SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.

Bruce Jancin/MDedge News

Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.

The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.

The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).

In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”

The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).

The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.

The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.

One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).

However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.

“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.

At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.

Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.

[email protected]

SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.

Bruce Jancin/MDedge News

Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.

The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.

The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).

In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”

The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).

The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.

The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.

One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).

However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.

“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.

At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.

Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.

[email protected]

SNOWMASS, COLO. – Recent data on long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy are “quite favorable” and will be considered in the deliberations of the task force charged with revising the 2011 American College of Cardiology/American Heart Association guidelines.

Bruce Jancin/MDedge News

Paul Sorajja, MD, a member of the task force and director of the Center of Valve and Structural Heart Disease at the Minneapolis Heart Institute, explained that the 2011 ACC/AHA guidelines on hypertrophic cardiomyopathy took an appropriately cautious stance regarding alcohol septal ablation (ASA) in light of a 2010 Dutch report warning of an increased risk of sudden cardiac death following the procedure (Circ Heart Fail. 2010 May;3[3]:362-9) and a dearth of evidence to the contrary.

The 2011 guidelines recommend surgical myectomy performed in an experienced center as the class I treatment of choice for patients with severely symptomatic, drug-refractory hypertrophic obstructive cardiomyopathy (HOCM). ASA gets a class IIa recommendation for patients at high surgical risk, and is class III – meaning don’t do it – for patients under age 40 years if myectomy is a viable option (J Am Coll Cardiol. 2011 Dec 13;58[25]:e212-60), Dr. Sorajja noted at the Annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

However, the cautionary Dutch study that influenced the 2011 guidelines is considered controversial, he explained. It was small – just 91 patients – and the operators used twice the normal volume of alcohol, with a resultant much larger, potentially arrhythmogenic myocardial ablation scar. So, many experts have been eagerly awaiting additional long-term studies. And that long-sought data has recently been piling up. Since the 2011 guidelines, six long-term studies have been published, including one led by Dr. Sorajja (Circulation. 2012 Nov 13;126[20]:2374-80). The results have been consistently favorable, with 5-year survival rates of 87%-96%, in line with rates in the general population.

The largest of these studies included 1,197 patients who underwent ASA at seven centers in four European countries. The 30-day mortality and pacemaker implantation rates were significantly lower in patients aged up to 50 years, compared with those aged 65 and up. The annual mortality rate during a mean follow-up of 5.4 years was 1% in patients age 50 years and younger, 2.1% in those aged 51-64, and 5.1% in the oldest group. Arrhythmic events occurred at a rate of about 1% per year in all three age groups. And 95% of patients in the youngest group were in New York Heart Association class I or II at last follow-up (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1134-43).

In an accompanying editorial, Michael A. Fifer, MD, of Massachusetts General Hospital, Boston, commented that “high-volume surgical myectomy centers are few and far between” and there is “a clear inverse relation between [surgical] procedure volume and outcomes.”

The study “provides the most robust data to date regarding the outcomes of ASA in younger patients, precisely the type of data that were missing at the time of writing of the ACCF/AHA and European Society of Cardiology guidelines. Given the favorable outcomes of ASA in this age group, and the unavailability of high-volume myectomy programs in many geographic regions, the time has come to liberalize the indication for ASA in younger patients,” declared Dr. Fifer (JACC Cardiovasc Interv. 2017 Jun 12;10[11]:1144-6).

The second-largest long-term study of ASA was a recent report on 952 German patients with a minimum 6-year follow-up. The estimated 5-, 10-, and 15-year survival rates were 95.8%, 88.3%, and 79.7%, respectively. Estimated survival free of cardiac events was 98.9% at 5 years, 97.0% at 10 years, and 96.5% at 15 years. About 5% of patients received an implantable cardioverter defibrillator.

The investigators concluded, “In this study, PTSMA [percutaneous transluminal septal myocardial ablation] could be proofed as a safe procedure with ongoing symptomatic improvement and excellent long-term survival. Therefore, PTSMA is a reasonable alternative to surgical myectomy in HOCM.” (J Am Coll Cardiol. 2018 Dec 18;72[24]:3087-94) It’s way too early in the ACC/AHA guideline revision process to say what the new recommendations will be, according to Dr. Sorajja.

One unsettled issue, in his view, is whether ASA outcomes are significantly better in high-volume centers. A study of all 11,248 patients who underwent surgical myectomy of ASA during 2003-2011 in a large U.S. inpatient database concluded that undergoing surgical myectomy in a bottom-tertile-volume hospital was independently associated with an adjusted 210% increased risk of inpatient all-cause mortality and a 280% increased risk of bleeding, but that being in the lowest tertile of ASA hospital volume wasn’t independently associated with increased risk after adjustment for potential confounders (JAMA Cardiol. 2016 Jun 1;1:[3]:324-32).

However, Dr. Sorajja indicated he didn’t find the statistically adjusted results in the ASA cohort persuasive.

“I will tell you that the favorable results in the long-term studies came from hospitals in the highest-volume tertile,” the cardiologist said.

At present, he considers surgical myectomy the gold standard therapy. With well-selected patients for ASA – that is, those for whom imaging has identified an appropriate septal artery for delivery of the alcohol, along with no more than 24 mm of septal hypertrophy so the alcohol dose can be limited to a maximum of 20-25 cc – it’s reasonable to expect gradient relief in more than 90% of patients, surgical-like results with optimal relief of left ventricular outflow tract obstruction and a residual gradient of less than 10 mm Hg in about 75%, and a procedural mortality of about 1%, he said.

Dr. Sorajja reported receiving research funding from Abbott Structural, Boston Scientific, Edwards Lifesciences, and Medtronic, and serving as a consultant to those companies and several others.

[email protected]

Click here to read the supplement. 

Historically, multiple sclerosis (MS) has not been com­monly studied in minority populations. However, important challenges must be overcome to provide optimal MS treatment in this patient population. In this supplement from Neurology Reviews, Dr. Castro-Borrero discusses MS in African Americans and Hispanic Americans, including:

• Incidence, age of onset, and disease progression
• Barriers to optimal treatment
• Recommendations for improved MS management

About the Author

Click here to read the supplement. 

Historically, multiple sclerosis (MS) has not been com­monly studied in minority populations. However, important challenges must be overcome to provide optimal MS treatment in this patient population. In this supplement from Neurology Reviews, Dr. Castro-Borrero discusses MS in African Americans and Hispanic Americans, including:

• Incidence, age of onset, and disease progression
• Barriers to optimal treatment
• Recommendations for improved MS management

About the Author

Click here to read the supplement. 

Historically, multiple sclerosis (MS) has not been com­monly studied in minority populations. However, important challenges must be overcome to provide optimal MS treatment in this patient population. In this supplement from Neurology Reviews, Dr. Castro-Borrero discusses MS in African Americans and Hispanic Americans, including:

• Incidence, age of onset, and disease progression
• Barriers to optimal treatment
• Recommendations for improved MS management

About the Author

The Diagnosis: Unilateral Dermatomal Trichoepithelioma  

Adnexal lesions presenting with a linear and/or dermatomal pattern rarely have been reported. Bolognia et al¹ performed a comprehensive review of Blaschko lines and skin conditions that follow such a pattern. The authors found that adnexal-related lesions included linear nevus comedonicus, linear basal cell nevus with comedones (linear basaloid follicular hamartoma), unilateral nevoid basal cell carcinoma (BCC), linear trichoepithelioma, linear trichodiscoma, linear hamartoma of the follicular infundibulum, nevus sebaceous, syringocystadenoma papilliferum, porokeratotic eccrine ostial and dermal duct nevus, linear eccrine poroma, linear spiradenoma, linear syringoma, and linear eccrine syringofibroadenoma.¹  

Trichoepithelioma is a hair follicle-related neoplastic lesion presenting most commonly as the autosomal-dominant multiple familial type with lesions mainly centered on the face. Initial genetic studies associated the disease with loss of heterozygosity in the 9p21 region and further studies identified mutations in the CYLD (cylindromatosis [turban tumor syndrome]) gene on chromosome 16q12-q13.^2,3 Unilateral, linear, and dermatomal forms of trichoepithelioma rarely are reported. In 1986, Geffner et al⁴ reported a case of linear and dermatomal trichoepithelioma in a 10-year-old girl. In addition to discrete solitary lesions affecting the face, she developed lesions on the left shoulder, left side of the trunk, and left lower leg following dermatomal distribution. In 2006, 2 cases of dermatomal trichoepitheliomas affecting the face in children, as in our case, were reported.^5,6 Another case involving the neck was reported in 2016.⁷ Although classic multiple familial trichoepithelioma can be part of conditions such as Brooke-Spiegler⁸ and Rombo syndromes,⁹ no syndromal association has been reported thus far with the unilateral, linear, or dermatomal variants.  

Our case showed typical histopathologic features of trichoepithelioma, including discrete islands of basaloid cells in the dermis set in a conspicuous fibroblastic stroma. Focal connection with the epidermis was present. Most of the islands showed peripheral palisading and horn cysts lined by eosinophilic cells. The fibroblastic component was tightly adherent to the epithelial component, and only stromal clefts were detected. Papillary mesenchymal bodies also were detected as oval aggregates of fibroblastic cells invaginating into epithelial islands to form hair papillae. 

Histopathologically, the 2 most important differential diagnoses of trichoepithelioma include BCC and basaloid follicular hamartoma. In differentiating BCC from trichoepithelioma, the presence of dense fibroblastic stroma and papillary mesenchymal bodies characterize trichoepithelioma, while a fibromucinous stroma with mucinous retraction artifacts and clefting between the basaloid islands and the stroma characterize BCC (Figure 1).¹⁰ Immunohistochemical studies using antibodies against Bcl-2, CD34, CD10, androgen receptor, Ki-67, cytokeratin 19, and PHLDA1 (pleckstrin homologylike domain family A member 1) have reportedly been utilized to differentiate trichoepithelioma from BCC.^11,12 Basaloid follicular hamartoma is characterized by thin anastomosing strands and branching cords of undifferentiated basaloid cells that replace or associate hair follicles in a latticelike pattern (Figure 2). The strands usually are vertically oriented perpendicular to the epidermis. Peripheral palisading is possible, and the basaloid strands are surrounded with cellular connective tissue stroma.¹³ Tumor islands in eccrine poroma show broad connections with the epidermis and are composed of poroid cells that show evident ductal differentiation with eosinophilic cuticles (Figure 3).¹⁴ Spiradenoma is characterized by capsulated deep-seated tumorous nodules not connected with the epidermis and composed of light and dark cells with ductal differentiation and vascular stroma (Figure 4). Scattered lymphocytes within the tumor lobules and in the stroma also are seen. Eosinophilic hyaline globules rarely can be present.¹⁵ 

Many pathologists consider trichoepithelioma as the superficial variant of trichoblastoma. According to the recent World Health Organization classification of benign tumors with follicular differentiation, trichoepithelioma is considered synonymous with trichoblastoma.¹⁶ 

Trichoepitheliomas are benign tumors, and therapy is mainly directed at removal for cosmetic purposes. Several methods of removal are available including electrocautery, laser therapy, and surgery. Awareness of the possible dermatomal distribution of hair follicle and other adnexal-related conditions is important, and such lesions should be thought of in the differential diagnosis of unilateral and/or dermatomal lesions.

The Diagnosis: Unilateral Dermatomal Trichoepithelioma  

Adnexal lesions presenting with a linear and/or dermatomal pattern rarely have been reported. Bolognia et al¹ performed a comprehensive review of Blaschko lines and skin conditions that follow such a pattern. The authors found that adnexal-related lesions included linear nevus comedonicus, linear basal cell nevus with comedones (linear basaloid follicular hamartoma), unilateral nevoid basal cell carcinoma (BCC), linear trichoepithelioma, linear trichodiscoma, linear hamartoma of the follicular infundibulum, nevus sebaceous, syringocystadenoma papilliferum, porokeratotic eccrine ostial and dermal duct nevus, linear eccrine poroma, linear spiradenoma, linear syringoma, and linear eccrine syringofibroadenoma.¹  

Trichoepithelioma is a hair follicle-related neoplastic lesion presenting most commonly as the autosomal-dominant multiple familial type with lesions mainly centered on the face. Initial genetic studies associated the disease with loss of heterozygosity in the 9p21 region and further studies identified mutations in the CYLD (cylindromatosis [turban tumor syndrome]) gene on chromosome 16q12-q13.^2,3 Unilateral, linear, and dermatomal forms of trichoepithelioma rarely are reported. In 1986, Geffner et al⁴ reported a case of linear and dermatomal trichoepithelioma in a 10-year-old girl. In addition to discrete solitary lesions affecting the face, she developed lesions on the left shoulder, left side of the trunk, and left lower leg following dermatomal distribution. In 2006, 2 cases of dermatomal trichoepitheliomas affecting the face in children, as in our case, were reported.^5,6 Another case involving the neck was reported in 2016.⁷ Although classic multiple familial trichoepithelioma can be part of conditions such as Brooke-Spiegler⁸ and Rombo syndromes,⁹ no syndromal association has been reported thus far with the unilateral, linear, or dermatomal variants.  

Our case showed typical histopathologic features of trichoepithelioma, including discrete islands of basaloid cells in the dermis set in a conspicuous fibroblastic stroma. Focal connection with the epidermis was present. Most of the islands showed peripheral palisading and horn cysts lined by eosinophilic cells. The fibroblastic component was tightly adherent to the epithelial component, and only stromal clefts were detected. Papillary mesenchymal bodies also were detected as oval aggregates of fibroblastic cells invaginating into epithelial islands to form hair papillae. 

Histopathologically, the 2 most important differential diagnoses of trichoepithelioma include BCC and basaloid follicular hamartoma. In differentiating BCC from trichoepithelioma, the presence of dense fibroblastic stroma and papillary mesenchymal bodies characterize trichoepithelioma, while a fibromucinous stroma with mucinous retraction artifacts and clefting between the basaloid islands and the stroma characterize BCC (Figure 1).¹⁰ Immunohistochemical studies using antibodies against Bcl-2, CD34, CD10, androgen receptor, Ki-67, cytokeratin 19, and PHLDA1 (pleckstrin homologylike domain family A member 1) have reportedly been utilized to differentiate trichoepithelioma from BCC.^11,12 Basaloid follicular hamartoma is characterized by thin anastomosing strands and branching cords of undifferentiated basaloid cells that replace or associate hair follicles in a latticelike pattern (Figure 2). The strands usually are vertically oriented perpendicular to the epidermis. Peripheral palisading is possible, and the basaloid strands are surrounded with cellular connective tissue stroma.¹³ Tumor islands in eccrine poroma show broad connections with the epidermis and are composed of poroid cells that show evident ductal differentiation with eosinophilic cuticles (Figure 3).¹⁴ Spiradenoma is characterized by capsulated deep-seated tumorous nodules not connected with the epidermis and composed of light and dark cells with ductal differentiation and vascular stroma (Figure 4). Scattered lymphocytes within the tumor lobules and in the stroma also are seen. Eosinophilic hyaline globules rarely can be present.¹⁵ 

Many pathologists consider trichoepithelioma as the superficial variant of trichoblastoma. According to the recent World Health Organization classification of benign tumors with follicular differentiation, trichoepithelioma is considered synonymous with trichoblastoma.¹⁶ 

Trichoepitheliomas are benign tumors, and therapy is mainly directed at removal for cosmetic purposes. Several methods of removal are available including electrocautery, laser therapy, and surgery. Awareness of the possible dermatomal distribution of hair follicle and other adnexal-related conditions is important, and such lesions should be thought of in the differential diagnosis of unilateral and/or dermatomal lesions.

The Diagnosis: Unilateral Dermatomal Trichoepithelioma  

Adnexal lesions presenting with a linear and/or dermatomal pattern rarely have been reported. Bolognia et al¹ performed a comprehensive review of Blaschko lines and skin conditions that follow such a pattern. The authors found that adnexal-related lesions included linear nevus comedonicus, linear basal cell nevus with comedones (linear basaloid follicular hamartoma), unilateral nevoid basal cell carcinoma (BCC), linear trichoepithelioma, linear trichodiscoma, linear hamartoma of the follicular infundibulum, nevus sebaceous, syringocystadenoma papilliferum, porokeratotic eccrine ostial and dermal duct nevus, linear eccrine poroma, linear spiradenoma, linear syringoma, and linear eccrine syringofibroadenoma.¹  

Trichoepithelioma is a hair follicle-related neoplastic lesion presenting most commonly as the autosomal-dominant multiple familial type with lesions mainly centered on the face. Initial genetic studies associated the disease with loss of heterozygosity in the 9p21 region and further studies identified mutations in the CYLD (cylindromatosis [turban tumor syndrome]) gene on chromosome 16q12-q13.^2,3 Unilateral, linear, and dermatomal forms of trichoepithelioma rarely are reported. In 1986, Geffner et al⁴ reported a case of linear and dermatomal trichoepithelioma in a 10-year-old girl. In addition to discrete solitary lesions affecting the face, she developed lesions on the left shoulder, left side of the trunk, and left lower leg following dermatomal distribution. In 2006, 2 cases of dermatomal trichoepitheliomas affecting the face in children, as in our case, were reported.^5,6 Another case involving the neck was reported in 2016.⁷ Although classic multiple familial trichoepithelioma can be part of conditions such as Brooke-Spiegler⁸ and Rombo syndromes,⁹ no syndromal association has been reported thus far with the unilateral, linear, or dermatomal variants.  

Our case showed typical histopathologic features of trichoepithelioma, including discrete islands of basaloid cells in the dermis set in a conspicuous fibroblastic stroma. Focal connection with the epidermis was present. Most of the islands showed peripheral palisading and horn cysts lined by eosinophilic cells. The fibroblastic component was tightly adherent to the epithelial component, and only stromal clefts were detected. Papillary mesenchymal bodies also were detected as oval aggregates of fibroblastic cells invaginating into epithelial islands to form hair papillae. 

Histopathologically, the 2 most important differential diagnoses of trichoepithelioma include BCC and basaloid follicular hamartoma. In differentiating BCC from trichoepithelioma, the presence of dense fibroblastic stroma and papillary mesenchymal bodies characterize trichoepithelioma, while a fibromucinous stroma with mucinous retraction artifacts and clefting between the basaloid islands and the stroma characterize BCC (Figure 1).¹⁰ Immunohistochemical studies using antibodies against Bcl-2, CD34, CD10, androgen receptor, Ki-67, cytokeratin 19, and PHLDA1 (pleckstrin homologylike domain family A member 1) have reportedly been utilized to differentiate trichoepithelioma from BCC.^11,12 Basaloid follicular hamartoma is characterized by thin anastomosing strands and branching cords of undifferentiated basaloid cells that replace or associate hair follicles in a latticelike pattern (Figure 2). The strands usually are vertically oriented perpendicular to the epidermis. Peripheral palisading is possible, and the basaloid strands are surrounded with cellular connective tissue stroma.¹³ Tumor islands in eccrine poroma show broad connections with the epidermis and are composed of poroid cells that show evident ductal differentiation with eosinophilic cuticles (Figure 3).¹⁴ Spiradenoma is characterized by capsulated deep-seated tumorous nodules not connected with the epidermis and composed of light and dark cells with ductal differentiation and vascular stroma (Figure 4). Scattered lymphocytes within the tumor lobules and in the stroma also are seen. Eosinophilic hyaline globules rarely can be present.¹⁵ 

Many pathologists consider trichoepithelioma as the superficial variant of trichoblastoma. According to the recent World Health Organization classification of benign tumors with follicular differentiation, trichoepithelioma is considered synonymous with trichoblastoma.¹⁶ 

Trichoepitheliomas are benign tumors, and therapy is mainly directed at removal for cosmetic purposes. Several methods of removal are available including electrocautery, laser therapy, and surgery. Awareness of the possible dermatomal distribution of hair follicle and other adnexal-related conditions is important, and such lesions should be thought of in the differential diagnosis of unilateral and/or dermatomal lesions.

Patients with psoriasis or psoriatic arthritis who started ustekinumab (Stelara) versus a tumor necrosis factor inhibitor had no differences in the overall risks of incident atrial fibrillation (AFib) or major adverse cardiovascular events (MACE), according to authors of a retrospective cohort study of two commercial insurance databases.

Subgroup analyses in the study also revealed “no statistically significant heterogeneity” in risk of AFib or MACE by age, sex, or presence of diabetes, Moa P. Lee, PharmD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her coauthors reported in JAMA Dermatology.

These findings provide additional evidence on cardiovascular risks with ustekinumab versus other treatments.

The findings are consistent with previous observations of a small but nonsignificant increase in cardiovascular disease among patients with psoriatic disease and provide new insight into the risk of AFib with psoriatic treatments with the two therapies, Dr. Lee and her colleagues wrote.

The retrospective study of two U.S. commercial health care claims databases included 60,028 adult patients with psoriasis or psoriatic arthritis who initiated therapy with ustekinumab (n = 9,071) or a tumor necrosis factor (TNF) inhibitor (n = 50,957), including adalimumab, certolizumab pegol, golimumab, etanercept, or infliximab. The investigators excluded any patient with an AFib diagnosis at baseline and those receiving any antiarrhythmic or anticoagulant treatment.

The incidence of AFib was 5.0 and 4.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, respectively, with an adjusted hazard ratio of 1.08 (95% CI, 0.76-1.54). The incidence of MACE (a composite endpoint of MI, stroke, and coronary revascularization) was 6.2 and 6.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, with an adjusted hazard ratio of 1.10 (95% CI, 0.80-1.52).

In subgroup analyses, the adjusted HR for AFib with ustekinumab versus TNF inhibitor was 1.46 (95% CI, 0.98-2.18) for patients aged 60 years and older and 1.47 (95% CI, 0.93-2.31) in patients with diabetes, the investigators wrote.

The adjusted HR for AFib with ustekinumab versus TNF inhibitors was 1.21 in men (95% CI, 0.87-1.69) and 0.82 in women (95% CI, 0.49-1.39), while for MACE, the HRs were 1.31 in men (95% CI, 0.97-1.76) and 0.91 in women (95% CI, 0.56-1.47).

“Although the risk of these cardiovascular outcomes appeared to be similar across the subpopulations included in our study, further investigations on potentially modifying treatment effects stratified by important risk factors may be warranted,” Dr. Lee and her coauthors wrote.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Several authors reported financial relationships with pharmaceutical companies marketing biologics for psoriasis and psoriatic arthritis.

SOURCE: Lee MP et al. JAMA Dermatol. 2019 Mar 27. doi: 10.1001/jamadermatol.2019.0001.

Patients with psoriasis or psoriatic arthritis who started ustekinumab (Stelara) versus a tumor necrosis factor inhibitor had no differences in the overall risks of incident atrial fibrillation (AFib) or major adverse cardiovascular events (MACE), according to authors of a retrospective cohort study of two commercial insurance databases.

Subgroup analyses in the study also revealed “no statistically significant heterogeneity” in risk of AFib or MACE by age, sex, or presence of diabetes, Moa P. Lee, PharmD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her coauthors reported in JAMA Dermatology.

These findings provide additional evidence on cardiovascular risks with ustekinumab versus other treatments.

The findings are consistent with previous observations of a small but nonsignificant increase in cardiovascular disease among patients with psoriatic disease and provide new insight into the risk of AFib with psoriatic treatments with the two therapies, Dr. Lee and her colleagues wrote.

The retrospective study of two U.S. commercial health care claims databases included 60,028 adult patients with psoriasis or psoriatic arthritis who initiated therapy with ustekinumab (n = 9,071) or a tumor necrosis factor (TNF) inhibitor (n = 50,957), including adalimumab, certolizumab pegol, golimumab, etanercept, or infliximab. The investigators excluded any patient with an AFib diagnosis at baseline and those receiving any antiarrhythmic or anticoagulant treatment.

The incidence of AFib was 5.0 and 4.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, respectively, with an adjusted hazard ratio of 1.08 (95% CI, 0.76-1.54). The incidence of MACE (a composite endpoint of MI, stroke, and coronary revascularization) was 6.2 and 6.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, with an adjusted hazard ratio of 1.10 (95% CI, 0.80-1.52).

In subgroup analyses, the adjusted HR for AFib with ustekinumab versus TNF inhibitor was 1.46 (95% CI, 0.98-2.18) for patients aged 60 years and older and 1.47 (95% CI, 0.93-2.31) in patients with diabetes, the investigators wrote.

The adjusted HR for AFib with ustekinumab versus TNF inhibitors was 1.21 in men (95% CI, 0.87-1.69) and 0.82 in women (95% CI, 0.49-1.39), while for MACE, the HRs were 1.31 in men (95% CI, 0.97-1.76) and 0.91 in women (95% CI, 0.56-1.47).

“Although the risk of these cardiovascular outcomes appeared to be similar across the subpopulations included in our study, further investigations on potentially modifying treatment effects stratified by important risk factors may be warranted,” Dr. Lee and her coauthors wrote.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Several authors reported financial relationships with pharmaceutical companies marketing biologics for psoriasis and psoriatic arthritis.

SOURCE: Lee MP et al. JAMA Dermatol. 2019 Mar 27. doi: 10.1001/jamadermatol.2019.0001.

Patients with psoriasis or psoriatic arthritis who started ustekinumab (Stelara) versus a tumor necrosis factor inhibitor had no differences in the overall risks of incident atrial fibrillation (AFib) or major adverse cardiovascular events (MACE), according to authors of a retrospective cohort study of two commercial insurance databases.

Subgroup analyses in the study also revealed “no statistically significant heterogeneity” in risk of AFib or MACE by age, sex, or presence of diabetes, Moa P. Lee, PharmD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, and her coauthors reported in JAMA Dermatology.

These findings provide additional evidence on cardiovascular risks with ustekinumab versus other treatments.

The findings are consistent with previous observations of a small but nonsignificant increase in cardiovascular disease among patients with psoriatic disease and provide new insight into the risk of AFib with psoriatic treatments with the two therapies, Dr. Lee and her colleagues wrote.

The retrospective study of two U.S. commercial health care claims databases included 60,028 adult patients with psoriasis or psoriatic arthritis who initiated therapy with ustekinumab (n = 9,071) or a tumor necrosis factor (TNF) inhibitor (n = 50,957), including adalimumab, certolizumab pegol, golimumab, etanercept, or infliximab. The investigators excluded any patient with an AFib diagnosis at baseline and those receiving any antiarrhythmic or anticoagulant treatment.

The incidence of AFib was 5.0 and 4.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, respectively, with an adjusted hazard ratio of 1.08 (95% CI, 0.76-1.54). The incidence of MACE (a composite endpoint of MI, stroke, and coronary revascularization) was 6.2 and 6.1 per 1,000 person-years in the ustekinumab and TNF inhibitor groups, with an adjusted hazard ratio of 1.10 (95% CI, 0.80-1.52).

In subgroup analyses, the adjusted HR for AFib with ustekinumab versus TNF inhibitor was 1.46 (95% CI, 0.98-2.18) for patients aged 60 years and older and 1.47 (95% CI, 0.93-2.31) in patients with diabetes, the investigators wrote.

The adjusted HR for AFib with ustekinumab versus TNF inhibitors was 1.21 in men (95% CI, 0.87-1.69) and 0.82 in women (95% CI, 0.49-1.39), while for MACE, the HRs were 1.31 in men (95% CI, 0.97-1.76) and 0.91 in women (95% CI, 0.56-1.47).

“Although the risk of these cardiovascular outcomes appeared to be similar across the subpopulations included in our study, further investigations on potentially modifying treatment effects stratified by important risk factors may be warranted,” Dr. Lee and her coauthors wrote.

The study was supported by the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital. Several authors reported financial relationships with pharmaceutical companies marketing biologics for psoriasis and psoriatic arthritis.

SOURCE: Lee MP et al. JAMA Dermatol. 2019 Mar 27. doi: 10.1001/jamadermatol.2019.0001.

A telementoring and medical education program dubbed ECHO Rheum has helped to widen the provision of best practice rheumatology care to underserved areas in New Mexico, according to the results of a qualitative and quantitative study.

Over a 9-year period, ECHO (Extension for Community Healthcare Outcomes) Rheum educated 2,230 primary care clinicians, the majority of whom were physicians (53%) or nurse practitioners (22%), and helped increase the clinicians’ confidence in managing rheumatic conditions locally while still having access to specialist guidance.

Participants in ECHO Rheum accrued a total of 1,958 CME credits between them, and 21 of 30 (70%) clinicians who participated in 2-day miniresidencies obtained online certification from the American College of Rheumatology.

“ECHO Rheum and programs like it have the potential to positively impact the national shortage of rheumatologic care for underserved patients,” Arthur Bankhurst, MD, and his associates from the University of New Mexico, Albuquerque wrote in Arthritis Care & Research. “Empowering the health care workforce by disseminating knowledge of best practice diagnosis and treatment has the potential to reduce suboptimal rheumatologic care and expand access for those suffering from rheumatologic conditions regardless of economic status or location.”

ECHO Rheum is part of the larger Project ECHO (Extension for Community Healthcare Outcomes), a program developed at UNM by gastroenterologist Sanjeev Arora, MD. Dr. Arora came up with the idea for the ECHO model in 2003 to try to improve access to best practice care for patients with hepatitis C. The potential of the model to translate across medical specialties was soon seen, however, and today, there are more than 40 teleECHO programs operating in New Mexico that also involve more than 400 community clinic sites. The ECHO model is also being used nationally, operating in more than 30 states, and globally in 31 countries.

According to information available via the Project ECHO website, “the ECHO model is not traditional ‘telemedicine’ where the specialist assumes care of the patient, but is instead telementoring, a guided practice model where the participating clinician retains responsibility for managing the patient.” The aim is to use medical education and care management to empower “clinicians everywhere to provide better care to more people, right where they live.”

The rheumatology arm of Project ECHO started in 2006 and follows the four main principles of the ECHO model: Using technology to leverage scarce resources, such as by facilitating regular educational sessions between central expert “hubs” at specialist centers and “spokes” at community practices; sharing best practice information to help reduce disparities in the quality of care; presenting and discussion around case histories; and evaluating and monitoring outcomes.

To demonstrate the effectiveness of ECHO Rheum, the team at UNM evaluated data on participants who had attended weekly teleconferencing sessions, lectures, grand rounds, and miniresidency training between June 2006 and June 2014.

The results demonstrated that “participation in ECHO Rheum provides clinicians in underresourced areas access to best practice knowledge and training in rheumatology,” Dr. Bankhurst and his coauthors observed.

Increased knowledge and confidence in managing rheumatic conditions among primary care physicians could help to reduce the ever-widening gap between the demand and supply of appropriate care. Indeed, while the projected population of adults with rheumatic disease is expected to grow to almost 67 million adults in the next 20 years, there is expected to be a shortfall of 4,700 full-time rheumatologists by 2030.

“Regular participation in teleECHO sessions creates a community of practice among rural clinicians,” the UNM team stated. Every week, participants were invited to attend a 90-minute virtual teleconference, either by video or telephone, that consisted of a brief evidence-based lecture by a subject matter expert and presentation of deidentified case histories submitted by the participants. Participants were able to obtain CME credits at no cost and learn how to use ACR-recommended disease activity measures, such as the Disease Activity Score in 28 joints.

Over the 9-year study period, 1,173 cases were presented, the majority of which (85%) reflected the three most common diagnoses seen in rheumatologic practice, namely RA (n = 715), fibromyalgia (n = 241), and systemic lupus erythematosus (n = 54). As might be expected, female cases were presented more often than male cases, as were cases involving patients aged 40-60 years, compared with other age groups.

“ECHO Rheum saw an increase in participation in 2010, when the ACR certification was offered at no cost, suggesting that ACR certification was an incentive for participation,” Dr. Bankhurst and his team observed.

In 2012, however, there was a drop-off in participation, which may have been caused by the end of funding for ACR certification or clinicians becoming “more confident in their abilities to diagnose and initiate treatment appropriately.” Clinical responsibilities may also have prevented clinicians from attending the weekly sessions.

“Although our formal collaboration with the ACR concluded when funds for this initiative came to an end, ECHO Rheum encourages clinicians to obtain certification in rheumatology and provides them with information about opportunities to offset the cost,” Dr. Bankhurst and his colleagues wrote.

Despite a decline in attendance at the weekly teleECHO sessions during the evaluation period, the UNM team believes that its continued use holds value for primary care practice. Since 2014, a further four clinicians have obtained ACR grant funding for certification and a number of the certified participants return to contribute to the weekly teleECHO sessions.

“This continued use of ECHO Rheum as a readily available resource for case presentations and acquisition of new learning about developments in treatment and medication demonstrates the long-term viability of the community of practice created by the program,” the team suggested.

“I think programs like this are going to be very important in addressing the physician shortage in rheumatology,” said Chad Deal, MD, in an interview.

Dr. Deal, who was not involved in the study, noted that such programs may work particularly well in underserved areas such as New Mexico, as shown in this study, as well as other states, such as in Alaska, North Dakota, and South Dakota. Essentially, “places where people are having to drive forever to get to a rheumatologist.”

“I like what they’ve done,” Dr. Deal said. It can make clinicians “feel much more comfortable with diagnosing and even treating inflammatory arthritis. I think that’s really important.”

It would be difficult to have harder outcomes measures, observed Dr. Deal, head of the Center for Osteoporosis and Metabolic Bone Disease and vice chair for quality and outcomes in the department of rheumatology at the Cleveland Clinic. “The goal is obviously early diagnosis and treatment of rheumatoid arthritis, let’s say, and improved outcomes, and that’s really difficult to show in any kind of program like this.”

Dr. Deal added that “maintaining any kind of program like this is difficult; physicians get busy, and like the authors note, sometimes clinicians get to a point where they are comfortable, and they don’t need it as much.”

Perhaps, these programs don’t need to run forever, he suggested. Perhaps a 1- or 2-year program may be sufficient for one group before moving on to focus on a different group of physicians.

Dr. Bankhurst and other authors of the study reported having no conflicts of interest. The work was funded by the Robert Wood Johnson Foundation, the New Mexico legislature, and the New Mexico Department of Health. Dr. Deal reported no conflicts of interest in relation to his comments.

SOURCE: Bankhurst A et al. Arthritis Care Res. 2019 Mar 30. doi: 10.1002/acr.23889.

A telementoring and medical education program dubbed ECHO Rheum has helped to widen the provision of best practice rheumatology care to underserved areas in New Mexico, according to the results of a qualitative and quantitative study.

Over a 9-year period, ECHO (Extension for Community Healthcare Outcomes) Rheum educated 2,230 primary care clinicians, the majority of whom were physicians (53%) or nurse practitioners (22%), and helped increase the clinicians’ confidence in managing rheumatic conditions locally while still having access to specialist guidance.

Participants in ECHO Rheum accrued a total of 1,958 CME credits between them, and 21 of 30 (70%) clinicians who participated in 2-day miniresidencies obtained online certification from the American College of Rheumatology.

“ECHO Rheum and programs like it have the potential to positively impact the national shortage of rheumatologic care for underserved patients,” Arthur Bankhurst, MD, and his associates from the University of New Mexico, Albuquerque wrote in Arthritis Care & Research. “Empowering the health care workforce by disseminating knowledge of best practice diagnosis and treatment has the potential to reduce suboptimal rheumatologic care and expand access for those suffering from rheumatologic conditions regardless of economic status or location.”

ECHO Rheum is part of the larger Project ECHO (Extension for Community Healthcare Outcomes), a program developed at UNM by gastroenterologist Sanjeev Arora, MD. Dr. Arora came up with the idea for the ECHO model in 2003 to try to improve access to best practice care for patients with hepatitis C. The potential of the model to translate across medical specialties was soon seen, however, and today, there are more than 40 teleECHO programs operating in New Mexico that also involve more than 400 community clinic sites. The ECHO model is also being used nationally, operating in more than 30 states, and globally in 31 countries.

According to information available via the Project ECHO website, “the ECHO model is not traditional ‘telemedicine’ where the specialist assumes care of the patient, but is instead telementoring, a guided practice model where the participating clinician retains responsibility for managing the patient.” The aim is to use medical education and care management to empower “clinicians everywhere to provide better care to more people, right where they live.”

The rheumatology arm of Project ECHO started in 2006 and follows the four main principles of the ECHO model: Using technology to leverage scarce resources, such as by facilitating regular educational sessions between central expert “hubs” at specialist centers and “spokes” at community practices; sharing best practice information to help reduce disparities in the quality of care; presenting and discussion around case histories; and evaluating and monitoring outcomes.

To demonstrate the effectiveness of ECHO Rheum, the team at UNM evaluated data on participants who had attended weekly teleconferencing sessions, lectures, grand rounds, and miniresidency training between June 2006 and June 2014.

The results demonstrated that “participation in ECHO Rheum provides clinicians in underresourced areas access to best practice knowledge and training in rheumatology,” Dr. Bankhurst and his coauthors observed.

Increased knowledge and confidence in managing rheumatic conditions among primary care physicians could help to reduce the ever-widening gap between the demand and supply of appropriate care. Indeed, while the projected population of adults with rheumatic disease is expected to grow to almost 67 million adults in the next 20 years, there is expected to be a shortfall of 4,700 full-time rheumatologists by 2030.

“Regular participation in teleECHO sessions creates a community of practice among rural clinicians,” the UNM team stated. Every week, participants were invited to attend a 90-minute virtual teleconference, either by video or telephone, that consisted of a brief evidence-based lecture by a subject matter expert and presentation of deidentified case histories submitted by the participants. Participants were able to obtain CME credits at no cost and learn how to use ACR-recommended disease activity measures, such as the Disease Activity Score in 28 joints.

Over the 9-year study period, 1,173 cases were presented, the majority of which (85%) reflected the three most common diagnoses seen in rheumatologic practice, namely RA (n = 715), fibromyalgia (n = 241), and systemic lupus erythematosus (n = 54). As might be expected, female cases were presented more often than male cases, as were cases involving patients aged 40-60 years, compared with other age groups.

“ECHO Rheum saw an increase in participation in 2010, when the ACR certification was offered at no cost, suggesting that ACR certification was an incentive for participation,” Dr. Bankhurst and his team observed.

In 2012, however, there was a drop-off in participation, which may have been caused by the end of funding for ACR certification or clinicians becoming “more confident in their abilities to diagnose and initiate treatment appropriately.” Clinical responsibilities may also have prevented clinicians from attending the weekly sessions.

“Although our formal collaboration with the ACR concluded when funds for this initiative came to an end, ECHO Rheum encourages clinicians to obtain certification in rheumatology and provides them with information about opportunities to offset the cost,” Dr. Bankhurst and his colleagues wrote.

Despite a decline in attendance at the weekly teleECHO sessions during the evaluation period, the UNM team believes that its continued use holds value for primary care practice. Since 2014, a further four clinicians have obtained ACR grant funding for certification and a number of the certified participants return to contribute to the weekly teleECHO sessions.

“This continued use of ECHO Rheum as a readily available resource for case presentations and acquisition of new learning about developments in treatment and medication demonstrates the long-term viability of the community of practice created by the program,” the team suggested.

“I think programs like this are going to be very important in addressing the physician shortage in rheumatology,” said Chad Deal, MD, in an interview.

Dr. Deal, who was not involved in the study, noted that such programs may work particularly well in underserved areas such as New Mexico, as shown in this study, as well as other states, such as in Alaska, North Dakota, and South Dakota. Essentially, “places where people are having to drive forever to get to a rheumatologist.”

“I like what they’ve done,” Dr. Deal said. It can make clinicians “feel much more comfortable with diagnosing and even treating inflammatory arthritis. I think that’s really important.”

It would be difficult to have harder outcomes measures, observed Dr. Deal, head of the Center for Osteoporosis and Metabolic Bone Disease and vice chair for quality and outcomes in the department of rheumatology at the Cleveland Clinic. “The goal is obviously early diagnosis and treatment of rheumatoid arthritis, let’s say, and improved outcomes, and that’s really difficult to show in any kind of program like this.”

Dr. Deal added that “maintaining any kind of program like this is difficult; physicians get busy, and like the authors note, sometimes clinicians get to a point where they are comfortable, and they don’t need it as much.”

Perhaps, these programs don’t need to run forever, he suggested. Perhaps a 1- or 2-year program may be sufficient for one group before moving on to focus on a different group of physicians.

Dr. Bankhurst and other authors of the study reported having no conflicts of interest. The work was funded by the Robert Wood Johnson Foundation, the New Mexico legislature, and the New Mexico Department of Health. Dr. Deal reported no conflicts of interest in relation to his comments.

SOURCE: Bankhurst A et al. Arthritis Care Res. 2019 Mar 30. doi: 10.1002/acr.23889.

A telementoring and medical education program dubbed ECHO Rheum has helped to widen the provision of best practice rheumatology care to underserved areas in New Mexico, according to the results of a qualitative and quantitative study.

Over a 9-year period, ECHO (Extension for Community Healthcare Outcomes) Rheum educated 2,230 primary care clinicians, the majority of whom were physicians (53%) or nurse practitioners (22%), and helped increase the clinicians’ confidence in managing rheumatic conditions locally while still having access to specialist guidance.

Participants in ECHO Rheum accrued a total of 1,958 CME credits between them, and 21 of 30 (70%) clinicians who participated in 2-day miniresidencies obtained online certification from the American College of Rheumatology.

“ECHO Rheum and programs like it have the potential to positively impact the national shortage of rheumatologic care for underserved patients,” Arthur Bankhurst, MD, and his associates from the University of New Mexico, Albuquerque wrote in Arthritis Care & Research. “Empowering the health care workforce by disseminating knowledge of best practice diagnosis and treatment has the potential to reduce suboptimal rheumatologic care and expand access for those suffering from rheumatologic conditions regardless of economic status or location.”

ECHO Rheum is part of the larger Project ECHO (Extension for Community Healthcare Outcomes), a program developed at UNM by gastroenterologist Sanjeev Arora, MD. Dr. Arora came up with the idea for the ECHO model in 2003 to try to improve access to best practice care for patients with hepatitis C. The potential of the model to translate across medical specialties was soon seen, however, and today, there are more than 40 teleECHO programs operating in New Mexico that also involve more than 400 community clinic sites. The ECHO model is also being used nationally, operating in more than 30 states, and globally in 31 countries.

According to information available via the Project ECHO website, “the ECHO model is not traditional ‘telemedicine’ where the specialist assumes care of the patient, but is instead telementoring, a guided practice model where the participating clinician retains responsibility for managing the patient.” The aim is to use medical education and care management to empower “clinicians everywhere to provide better care to more people, right where they live.”

The rheumatology arm of Project ECHO started in 2006 and follows the four main principles of the ECHO model: Using technology to leverage scarce resources, such as by facilitating regular educational sessions between central expert “hubs” at specialist centers and “spokes” at community practices; sharing best practice information to help reduce disparities in the quality of care; presenting and discussion around case histories; and evaluating and monitoring outcomes.

To demonstrate the effectiveness of ECHO Rheum, the team at UNM evaluated data on participants who had attended weekly teleconferencing sessions, lectures, grand rounds, and miniresidency training between June 2006 and June 2014.

The results demonstrated that “participation in ECHO Rheum provides clinicians in underresourced areas access to best practice knowledge and training in rheumatology,” Dr. Bankhurst and his coauthors observed.

Increased knowledge and confidence in managing rheumatic conditions among primary care physicians could help to reduce the ever-widening gap between the demand and supply of appropriate care. Indeed, while the projected population of adults with rheumatic disease is expected to grow to almost 67 million adults in the next 20 years, there is expected to be a shortfall of 4,700 full-time rheumatologists by 2030.

“Regular participation in teleECHO sessions creates a community of practice among rural clinicians,” the UNM team stated. Every week, participants were invited to attend a 90-minute virtual teleconference, either by video or telephone, that consisted of a brief evidence-based lecture by a subject matter expert and presentation of deidentified case histories submitted by the participants. Participants were able to obtain CME credits at no cost and learn how to use ACR-recommended disease activity measures, such as the Disease Activity Score in 28 joints.

Over the 9-year study period, 1,173 cases were presented, the majority of which (85%) reflected the three most common diagnoses seen in rheumatologic practice, namely RA (n = 715), fibromyalgia (n = 241), and systemic lupus erythematosus (n = 54). As might be expected, female cases were presented more often than male cases, as were cases involving patients aged 40-60 years, compared with other age groups.

“ECHO Rheum saw an increase in participation in 2010, when the ACR certification was offered at no cost, suggesting that ACR certification was an incentive for participation,” Dr. Bankhurst and his team observed.

In 2012, however, there was a drop-off in participation, which may have been caused by the end of funding for ACR certification or clinicians becoming “more confident in their abilities to diagnose and initiate treatment appropriately.” Clinical responsibilities may also have prevented clinicians from attending the weekly sessions.

“Although our formal collaboration with the ACR concluded when funds for this initiative came to an end, ECHO Rheum encourages clinicians to obtain certification in rheumatology and provides them with information about opportunities to offset the cost,” Dr. Bankhurst and his colleagues wrote.

Despite a decline in attendance at the weekly teleECHO sessions during the evaluation period, the UNM team believes that its continued use holds value for primary care practice. Since 2014, a further four clinicians have obtained ACR grant funding for certification and a number of the certified participants return to contribute to the weekly teleECHO sessions.

“This continued use of ECHO Rheum as a readily available resource for case presentations and acquisition of new learning about developments in treatment and medication demonstrates the long-term viability of the community of practice created by the program,” the team suggested.

“I think programs like this are going to be very important in addressing the physician shortage in rheumatology,” said Chad Deal, MD, in an interview.

Dr. Deal, who was not involved in the study, noted that such programs may work particularly well in underserved areas such as New Mexico, as shown in this study, as well as other states, such as in Alaska, North Dakota, and South Dakota. Essentially, “places where people are having to drive forever to get to a rheumatologist.”

“I like what they’ve done,” Dr. Deal said. It can make clinicians “feel much more comfortable with diagnosing and even treating inflammatory arthritis. I think that’s really important.”

It would be difficult to have harder outcomes measures, observed Dr. Deal, head of the Center for Osteoporosis and Metabolic Bone Disease and vice chair for quality and outcomes in the department of rheumatology at the Cleveland Clinic. “The goal is obviously early diagnosis and treatment of rheumatoid arthritis, let’s say, and improved outcomes, and that’s really difficult to show in any kind of program like this.”

Dr. Deal added that “maintaining any kind of program like this is difficult; physicians get busy, and like the authors note, sometimes clinicians get to a point where they are comfortable, and they don’t need it as much.”

Perhaps, these programs don’t need to run forever, he suggested. Perhaps a 1- or 2-year program may be sufficient for one group before moving on to focus on a different group of physicians.

Dr. Bankhurst and other authors of the study reported having no conflicts of interest. The work was funded by the Robert Wood Johnson Foundation, the New Mexico legislature, and the New Mexico Department of Health. Dr. Deal reported no conflicts of interest in relation to his comments.

SOURCE: Bankhurst A et al. Arthritis Care Res. 2019 Mar 30. doi: 10.1002/acr.23889.

Clinical question: How does inferior vena cava (IVC) filter placement affect 30-day mortality in patients with venous thromboembolism (VTE) with increased risk of bleeding when anticoagulation is not feasible?

Background: Standard treatment for VTE, including deep venous thrombosis (DVT) and pulmonary embolism (PE), is anticoagulation. However, for patients with active bleeding or increased risk of bleeding, anticoagulation may be contraindicated. In these circumstances, placing an IVC filter is recommended by major professional societies; however, the mortality benefit of IVC filter placement is uncertain.

Study design: A retrospective cohort study.

Setting: State Inpatient and Emergency Department Databases from California, Florida, and New York hospitals from 2005 to 2012.

Synopsis: The authors compared the 30-day mortality rates in 45,771 hospitalized adult patients with inpatient diagnosis codes of PE and/or DVT, as well as a contraindication to anticoagulation, who underwent IVC filter placement with 80,259 similar patients who did not undergo IVC filter placement. Baseline characteristics and coexisting conditions were similar in the two populations. The authors found that patients with IVC filter placement had an increased risk of 30-day mortality, compared with patients without an IVC filter placed (HR, 1.18; 95% CI, 1.13-1.22; P less than .001).

This study used observational data derived from reimbursement codes, which lacked unmeasured confounders (for example, severity of VTE and fragility score), so randomized, controlled trials are required to confirm the results. Nevertheless, this study should prompt physicians to carefully consider decisions to place an IVC filter in the setting of a contraindication to anticoagulation.

Bottom line: IVC filter placement in patients with VTE and contraindication for anticoagulation was associated with an increased 30-day mortality. Randomized, controlled trials are required to confirm the observed results.

Citation: Turner TE et al. Association of inferior vena cava filter placement for venous thromboembolic disease and a contraindication to anticoagulation with 30-day mortality. JAMA Network Open. 2018;1(3):e180452.

Dr. Kobaidze is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.

Clinical question: How does inferior vena cava (IVC) filter placement affect 30-day mortality in patients with venous thromboembolism (VTE) with increased risk of bleeding when anticoagulation is not feasible?

Background: Standard treatment for VTE, including deep venous thrombosis (DVT) and pulmonary embolism (PE), is anticoagulation. However, for patients with active bleeding or increased risk of bleeding, anticoagulation may be contraindicated. In these circumstances, placing an IVC filter is recommended by major professional societies; however, the mortality benefit of IVC filter placement is uncertain.

Study design: A retrospective cohort study.

Setting: State Inpatient and Emergency Department Databases from California, Florida, and New York hospitals from 2005 to 2012.

Synopsis: The authors compared the 30-day mortality rates in 45,771 hospitalized adult patients with inpatient diagnosis codes of PE and/or DVT, as well as a contraindication to anticoagulation, who underwent IVC filter placement with 80,259 similar patients who did not undergo IVC filter placement. Baseline characteristics and coexisting conditions were similar in the two populations. The authors found that patients with IVC filter placement had an increased risk of 30-day mortality, compared with patients without an IVC filter placed (HR, 1.18; 95% CI, 1.13-1.22; P less than .001).

This study used observational data derived from reimbursement codes, which lacked unmeasured confounders (for example, severity of VTE and fragility score), so randomized, controlled trials are required to confirm the results. Nevertheless, this study should prompt physicians to carefully consider decisions to place an IVC filter in the setting of a contraindication to anticoagulation.

Bottom line: IVC filter placement in patients with VTE and contraindication for anticoagulation was associated with an increased 30-day mortality. Randomized, controlled trials are required to confirm the observed results.

Citation: Turner TE et al. Association of inferior vena cava filter placement for venous thromboembolic disease and a contraindication to anticoagulation with 30-day mortality. JAMA Network Open. 2018;1(3):e180452.

Dr. Kobaidze is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.

Clinical question: How does inferior vena cava (IVC) filter placement affect 30-day mortality in patients with venous thromboembolism (VTE) with increased risk of bleeding when anticoagulation is not feasible?

Background: Standard treatment for VTE, including deep venous thrombosis (DVT) and pulmonary embolism (PE), is anticoagulation. However, for patients with active bleeding or increased risk of bleeding, anticoagulation may be contraindicated. In these circumstances, placing an IVC filter is recommended by major professional societies; however, the mortality benefit of IVC filter placement is uncertain.

Study design: A retrospective cohort study.

Setting: State Inpatient and Emergency Department Databases from California, Florida, and New York hospitals from 2005 to 2012.

Synopsis: The authors compared the 30-day mortality rates in 45,771 hospitalized adult patients with inpatient diagnosis codes of PE and/or DVT, as well as a contraindication to anticoagulation, who underwent IVC filter placement with 80,259 similar patients who did not undergo IVC filter placement. Baseline characteristics and coexisting conditions were similar in the two populations. The authors found that patients with IVC filter placement had an increased risk of 30-day mortality, compared with patients without an IVC filter placed (HR, 1.18; 95% CI, 1.13-1.22; P less than .001).

This study used observational data derived from reimbursement codes, which lacked unmeasured confounders (for example, severity of VTE and fragility score), so randomized, controlled trials are required to confirm the results. Nevertheless, this study should prompt physicians to carefully consider decisions to place an IVC filter in the setting of a contraindication to anticoagulation.

Bottom line: IVC filter placement in patients with VTE and contraindication for anticoagulation was associated with an increased 30-day mortality. Randomized, controlled trials are required to confirm the observed results.

Citation: Turner TE et al. Association of inferior vena cava filter placement for venous thromboembolic disease and a contraindication to anticoagulation with 30-day mortality. JAMA Network Open. 2018;1(3):e180452.

Dr. Kobaidze is an assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.

New systemic lupus erythematosus guidelines from the European League Against Rheumatism go far beyond the group’s previous effort in 2008, with much broader and more detailed advice.

enot-poloskun/iStock/Getty Images Plus

The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.

The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).

A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.

The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.

Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.

For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.


Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.

[email protected]

SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089

New systemic lupus erythematosus guidelines from the European League Against Rheumatism go far beyond the group’s previous effort in 2008, with much broader and more detailed advice.

enot-poloskun/iStock/Getty Images Plus

The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.

The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).

A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.

The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.

Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.

For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.


Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.

[email protected]

SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089

New systemic lupus erythematosus guidelines from the European League Against Rheumatism go far beyond the group’s previous effort in 2008, with much broader and more detailed advice.

enot-poloskun/iStock/Getty Images Plus

The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.

The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).

A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.

The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.

Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.

For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.


Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.

[email protected]

SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089

For patients with centrally located lung cancers in a multicenter phase 1/2 trial, a specific five-fraction radiotherapy schedule was well tolerated and linked to fairly low rates of treatment-related toxicity, investigators say.

The 12-Gy/fraction schedule of stereotactic body radiotherapy (SBRT) had a 7.2% rate of dose-limiting toxicities and a high tumor-control rate in the NRG Oncology/RTOG 0813 trial, which enrolled 120 patients with medically inoperable stage T1/2 N0M0 non–small cell lung cancers at 43 centers in the United States and Canada.

This is an important study that has implications for clinical practice, according to the investigators, led by Andrea Bezjak, MD, of Princess Margaret Cancer Centre in Toronto.

“The ability to treat patients with centrally located node-negative tumors in multiple institutions across the United States and Canada while maintaining plan qualities and achieving good patient outcomes and relatively modest rates of toxicity is an important achievement,” Dr. Bezjak and coinvestigators said in the Journal of Clinical Oncology.

These patients are frequently at increased risk from surgery, because of advanced age and the comorbidities that come with it, they added.

The 12-Gy/fraction dose level was the highest of nine dose levels included in the study protocol. Doses were delivered in five fractions over the course of 1.5-2 weeks. Investigators sought to determine the maximum tolerated dose of SRBT, defined as the level at which the probability of dose-limiting toxicities (grade 3 or greater) within the first year was as close to 20% as possible, without going over.

Thus, the 7.2% rate of dose-limiting toxicities at this highest-allowed dose level was “well below” that protocol-specified threshold, investigators said, commenting on results of the study.

The rate of local control at 2 years was 89.4% for the 12-Gy/fraction dose level. The 2-year overall survival was 70%, which compared favorably to what has been seen previously with use of SBRT in similar patients with peripheral tumors, according to Dr. Bezjak and colleagues.

Most deaths in the study were attributable to causes other than lung cancer, according to investigators, who noted that all accrued patients were deemed medically inoperable by an experienced thoracic surgeon.

“Thus, this study provides robust data about the safety and efficacy of a five-fraction SBRT schedule that is well tolerated and associated with relatively low rates of serious treatment-related toxicity,” they concluded.

Dr. Bezjak reported disclosures related to AstraZeneca and Abbvie. Coauthors provided disclosures related to Varian Medical Systems, Elekta, Accuray, Seattle Genetics, Celgene, Exelixis, Gilead Sciences, Illumina, Ions Pharmaceuticals, and EMD Serono, among others.

SOURCE: Bezjak A et al. J Clin Oncol. 2019 Apr 3. doi: 10.1200/JCO.18.00622.

For patients with centrally located lung cancers in a multicenter phase 1/2 trial, a specific five-fraction radiotherapy schedule was well tolerated and linked to fairly low rates of treatment-related toxicity, investigators say.

The 12-Gy/fraction schedule of stereotactic body radiotherapy (SBRT) had a 7.2% rate of dose-limiting toxicities and a high tumor-control rate in the NRG Oncology/RTOG 0813 trial, which enrolled 120 patients with medically inoperable stage T1/2 N0M0 non–small cell lung cancers at 43 centers in the United States and Canada.

This is an important study that has implications for clinical practice, according to the investigators, led by Andrea Bezjak, MD, of Princess Margaret Cancer Centre in Toronto.

“The ability to treat patients with centrally located node-negative tumors in multiple institutions across the United States and Canada while maintaining plan qualities and achieving good patient outcomes and relatively modest rates of toxicity is an important achievement,” Dr. Bezjak and coinvestigators said in the Journal of Clinical Oncology.

These patients are frequently at increased risk from surgery, because of advanced age and the comorbidities that come with it, they added.

The 12-Gy/fraction dose level was the highest of nine dose levels included in the study protocol. Doses were delivered in five fractions over the course of 1.5-2 weeks. Investigators sought to determine the maximum tolerated dose of SRBT, defined as the level at which the probability of dose-limiting toxicities (grade 3 or greater) within the first year was as close to 20% as possible, without going over.

Thus, the 7.2% rate of dose-limiting toxicities at this highest-allowed dose level was “well below” that protocol-specified threshold, investigators said, commenting on results of the study.

The rate of local control at 2 years was 89.4% for the 12-Gy/fraction dose level. The 2-year overall survival was 70%, which compared favorably to what has been seen previously with use of SBRT in similar patients with peripheral tumors, according to Dr. Bezjak and colleagues.

Most deaths in the study were attributable to causes other than lung cancer, according to investigators, who noted that all accrued patients were deemed medically inoperable by an experienced thoracic surgeon.

“Thus, this study provides robust data about the safety and efficacy of a five-fraction SBRT schedule that is well tolerated and associated with relatively low rates of serious treatment-related toxicity,” they concluded.

Dr. Bezjak reported disclosures related to AstraZeneca and Abbvie. Coauthors provided disclosures related to Varian Medical Systems, Elekta, Accuray, Seattle Genetics, Celgene, Exelixis, Gilead Sciences, Illumina, Ions Pharmaceuticals, and EMD Serono, among others.

SOURCE: Bezjak A et al. J Clin Oncol. 2019 Apr 3. doi: 10.1200/JCO.18.00622.

For patients with centrally located lung cancers in a multicenter phase 1/2 trial, a specific five-fraction radiotherapy schedule was well tolerated and linked to fairly low rates of treatment-related toxicity, investigators say.

The 12-Gy/fraction schedule of stereotactic body radiotherapy (SBRT) had a 7.2% rate of dose-limiting toxicities and a high tumor-control rate in the NRG Oncology/RTOG 0813 trial, which enrolled 120 patients with medically inoperable stage T1/2 N0M0 non–small cell lung cancers at 43 centers in the United States and Canada.

This is an important study that has implications for clinical practice, according to the investigators, led by Andrea Bezjak, MD, of Princess Margaret Cancer Centre in Toronto.

“The ability to treat patients with centrally located node-negative tumors in multiple institutions across the United States and Canada while maintaining plan qualities and achieving good patient outcomes and relatively modest rates of toxicity is an important achievement,” Dr. Bezjak and coinvestigators said in the Journal of Clinical Oncology.

These patients are frequently at increased risk from surgery, because of advanced age and the comorbidities that come with it, they added.

The 12-Gy/fraction dose level was the highest of nine dose levels included in the study protocol. Doses were delivered in five fractions over the course of 1.5-2 weeks. Investigators sought to determine the maximum tolerated dose of SRBT, defined as the level at which the probability of dose-limiting toxicities (grade 3 or greater) within the first year was as close to 20% as possible, without going over.

Thus, the 7.2% rate of dose-limiting toxicities at this highest-allowed dose level was “well below” that protocol-specified threshold, investigators said, commenting on results of the study.

The rate of local control at 2 years was 89.4% for the 12-Gy/fraction dose level. The 2-year overall survival was 70%, which compared favorably to what has been seen previously with use of SBRT in similar patients with peripheral tumors, according to Dr. Bezjak and colleagues.

Most deaths in the study were attributable to causes other than lung cancer, according to investigators, who noted that all accrued patients were deemed medically inoperable by an experienced thoracic surgeon.

“Thus, this study provides robust data about the safety and efficacy of a five-fraction SBRT schedule that is well tolerated and associated with relatively low rates of serious treatment-related toxicity,” they concluded.

Dr. Bezjak reported disclosures related to AstraZeneca and Abbvie. Coauthors provided disclosures related to Varian Medical Systems, Elekta, Accuray, Seattle Genetics, Celgene, Exelixis, Gilead Sciences, Illumina, Ions Pharmaceuticals, and EMD Serono, among others.

SOURCE: Bezjak A et al. J Clin Oncol. 2019 Apr 3. doi: 10.1200/JCO.18.00622.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 59-year-old man with cirrhosis secondary to nonalcoholic steatohepatitis was admitted to the intensive care unit (ICU) for management of hepatorenal syndrome and work-up for liver transplantation. On admission, his platelet count was 90 × 109/L (normal 150-400 × 109/L), and he was started on thromboprophylaxis with unfractionated heparin (UFH) 5,000 units subcutaneously twice daily. His platelet count began to fall two days after admission. He did have a history of prior heparin exposure associated with his hemodialysis sessions in the past 30 days. During this period, he also had an episode of fever, and antibiotics were initiated for a presumed line infection. He also required periodic vasopressor support for hypotension. His platelet count reached 14 × 109/L by the end of two weeks. He did not have any symptoms of thrombosis, skin necrosis, or reaction to heparin exposure.

Thrombocytopenia is common, especially during critical illness, occurring in up to 50% of patients.¹ In this population, thrombocytopenia is often due to sepsis, hemorrhage, liver dysfunction, and drug reactions.^1,2 Heparin-induced thrombocytopenia (HIT) is an acquired thrombotic drug reaction resulting from platelet activation secondary to antibodies formed against the heparin-modified platelet factor 4 (PF4) complexes.³ This leads to platelet aggregation and dysregulation of the coagulation cascade, which can result in arterial or venous thromboembolic events in up to 50% of patients.³ Mortality associated with HIT can be as high as 30% in this critically ill population.³ Diagnosis of HIT can be made initially through the enzyme-linked immunosorbent assay (ELISA). Management of HIT involves immediate cessation of heparin and initiation of therapeutic anticoagulation with nonheparin agents in order to prevent or treat the thrombotic events.^4,5

The true incidence of HIT remains low, occurring in 0.2% to 5% of patients exposed to heparin and less than 1% in the ICU population.^2,3,6,7 However, given the high incidence of thrombocytopenia in the ICU, the diagnosis of HIT is often considered, resulting in over-testing in this population. Studies suggest that more than 200 ELISAs are requested per year at many hospitals.^8,9 This can lead to significant clinical and economic consequences.

Thrombocytopenia is common in hospitalized patients while heparin is frequently used for thromboprophylaxis or therapeutic anticoagulation. As a result, a diagnosis of HIT is often considered.¹ The high stakes of the inpatient environment, coupled with the increased frequency of thrombocytopenia and heparin exposure, has led to increased use of HIT testing in this population.¹⁰

The most widely available diagnostic test for HIT is the ELISA which detects anti-PF4-heparin antibodies but also nonpathogenic antibodies.¹¹ As a result, the ELISA has a sensitivity close to 100%, allowing physicians to rule out HIT if the test is negative, as indicated by an optical density (OD) of less than 0.4.⁷ Confirmatory testing with the functional serotonin release assay (SRA) is the reference standard as it confers both a high sensitivity and specificity for HIT.¹¹ Due to technical aspects, SRA, unlike the ELISA, is not available in every center and is often outsourced to external labs. Turn-around time for external SRA testing can vary from days to weeks versus hours for the ELISA. The cost for SRA is approximately $120 (USD) per test compared to $30 (USD) per ELISA. Therefore, the ELISA is the recommended initial test due to its quick turn-around time and lower costs.^12,13 For these reasons, the SRA test should not be used initially, but rather to confirm the diagnosis of HIT in patients with a positive ELISA.

The “4T’s” scoring system is a clinical scoring system that estimates the pretest probability of HIT using clinical and basic laboratory parameters (Table).¹⁴ The 4T’s score provides a pretest probability for HIT using four parameters: platelet count, timing of platelet fall, presence of thrombotic events, and the likelihood of another cause of thrombocytopenia. Based on these parameters, the pretest probability for HIT can be divided into three categories: low (4T’s score of ≤3), intermediate (score 4-5), or high (score 6-8).^14-16

Validation of the 4T’s score has shown that a low probability score carries a negative predictive value of 99% in a patient population with varying HIT prevalence rates.¹⁴ Therefore, having a low score is sufficient to rule out HIT without the need for further laboratory testing.^14-16 Although the HIT ELISA confers high sensitivity, due to its detection of nonpathogenic antibodies, its specificity can range from 74% to 84%.¹⁵ Therefore, in the setting of a low 4T’s score, HIT testing is not only unnecessary, it can be harmful due to the risk of treating a false positive result. For instance, assuming an average HIT prevalence of 1% and a false positive rate of 16% (specificity 84%), 1/17 (5.6%) patients with a positive ELISA will have HIT if testing is pursued in an indiscriminate manner. The American Society of Hematology Choosing Wisely^® Campaign has highlighted this concern by advising physicians that they should “not test or treat for suspected HIT in patients with a low pretest probability of HIT.”¹⁷

False positive results on HIT tests are not a trivial concern. The most recognizable adverse event associated with HIT treatment is an elevated risk of bleeding while receiving nonheparin agents. Availability of nonheparin anticoagulants vary by center; however, the most commonly used agents include argatroban, danaparoid, bivalirudin, and off-label fondaparinux.⁴ Due to its short half-life and hepatic clearance, argatroban is commonly used for cases of confirmed or suspected HIT. A retrospective study assessing the bleeding risk of critically ill patients on argatroban therapy suggests a major bleeding risk of 10% within two days of argatroban initiation.¹⁸ In addition, factors such as the presence of elevated bilirubin, major surgery, weight >90 kg, and platelet count <70 × 109/L were found to be associated with increased risk for major bleeding.¹⁸ These identified risk factors are very common in the inpatient setting. As a result, monitoring and titration of argatroban can be challenging.

Over-diagnosis and over-treatment can also lead to significant costs to the healthcare system. A retrospective study assessing the use of HIT testing found that out of 218 HIT ELISA’s sent over a one-year period at a single institution, 161 (74%) were sent inappropriately (ie, in patients with a low pretest probability), with only one resulting in confirmed HIT by SRA. This incurred an additional cost of $33,000 (USD) for testing alone.⁸ A retrospective study of 85 patients assessed the costs of treating patients with a false positive HIT assay. They found that the average duration of treatment with a nonheparin agent was three days and the total cost per patient was $982 (USD).¹⁹ Treatment with a nonheparin agent such as argatroban costs more than $700 (USD) per day while the continuation of unfractionated heparin for prophylaxis costs less than $10 (USD) per day.²⁰Lastly, a diagnosis of HIT can also result in late consequences due to heparin re-exposure. Clinicians may be wary of exposing patients to heparin in situations where heparin may be the most appropriate agent such as cardiovascular surgery, percutaneous interventions, routine thromboprophylaxis, or therapeutic anticoagulation. In these situations when heparin is the agent of choice, determining safety for re-exposure requires further antibody testing which may delay procedures or result in the use of alternative agents with their associated risks and cost implications.⁴

Laboratory testing for HIT is appropriate when the pretest probability for HIT is intermediate or high based on the 4T’s score.^14-16 Studies assessing the application of the 4T’s score have shown that a moderate or high pretest probability carries a probability of having true HIT in 14% and 64% of the cases respectively.¹⁴ However, due to the subjective nature of the 4T’s score components, it is important to recognize that in nonexpert hands, the 4T’s scoring system can suffer from a lack of interrater reliability.¹⁶

As discussed above, a negative ELISA (OD < 0.4) helps to rule out HIT and allow heparin to be safely reintroduced without any further testing. If ELISA is positive (OD ≥ 0.4) confirmation testing with SRA should be performed.⁵ However, studies suggest that the magnitude of the OD is associated with increased likelihood for true HIT, with an OD of greater than 2.00 associated with a positive SRA approximately 90% of the time.²¹ This suggests that if OD values are strongly positive (≥2.00), SRA can be deferred.⁵

Due to the SRA limited availability, confirmatory testing is not always possible or in some situations, SRA results may be negative despite a positive OD. In both these cases, discussion with the Hematology service is recommended.

When presented with a case of thrombocytopenia, it is important for clinicians to consider a broad approach in their differential diagnosis. Hospitalists should investigate common etiologies, consider the coagulation parameters, liver enzymes, nutritional status, peripheral blood smear, and a detailed history and physical exam to identify other common potential cause such as sepsis.

The 4T’s score should be applied in patients who have had recent heparin exposure. A score of ≤3 indicates a low pretest probability; therefore, HIT is unlikely and further testing is not needed. A score of ≥4 indicates an intermediate or high pretest probability and should prompt clinicians to consider further HIT testing with ELISA. In these situations, heparin should be held, and nonheparin agents should be initiated to prevent thromboembolic complications. In their study of ICU patients, Pierce et al. found that 17% of patients did not have a concurrent cessation of heparin and initiation of alternative agents despite a high clinical suspicion for HIT.¹ Lastly, if hospitalists have concerns regarding HIT testing or management, expert consultation with the Hematology service is recommended.

• Consider a broad differential diagnosis when presented with a hospitalized patient with new thrombocytopenia given the low incidence of HIT (<5%).
• Apply the 4T’s score in those who have thrombocytopenia and recent heparin exposure. A low scores 4T’s score (≤3) predicts a low pretest probability and further testing is not required.
• Patients with moderate or high 4T’s score (≥4) should have the ELISA test. During this time, heparin should be discontinued and nonheparin agents initiated while waiting for test results.
• Confirmatory testing with SRA should be performed for all positive ELISAs; however, they can be deferred in patients with strongly positive OD (≥2.00) on ELISA.

In the opening clinical scenario, the 4T’s score would have been 2 (1 point for the platelet count, 1 point for the platelet count fall after 10 days, 0 points for thrombosis, and 0 points for an alternative cause of thrombocytopenia), indicating a low pretest probability. Further HIT testing should be deferred as the likelihood for HIT is low. In this case, the more likely etiology for his thrombocytopenia would be sepsis. Therefore, heparin can be safely reinitiated once the platelet count recovers. This case helps to illustrate the importance of keeping a broad differential in cases of thrombocytopenia in the hospitalized patient while concurrently applying the 4T’s score to determine appropriateness for further HIT testing. Ultimately by choosing wisely, we can help reduce the cost and safety implications of a falsely positive HIT diagnosis.

What do you do?

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter.

Disclosures

The authors report no conflict of interest.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 59-year-old man with cirrhosis secondary to nonalcoholic steatohepatitis was admitted to the intensive care unit (ICU) for management of hepatorenal syndrome and work-up for liver transplantation. On admission, his platelet count was 90 × 109/L (normal 150-400 × 109/L), and he was started on thromboprophylaxis with unfractionated heparin (UFH) 5,000 units subcutaneously twice daily. His platelet count began to fall two days after admission. He did have a history of prior heparin exposure associated with his hemodialysis sessions in the past 30 days. During this period, he also had an episode of fever, and antibiotics were initiated for a presumed line infection. He also required periodic vasopressor support for hypotension. His platelet count reached 14 × 109/L by the end of two weeks. He did not have any symptoms of thrombosis, skin necrosis, or reaction to heparin exposure.

Thrombocytopenia is common, especially during critical illness, occurring in up to 50% of patients.¹ In this population, thrombocytopenia is often due to sepsis, hemorrhage, liver dysfunction, and drug reactions.^1,2 Heparin-induced thrombocytopenia (HIT) is an acquired thrombotic drug reaction resulting from platelet activation secondary to antibodies formed against the heparin-modified platelet factor 4 (PF4) complexes.³ This leads to platelet aggregation and dysregulation of the coagulation cascade, which can result in arterial or venous thromboembolic events in up to 50% of patients.³ Mortality associated with HIT can be as high as 30% in this critically ill population.³ Diagnosis of HIT can be made initially through the enzyme-linked immunosorbent assay (ELISA). Management of HIT involves immediate cessation of heparin and initiation of therapeutic anticoagulation with nonheparin agents in order to prevent or treat the thrombotic events.^4,5

The true incidence of HIT remains low, occurring in 0.2% to 5% of patients exposed to heparin and less than 1% in the ICU population.^2,3,6,7 However, given the high incidence of thrombocytopenia in the ICU, the diagnosis of HIT is often considered, resulting in over-testing in this population. Studies suggest that more than 200 ELISAs are requested per year at many hospitals.^8,9 This can lead to significant clinical and economic consequences.

Thrombocytopenia is common in hospitalized patients while heparin is frequently used for thromboprophylaxis or therapeutic anticoagulation. As a result, a diagnosis of HIT is often considered.¹ The high stakes of the inpatient environment, coupled with the increased frequency of thrombocytopenia and heparin exposure, has led to increased use of HIT testing in this population.¹⁰

The most widely available diagnostic test for HIT is the ELISA which detects anti-PF4-heparin antibodies but also nonpathogenic antibodies.¹¹ As a result, the ELISA has a sensitivity close to 100%, allowing physicians to rule out HIT if the test is negative, as indicated by an optical density (OD) of less than 0.4.⁷ Confirmatory testing with the functional serotonin release assay (SRA) is the reference standard as it confers both a high sensitivity and specificity for HIT.¹¹ Due to technical aspects, SRA, unlike the ELISA, is not available in every center and is often outsourced to external labs. Turn-around time for external SRA testing can vary from days to weeks versus hours for the ELISA. The cost for SRA is approximately $120 (USD) per test compared to $30 (USD) per ELISA. Therefore, the ELISA is the recommended initial test due to its quick turn-around time and lower costs.^12,13 For these reasons, the SRA test should not be used initially, but rather to confirm the diagnosis of HIT in patients with a positive ELISA.

The “4T’s” scoring system is a clinical scoring system that estimates the pretest probability of HIT using clinical and basic laboratory parameters (Table).¹⁴ The 4T’s score provides a pretest probability for HIT using four parameters: platelet count, timing of platelet fall, presence of thrombotic events, and the likelihood of another cause of thrombocytopenia. Based on these parameters, the pretest probability for HIT can be divided into three categories: low (4T’s score of ≤3), intermediate (score 4-5), or high (score 6-8).^14-16

Validation of the 4T’s score has shown that a low probability score carries a negative predictive value of 99% in a patient population with varying HIT prevalence rates.¹⁴ Therefore, having a low score is sufficient to rule out HIT without the need for further laboratory testing.^14-16 Although the HIT ELISA confers high sensitivity, due to its detection of nonpathogenic antibodies, its specificity can range from 74% to 84%.¹⁵ Therefore, in the setting of a low 4T’s score, HIT testing is not only unnecessary, it can be harmful due to the risk of treating a false positive result. For instance, assuming an average HIT prevalence of 1% and a false positive rate of 16% (specificity 84%), 1/17 (5.6%) patients with a positive ELISA will have HIT if testing is pursued in an indiscriminate manner. The American Society of Hematology Choosing Wisely^® Campaign has highlighted this concern by advising physicians that they should “not test or treat for suspected HIT in patients with a low pretest probability of HIT.”¹⁷

False positive results on HIT tests are not a trivial concern. The most recognizable adverse event associated with HIT treatment is an elevated risk of bleeding while receiving nonheparin agents. Availability of nonheparin anticoagulants vary by center; however, the most commonly used agents include argatroban, danaparoid, bivalirudin, and off-label fondaparinux.⁴ Due to its short half-life and hepatic clearance, argatroban is commonly used for cases of confirmed or suspected HIT. A retrospective study assessing the bleeding risk of critically ill patients on argatroban therapy suggests a major bleeding risk of 10% within two days of argatroban initiation.¹⁸ In addition, factors such as the presence of elevated bilirubin, major surgery, weight >90 kg, and platelet count <70 × 109/L were found to be associated with increased risk for major bleeding.¹⁸ These identified risk factors are very common in the inpatient setting. As a result, monitoring and titration of argatroban can be challenging.

Over-diagnosis and over-treatment can also lead to significant costs to the healthcare system. A retrospective study assessing the use of HIT testing found that out of 218 HIT ELISA’s sent over a one-year period at a single institution, 161 (74%) were sent inappropriately (ie, in patients with a low pretest probability), with only one resulting in confirmed HIT by SRA. This incurred an additional cost of $33,000 (USD) for testing alone.⁸ A retrospective study of 85 patients assessed the costs of treating patients with a false positive HIT assay. They found that the average duration of treatment with a nonheparin agent was three days and the total cost per patient was $982 (USD).¹⁹ Treatment with a nonheparin agent such as argatroban costs more than $700 (USD) per day while the continuation of unfractionated heparin for prophylaxis costs less than $10 (USD) per day.²⁰Lastly, a diagnosis of HIT can also result in late consequences due to heparin re-exposure. Clinicians may be wary of exposing patients to heparin in situations where heparin may be the most appropriate agent such as cardiovascular surgery, percutaneous interventions, routine thromboprophylaxis, or therapeutic anticoagulation. In these situations when heparin is the agent of choice, determining safety for re-exposure requires further antibody testing which may delay procedures or result in the use of alternative agents with their associated risks and cost implications.⁴

Laboratory testing for HIT is appropriate when the pretest probability for HIT is intermediate or high based on the 4T’s score.^14-16 Studies assessing the application of the 4T’s score have shown that a moderate or high pretest probability carries a probability of having true HIT in 14% and 64% of the cases respectively.¹⁴ However, due to the subjective nature of the 4T’s score components, it is important to recognize that in nonexpert hands, the 4T’s scoring system can suffer from a lack of interrater reliability.¹⁶

As discussed above, a negative ELISA (OD < 0.4) helps to rule out HIT and allow heparin to be safely reintroduced without any further testing. If ELISA is positive (OD ≥ 0.4) confirmation testing with SRA should be performed.⁵ However, studies suggest that the magnitude of the OD is associated with increased likelihood for true HIT, with an OD of greater than 2.00 associated with a positive SRA approximately 90% of the time.²¹ This suggests that if OD values are strongly positive (≥2.00), SRA can be deferred.⁵

Due to the SRA limited availability, confirmatory testing is not always possible or in some situations, SRA results may be negative despite a positive OD. In both these cases, discussion with the Hematology service is recommended.

When presented with a case of thrombocytopenia, it is important for clinicians to consider a broad approach in their differential diagnosis. Hospitalists should investigate common etiologies, consider the coagulation parameters, liver enzymes, nutritional status, peripheral blood smear, and a detailed history and physical exam to identify other common potential cause such as sepsis.

The 4T’s score should be applied in patients who have had recent heparin exposure. A score of ≤3 indicates a low pretest probability; therefore, HIT is unlikely and further testing is not needed. A score of ≥4 indicates an intermediate or high pretest probability and should prompt clinicians to consider further HIT testing with ELISA. In these situations, heparin should be held, and nonheparin agents should be initiated to prevent thromboembolic complications. In their study of ICU patients, Pierce et al. found that 17% of patients did not have a concurrent cessation of heparin and initiation of alternative agents despite a high clinical suspicion for HIT.¹ Lastly, if hospitalists have concerns regarding HIT testing or management, expert consultation with the Hematology service is recommended.

• Consider a broad differential diagnosis when presented with a hospitalized patient with new thrombocytopenia given the low incidence of HIT (<5%).
• Apply the 4T’s score in those who have thrombocytopenia and recent heparin exposure. A low scores 4T’s score (≤3) predicts a low pretest probability and further testing is not required.
• Patients with moderate or high 4T’s score (≥4) should have the ELISA test. During this time, heparin should be discontinued and nonheparin agents initiated while waiting for test results.
• Confirmatory testing with SRA should be performed for all positive ELISAs; however, they can be deferred in patients with strongly positive OD (≥2.00) on ELISA.

In the opening clinical scenario, the 4T’s score would have been 2 (1 point for the platelet count, 1 point for the platelet count fall after 10 days, 0 points for thrombosis, and 0 points for an alternative cause of thrombocytopenia), indicating a low pretest probability. Further HIT testing should be deferred as the likelihood for HIT is low. In this case, the more likely etiology for his thrombocytopenia would be sepsis. Therefore, heparin can be safely reinitiated once the platelet count recovers. This case helps to illustrate the importance of keeping a broad differential in cases of thrombocytopenia in the hospitalized patient while concurrently applying the 4T’s score to determine appropriateness for further HIT testing. Ultimately by choosing wisely, we can help reduce the cost and safety implications of a falsely positive HIT diagnosis.

What do you do?

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter.

Disclosures

The authors report no conflict of interest.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 59-year-old man with cirrhosis secondary to nonalcoholic steatohepatitis was admitted to the intensive care unit (ICU) for management of hepatorenal syndrome and work-up for liver transplantation. On admission, his platelet count was 90 × 109/L (normal 150-400 × 109/L), and he was started on thromboprophylaxis with unfractionated heparin (UFH) 5,000 units subcutaneously twice daily. His platelet count began to fall two days after admission. He did have a history of prior heparin exposure associated with his hemodialysis sessions in the past 30 days. During this period, he also had an episode of fever, and antibiotics were initiated for a presumed line infection. He also required periodic vasopressor support for hypotension. His platelet count reached 14 × 109/L by the end of two weeks. He did not have any symptoms of thrombosis, skin necrosis, or reaction to heparin exposure.

Thrombocytopenia is common, especially during critical illness, occurring in up to 50% of patients.¹ In this population, thrombocytopenia is often due to sepsis, hemorrhage, liver dysfunction, and drug reactions.^1,2 Heparin-induced thrombocytopenia (HIT) is an acquired thrombotic drug reaction resulting from platelet activation secondary to antibodies formed against the heparin-modified platelet factor 4 (PF4) complexes.³ This leads to platelet aggregation and dysregulation of the coagulation cascade, which can result in arterial or venous thromboembolic events in up to 50% of patients.³ Mortality associated with HIT can be as high as 30% in this critically ill population.³ Diagnosis of HIT can be made initially through the enzyme-linked immunosorbent assay (ELISA). Management of HIT involves immediate cessation of heparin and initiation of therapeutic anticoagulation with nonheparin agents in order to prevent or treat the thrombotic events.^4,5

The true incidence of HIT remains low, occurring in 0.2% to 5% of patients exposed to heparin and less than 1% in the ICU population.^2,3,6,7 However, given the high incidence of thrombocytopenia in the ICU, the diagnosis of HIT is often considered, resulting in over-testing in this population. Studies suggest that more than 200 ELISAs are requested per year at many hospitals.^8,9 This can lead to significant clinical and economic consequences.

Thrombocytopenia is common in hospitalized patients while heparin is frequently used for thromboprophylaxis or therapeutic anticoagulation. As a result, a diagnosis of HIT is often considered.¹ The high stakes of the inpatient environment, coupled with the increased frequency of thrombocytopenia and heparin exposure, has led to increased use of HIT testing in this population.¹⁰

The most widely available diagnostic test for HIT is the ELISA which detects anti-PF4-heparin antibodies but also nonpathogenic antibodies.¹¹ As a result, the ELISA has a sensitivity close to 100%, allowing physicians to rule out HIT if the test is negative, as indicated by an optical density (OD) of less than 0.4.⁷ Confirmatory testing with the functional serotonin release assay (SRA) is the reference standard as it confers both a high sensitivity and specificity for HIT.¹¹ Due to technical aspects, SRA, unlike the ELISA, is not available in every center and is often outsourced to external labs. Turn-around time for external SRA testing can vary from days to weeks versus hours for the ELISA. The cost for SRA is approximately $120 (USD) per test compared to $30 (USD) per ELISA. Therefore, the ELISA is the recommended initial test due to its quick turn-around time and lower costs.^12,13 For these reasons, the SRA test should not be used initially, but rather to confirm the diagnosis of HIT in patients with a positive ELISA.

The “4T’s” scoring system is a clinical scoring system that estimates the pretest probability of HIT using clinical and basic laboratory parameters (Table).¹⁴ The 4T’s score provides a pretest probability for HIT using four parameters: platelet count, timing of platelet fall, presence of thrombotic events, and the likelihood of another cause of thrombocytopenia. Based on these parameters, the pretest probability for HIT can be divided into three categories: low (4T’s score of ≤3), intermediate (score 4-5), or high (score 6-8).^14-16

Validation of the 4T’s score has shown that a low probability score carries a negative predictive value of 99% in a patient population with varying HIT prevalence rates.¹⁴ Therefore, having a low score is sufficient to rule out HIT without the need for further laboratory testing.^14-16 Although the HIT ELISA confers high sensitivity, due to its detection of nonpathogenic antibodies, its specificity can range from 74% to 84%.¹⁵ Therefore, in the setting of a low 4T’s score, HIT testing is not only unnecessary, it can be harmful due to the risk of treating a false positive result. For instance, assuming an average HIT prevalence of 1% and a false positive rate of 16% (specificity 84%), 1/17 (5.6%) patients with a positive ELISA will have HIT if testing is pursued in an indiscriminate manner. The American Society of Hematology Choosing Wisely^® Campaign has highlighted this concern by advising physicians that they should “not test or treat for suspected HIT in patients with a low pretest probability of HIT.”¹⁷

False positive results on HIT tests are not a trivial concern. The most recognizable adverse event associated with HIT treatment is an elevated risk of bleeding while receiving nonheparin agents. Availability of nonheparin anticoagulants vary by center; however, the most commonly used agents include argatroban, danaparoid, bivalirudin, and off-label fondaparinux.⁴ Due to its short half-life and hepatic clearance, argatroban is commonly used for cases of confirmed or suspected HIT. A retrospective study assessing the bleeding risk of critically ill patients on argatroban therapy suggests a major bleeding risk of 10% within two days of argatroban initiation.¹⁸ In addition, factors such as the presence of elevated bilirubin, major surgery, weight >90 kg, and platelet count <70 × 109/L were found to be associated with increased risk for major bleeding.¹⁸ These identified risk factors are very common in the inpatient setting. As a result, monitoring and titration of argatroban can be challenging.

Over-diagnosis and over-treatment can also lead to significant costs to the healthcare system. A retrospective study assessing the use of HIT testing found that out of 218 HIT ELISA’s sent over a one-year period at a single institution, 161 (74%) were sent inappropriately (ie, in patients with a low pretest probability), with only one resulting in confirmed HIT by SRA. This incurred an additional cost of $33,000 (USD) for testing alone.⁸ A retrospective study of 85 patients assessed the costs of treating patients with a false positive HIT assay. They found that the average duration of treatment with a nonheparin agent was three days and the total cost per patient was $982 (USD).¹⁹ Treatment with a nonheparin agent such as argatroban costs more than $700 (USD) per day while the continuation of unfractionated heparin for prophylaxis costs less than $10 (USD) per day.²⁰Lastly, a diagnosis of HIT can also result in late consequences due to heparin re-exposure. Clinicians may be wary of exposing patients to heparin in situations where heparin may be the most appropriate agent such as cardiovascular surgery, percutaneous interventions, routine thromboprophylaxis, or therapeutic anticoagulation. In these situations when heparin is the agent of choice, determining safety for re-exposure requires further antibody testing which may delay procedures or result in the use of alternative agents with their associated risks and cost implications.⁴

Laboratory testing for HIT is appropriate when the pretest probability for HIT is intermediate or high based on the 4T’s score.^14-16 Studies assessing the application of the 4T’s score have shown that a moderate or high pretest probability carries a probability of having true HIT in 14% and 64% of the cases respectively.¹⁴ However, due to the subjective nature of the 4T’s score components, it is important to recognize that in nonexpert hands, the 4T’s scoring system can suffer from a lack of interrater reliability.¹⁶

As discussed above, a negative ELISA (OD < 0.4) helps to rule out HIT and allow heparin to be safely reintroduced without any further testing. If ELISA is positive (OD ≥ 0.4) confirmation testing with SRA should be performed.⁵ However, studies suggest that the magnitude of the OD is associated with increased likelihood for true HIT, with an OD of greater than 2.00 associated with a positive SRA approximately 90% of the time.²¹ This suggests that if OD values are strongly positive (≥2.00), SRA can be deferred.⁵

Due to the SRA limited availability, confirmatory testing is not always possible or in some situations, SRA results may be negative despite a positive OD. In both these cases, discussion with the Hematology service is recommended.

When presented with a case of thrombocytopenia, it is important for clinicians to consider a broad approach in their differential diagnosis. Hospitalists should investigate common etiologies, consider the coagulation parameters, liver enzymes, nutritional status, peripheral blood smear, and a detailed history and physical exam to identify other common potential cause such as sepsis.

The 4T’s score should be applied in patients who have had recent heparin exposure. A score of ≤3 indicates a low pretest probability; therefore, HIT is unlikely and further testing is not needed. A score of ≥4 indicates an intermediate or high pretest probability and should prompt clinicians to consider further HIT testing with ELISA. In these situations, heparin should be held, and nonheparin agents should be initiated to prevent thromboembolic complications. In their study of ICU patients, Pierce et al. found that 17% of patients did not have a concurrent cessation of heparin and initiation of alternative agents despite a high clinical suspicion for HIT.¹ Lastly, if hospitalists have concerns regarding HIT testing or management, expert consultation with the Hematology service is recommended.

• Consider a broad differential diagnosis when presented with a hospitalized patient with new thrombocytopenia given the low incidence of HIT (<5%).
• Apply the 4T’s score in those who have thrombocytopenia and recent heparin exposure. A low scores 4T’s score (≤3) predicts a low pretest probability and further testing is not required.
• Patients with moderate or high 4T’s score (≥4) should have the ELISA test. During this time, heparin should be discontinued and nonheparin agents initiated while waiting for test results.
• Confirmatory testing with SRA should be performed for all positive ELISAs; however, they can be deferred in patients with strongly positive OD (≥2.00) on ELISA.

In the opening clinical scenario, the 4T’s score would have been 2 (1 point for the platelet count, 1 point for the platelet count fall after 10 days, 0 points for thrombosis, and 0 points for an alternative cause of thrombocytopenia), indicating a low pretest probability. Further HIT testing should be deferred as the likelihood for HIT is low. In this case, the more likely etiology for his thrombocytopenia would be sepsis. Therefore, heparin can be safely reinitiated once the platelet count recovers. This case helps to illustrate the importance of keeping a broad differential in cases of thrombocytopenia in the hospitalized patient while concurrently applying the 4T’s score to determine appropriateness for further HIT testing. Ultimately by choosing wisely, we can help reduce the cost and safety implications of a falsely positive HIT diagnosis.

What do you do?

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter.

Disclosures

The authors report no conflict of interest.

Occupational and Environmental Health

Black lung disease in the 21st century

Inhalation and deposition of coal dust particles cause a range of lung injury from coal workers’ pneumoconiosis (CWP) to dust-related diffuse fibrosis to COPD. Despite workplace standards and improved environmental controls to limit dust exposure within coal mines, incidence of “black lung disease” in the United States has increased since the turn of the century (Antao VC, et al. Occup Environ Med. 2005;62[10]:670). Coal miners working in the Appalachian Mountains have been particularly vulnerable to developing rapidly progressive and severe pneumoconiosis. In 2018, three black lung clinics in central Appalachia uncovered the largest cluster of progressive massive fibrosis (PMF) ever reported (Blackley DJ, et al. JAMA. 2018;319[5]:500). An investigation by National Public Radio (NPR) and the Public Broadcasting Service (PBS) program Frontline identified more than 2,000 Appalachian coal miners suffering with PMF from 2011 to 2016, while only 99 cases of PMF were identified by the current federal monitoring program during the same period (https://goo.gl/ZJXp1W). Only about one-third of coal miners may participate in screening for black lung disease, and lack of participation could result from barriers such as fear of retaliation from employers (Siddons A. CQ-Roll Call, Inc. March 1, 2019; https://goo.gl/5mfVFvl). Ongoing research is studying factors leading to the resurgence in CWP. Increasing silica content in coal dust is a likely culprit that has escaped mine safety regulations. Given the rising incidence and the increasing morbidity and mortality of black lung disease, there is a need to educate and engage pulmonologists and others to improve surveillance and early recognition of the spectrum of coal-dust-related lung diseases to decrease morbidity and mortality among this vulnerable occupational group.

Drew Harris, MD
Amy Ahasic, MD, MPH, FCCP
Steering Committee Members

Palliative and End-of-Life Care

Importance of language and word choice when discussing cardiopulmonary resuscitation (CPR)

Words matter. Whether spoken or written, the words we choose when communicating with each other are fundamentally important, both by intention of the originator and the understanding of the audience, whether or not the meaning is imparted faithfully.

Respiratory Care

Low-tidal volume ventilation

Respir CMechanical ventilation in postoperative (post-op) patients is essential in care because it can determine the patient’s overall outcome, especially in post-op cardiovascular surgery patients. The risks of hemodynamic instability and consideration of total body organ function make choosing the correct strategy of mechanical ventilation vital (Ball, et al. Crit Care. 2016;22[4]:386). The current standard of practice for mechanically ventilated patients is to use low-tidal volume (LTV) ventilation, meaning administering 6-7 mL/kg of ideal body weight (Hoegl, et al. Anesthesiology. 2016;29[4]:94). The benefits of LTV ventilation include significantly decreased risk in lung injury, decreased risk of developing ARDS, and lessening of hemodynamic compromise (Hoegl, et al. 2016); (Stephens, et al. Crit Care Med. 2015;43:1477). Also, due to its high efficacy in terms of cost-effective care, such as shorter ICU stays and less number of days supported by mechanical ventilation, many hospitals have incorporated LTV strategy into the care of almost all post-op patients (Stephens, et al. 2015). However, no randomized controlled trials have been conducted in post-op cardiovascular patients undergoing mechanical ventilation to determine if LTV ventilation (6-7 mL/kg) has superior efficacy over higher levels of ventilation (8-10 mL/kg). This patient population tends to have normal lung function and, therefore, a LTV strategy could possibly be too conservative, whereas larger tidal volumes may be more comfortable and provide better ventilation considering the increased dead space in post-op cardiovascular patients. In order to address this gap in the literature, it is essential to determine if significant differences exist in patient mortality, ventilator days, hospital stay, and incidence of pulmonary complications for this population undergoing ventilation volumes of approximately 6 mL/kg or 8 mL/kg of ideal body weight.

Bethlehem Markos
Fellow-in-Training

Sleep Medicine

In case you missed it: Recent findings in obstructive sleep apnea

Lauren Tobias, MD
Steering Committee Member

Occupational and Environmental Health

Black lung disease in the 21st century

Inhalation and deposition of coal dust particles cause a range of lung injury from coal workers’ pneumoconiosis (CWP) to dust-related diffuse fibrosis to COPD. Despite workplace standards and improved environmental controls to limit dust exposure within coal mines, incidence of “black lung disease” in the United States has increased since the turn of the century (Antao VC, et al. Occup Environ Med. 2005;62[10]:670). Coal miners working in the Appalachian Mountains have been particularly vulnerable to developing rapidly progressive and severe pneumoconiosis. In 2018, three black lung clinics in central Appalachia uncovered the largest cluster of progressive massive fibrosis (PMF) ever reported (Blackley DJ, et al. JAMA. 2018;319[5]:500). An investigation by National Public Radio (NPR) and the Public Broadcasting Service (PBS) program Frontline identified more than 2,000 Appalachian coal miners suffering with PMF from 2011 to 2016, while only 99 cases of PMF were identified by the current federal monitoring program during the same period (https://goo.gl/ZJXp1W). Only about one-third of coal miners may participate in screening for black lung disease, and lack of participation could result from barriers such as fear of retaliation from employers (Siddons A. CQ-Roll Call, Inc. March 1, 2019; https://goo.gl/5mfVFvl). Ongoing research is studying factors leading to the resurgence in CWP. Increasing silica content in coal dust is a likely culprit that has escaped mine safety regulations. Given the rising incidence and the increasing morbidity and mortality of black lung disease, there is a need to educate and engage pulmonologists and others to improve surveillance and early recognition of the spectrum of coal-dust-related lung diseases to decrease morbidity and mortality among this vulnerable occupational group.

Drew Harris, MD
Amy Ahasic, MD, MPH, FCCP
Steering Committee Members

Palliative and End-of-Life Care

Importance of language and word choice when discussing cardiopulmonary resuscitation (CPR)

Words matter. Whether spoken or written, the words we choose when communicating with each other are fundamentally important, both by intention of the originator and the understanding of the audience, whether or not the meaning is imparted faithfully.

Respiratory Care

Low-tidal volume ventilation

Respir CMechanical ventilation in postoperative (post-op) patients is essential in care because it can determine the patient’s overall outcome, especially in post-op cardiovascular surgery patients. The risks of hemodynamic instability and consideration of total body organ function make choosing the correct strategy of mechanical ventilation vital (Ball, et al. Crit Care. 2016;22[4]:386). The current standard of practice for mechanically ventilated patients is to use low-tidal volume (LTV) ventilation, meaning administering 6-7 mL/kg of ideal body weight (Hoegl, et al. Anesthesiology. 2016;29[4]:94). The benefits of LTV ventilation include significantly decreased risk in lung injury, decreased risk of developing ARDS, and lessening of hemodynamic compromise (Hoegl, et al. 2016); (Stephens, et al. Crit Care Med. 2015;43:1477). Also, due to its high efficacy in terms of cost-effective care, such as shorter ICU stays and less number of days supported by mechanical ventilation, many hospitals have incorporated LTV strategy into the care of almost all post-op patients (Stephens, et al. 2015). However, no randomized controlled trials have been conducted in post-op cardiovascular patients undergoing mechanical ventilation to determine if LTV ventilation (6-7 mL/kg) has superior efficacy over higher levels of ventilation (8-10 mL/kg). This patient population tends to have normal lung function and, therefore, a LTV strategy could possibly be too conservative, whereas larger tidal volumes may be more comfortable and provide better ventilation considering the increased dead space in post-op cardiovascular patients. In order to address this gap in the literature, it is essential to determine if significant differences exist in patient mortality, ventilator days, hospital stay, and incidence of pulmonary complications for this population undergoing ventilation volumes of approximately 6 mL/kg or 8 mL/kg of ideal body weight.

Bethlehem Markos
Fellow-in-Training

Sleep Medicine

In case you missed it: Recent findings in obstructive sleep apnea

Lauren Tobias, MD
Steering Committee Member

Occupational and Environmental Health

Black lung disease in the 21st century

Inhalation and deposition of coal dust particles cause a range of lung injury from coal workers’ pneumoconiosis (CWP) to dust-related diffuse fibrosis to COPD. Despite workplace standards and improved environmental controls to limit dust exposure within coal mines, incidence of “black lung disease” in the United States has increased since the turn of the century (Antao VC, et al. Occup Environ Med. 2005;62[10]:670). Coal miners working in the Appalachian Mountains have been particularly vulnerable to developing rapidly progressive and severe pneumoconiosis. In 2018, three black lung clinics in central Appalachia uncovered the largest cluster of progressive massive fibrosis (PMF) ever reported (Blackley DJ, et al. JAMA. 2018;319[5]:500). An investigation by National Public Radio (NPR) and the Public Broadcasting Service (PBS) program Frontline identified more than 2,000 Appalachian coal miners suffering with PMF from 2011 to 2016, while only 99 cases of PMF were identified by the current federal monitoring program during the same period (https://goo.gl/ZJXp1W). Only about one-third of coal miners may participate in screening for black lung disease, and lack of participation could result from barriers such as fear of retaliation from employers (Siddons A. CQ-Roll Call, Inc. March 1, 2019; https://goo.gl/5mfVFvl). Ongoing research is studying factors leading to the resurgence in CWP. Increasing silica content in coal dust is a likely culprit that has escaped mine safety regulations. Given the rising incidence and the increasing morbidity and mortality of black lung disease, there is a need to educate and engage pulmonologists and others to improve surveillance and early recognition of the spectrum of coal-dust-related lung diseases to decrease morbidity and mortality among this vulnerable occupational group.

Drew Harris, MD
Amy Ahasic, MD, MPH, FCCP
Steering Committee Members

Palliative and End-of-Life Care

Importance of language and word choice when discussing cardiopulmonary resuscitation (CPR)

Words matter. Whether spoken or written, the words we choose when communicating with each other are fundamentally important, both by intention of the originator and the understanding of the audience, whether or not the meaning is imparted faithfully.

Respiratory Care

Low-tidal volume ventilation

Respir CMechanical ventilation in postoperative (post-op) patients is essential in care because it can determine the patient’s overall outcome, especially in post-op cardiovascular surgery patients. The risks of hemodynamic instability and consideration of total body organ function make choosing the correct strategy of mechanical ventilation vital (Ball, et al. Crit Care. 2016;22[4]:386). The current standard of practice for mechanically ventilated patients is to use low-tidal volume (LTV) ventilation, meaning administering 6-7 mL/kg of ideal body weight (Hoegl, et al. Anesthesiology. 2016;29[4]:94). The benefits of LTV ventilation include significantly decreased risk in lung injury, decreased risk of developing ARDS, and lessening of hemodynamic compromise (Hoegl, et al. 2016); (Stephens, et al. Crit Care Med. 2015;43:1477). Also, due to its high efficacy in terms of cost-effective care, such as shorter ICU stays and less number of days supported by mechanical ventilation, many hospitals have incorporated LTV strategy into the care of almost all post-op patients (Stephens, et al. 2015). However, no randomized controlled trials have been conducted in post-op cardiovascular patients undergoing mechanical ventilation to determine if LTV ventilation (6-7 mL/kg) has superior efficacy over higher levels of ventilation (8-10 mL/kg). This patient population tends to have normal lung function and, therefore, a LTV strategy could possibly be too conservative, whereas larger tidal volumes may be more comfortable and provide better ventilation considering the increased dead space in post-op cardiovascular patients. In order to address this gap in the literature, it is essential to determine if significant differences exist in patient mortality, ventilator days, hospital stay, and incidence of pulmonary complications for this population undergoing ventilation volumes of approximately 6 mL/kg or 8 mL/kg of ideal body weight.

Bethlehem Markos
Fellow-in-Training

Sleep Medicine

In case you missed it: Recent findings in obstructive sleep apnea

Lauren Tobias, MD
Steering Committee Member