchers decided to target the mosquito glutamate gated chloride channel (AgGluCl), which is an essential component of the insect’s nervous system.

They generated antibodies that specifically targeted a portion of the protein exposed on the surface of nerves, a strategy they acknowledged was somewhat risky.

“Antibodies against a single mosquito antigen have never been shown to have mosquitocidal properties before, and the majority of previous research had focused on midgut antigens, while we were targeting a neuronal antigen expressed only in tissues found outside of the midgut,” said study author Jacob Meyers, a graduate student at Colorado State University in Fort Collins.

After injecting rabbits with a tiny portion of the surface of the AgGluCl protein channel, the researchers waited for the rabbits’ immune systems to begin producing antibodies tailored to the channel.

Then, the team collected the antibodies, mixed them with fresh blood, and fed the mixture to malaria-carrying mosquitoes (Anopheles gambiae), yellow fever-carrying mosquitoes (Aedes aegypti), and mosquitoes that carry the West Nile virus (Culex tarsalis).

Neither the yellow fever nor West Nile virus mosquitoes responded to the spiked blood. However, significant numbers of Anopheles gambiae mosquitoes died after consuming the blood/antibody cocktail. The highest antibody doses killed more than 90% of the insects within a day.

The researchers looked into why the yellow fever and West Nile virus mosquitoes had been immune to the antibodies and found the antibodies could not pass across the mosquitoes’ guts into the hemolymph. But the antibodies passed into the hemolymph of Anopheles gambiae mosquitoes with ease.

Intrigued by the antibodies’ mode of action, the researchers fed the insects a blood meal laced with the antibodies and a lethal dose of ivermectin, an insecticide that also targets the AgGluCl protein channel.

Then, the team monitored the mosquitoes’ survival to find out more about how the antibodies may destroy the insects. Mosquitoes that received ivermectin with the antibodies were more likely to survive than insects that received ivermectin alone.

“We believe that ivermectin is able to bind to AgGluCl,” Meyers said, “but the antibody keeps the channel from opening and becoming active.”

Having shown that antibodies targeted to the glutamate gated chloride channel in blood meals can be effective insecticides, the researchers are interested to find out if antibody-laced blood meals are equally deadly outside the lab.

First, though, the team plans to immunize cattle against the AgGluCl antigen and feed Anopheles gambiae on the immunized cattle in the lab. If the strategy proves successful, Meyers envisages a large-scale cattle immunization program as part of a combined attack on the malaria parasite.

Blood for transfusion

Photo courtesy of UAB Hospital

A computerized system that analyzes vital signs can help healthcare professionals more accurately diagnose trauma patients with life-threatening bleeding, according to research published in Shock.

The system, known as APPRAISE, simultaneously analyzes blood pressure, heart rate, and breathing patterns during emergency transport.

And investigators found that APPRAISE accurately detected most cases of life-threatening bleeding.

“Providing faster care to patients who are bleeding to death saves lives,” said study author Andrew Reisner, MD, of Massachusetts General Hospital in Boston.

“While the clinical information that ambulance crews call in to trauma centers was sufficient to determine the presence of a life-threatening hemorrhage in about half the patients we studied, many other patients were in a ‘gray area’ and may or may not have been at risk of bleeding to death.”

“Our study demonstrated that automated analysis of patients’ vital signs during prehospital transport was significantly better at discriminating between patients who did and did not have life-threatening hemorrhage.”

The APPRAISE system incorporates software based on statistical techniques currently used in stock market trading and manufacturing to determine whether particular data points represent real problems and not random fluctuations.

The system uses an ultracompact personal computer to analyze data gathered by a standard patient monitor used in emergency transport vehicles.

For this study, the system was installed in 2 MedFlight helicopters and collected data on more than 200 trauma patients transported to participating Boston hospitals from February 2010 to December 2012. So that patients’ care was not affected by a still-unproven system, the APPRAISE system’s analysis was not provided to MedFlight crews.

The researchers also analyzed information from a 2005 study of vital sign data gathered manually by a Houston-based air ambulance system.

The team found the APPRAISE system could identify, with 76% sensitivity, patients who needed 9 or more units of packed red blood cells within 24 hours.

This was significantly more sensitive (P<0.05) than any prehospital Shock Index of 1.4 or higher (59%), initial systolic blood pressure less than 110 mmHg (50%), and any prehospital systolic blood pressure less than 90 mmHg (50%).

However, there was no signficant difference between the different measures with regard to specificity for identifying patients who did not need a blood transfusion within 24 hours.

Specificity was 87% for APPRAISE, 88% for any Shock Index of 1.4 or higher, 88% for initial systolic blood pressure less than 110 mmHg, and 90% for any prehospital systolic blood pressure less than 90 mmHg.

Notifications provided by APPRAISE would have been available within 10 minutes of initial monitoring and a median of 20 minutes before patients arrived at the trauma centers.

“The fact that decisions to proceed with surgery or to replenish lost blood often occur only after patients’ arrival means there are delays—sometimes brief but sometimes prolonged—in initiating such life-saving interventions,” Dr Reisner said.

“We are now working on a follow-up study to use this system in actual trauma care and will be measuring whether it truly leads to faster treatment of life-threatening hemorrhage and better patient outcomes. This approach could also be helpful for patients transported by ground ambulance and for hospitalized patients at risk of unexpected hemorrhage, such as during recovery from major surgery.”

Blood for transfusion

Photo courtesy of UAB Hospital

A computerized system that analyzes vital signs can help healthcare professionals more accurately diagnose trauma patients with life-threatening bleeding, according to research published in Shock.

The system, known as APPRAISE, simultaneously analyzes blood pressure, heart rate, and breathing patterns during emergency transport.

And investigators found that APPRAISE accurately detected most cases of life-threatening bleeding.

“Providing faster care to patients who are bleeding to death saves lives,” said study author Andrew Reisner, MD, of Massachusetts General Hospital in Boston.

“While the clinical information that ambulance crews call in to trauma centers was sufficient to determine the presence of a life-threatening hemorrhage in about half the patients we studied, many other patients were in a ‘gray area’ and may or may not have been at risk of bleeding to death.”

“Our study demonstrated that automated analysis of patients’ vital signs during prehospital transport was significantly better at discriminating between patients who did and did not have life-threatening hemorrhage.”

The APPRAISE system incorporates software based on statistical techniques currently used in stock market trading and manufacturing to determine whether particular data points represent real problems and not random fluctuations.

The system uses an ultracompact personal computer to analyze data gathered by a standard patient monitor used in emergency transport vehicles.

For this study, the system was installed in 2 MedFlight helicopters and collected data on more than 200 trauma patients transported to participating Boston hospitals from February 2010 to December 2012. So that patients’ care was not affected by a still-unproven system, the APPRAISE system’s analysis was not provided to MedFlight crews.

The researchers also analyzed information from a 2005 study of vital sign data gathered manually by a Houston-based air ambulance system.

The team found the APPRAISE system could identify, with 76% sensitivity, patients who needed 9 or more units of packed red blood cells within 24 hours.

This was significantly more sensitive (P<0.05) than any prehospital Shock Index of 1.4 or higher (59%), initial systolic blood pressure less than 110 mmHg (50%), and any prehospital systolic blood pressure less than 90 mmHg (50%).

However, there was no signficant difference between the different measures with regard to specificity for identifying patients who did not need a blood transfusion within 24 hours.

Specificity was 87% for APPRAISE, 88% for any Shock Index of 1.4 or higher, 88% for initial systolic blood pressure less than 110 mmHg, and 90% for any prehospital systolic blood pressure less than 90 mmHg.

Notifications provided by APPRAISE would have been available within 10 minutes of initial monitoring and a median of 20 minutes before patients arrived at the trauma centers.

“The fact that decisions to proceed with surgery or to replenish lost blood often occur only after patients’ arrival means there are delays—sometimes brief but sometimes prolonged—in initiating such life-saving interventions,” Dr Reisner said.

“We are now working on a follow-up study to use this system in actual trauma care and will be measuring whether it truly leads to faster treatment of life-threatening hemorrhage and better patient outcomes. This approach could also be helpful for patients transported by ground ambulance and for hospitalized patients at risk of unexpected hemorrhage, such as during recovery from major surgery.”

Blood for transfusion

Photo courtesy of UAB Hospital

A computerized system that analyzes vital signs can help healthcare professionals more accurately diagnose trauma patients with life-threatening bleeding, according to research published in Shock.

The system, known as APPRAISE, simultaneously analyzes blood pressure, heart rate, and breathing patterns during emergency transport.

And investigators found that APPRAISE accurately detected most cases of life-threatening bleeding.

“Providing faster care to patients who are bleeding to death saves lives,” said study author Andrew Reisner, MD, of Massachusetts General Hospital in Boston.

“While the clinical information that ambulance crews call in to trauma centers was sufficient to determine the presence of a life-threatening hemorrhage in about half the patients we studied, many other patients were in a ‘gray area’ and may or may not have been at risk of bleeding to death.”

“Our study demonstrated that automated analysis of patients’ vital signs during prehospital transport was significantly better at discriminating between patients who did and did not have life-threatening hemorrhage.”

The APPRAISE system incorporates software based on statistical techniques currently used in stock market trading and manufacturing to determine whether particular data points represent real problems and not random fluctuations.

The system uses an ultracompact personal computer to analyze data gathered by a standard patient monitor used in emergency transport vehicles.

For this study, the system was installed in 2 MedFlight helicopters and collected data on more than 200 trauma patients transported to participating Boston hospitals from February 2010 to December 2012. So that patients’ care was not affected by a still-unproven system, the APPRAISE system’s analysis was not provided to MedFlight crews.

The researchers also analyzed information from a 2005 study of vital sign data gathered manually by a Houston-based air ambulance system.

The team found the APPRAISE system could identify, with 76% sensitivity, patients who needed 9 or more units of packed red blood cells within 24 hours.

This was significantly more sensitive (P<0.05) than any prehospital Shock Index of 1.4 or higher (59%), initial systolic blood pressure less than 110 mmHg (50%), and any prehospital systolic blood pressure less than 90 mmHg (50%).

However, there was no signficant difference between the different measures with regard to specificity for identifying patients who did not need a blood transfusion within 24 hours.

Specificity was 87% for APPRAISE, 88% for any Shock Index of 1.4 or higher, 88% for initial systolic blood pressure less than 110 mmHg, and 90% for any prehospital systolic blood pressure less than 90 mmHg.

Notifications provided by APPRAISE would have been available within 10 minutes of initial monitoring and a median of 20 minutes before patients arrived at the trauma centers.

“The fact that decisions to proceed with surgery or to replenish lost blood often occur only after patients’ arrival means there are delays—sometimes brief but sometimes prolonged—in initiating such life-saving interventions,” Dr Reisner said.

“We are now working on a follow-up study to use this system in actual trauma care and will be measuring whether it truly leads to faster treatment of life-threatening hemorrhage and better patient outcomes. This approach could also be helpful for patients transported by ground ambulance and for hospitalized patients at risk of unexpected hemorrhage, such as during recovery from major surgery.”

Bone marrow

Image by Daniel E. Sabath

Modified T cells derived from patients’ bone marrow can help treat multiple myeloma (MM), according to researchers.

They modified marrow-infiltrating lymphocytes (MILs) to target MM cells and administered them to patients following chemotherapy and hematopoietic stem cell transplant (HSCT).

Seven of the 22 patients treated achieved at least a 90% reduction in disease burden, which translated to an improvement in progression-free survival.

The researchers reported these results in Science Translational Medicine.

“What we learned in this small trial is that large numbers of activated MILs can selectively target and kill myeloma cells,” said Ivan Borrello, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Borrello and his colleagues set out to test the MILs in 25 patients with newly diagnosed (n=14) or relapsed (n=11) MM. The patients’ median age was 56 years (range, 30-71), 64% were male, and 82% were white.

The median number of prior treatments was 2.13 (range, 1-6). For this trial, the patients received high-dose melphalan, autologous HSCT, and MIL therapy.

Patient outcomes

Prior to HSCT, 14 patients had a partial response (PR, 64%), 3 had a very good PR (14%), 2 had a minor response (8%), and 3 had stable disease (SD, 14%). After HSCT, 7 patients were in complete response (CR, 32%), 6 had a PR (27%), 6 had SD (27%), and 3 had progressive disease (PD, 14%).

Patients received MILs when they obtained the maximal response to the last therapy. The researchers retrieved MILs from each patient’s bone marrow and expanded them with anti-CD3/CD28 beads plus interleukin-2.

Twenty-two patients received a median of 9.5×10⁸ MILs. Three patients relapsed before they could receive the MILs.

After MIL treatment, the overall response rate was 54%. Twenty-seven percent of patients achieved a CR, 27% had a PR, 23% had SD, and 14% had PD.

Patients who achieved at least a 90% reduction in disease burden (n=7) had superior progression-free survival compared to patients who did not respond as well to treatment (n=15).

The median progression-free survival was 25.1 months and 11.8 months, respectively (P=0.01). There was no significant difference between the groups with regard to overall survival.

The researchers said none of the patients experienced serious adverse events related to the MIL therapy.

Future directions

Dr Borrello said several US cancer centers have tested similar experimental treatments, but his team is believed to be the only one testing MILs. Other types of tumor-infiltrating cells can be used, but they are usually less plentiful in patients’ tumors and may not grow as well outside the body, he said.

“Typically, immune cells from solid tumors, called tumor-infiltrating lymphocytes, can be harvested and grown in only about 25% of patients who could potentially be eligible for the therapy,” said Kimberly Noonan, PhD, also of the Johns Hopkins University School of Medicine. “But in our clinical trial, we were able to harvest and grow MILs from all 22 patients.”

Dr Noonan said this small trial helped the researchers learn more about which patients may benefit from MIL therapy. For example, the team was able to determine how many of the MILs grown in the lab were specifically targeted to a patient’s tumor and whether they continued to target the tumor after being infused.

Additionally, the researchers found that patients with a high number of central memory cells before treatment had a better response to MIL therapy. Patients who began treatment with signs of an overactive immune response did not respond as well.

Dr Noonan said the team has used these data to guide 2 other ongoing trials of MILs. Those studies, she said, are trying to extend antitumor response and tumor specificity by combining the MILs with a cancer vaccine called GVAX and the drug lenalidomide, which stimulates T-cell responses.

All of the trials have also shed light on new ways to grow the MILs.

“In most of these trials, you see that the more cells you get, the better response you get in patients,” Dr Noonan said. “Learning how to improve cell growth may therefore improve the therapy.”

Researchers are also developing MILs to treat solid tumors such as lung, esophageal, and gastric cancers, as well as the pediatric cancers neuroblastoma and Ewing’s sarcoma.

Bone marrow

Image by Daniel E. Sabath

Modified T cells derived from patients’ bone marrow can help treat multiple myeloma (MM), according to researchers.

They modified marrow-infiltrating lymphocytes (MILs) to target MM cells and administered them to patients following chemotherapy and hematopoietic stem cell transplant (HSCT).

Seven of the 22 patients treated achieved at least a 90% reduction in disease burden, which translated to an improvement in progression-free survival.

The researchers reported these results in Science Translational Medicine.

“What we learned in this small trial is that large numbers of activated MILs can selectively target and kill myeloma cells,” said Ivan Borrello, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Borrello and his colleagues set out to test the MILs in 25 patients with newly diagnosed (n=14) or relapsed (n=11) MM. The patients’ median age was 56 years (range, 30-71), 64% were male, and 82% were white.

The median number of prior treatments was 2.13 (range, 1-6). For this trial, the patients received high-dose melphalan, autologous HSCT, and MIL therapy.

Patient outcomes

Prior to HSCT, 14 patients had a partial response (PR, 64%), 3 had a very good PR (14%), 2 had a minor response (8%), and 3 had stable disease (SD, 14%). After HSCT, 7 patients were in complete response (CR, 32%), 6 had a PR (27%), 6 had SD (27%), and 3 had progressive disease (PD, 14%).

Patients received MILs when they obtained the maximal response to the last therapy. The researchers retrieved MILs from each patient’s bone marrow and expanded them with anti-CD3/CD28 beads plus interleukin-2.

Twenty-two patients received a median of 9.5×10⁸ MILs. Three patients relapsed before they could receive the MILs.

After MIL treatment, the overall response rate was 54%. Twenty-seven percent of patients achieved a CR, 27% had a PR, 23% had SD, and 14% had PD.

Patients who achieved at least a 90% reduction in disease burden (n=7) had superior progression-free survival compared to patients who did not respond as well to treatment (n=15).

The median progression-free survival was 25.1 months and 11.8 months, respectively (P=0.01). There was no significant difference between the groups with regard to overall survival.

The researchers said none of the patients experienced serious adverse events related to the MIL therapy.

Future directions

Dr Borrello said several US cancer centers have tested similar experimental treatments, but his team is believed to be the only one testing MILs. Other types of tumor-infiltrating cells can be used, but they are usually less plentiful in patients’ tumors and may not grow as well outside the body, he said.

“Typically, immune cells from solid tumors, called tumor-infiltrating lymphocytes, can be harvested and grown in only about 25% of patients who could potentially be eligible for the therapy,” said Kimberly Noonan, PhD, also of the Johns Hopkins University School of Medicine. “But in our clinical trial, we were able to harvest and grow MILs from all 22 patients.”

Dr Noonan said this small trial helped the researchers learn more about which patients may benefit from MIL therapy. For example, the team was able to determine how many of the MILs grown in the lab were specifically targeted to a patient’s tumor and whether they continued to target the tumor after being infused.

Additionally, the researchers found that patients with a high number of central memory cells before treatment had a better response to MIL therapy. Patients who began treatment with signs of an overactive immune response did not respond as well.

Dr Noonan said the team has used these data to guide 2 other ongoing trials of MILs. Those studies, she said, are trying to extend antitumor response and tumor specificity by combining the MILs with a cancer vaccine called GVAX and the drug lenalidomide, which stimulates T-cell responses.

All of the trials have also shed light on new ways to grow the MILs.

“In most of these trials, you see that the more cells you get, the better response you get in patients,” Dr Noonan said. “Learning how to improve cell growth may therefore improve the therapy.”

Researchers are also developing MILs to treat solid tumors such as lung, esophageal, and gastric cancers, as well as the pediatric cancers neuroblastoma and Ewing’s sarcoma.

Bone marrow

Image by Daniel E. Sabath

Modified T cells derived from patients’ bone marrow can help treat multiple myeloma (MM), according to researchers.

They modified marrow-infiltrating lymphocytes (MILs) to target MM cells and administered them to patients following chemotherapy and hematopoietic stem cell transplant (HSCT).

Seven of the 22 patients treated achieved at least a 90% reduction in disease burden, which translated to an improvement in progression-free survival.

The researchers reported these results in Science Translational Medicine.

“What we learned in this small trial is that large numbers of activated MILs can selectively target and kill myeloma cells,” said Ivan Borrello, MD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Borrello and his colleagues set out to test the MILs in 25 patients with newly diagnosed (n=14) or relapsed (n=11) MM. The patients’ median age was 56 years (range, 30-71), 64% were male, and 82% were white.

The median number of prior treatments was 2.13 (range, 1-6). For this trial, the patients received high-dose melphalan, autologous HSCT, and MIL therapy.

Patient outcomes

Prior to HSCT, 14 patients had a partial response (PR, 64%), 3 had a very good PR (14%), 2 had a minor response (8%), and 3 had stable disease (SD, 14%). After HSCT, 7 patients were in complete response (CR, 32%), 6 had a PR (27%), 6 had SD (27%), and 3 had progressive disease (PD, 14%).

Patients received MILs when they obtained the maximal response to the last therapy. The researchers retrieved MILs from each patient’s bone marrow and expanded them with anti-CD3/CD28 beads plus interleukin-2.

Twenty-two patients received a median of 9.5×10⁸ MILs. Three patients relapsed before they could receive the MILs.

After MIL treatment, the overall response rate was 54%. Twenty-seven percent of patients achieved a CR, 27% had a PR, 23% had SD, and 14% had PD.

Patients who achieved at least a 90% reduction in disease burden (n=7) had superior progression-free survival compared to patients who did not respond as well to treatment (n=15).

The median progression-free survival was 25.1 months and 11.8 months, respectively (P=0.01). There was no significant difference between the groups with regard to overall survival.

The researchers said none of the patients experienced serious adverse events related to the MIL therapy.

Future directions

Dr Borrello said several US cancer centers have tested similar experimental treatments, but his team is believed to be the only one testing MILs. Other types of tumor-infiltrating cells can be used, but they are usually less plentiful in patients’ tumors and may not grow as well outside the body, he said.

“Typically, immune cells from solid tumors, called tumor-infiltrating lymphocytes, can be harvested and grown in only about 25% of patients who could potentially be eligible for the therapy,” said Kimberly Noonan, PhD, also of the Johns Hopkins University School of Medicine. “But in our clinical trial, we were able to harvest and grow MILs from all 22 patients.”

Dr Noonan said this small trial helped the researchers learn more about which patients may benefit from MIL therapy. For example, the team was able to determine how many of the MILs grown in the lab were specifically targeted to a patient’s tumor and whether they continued to target the tumor after being infused.

Additionally, the researchers found that patients with a high number of central memory cells before treatment had a better response to MIL therapy. Patients who began treatment with signs of an overactive immune response did not respond as well.

Dr Noonan said the team has used these data to guide 2 other ongoing trials of MILs. Those studies, she said, are trying to extend antitumor response and tumor specificity by combining the MILs with a cancer vaccine called GVAX and the drug lenalidomide, which stimulates T-cell responses.

All of the trials have also shed light on new ways to grow the MILs.

“In most of these trials, you see that the more cells you get, the better response you get in patients,” Dr Noonan said. “Learning how to improve cell growth may therefore improve the therapy.”

Researchers are also developing MILs to treat solid tumors such as lung, esophageal, and gastric cancers, as well as the pediatric cancers neuroblastoma and Ewing’s sarcoma.

Welcome to a new column about rural surgery! This quarterly feature will be a foray into the world of the rural surgeon by someone who has lived and worked in the rural milieu for many years. I want to bring to you a view of rural surgery from the “front lines.”

“Rural surgery: A view from the front lines” will be the second series about this timely topic published by ACS Surgery News. The first, “The Rural Surgeon” appeared in 2015 and was coordinated by Philip Caropreso, MD, FACS, a prominent and eloquent advocate for rural surgeons. The series was a great success. I was prevailed upon to begin another series. The goal for the new series is to delve into not only the important issues that rural surgeons face, but also to convey to readers who practice far from rural America what goes on in a rural practice.

Dr. Puls is a general surgeon in Alpena, Mich. He serves as vice chair of the ACS Advisory Council for Rural Surgery.

Welcome to a new column about rural surgery! This quarterly feature will be a foray into the world of the rural surgeon by someone who has lived and worked in the rural milieu for many years. I want to bring to you a view of rural surgery from the “front lines.”

“Rural surgery: A view from the front lines” will be the second series about this timely topic published by ACS Surgery News. The first, “The Rural Surgeon” appeared in 2015 and was coordinated by Philip Caropreso, MD, FACS, a prominent and eloquent advocate for rural surgeons. The series was a great success. I was prevailed upon to begin another series. The goal for the new series is to delve into not only the important issues that rural surgeons face, but also to convey to readers who practice far from rural America what goes on in a rural practice.

Dr. Puls is a general surgeon in Alpena, Mich. He serves as vice chair of the ACS Advisory Council for Rural Surgery.

Welcome to a new column about rural surgery! This quarterly feature will be a foray into the world of the rural surgeon by someone who has lived and worked in the rural milieu for many years. I want to bring to you a view of rural surgery from the “front lines.”

“Rural surgery: A view from the front lines” will be the second series about this timely topic published by ACS Surgery News. The first, “The Rural Surgeon” appeared in 2015 and was coordinated by Philip Caropreso, MD, FACS, a prominent and eloquent advocate for rural surgeons. The series was a great success. I was prevailed upon to begin another series. The goal for the new series is to delve into not only the important issues that rural surgeons face, but also to convey to readers who practice far from rural America what goes on in a rural practice.

Dr. Puls is a general surgeon in Alpena, Mich. He serves as vice chair of the ACS Advisory Council for Rural Surgery.

WASHINGTON – A new blood test could conclusively determine if a patient with chronic diarrhea has diarrhea-predominant irritable bowel syndrome (D-IBS).

The IBSchek blood test detects the presence of antibodies to cytolethal distending toxin B and vinculin. In a study presented at the annual Digestive Disease Week and published in PLoS ONE, the positive predictive value for D-IBS of just one of the antibodies was greater than 98%, explained study lead author Dr. Mark Pimentel of Cedars-Sinai Medical Center, Los Angeles. If the test is positive for both antibodies, “the post-test probability is 95% that you have IBS.”

In a video interview, Dr. Pimentel discussed the study’s findings and the potential impact for physicians and patients. The search for diagnostic answers leads to “a lot of doctor-shopping, certainly a lot of colonoscopies and unnecessary testing that are always negative with these patients,” he noted. “Maybe this will put an end to that.

“People used to think this is all psychological,” Dr. Pimentel added. “Now we can say, No, it’s organic. There’s something real going on; I’ve got a test that proves that.”

Dr. Pimentel has received consulting fees from Commonwealth Laboratories, which makes the IBSchek blood test.

[email protected]

WASHINGTON – A new blood test could conclusively determine if a patient with chronic diarrhea has diarrhea-predominant irritable bowel syndrome (D-IBS).

The IBSchek blood test detects the presence of antibodies to cytolethal distending toxin B and vinculin. In a study presented at the annual Digestive Disease Week and published in PLoS ONE, the positive predictive value for D-IBS of just one of the antibodies was greater than 98%, explained study lead author Dr. Mark Pimentel of Cedars-Sinai Medical Center, Los Angeles. If the test is positive for both antibodies, “the post-test probability is 95% that you have IBS.”

In a video interview, Dr. Pimentel discussed the study’s findings and the potential impact for physicians and patients. The search for diagnostic answers leads to “a lot of doctor-shopping, certainly a lot of colonoscopies and unnecessary testing that are always negative with these patients,” he noted. “Maybe this will put an end to that.

“People used to think this is all psychological,” Dr. Pimentel added. “Now we can say, No, it’s organic. There’s something real going on; I’ve got a test that proves that.”

Dr. Pimentel has received consulting fees from Commonwealth Laboratories, which makes the IBSchek blood test.

[email protected]

WASHINGTON – A new blood test could conclusively determine if a patient with chronic diarrhea has diarrhea-predominant irritable bowel syndrome (D-IBS).

The IBSchek blood test detects the presence of antibodies to cytolethal distending toxin B and vinculin. In a study presented at the annual Digestive Disease Week and published in PLoS ONE, the positive predictive value for D-IBS of just one of the antibodies was greater than 98%, explained study lead author Dr. Mark Pimentel of Cedars-Sinai Medical Center, Los Angeles. If the test is positive for both antibodies, “the post-test probability is 95% that you have IBS.”

In a video interview, Dr. Pimentel discussed the study’s findings and the potential impact for physicians and patients. The search for diagnostic answers leads to “a lot of doctor-shopping, certainly a lot of colonoscopies and unnecessary testing that are always negative with these patients,” he noted. “Maybe this will put an end to that.

“People used to think this is all psychological,” Dr. Pimentel added. “Now we can say, No, it’s organic. There’s something real going on; I’ve got a test that proves that.”

Dr. Pimentel has received consulting fees from Commonwealth Laboratories, which makes the IBSchek blood test.

[email protected]

The Autar scale is a successful tool for identifying orthopedic surgery patients at risk for deep vein thrombosis (DVT) – and can prevent DVT when patients follow prophylactic measures corresponding with their DVT risk level, according to researchers.

The study comprised 216 patients who were undergoing orthopedic surgery to the lower extremities in Henan, China. They were divided into a control group and an intervention group, consisting of 106 and 110 patients, respectively. Researchers used the Autar scale to assess the risk of a DVT occurring in all of the patients.

The scale is used mainly for evaluating the probability of DVT in a hospitalized patient undergoing surgery. It includes seven risk categories and 41 items, and is used to assign scores to patients indicating whether they are at no, low, moderate, or high risk of DVT.

Specific preventive measures were implemented among the intervention group’s members based on the Autar scale scores of each of these patients. The scores of patients in the control group were not used to implement DVT prophylaxis. Such patients, however, did receive routine nursing and mechanical and pharmacological prophylactic measures, if clinical experience and basic information caused their health care providers to identify them as being at high risk for DVT.

The Autar scale’s efficacy was confirmed by the fact that “the number of patients with DVT was in line with the number of high-risk patients in both groups,” according to Hui-Zhen Yin and Professor Ci-Ming Shan of Zhengzhou (China) University.

The numbers of DVTs that occurred in each group were significantly different from each other; 1.82% of patients in the intervention group got DVTs, compared to 9.43% of patients in the control group. Therefore, the study showed that the Autar scale is useful not only for predicting DVT, but also for preventing its incidence when patients receive the appropriate prophylactic and nursing interventions, the researchers noted.

They recommend wide use of the scale, because they believe it is “a comprehensive and valid instrument that improves the consistency of nursing assessment and creates a reference for preventing DVT in nursing practice.”

Read the full study in International Journal of Nursing Sciences (doi:10.1016/j.ijnss.2015.04.003).

The Autar scale is a successful tool for identifying orthopedic surgery patients at risk for deep vein thrombosis (DVT) – and can prevent DVT when patients follow prophylactic measures corresponding with their DVT risk level, according to researchers.

The study comprised 216 patients who were undergoing orthopedic surgery to the lower extremities in Henan, China. They were divided into a control group and an intervention group, consisting of 106 and 110 patients, respectively. Researchers used the Autar scale to assess the risk of a DVT occurring in all of the patients.

The scale is used mainly for evaluating the probability of DVT in a hospitalized patient undergoing surgery. It includes seven risk categories and 41 items, and is used to assign scores to patients indicating whether they are at no, low, moderate, or high risk of DVT.

Specific preventive measures were implemented among the intervention group’s members based on the Autar scale scores of each of these patients. The scores of patients in the control group were not used to implement DVT prophylaxis. Such patients, however, did receive routine nursing and mechanical and pharmacological prophylactic measures, if clinical experience and basic information caused their health care providers to identify them as being at high risk for DVT.

The Autar scale’s efficacy was confirmed by the fact that “the number of patients with DVT was in line with the number of high-risk patients in both groups,” according to Hui-Zhen Yin and Professor Ci-Ming Shan of Zhengzhou (China) University.

The numbers of DVTs that occurred in each group were significantly different from each other; 1.82% of patients in the intervention group got DVTs, compared to 9.43% of patients in the control group. Therefore, the study showed that the Autar scale is useful not only for predicting DVT, but also for preventing its incidence when patients receive the appropriate prophylactic and nursing interventions, the researchers noted.

They recommend wide use of the scale, because they believe it is “a comprehensive and valid instrument that improves the consistency of nursing assessment and creates a reference for preventing DVT in nursing practice.”

Read the full study in International Journal of Nursing Sciences (doi:10.1016/j.ijnss.2015.04.003).

The Autar scale is a successful tool for identifying orthopedic surgery patients at risk for deep vein thrombosis (DVT) – and can prevent DVT when patients follow prophylactic measures corresponding with their DVT risk level, according to researchers.

The study comprised 216 patients who were undergoing orthopedic surgery to the lower extremities in Henan, China. They were divided into a control group and an intervention group, consisting of 106 and 110 patients, respectively. Researchers used the Autar scale to assess the risk of a DVT occurring in all of the patients.

The scale is used mainly for evaluating the probability of DVT in a hospitalized patient undergoing surgery. It includes seven risk categories and 41 items, and is used to assign scores to patients indicating whether they are at no, low, moderate, or high risk of DVT.

Specific preventive measures were implemented among the intervention group’s members based on the Autar scale scores of each of these patients. The scores of patients in the control group were not used to implement DVT prophylaxis. Such patients, however, did receive routine nursing and mechanical and pharmacological prophylactic measures, if clinical experience and basic information caused their health care providers to identify them as being at high risk for DVT.

The Autar scale’s efficacy was confirmed by the fact that “the number of patients with DVT was in line with the number of high-risk patients in both groups,” according to Hui-Zhen Yin and Professor Ci-Ming Shan of Zhengzhou (China) University.

The numbers of DVTs that occurred in each group were significantly different from each other; 1.82% of patients in the intervention group got DVTs, compared to 9.43% of patients in the control group. Therefore, the study showed that the Autar scale is useful not only for predicting DVT, but also for preventing its incidence when patients receive the appropriate prophylactic and nursing interventions, the researchers noted.

They recommend wide use of the scale, because they believe it is “a comprehensive and valid instrument that improves the consistency of nursing assessment and creates a reference for preventing DVT in nursing practice.”

Read the full study in International Journal of Nursing Sciences (doi:10.1016/j.ijnss.2015.04.003).