SAN DIEGO – Visceral hypersensitivity may be an independent contributor to gastrointestinal symptoms in patients with functional GI disorders, a study showed.

The association was independent of the subjects’ tendency to report non-GI symptoms and independent of psychological distress.

iStockphoto.com

“We found a gradual increase in GI symptom severity related to hypersensitivity tertiles in irritable bowel syndrome and dyspepsia, and small but significant correlations between pain/discomfort thresholds and GI symptom severity across several large patient groups from different countries,” said presenting author Dr. Magnus Simren. “This association was independent of the tendency to report GI symptoms or comorbid anxiety and depression.”

The relationship between visceral hypersensitivity and GI symptoms has been questionable, with some studies suggesting an association between visceral hypersensitivity and symptom severity and pain in irritable bowel syndrome (IBS), dyspepsia, and other GI disorders.

However, some negative studies have failed to confirm this association, explained Dr. Simren. “The thinking is that reporting GI symptoms and severity of symptoms may reflect a general tendency to report symptoms that [are] explained by comorbid psychological stress,” he noted.

The study Dr. Simren presented at the annual Digestive Disease Week sought to determine the association between visceral hypersensitivity and GI symptoms and symptom severity, adjusted for psychological distress (anxiety and depression) as well as a tendency to report symptoms.

The study enrolled five patient cohorts with functional GI disorders at three different centers. Subjects underwent balloon distension (a validated method to determine GI hypersensitivity) and completed questionnaires to assess GI symptom severity, somatization, anxiety, and depression.

The five cohorts were the Belgian functional dyspepsia cohort (n = 242), IBS cohort 1 in the United States (n = 243), U.S. IBS cohort 2 (n = 159), Swedish IBS cohort 1 (n = 353), and Swedish IBS cohort 2 (n = 147). Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds.

Dr. Simren pointed out that the three different countries used questionnaires with subtle differences to measure GI symptoms, anxiety, and depression. Therefore, the total scores of all GI questionnaires were recalculated to z scores for comparisons.

The barostat protocols also differed among the three countries, and different pain thresholds were used, he noted.

For statistical analysis, sensitivity tertiles (low, medium, and high) were constructed based on pain/discomfort thresholds. GI symptom severity was compared between tertiles and adjusted for anxiety and depression as well as for non-GI symptom reporting.

Then GI hypersensitivity (high and low thresholds) was correlated with symptom severity total scores and pain/discomfort thresholds. Significant differences in GI symptom severity were found between high and low threshold hypersensitivity tertiles across all five cohorts. These differences remained after investigators controlled for the presence of anxiety or depression. The same association was seen when investigators controlled for reporting of non-GI symptoms.

Dr. Simren acknowledged that these barostat tests are used in a research setting. “But you can use this information in managing patients. We would need a simpler test for clinical utility,” he said.

“These findings confirm that visceral hypersensitivity is a contributor to symptom generation in functional GI disease,” Dr. Simren said.

SAN DIEGO – Visceral hypersensitivity may be an independent contributor to gastrointestinal symptoms in patients with functional GI disorders, a study showed.

The association was independent of the subjects’ tendency to report non-GI symptoms and independent of psychological distress.

iStockphoto.com

“We found a gradual increase in GI symptom severity related to hypersensitivity tertiles in irritable bowel syndrome and dyspepsia, and small but significant correlations between pain/discomfort thresholds and GI symptom severity across several large patient groups from different countries,” said presenting author Dr. Magnus Simren. “This association was independent of the tendency to report GI symptoms or comorbid anxiety and depression.”

The relationship between visceral hypersensitivity and GI symptoms has been questionable, with some studies suggesting an association between visceral hypersensitivity and symptom severity and pain in irritable bowel syndrome (IBS), dyspepsia, and other GI disorders.

However, some negative studies have failed to confirm this association, explained Dr. Simren. “The thinking is that reporting GI symptoms and severity of symptoms may reflect a general tendency to report symptoms that [are] explained by comorbid psychological stress,” he noted.

The study Dr. Simren presented at the annual Digestive Disease Week sought to determine the association between visceral hypersensitivity and GI symptoms and symptom severity, adjusted for psychological distress (anxiety and depression) as well as a tendency to report symptoms.

The study enrolled five patient cohorts with functional GI disorders at three different centers. Subjects underwent balloon distension (a validated method to determine GI hypersensitivity) and completed questionnaires to assess GI symptom severity, somatization, anxiety, and depression.

The five cohorts were the Belgian functional dyspepsia cohort (n = 242), IBS cohort 1 in the United States (n = 243), U.S. IBS cohort 2 (n = 159), Swedish IBS cohort 1 (n = 353), and Swedish IBS cohort 2 (n = 147). Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds.

Dr. Simren pointed out that the three different countries used questionnaires with subtle differences to measure GI symptoms, anxiety, and depression. Therefore, the total scores of all GI questionnaires were recalculated to z scores for comparisons.

The barostat protocols also differed among the three countries, and different pain thresholds were used, he noted.

For statistical analysis, sensitivity tertiles (low, medium, and high) were constructed based on pain/discomfort thresholds. GI symptom severity was compared between tertiles and adjusted for anxiety and depression as well as for non-GI symptom reporting.

Then GI hypersensitivity (high and low thresholds) was correlated with symptom severity total scores and pain/discomfort thresholds. Significant differences in GI symptom severity were found between high and low threshold hypersensitivity tertiles across all five cohorts. These differences remained after investigators controlled for the presence of anxiety or depression. The same association was seen when investigators controlled for reporting of non-GI symptoms.

Dr. Simren acknowledged that these barostat tests are used in a research setting. “But you can use this information in managing patients. We would need a simpler test for clinical utility,” he said.

“These findings confirm that visceral hypersensitivity is a contributor to symptom generation in functional GI disease,” Dr. Simren said.

SAN DIEGO – Visceral hypersensitivity may be an independent contributor to gastrointestinal symptoms in patients with functional GI disorders, a study showed.

The association was independent of the subjects’ tendency to report non-GI symptoms and independent of psychological distress.

iStockphoto.com

“We found a gradual increase in GI symptom severity related to hypersensitivity tertiles in irritable bowel syndrome and dyspepsia, and small but significant correlations between pain/discomfort thresholds and GI symptom severity across several large patient groups from different countries,” said presenting author Dr. Magnus Simren. “This association was independent of the tendency to report GI symptoms or comorbid anxiety and depression.”

The relationship between visceral hypersensitivity and GI symptoms has been questionable, with some studies suggesting an association between visceral hypersensitivity and symptom severity and pain in irritable bowel syndrome (IBS), dyspepsia, and other GI disorders.

However, some negative studies have failed to confirm this association, explained Dr. Simren. “The thinking is that reporting GI symptoms and severity of symptoms may reflect a general tendency to report symptoms that [are] explained by comorbid psychological stress,” he noted.

The study Dr. Simren presented at the annual Digestive Disease Week sought to determine the association between visceral hypersensitivity and GI symptoms and symptom severity, adjusted for psychological distress (anxiety and depression) as well as a tendency to report symptoms.

The study enrolled five patient cohorts with functional GI disorders at three different centers. Subjects underwent balloon distension (a validated method to determine GI hypersensitivity) and completed questionnaires to assess GI symptom severity, somatization, anxiety, and depression.

The five cohorts were the Belgian functional dyspepsia cohort (n = 242), IBS cohort 1 in the United States (n = 243), U.S. IBS cohort 2 (n = 159), Swedish IBS cohort 1 (n = 353), and Swedish IBS cohort 2 (n = 147). Subjects were divided into sensitivity tertiles based on pain/discomfort thresholds.

Dr. Simren pointed out that the three different countries used questionnaires with subtle differences to measure GI symptoms, anxiety, and depression. Therefore, the total scores of all GI questionnaires were recalculated to z scores for comparisons.

The barostat protocols also differed among the three countries, and different pain thresholds were used, he noted.

For statistical analysis, sensitivity tertiles (low, medium, and high) were constructed based on pain/discomfort thresholds. GI symptom severity was compared between tertiles and adjusted for anxiety and depression as well as for non-GI symptom reporting.

Then GI hypersensitivity (high and low thresholds) was correlated with symptom severity total scores and pain/discomfort thresholds. Significant differences in GI symptom severity were found between high and low threshold hypersensitivity tertiles across all five cohorts. These differences remained after investigators controlled for the presence of anxiety or depression. The same association was seen when investigators controlled for reporting of non-GI symptoms.

Dr. Simren acknowledged that these barostat tests are used in a research setting. “But you can use this information in managing patients. We would need a simpler test for clinical utility,” he said.

“These findings confirm that visceral hypersensitivity is a contributor to symptom generation in functional GI disease,” Dr. Simren said.

WASHINGTON – Sodium fluorescein is proving to be an excellent agent for helping to verify ureteral efflux during intraoperative cystoscopy, Dr. Jay Goldberg said at the annual meeting of the American College of Obstetricians and Gynecologists.

Dr. Goldberg said he first read about the use of the dye as an alternative to indigo carmine, which is no longer available, in a study published in 2015; the study reported good results with a 10% preparation of sodium fluorescein administered at 0.25-1 mL intravenously during intraoperative cystoscopy (Obstet Gynecol. 2015 Mar;125[3]:548-50).

Since then, he and his colleagues at Einstein Medical Center, Philadelphia, have been evaluating the use of 0.1 mL of 10% sodium fluorescein IV during cystoscopies performed at the end of gynecologic surgeries, measuring the time to visualization and the level of satisfaction with the dye.

Thus far, in more than 50 cases, the average time until colored ureteral jets were seen has been 4.3 minutes (a range of 2-6.8 minutes, consistent with the 2015 study). And according to questionnaires completed by each surgeon, the degree of certainty for visualizing the ureteral jets was improved with fluorescein (a rating of 5 on a 5-point scale, compared with 2.9 without the dye).

Compared with both indigo carmine and methylene blue, fluorescein was preferred, Dr. Goldberg reported, with surgeons citing quicker onset, better color contrast, cheaper cost, and fewer side effects.

“Given that it’s at least equivalent and probably better, and that it’s 50 times cheaper [than indigo carmine], even if indigo carmine comes back again, I’m certainly not going to be switching back,” Dr. Goldberg said during a seminar on cystoscopy after hysterectomy.

Intravenous sodium fluorescein is routinely used in ophthalmology in retinal angiography, at a dosage of 5 mL of 10% fluorescein, he said. The most common complications reported in the literature are nausea, vomiting, and flushing or rash (rates of 2.9%, 1.2%, and 0.5%, respectively, according to a 1991 report). None of their patients has experienced any complications, Dr. Goldberg said.

Methylene blue (50 mg IV over a period of 5 minutes) appears to have been a common go-to dye for gynecologic surgeons, along with pyridium (a 200-mg oral dose prior to surgery), ever since production of indigo carmine was discontinued because of a lack of raw material.

“But with methylene blue, it may take longer to see the blue urine efflux from the ureteral orifices,” Dr. Goldberg said. And with pyridium, “by the time cystoscopy is performed, the bladder will have already been stained orange, making it more difficult to see the same colored urine jets.”

“Sodium fluorescein is very quick in onset. I wait [to have it administered] until I am actually ready to insert the cystoscope,” he said.

And at 60 cents per dose, fluorescein is less expensive than methylene blue ($1.50) and significantly less expensive than indigo carmine ($30 a dose), he said.

Dr. Goldberg reported having no relevant financial conflicts.

WASHINGTON – Sodium fluorescein is proving to be an excellent agent for helping to verify ureteral efflux during intraoperative cystoscopy, Dr. Jay Goldberg said at the annual meeting of the American College of Obstetricians and Gynecologists.

Dr. Goldberg said he first read about the use of the dye as an alternative to indigo carmine, which is no longer available, in a study published in 2015; the study reported good results with a 10% preparation of sodium fluorescein administered at 0.25-1 mL intravenously during intraoperative cystoscopy (Obstet Gynecol. 2015 Mar;125[3]:548-50).

Since then, he and his colleagues at Einstein Medical Center, Philadelphia, have been evaluating the use of 0.1 mL of 10% sodium fluorescein IV during cystoscopies performed at the end of gynecologic surgeries, measuring the time to visualization and the level of satisfaction with the dye.

Thus far, in more than 50 cases, the average time until colored ureteral jets were seen has been 4.3 minutes (a range of 2-6.8 minutes, consistent with the 2015 study). And according to questionnaires completed by each surgeon, the degree of certainty for visualizing the ureteral jets was improved with fluorescein (a rating of 5 on a 5-point scale, compared with 2.9 without the dye).

Compared with both indigo carmine and methylene blue, fluorescein was preferred, Dr. Goldberg reported, with surgeons citing quicker onset, better color contrast, cheaper cost, and fewer side effects.

“Given that it’s at least equivalent and probably better, and that it’s 50 times cheaper [than indigo carmine], even if indigo carmine comes back again, I’m certainly not going to be switching back,” Dr. Goldberg said during a seminar on cystoscopy after hysterectomy.

Intravenous sodium fluorescein is routinely used in ophthalmology in retinal angiography, at a dosage of 5 mL of 10% fluorescein, he said. The most common complications reported in the literature are nausea, vomiting, and flushing or rash (rates of 2.9%, 1.2%, and 0.5%, respectively, according to a 1991 report). None of their patients has experienced any complications, Dr. Goldberg said.

Methylene blue (50 mg IV over a period of 5 minutes) appears to have been a common go-to dye for gynecologic surgeons, along with pyridium (a 200-mg oral dose prior to surgery), ever since production of indigo carmine was discontinued because of a lack of raw material.

“But with methylene blue, it may take longer to see the blue urine efflux from the ureteral orifices,” Dr. Goldberg said. And with pyridium, “by the time cystoscopy is performed, the bladder will have already been stained orange, making it more difficult to see the same colored urine jets.”

“Sodium fluorescein is very quick in onset. I wait [to have it administered] until I am actually ready to insert the cystoscope,” he said.

And at 60 cents per dose, fluorescein is less expensive than methylene blue ($1.50) and significantly less expensive than indigo carmine ($30 a dose), he said.

Dr. Goldberg reported having no relevant financial conflicts.

WASHINGTON – Sodium fluorescein is proving to be an excellent agent for helping to verify ureteral efflux during intraoperative cystoscopy, Dr. Jay Goldberg said at the annual meeting of the American College of Obstetricians and Gynecologists.

Dr. Goldberg said he first read about the use of the dye as an alternative to indigo carmine, which is no longer available, in a study published in 2015; the study reported good results with a 10% preparation of sodium fluorescein administered at 0.25-1 mL intravenously during intraoperative cystoscopy (Obstet Gynecol. 2015 Mar;125[3]:548-50).

Since then, he and his colleagues at Einstein Medical Center, Philadelphia, have been evaluating the use of 0.1 mL of 10% sodium fluorescein IV during cystoscopies performed at the end of gynecologic surgeries, measuring the time to visualization and the level of satisfaction with the dye.

Thus far, in more than 50 cases, the average time until colored ureteral jets were seen has been 4.3 minutes (a range of 2-6.8 minutes, consistent with the 2015 study). And according to questionnaires completed by each surgeon, the degree of certainty for visualizing the ureteral jets was improved with fluorescein (a rating of 5 on a 5-point scale, compared with 2.9 without the dye).

Compared with both indigo carmine and methylene blue, fluorescein was preferred, Dr. Goldberg reported, with surgeons citing quicker onset, better color contrast, cheaper cost, and fewer side effects.

“Given that it’s at least equivalent and probably better, and that it’s 50 times cheaper [than indigo carmine], even if indigo carmine comes back again, I’m certainly not going to be switching back,” Dr. Goldberg said during a seminar on cystoscopy after hysterectomy.

Intravenous sodium fluorescein is routinely used in ophthalmology in retinal angiography, at a dosage of 5 mL of 10% fluorescein, he said. The most common complications reported in the literature are nausea, vomiting, and flushing or rash (rates of 2.9%, 1.2%, and 0.5%, respectively, according to a 1991 report). None of their patients has experienced any complications, Dr. Goldberg said.

Methylene blue (50 mg IV over a period of 5 minutes) appears to have been a common go-to dye for gynecologic surgeons, along with pyridium (a 200-mg oral dose prior to surgery), ever since production of indigo carmine was discontinued because of a lack of raw material.

“But with methylene blue, it may take longer to see the blue urine efflux from the ureteral orifices,” Dr. Goldberg said. And with pyridium, “by the time cystoscopy is performed, the bladder will have already been stained orange, making it more difficult to see the same colored urine jets.”

“Sodium fluorescein is very quick in onset. I wait [to have it administered] until I am actually ready to insert the cystoscope,” he said.

And at 60 cents per dose, fluorescein is less expensive than methylene blue ($1.50) and significantly less expensive than indigo carmine ($30 a dose), he said.

Dr. Goldberg reported having no relevant financial conflicts.

Stem Cell Transplantation Is Safe in Hemorrhagic Stroke

Intraventricular transplantation using bone marrow mesenchymal stem cells is safe in patients with hemorrhagic stroke, according to research presented by Asra Al Fauzi, MD, a neurosurgeon at Soetomo General Hospital in Surabaya, Indonesia.

This study examined a group of eight patients with supratentorial hemorrhagic stroke. All patients had received six months of treatment and had stable neurologic deficits and NIH Stroke Scale (NIHSS) scores of five to 25. Clinical outcomes were measured using the NIHSS scale six months after transplantation. Bone marrow was aspirated and taken from the patient to whom it was to be administered under aseptic conditions. Expansion of mesenchymal stem cells took three to four weeks. All patients were administered a mean of 20 × 106 cells intraventricularly.

Results showed improvement of the NIHSS score in five patients after treatment; three patients had no change in status. No important adverse events associated with transplant or surgery were observed during a six-month follow up. The study demonstrates that bone marrow mesenchymal stem cell can be transplanted intraventricularly with excellent tolerance and without complications, said Dr. Al Fauzi. Stem cell transplantation aiming to restore function in stroke is safe and feasible. Further randomized controlled trials are needed to evaluate its efficacy.

How Does Surgery for Cerebral Arteriovenous Malformation Affect Pulsatility and Resistance?

Embolization reduces flow in cerebral arteriovenous malformations (AVMs) before surgical resection, but changes in pulsatility index (PI) and resistance index (RI) are unknown. Sophia F. Shakur, MD, a neurosurgery resident at the University of Chicago Medical Center, and colleagues measured PI and RI in AVM arterial feeders before and after embolization or surgery.

The researchers reviewed the records of patients who underwent AVM embolization and surgical resection at a single institution between 2007 and 2014.Patients who had PI, RI, and flows obtained using quantitative magnetic resonance angiography were retrospectively reviewed. Hemodynamic parameters were compared between the feeder and contralateral artery before and after embolization or surgery.

Thirty-two patients with 48 feeder arteries underwent embolization (mean 1.3 sessions). Another 32 patients with 49 feeder arteries had surgery with or without preoperative embolization. Before treatment, flow volume rate and mean, systolic and diastolic flow velocities were significantly higher in feeders versus contralateral counterparts. PI and RI were significantly lower in feeder vessels, compared with contralateral vessels. After embolization, mean, systolic, and diastolic flow velocities increased significantly, but PI and RI did not change significantly. However, after surgery, mean, systolic, and diastolic flow velocities within feeders decreased significantly, and PI and RI normalized to match the indices of their contralateral counterparts.

Following partial AVM embolization, PI and RI were unchanged, and flow velocities in feeder arteries increased significantly, likely due to redistribution of flow through residual nidus. Complete surgical resection resulted in normalization of PI and RI and a concomitant decrease in flow velocities.

Temporal Evolution of ICP and PRx May Have Prognostic Significance

Studies of large cohorts of patients with traumatic brain injury (TBI) have shown that intracranial pressure (ICP) and the pressure reactivity index (PRx) are independently associated with patient outcome. How these parameters evolve over the course of the stay in an intensive care unit, and the question of whether this evolution has any prognostic importance, has not been well studied, however.

Hadie Adams, MD, a postdoctoral fellow at Johns Hopkins School of Medicine in Baltimore, and colleagues monitored ICP and PRx in 573 patients with severe TBI in a regional neurocritical care unit. Data were calculated in 12-hour epochs for the first 168 hours (ie, seven days) after the time of incident. Data were stratified by the presence of diffuse TBI (dTBI) or space occupying lesions (SOL), as well as by fatal or nonfatal outcome at six months post injury. Mixed linear modeling was used to assess change of ICP and PRx over time to detect differences in mortality.

Mean ICP peaked at between 24 hours and 36 hours after injury, but only in patients who died. The difference in mean ICP between patients with fatal and nonfatal outcome was significant for the first 120 hours after ictus. For PRx, patients with a fatal outcome also had higher (ie, more impaired) PRx throughout the first 168 hours after ictus. The separation of ICP and PRx was greatest in the first 72 hours after ictus. Also, mean differences of ICP and PRx between the outcome groups were more pronounced in patients with dTBI than those with SOL.

In this cohort of 573 patients with TBI and high-resolution physiologic data, ICP and PRx displayed a distinctive temporal evolution. Importantly, early ICP and PRx allowed for the clearest prognostic delineation, said Dr. Adams.

The optimal thresholds, prognostic significance, and clinical correlations of ICP and PRx are likely to be time-dependent, he added.

How Common Is Position-Related Neuropraxia In Spine Surgery?

Gurpreet Surinder Gandhoke, MD, a neurosurgeon in Pittsburgh, and colleagues examined the incidence of position-related neuropraxia in 4,489 consecutive patients undergoing spine surgery at a university hospital. Some patients in the group had peripheral nerve injury from positioning. The authors observed intraoperative monitoring (IOM) changes related to arm and leg positioning and calculated their sensitivity and specificity in predicting the development of a new position-related peripheral nerve injury. Impact of length of surgery and other variables, including age, sex, BMI, diabetes, hypertension, coronary artery disease, cardiovascular disease, and a history of smoking on the development of a new peripheral nerve injury were defined.

Patients were in the following positions: arms abducted and flexed at the elbow (64.7%), arms tucked at the side (35%), and the lateral position (0.3%). Thirteen of 4,489 patients developed a new positioning-related peripheral nerve deficit, 54% developed meralgia paresthetica, and 46% developed ulnar neuropathy.

Seventy-two patients (1.6%) developed IOM changes from positioning, and all of these patients underwent a repositioning maneuver. One of these 72 patients (1.3%) developed a new position-related nerve deficit. Of the 98.4% of patients who did not develop position-related IOM changes, 0.3% developed a new position-related nerve deficit.

Sensitivity of IOM to detect a new position-related nerve deficit was 7.69%, and the specificity was 98.41%. Neither length of surgery nor any analyzed patient-related variable significantly affected the development of a new neuropraxia. The incidence of a new position-related nerve deficit in spine surgery was less than 0.3%. IOM had high specificity and low sensitivity in detecting a positioning-related deficit.

Stem Cell Transplantation Is Safe in Hemorrhagic Stroke

Intraventricular transplantation using bone marrow mesenchymal stem cells is safe in patients with hemorrhagic stroke, according to research presented by Asra Al Fauzi, MD, a neurosurgeon at Soetomo General Hospital in Surabaya, Indonesia.

This study examined a group of eight patients with supratentorial hemorrhagic stroke. All patients had received six months of treatment and had stable neurologic deficits and NIH Stroke Scale (NIHSS) scores of five to 25. Clinical outcomes were measured using the NIHSS scale six months after transplantation. Bone marrow was aspirated and taken from the patient to whom it was to be administered under aseptic conditions. Expansion of mesenchymal stem cells took three to four weeks. All patients were administered a mean of 20 × 106 cells intraventricularly.

Results showed improvement of the NIHSS score in five patients after treatment; three patients had no change in status. No important adverse events associated with transplant or surgery were observed during a six-month follow up. The study demonstrates that bone marrow mesenchymal stem cell can be transplanted intraventricularly with excellent tolerance and without complications, said Dr. Al Fauzi. Stem cell transplantation aiming to restore function in stroke is safe and feasible. Further randomized controlled trials are needed to evaluate its efficacy.

How Does Surgery for Cerebral Arteriovenous Malformation Affect Pulsatility and Resistance?

Embolization reduces flow in cerebral arteriovenous malformations (AVMs) before surgical resection, but changes in pulsatility index (PI) and resistance index (RI) are unknown. Sophia F. Shakur, MD, a neurosurgery resident at the University of Chicago Medical Center, and colleagues measured PI and RI in AVM arterial feeders before and after embolization or surgery.

The researchers reviewed the records of patients who underwent AVM embolization and surgical resection at a single institution between 2007 and 2014.Patients who had PI, RI, and flows obtained using quantitative magnetic resonance angiography were retrospectively reviewed. Hemodynamic parameters were compared between the feeder and contralateral artery before and after embolization or surgery.

Thirty-two patients with 48 feeder arteries underwent embolization (mean 1.3 sessions). Another 32 patients with 49 feeder arteries had surgery with or without preoperative embolization. Before treatment, flow volume rate and mean, systolic and diastolic flow velocities were significantly higher in feeders versus contralateral counterparts. PI and RI were significantly lower in feeder vessels, compared with contralateral vessels. After embolization, mean, systolic, and diastolic flow velocities increased significantly, but PI and RI did not change significantly. However, after surgery, mean, systolic, and diastolic flow velocities within feeders decreased significantly, and PI and RI normalized to match the indices of their contralateral counterparts.

Following partial AVM embolization, PI and RI were unchanged, and flow velocities in feeder arteries increased significantly, likely due to redistribution of flow through residual nidus. Complete surgical resection resulted in normalization of PI and RI and a concomitant decrease in flow velocities.

Temporal Evolution of ICP and PRx May Have Prognostic Significance

Studies of large cohorts of patients with traumatic brain injury (TBI) have shown that intracranial pressure (ICP) and the pressure reactivity index (PRx) are independently associated with patient outcome. How these parameters evolve over the course of the stay in an intensive care unit, and the question of whether this evolution has any prognostic importance, has not been well studied, however.

Hadie Adams, MD, a postdoctoral fellow at Johns Hopkins School of Medicine in Baltimore, and colleagues monitored ICP and PRx in 573 patients with severe TBI in a regional neurocritical care unit. Data were calculated in 12-hour epochs for the first 168 hours (ie, seven days) after the time of incident. Data were stratified by the presence of diffuse TBI (dTBI) or space occupying lesions (SOL), as well as by fatal or nonfatal outcome at six months post injury. Mixed linear modeling was used to assess change of ICP and PRx over time to detect differences in mortality.

Mean ICP peaked at between 24 hours and 36 hours after injury, but only in patients who died. The difference in mean ICP between patients with fatal and nonfatal outcome was significant for the first 120 hours after ictus. For PRx, patients with a fatal outcome also had higher (ie, more impaired) PRx throughout the first 168 hours after ictus. The separation of ICP and PRx was greatest in the first 72 hours after ictus. Also, mean differences of ICP and PRx between the outcome groups were more pronounced in patients with dTBI than those with SOL.

In this cohort of 573 patients with TBI and high-resolution physiologic data, ICP and PRx displayed a distinctive temporal evolution. Importantly, early ICP and PRx allowed for the clearest prognostic delineation, said Dr. Adams.

The optimal thresholds, prognostic significance, and clinical correlations of ICP and PRx are likely to be time-dependent, he added.

How Common Is Position-Related Neuropraxia In Spine Surgery?

Gurpreet Surinder Gandhoke, MD, a neurosurgeon in Pittsburgh, and colleagues examined the incidence of position-related neuropraxia in 4,489 consecutive patients undergoing spine surgery at a university hospital. Some patients in the group had peripheral nerve injury from positioning. The authors observed intraoperative monitoring (IOM) changes related to arm and leg positioning and calculated their sensitivity and specificity in predicting the development of a new position-related peripheral nerve injury. Impact of length of surgery and other variables, including age, sex, BMI, diabetes, hypertension, coronary artery disease, cardiovascular disease, and a history of smoking on the development of a new peripheral nerve injury were defined.

Patients were in the following positions: arms abducted and flexed at the elbow (64.7%), arms tucked at the side (35%), and the lateral position (0.3%). Thirteen of 4,489 patients developed a new positioning-related peripheral nerve deficit, 54% developed meralgia paresthetica, and 46% developed ulnar neuropathy.

Seventy-two patients (1.6%) developed IOM changes from positioning, and all of these patients underwent a repositioning maneuver. One of these 72 patients (1.3%) developed a new position-related nerve deficit. Of the 98.4% of patients who did not develop position-related IOM changes, 0.3% developed a new position-related nerve deficit.

Sensitivity of IOM to detect a new position-related nerve deficit was 7.69%, and the specificity was 98.41%. Neither length of surgery nor any analyzed patient-related variable significantly affected the development of a new neuropraxia. The incidence of a new position-related nerve deficit in spine surgery was less than 0.3%. IOM had high specificity and low sensitivity in detecting a positioning-related deficit.

Stem Cell Transplantation Is Safe in Hemorrhagic Stroke

Intraventricular transplantation using bone marrow mesenchymal stem cells is safe in patients with hemorrhagic stroke, according to research presented by Asra Al Fauzi, MD, a neurosurgeon at Soetomo General Hospital in Surabaya, Indonesia.

This study examined a group of eight patients with supratentorial hemorrhagic stroke. All patients had received six months of treatment and had stable neurologic deficits and NIH Stroke Scale (NIHSS) scores of five to 25. Clinical outcomes were measured using the NIHSS scale six months after transplantation. Bone marrow was aspirated and taken from the patient to whom it was to be administered under aseptic conditions. Expansion of mesenchymal stem cells took three to four weeks. All patients were administered a mean of 20 × 106 cells intraventricularly.

Results showed improvement of the NIHSS score in five patients after treatment; three patients had no change in status. No important adverse events associated with transplant or surgery were observed during a six-month follow up. The study demonstrates that bone marrow mesenchymal stem cell can be transplanted intraventricularly with excellent tolerance and without complications, said Dr. Al Fauzi. Stem cell transplantation aiming to restore function in stroke is safe and feasible. Further randomized controlled trials are needed to evaluate its efficacy.

How Does Surgery for Cerebral Arteriovenous Malformation Affect Pulsatility and Resistance?

Embolization reduces flow in cerebral arteriovenous malformations (AVMs) before surgical resection, but changes in pulsatility index (PI) and resistance index (RI) are unknown. Sophia F. Shakur, MD, a neurosurgery resident at the University of Chicago Medical Center, and colleagues measured PI and RI in AVM arterial feeders before and after embolization or surgery.

The researchers reviewed the records of patients who underwent AVM embolization and surgical resection at a single institution between 2007 and 2014.Patients who had PI, RI, and flows obtained using quantitative magnetic resonance angiography were retrospectively reviewed. Hemodynamic parameters were compared between the feeder and contralateral artery before and after embolization or surgery.

Thirty-two patients with 48 feeder arteries underwent embolization (mean 1.3 sessions). Another 32 patients with 49 feeder arteries had surgery with or without preoperative embolization. Before treatment, flow volume rate and mean, systolic and diastolic flow velocities were significantly higher in feeders versus contralateral counterparts. PI and RI were significantly lower in feeder vessels, compared with contralateral vessels. After embolization, mean, systolic, and diastolic flow velocities increased significantly, but PI and RI did not change significantly. However, after surgery, mean, systolic, and diastolic flow velocities within feeders decreased significantly, and PI and RI normalized to match the indices of their contralateral counterparts.

Following partial AVM embolization, PI and RI were unchanged, and flow velocities in feeder arteries increased significantly, likely due to redistribution of flow through residual nidus. Complete surgical resection resulted in normalization of PI and RI and a concomitant decrease in flow velocities.

Temporal Evolution of ICP and PRx May Have Prognostic Significance

Studies of large cohorts of patients with traumatic brain injury (TBI) have shown that intracranial pressure (ICP) and the pressure reactivity index (PRx) are independently associated with patient outcome. How these parameters evolve over the course of the stay in an intensive care unit, and the question of whether this evolution has any prognostic importance, has not been well studied, however.

Hadie Adams, MD, a postdoctoral fellow at Johns Hopkins School of Medicine in Baltimore, and colleagues monitored ICP and PRx in 573 patients with severe TBI in a regional neurocritical care unit. Data were calculated in 12-hour epochs for the first 168 hours (ie, seven days) after the time of incident. Data were stratified by the presence of diffuse TBI (dTBI) or space occupying lesions (SOL), as well as by fatal or nonfatal outcome at six months post injury. Mixed linear modeling was used to assess change of ICP and PRx over time to detect differences in mortality.

Mean ICP peaked at between 24 hours and 36 hours after injury, but only in patients who died. The difference in mean ICP between patients with fatal and nonfatal outcome was significant for the first 120 hours after ictus. For PRx, patients with a fatal outcome also had higher (ie, more impaired) PRx throughout the first 168 hours after ictus. The separation of ICP and PRx was greatest in the first 72 hours after ictus. Also, mean differences of ICP and PRx between the outcome groups were more pronounced in patients with dTBI than those with SOL.

In this cohort of 573 patients with TBI and high-resolution physiologic data, ICP and PRx displayed a distinctive temporal evolution. Importantly, early ICP and PRx allowed for the clearest prognostic delineation, said Dr. Adams.

The optimal thresholds, prognostic significance, and clinical correlations of ICP and PRx are likely to be time-dependent, he added.

How Common Is Position-Related Neuropraxia In Spine Surgery?

Gurpreet Surinder Gandhoke, MD, a neurosurgeon in Pittsburgh, and colleagues examined the incidence of position-related neuropraxia in 4,489 consecutive patients undergoing spine surgery at a university hospital. Some patients in the group had peripheral nerve injury from positioning. The authors observed intraoperative monitoring (IOM) changes related to arm and leg positioning and calculated their sensitivity and specificity in predicting the development of a new position-related peripheral nerve injury. Impact of length of surgery and other variables, including age, sex, BMI, diabetes, hypertension, coronary artery disease, cardiovascular disease, and a history of smoking on the development of a new peripheral nerve injury were defined.

Patients were in the following positions: arms abducted and flexed at the elbow (64.7%), arms tucked at the side (35%), and the lateral position (0.3%). Thirteen of 4,489 patients developed a new positioning-related peripheral nerve deficit, 54% developed meralgia paresthetica, and 46% developed ulnar neuropathy.

Seventy-two patients (1.6%) developed IOM changes from positioning, and all of these patients underwent a repositioning maneuver. One of these 72 patients (1.3%) developed a new position-related nerve deficit. Of the 98.4% of patients who did not develop position-related IOM changes, 0.3% developed a new position-related nerve deficit.

Sensitivity of IOM to detect a new position-related nerve deficit was 7.69%, and the specificity was 98.41%. Neither length of surgery nor any analyzed patient-related variable significantly affected the development of a new neuropraxia. The incidence of a new position-related nerve deficit in spine surgery was less than 0.3%. IOM had high specificity and low sensitivity in detecting a positioning-related deficit.

Obeticholic acid (Ocaliva) has been granted accelerated approval for use in combination with ursodeoxycholic acid (UDCA) for the treatment of primary biliary cholangitis in adults with an inadequate response to UDCA, and for use as a single therapy in adults unable to tolerate UDCA, the U.S. Food and Drug Administration announced.

Obeticholic acid should not be used in patients with complete biliary obstruction.

Given orally, obeticholic acid binds to the farnesoid X receptor (FXR), a receptor found in cells of the liver and intestine. FXR is a key regulator of bile acid metabolic pathways. Obeticholic acid increases bile flow from the liver and suppresses bile acid production in the liver, thus reducing exposure to toxic levels of bile acids.

Obeticholic acid was shown to reduce levels of alkaline phosphatase, which was used as a surrogate endpoint to predict clinical benefit, including an improvement in transplant-free survival. The FDA’s accelerated approval program allows approval based on a surrogate endpoint that is reasonably likely to predict clinical benefit. The manufacturer will conduct confirmatory clinical trials to examine any improvements in survival, progression to cirrhosis, or other disease-related symptoms.

After 12 months, in a controlled clinical trial with 216 participants, the proportion of participants achieving reductions in levels of alkaline phosphatase was higher among treated participants than in participants given placebo. Pruritus, fatigue, abdominal pain and discomfort, arthralgia, oropharyngeal pain, dizziness, and constipation were the drug’s most common side effects in the study.

Obeticholic acid is manufactured by Intercept Pharmaceuticals.

[email protected]

Obeticholic acid (Ocaliva) has been granted accelerated approval for use in combination with ursodeoxycholic acid (UDCA) for the treatment of primary biliary cholangitis in adults with an inadequate response to UDCA, and for use as a single therapy in adults unable to tolerate UDCA, the U.S. Food and Drug Administration announced.

Obeticholic acid should not be used in patients with complete biliary obstruction.

Given orally, obeticholic acid binds to the farnesoid X receptor (FXR), a receptor found in cells of the liver and intestine. FXR is a key regulator of bile acid metabolic pathways. Obeticholic acid increases bile flow from the liver and suppresses bile acid production in the liver, thus reducing exposure to toxic levels of bile acids.

Obeticholic acid was shown to reduce levels of alkaline phosphatase, which was used as a surrogate endpoint to predict clinical benefit, including an improvement in transplant-free survival. The FDA’s accelerated approval program allows approval based on a surrogate endpoint that is reasonably likely to predict clinical benefit. The manufacturer will conduct confirmatory clinical trials to examine any improvements in survival, progression to cirrhosis, or other disease-related symptoms.

After 12 months, in a controlled clinical trial with 216 participants, the proportion of participants achieving reductions in levels of alkaline phosphatase was higher among treated participants than in participants given placebo. Pruritus, fatigue, abdominal pain and discomfort, arthralgia, oropharyngeal pain, dizziness, and constipation were the drug’s most common side effects in the study.

Obeticholic acid is manufactured by Intercept Pharmaceuticals.

[email protected]

Obeticholic acid (Ocaliva) has been granted accelerated approval for use in combination with ursodeoxycholic acid (UDCA) for the treatment of primary biliary cholangitis in adults with an inadequate response to UDCA, and for use as a single therapy in adults unable to tolerate UDCA, the U.S. Food and Drug Administration announced.

Obeticholic acid should not be used in patients with complete biliary obstruction.

Given orally, obeticholic acid binds to the farnesoid X receptor (FXR), a receptor found in cells of the liver and intestine. FXR is a key regulator of bile acid metabolic pathways. Obeticholic acid increases bile flow from the liver and suppresses bile acid production in the liver, thus reducing exposure to toxic levels of bile acids.

Obeticholic acid was shown to reduce levels of alkaline phosphatase, which was used as a surrogate endpoint to predict clinical benefit, including an improvement in transplant-free survival. The FDA’s accelerated approval program allows approval based on a surrogate endpoint that is reasonably likely to predict clinical benefit. The manufacturer will conduct confirmatory clinical trials to examine any improvements in survival, progression to cirrhosis, or other disease-related symptoms.

After 12 months, in a controlled clinical trial with 216 participants, the proportion of participants achieving reductions in levels of alkaline phosphatase was higher among treated participants than in participants given placebo. Pruritus, fatigue, abdominal pain and discomfort, arthralgia, oropharyngeal pain, dizziness, and constipation were the drug’s most common side effects in the study.

Obeticholic acid is manufactured by Intercept Pharmaceuticals.

[email protected]

PARIS – The first-ever study of the long-term durability of transcatheter bioprosthetic aortic valves has documented a disturbing rise in the valve degeneration rate occurring 5-7 years post implant.

Prior consistently reassuring follow-up studies have been intermediate in length, with a maximum of 5 years. The PARTNER 2A trial, which generated enormous enthusiasm for moving TAVR to intermediate-risk patients on the basis of positive results presented at the 2016 meeting of the American College of Cardiology, reported 2-year results.

Bruce Jancin/Frontline Medical News

“We found, as have others, that there’s very little degeneration in the first 4 years: 94% freedom from degeneration. But at 6 years, it’s 82%, and we estimate that by 8 years, it’s about 50%,” Dr. Danny Dvir reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

“We need to be cautious: This is our first look at the data. But we have a signal for a problem,” said Dr. Dvir of St. Paul’s Hospital in Vancouver.

He presented a retrospective study of 378 patients who underwent TAVR 5-14 years ago at two pioneering centers for the procedure: St. Paul’s and Charles Nicolle Hospital in Rouen, France. Patients’ average age at the time of TAVR was 82.3 years, with an STS score of 8.3%. The study featured serial echocardiography conducted during house calls in this frail elderly population.

Thirty-five patients developed prosthetic valve degeneration, defined by at least moderate regurgitation and/or a mean gradient of at least 20 mm Hg in 23 cases and stenosis in 12. The risk of degeneration was unrelated to the use of warfarin, a finding that suggests the valve deterioration issue is unrelated to clotting. The strongest risk factor for transcatheter valve degeneration in this study was baseline renal failure at the time of TAVR.

Dr. Dvir’s presentation was the talk of the meeting, and it cast a pall over the proceedings. The red flag raised by the study regarding valve durability has major implications regarding the current enthusiasm among many interventional cardiologists to routinely extend TAVR to intermediate and even lower-risk patients. As one audience member later confessed, “I have felt sick since hearing that presentation.”

Bruce Jancin/Frontline Medical News

Discussant Dr. A. Pieter Kappetein observed that transcatheter heart valve durability was a hot topic of discussion about 4 years ago but subsequently faded below the radar as a concern – until Dr. Dvir’s study.

“This is a very important study that puts transcatheter heart valve implantation in a little bit different light,” said Dr. Kappetein, professor of cardiothoracic surgery at Erasmus University in Rotterdam, the Netherlands.

He noted that the surgical aortic valve replacement (SAVR) literature shows that the rate of structural valve deterioration is age related. It’s higher in 75-year-olds than in 85-year-olds, and higher still in 65-year-olds.

“Valve degeneration didn’t play a major role when we were doing TAVR in 80- and 85-year-olds because of their limited life expectancy, but it will play a role in younger patients. So I think we have to be careful before we move toward lower-risk patients,” the surgeon continued.

Dr. Jean-Francois Obadia, who performs both SAVR and TAVR, noted that the median duration of freedom from valve degeneration for Edwards Lifescience’s Carpentier surgical aortic valve is a hefty 17.9 years.

“This should be the gold standard,” declared Dr. Obadia, head of the department of adult cardiovascular surgery and heart transplantation at the Louis Pradel Cardiothoracic Hospital of Claude Bernard University in Lyon, France.

“Dr. Dvir’s study is one of the key messages we all should take back home: a 50% rate of valve deterioration at 8 years. Valve deterioration is the Achilles’ heel of bioprostheses. There is a lot of improvement left to do for the TAVR,” he said.

Dr. Dvir and others were quick to note that his long-term study was of necessity restricted to early-generation, balloon-expandable devices: the Cribier Edwards, Edwards Sapien, and Sapien XT valves. Contemporary valves, patient selection methods, and procedural techniques are far advanced in comparison.

“The Sapien 3 has much less paravalvular leakage than earlier-generation valves. Maybe with less paravalvular leakage and better hemodynamics there will be a decreased rate of degeneration. It could be. We need to see. We have to wait a few more years to see if later-generation transcatheter heart valves are more durable,” Dr. Dvir said.

To gain a better understanding of the full dimensions of the valve degeneration issue, he and his coinvestigators have formed the VALID (VAlve Long-term Durability International Data) registry. Operators interested in contributing patients to what is hoped will be a very large and informative data base are encouraged to contact Dr. Dvir ([email protected]).

In the meantime, he has reservations about extending TAVR to intermediate-risk patients outside of the rigorous clinical trial setting. He added that he’d feel far more comfortable in performing TAVR in intermediate-risk 70- to 75-year-olds if there was a tried and true valve-in-valve replacement method, something that doesn’t yet exist. The major limitation of current attempts at valve-in-valve replacement is underexpansion because the former valve doesn’t allow sufficient room for the new one to expand fully, resulting in residual stenosis.

“If you tell me that you can implant a platform that will enable a safe valve-in-valve procedure in 5, 7, 10 years – a less invasive bailout for a failed prosthetic valve – if you can do that safely and effectively I would be more keen to do TAVR even in a young patient,” the interventional cardiologist said.

He and others are working on this unmet need. Dr. Dvir’s novel valve, being developed with Edwards Lifesciences, has performed well in valve-in-valve procedures in cadavers and animals. The first clinical trials are being planned.

“We need to think always that a bioprosthetic valve is not a cure, it’s a palliation. We treat the patients, they feel better, but we leave them with some kind of a chronic disease that’s prone to thrombosis, prone to degeneration and failure, prone to many different things,” he reflected.

The study was conducted without commercial support. Dr. Dvir reported serving as a consultant to Edwards Lifesciences, Medtronic, and St. Jude Medical.

[email protected]

PARIS – The first-ever study of the long-term durability of transcatheter bioprosthetic aortic valves has documented a disturbing rise in the valve degeneration rate occurring 5-7 years post implant.

Prior consistently reassuring follow-up studies have been intermediate in length, with a maximum of 5 years. The PARTNER 2A trial, which generated enormous enthusiasm for moving TAVR to intermediate-risk patients on the basis of positive results presented at the 2016 meeting of the American College of Cardiology, reported 2-year results.

Bruce Jancin/Frontline Medical News

“We found, as have others, that there’s very little degeneration in the first 4 years: 94% freedom from degeneration. But at 6 years, it’s 82%, and we estimate that by 8 years, it’s about 50%,” Dr. Danny Dvir reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

“We need to be cautious: This is our first look at the data. But we have a signal for a problem,” said Dr. Dvir of St. Paul’s Hospital in Vancouver.

He presented a retrospective study of 378 patients who underwent TAVR 5-14 years ago at two pioneering centers for the procedure: St. Paul’s and Charles Nicolle Hospital in Rouen, France. Patients’ average age at the time of TAVR was 82.3 years, with an STS score of 8.3%. The study featured serial echocardiography conducted during house calls in this frail elderly population.

Thirty-five patients developed prosthetic valve degeneration, defined by at least moderate regurgitation and/or a mean gradient of at least 20 mm Hg in 23 cases and stenosis in 12. The risk of degeneration was unrelated to the use of warfarin, a finding that suggests the valve deterioration issue is unrelated to clotting. The strongest risk factor for transcatheter valve degeneration in this study was baseline renal failure at the time of TAVR.

Dr. Dvir’s presentation was the talk of the meeting, and it cast a pall over the proceedings. The red flag raised by the study regarding valve durability has major implications regarding the current enthusiasm among many interventional cardiologists to routinely extend TAVR to intermediate and even lower-risk patients. As one audience member later confessed, “I have felt sick since hearing that presentation.”

Bruce Jancin/Frontline Medical News

Discussant Dr. A. Pieter Kappetein observed that transcatheter heart valve durability was a hot topic of discussion about 4 years ago but subsequently faded below the radar as a concern – until Dr. Dvir’s study.

“This is a very important study that puts transcatheter heart valve implantation in a little bit different light,” said Dr. Kappetein, professor of cardiothoracic surgery at Erasmus University in Rotterdam, the Netherlands.

He noted that the surgical aortic valve replacement (SAVR) literature shows that the rate of structural valve deterioration is age related. It’s higher in 75-year-olds than in 85-year-olds, and higher still in 65-year-olds.

“Valve degeneration didn’t play a major role when we were doing TAVR in 80- and 85-year-olds because of their limited life expectancy, but it will play a role in younger patients. So I think we have to be careful before we move toward lower-risk patients,” the surgeon continued.

Dr. Jean-Francois Obadia, who performs both SAVR and TAVR, noted that the median duration of freedom from valve degeneration for Edwards Lifescience’s Carpentier surgical aortic valve is a hefty 17.9 years.

“This should be the gold standard,” declared Dr. Obadia, head of the department of adult cardiovascular surgery and heart transplantation at the Louis Pradel Cardiothoracic Hospital of Claude Bernard University in Lyon, France.

“Dr. Dvir’s study is one of the key messages we all should take back home: a 50% rate of valve deterioration at 8 years. Valve deterioration is the Achilles’ heel of bioprostheses. There is a lot of improvement left to do for the TAVR,” he said.

Dr. Dvir and others were quick to note that his long-term study was of necessity restricted to early-generation, balloon-expandable devices: the Cribier Edwards, Edwards Sapien, and Sapien XT valves. Contemporary valves, patient selection methods, and procedural techniques are far advanced in comparison.

“The Sapien 3 has much less paravalvular leakage than earlier-generation valves. Maybe with less paravalvular leakage and better hemodynamics there will be a decreased rate of degeneration. It could be. We need to see. We have to wait a few more years to see if later-generation transcatheter heart valves are more durable,” Dr. Dvir said.

To gain a better understanding of the full dimensions of the valve degeneration issue, he and his coinvestigators have formed the VALID (VAlve Long-term Durability International Data) registry. Operators interested in contributing patients to what is hoped will be a very large and informative data base are encouraged to contact Dr. Dvir ([email protected]).

In the meantime, he has reservations about extending TAVR to intermediate-risk patients outside of the rigorous clinical trial setting. He added that he’d feel far more comfortable in performing TAVR in intermediate-risk 70- to 75-year-olds if there was a tried and true valve-in-valve replacement method, something that doesn’t yet exist. The major limitation of current attempts at valve-in-valve replacement is underexpansion because the former valve doesn’t allow sufficient room for the new one to expand fully, resulting in residual stenosis.

“If you tell me that you can implant a platform that will enable a safe valve-in-valve procedure in 5, 7, 10 years – a less invasive bailout for a failed prosthetic valve – if you can do that safely and effectively I would be more keen to do TAVR even in a young patient,” the interventional cardiologist said.

He and others are working on this unmet need. Dr. Dvir’s novel valve, being developed with Edwards Lifesciences, has performed well in valve-in-valve procedures in cadavers and animals. The first clinical trials are being planned.

“We need to think always that a bioprosthetic valve is not a cure, it’s a palliation. We treat the patients, they feel better, but we leave them with some kind of a chronic disease that’s prone to thrombosis, prone to degeneration and failure, prone to many different things,” he reflected.

The study was conducted without commercial support. Dr. Dvir reported serving as a consultant to Edwards Lifesciences, Medtronic, and St. Jude Medical.

[email protected]

PARIS – The first-ever study of the long-term durability of transcatheter bioprosthetic aortic valves has documented a disturbing rise in the valve degeneration rate occurring 5-7 years post implant.

Prior consistently reassuring follow-up studies have been intermediate in length, with a maximum of 5 years. The PARTNER 2A trial, which generated enormous enthusiasm for moving TAVR to intermediate-risk patients on the basis of positive results presented at the 2016 meeting of the American College of Cardiology, reported 2-year results.

Bruce Jancin/Frontline Medical News

“We found, as have others, that there’s very little degeneration in the first 4 years: 94% freedom from degeneration. But at 6 years, it’s 82%, and we estimate that by 8 years, it’s about 50%,” Dr. Danny Dvir reported at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.

“We need to be cautious: This is our first look at the data. But we have a signal for a problem,” said Dr. Dvir of St. Paul’s Hospital in Vancouver.

He presented a retrospective study of 378 patients who underwent TAVR 5-14 years ago at two pioneering centers for the procedure: St. Paul’s and Charles Nicolle Hospital in Rouen, France. Patients’ average age at the time of TAVR was 82.3 years, with an STS score of 8.3%. The study featured serial echocardiography conducted during house calls in this frail elderly population.

Thirty-five patients developed prosthetic valve degeneration, defined by at least moderate regurgitation and/or a mean gradient of at least 20 mm Hg in 23 cases and stenosis in 12. The risk of degeneration was unrelated to the use of warfarin, a finding that suggests the valve deterioration issue is unrelated to clotting. The strongest risk factor for transcatheter valve degeneration in this study was baseline renal failure at the time of TAVR.

Dr. Dvir’s presentation was the talk of the meeting, and it cast a pall over the proceedings. The red flag raised by the study regarding valve durability has major implications regarding the current enthusiasm among many interventional cardiologists to routinely extend TAVR to intermediate and even lower-risk patients. As one audience member later confessed, “I have felt sick since hearing that presentation.”

Bruce Jancin/Frontline Medical News

Discussant Dr. A. Pieter Kappetein observed that transcatheter heart valve durability was a hot topic of discussion about 4 years ago but subsequently faded below the radar as a concern – until Dr. Dvir’s study.

“This is a very important study that puts transcatheter heart valve implantation in a little bit different light,” said Dr. Kappetein, professor of cardiothoracic surgery at Erasmus University in Rotterdam, the Netherlands.

He noted that the surgical aortic valve replacement (SAVR) literature shows that the rate of structural valve deterioration is age related. It’s higher in 75-year-olds than in 85-year-olds, and higher still in 65-year-olds.

“Valve degeneration didn’t play a major role when we were doing TAVR in 80- and 85-year-olds because of their limited life expectancy, but it will play a role in younger patients. So I think we have to be careful before we move toward lower-risk patients,” the surgeon continued.

Dr. Jean-Francois Obadia, who performs both SAVR and TAVR, noted that the median duration of freedom from valve degeneration for Edwards Lifescience’s Carpentier surgical aortic valve is a hefty 17.9 years.

“This should be the gold standard,” declared Dr. Obadia, head of the department of adult cardiovascular surgery and heart transplantation at the Louis Pradel Cardiothoracic Hospital of Claude Bernard University in Lyon, France.

“Dr. Dvir’s study is one of the key messages we all should take back home: a 50% rate of valve deterioration at 8 years. Valve deterioration is the Achilles’ heel of bioprostheses. There is a lot of improvement left to do for the TAVR,” he said.

Dr. Dvir and others were quick to note that his long-term study was of necessity restricted to early-generation, balloon-expandable devices: the Cribier Edwards, Edwards Sapien, and Sapien XT valves. Contemporary valves, patient selection methods, and procedural techniques are far advanced in comparison.

“The Sapien 3 has much less paravalvular leakage than earlier-generation valves. Maybe with less paravalvular leakage and better hemodynamics there will be a decreased rate of degeneration. It could be. We need to see. We have to wait a few more years to see if later-generation transcatheter heart valves are more durable,” Dr. Dvir said.

To gain a better understanding of the full dimensions of the valve degeneration issue, he and his coinvestigators have formed the VALID (VAlve Long-term Durability International Data) registry. Operators interested in contributing patients to what is hoped will be a very large and informative data base are encouraged to contact Dr. Dvir ([email protected]).

In the meantime, he has reservations about extending TAVR to intermediate-risk patients outside of the rigorous clinical trial setting. He added that he’d feel far more comfortable in performing TAVR in intermediate-risk 70- to 75-year-olds if there was a tried and true valve-in-valve replacement method, something that doesn’t yet exist. The major limitation of current attempts at valve-in-valve replacement is underexpansion because the former valve doesn’t allow sufficient room for the new one to expand fully, resulting in residual stenosis.

“If you tell me that you can implant a platform that will enable a safe valve-in-valve procedure in 5, 7, 10 years – a less invasive bailout for a failed prosthetic valve – if you can do that safely and effectively I would be more keen to do TAVR even in a young patient,” the interventional cardiologist said.

He and others are working on this unmet need. Dr. Dvir’s novel valve, being developed with Edwards Lifesciences, has performed well in valve-in-valve procedures in cadavers and animals. The first clinical trials are being planned.

“We need to think always that a bioprosthetic valve is not a cure, it’s a palliation. We treat the patients, they feel better, but we leave them with some kind of a chronic disease that’s prone to thrombosis, prone to degeneration and failure, prone to many different things,” he reflected.

The study was conducted without commercial support. Dr. Dvir reported serving as a consultant to Edwards Lifesciences, Medtronic, and St. Jude Medical.

[email protected]

Daclizumab (Zinbryta) has been approved as a patient-injected, once-monthly treatment for adults with relapsing forms of multiple sclerosis (MS), according to the Food and Drug Administration.

Daclizumab has serious safety risks, including severe and potentially life-threatening liver injury and immune disorders, and should generally be used only when patients have an inadequate response to two or more MS drugs, the FDA said in a press release. The drug has a boxed warning and is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy.

Liver function tests should be performed before starting daclizumab, and liver function should be monitored monthly before each dose, and for up to 6 months after the last dose. Immune disorders associated with use of daclizumab include noninfectious colitis, skin reactions, and lymphadenopathy. Other highlighted warnings include anaphylaxis and angioedema, increased risk of infections, and symptoms of depression and suicidal ideation.

Daclizumab was associated with a reduction in clinical relapses in a comparator trial of 1,841 participants who received either daclizumab or interferon beta-1a (Avonex) and were studied for 144 weeks. Fewer relapses also were seen with daclizumab than with placebo in a second 52-week study of 412 participants.

The most common adverse reactions reported by patients receiving daclizumab in the comparator trial included nasopharyngitis, upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal pain, eczema, and enlargement of lymph nodes. The most common adverse reactions reported in the placebo trial were depression, rash, and increased levels of alanine aminotransferase.

Daclizumab will be marketed as Zinbryta by Biogen.

Read the FDA’s full statement on the FDA website.

[email protected]

Daclizumab (Zinbryta) has been approved as a patient-injected, once-monthly treatment for adults with relapsing forms of multiple sclerosis (MS), according to the Food and Drug Administration.

Daclizumab has serious safety risks, including severe and potentially life-threatening liver injury and immune disorders, and should generally be used only when patients have an inadequate response to two or more MS drugs, the FDA said in a press release. The drug has a boxed warning and is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy.

Liver function tests should be performed before starting daclizumab, and liver function should be monitored monthly before each dose, and for up to 6 months after the last dose. Immune disorders associated with use of daclizumab include noninfectious colitis, skin reactions, and lymphadenopathy. Other highlighted warnings include anaphylaxis and angioedema, increased risk of infections, and symptoms of depression and suicidal ideation.

Daclizumab was associated with a reduction in clinical relapses in a comparator trial of 1,841 participants who received either daclizumab or interferon beta-1a (Avonex) and were studied for 144 weeks. Fewer relapses also were seen with daclizumab than with placebo in a second 52-week study of 412 participants.

The most common adverse reactions reported by patients receiving daclizumab in the comparator trial included nasopharyngitis, upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal pain, eczema, and enlargement of lymph nodes. The most common adverse reactions reported in the placebo trial were depression, rash, and increased levels of alanine aminotransferase.

Daclizumab will be marketed as Zinbryta by Biogen.

Read the FDA’s full statement on the FDA website.

[email protected]

Daclizumab (Zinbryta) has been approved as a patient-injected, once-monthly treatment for adults with relapsing forms of multiple sclerosis (MS), according to the Food and Drug Administration.

Daclizumab has serious safety risks, including severe and potentially life-threatening liver injury and immune disorders, and should generally be used only when patients have an inadequate response to two or more MS drugs, the FDA said in a press release. The drug has a boxed warning and is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy.

Liver function tests should be performed before starting daclizumab, and liver function should be monitored monthly before each dose, and for up to 6 months after the last dose. Immune disorders associated with use of daclizumab include noninfectious colitis, skin reactions, and lymphadenopathy. Other highlighted warnings include anaphylaxis and angioedema, increased risk of infections, and symptoms of depression and suicidal ideation.

Daclizumab was associated with a reduction in clinical relapses in a comparator trial of 1,841 participants who received either daclizumab or interferon beta-1a (Avonex) and were studied for 144 weeks. Fewer relapses also were seen with daclizumab than with placebo in a second 52-week study of 412 participants.

The most common adverse reactions reported by patients receiving daclizumab in the comparator trial included nasopharyngitis, upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal pain, eczema, and enlargement of lymph nodes. The most common adverse reactions reported in the placebo trial were depression, rash, and increased levels of alanine aminotransferase.

Daclizumab will be marketed as Zinbryta by Biogen.

Read the FDA’s full statement on the FDA website.

[email protected]

CHICAGO – Elective ventral hernia repair improves hernia-related quality of life for low- to moderate-risk patients, according to findings from a prospective patient-centered study.

The findings suggest that the risks and benefits of a conservative operative strategy should be reassessed, and that patient-centered outcomes should be considered, Dr. Julie Holihan reported at the annual meeting of the American Surgical Association.

Of 152 patients with a ventral hernia from a single hernia clinic, 97 were managed non-operatively, and 55 were managed operatively. In a propensity-matched cohort of 90 patients with similar demographics, baseline comorbidities, and quality of life scores, only operatively managed patients had improved quality of life scores at 6 months (improvement from 34.7 to 56.9 vs. from 35.6 to 36.6), according to Dr. Holihan of the University of Texas, Houston.

Further, satisfaction scores increased significantly more in the operative than in the non-operative group at follow-up (from a median score of 2 at baseline in both groups to scores of 9 and 3, respectively), and pain scores decreased significantly more in the operative group than in the non-operative group (from a baseline score of 5 down to 3 in the operative group, with no change [score of 6] in the non-operative group).

Two surgical site infections and one hernia recurrence occurred in the operative group.

Notably, the predicted risk of surgery in the cohort was much greater than the observed risk.

“We may be overestimating surgical risk in these patients,” she said.

Based on a multivariable analysis in the overall cohort, non-operative management was strongly associated with lower quality of life score (coefficient, -26.5), Dr. Holihan said.

Nonoperative management of ventral hernias is often recommended for patients, particularly in those with increased risk of surgical complications due to factors such as obesity, poorly controlled diabetes, smoking, or significant comorbidities like coronary artery disease, but this approach to management has not been well studied with respect to patient-centered outcomes such as quality of life and function, she explained.

Traditional outcomes that have been studied, including infection and hernia recurrence, may not be the outcomes that are most important to patients, she added.

For the current study, patients with ventral hernias were prospectively enrolled between June 2014 and June 2015. Non-operative management was recommended for smokers, those with a body mass index greater than 33 kg/m², and those with poorly controlled diabetes. Measured outcomes included surgical site infection, hernia recurrence, and quality of life using a validated quality of life measure.

This is the first prospective study comparing management strategies in ventral hernia patients with comorbidities, Dr. Holihan said.

She concluded that “the elective repair of ventral hernia, compared with non-operative management, improves patient-centered outcomes in similar-risk patients.”

“Furthermore, the low occurrence of complications suggests that we may be overestimating surgical risk and that we may be too conservative in our patient selection for elective ventral hernia repair. It may be time to reevaluate patient selection criteria in order to better incorporate patient-centered outcomes,” she said.

In response to a question about managing patients with higher risk and/or higher BMI, Dr. Holihan’s coauthor, Dr. Mike K. Liang, also of the University of Texas, Houston, noted that the findings of the study provide estimates for potential future randomized trials. He also noted that the moderate-risk patients at the center often undergo “prehabilitation,” or a preoperative exercise and diet program designed to help optimize outcomes. Currently, patients with BMI of 30-40 kg/m² are randomized to preoperative rehabilitation vs. current care.

“BMI is a very important decision making factor. We were not able to pick a standardized point [with respect to BMI] for when to operate vs. non-operate. Because of that, we used BMI as a factor in developing our propensity score,” he said, explaining that this is why the propensity-matched groups had similar BMI, while the non-operative group in the overall cohort had substantially higher BMI.

A randomized trial on prehabilitation may be able to provide some insight into the effects of rapid changes in weight and how they affect outcomes in order to make the best choices regarding surgery.

“We do hypothesize that significant weight loss prior to surgery may improve outcomes, and may make the abdominal wall more compliant and enable us to tackle more challenging hernias. We also hypothesize that patients who have a sudden increase in weight after having their ventral hernia repaired may end up having worse outcomes. Hopefully in the next year we will be able to shed more light on these very important questions.”

The authors reported having no disclosures.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

[email protected]

CHICAGO – Elective ventral hernia repair improves hernia-related quality of life for low- to moderate-risk patients, according to findings from a prospective patient-centered study.

The findings suggest that the risks and benefits of a conservative operative strategy should be reassessed, and that patient-centered outcomes should be considered, Dr. Julie Holihan reported at the annual meeting of the American Surgical Association.

Of 152 patients with a ventral hernia from a single hernia clinic, 97 were managed non-operatively, and 55 were managed operatively. In a propensity-matched cohort of 90 patients with similar demographics, baseline comorbidities, and quality of life scores, only operatively managed patients had improved quality of life scores at 6 months (improvement from 34.7 to 56.9 vs. from 35.6 to 36.6), according to Dr. Holihan of the University of Texas, Houston.

Further, satisfaction scores increased significantly more in the operative than in the non-operative group at follow-up (from a median score of 2 at baseline in both groups to scores of 9 and 3, respectively), and pain scores decreased significantly more in the operative group than in the non-operative group (from a baseline score of 5 down to 3 in the operative group, with no change [score of 6] in the non-operative group).

Two surgical site infections and one hernia recurrence occurred in the operative group.

Notably, the predicted risk of surgery in the cohort was much greater than the observed risk.

“We may be overestimating surgical risk in these patients,” she said.

Based on a multivariable analysis in the overall cohort, non-operative management was strongly associated with lower quality of life score (coefficient, -26.5), Dr. Holihan said.

Nonoperative management of ventral hernias is often recommended for patients, particularly in those with increased risk of surgical complications due to factors such as obesity, poorly controlled diabetes, smoking, or significant comorbidities like coronary artery disease, but this approach to management has not been well studied with respect to patient-centered outcomes such as quality of life and function, she explained.

Traditional outcomes that have been studied, including infection and hernia recurrence, may not be the outcomes that are most important to patients, she added.

For the current study, patients with ventral hernias were prospectively enrolled between June 2014 and June 2015. Non-operative management was recommended for smokers, those with a body mass index greater than 33 kg/m², and those with poorly controlled diabetes. Measured outcomes included surgical site infection, hernia recurrence, and quality of life using a validated quality of life measure.

This is the first prospective study comparing management strategies in ventral hernia patients with comorbidities, Dr. Holihan said.

She concluded that “the elective repair of ventral hernia, compared with non-operative management, improves patient-centered outcomes in similar-risk patients.”

“Furthermore, the low occurrence of complications suggests that we may be overestimating surgical risk and that we may be too conservative in our patient selection for elective ventral hernia repair. It may be time to reevaluate patient selection criteria in order to better incorporate patient-centered outcomes,” she said.

In response to a question about managing patients with higher risk and/or higher BMI, Dr. Holihan’s coauthor, Dr. Mike K. Liang, also of the University of Texas, Houston, noted that the findings of the study provide estimates for potential future randomized trials. He also noted that the moderate-risk patients at the center often undergo “prehabilitation,” or a preoperative exercise and diet program designed to help optimize outcomes. Currently, patients with BMI of 30-40 kg/m² are randomized to preoperative rehabilitation vs. current care.

“BMI is a very important decision making factor. We were not able to pick a standardized point [with respect to BMI] for when to operate vs. non-operate. Because of that, we used BMI as a factor in developing our propensity score,” he said, explaining that this is why the propensity-matched groups had similar BMI, while the non-operative group in the overall cohort had substantially higher BMI.

A randomized trial on prehabilitation may be able to provide some insight into the effects of rapid changes in weight and how they affect outcomes in order to make the best choices regarding surgery.

“We do hypothesize that significant weight loss prior to surgery may improve outcomes, and may make the abdominal wall more compliant and enable us to tackle more challenging hernias. We also hypothesize that patients who have a sudden increase in weight after having their ventral hernia repaired may end up having worse outcomes. Hopefully in the next year we will be able to shed more light on these very important questions.”

The authors reported having no disclosures.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

[email protected]

CHICAGO – Elective ventral hernia repair improves hernia-related quality of life for low- to moderate-risk patients, according to findings from a prospective patient-centered study.

The findings suggest that the risks and benefits of a conservative operative strategy should be reassessed, and that patient-centered outcomes should be considered, Dr. Julie Holihan reported at the annual meeting of the American Surgical Association.

Of 152 patients with a ventral hernia from a single hernia clinic, 97 were managed non-operatively, and 55 were managed operatively. In a propensity-matched cohort of 90 patients with similar demographics, baseline comorbidities, and quality of life scores, only operatively managed patients had improved quality of life scores at 6 months (improvement from 34.7 to 56.9 vs. from 35.6 to 36.6), according to Dr. Holihan of the University of Texas, Houston.

Further, satisfaction scores increased significantly more in the operative than in the non-operative group at follow-up (from a median score of 2 at baseline in both groups to scores of 9 and 3, respectively), and pain scores decreased significantly more in the operative group than in the non-operative group (from a baseline score of 5 down to 3 in the operative group, with no change [score of 6] in the non-operative group).

Two surgical site infections and one hernia recurrence occurred in the operative group.

Notably, the predicted risk of surgery in the cohort was much greater than the observed risk.

“We may be overestimating surgical risk in these patients,” she said.

Based on a multivariable analysis in the overall cohort, non-operative management was strongly associated with lower quality of life score (coefficient, -26.5), Dr. Holihan said.

Nonoperative management of ventral hernias is often recommended for patients, particularly in those with increased risk of surgical complications due to factors such as obesity, poorly controlled diabetes, smoking, or significant comorbidities like coronary artery disease, but this approach to management has not been well studied with respect to patient-centered outcomes such as quality of life and function, she explained.

Traditional outcomes that have been studied, including infection and hernia recurrence, may not be the outcomes that are most important to patients, she added.

For the current study, patients with ventral hernias were prospectively enrolled between June 2014 and June 2015. Non-operative management was recommended for smokers, those with a body mass index greater than 33 kg/m², and those with poorly controlled diabetes. Measured outcomes included surgical site infection, hernia recurrence, and quality of life using a validated quality of life measure.

This is the first prospective study comparing management strategies in ventral hernia patients with comorbidities, Dr. Holihan said.

She concluded that “the elective repair of ventral hernia, compared with non-operative management, improves patient-centered outcomes in similar-risk patients.”

“Furthermore, the low occurrence of complications suggests that we may be overestimating surgical risk and that we may be too conservative in our patient selection for elective ventral hernia repair. It may be time to reevaluate patient selection criteria in order to better incorporate patient-centered outcomes,” she said.

In response to a question about managing patients with higher risk and/or higher BMI, Dr. Holihan’s coauthor, Dr. Mike K. Liang, also of the University of Texas, Houston, noted that the findings of the study provide estimates for potential future randomized trials. He also noted that the moderate-risk patients at the center often undergo “prehabilitation,” or a preoperative exercise and diet program designed to help optimize outcomes. Currently, patients with BMI of 30-40 kg/m² are randomized to preoperative rehabilitation vs. current care.

“BMI is a very important decision making factor. We were not able to pick a standardized point [with respect to BMI] for when to operate vs. non-operate. Because of that, we used BMI as a factor in developing our propensity score,” he said, explaining that this is why the propensity-matched groups had similar BMI, while the non-operative group in the overall cohort had substantially higher BMI.

A randomized trial on prehabilitation may be able to provide some insight into the effects of rapid changes in weight and how they affect outcomes in order to make the best choices regarding surgery.

“We do hypothesize that significant weight loss prior to surgery may improve outcomes, and may make the abdominal wall more compliant and enable us to tackle more challenging hernias. We also hypothesize that patients who have a sudden increase in weight after having their ventral hernia repaired may end up having worse outcomes. Hopefully in the next year we will be able to shed more light on these very important questions.”

The authors reported having no disclosures.

The complete manuscript of this presentation is anticipated to be published in the Annals of Surgery pending editorial review.

[email protected]

ANSWER
The correct interpretation of this ECG includes normal sinus rhythm, biatrial enlargement, nonspecific ST-T wave abnormality, and an RSR’ or QR pattern in V₁, suggestive of right ventricular conduction delay.

Biatrial enlargement by definition encompasses right atrial enlargement (criteria include P waves in leads II, III, and aVF measuring 2.5 mm or more) and left atrial enlargement (evidenced by P waves in lead I ≥ 110 ms, and a biphasic, or “notched,” P wave with terminal negativity in lead V₁).

Lead V₁ may be interpreted as either an RSR’ or a QR pattern. However, the QRS duration of < 120 ms precludes this from meeting criteria for a right bundle branch block.

Finally, nonspecific ST-T wave changes were present in the precordial leads. These may be consistent with pulmonary disease.

ANSWER
The correct interpretation of this ECG includes normal sinus rhythm, biatrial enlargement, nonspecific ST-T wave abnormality, and an RSR’ or QR pattern in V₁, suggestive of right ventricular conduction delay.

Biatrial enlargement by definition encompasses right atrial enlargement (criteria include P waves in leads II, III, and aVF measuring 2.5 mm or more) and left atrial enlargement (evidenced by P waves in lead I ≥ 110 ms, and a biphasic, or “notched,” P wave with terminal negativity in lead V₁).

Lead V₁ may be interpreted as either an RSR’ or a QR pattern. However, the QRS duration of < 120 ms precludes this from meeting criteria for a right bundle branch block.

Finally, nonspecific ST-T wave changes were present in the precordial leads. These may be consistent with pulmonary disease.

ANSWER
The correct interpretation of this ECG includes normal sinus rhythm, biatrial enlargement, nonspecific ST-T wave abnormality, and an RSR’ or QR pattern in V₁, suggestive of right ventricular conduction delay.

Biatrial enlargement by definition encompasses right atrial enlargement (criteria include P waves in leads II, III, and aVF measuring 2.5 mm or more) and left atrial enlargement (evidenced by P waves in lead I ≥ 110 ms, and a biphasic, or “notched,” P wave with terminal negativity in lead V₁).

Lead V₁ may be interpreted as either an RSR’ or a QR pattern. However, the QRS duration of < 120 ms precludes this from meeting criteria for a right bundle branch block.

Finally, nonspecific ST-T wave changes were present in the precordial leads. These may be consistent with pulmonary disease.

In what is believed to be the first case of its kind in the United States, researchers identified a female patient with colistin-resistant Escherichia coli. The patient harbored mcr-1, a gene resistant to colistin, an antibiotic used as a last resort for infections that are resistant to carbapenems.

The finding comes at a time when a search for colistin-resistant bacteria by officials from the U.S. Department of Agriculture and the U.S. Department of Health and Human Services revealed colistin-resistant E. coli in a single sample from a pig intestine. Combined, “these discoveries are of concern because colistin is used as a last-resort drug to treat patients with multidrug resistant infections,” according to a communication from the HHS dated May 26. “Finding colistin-resistant bacteria in the United States is important, as it was only last November that scientists in China first reported that the mcr-1 gene in bacteria confers colistin resistance.”

Researchers led by Patrick McGann, Ph.D., who reported the human case in an article published online May 26 in Antimicrobial Agents and Chemotherapy, wrote that the recent discovery of a plasmid-borne colistin resistance gene, mcr-1, “heralds the emergence of truly pan-drug resistant bacteria. The gene has been found primarily in Escherichia coli, but has also been identified in other members of the Enterobacteriaceae from human, animal, food and environmental samples on every continent” (Antimicrob Agents Chemother. 2016 May 26. doi: 10.1128/AAC.01103-16).

As a result of this threat, in May, Dr. McGann, of the Department of Defense’s Multidrug-resistant Organism Repository and Surveillance Network at Walter Reed Army Institute of Research, Silver Spring, Md., and his associates began analyzing all extended-spectrum beta-lactamase (ESBL)–producing E. coli clinical isolates submitted to Walter Reed National Military Medical Center for analysis for resistance to colistin by E-test.

The case of interest was the presence of mcr-1 in an E. coli isolate cultured from a 49-year-old woman who presented to a military clinic in Pennsylvania with symptoms suggestive of a urinary tract infection, and who reported no travel history within the prior 5 months. Susceptibility testing at Walter Reed indicated an ESBL phenotype.

“The isolate was included in the first 6 ESBL-producing E. coli selected for colistin susceptibility testing, and it was the only isolate to have a MIC of colistin of 4 mcg/mL [all others had MICs of 0.25 mcg/mL or less]. Colistin MIC was confirmed by microbroth dilution and mcr-1 detected by real-time PCR.”

Since mcr-1 testing at Walter Reed has been underway for a short time, “it remains unclear what the true prevalence of mcr-1 is in the population,” the researchers noted. “The association between mcr-1 and IncF plasmids is concerning as these plasmids are vehicles for the dissemination of antibiotic resistance and virulence genes against Enterobacteriaceae. Continued surveillance to determine the true frequency for this gene in the USA is critical.”

The researchers reported having no financial disclosures.

[email protected]

In what is believed to be the first case of its kind in the United States, researchers identified a female patient with colistin-resistant Escherichia coli. The patient harbored mcr-1, a gene resistant to colistin, an antibiotic used as a last resort for infections that are resistant to carbapenems.

The finding comes at a time when a search for colistin-resistant bacteria by officials from the U.S. Department of Agriculture and the U.S. Department of Health and Human Services revealed colistin-resistant E. coli in a single sample from a pig intestine. Combined, “these discoveries are of concern because colistin is used as a last-resort drug to treat patients with multidrug resistant infections,” according to a communication from the HHS dated May 26. “Finding colistin-resistant bacteria in the United States is important, as it was only last November that scientists in China first reported that the mcr-1 gene in bacteria confers colistin resistance.”

Researchers led by Patrick McGann, Ph.D., who reported the human case in an article published online May 26 in Antimicrobial Agents and Chemotherapy, wrote that the recent discovery of a plasmid-borne colistin resistance gene, mcr-1, “heralds the emergence of truly pan-drug resistant bacteria. The gene has been found primarily in Escherichia coli, but has also been identified in other members of the Enterobacteriaceae from human, animal, food and environmental samples on every continent” (Antimicrob Agents Chemother. 2016 May 26. doi: 10.1128/AAC.01103-16).

As a result of this threat, in May, Dr. McGann, of the Department of Defense’s Multidrug-resistant Organism Repository and Surveillance Network at Walter Reed Army Institute of Research, Silver Spring, Md., and his associates began analyzing all extended-spectrum beta-lactamase (ESBL)–producing E. coli clinical isolates submitted to Walter Reed National Military Medical Center for analysis for resistance to colistin by E-test.

The case of interest was the presence of mcr-1 in an E. coli isolate cultured from a 49-year-old woman who presented to a military clinic in Pennsylvania with symptoms suggestive of a urinary tract infection, and who reported no travel history within the prior 5 months. Susceptibility testing at Walter Reed indicated an ESBL phenotype.

“The isolate was included in the first 6 ESBL-producing E. coli selected for colistin susceptibility testing, and it was the only isolate to have a MIC of colistin of 4 mcg/mL [all others had MICs of 0.25 mcg/mL or less]. Colistin MIC was confirmed by microbroth dilution and mcr-1 detected by real-time PCR.”

Since mcr-1 testing at Walter Reed has been underway for a short time, “it remains unclear what the true prevalence of mcr-1 is in the population,” the researchers noted. “The association between mcr-1 and IncF plasmids is concerning as these plasmids are vehicles for the dissemination of antibiotic resistance and virulence genes against Enterobacteriaceae. Continued surveillance to determine the true frequency for this gene in the USA is critical.”

The researchers reported having no financial disclosures.

[email protected]

In what is believed to be the first case of its kind in the United States, researchers identified a female patient with colistin-resistant Escherichia coli. The patient harbored mcr-1, a gene resistant to colistin, an antibiotic used as a last resort for infections that are resistant to carbapenems.

The finding comes at a time when a search for colistin-resistant bacteria by officials from the U.S. Department of Agriculture and the U.S. Department of Health and Human Services revealed colistin-resistant E. coli in a single sample from a pig intestine. Combined, “these discoveries are of concern because colistin is used as a last-resort drug to treat patients with multidrug resistant infections,” according to a communication from the HHS dated May 26. “Finding colistin-resistant bacteria in the United States is important, as it was only last November that scientists in China first reported that the mcr-1 gene in bacteria confers colistin resistance.”

Researchers led by Patrick McGann, Ph.D., who reported the human case in an article published online May 26 in Antimicrobial Agents and Chemotherapy, wrote that the recent discovery of a plasmid-borne colistin resistance gene, mcr-1, “heralds the emergence of truly pan-drug resistant bacteria. The gene has been found primarily in Escherichia coli, but has also been identified in other members of the Enterobacteriaceae from human, animal, food and environmental samples on every continent” (Antimicrob Agents Chemother. 2016 May 26. doi: 10.1128/AAC.01103-16).

As a result of this threat, in May, Dr. McGann, of the Department of Defense’s Multidrug-resistant Organism Repository and Surveillance Network at Walter Reed Army Institute of Research, Silver Spring, Md., and his associates began analyzing all extended-spectrum beta-lactamase (ESBL)–producing E. coli clinical isolates submitted to Walter Reed National Military Medical Center for analysis for resistance to colistin by E-test.

The case of interest was the presence of mcr-1 in an E. coli isolate cultured from a 49-year-old woman who presented to a military clinic in Pennsylvania with symptoms suggestive of a urinary tract infection, and who reported no travel history within the prior 5 months. Susceptibility testing at Walter Reed indicated an ESBL phenotype.

“The isolate was included in the first 6 ESBL-producing E. coli selected for colistin susceptibility testing, and it was the only isolate to have a MIC of colistin of 4 mcg/mL [all others had MICs of 0.25 mcg/mL or less]. Colistin MIC was confirmed by microbroth dilution and mcr-1 detected by real-time PCR.”

Since mcr-1 testing at Walter Reed has been underway for a short time, “it remains unclear what the true prevalence of mcr-1 is in the population,” the researchers noted. “The association between mcr-1 and IncF plasmids is concerning as these plasmids are vehicles for the dissemination of antibiotic resistance and virulence genes against Enterobacteriaceae. Continued surveillance to determine the true frequency for this gene in the USA is critical.”

The researchers reported having no financial disclosures.

[email protected]