Photo courtesy of GSK

The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).

Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.

Eltrombopag received breakthrough therapy designation and priority review for this indication.

Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.

The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.

Updated results from the trial are available in the prescribing information for eltrombopag.

The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.

The starting dose of eltrombopag was:

• 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
• 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
• 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).

Patients were divided into three cohorts with different dosing schedules.

The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.

Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.

The median duration of both overall and complete response was 24.3 months.

The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).

Eltrombopag is a product of Novartis.

Photo courtesy of GSK

The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).

Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.

Eltrombopag received breakthrough therapy designation and priority review for this indication.

Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.

The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.

Updated results from the trial are available in the prescribing information for eltrombopag.

The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.

The starting dose of eltrombopag was:

• 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
• 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
• 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).

Patients were divided into three cohorts with different dosing schedules.

The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.

Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.

The median duration of both overall and complete response was 24.3 months.

The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).

Eltrombopag is a product of Novartis.

Photo courtesy of GSK

The U.S. Food and Drug Administration (FDA) has expanded the approved use of eltrombopag (Promacta®) in severe aplastic anemia (SAA).

Eltrombopag is now approved for use in combination with standard immunosuppressive therapy as first-line treatment for adults and pediatric patients age 2 and older with SAA.

Eltrombopag received breakthrough therapy designation and priority review for this indication.

Eltrombopag is also FDA-approved for SAA patients who have had an insufficient response to immunosuppressive therapy, for patients with chronic immune thrombocytopenia who have had an insufficient response to other treatments, and to treat thrombocytopenia in patients with chronic hepatitis C virus infection.

The FDA’s latest approval of eltrombopag is based on results from a phase 1/2 trial (NCT01623167), which were published in The New England Journal of Medicine in April 2017.

Updated results from the trial are available in the prescribing information for eltrombopag.

The trial included 153 previously untreated SAA patients age 2 and older. The patients received eltrombopag in combination with horse antithymocyte globulin and cyclosporine.

The starting dose of eltrombopag was:

• 150 mg once daily for patients age 12 and older (75 mg for East and Southeast Asians)
• 75 mg once daily for patients ages 6 to 11 (37.5 mg for East and Southeast Asians)
• 5 mg/kg once daily for patients ages 2 to 5 (1.25 mg/kg for East and Southeast Asians).

Patients were divided into three cohorts with different dosing schedules.

The recommended schedule, from the third cohort (n=92), was eltrombopag from day 1 to month 6, plus horse antithymocyte globulin and cyclosporine. All patients in this cohort were eligible to receive a low dose of cyclosporine for an additional 18 months if they achieved a hematologic response at 6 months.

Among the patients treated at the recommended dosing schedule, the 6-month overall response rate was 79%, and the complete response rate was 44%.

The median duration of both overall and complete response was 24.3 months.

The most common adverse events in these patients were ALT increase (29%), AST increase (17%), blood bilirubin increase (17%), rash (8%), and skin discoloration including hyperpigmentation (5%).

Eltrombopag is a product of Novartis.

Patients with migrane are more sensitive to all colors of light during the ictal phase than the during interictal phase, according to a recent study, but control subjects do not experience pain when exposed to different colors of light. In order to identify the origin of this photophobia in migraineurs, researchers compared the electrical waveforms that were generated in the retina and visual cortex of 46 interictal migraineurs to those generated in 42 healthy controls using color-based electroretinography and visual evoked potential paradigms. They found:

• Unexpectedly, it was the amplitude of the retinal rod-driven b-wave, which was consistently larger in the migraineurs than in the controls, rather than the retinal cone-driven a-wave or the visual evoked potentials that differ most strikingly between the 2 groups.
• Mechanistically, these findings suggest that the inherent hypersensitivity to light among migraine patients may originate in the retinal rods rather than retinal cones or the visual cortex.

Clinically, these findings may explain why migraineurs complain that the light is too bright even when it is dim.

Bernstein CA, N R-R, Noseda R, et al. The migraine eye: distinct rod-driven retinal pathways’ response to dim light challenges the visual cortex hyperexcitability theory. [Published online ahead of print October 29, 2018]. Pain. doi:10.1097/j.pain.0000000000001434.

Patients with migrane are more sensitive to all colors of light during the ictal phase than the during interictal phase, according to a recent study, but control subjects do not experience pain when exposed to different colors of light. In order to identify the origin of this photophobia in migraineurs, researchers compared the electrical waveforms that were generated in the retina and visual cortex of 46 interictal migraineurs to those generated in 42 healthy controls using color-based electroretinography and visual evoked potential paradigms. They found:

• Unexpectedly, it was the amplitude of the retinal rod-driven b-wave, which was consistently larger in the migraineurs than in the controls, rather than the retinal cone-driven a-wave or the visual evoked potentials that differ most strikingly between the 2 groups.
• Mechanistically, these findings suggest that the inherent hypersensitivity to light among migraine patients may originate in the retinal rods rather than retinal cones or the visual cortex.

Clinically, these findings may explain why migraineurs complain that the light is too bright even when it is dim.

Bernstein CA, N R-R, Noseda R, et al. The migraine eye: distinct rod-driven retinal pathways’ response to dim light challenges the visual cortex hyperexcitability theory. [Published online ahead of print October 29, 2018]. Pain. doi:10.1097/j.pain.0000000000001434.

Patients with migrane are more sensitive to all colors of light during the ictal phase than the during interictal phase, according to a recent study, but control subjects do not experience pain when exposed to different colors of light. In order to identify the origin of this photophobia in migraineurs, researchers compared the electrical waveforms that were generated in the retina and visual cortex of 46 interictal migraineurs to those generated in 42 healthy controls using color-based electroretinography and visual evoked potential paradigms. They found:

• Unexpectedly, it was the amplitude of the retinal rod-driven b-wave, which was consistently larger in the migraineurs than in the controls, rather than the retinal cone-driven a-wave or the visual evoked potentials that differ most strikingly between the 2 groups.
• Mechanistically, these findings suggest that the inherent hypersensitivity to light among migraine patients may originate in the retinal rods rather than retinal cones or the visual cortex.

Clinically, these findings may explain why migraineurs complain that the light is too bright even when it is dim.

Bernstein CA, N R-R, Noseda R, et al. The migraine eye: distinct rod-driven retinal pathways’ response to dim light challenges the visual cortex hyperexcitability theory. [Published online ahead of print October 29, 2018]. Pain. doi:10.1097/j.pain.0000000000001434.

Parental migraine impacts children aged 11 to 17 living in the home, particularly in the domains of global well‐being and the parent/child relationship, according to a recent study. This cross‐sectional observational study included parents who met International Classification of Headache Disorders criteria for migraine and their 11- to 17‐year‐old children currently living with the parent with migraine recruited from neurologist offices and online. Researchers found:

• Children (n=40) reported the greatest impact of their parent’s migraine on the Global Well‐Being and Parent/Child Relationship subscales.
• There were no significant differences between the average child and parent rating of parental migraine impact on children.
• Correlations between parent and child ratings of parental migraine impact were strongest for the Social Impact subscale, and non‐significant for the Parent/Child Relationship and Friends Reactions subscales.

Seng EK, Mauser ED, Marzouk N, Patel ZS, Rosen N, Buse DC. When mom has migraine: An observational study of the impact of parental migraine on adolescent children. [Published online ahead of print October 31, 2018]. Headache. doi:10.1111/head.13433.

Parental migraine impacts children aged 11 to 17 living in the home, particularly in the domains of global well‐being and the parent/child relationship, according to a recent study. This cross‐sectional observational study included parents who met International Classification of Headache Disorders criteria for migraine and their 11- to 17‐year‐old children currently living with the parent with migraine recruited from neurologist offices and online. Researchers found:

• Children (n=40) reported the greatest impact of their parent’s migraine on the Global Well‐Being and Parent/Child Relationship subscales.
• There were no significant differences between the average child and parent rating of parental migraine impact on children.
• Correlations between parent and child ratings of parental migraine impact were strongest for the Social Impact subscale, and non‐significant for the Parent/Child Relationship and Friends Reactions subscales.

Seng EK, Mauser ED, Marzouk N, Patel ZS, Rosen N, Buse DC. When mom has migraine: An observational study of the impact of parental migraine on adolescent children. [Published online ahead of print October 31, 2018]. Headache. doi:10.1111/head.13433.

Parental migraine impacts children aged 11 to 17 living in the home, particularly in the domains of global well‐being and the parent/child relationship, according to a recent study. This cross‐sectional observational study included parents who met International Classification of Headache Disorders criteria for migraine and their 11- to 17‐year‐old children currently living with the parent with migraine recruited from neurologist offices and online. Researchers found:

• Children (n=40) reported the greatest impact of their parent’s migraine on the Global Well‐Being and Parent/Child Relationship subscales.
• There were no significant differences between the average child and parent rating of parental migraine impact on children.
• Correlations between parent and child ratings of parental migraine impact were strongest for the Social Impact subscale, and non‐significant for the Parent/Child Relationship and Friends Reactions subscales.

Seng EK, Mauser ED, Marzouk N, Patel ZS, Rosen N, Buse DC. When mom has migraine: An observational study of the impact of parental migraine on adolescent children. [Published online ahead of print October 31, 2018]. Headache. doi:10.1111/head.13433.

Headache disorders, and migraine in particular, are important causes of disability worldwide, and deserve greater attention in health policy debates and research resource allocation. This according to a recent investigation that used data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2016 study to provide new estimates for prevalence and years of life lived with disability (YLDs) for migraine and tension-type headache. Prevalence for gender and 5-year age group interval at different time points from 1990 and 2016 in all countries and GBD regions were estimated using a Bayesian meta-regression model. Researchers found:

• Almost 3 billion individuals were estimated to have a migraine or tension-type headache in 2016: 1.89 billion with tension-type headache and 1.04 billion with migraine.
• However, because migraine had a much higher disability weight than tension-type headache, migraine caused 45.1 million and tension-type headache only 7.2 million YLDs globally in 2016.
• The headaches were most burdensome in women between ages 15 and 49 years, with migraine causing 20.3 million and tension-type headache 2.9 million YLDs in 2016, which was 11.2% of all YLDs in this age group and sex.

Stovner LJ, Nichols E, Steiner TJ, et al. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):954-976. doi:10.1016/S1474-4422(18)30322-3.

Headache disorders, and migraine in particular, are important causes of disability worldwide, and deserve greater attention in health policy debates and research resource allocation. This according to a recent investigation that used data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2016 study to provide new estimates for prevalence and years of life lived with disability (YLDs) for migraine and tension-type headache. Prevalence for gender and 5-year age group interval at different time points from 1990 and 2016 in all countries and GBD regions were estimated using a Bayesian meta-regression model. Researchers found:

• Almost 3 billion individuals were estimated to have a migraine or tension-type headache in 2016: 1.89 billion with tension-type headache and 1.04 billion with migraine.
• However, because migraine had a much higher disability weight than tension-type headache, migraine caused 45.1 million and tension-type headache only 7.2 million YLDs globally in 2016.
• The headaches were most burdensome in women between ages 15 and 49 years, with migraine causing 20.3 million and tension-type headache 2.9 million YLDs in 2016, which was 11.2% of all YLDs in this age group and sex.

Stovner LJ, Nichols E, Steiner TJ, et al. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):954-976. doi:10.1016/S1474-4422(18)30322-3.

Headache disorders, and migraine in particular, are important causes of disability worldwide, and deserve greater attention in health policy debates and research resource allocation. This according to a recent investigation that used data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2016 study to provide new estimates for prevalence and years of life lived with disability (YLDs) for migraine and tension-type headache. Prevalence for gender and 5-year age group interval at different time points from 1990 and 2016 in all countries and GBD regions were estimated using a Bayesian meta-regression model. Researchers found:

• Almost 3 billion individuals were estimated to have a migraine or tension-type headache in 2016: 1.89 billion with tension-type headache and 1.04 billion with migraine.
• However, because migraine had a much higher disability weight than tension-type headache, migraine caused 45.1 million and tension-type headache only 7.2 million YLDs globally in 2016.
• The headaches were most burdensome in women between ages 15 and 49 years, with migraine causing 20.3 million and tension-type headache 2.9 million YLDs in 2016, which was 11.2% of all YLDs in this age group and sex.

Stovner LJ, Nichols E, Steiner TJ, et al. GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):954-976. doi:10.1016/S1474-4422(18)30322-3.

Although ambulatory EEGs (aEEGs) can help distinguish epileptic attacks from non-epileptic attacks, they have their limitations. A recent retrospective review of EEG procedure notes from the Stanford Comprehensive Epilepsy Center has found that they rarely yield useful information beyond 24 hours duration.

• Stanford researchers analyzed 358 adult aEEG readings from 2010 to 2017 and found epileptiform discharges or epileptic seizures in 101 of the readings (28%).
• The analysis compared detection rates for 20-30 hours, 30-50 hours, and 50-76 hours and found little difference.
• Epilepsy seizures were observed in 11%, 7%, and 10% respectively for the 3 duration periods.
• An analysis of the epileptiform abnormalities revealed no significant differences in detection rates for the 3 duration periods.
• Among aEEGs that were ordered to characterize suspected events, however, 72 hours was the best option because it generated a higher rate of capture.

Kuo J, Lee-Messer C, Le S. Optimal recording duration of ambulatory EEG (aEEG). Epilepsy Res. 2018;149:9-12.

Although ambulatory EEGs (aEEGs) can help distinguish epileptic attacks from non-epileptic attacks, they have their limitations. A recent retrospective review of EEG procedure notes from the Stanford Comprehensive Epilepsy Center has found that they rarely yield useful information beyond 24 hours duration.

• Stanford researchers analyzed 358 adult aEEG readings from 2010 to 2017 and found epileptiform discharges or epileptic seizures in 101 of the readings (28%).
• The analysis compared detection rates for 20-30 hours, 30-50 hours, and 50-76 hours and found little difference.
• Epilepsy seizures were observed in 11%, 7%, and 10% respectively for the 3 duration periods.
• An analysis of the epileptiform abnormalities revealed no significant differences in detection rates for the 3 duration periods.
• Among aEEGs that were ordered to characterize suspected events, however, 72 hours was the best option because it generated a higher rate of capture.

Kuo J, Lee-Messer C, Le S. Optimal recording duration of ambulatory EEG (aEEG). Epilepsy Res. 2018;149:9-12.

Although ambulatory EEGs (aEEGs) can help distinguish epileptic attacks from non-epileptic attacks, they have their limitations. A recent retrospective review of EEG procedure notes from the Stanford Comprehensive Epilepsy Center has found that they rarely yield useful information beyond 24 hours duration.

• Stanford researchers analyzed 358 adult aEEG readings from 2010 to 2017 and found epileptiform discharges or epileptic seizures in 101 of the readings (28%).
• The analysis compared detection rates for 20-30 hours, 30-50 hours, and 50-76 hours and found little difference.
• Epilepsy seizures were observed in 11%, 7%, and 10% respectively for the 3 duration periods.
• An analysis of the epileptiform abnormalities revealed no significant differences in detection rates for the 3 duration periods.
• Among aEEGs that were ordered to characterize suspected events, however, 72 hours was the best option because it generated a higher rate of capture.

Kuo J, Lee-Messer C, Le S. Optimal recording duration of ambulatory EEG (aEEG). Epilepsy Res. 2018;149:9-12.

Trying to predict morbidity and mortality among patients with status epilepticus has proven difficult, and the 2 scoring metrics designed to accomplish that feat have significant shortcomings, according to a retrospective analysis of status epilepticus patients conducted at the Ohio State University Wexner Medical Center.

• Investigators reviewed the records of 46 affected patients admitted to the hospital’s neuro-critical care unit.
• Data from the status epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in Status Epilepticus (EMSE) were analyzed.
• Sensitivity of EMSE was 100% and sensitivity of STESS was 90%.
• The specificity of both metrics was wanting, however: EMSE, 28.6% and STESS, 42.9%.
• Researchers concluded that both scoring systems may help predict clinical outcomes in status epilepticus patients who have few co-existing conditions but are less valuable in populations with several medical problems.

Yechoor A, Adeli A, Hafeez S. External validation of the epidemiology-based mortality score in status epilepticus in an American intensive care population. Epilepsy Res. 2018;148:32-36.

Trying to predict morbidity and mortality among patients with status epilepticus has proven difficult, and the 2 scoring metrics designed to accomplish that feat have significant shortcomings, according to a retrospective analysis of status epilepticus patients conducted at the Ohio State University Wexner Medical Center.

• Investigators reviewed the records of 46 affected patients admitted to the hospital’s neuro-critical care unit.
• Data from the status epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in Status Epilepticus (EMSE) were analyzed.
• Sensitivity of EMSE was 100% and sensitivity of STESS was 90%.
• The specificity of both metrics was wanting, however: EMSE, 28.6% and STESS, 42.9%.
• Researchers concluded that both scoring systems may help predict clinical outcomes in status epilepticus patients who have few co-existing conditions but are less valuable in populations with several medical problems.

Yechoor A, Adeli A, Hafeez S. External validation of the epidemiology-based mortality score in status epilepticus in an American intensive care population. Epilepsy Res. 2018;148:32-36.

Trying to predict morbidity and mortality among patients with status epilepticus has proven difficult, and the 2 scoring metrics designed to accomplish that feat have significant shortcomings, according to a retrospective analysis of status epilepticus patients conducted at the Ohio State University Wexner Medical Center.

• Investigators reviewed the records of 46 affected patients admitted to the hospital’s neuro-critical care unit.
• Data from the status epilepticus Severity Score (STESS) and Epidemiology-based Mortality Score in Status Epilepticus (EMSE) were analyzed.
• Sensitivity of EMSE was 100% and sensitivity of STESS was 90%.
• The specificity of both metrics was wanting, however: EMSE, 28.6% and STESS, 42.9%.
• Researchers concluded that both scoring systems may help predict clinical outcomes in status epilepticus patients who have few co-existing conditions but are less valuable in populations with several medical problems.

Yechoor A, Adeli A, Hafeez S. External validation of the epidemiology-based mortality score in status epilepticus in an American intensive care population. Epilepsy Res. 2018;148:32-36.

Among children who have had surgical resection of epileptic lesions, it may be wise to continue postoperative invasive monitoring, suggests this investigation of 71 patients published in Epilepsy Research.

• A retrospective analysis of 5 patients with MRI-negative epilepsy and 66 patients with MRI-identified neocortical lesions, post-resection invasive monitoring yielded positive outcomes in 86%.
• In 55 of 71 patients, post-resection monitoring resulted in additional resections.
• Postop monitoring detected clinical seizures at the resection margins, subclinical seizures and interictal discharges at the resection margins, and both clinical and subclinical seizures that indicated a new epileptogenic focus.

Hidalgo ET, Frankel HG, Rodriguez C, et al. Invasive monitoring after resection of epileptogenic neocortical lesions in multi-staged epilepsy surgery in children. Epilepsy Res. 2018; 148:48-54.   

Among children who have had surgical resection of epileptic lesions, it may be wise to continue postoperative invasive monitoring, suggests this investigation of 71 patients published in Epilepsy Research.

• A retrospective analysis of 5 patients with MRI-negative epilepsy and 66 patients with MRI-identified neocortical lesions, post-resection invasive monitoring yielded positive outcomes in 86%.
• In 55 of 71 patients, post-resection monitoring resulted in additional resections.
• Postop monitoring detected clinical seizures at the resection margins, subclinical seizures and interictal discharges at the resection margins, and both clinical and subclinical seizures that indicated a new epileptogenic focus.

Hidalgo ET, Frankel HG, Rodriguez C, et al. Invasive monitoring after resection of epileptogenic neocortical lesions in multi-staged epilepsy surgery in children. Epilepsy Res. 2018; 148:48-54.   

Among children who have had surgical resection of epileptic lesions, it may be wise to continue postoperative invasive monitoring, suggests this investigation of 71 patients published in Epilepsy Research.

• A retrospective analysis of 5 patients with MRI-negative epilepsy and 66 patients with MRI-identified neocortical lesions, post-resection invasive monitoring yielded positive outcomes in 86%.
• In 55 of 71 patients, post-resection monitoring resulted in additional resections.
• Postop monitoring detected clinical seizures at the resection margins, subclinical seizures and interictal discharges at the resection margins, and both clinical and subclinical seizures that indicated a new epileptogenic focus.

Hidalgo ET, Frankel HG, Rodriguez C, et al. Invasive monitoring after resection of epileptogenic neocortical lesions in multi-staged epilepsy surgery in children. Epilepsy Res. 2018; 148:48-54.   

During a wound repair process in rats, metaplastic columnar-lined esophagus was produced and increased in length following esophagojejunostomy, which may be independent of stem cell reprogramming, according to results from an anastomosed rodent study.

The investigators studied esophageal and tissue sections of 52 rats at different time points after esophagojejunostomy and samples were analyzed for length, type, and location of columnar lining. In addition, the sections were examined immunophenotypically to elucidate the molecular changes that occur during ulceration. Agoston T. Agoston, MD, PhD, of Brigham and Women’s Hospital and the department of pathology at Harvard Medical School, Boston, and colleagues reported the findings in Cellular and Molecular Gastroenterology and Hepatology.

“This rodent columnar-lined esophagus has been proposed to develop from cellular reprogramming of progenitor cells, but studies on early columnar-lined esophagus development are lacking,” the researchers wrote.

In the model, ulceration was seen 2 weeks after surgery, which began distally at the esophagojejunal anastomosis. Representative of wound healing, reepithelialization of the ulcer region took place through formation of immature glands, which were found to bud directly from jejunal crypts.

After immunophenotypic analysis, the researchers reported that “immunohistochemical characterization of neoglandular epithelium located immediately proximal to the anastomosis showed features similar to those of the native nonproliferating jejunal epithelium located immediately distal to the anastomosis.” They further reported that “the columnar-lined esophagus’s immunoprofile was similar to jejunal crypt epithelium.”

Upon further examination of the ulcer segment, Dr. Agoston and colleagues found that columnar-lined esophagus elongated from 0.15 mm (standard error of the mean, ± 0.1) to 5.22 mm (SEM, ± 0.37) at 2 and 32 weeks post esophagojejunostomy, respectively.

“There was a highly significant linear relationship between the length of the neoglandular epithelium in the distal esophagus and the number of weeks after surgery (correlation coefficient, 0.94; P less than .0001),” the investigators stated.

Locational analysis revealed epithelial-mesenchymal transition markers being expressed by spindle-shaped cells at the leading edge of the columnar-lined esophagus. In addition, neoglands were identified within esophageal ulcer beds and actively dividing squamous epithelium was seen exclusively at the proximal ulcer border.

Following the systematic analysis, the authors noted that the columnar-lined esophagus was most likely the result of jejunal cell migration into the esophagus. They suggested that if compared, jejunal cells may competitively dominate squamous cells in the context of chronic gastroesophageal reflux disease. Furthermore, they observed that the region of ulceration following esophagojejunostomy in their model was more expansive than that reported in other comparable rodent models of reflux esophagitis.

“The reason for this difference is not clear, but we speculate that it is the result of technical aspects of our reflux-inducing surgery,” the researchers wrote. They further explained that “we intentionally fashioned a large anastomotic orifice between the esophagus and jejunum, perhaps larger than that fashioned by other investigators.” And they concluded, “we suspect that this larger orifice resulted in esophageal exposure to larger volumes of refluxate and, consequently, larger areas of ulceration.”

The authors acknowledged their results may not be fully applicable in the context of human Barrett’s esophagus, given the rodent model. However, they do believe the findings may provide a basis to help understand the wound repair process, particularly the distal edge of ulcers that border the columnar epithelium.

“Using a rat model of reflux esophagitis via surgical esophagojejunostomy, we have shown that a metaplastic, columnar-lined esophagus develops via a wound healing process, and not via genetic reprogramming of progenitor cells,” the researchers concluded.

The study was supported by grant funding from the National Institutes of Health and the Baylor Scott and White Research Institute. The authors reported no conflicts of interest.

SOURCE: Agoston AT et al. Cell Mol Gastroenterol Hepatol. 2018 Jun 26. doi: 10.1016/j.jcmgh.2018.06.007.

During a wound repair process in rats, metaplastic columnar-lined esophagus was produced and increased in length following esophagojejunostomy, which may be independent of stem cell reprogramming, according to results from an anastomosed rodent study.

The investigators studied esophageal and tissue sections of 52 rats at different time points after esophagojejunostomy and samples were analyzed for length, type, and location of columnar lining. In addition, the sections were examined immunophenotypically to elucidate the molecular changes that occur during ulceration. Agoston T. Agoston, MD, PhD, of Brigham and Women’s Hospital and the department of pathology at Harvard Medical School, Boston, and colleagues reported the findings in Cellular and Molecular Gastroenterology and Hepatology.

“This rodent columnar-lined esophagus has been proposed to develop from cellular reprogramming of progenitor cells, but studies on early columnar-lined esophagus development are lacking,” the researchers wrote.

In the model, ulceration was seen 2 weeks after surgery, which began distally at the esophagojejunal anastomosis. Representative of wound healing, reepithelialization of the ulcer region took place through formation of immature glands, which were found to bud directly from jejunal crypts.

After immunophenotypic analysis, the researchers reported that “immunohistochemical characterization of neoglandular epithelium located immediately proximal to the anastomosis showed features similar to those of the native nonproliferating jejunal epithelium located immediately distal to the anastomosis.” They further reported that “the columnar-lined esophagus’s immunoprofile was similar to jejunal crypt epithelium.”

Upon further examination of the ulcer segment, Dr. Agoston and colleagues found that columnar-lined esophagus elongated from 0.15 mm (standard error of the mean, ± 0.1) to 5.22 mm (SEM, ± 0.37) at 2 and 32 weeks post esophagojejunostomy, respectively.

“There was a highly significant linear relationship between the length of the neoglandular epithelium in the distal esophagus and the number of weeks after surgery (correlation coefficient, 0.94; P less than .0001),” the investigators stated.

Locational analysis revealed epithelial-mesenchymal transition markers being expressed by spindle-shaped cells at the leading edge of the columnar-lined esophagus. In addition, neoglands were identified within esophageal ulcer beds and actively dividing squamous epithelium was seen exclusively at the proximal ulcer border.

Following the systematic analysis, the authors noted that the columnar-lined esophagus was most likely the result of jejunal cell migration into the esophagus. They suggested that if compared, jejunal cells may competitively dominate squamous cells in the context of chronic gastroesophageal reflux disease. Furthermore, they observed that the region of ulceration following esophagojejunostomy in their model was more expansive than that reported in other comparable rodent models of reflux esophagitis.

“The reason for this difference is not clear, but we speculate that it is the result of technical aspects of our reflux-inducing surgery,” the researchers wrote. They further explained that “we intentionally fashioned a large anastomotic orifice between the esophagus and jejunum, perhaps larger than that fashioned by other investigators.” And they concluded, “we suspect that this larger orifice resulted in esophageal exposure to larger volumes of refluxate and, consequently, larger areas of ulceration.”

The authors acknowledged their results may not be fully applicable in the context of human Barrett’s esophagus, given the rodent model. However, they do believe the findings may provide a basis to help understand the wound repair process, particularly the distal edge of ulcers that border the columnar epithelium.

“Using a rat model of reflux esophagitis via surgical esophagojejunostomy, we have shown that a metaplastic, columnar-lined esophagus develops via a wound healing process, and not via genetic reprogramming of progenitor cells,” the researchers concluded.

The study was supported by grant funding from the National Institutes of Health and the Baylor Scott and White Research Institute. The authors reported no conflicts of interest.

SOURCE: Agoston AT et al. Cell Mol Gastroenterol Hepatol. 2018 Jun 26. doi: 10.1016/j.jcmgh.2018.06.007.

During a wound repair process in rats, metaplastic columnar-lined esophagus was produced and increased in length following esophagojejunostomy, which may be independent of stem cell reprogramming, according to results from an anastomosed rodent study.

The investigators studied esophageal and tissue sections of 52 rats at different time points after esophagojejunostomy and samples were analyzed for length, type, and location of columnar lining. In addition, the sections were examined immunophenotypically to elucidate the molecular changes that occur during ulceration. Agoston T. Agoston, MD, PhD, of Brigham and Women’s Hospital and the department of pathology at Harvard Medical School, Boston, and colleagues reported the findings in Cellular and Molecular Gastroenterology and Hepatology.

“This rodent columnar-lined esophagus has been proposed to develop from cellular reprogramming of progenitor cells, but studies on early columnar-lined esophagus development are lacking,” the researchers wrote.

In the model, ulceration was seen 2 weeks after surgery, which began distally at the esophagojejunal anastomosis. Representative of wound healing, reepithelialization of the ulcer region took place through formation of immature glands, which were found to bud directly from jejunal crypts.

After immunophenotypic analysis, the researchers reported that “immunohistochemical characterization of neoglandular epithelium located immediately proximal to the anastomosis showed features similar to those of the native nonproliferating jejunal epithelium located immediately distal to the anastomosis.” They further reported that “the columnar-lined esophagus’s immunoprofile was similar to jejunal crypt epithelium.”

Upon further examination of the ulcer segment, Dr. Agoston and colleagues found that columnar-lined esophagus elongated from 0.15 mm (standard error of the mean, ± 0.1) to 5.22 mm (SEM, ± 0.37) at 2 and 32 weeks post esophagojejunostomy, respectively.

“There was a highly significant linear relationship between the length of the neoglandular epithelium in the distal esophagus and the number of weeks after surgery (correlation coefficient, 0.94; P less than .0001),” the investigators stated.

Locational analysis revealed epithelial-mesenchymal transition markers being expressed by spindle-shaped cells at the leading edge of the columnar-lined esophagus. In addition, neoglands were identified within esophageal ulcer beds and actively dividing squamous epithelium was seen exclusively at the proximal ulcer border.

Following the systematic analysis, the authors noted that the columnar-lined esophagus was most likely the result of jejunal cell migration into the esophagus. They suggested that if compared, jejunal cells may competitively dominate squamous cells in the context of chronic gastroesophageal reflux disease. Furthermore, they observed that the region of ulceration following esophagojejunostomy in their model was more expansive than that reported in other comparable rodent models of reflux esophagitis.

“The reason for this difference is not clear, but we speculate that it is the result of technical aspects of our reflux-inducing surgery,” the researchers wrote. They further explained that “we intentionally fashioned a large anastomotic orifice between the esophagus and jejunum, perhaps larger than that fashioned by other investigators.” And they concluded, “we suspect that this larger orifice resulted in esophageal exposure to larger volumes of refluxate and, consequently, larger areas of ulceration.”

The authors acknowledged their results may not be fully applicable in the context of human Barrett’s esophagus, given the rodent model. However, they do believe the findings may provide a basis to help understand the wound repair process, particularly the distal edge of ulcers that border the columnar epithelium.

“Using a rat model of reflux esophagitis via surgical esophagojejunostomy, we have shown that a metaplastic, columnar-lined esophagus develops via a wound healing process, and not via genetic reprogramming of progenitor cells,” the researchers concluded.

The study was supported by grant funding from the National Institutes of Health and the Baylor Scott and White Research Institute. The authors reported no conflicts of interest.

SOURCE: Agoston AT et al. Cell Mol Gastroenterol Hepatol. 2018 Jun 26. doi: 10.1016/j.jcmgh.2018.06.007.

Among patients with adult congenital heart disease (ACHD), hepatitis C virus antibody positivity was significantly associated with a composite end point that comprised cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation, according to a report published online in the American Journal of Cardiology.

American Heart Association

The study retrospectively enrolled 243 ACHD patients (mean age 26 years) who underwent cardiac surgery before 1992 and visited a single hospital during 1995-2015. Clinical characteristics, including cardiac function and long-term prognosis, were compared between HCV antibody–positive (48) and –negative (195) patients, according to Ryo Konno, MD, of Tohoku University, Sendai, Japan, and his colleagues.

They found that the prevalence of reduced systemic ventricular ejection fraction less than 50% was significantly higher in the HCV antibody–positive group than in the HCV antibody–negative group (17 vs. 5.4%; P = .014), and that during a mean follow-up of 10 years the composite end point occurred in 51 patients.

Overall, Kaplan-Meier analysis showed the HCV antibody–positive group had significantly poorer event-free survival than the HCV antibody–negative group (P = .002). In addition, HCV antibody positivity was significantly associated with the composite end point in both univariable and multivariable Cox regression models (hazard ratio, 2.37; P = .005 and HR, 1.96; P = .032, respectively).

“These results indicate that screening for HCV should be performed in all ACHD patients with a history of heart surgery before 1992. Further, cardiac functions should be monitored more frequently to detect [stroke volume] dysfunction earlier in case of a positive result. These management strategies may have a beneficial impact on the long-term prognosis in this population,” Dr. Konno and his colleagues concluded.

The research was supported by the Japan Agency for Medical Research and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Konno R. et al. Am J Card. 2018;122:1965-71.

Among patients with adult congenital heart disease (ACHD), hepatitis C virus antibody positivity was significantly associated with a composite end point that comprised cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation, according to a report published online in the American Journal of Cardiology.

American Heart Association

The study retrospectively enrolled 243 ACHD patients (mean age 26 years) who underwent cardiac surgery before 1992 and visited a single hospital during 1995-2015. Clinical characteristics, including cardiac function and long-term prognosis, were compared between HCV antibody–positive (48) and –negative (195) patients, according to Ryo Konno, MD, of Tohoku University, Sendai, Japan, and his colleagues.

They found that the prevalence of reduced systemic ventricular ejection fraction less than 50% was significantly higher in the HCV antibody–positive group than in the HCV antibody–negative group (17 vs. 5.4%; P = .014), and that during a mean follow-up of 10 years the composite end point occurred in 51 patients.

Overall, Kaplan-Meier analysis showed the HCV antibody–positive group had significantly poorer event-free survival than the HCV antibody–negative group (P = .002). In addition, HCV antibody positivity was significantly associated with the composite end point in both univariable and multivariable Cox regression models (hazard ratio, 2.37; P = .005 and HR, 1.96; P = .032, respectively).

“These results indicate that screening for HCV should be performed in all ACHD patients with a history of heart surgery before 1992. Further, cardiac functions should be monitored more frequently to detect [stroke volume] dysfunction earlier in case of a positive result. These management strategies may have a beneficial impact on the long-term prognosis in this population,” Dr. Konno and his colleagues concluded.

The research was supported by the Japan Agency for Medical Research and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Konno R. et al. Am J Card. 2018;122:1965-71.

Among patients with adult congenital heart disease (ACHD), hepatitis C virus antibody positivity was significantly associated with a composite end point that comprised cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation, according to a report published online in the American Journal of Cardiology.

American Heart Association

The study retrospectively enrolled 243 ACHD patients (mean age 26 years) who underwent cardiac surgery before 1992 and visited a single hospital during 1995-2015. Clinical characteristics, including cardiac function and long-term prognosis, were compared between HCV antibody–positive (48) and –negative (195) patients, according to Ryo Konno, MD, of Tohoku University, Sendai, Japan, and his colleagues.

They found that the prevalence of reduced systemic ventricular ejection fraction less than 50% was significantly higher in the HCV antibody–positive group than in the HCV antibody–negative group (17 vs. 5.4%; P = .014), and that during a mean follow-up of 10 years the composite end point occurred in 51 patients.

Overall, Kaplan-Meier analysis showed the HCV antibody–positive group had significantly poorer event-free survival than the HCV antibody–negative group (P = .002). In addition, HCV antibody positivity was significantly associated with the composite end point in both univariable and multivariable Cox regression models (hazard ratio, 2.37; P = .005 and HR, 1.96; P = .032, respectively).

“These results indicate that screening for HCV should be performed in all ACHD patients with a history of heart surgery before 1992. Further, cardiac functions should be monitored more frequently to detect [stroke volume] dysfunction earlier in case of a positive result. These management strategies may have a beneficial impact on the long-term prognosis in this population,” Dr. Konno and his colleagues concluded.

The research was supported by the Japan Agency for Medical Research and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Konno R. et al. Am J Card. 2018;122:1965-71.

NEW YORK – Vascular surgeons are the only specialty qualified to treat all vascular disorders with open surgery and/or endovascular treatment, including the thoracic aorta, according to the updated “Guidelines for hospital privileges in vascular surgery and endovascular interventions: Recommendations of the Society for Vascular Surgery.”

The guidelines, published in May’s Journal of Vascular Surgery, were last updated in 2008, said Keith D. Calligaro, MD, who spoke on their importance and potential benefits to vascular surgeons during his presentation at the VEITHsymposium.

The thoracic aorta component of the guidelines addresses scope of practice concerns between vascular and thoracic surgeons, said Dr. Calligaro, who is a clinical professor of surgery, University of Pennsylvania, and chief of vascular surgery and endovascular therapy at Pennsylvania Hospital, both in Philadelphia.

The guidelines relied on training requirements to provide some of the data to define vascular surgeons and privileges. The open vascular surgery training requirements still are defined by the Residency Review Committee for surgery, and those requirements include 250 major open vascular cases during training, including 30 open abdominal operations, 25 carotid, 45 peripheral open surgery cases, and 10 complex vascular surgeries, said Dr. Calligaro. “In terms of endovascular treatment, the training requirements are over 100 diagnostic caths and over 80 therapeutic interventions, and during training you would have had to have done more than 20 EVARs [endovascular aneurysm repairs].” That number jumped up from five EVARs in the previous guidelines.

Ultimately, “the SVS is basically saying ‘you need to be a vascular surgeon to perform vascular surgery,’ and you need have to have completed an Accreditation Council for Graduate Medical Education–accredited vascular residency.

“So if you are a general surgeon or a heart surgeon and you go to a new hospital and say ‘I want to do vascular,’ the vascular surgeon at that institution can refer to this document and say ‘no, the SVS is saying [the surgeon doesn’t] have the training.’ And I think that’s a pretty gutsy and important call,” said Dr. Calligaro.

It is a different case for endovascular surgery, he said. In this case, the requirement is to have completed an ACGME-accredited program in either vascular surgery, interventional radiology, or interventional cardiology to indicate the appropriate level of training. But SVS agreed with the recommendation by the American College of Cardiology that cardiologists not only had to complete 1 year of coronary interventions but also 1 year of peripheral intervention training, as well.

“So if you are at your hospital and have a cardiologist who is starting to do peripheral vascular stuff, now at least you can wave part of this document and say ‘Hey, look, the most important vascular society in the country is saying that, unless this individual had a year of peripheral training, this cardiologist should not be allowed to do endovascular peripheral interventions,’ ” Dr. Calligaro said.

[email protected]

SOURCE: Calligaro KD et al. J Vasc Surg. 2018 May;67(5):1337-44.

NEW YORK – Vascular surgeons are the only specialty qualified to treat all vascular disorders with open surgery and/or endovascular treatment, including the thoracic aorta, according to the updated “Guidelines for hospital privileges in vascular surgery and endovascular interventions: Recommendations of the Society for Vascular Surgery.”

The guidelines, published in May’s Journal of Vascular Surgery, were last updated in 2008, said Keith D. Calligaro, MD, who spoke on their importance and potential benefits to vascular surgeons during his presentation at the VEITHsymposium.

The thoracic aorta component of the guidelines addresses scope of practice concerns between vascular and thoracic surgeons, said Dr. Calligaro, who is a clinical professor of surgery, University of Pennsylvania, and chief of vascular surgery and endovascular therapy at Pennsylvania Hospital, both in Philadelphia.

The guidelines relied on training requirements to provide some of the data to define vascular surgeons and privileges. The open vascular surgery training requirements still are defined by the Residency Review Committee for surgery, and those requirements include 250 major open vascular cases during training, including 30 open abdominal operations, 25 carotid, 45 peripheral open surgery cases, and 10 complex vascular surgeries, said Dr. Calligaro. “In terms of endovascular treatment, the training requirements are over 100 diagnostic caths and over 80 therapeutic interventions, and during training you would have had to have done more than 20 EVARs [endovascular aneurysm repairs].” That number jumped up from five EVARs in the previous guidelines.

Ultimately, “the SVS is basically saying ‘you need to be a vascular surgeon to perform vascular surgery,’ and you need have to have completed an Accreditation Council for Graduate Medical Education–accredited vascular residency.

“So if you are a general surgeon or a heart surgeon and you go to a new hospital and say ‘I want to do vascular,’ the vascular surgeon at that institution can refer to this document and say ‘no, the SVS is saying [the surgeon doesn’t] have the training.’ And I think that’s a pretty gutsy and important call,” said Dr. Calligaro.

It is a different case for endovascular surgery, he said. In this case, the requirement is to have completed an ACGME-accredited program in either vascular surgery, interventional radiology, or interventional cardiology to indicate the appropriate level of training. But SVS agreed with the recommendation by the American College of Cardiology that cardiologists not only had to complete 1 year of coronary interventions but also 1 year of peripheral intervention training, as well.

“So if you are at your hospital and have a cardiologist who is starting to do peripheral vascular stuff, now at least you can wave part of this document and say ‘Hey, look, the most important vascular society in the country is saying that, unless this individual had a year of peripheral training, this cardiologist should not be allowed to do endovascular peripheral interventions,’ ” Dr. Calligaro said.

[email protected]

SOURCE: Calligaro KD et al. J Vasc Surg. 2018 May;67(5):1337-44.

NEW YORK – Vascular surgeons are the only specialty qualified to treat all vascular disorders with open surgery and/or endovascular treatment, including the thoracic aorta, according to the updated “Guidelines for hospital privileges in vascular surgery and endovascular interventions: Recommendations of the Society for Vascular Surgery.”

The guidelines, published in May’s Journal of Vascular Surgery, were last updated in 2008, said Keith D. Calligaro, MD, who spoke on their importance and potential benefits to vascular surgeons during his presentation at the VEITHsymposium.

The thoracic aorta component of the guidelines addresses scope of practice concerns between vascular and thoracic surgeons, said Dr. Calligaro, who is a clinical professor of surgery, University of Pennsylvania, and chief of vascular surgery and endovascular therapy at Pennsylvania Hospital, both in Philadelphia.

The guidelines relied on training requirements to provide some of the data to define vascular surgeons and privileges. The open vascular surgery training requirements still are defined by the Residency Review Committee for surgery, and those requirements include 250 major open vascular cases during training, including 30 open abdominal operations, 25 carotid, 45 peripheral open surgery cases, and 10 complex vascular surgeries, said Dr. Calligaro. “In terms of endovascular treatment, the training requirements are over 100 diagnostic caths and over 80 therapeutic interventions, and during training you would have had to have done more than 20 EVARs [endovascular aneurysm repairs].” That number jumped up from five EVARs in the previous guidelines.

Ultimately, “the SVS is basically saying ‘you need to be a vascular surgeon to perform vascular surgery,’ and you need have to have completed an Accreditation Council for Graduate Medical Education–accredited vascular residency.

“So if you are a general surgeon or a heart surgeon and you go to a new hospital and say ‘I want to do vascular,’ the vascular surgeon at that institution can refer to this document and say ‘no, the SVS is saying [the surgeon doesn’t] have the training.’ And I think that’s a pretty gutsy and important call,” said Dr. Calligaro.

It is a different case for endovascular surgery, he said. In this case, the requirement is to have completed an ACGME-accredited program in either vascular surgery, interventional radiology, or interventional cardiology to indicate the appropriate level of training. But SVS agreed with the recommendation by the American College of Cardiology that cardiologists not only had to complete 1 year of coronary interventions but also 1 year of peripheral intervention training, as well.

“So if you are at your hospital and have a cardiologist who is starting to do peripheral vascular stuff, now at least you can wave part of this document and say ‘Hey, look, the most important vascular society in the country is saying that, unless this individual had a year of peripheral training, this cardiologist should not be allowed to do endovascular peripheral interventions,’ ” Dr. Calligaro said.

[email protected]

SOURCE: Calligaro KD et al. J Vasc Surg. 2018 May;67(5):1337-44.