Cutaneous angiosarcoma is a rare malignant tumor of vascular endothelial cells that has the propensity to arise in various clinical settings. This tumor predominantly occurs in the head and neck region in elderly patients, but it also has been reported to develop postradiotherapy or in the setting of chronic lymphedema in the extremities.^1-3 In all settings, the diagnosis carries a very poor prognosis with a high likelihood of local recurrence and rapid dissemination. The mortality rate typically is 80% or higher.^2,4-6

Making the correct clinical diagnosis of cutaneous angiosarcoma may be difficult given the variety of patient symptoms and clinical appearances that can be demonstrated on presentation. Lesions can appear as bluish or violaceous plaques, macules, or nodules, and ulceration may be present in some advanced cases.^5,7 Clinical misdiagnosis is common, as cutaneous angiosarcomas may be mistaken for infectious processes, benign vascular malformations, and other cutaneous malignancies.¹ Biopsy often is delayed given the initial benign appearance of the lesions, and this frequently results in aggressive and extensive disease at the time of diagnosis, which is unfortunate given that small tumor size has been shown to be one of the only favorable prognostic indicators in cutaneous angiosarcoma.^1,2,6,8

Microscopically, diagnosis of cutaneous angiosarcoma can present a challenge, as the histology varies between a well-differentiated vascular neoplasm and a considerably anaplastic and poorly differentiated malignancy. On low power, some areas may appear as benign hemangiomas with other areas showing frank sarcomatous features.⁹ As a result, these tumors can be mistaken for a variety of other diseases including melanomas, carcinomas, or other vascular tumors.^6,8,9 Previously, electron microscopy has been utilized on undifferentiated tumors to help distinguish cutaneous angiosarcomas from other potential diagnoses. The atypical tumor cells of cutaneous angiosarcoma display common features of endothelial cells (eg, pinocytotic vesicles, tubulated bodies).⁷ Historically, it has been noted that the histologic findings and tumor grade provide little evidence regarding the aggressiveness of the tumor, and all cutaneous angiosarcoma diagnoses receive a poor prognosis.^6,8

Classically, the histologic findings of cutaneous angiosarcoma include a highly infiltrative neoplasm forming irregular vascular channels that penetrate through the cutaneous soft tissues and frequently extend into the subcutaneous fat. The vascular spaces are lined by hyperchromatic endothelial cells with varying degrees of atypia.^1,2,4,6,7,10 Occasionally, prominent endothelial cells lining a papillary structure within the lumen of the neoformed vessel may also be observed. Currently, immunohistochemical staining for MYC, Ki-67, D2-40, and various other markers complement the histologic findings to aid in the diagnosis of cutaneous angiosarcoma.^11,12 An additional diagnostic clue that has been described in cases of postirradiation cutaneous angiosarcoma shows free-floating or tufted pleomorphic spindle cells within the vascular lumen (Figure). This finding has been described as “fish in the creek.”¹¹ In this study, we aimed to determine the frequency and subsequent diagnostic utility of the fish-in-the-creek finding in cases of cutaneous angiosarcoma.

Methods

A natural language search of our institutional archives over a 20-year period (1997–2017) using the term angiosarcoma was performed. Fifteen cases of cutaneous angiosarcoma were identified. Fifteen additional benign and malignant vascular tumors with cutaneous angiosarcoma in the histologic differential diagnosis were selected from the archives over a similar time frame. The additional lesions included Kaposi sarcoma (n=3), atypical vascular lesion (n=6), atypical hemangioma (n=1), tufted angioma (n=1), epithelioid hemangioma (n=1), epithelioid hemangioendothelioma (n=1), sinusoidal hemangioma (n=1), and angiofibroma (n=1). The pathologists were blinded to the original diagnosis of each case and were instructed to evaluate the histology slides for the sole feature of free-floating intraluminal spindle cells or spindle cells tufting off the endothelium. Epithelial cells lining papillae found within the vessel lumen were not counted as a positive finding, as they do not fit the criteria described for the histologic pattern of fish in the creek. Following microscopic evaluation, the original diagnoses were reassigned to their respective cases to evaluate the diagnostic utility of this feature.

Results

The histologic pattern of fish in the creek was identified in all 15 cases of cutaneous angiosarcoma and was absent in the other 15 malignancies examined in this study. This finding shows the potential for the fish-in-the-creek pattern to be used as an additional diagnostic tool for dermatopathologists.

Comment

Cutaneous angiosarcoma is a rare but aggressive malignancy that proves difficult to diagnose both clinically and histologically as well as to treat effectively.^1,5-8 Our results indicate that fish in the creek may be a useful and salient histologic feature in cutaneous angiosarcoma. It is important to recognize, however, that this finding should not be the sole feature upon which a diagnosis of cutaneous angiosarcoma is made, as it requires corroboration with positivity of MYC and D2-40 as well as a high Ki-67 proliferation index (>20%).^11,12 Finding a fish-in-the-creek pattern should prompt dermatopathologists to consider a diagnosis of cutaneous angiosarcoma in the appropriate clinical and histologic settings.

The chief limitation of this study was the small sample size, with only 15 cases of cutaneous angiosarcoma available in the last 20 years at our institution. The limited sample size did not allow us to make claims on sensitivity and specificity regarding this histologic feature; however, with a larger sample size, the true diagnostic potential could be elucidated. Although the pathologists were blinded to the original diagnoses as they examined it for fish in the creek, it is possible they were able to make the correct diagnosis based on other histopathologic clues and therefore were biased.

Although the fish-in-the-creek pattern is present in cutaneous angiosarcoma, there may be other mimickers to consider. Intraluminal papillary projections lined by endothelial cells may be sectioned in a manner imitating this finding.³ In such a case, these endothelial cells must be differentiated from the free-floating or tufted spindle cells in order to have a positive finding for fish in the creek. There can be confusion if the biopsy cuts through a section of spindled cells, resulting in difficulty differentiating cutaneous angiosarcoma from other spindle tumors such as spindle cell melanoma or spindle cell squamous cell carcinoma.⁶ In such cases, immunohistochemistry may be helpful, as spindle cell melanoma would stain positive for S100 and SOX10 and spindle cell squamous cell carcinoma would stain positive for p63 and cytokeratin.

Various treatment strategies for cutaneous angiosarcoma have been employed, with the majority still resulting in poor outcomes.^2,4-6 The recommended treatment is radical surgical excision of the primary tumor with lymph node clearance if possible. Following excision, the patient should undergo high-dose, wide-field radiotherapy to the region.^5,8 Cutaneous angiosarcomas also have the ability to spread extensively through the dermis and can result in subclinical or clinically obvious widespread disease with multifocal or satellite lesions present. Distant metastases occur most frequently in the cervical lymph nodes and lungs.⁷ In cases where the disease is too extensive for surgery, palliative radiation monotherapy can be used.^5,6

As atypical vascular lesions are considered to be a precursor to cutaneous angiosarcoma, it is important to note that the fish-in-the-creek feature was absent in all 6 of the atypical vascular lesions observed in the study. The differentiation generally is made based on MYC, which is present in cutaneous angiosarcomas and absent in atypical vascular lesions.¹⁰ The feature of fish in the creek may now be an additional clue for dermatopathologists to differentiate between angiosarcomas and other similar-appearing tumors.

Conclusion

Our study aimed to highlight an important histologic feature of cutaneous angiosarcomas that can aid in the diagnosis of this deceptive malignancy. Our findings warrant further study of the fish-in-the-creek histologic pattern in a larger sample size to determine its success as a diagnostic tool for cutaneous angiosarcomas. As noted previously, tumor grade does not impact survival outcome, but small tumor size has been one of the only features found to result in a more favorable prognosis.^1,6,8 Future studies to identify a correlation between the histologic finding of fish in the creek and disease outcome in cutaneous angiosarcoma may be helpful to determine if these histologic findings provide prognostic significance in cases of cutaneous angiosarcoma.

Cutaneous angiosarcoma is a rare malignant tumor of vascular endothelial cells that has the propensity to arise in various clinical settings. This tumor predominantly occurs in the head and neck region in elderly patients, but it also has been reported to develop postradiotherapy or in the setting of chronic lymphedema in the extremities.^1-3 In all settings, the diagnosis carries a very poor prognosis with a high likelihood of local recurrence and rapid dissemination. The mortality rate typically is 80% or higher.^2,4-6

Making the correct clinical diagnosis of cutaneous angiosarcoma may be difficult given the variety of patient symptoms and clinical appearances that can be demonstrated on presentation. Lesions can appear as bluish or violaceous plaques, macules, or nodules, and ulceration may be present in some advanced cases.^5,7 Clinical misdiagnosis is common, as cutaneous angiosarcomas may be mistaken for infectious processes, benign vascular malformations, and other cutaneous malignancies.¹ Biopsy often is delayed given the initial benign appearance of the lesions, and this frequently results in aggressive and extensive disease at the time of diagnosis, which is unfortunate given that small tumor size has been shown to be one of the only favorable prognostic indicators in cutaneous angiosarcoma.^1,2,6,8

Microscopically, diagnosis of cutaneous angiosarcoma can present a challenge, as the histology varies between a well-differentiated vascular neoplasm and a considerably anaplastic and poorly differentiated malignancy. On low power, some areas may appear as benign hemangiomas with other areas showing frank sarcomatous features.⁹ As a result, these tumors can be mistaken for a variety of other diseases including melanomas, carcinomas, or other vascular tumors.^6,8,9 Previously, electron microscopy has been utilized on undifferentiated tumors to help distinguish cutaneous angiosarcomas from other potential diagnoses. The atypical tumor cells of cutaneous angiosarcoma display common features of endothelial cells (eg, pinocytotic vesicles, tubulated bodies).⁷ Historically, it has been noted that the histologic findings and tumor grade provide little evidence regarding the aggressiveness of the tumor, and all cutaneous angiosarcoma diagnoses receive a poor prognosis.^6,8

Classically, the histologic findings of cutaneous angiosarcoma include a highly infiltrative neoplasm forming irregular vascular channels that penetrate through the cutaneous soft tissues and frequently extend into the subcutaneous fat. The vascular spaces are lined by hyperchromatic endothelial cells with varying degrees of atypia.^1,2,4,6,7,10 Occasionally, prominent endothelial cells lining a papillary structure within the lumen of the neoformed vessel may also be observed. Currently, immunohistochemical staining for MYC, Ki-67, D2-40, and various other markers complement the histologic findings to aid in the diagnosis of cutaneous angiosarcoma.^11,12 An additional diagnostic clue that has been described in cases of postirradiation cutaneous angiosarcoma shows free-floating or tufted pleomorphic spindle cells within the vascular lumen (Figure). This finding has been described as “fish in the creek.”¹¹ In this study, we aimed to determine the frequency and subsequent diagnostic utility of the fish-in-the-creek finding in cases of cutaneous angiosarcoma.

Methods

A natural language search of our institutional archives over a 20-year period (1997–2017) using the term angiosarcoma was performed. Fifteen cases of cutaneous angiosarcoma were identified. Fifteen additional benign and malignant vascular tumors with cutaneous angiosarcoma in the histologic differential diagnosis were selected from the archives over a similar time frame. The additional lesions included Kaposi sarcoma (n=3), atypical vascular lesion (n=6), atypical hemangioma (n=1), tufted angioma (n=1), epithelioid hemangioma (n=1), epithelioid hemangioendothelioma (n=1), sinusoidal hemangioma (n=1), and angiofibroma (n=1). The pathologists were blinded to the original diagnosis of each case and were instructed to evaluate the histology slides for the sole feature of free-floating intraluminal spindle cells or spindle cells tufting off the endothelium. Epithelial cells lining papillae found within the vessel lumen were not counted as a positive finding, as they do not fit the criteria described for the histologic pattern of fish in the creek. Following microscopic evaluation, the original diagnoses were reassigned to their respective cases to evaluate the diagnostic utility of this feature.

Results

The histologic pattern of fish in the creek was identified in all 15 cases of cutaneous angiosarcoma and was absent in the other 15 malignancies examined in this study. This finding shows the potential for the fish-in-the-creek pattern to be used as an additional diagnostic tool for dermatopathologists.

Comment

Cutaneous angiosarcoma is a rare but aggressive malignancy that proves difficult to diagnose both clinically and histologically as well as to treat effectively.^1,5-8 Our results indicate that fish in the creek may be a useful and salient histologic feature in cutaneous angiosarcoma. It is important to recognize, however, that this finding should not be the sole feature upon which a diagnosis of cutaneous angiosarcoma is made, as it requires corroboration with positivity of MYC and D2-40 as well as a high Ki-67 proliferation index (>20%).^11,12 Finding a fish-in-the-creek pattern should prompt dermatopathologists to consider a diagnosis of cutaneous angiosarcoma in the appropriate clinical and histologic settings.

The chief limitation of this study was the small sample size, with only 15 cases of cutaneous angiosarcoma available in the last 20 years at our institution. The limited sample size did not allow us to make claims on sensitivity and specificity regarding this histologic feature; however, with a larger sample size, the true diagnostic potential could be elucidated. Although the pathologists were blinded to the original diagnoses as they examined it for fish in the creek, it is possible they were able to make the correct diagnosis based on other histopathologic clues and therefore were biased.

Although the fish-in-the-creek pattern is present in cutaneous angiosarcoma, there may be other mimickers to consider. Intraluminal papillary projections lined by endothelial cells may be sectioned in a manner imitating this finding.³ In such a case, these endothelial cells must be differentiated from the free-floating or tufted spindle cells in order to have a positive finding for fish in the creek. There can be confusion if the biopsy cuts through a section of spindled cells, resulting in difficulty differentiating cutaneous angiosarcoma from other spindle tumors such as spindle cell melanoma or spindle cell squamous cell carcinoma.⁶ In such cases, immunohistochemistry may be helpful, as spindle cell melanoma would stain positive for S100 and SOX10 and spindle cell squamous cell carcinoma would stain positive for p63 and cytokeratin.

Various treatment strategies for cutaneous angiosarcoma have been employed, with the majority still resulting in poor outcomes.^2,4-6 The recommended treatment is radical surgical excision of the primary tumor with lymph node clearance if possible. Following excision, the patient should undergo high-dose, wide-field radiotherapy to the region.^5,8 Cutaneous angiosarcomas also have the ability to spread extensively through the dermis and can result in subclinical or clinically obvious widespread disease with multifocal or satellite lesions present. Distant metastases occur most frequently in the cervical lymph nodes and lungs.⁷ In cases where the disease is too extensive for surgery, palliative radiation monotherapy can be used.^5,6

As atypical vascular lesions are considered to be a precursor to cutaneous angiosarcoma, it is important to note that the fish-in-the-creek feature was absent in all 6 of the atypical vascular lesions observed in the study. The differentiation generally is made based on MYC, which is present in cutaneous angiosarcomas and absent in atypical vascular lesions.¹⁰ The feature of fish in the creek may now be an additional clue for dermatopathologists to differentiate between angiosarcomas and other similar-appearing tumors.

Conclusion

Our study aimed to highlight an important histologic feature of cutaneous angiosarcomas that can aid in the diagnosis of this deceptive malignancy. Our findings warrant further study of the fish-in-the-creek histologic pattern in a larger sample size to determine its success as a diagnostic tool for cutaneous angiosarcomas. As noted previously, tumor grade does not impact survival outcome, but small tumor size has been one of the only features found to result in a more favorable prognosis.^1,6,8 Future studies to identify a correlation between the histologic finding of fish in the creek and disease outcome in cutaneous angiosarcoma may be helpful to determine if these histologic findings provide prognostic significance in cases of cutaneous angiosarcoma.

Cutaneous angiosarcoma is a rare malignant tumor of vascular endothelial cells that has the propensity to arise in various clinical settings. This tumor predominantly occurs in the head and neck region in elderly patients, but it also has been reported to develop postradiotherapy or in the setting of chronic lymphedema in the extremities.^1-3 In all settings, the diagnosis carries a very poor prognosis with a high likelihood of local recurrence and rapid dissemination. The mortality rate typically is 80% or higher.^2,4-6

Making the correct clinical diagnosis of cutaneous angiosarcoma may be difficult given the variety of patient symptoms and clinical appearances that can be demonstrated on presentation. Lesions can appear as bluish or violaceous plaques, macules, or nodules, and ulceration may be present in some advanced cases.^5,7 Clinical misdiagnosis is common, as cutaneous angiosarcomas may be mistaken for infectious processes, benign vascular malformations, and other cutaneous malignancies.¹ Biopsy often is delayed given the initial benign appearance of the lesions, and this frequently results in aggressive and extensive disease at the time of diagnosis, which is unfortunate given that small tumor size has been shown to be one of the only favorable prognostic indicators in cutaneous angiosarcoma.^1,2,6,8

Microscopically, diagnosis of cutaneous angiosarcoma can present a challenge, as the histology varies between a well-differentiated vascular neoplasm and a considerably anaplastic and poorly differentiated malignancy. On low power, some areas may appear as benign hemangiomas with other areas showing frank sarcomatous features.⁹ As a result, these tumors can be mistaken for a variety of other diseases including melanomas, carcinomas, or other vascular tumors.^6,8,9 Previously, electron microscopy has been utilized on undifferentiated tumors to help distinguish cutaneous angiosarcomas from other potential diagnoses. The atypical tumor cells of cutaneous angiosarcoma display common features of endothelial cells (eg, pinocytotic vesicles, tubulated bodies).⁷ Historically, it has been noted that the histologic findings and tumor grade provide little evidence regarding the aggressiveness of the tumor, and all cutaneous angiosarcoma diagnoses receive a poor prognosis.^6,8

Classically, the histologic findings of cutaneous angiosarcoma include a highly infiltrative neoplasm forming irregular vascular channels that penetrate through the cutaneous soft tissues and frequently extend into the subcutaneous fat. The vascular spaces are lined by hyperchromatic endothelial cells with varying degrees of atypia.^1,2,4,6,7,10 Occasionally, prominent endothelial cells lining a papillary structure within the lumen of the neoformed vessel may also be observed. Currently, immunohistochemical staining for MYC, Ki-67, D2-40, and various other markers complement the histologic findings to aid in the diagnosis of cutaneous angiosarcoma.^11,12 An additional diagnostic clue that has been described in cases of postirradiation cutaneous angiosarcoma shows free-floating or tufted pleomorphic spindle cells within the vascular lumen (Figure). This finding has been described as “fish in the creek.”¹¹ In this study, we aimed to determine the frequency and subsequent diagnostic utility of the fish-in-the-creek finding in cases of cutaneous angiosarcoma.

Methods

A natural language search of our institutional archives over a 20-year period (1997–2017) using the term angiosarcoma was performed. Fifteen cases of cutaneous angiosarcoma were identified. Fifteen additional benign and malignant vascular tumors with cutaneous angiosarcoma in the histologic differential diagnosis were selected from the archives over a similar time frame. The additional lesions included Kaposi sarcoma (n=3), atypical vascular lesion (n=6), atypical hemangioma (n=1), tufted angioma (n=1), epithelioid hemangioma (n=1), epithelioid hemangioendothelioma (n=1), sinusoidal hemangioma (n=1), and angiofibroma (n=1). The pathologists were blinded to the original diagnosis of each case and were instructed to evaluate the histology slides for the sole feature of free-floating intraluminal spindle cells or spindle cells tufting off the endothelium. Epithelial cells lining papillae found within the vessel lumen were not counted as a positive finding, as they do not fit the criteria described for the histologic pattern of fish in the creek. Following microscopic evaluation, the original diagnoses were reassigned to their respective cases to evaluate the diagnostic utility of this feature.

Results

The histologic pattern of fish in the creek was identified in all 15 cases of cutaneous angiosarcoma and was absent in the other 15 malignancies examined in this study. This finding shows the potential for the fish-in-the-creek pattern to be used as an additional diagnostic tool for dermatopathologists.

Comment

Cutaneous angiosarcoma is a rare but aggressive malignancy that proves difficult to diagnose both clinically and histologically as well as to treat effectively.^1,5-8 Our results indicate that fish in the creek may be a useful and salient histologic feature in cutaneous angiosarcoma. It is important to recognize, however, that this finding should not be the sole feature upon which a diagnosis of cutaneous angiosarcoma is made, as it requires corroboration with positivity of MYC and D2-40 as well as a high Ki-67 proliferation index (>20%).^11,12 Finding a fish-in-the-creek pattern should prompt dermatopathologists to consider a diagnosis of cutaneous angiosarcoma in the appropriate clinical and histologic settings.

The chief limitation of this study was the small sample size, with only 15 cases of cutaneous angiosarcoma available in the last 20 years at our institution. The limited sample size did not allow us to make claims on sensitivity and specificity regarding this histologic feature; however, with a larger sample size, the true diagnostic potential could be elucidated. Although the pathologists were blinded to the original diagnoses as they examined it for fish in the creek, it is possible they were able to make the correct diagnosis based on other histopathologic clues and therefore were biased.

Although the fish-in-the-creek pattern is present in cutaneous angiosarcoma, there may be other mimickers to consider. Intraluminal papillary projections lined by endothelial cells may be sectioned in a manner imitating this finding.³ In such a case, these endothelial cells must be differentiated from the free-floating or tufted spindle cells in order to have a positive finding for fish in the creek. There can be confusion if the biopsy cuts through a section of spindled cells, resulting in difficulty differentiating cutaneous angiosarcoma from other spindle tumors such as spindle cell melanoma or spindle cell squamous cell carcinoma.⁶ In such cases, immunohistochemistry may be helpful, as spindle cell melanoma would stain positive for S100 and SOX10 and spindle cell squamous cell carcinoma would stain positive for p63 and cytokeratin.

Various treatment strategies for cutaneous angiosarcoma have been employed, with the majority still resulting in poor outcomes.^2,4-6 The recommended treatment is radical surgical excision of the primary tumor with lymph node clearance if possible. Following excision, the patient should undergo high-dose, wide-field radiotherapy to the region.^5,8 Cutaneous angiosarcomas also have the ability to spread extensively through the dermis and can result in subclinical or clinically obvious widespread disease with multifocal or satellite lesions present. Distant metastases occur most frequently in the cervical lymph nodes and lungs.⁷ In cases where the disease is too extensive for surgery, palliative radiation monotherapy can be used.^5,6

As atypical vascular lesions are considered to be a precursor to cutaneous angiosarcoma, it is important to note that the fish-in-the-creek feature was absent in all 6 of the atypical vascular lesions observed in the study. The differentiation generally is made based on MYC, which is present in cutaneous angiosarcomas and absent in atypical vascular lesions.¹⁰ The feature of fish in the creek may now be an additional clue for dermatopathologists to differentiate between angiosarcomas and other similar-appearing tumors.

Conclusion

Our study aimed to highlight an important histologic feature of cutaneous angiosarcomas that can aid in the diagnosis of this deceptive malignancy. Our findings warrant further study of the fish-in-the-creek histologic pattern in a larger sample size to determine its success as a diagnostic tool for cutaneous angiosarcomas. As noted previously, tumor grade does not impact survival outcome, but small tumor size has been one of the only features found to result in a more favorable prognosis.^1,6,8 Future studies to identify a correlation between the histologic finding of fish in the creek and disease outcome in cutaneous angiosarcoma may be helpful to determine if these histologic findings provide prognostic significance in cases of cutaneous angiosarcoma.

CHICAGO – Levothyroxine treatment is associated with increased mortality in patients 65 years and older with subclinical hypothyroidism, according to a study presented at the annual meeting of the Endocrine Society.

With increased mortality and similar prevalence of atrial fibrillation and femoral fractures between study and control groups, physicians may want to reevaluate giving their elderly patients levothyroxine until more information is available, according to presenter Joseph Meyerovitch, MD, of Schneider Children’s Medical Center, Ramat Hasharon, Israel.

The case-control study included 416 patients 65 years or older with TSH levels of 4.2-10 mIU/L who died between 2012 and 2016, and 1,461 patients with comparable TSH levels who did not die during that time.

Most of the patients in both the control and study group were women. The average age of the patients was 84 years, and most had some form of dementia or senility (86.4%).

Mortality was 19% more likely in the group taking levothyroxine, according to an analysis by Dr. Meyerovitch and his fellow investigators.

When broken down further, presence of certain comorbidities increased mortality dramatically, including dementia (odds ratio, 1.61), heart failure (OR, 2.67), chronic renal failure (OR, 1.89), and cerebrovascular disease (OR, 1.94).

There was no significant difference in prevalence of atrial fibrillation between the test and control groups with thyroid stimulating hormone (TSH) testing, nor any difference in femur fracture prevalence.

Patients were given a TSH test three times during follow-up and showed significantly lower TSH levels compared with controls, according to Dr. Meyerovitch.

Dr. Meyerovitch acknowledged that the data he and his team used did not include the reason for a TSH evaluation, nor why patients began levothyroxine treatment. This leaves unanswered questions about the initial baseline mortality risk in patients included in the study.

“This may have resulted in treatment of patients with a higher risk, since we don’t know the reason for the treatment,” he said. “There may have been other reasons that were not included in the database that caused the physician to treat with levothyroxine.”

Details on the cause of death were not included.

Despite these limitations, Dr. Meyerovitch and his team stressed the need for more research before continuing to recommend this treatment to their elderly patients.

Dr. Meyerovitch reported no relevant financial disclosures.

ezimmerman@mdedge.com

Source: Meyerovitch J et al. ENDO 2018 Abstract OR34-2.

CHICAGO – Levothyroxine treatment is associated with increased mortality in patients 65 years and older with subclinical hypothyroidism, according to a study presented at the annual meeting of the Endocrine Society.

With increased mortality and similar prevalence of atrial fibrillation and femoral fractures between study and control groups, physicians may want to reevaluate giving their elderly patients levothyroxine until more information is available, according to presenter Joseph Meyerovitch, MD, of Schneider Children’s Medical Center, Ramat Hasharon, Israel.

The case-control study included 416 patients 65 years or older with TSH levels of 4.2-10 mIU/L who died between 2012 and 2016, and 1,461 patients with comparable TSH levels who did not die during that time.

Most of the patients in both the control and study group were women. The average age of the patients was 84 years, and most had some form of dementia or senility (86.4%).

Mortality was 19% more likely in the group taking levothyroxine, according to an analysis by Dr. Meyerovitch and his fellow investigators.

When broken down further, presence of certain comorbidities increased mortality dramatically, including dementia (odds ratio, 1.61), heart failure (OR, 2.67), chronic renal failure (OR, 1.89), and cerebrovascular disease (OR, 1.94).

There was no significant difference in prevalence of atrial fibrillation between the test and control groups with thyroid stimulating hormone (TSH) testing, nor any difference in femur fracture prevalence.

Patients were given a TSH test three times during follow-up and showed significantly lower TSH levels compared with controls, according to Dr. Meyerovitch.

Dr. Meyerovitch acknowledged that the data he and his team used did not include the reason for a TSH evaluation, nor why patients began levothyroxine treatment. This leaves unanswered questions about the initial baseline mortality risk in patients included in the study.

“This may have resulted in treatment of patients with a higher risk, since we don’t know the reason for the treatment,” he said. “There may have been other reasons that were not included in the database that caused the physician to treat with levothyroxine.”

Details on the cause of death were not included.

Despite these limitations, Dr. Meyerovitch and his team stressed the need for more research before continuing to recommend this treatment to their elderly patients.

Dr. Meyerovitch reported no relevant financial disclosures.

ezimmerman@mdedge.com

Source: Meyerovitch J et al. ENDO 2018 Abstract OR34-2.

CHICAGO – Levothyroxine treatment is associated with increased mortality in patients 65 years and older with subclinical hypothyroidism, according to a study presented at the annual meeting of the Endocrine Society.

With increased mortality and similar prevalence of atrial fibrillation and femoral fractures between study and control groups, physicians may want to reevaluate giving their elderly patients levothyroxine until more information is available, according to presenter Joseph Meyerovitch, MD, of Schneider Children’s Medical Center, Ramat Hasharon, Israel.

The case-control study included 416 patients 65 years or older with TSH levels of 4.2-10 mIU/L who died between 2012 and 2016, and 1,461 patients with comparable TSH levels who did not die during that time.

Most of the patients in both the control and study group were women. The average age of the patients was 84 years, and most had some form of dementia or senility (86.4%).

Mortality was 19% more likely in the group taking levothyroxine, according to an analysis by Dr. Meyerovitch and his fellow investigators.

When broken down further, presence of certain comorbidities increased mortality dramatically, including dementia (odds ratio, 1.61), heart failure (OR, 2.67), chronic renal failure (OR, 1.89), and cerebrovascular disease (OR, 1.94).

There was no significant difference in prevalence of atrial fibrillation between the test and control groups with thyroid stimulating hormone (TSH) testing, nor any difference in femur fracture prevalence.

Patients were given a TSH test three times during follow-up and showed significantly lower TSH levels compared with controls, according to Dr. Meyerovitch.

Dr. Meyerovitch acknowledged that the data he and his team used did not include the reason for a TSH evaluation, nor why patients began levothyroxine treatment. This leaves unanswered questions about the initial baseline mortality risk in patients included in the study.

“This may have resulted in treatment of patients with a higher risk, since we don’t know the reason for the treatment,” he said. “There may have been other reasons that were not included in the database that caused the physician to treat with levothyroxine.”

Details on the cause of death were not included.

Despite these limitations, Dr. Meyerovitch and his team stressed the need for more research before continuing to recommend this treatment to their elderly patients.

Dr. Meyerovitch reported no relevant financial disclosures.

ezimmerman@mdedge.com

Source: Meyerovitch J et al. ENDO 2018 Abstract OR34-2.

Three vibration-based detection tools vary widely in their sensitivity for detection of diabetic peripheral neuropathy. Researchers are suggesting that physicians use more than a single vibration-based device when they check the sensitivity of their diabetic patients’ feet.

“This would significantly reduce the proportion of patients with diabetes who would be falsely identified as having no peripheral neuropathy and subsequently denied the benefit of beneficial and effective secondary risk factor control,” said study coauthor Cynthia Formosa, PhD, of the University of Malta, Msida, and Staffordshire University, Stoke-on-Trent, England, in an interview.

Researchers have estimated that 50% of patients with diabetes develop diabetic polyneuropathy over their lives, and that the condition is responsible for more than a quarter of all diabetes spending. “Despite a long history of research in this area, we are only starting to understand the pathophysiology of the disease,” reports a 2016 review of recent findings.

In a previous report, several of the authors of the new study analyzed 10 sets of guidelines regarding diabetic foot and found that some lacked information to back up the recommendations. Guideline limitations “are responsible for the current gaps between guidelines, standard clinical practice, and development of complications,” the researchers wrote (Rev Diabet Stud. 2016, 13[2-3]:158-86).

Most of the guidelines recommended the use of a 10-g monofilament test, in which a monofilament is placed against the skin, plus a vibration-based test, the researchers reported.

For the new study in Primary Care Diabetes, the researchers examined the efficacy of three noninvasive tools that are used to detect neuropathy in the foot: the 128-Hz tuning fork; the VibraTip, a pocket-sized, motorized device; and the neurothesiometer, a 7-pound electromechanical device that comes in a carrying case and includes an attachment that delivers vibrations to the body.

According to Dr. Formosa, the tuning fork is the most commonly used testing device in normal clinical practice.

SOURCE: Azzopardia K et al. Prim Care Diabetes. 2018 Apr;12(2):111-5.

Three vibration-based detection tools vary widely in their sensitivity for detection of diabetic peripheral neuropathy. Researchers are suggesting that physicians use more than a single vibration-based device when they check the sensitivity of their diabetic patients’ feet.

“This would significantly reduce the proportion of patients with diabetes who would be falsely identified as having no peripheral neuropathy and subsequently denied the benefit of beneficial and effective secondary risk factor control,” said study coauthor Cynthia Formosa, PhD, of the University of Malta, Msida, and Staffordshire University, Stoke-on-Trent, England, in an interview.

Researchers have estimated that 50% of patients with diabetes develop diabetic polyneuropathy over their lives, and that the condition is responsible for more than a quarter of all diabetes spending. “Despite a long history of research in this area, we are only starting to understand the pathophysiology of the disease,” reports a 2016 review of recent findings.

In a previous report, several of the authors of the new study analyzed 10 sets of guidelines regarding diabetic foot and found that some lacked information to back up the recommendations. Guideline limitations “are responsible for the current gaps between guidelines, standard clinical practice, and development of complications,” the researchers wrote (Rev Diabet Stud. 2016, 13[2-3]:158-86).

Most of the guidelines recommended the use of a 10-g monofilament test, in which a monofilament is placed against the skin, plus a vibration-based test, the researchers reported.

For the new study in Primary Care Diabetes, the researchers examined the efficacy of three noninvasive tools that are used to detect neuropathy in the foot: the 128-Hz tuning fork; the VibraTip, a pocket-sized, motorized device; and the neurothesiometer, a 7-pound electromechanical device that comes in a carrying case and includes an attachment that delivers vibrations to the body.

According to Dr. Formosa, the tuning fork is the most commonly used testing device in normal clinical practice.

SOURCE: Azzopardia K et al. Prim Care Diabetes. 2018 Apr;12(2):111-5.

Three vibration-based detection tools vary widely in their sensitivity for detection of diabetic peripheral neuropathy. Researchers are suggesting that physicians use more than a single vibration-based device when they check the sensitivity of their diabetic patients’ feet.

“This would significantly reduce the proportion of patients with diabetes who would be falsely identified as having no peripheral neuropathy and subsequently denied the benefit of beneficial and effective secondary risk factor control,” said study coauthor Cynthia Formosa, PhD, of the University of Malta, Msida, and Staffordshire University, Stoke-on-Trent, England, in an interview.

Researchers have estimated that 50% of patients with diabetes develop diabetic polyneuropathy over their lives, and that the condition is responsible for more than a quarter of all diabetes spending. “Despite a long history of research in this area, we are only starting to understand the pathophysiology of the disease,” reports a 2016 review of recent findings.

In a previous report, several of the authors of the new study analyzed 10 sets of guidelines regarding diabetic foot and found that some lacked information to back up the recommendations. Guideline limitations “are responsible for the current gaps between guidelines, standard clinical practice, and development of complications,” the researchers wrote (Rev Diabet Stud. 2016, 13[2-3]:158-86).

Most of the guidelines recommended the use of a 10-g monofilament test, in which a monofilament is placed against the skin, plus a vibration-based test, the researchers reported.

For the new study in Primary Care Diabetes, the researchers examined the efficacy of three noninvasive tools that are used to detect neuropathy in the foot: the 128-Hz tuning fork; the VibraTip, a pocket-sized, motorized device; and the neurothesiometer, a 7-pound electromechanical device that comes in a carrying case and includes an attachment that delivers vibrations to the body.

According to Dr. Formosa, the tuning fork is the most commonly used testing device in normal clinical practice.

SOURCE: Azzopardia K et al. Prim Care Diabetes. 2018 Apr;12(2):111-5.

ORLANDO – Intraoperative and serious postoperative adverse events do not occur more frequently with concurrent urogynecologic and gynecologic oncology procedures versus the latter alone, but minor adverse events are more common, according to findings from a retrospective matched cohort study.

The study also showed that 10% of planned urogynecologic procedures are modified or abandoned at the time of gynecologic oncology surgery, Emily R. Davidson, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.

Sharon Worcester/MDedge News

Sharon Worcester/MDedge News

sworcester@mdedge.com

SOURCE: Davidson ER et al. SGS 2018, Oral Presentation 13.

ORLANDO – Intraoperative and serious postoperative adverse events do not occur more frequently with concurrent urogynecologic and gynecologic oncology procedures versus the latter alone, but minor adverse events are more common, according to findings from a retrospective matched cohort study.

The study also showed that 10% of planned urogynecologic procedures are modified or abandoned at the time of gynecologic oncology surgery, Emily R. Davidson, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.

Sharon Worcester/MDedge News

Sharon Worcester/MDedge News

sworcester@mdedge.com

SOURCE: Davidson ER et al. SGS 2018, Oral Presentation 13.

ORLANDO – Intraoperative and serious postoperative adverse events do not occur more frequently with concurrent urogynecologic and gynecologic oncology procedures versus the latter alone, but minor adverse events are more common, according to findings from a retrospective matched cohort study.

The study also showed that 10% of planned urogynecologic procedures are modified or abandoned at the time of gynecologic oncology surgery, Emily R. Davidson, MD, reported at the annual scientific meeting of the Society of Gynecologic Surgeons.

Sharon Worcester/MDedge News

Sharon Worcester/MDedge News

sworcester@mdedge.com

SOURCE: Davidson ER et al. SGS 2018, Oral Presentation 13.

Men with schizophrenia and healthy women who were exposed to childhood trauma have shorter leukocyte telomere length (LTL) than do their counterparts in both groups, a small study shows.

“This converse sex-association in schizophrenia compared to the healthy controls is yet another measure suggesting that the pathobiology of schizophrenia may lie, in part, in the mechanisms related to sexual differentiation,” wrote Gabriella Riley, MD, of the department of psychiatry at New York University, and her associates.

To conduct the study, Dr. Riley and her associates recruited 48 inpatients and outpatients with schizophrenia and schizoaffective disorders, as defined by the DSM-5, who were stabilized on medication. Eighteen controls were recruited from postings in the area and Internet recruitment efforts, the researchers reported (Schizophr Res. 2018. doi: 10.1016/j.schres.2018.02.059).

©Gio_tto/Thinkstock.com

ghenderson@mdedge.com

Men with schizophrenia and healthy women who were exposed to childhood trauma have shorter leukocyte telomere length (LTL) than do their counterparts in both groups, a small study shows.

“This converse sex-association in schizophrenia compared to the healthy controls is yet another measure suggesting that the pathobiology of schizophrenia may lie, in part, in the mechanisms related to sexual differentiation,” wrote Gabriella Riley, MD, of the department of psychiatry at New York University, and her associates.

To conduct the study, Dr. Riley and her associates recruited 48 inpatients and outpatients with schizophrenia and schizoaffective disorders, as defined by the DSM-5, who were stabilized on medication. Eighteen controls were recruited from postings in the area and Internet recruitment efforts, the researchers reported (Schizophr Res. 2018. doi: 10.1016/j.schres.2018.02.059).

©Gio_tto/Thinkstock.com

ghenderson@mdedge.com

Men with schizophrenia and healthy women who were exposed to childhood trauma have shorter leukocyte telomere length (LTL) than do their counterparts in both groups, a small study shows.

“This converse sex-association in schizophrenia compared to the healthy controls is yet another measure suggesting that the pathobiology of schizophrenia may lie, in part, in the mechanisms related to sexual differentiation,” wrote Gabriella Riley, MD, of the department of psychiatry at New York University, and her associates.

To conduct the study, Dr. Riley and her associates recruited 48 inpatients and outpatients with schizophrenia and schizoaffective disorders, as defined by the DSM-5, who were stabilized on medication. Eighteen controls were recruited from postings in the area and Internet recruitment efforts, the researchers reported (Schizophr Res. 2018. doi: 10.1016/j.schres.2018.02.059).

©Gio_tto/Thinkstock.com

ghenderson@mdedge.com

SAN DIEGO – A new study finds that the risk of skin cancers in organ transplant recipients may vary widely by ethnicity.

“The most important findings from our study are the high rates of keratinocyte neoplasms observed in our white Northern European patients, but also in those of Far East Asian descent. Dermatologists should also appreciate the high risk of Kaposi’s sarcoma (KS) in patients originating from Sub-Saharan Africa,” Jonathan Kentley, MBBS, of Royal London Hospital, said in an interview. He presented the study findings at the annual meeting of the American Academy of Dermatology.

SOURCE: Kentley J et al. AAD 2018, Session F055.

SAN DIEGO – A new study finds that the risk of skin cancers in organ transplant recipients may vary widely by ethnicity.

“The most important findings from our study are the high rates of keratinocyte neoplasms observed in our white Northern European patients, but also in those of Far East Asian descent. Dermatologists should also appreciate the high risk of Kaposi’s sarcoma (KS) in patients originating from Sub-Saharan Africa,” Jonathan Kentley, MBBS, of Royal London Hospital, said in an interview. He presented the study findings at the annual meeting of the American Academy of Dermatology.

SOURCE: Kentley J et al. AAD 2018, Session F055.

SAN DIEGO – A new study finds that the risk of skin cancers in organ transplant recipients may vary widely by ethnicity.

“The most important findings from our study are the high rates of keratinocyte neoplasms observed in our white Northern European patients, but also in those of Far East Asian descent. Dermatologists should also appreciate the high risk of Kaposi’s sarcoma (KS) in patients originating from Sub-Saharan Africa,” Jonathan Kentley, MBBS, of Royal London Hospital, said in an interview. He presented the study findings at the annual meeting of the American Academy of Dermatology.

SOURCE: Kentley J et al. AAD 2018, Session F055.

The Centers for Disease Control and Prevention’s Antibiotic Resistance (AR) Lab Network has detected 221 instances of bacteria with especially rare resistance genes in the United States, according to a Vital Signs report published online and expanded upon in CDC’s MMWR Weekly.

The MMWR Weekly report, “Containment of Novel Multidrug-Resistant Organisms and Resistance Mechanisms,” which goes deeper into the science behind the issue, shows that in 9 months, in all states and Puerto Rico, health department workers in the AR lab network tested 5,776 samples of highly resistant bacteria, according to Anne Schuchat, MD, principal deputy director of the CDC. These bacteria were immediately tested for unusual resistance – “those genes that were highly resistant, or rare, with special resistance that could spread,” she said.

“Of the 5,776, about 1 in 4 of the bacteria had a gene that helped it spread its resistance. And there were 221 instances of an especially rare resistance gene,” she added. This prompted intense screening, revealing “that 1 in 10 tests were also positive. Meaning the unusual resistance may have spread to other patients. And could have continued spreading if left undetected.”

The report looked at carbapenem-resistant Enterobacteriaceae (CRE) and Enterobacteriaceae with extended-spectrum beta-lactamases (ESBL) infection data from the National Healthcare Safety Network from 2006-2015 to calculate changes in the year over year proportions of these infections and how an enhanced detection and control strategy curbs carbapenem resistance.

This strategy includes components such as timely implementation of appropriate infection control measures, conducting a health care and contact investigation with follow-up, and implementing a system to ensure adherence to infection control measures.

“With independent, or single facility approaches to control spread, a dangerous type of unusual resistance in Enterobacteriaceae [ESBL phenotype] decreased by about 2% per year [(risk ratio [RR] = 0.98, P less than .001)].” With a more aggressive approach, using guidance such as CDC’s CRE toolkit, released in 2009, another type of unusual resistance [CRE] in the same bacteria (Enterobacteriaceae) decreased by nearly 15% per year (RR = 0.85, P less than .01).

The difference may be due in part to the more directed response utilized to slow the spread of the “nightmare bacteria,” once it was identified, said Dr. Schuchat.

These results show massive promise even if only partially effective, specifically for CRE.

ilacy@mdedge.com

The Centers for Disease Control and Prevention’s Antibiotic Resistance (AR) Lab Network has detected 221 instances of bacteria with especially rare resistance genes in the United States, according to a Vital Signs report published online and expanded upon in CDC’s MMWR Weekly.

The MMWR Weekly report, “Containment of Novel Multidrug-Resistant Organisms and Resistance Mechanisms,” which goes deeper into the science behind the issue, shows that in 9 months, in all states and Puerto Rico, health department workers in the AR lab network tested 5,776 samples of highly resistant bacteria, according to Anne Schuchat, MD, principal deputy director of the CDC. These bacteria were immediately tested for unusual resistance – “those genes that were highly resistant, or rare, with special resistance that could spread,” she said.

“Of the 5,776, about 1 in 4 of the bacteria had a gene that helped it spread its resistance. And there were 221 instances of an especially rare resistance gene,” she added. This prompted intense screening, revealing “that 1 in 10 tests were also positive. Meaning the unusual resistance may have spread to other patients. And could have continued spreading if left undetected.”

The report looked at carbapenem-resistant Enterobacteriaceae (CRE) and Enterobacteriaceae with extended-spectrum beta-lactamases (ESBL) infection data from the National Healthcare Safety Network from 2006-2015 to calculate changes in the year over year proportions of these infections and how an enhanced detection and control strategy curbs carbapenem resistance.

This strategy includes components such as timely implementation of appropriate infection control measures, conducting a health care and contact investigation with follow-up, and implementing a system to ensure adherence to infection control measures.

“With independent, or single facility approaches to control spread, a dangerous type of unusual resistance in Enterobacteriaceae [ESBL phenotype] decreased by about 2% per year [(risk ratio [RR] = 0.98, P less than .001)].” With a more aggressive approach, using guidance such as CDC’s CRE toolkit, released in 2009, another type of unusual resistance [CRE] in the same bacteria (Enterobacteriaceae) decreased by nearly 15% per year (RR = 0.85, P less than .01).

The difference may be due in part to the more directed response utilized to slow the spread of the “nightmare bacteria,” once it was identified, said Dr. Schuchat.

These results show massive promise even if only partially effective, specifically for CRE.

ilacy@mdedge.com

The Centers for Disease Control and Prevention’s Antibiotic Resistance (AR) Lab Network has detected 221 instances of bacteria with especially rare resistance genes in the United States, according to a Vital Signs report published online and expanded upon in CDC’s MMWR Weekly.

The MMWR Weekly report, “Containment of Novel Multidrug-Resistant Organisms and Resistance Mechanisms,” which goes deeper into the science behind the issue, shows that in 9 months, in all states and Puerto Rico, health department workers in the AR lab network tested 5,776 samples of highly resistant bacteria, according to Anne Schuchat, MD, principal deputy director of the CDC. These bacteria were immediately tested for unusual resistance – “those genes that were highly resistant, or rare, with special resistance that could spread,” she said.

“Of the 5,776, about 1 in 4 of the bacteria had a gene that helped it spread its resistance. And there were 221 instances of an especially rare resistance gene,” she added. This prompted intense screening, revealing “that 1 in 10 tests were also positive. Meaning the unusual resistance may have spread to other patients. And could have continued spreading if left undetected.”

The report looked at carbapenem-resistant Enterobacteriaceae (CRE) and Enterobacteriaceae with extended-spectrum beta-lactamases (ESBL) infection data from the National Healthcare Safety Network from 2006-2015 to calculate changes in the year over year proportions of these infections and how an enhanced detection and control strategy curbs carbapenem resistance.

This strategy includes components such as timely implementation of appropriate infection control measures, conducting a health care and contact investigation with follow-up, and implementing a system to ensure adherence to infection control measures.

“With independent, or single facility approaches to control spread, a dangerous type of unusual resistance in Enterobacteriaceae [ESBL phenotype] decreased by about 2% per year [(risk ratio [RR] = 0.98, P less than .001)].” With a more aggressive approach, using guidance such as CDC’s CRE toolkit, released in 2009, another type of unusual resistance [CRE] in the same bacteria (Enterobacteriaceae) decreased by nearly 15% per year (RR = 0.85, P less than .01).

The difference may be due in part to the more directed response utilized to slow the spread of the “nightmare bacteria,” once it was identified, said Dr. Schuchat.

These results show massive promise even if only partially effective, specifically for CRE.

ilacy@mdedge.com

LOS ANGELES—When performed between six and 16 hours after stroke onset, thrombectomy plus standard medical management yields better functional outcomes than medical management alone, according to research presented at the International Stroke Conference 2018. Adjunctive thrombectomy also reduces the rates of death and severe disability, compared with medical management alone.

In 2006, Gregory W. Albers, MD, Coyote Foundation Professor of Neurology and Neurological Sciences and Professor, by courtesy, of Neurosurgery at Stanford University Medical Center in California, and colleagues found that MRI could identify patients with stroke who would benefit from IV t-PA as late as six hours after onset. The investigators developed software called RAPID that could determine how much brain tissue was salvageable in a patient with stroke. In a subsequent study, the software allowed researchers to identify patients who would benefit from thrombectomy at a later point after stroke onset than had been considered possible.

The DEFUSE 3 Trial

Dr. Albers and colleagues conducted the DEFUSE 3 study to analyze whether patients could benefit from thrombectomy if administered between six and 16 hours after stroke onset. Eligible participants in the open-label trial had an occlusion in the middle cerebral artery or the internal carotid artery, an initial infarct size of less than 70 mL, and a ratio of ischemic tissue volume to infarct volume of 1.8 or more on perfusion imaging. The researchers used the RAPID software to determine how much salvageable tissue each patient had.

“We used fairly broad inclusion criteria,” said Dr. Albers. Patients as old as 90 were included, as were patients with moderate to severe strokes. Participants were required to be free of disability at stroke onset.

Patients were randomized to standard medical management alone or thrombectomy plus standard medical management. Medical management included standard stroke prevention therapies, management of blood pressure, and interventions to prevent complications for stroke such as deep venous thrombosis. The primary efficacy end point was modified Rankin scale score at 90 days. The secondary efficacy outcome was modified Rankin scale score of 0 to 2 at 90 days (ie, functional independence). The primary safety outcomes were death within 90 days and symptomatic intracranial hemorrhage within 36 hours.

Study Was Terminated Early

The patients in DEFUSE 3 were similar to those included in trials of thrombectomy administered within six hours, said Dr. Albers. Median age was about 70 in both study arms. About 50% of the study population was female, and median NIH Stroke Scale score was 16.

The researchers conducted an interim analysis when 182 patients had been enrolled at 38 sites, including 92 randomized to thrombectomy. The results of the analysis prompted them to end the study early because of treatment efficacy.

The unadjusted odds ratio (OR) of a favorable outcome on the modified Rankin scale at 90 days was 2.77 in the thrombectomy group, compared with the medical management group. After adjusting for between-group differences, the OR was 3.36. This result “is the largest odds ratio ever reported for a thrombectomy study,” said Dr. Albers. Approximately 45% of participants in the thrombectomy group achieved functional independence, compared with 17% in the medical management group.

The rate of mortality at 90 days was 14% in the thrombectomy arm and 26% in the medical management arm. The combined rate of death or severe disability was 22% in the thrombectomy group and 42% in the medical management group. The rate of symptomatic intracranial hemorrhage did not differ significantly between groups.

The benefit of thrombectomy on the primary and secondary end points was similar for patients with wake-up stroke and patients for whom stroke onset had been witnessed. “This [result] demonstrates that the DEFUSE 3 treatment benefit is not explained by a potentially shorter onset to treatment time in the wake-up group,” said Dr. Albers. The rate of good outcome was also similar in all three prespecified time periods that the investigators examined (ie, treatment at six to nine hours, nine to 12 hours, and 12 to 16 hours after onset).

Results Informed New Stroke Guidelines

The treatment benefits in this study are “even more significant” than when patients receive treatment within six hours of stroke onset, said Dr. Albers. Part of the reason for this difference is that the doctors who performed thrombectomy were successful at reperfusing the brain. About 80% of patients in the thrombectomy arm had excellent reperfusion, but spontaneous reperfusion occurred in less than 20% of the medical arm.

The updated guidelines from the American Heart Association and American Stroke Association for the management of acute ischemic stroke, which were published in the March issue of Stroke, recommend that neurologists use the DEFUSE 3 criteria to select patients for thrombectomy at six to 16 hours after stroke onset.

“Now that we know that we can successfully treat patients in later time windows, it is going to be important for primary stroke centers to be able to do the type of imaging that was done in the DEFUSE 3 and DAWN trials,” said Dr. Albers.

He added that it is still important to rush as quickly as possible to evaluate stroke patients. “Every minute still counts, and there are some unfortunate individuals whose minutes run dry even when they present during the golden hours after symptom onset. But more importantly, we now know that many stroke patients are considerably more fortunate; their hourglass is much kinder and affords medical providers with a golden opportunity to improve outcomes even in time frames that were once thought to be impossible.”

—Erik Greb

Suggested Reading

Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378(8):708-718.

Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e110.

LOS ANGELES—When performed between six and 16 hours after stroke onset, thrombectomy plus standard medical management yields better functional outcomes than medical management alone, according to research presented at the International Stroke Conference 2018. Adjunctive thrombectomy also reduces the rates of death and severe disability, compared with medical management alone.

In 2006, Gregory W. Albers, MD, Coyote Foundation Professor of Neurology and Neurological Sciences and Professor, by courtesy, of Neurosurgery at Stanford University Medical Center in California, and colleagues found that MRI could identify patients with stroke who would benefit from IV t-PA as late as six hours after onset. The investigators developed software called RAPID that could determine how much brain tissue was salvageable in a patient with stroke. In a subsequent study, the software allowed researchers to identify patients who would benefit from thrombectomy at a later point after stroke onset than had been considered possible.

The DEFUSE 3 Trial

Dr. Albers and colleagues conducted the DEFUSE 3 study to analyze whether patients could benefit from thrombectomy if administered between six and 16 hours after stroke onset. Eligible participants in the open-label trial had an occlusion in the middle cerebral artery or the internal carotid artery, an initial infarct size of less than 70 mL, and a ratio of ischemic tissue volume to infarct volume of 1.8 or more on perfusion imaging. The researchers used the RAPID software to determine how much salvageable tissue each patient had.

“We used fairly broad inclusion criteria,” said Dr. Albers. Patients as old as 90 were included, as were patients with moderate to severe strokes. Participants were required to be free of disability at stroke onset.

Patients were randomized to standard medical management alone or thrombectomy plus standard medical management. Medical management included standard stroke prevention therapies, management of blood pressure, and interventions to prevent complications for stroke such as deep venous thrombosis. The primary efficacy end point was modified Rankin scale score at 90 days. The secondary efficacy outcome was modified Rankin scale score of 0 to 2 at 90 days (ie, functional independence). The primary safety outcomes were death within 90 days and symptomatic intracranial hemorrhage within 36 hours.

Study Was Terminated Early

The patients in DEFUSE 3 were similar to those included in trials of thrombectomy administered within six hours, said Dr. Albers. Median age was about 70 in both study arms. About 50% of the study population was female, and median NIH Stroke Scale score was 16.

The researchers conducted an interim analysis when 182 patients had been enrolled at 38 sites, including 92 randomized to thrombectomy. The results of the analysis prompted them to end the study early because of treatment efficacy.

The unadjusted odds ratio (OR) of a favorable outcome on the modified Rankin scale at 90 days was 2.77 in the thrombectomy group, compared with the medical management group. After adjusting for between-group differences, the OR was 3.36. This result “is the largest odds ratio ever reported for a thrombectomy study,” said Dr. Albers. Approximately 45% of participants in the thrombectomy group achieved functional independence, compared with 17% in the medical management group.

The rate of mortality at 90 days was 14% in the thrombectomy arm and 26% in the medical management arm. The combined rate of death or severe disability was 22% in the thrombectomy group and 42% in the medical management group. The rate of symptomatic intracranial hemorrhage did not differ significantly between groups.

The benefit of thrombectomy on the primary and secondary end points was similar for patients with wake-up stroke and patients for whom stroke onset had been witnessed. “This [result] demonstrates that the DEFUSE 3 treatment benefit is not explained by a potentially shorter onset to treatment time in the wake-up group,” said Dr. Albers. The rate of good outcome was also similar in all three prespecified time periods that the investigators examined (ie, treatment at six to nine hours, nine to 12 hours, and 12 to 16 hours after onset).

Results Informed New Stroke Guidelines

The treatment benefits in this study are “even more significant” than when patients receive treatment within six hours of stroke onset, said Dr. Albers. Part of the reason for this difference is that the doctors who performed thrombectomy were successful at reperfusing the brain. About 80% of patients in the thrombectomy arm had excellent reperfusion, but spontaneous reperfusion occurred in less than 20% of the medical arm.

The updated guidelines from the American Heart Association and American Stroke Association for the management of acute ischemic stroke, which were published in the March issue of Stroke, recommend that neurologists use the DEFUSE 3 criteria to select patients for thrombectomy at six to 16 hours after stroke onset.

“Now that we know that we can successfully treat patients in later time windows, it is going to be important for primary stroke centers to be able to do the type of imaging that was done in the DEFUSE 3 and DAWN trials,” said Dr. Albers.

He added that it is still important to rush as quickly as possible to evaluate stroke patients. “Every minute still counts, and there are some unfortunate individuals whose minutes run dry even when they present during the golden hours after symptom onset. But more importantly, we now know that many stroke patients are considerably more fortunate; their hourglass is much kinder and affords medical providers with a golden opportunity to improve outcomes even in time frames that were once thought to be impossible.”

—Erik Greb

Suggested Reading

Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378(8):708-718.

Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e110.

LOS ANGELES—When performed between six and 16 hours after stroke onset, thrombectomy plus standard medical management yields better functional outcomes than medical management alone, according to research presented at the International Stroke Conference 2018. Adjunctive thrombectomy also reduces the rates of death and severe disability, compared with medical management alone.

In 2006, Gregory W. Albers, MD, Coyote Foundation Professor of Neurology and Neurological Sciences and Professor, by courtesy, of Neurosurgery at Stanford University Medical Center in California, and colleagues found that MRI could identify patients with stroke who would benefit from IV t-PA as late as six hours after onset. The investigators developed software called RAPID that could determine how much brain tissue was salvageable in a patient with stroke. In a subsequent study, the software allowed researchers to identify patients who would benefit from thrombectomy at a later point after stroke onset than had been considered possible.

The DEFUSE 3 Trial

Dr. Albers and colleagues conducted the DEFUSE 3 study to analyze whether patients could benefit from thrombectomy if administered between six and 16 hours after stroke onset. Eligible participants in the open-label trial had an occlusion in the middle cerebral artery or the internal carotid artery, an initial infarct size of less than 70 mL, and a ratio of ischemic tissue volume to infarct volume of 1.8 or more on perfusion imaging. The researchers used the RAPID software to determine how much salvageable tissue each patient had.

“We used fairly broad inclusion criteria,” said Dr. Albers. Patients as old as 90 were included, as were patients with moderate to severe strokes. Participants were required to be free of disability at stroke onset.

Patients were randomized to standard medical management alone or thrombectomy plus standard medical management. Medical management included standard stroke prevention therapies, management of blood pressure, and interventions to prevent complications for stroke such as deep venous thrombosis. The primary efficacy end point was modified Rankin scale score at 90 days. The secondary efficacy outcome was modified Rankin scale score of 0 to 2 at 90 days (ie, functional independence). The primary safety outcomes were death within 90 days and symptomatic intracranial hemorrhage within 36 hours.

Study Was Terminated Early

The patients in DEFUSE 3 were similar to those included in trials of thrombectomy administered within six hours, said Dr. Albers. Median age was about 70 in both study arms. About 50% of the study population was female, and median NIH Stroke Scale score was 16.

The researchers conducted an interim analysis when 182 patients had been enrolled at 38 sites, including 92 randomized to thrombectomy. The results of the analysis prompted them to end the study early because of treatment efficacy.

The unadjusted odds ratio (OR) of a favorable outcome on the modified Rankin scale at 90 days was 2.77 in the thrombectomy group, compared with the medical management group. After adjusting for between-group differences, the OR was 3.36. This result “is the largest odds ratio ever reported for a thrombectomy study,” said Dr. Albers. Approximately 45% of participants in the thrombectomy group achieved functional independence, compared with 17% in the medical management group.

The rate of mortality at 90 days was 14% in the thrombectomy arm and 26% in the medical management arm. The combined rate of death or severe disability was 22% in the thrombectomy group and 42% in the medical management group. The rate of symptomatic intracranial hemorrhage did not differ significantly between groups.

The benefit of thrombectomy on the primary and secondary end points was similar for patients with wake-up stroke and patients for whom stroke onset had been witnessed. “This [result] demonstrates that the DEFUSE 3 treatment benefit is not explained by a potentially shorter onset to treatment time in the wake-up group,” said Dr. Albers. The rate of good outcome was also similar in all three prespecified time periods that the investigators examined (ie, treatment at six to nine hours, nine to 12 hours, and 12 to 16 hours after onset).

Results Informed New Stroke Guidelines

The treatment benefits in this study are “even more significant” than when patients receive treatment within six hours of stroke onset, said Dr. Albers. Part of the reason for this difference is that the doctors who performed thrombectomy were successful at reperfusing the brain. About 80% of patients in the thrombectomy arm had excellent reperfusion, but spontaneous reperfusion occurred in less than 20% of the medical arm.

The updated guidelines from the American Heart Association and American Stroke Association for the management of acute ischemic stroke, which were published in the March issue of Stroke, recommend that neurologists use the DEFUSE 3 criteria to select patients for thrombectomy at six to 16 hours after stroke onset.

“Now that we know that we can successfully treat patients in later time windows, it is going to be important for primary stroke centers to be able to do the type of imaging that was done in the DEFUSE 3 and DAWN trials,” said Dr. Albers.

He added that it is still important to rush as quickly as possible to evaluate stroke patients. “Every minute still counts, and there are some unfortunate individuals whose minutes run dry even when they present during the golden hours after symptom onset. But more importantly, we now know that many stroke patients are considerably more fortunate; their hourglass is much kinder and affords medical providers with a golden opportunity to improve outcomes even in time frames that were once thought to be impossible.”

—Erik Greb

Suggested Reading

Albers GW, Marks MP, Kemp S, et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging. N Engl J Med. 2018;378(8):708-718.

Powers WJ, Rabinstein AA, Ackerson T, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3):e46-e110.

The overall death rate from heart disease is down 68% since 1968 in the United States, but the disparity between blacks and whites has increased over that time, according to the Centers for Disease Control and Prevention.

Overall, heart disease mortality for adults aged 35 years and older went from 1,035 per 100,000 population in 1968 to 327 per 100,000 in 2015, a drop of 68%. For whites, the story was very similar: The death rate dropped from 1,032 to 326, or 68%. For blacks, who had a higher death rate to begin with, at 1,072 per 100,000, the drop was 63% to 396 per 100,000, Miriam Van Dyke, MPH, of Emory University, Atlanta, and her associates reported in MMWR Surveillance Summaries.

SOURCE: Van Dyke M et al. MMWR Surveill Summ. 2018 Mar 30;67(5):1-11.

The overall death rate from heart disease is down 68% since 1968 in the United States, but the disparity between blacks and whites has increased over that time, according to the Centers for Disease Control and Prevention.

Overall, heart disease mortality for adults aged 35 years and older went from 1,035 per 100,000 population in 1968 to 327 per 100,000 in 2015, a drop of 68%. For whites, the story was very similar: The death rate dropped from 1,032 to 326, or 68%. For blacks, who had a higher death rate to begin with, at 1,072 per 100,000, the drop was 63% to 396 per 100,000, Miriam Van Dyke, MPH, of Emory University, Atlanta, and her associates reported in MMWR Surveillance Summaries.

SOURCE: Van Dyke M et al. MMWR Surveill Summ. 2018 Mar 30;67(5):1-11.

The overall death rate from heart disease is down 68% since 1968 in the United States, but the disparity between blacks and whites has increased over that time, according to the Centers for Disease Control and Prevention.

Overall, heart disease mortality for adults aged 35 years and older went from 1,035 per 100,000 population in 1968 to 327 per 100,000 in 2015, a drop of 68%. For whites, the story was very similar: The death rate dropped from 1,032 to 326, or 68%. For blacks, who had a higher death rate to begin with, at 1,072 per 100,000, the drop was 63% to 396 per 100,000, Miriam Van Dyke, MPH, of Emory University, Atlanta, and her associates reported in MMWR Surveillance Summaries.

SOURCE: Van Dyke M et al. MMWR Surveill Summ. 2018 Mar 30;67(5):1-11.

NextSource Pharma’s decision to increase the price of Gleostine (lomustine) has caught the eye of a trio of senators.

The drug, which is used to treat Hodgkin lymphoma and brain cancer, has seen its price increase by 1,400% ($50 to $786) since NextSource acquired it. Gleostine, which was approved by the Food and Drug Administration in 1976 and has long been off patent, has no generic competition.

“Recent reports of price increases for off-patent drugs have demonstrated the need for continued oversight by the United States Senate,” Sen. Susan Collins (R-Maine), Sen. Claire McCaskill (D-Mo.), and Sen. Catherine Cortez Masto (D-Nev.) wrote in a letter to Tri-Source Pharma CEO Robert DiCrisci. Tri-Source is the parent company of NextSource.

©Dynamic Graphics/Thinkstockphotos.com

gtwachtman@mdedge.com

NextSource Pharma’s decision to increase the price of Gleostine (lomustine) has caught the eye of a trio of senators.

The drug, which is used to treat Hodgkin lymphoma and brain cancer, has seen its price increase by 1,400% ($50 to $786) since NextSource acquired it. Gleostine, which was approved by the Food and Drug Administration in 1976 and has long been off patent, has no generic competition.

“Recent reports of price increases for off-patent drugs have demonstrated the need for continued oversight by the United States Senate,” Sen. Susan Collins (R-Maine), Sen. Claire McCaskill (D-Mo.), and Sen. Catherine Cortez Masto (D-Nev.) wrote in a letter to Tri-Source Pharma CEO Robert DiCrisci. Tri-Source is the parent company of NextSource.

©Dynamic Graphics/Thinkstockphotos.com

gtwachtman@mdedge.com

NextSource Pharma’s decision to increase the price of Gleostine (lomustine) has caught the eye of a trio of senators.

The drug, which is used to treat Hodgkin lymphoma and brain cancer, has seen its price increase by 1,400% ($50 to $786) since NextSource acquired it. Gleostine, which was approved by the Food and Drug Administration in 1976 and has long been off patent, has no generic competition.

“Recent reports of price increases for off-patent drugs have demonstrated the need for continued oversight by the United States Senate,” Sen. Susan Collins (R-Maine), Sen. Claire McCaskill (D-Mo.), and Sen. Catherine Cortez Masto (D-Nev.) wrote in a letter to Tri-Source Pharma CEO Robert DiCrisci. Tri-Source is the parent company of NextSource.

©Dynamic Graphics/Thinkstockphotos.com

gtwachtman@mdedge.com