User login
Study reveals global inequalities in childhood leukemia survival
New research has revealed global inequalities in survival rates for pediatric patients with leukemia.
Investigators analyzed data on nearly 90,000 pediatric leukemia patients treated in 53 countries.
In most countries, patients with lymphoid leukemias or acute myeloid leukemia (AML) saw an increase in 5-year survival between 1995 and 2009.
However, there were wide variations in survival between the countries.
The investigators reported these findings in The Lancet Haematology.
They evaluated data from 89,828 leukemia patients (ages 0 to 14) included in 198 cancer registries in 53 countries.
The team estimated 5-year net survival for patients with AML or lymphoid leukemias (controlling for non-leukemia-related deaths) by calendar period of diagnosis—1995–1999, 2000–2004, and 2005–2009—in each country.
For children diagnosed with lymphoid leukemias between 1995 and 1999, 5-year survival rates ranged from 10.6% (in China) to 86.8% (in Austria). For children diagnosed between 2005 and 2009, the rates ranged from 52.4% (Colombia) to 91.6% (Germany).
For AML, 5-year survival rates ranged from 4.2% (China) to 72.2% (Sweden) in patients diagnosed between 1995 and 1999. For children diagnosed between 2005 and 2009, 5-year survival rates ranged from 33.3% (Bulgaria) to 78.2% (Germany).
The investigators noted that, in some countries, survival for both groups of leukemia patients was consistently high.
In Austria, for example, 5-year survival rates for lymphoid leukemias were 86.8% in 1995-1999 and 91.1% in 2005-2009. For AML, rates were 60.1% and 72.6%, respectively.
Other countries saw substantial increases in survival over time.
In China, the 5-year survival rate for patients with lymphoid leukemias increased from 10.6% in 1995-1999 to 69.2% in 2005-2009. For patients with AML, the rate increased from 4.2% to 41.1%.
“These findings show the extent of worldwide inequalities in access to optimal healthcare for children with cancer,” said study author Audrey Bonaventure, MD, PhD, of the London School of Hygiene & Tropical Medicine in the UK.
“Providing additional resources, alongside evidence-based initiatives such as international collaborations and treatment guidelines, could improve access to efficient treatment and care for all children with leukemia. This would contribute substantially to reducing worldwide inequalities in survival.” 
New research has revealed global inequalities in survival rates for pediatric patients with leukemia.
Investigators analyzed data on nearly 90,000 pediatric leukemia patients treated in 53 countries.
In most countries, patients with lymphoid leukemias or acute myeloid leukemia (AML) saw an increase in 5-year survival between 1995 and 2009.
However, there were wide variations in survival between the countries.
The investigators reported these findings in The Lancet Haematology.
They evaluated data from 89,828 leukemia patients (ages 0 to 14) included in 198 cancer registries in 53 countries.
The team estimated 5-year net survival for patients with AML or lymphoid leukemias (controlling for non-leukemia-related deaths) by calendar period of diagnosis—1995–1999, 2000–2004, and 2005–2009—in each country.
For children diagnosed with lymphoid leukemias between 1995 and 1999, 5-year survival rates ranged from 10.6% (in China) to 86.8% (in Austria). For children diagnosed between 2005 and 2009, the rates ranged from 52.4% (Colombia) to 91.6% (Germany).
For AML, 5-year survival rates ranged from 4.2% (China) to 72.2% (Sweden) in patients diagnosed between 1995 and 1999. For children diagnosed between 2005 and 2009, 5-year survival rates ranged from 33.3% (Bulgaria) to 78.2% (Germany).
The investigators noted that, in some countries, survival for both groups of leukemia patients was consistently high.
In Austria, for example, 5-year survival rates for lymphoid leukemias were 86.8% in 1995-1999 and 91.1% in 2005-2009. For AML, rates were 60.1% and 72.6%, respectively.
Other countries saw substantial increases in survival over time.
In China, the 5-year survival rate for patients with lymphoid leukemias increased from 10.6% in 1995-1999 to 69.2% in 2005-2009. For patients with AML, the rate increased from 4.2% to 41.1%.
“These findings show the extent of worldwide inequalities in access to optimal healthcare for children with cancer,” said study author Audrey Bonaventure, MD, PhD, of the London School of Hygiene & Tropical Medicine in the UK.
“Providing additional resources, alongside evidence-based initiatives such as international collaborations and treatment guidelines, could improve access to efficient treatment and care for all children with leukemia. This would contribute substantially to reducing worldwide inequalities in survival.”
New research has revealed global inequalities in survival rates for pediatric patients with leukemia.
Investigators analyzed data on nearly 90,000 pediatric leukemia patients treated in 53 countries.
In most countries, patients with lymphoid leukemias or acute myeloid leukemia (AML) saw an increase in 5-year survival between 1995 and 2009.
However, there were wide variations in survival between the countries.
The investigators reported these findings in The Lancet Haematology.
They evaluated data from 89,828 leukemia patients (ages 0 to 14) included in 198 cancer registries in 53 countries.
The team estimated 5-year net survival for patients with AML or lymphoid leukemias (controlling for non-leukemia-related deaths) by calendar period of diagnosis—1995–1999, 2000–2004, and 2005–2009—in each country.
For children diagnosed with lymphoid leukemias between 1995 and 1999, 5-year survival rates ranged from 10.6% (in China) to 86.8% (in Austria). For children diagnosed between 2005 and 2009, the rates ranged from 52.4% (Colombia) to 91.6% (Germany).
For AML, 5-year survival rates ranged from 4.2% (China) to 72.2% (Sweden) in patients diagnosed between 1995 and 1999. For children diagnosed between 2005 and 2009, 5-year survival rates ranged from 33.3% (Bulgaria) to 78.2% (Germany).
The investigators noted that, in some countries, survival for both groups of leukemia patients was consistently high.
In Austria, for example, 5-year survival rates for lymphoid leukemias were 86.8% in 1995-1999 and 91.1% in 2005-2009. For AML, rates were 60.1% and 72.6%, respectively.
Other countries saw substantial increases in survival over time.
In China, the 5-year survival rate for patients with lymphoid leukemias increased from 10.6% in 1995-1999 to 69.2% in 2005-2009. For patients with AML, the rate increased from 4.2% to 41.1%.
“These findings show the extent of worldwide inequalities in access to optimal healthcare for children with cancer,” said study author Audrey Bonaventure, MD, PhD, of the London School of Hygiene & Tropical Medicine in the UK.
“Providing additional resources, alongside evidence-based initiatives such as international collaborations and treatment guidelines, could improve access to efficient treatment and care for all children with leukemia. This would contribute substantially to reducing worldwide inequalities in survival.”
FDA clears test for individual WBD platelet units
The US Food and Drug Administration (FDA) has granted new clearance for Verax Biomedical’s Platelet PGD® Test.
This qualitative immunoassay is designed to detect aerobic and anaerobic Gram-positive and Gram-negative bacteria in platelets.
The test is now cleared for use on single units of leukocyte-reduced or non-leukocyte-reduced whole blood-derived (WBD) platelets in plasma.
The Platelet PGD Test was previously cleared by the FDA as a safety measure to be used following testing with a growth-based, quality control (QC) test for platelet components that is cleared by the FDA.
For this indication, the Platelet PGD Test can be used within 24 hours of transfusion on:
- Leukocyte-reduced apheresis platelets suspended in plasma
- Leukocyte-reduced apheresis platelets suspended in platelet additive solution C and plasma
- Pre-storage pools of up to 6 leukocyte-reduced WBD platelets suspended in plasma.
When used as a safety measure, the Platelet PGD Test can extend the dating of apheresis platelets in plasma from 5 to 7 days.
The Platelet PGD Test also has FDA clearance as a QC test for use on pools of up to 6 units of leukocyte-reduced and non-leukocyte-reduced WBD platelets suspended in plasma that are pooled within 4 hours of transfusion.
The latest FDA clearance extends this use to individual units of WBD platelets in plasma.
“[The new clearance] has been requested by current users of PGD as well as being outlined as a need in pending FDA Draft Guidance to address the risk of bacterial contamination in platelets,” said Jim Lousararian, chief executive officer of Verax Biomedical.
According to the company, the new clearance is intended to help reduce the risk of bacterial contamination for pediatric patients receiving platelet transfusions.
“Pediatric patients pose unique challenges in transfusion medicine,” said Paul Mintz, MD, chief medical officer of Verax Biomedical.
“They require small platelet doses and possess fragile immune systems. PGD testing individual WBD units for transfusion makes it practical to provide bacterially tested platelets to this most vulnerable group of patients.”
Multicenter study
The Verax PGD® test was evaluated in a 2-year study including 18 US hospitals. The results were published in Transfusion in 2011.
The objective of the study was to evaluate the test’s ability to detect bacterially contaminated units in the US apheresis inventory that tested negative for contamination by existing growth-based QC tests.
A total of 9 contaminated units were detected by PGD and confirmed as bacterially contaminated in a population of 27,620 leukocyte-reduced apheresis units (1:3,069 doses tested).
All 9 units had previously tested negative by growth-based QC methods applied earlier in unit life in conformance with all applicable AABB and CAP standards for bacterial testing.
Researchers said the study clearly demonstrated the ability of the Platelet PGD Test to detect and interdict contaminated units missed by current QC testing methods.
The US Food and Drug Administration (FDA) has granted new clearance for Verax Biomedical’s Platelet PGD® Test.
This qualitative immunoassay is designed to detect aerobic and anaerobic Gram-positive and Gram-negative bacteria in platelets.
The test is now cleared for use on single units of leukocyte-reduced or non-leukocyte-reduced whole blood-derived (WBD) platelets in plasma.
The Platelet PGD Test was previously cleared by the FDA as a safety measure to be used following testing with a growth-based, quality control (QC) test for platelet components that is cleared by the FDA.
For this indication, the Platelet PGD Test can be used within 24 hours of transfusion on:
- Leukocyte-reduced apheresis platelets suspended in plasma
- Leukocyte-reduced apheresis platelets suspended in platelet additive solution C and plasma
- Pre-storage pools of up to 6 leukocyte-reduced WBD platelets suspended in plasma.
When used as a safety measure, the Platelet PGD Test can extend the dating of apheresis platelets in plasma from 5 to 7 days.
The Platelet PGD Test also has FDA clearance as a QC test for use on pools of up to 6 units of leukocyte-reduced and non-leukocyte-reduced WBD platelets suspended in plasma that are pooled within 4 hours of transfusion.
The latest FDA clearance extends this use to individual units of WBD platelets in plasma.
“[The new clearance] has been requested by current users of PGD as well as being outlined as a need in pending FDA Draft Guidance to address the risk of bacterial contamination in platelets,” said Jim Lousararian, chief executive officer of Verax Biomedical.
According to the company, the new clearance is intended to help reduce the risk of bacterial contamination for pediatric patients receiving platelet transfusions.
“Pediatric patients pose unique challenges in transfusion medicine,” said Paul Mintz, MD, chief medical officer of Verax Biomedical.
“They require small platelet doses and possess fragile immune systems. PGD testing individual WBD units for transfusion makes it practical to provide bacterially tested platelets to this most vulnerable group of patients.”
Multicenter study
The Verax PGD® test was evaluated in a 2-year study including 18 US hospitals. The results were published in Transfusion in 2011.
The objective of the study was to evaluate the test’s ability to detect bacterially contaminated units in the US apheresis inventory that tested negative for contamination by existing growth-based QC tests.
A total of 9 contaminated units were detected by PGD and confirmed as bacterially contaminated in a population of 27,620 leukocyte-reduced apheresis units (1:3,069 doses tested).
All 9 units had previously tested negative by growth-based QC methods applied earlier in unit life in conformance with all applicable AABB and CAP standards for bacterial testing.
Researchers said the study clearly demonstrated the ability of the Platelet PGD Test to detect and interdict contaminated units missed by current QC testing methods.
The US Food and Drug Administration (FDA) has granted new clearance for Verax Biomedical’s Platelet PGD® Test.
This qualitative immunoassay is designed to detect aerobic and anaerobic Gram-positive and Gram-negative bacteria in platelets.
The test is now cleared for use on single units of leukocyte-reduced or non-leukocyte-reduced whole blood-derived (WBD) platelets in plasma.
The Platelet PGD Test was previously cleared by the FDA as a safety measure to be used following testing with a growth-based, quality control (QC) test for platelet components that is cleared by the FDA.
For this indication, the Platelet PGD Test can be used within 24 hours of transfusion on:
- Leukocyte-reduced apheresis platelets suspended in plasma
- Leukocyte-reduced apheresis platelets suspended in platelet additive solution C and plasma
- Pre-storage pools of up to 6 leukocyte-reduced WBD platelets suspended in plasma.
When used as a safety measure, the Platelet PGD Test can extend the dating of apheresis platelets in plasma from 5 to 7 days.
The Platelet PGD Test also has FDA clearance as a QC test for use on pools of up to 6 units of leukocyte-reduced and non-leukocyte-reduced WBD platelets suspended in plasma that are pooled within 4 hours of transfusion.
The latest FDA clearance extends this use to individual units of WBD platelets in plasma.
“[The new clearance] has been requested by current users of PGD as well as being outlined as a need in pending FDA Draft Guidance to address the risk of bacterial contamination in platelets,” said Jim Lousararian, chief executive officer of Verax Biomedical.
According to the company, the new clearance is intended to help reduce the risk of bacterial contamination for pediatric patients receiving platelet transfusions.
“Pediatric patients pose unique challenges in transfusion medicine,” said Paul Mintz, MD, chief medical officer of Verax Biomedical.
“They require small platelet doses and possess fragile immune systems. PGD testing individual WBD units for transfusion makes it practical to provide bacterially tested platelets to this most vulnerable group of patients.”
Multicenter study
The Verax PGD® test was evaluated in a 2-year study including 18 US hospitals. The results were published in Transfusion in 2011.
The objective of the study was to evaluate the test’s ability to detect bacterially contaminated units in the US apheresis inventory that tested negative for contamination by existing growth-based QC tests.
A total of 9 contaminated units were detected by PGD and confirmed as bacterially contaminated in a population of 27,620 leukocyte-reduced apheresis units (1:3,069 doses tested).
All 9 units had previously tested negative by growth-based QC methods applied earlier in unit life in conformance with all applicable AABB and CAP standards for bacterial testing.
Researchers said the study clearly demonstrated the ability of the Platelet PGD Test to detect and interdict contaminated units missed by current QC testing methods.
FDA authorizes use of first fully automated Zika IgM test
The US Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for DiaSorin Incorporated’s LIAISON® XL Zika Capture IgM assay, the first fully automated serology assay for the detection of Zika virus infection.
The LIAISON® XL Zika Capture IgM assay is intended for the presumptive qualitative detection of Zika virus IgM antibodies in human sera.
The FDA’s decision to grant an EUA means the LIAISON® XL Zika Capture IgM assay can be used to test serum samples collected from individuals meeting criteria for Zika virus testing set forth by the US Centers for Disease Control and Prevention.
This includes clinical criteria—such as a history of clinical signs and symptoms associated with Zika virus infection—and/or epidemiological criteria—such as a history of residence in or travel to a geographic region with active Zika transmission.
Specimens used with the LIAISON® XL Zika Capture IgM assay should be collected between 8 days and 10 weeks after the onset of symptoms or risk of exposure to Zika.
The assay is intended for use in US laboratories that are certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high-complexity tests, or by similarly qualified non-US laboratories, pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 360bbb-3).
Where there are presumptive Zika IgM positive and presumptive recent Zika positive results from the LIAISON® XL Zika Capture IgM assay, confirmation of the presence of anti-Zika IgM antibodies requires additional testing and/or consideration alongside test results for other patient-matched specimens using the latest CDC testing algorithms for the diagnosis of Zika virus infection.
More information on the LIAISON® XL Zika Capture IgM assay and other Zika assays granted EUAs can be found on the FDA’s EUA page.
Funding for the LIAISON® XL Zika Capture IgM assay was provided by the US Department of Health and Human Services, which granted DiaSorin a $2.6 million contract in the fall of 2016.
About the EUA
The EUA does not mean the LIAISON® XL Zika Capture IgM assay is FDA cleared or approved.
An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
This means the LIAISON® XL Zika Capture IgM assay is only authorized as long as circumstances exist to justify the emergency use of in vitro diagnostics for the detection of Zika virus, unless the authorization is terminated or revoked sooner.
The US Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for DiaSorin Incorporated’s LIAISON® XL Zika Capture IgM assay, the first fully automated serology assay for the detection of Zika virus infection.
The LIAISON® XL Zika Capture IgM assay is intended for the presumptive qualitative detection of Zika virus IgM antibodies in human sera.
The FDA’s decision to grant an EUA means the LIAISON® XL Zika Capture IgM assay can be used to test serum samples collected from individuals meeting criteria for Zika virus testing set forth by the US Centers for Disease Control and Prevention.
This includes clinical criteria—such as a history of clinical signs and symptoms associated with Zika virus infection—and/or epidemiological criteria—such as a history of residence in or travel to a geographic region with active Zika transmission.
Specimens used with the LIAISON® XL Zika Capture IgM assay should be collected between 8 days and 10 weeks after the onset of symptoms or risk of exposure to Zika.
The assay is intended for use in US laboratories that are certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high-complexity tests, or by similarly qualified non-US laboratories, pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 360bbb-3).
Where there are presumptive Zika IgM positive and presumptive recent Zika positive results from the LIAISON® XL Zika Capture IgM assay, confirmation of the presence of anti-Zika IgM antibodies requires additional testing and/or consideration alongside test results for other patient-matched specimens using the latest CDC testing algorithms for the diagnosis of Zika virus infection.
More information on the LIAISON® XL Zika Capture IgM assay and other Zika assays granted EUAs can be found on the FDA’s EUA page.
Funding for the LIAISON® XL Zika Capture IgM assay was provided by the US Department of Health and Human Services, which granted DiaSorin a $2.6 million contract in the fall of 2016.
About the EUA
The EUA does not mean the LIAISON® XL Zika Capture IgM assay is FDA cleared or approved.
An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
This means the LIAISON® XL Zika Capture IgM assay is only authorized as long as circumstances exist to justify the emergency use of in vitro diagnostics for the detection of Zika virus, unless the authorization is terminated or revoked sooner.
The US Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for DiaSorin Incorporated’s LIAISON® XL Zika Capture IgM assay, the first fully automated serology assay for the detection of Zika virus infection.
The LIAISON® XL Zika Capture IgM assay is intended for the presumptive qualitative detection of Zika virus IgM antibodies in human sera.
The FDA’s decision to grant an EUA means the LIAISON® XL Zika Capture IgM assay can be used to test serum samples collected from individuals meeting criteria for Zika virus testing set forth by the US Centers for Disease Control and Prevention.
This includes clinical criteria—such as a history of clinical signs and symptoms associated with Zika virus infection—and/or epidemiological criteria—such as a history of residence in or travel to a geographic region with active Zika transmission.
Specimens used with the LIAISON® XL Zika Capture IgM assay should be collected between 8 days and 10 weeks after the onset of symptoms or risk of exposure to Zika.
The assay is intended for use in US laboratories that are certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high-complexity tests, or by similarly qualified non-US laboratories, pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 360bbb-3).
Where there are presumptive Zika IgM positive and presumptive recent Zika positive results from the LIAISON® XL Zika Capture IgM assay, confirmation of the presence of anti-Zika IgM antibodies requires additional testing and/or consideration alongside test results for other patient-matched specimens using the latest CDC testing algorithms for the diagnosis of Zika virus infection.
More information on the LIAISON® XL Zika Capture IgM assay and other Zika assays granted EUAs can be found on the FDA’s EUA page.
Funding for the LIAISON® XL Zika Capture IgM assay was provided by the US Department of Health and Human Services, which granted DiaSorin a $2.6 million contract in the fall of 2016.
About the EUA
The EUA does not mean the LIAISON® XL Zika Capture IgM assay is FDA cleared or approved.
An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
This means the LIAISON® XL Zika Capture IgM assay is only authorized as long as circumstances exist to justify the emergency use of in vitro diagnostics for the detection of Zika virus, unless the authorization is terminated or revoked sooner.
When to Discontinue RAAS Therapy in CKD Patients
Q) A speaker at a meeting I attended said that ACEis/ARBs can be used in all stages of CKD. But locally, our nephrologists discontinue use when the GFR falls below 20 mL/min. Who is correct?
Definitive data on whether to continue use of ACE inhibitors (ACEis) and angiotensin-II receptor blockers (ARBs) in patients with chronic kidney disease (CKD) is lacking.¹ At this time, it is difficult to prove that the renoprotective effects of renin-angiotensin-aldosterone system (RAAS) inhibitors are separate from their antihypertensive effects. Few studies have investigated the effects of RAAS therapy on patients with advanced CKD at baseline (CKD stage 4 or 5; glomerular filtration rate [GFR], < 30 mL/min).2
ACEis and ARBs are indicated for use in CKD patients with hypertension, proteinuria/albuminuria, heart failure with reduced ejection fraction, and left ventricle dysfunction post–myocardial infarction.3 While these medications are the main pharmacologic therapy for reducing albuminuria in CKD patients, they increase serum creatinine by 20% to 30% and thereby decrease GFR.2,4
The decision to continue or discontinue ACEi/ARB use when patients reach CKD stage 4 or 5 is controversial. On one hand, risks associated with continuation include hyperkalemia, metabolic acidosis, and possible reduction in GFR. The decision to discontinue these medications may result in increased GFR, improved kidney function, and delayed onset of kidney failure or need for dialysis.3,4 In a 2011 study examining outcomes in patients with stage 4 CKD two years after stopping their ACEis/ARBs, the researchers found that patients who were alive without renal replacement therapy were hypertensive but had the highest GFRs.3
On the other hand, ACEis/ARBs have been shown to reduce incidence of cardiovascular disease (CVD) in patients without CKD. It is widely known that patients with CKD have increased risk for CVD, though there is little data examining the effects of RAAS inhibitors on CVD in this population.¹ A recent study found a reduced risk for fatal CVD in peritoneal dialysis patients treated with ACEis.5 Another study reported improved renal outcomes in nondiabetic patients with advanced CKD who were treated with ACEis.6 The National Kidney Foundation/Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines on Hypertension currently state that with careful monitoring, most patients with advanced CKD can continue taking ACEis/ARBs.7
More studies are needed to confidently close this controversial debate. Fortunately, the STOP-ACEi study, a three-year trial that began in 2014 in the UK, is examining the effects of ACEi/ARB use in patients with advanced CKD. It aims to determine whether discontinuation of ACEis/ARBs in these patients can help to stabilize or improve renal function, compared to continued use. By maintaining good blood pressure control in these patients, the researchers hope to distinguish the antihypertensive effects from other potential benefits of the RAAS inhibitors.2 The results of this trial may provide additional clarity for making decisions about ACEi/ARB treatment in our patients with advanced CKD. —RVR, SMR
Rebecca V. Rokosky, MSN, APRN, FNP-BC
Sub Investigator in the Clinical Advancement Center, PPLC, San Antonio, Texas
Shannon M. Rice, MS, PA-C
Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego
1. Ahmed A, Jorna T, Bhandari S. Should we STOP angiotensin converting enzyme inhibitors/angiotensin receptor blockers in advanced kidney disease? Nephron. 2016; 133(3):147-158.
2. Bhandari S, Ives N, Brettell EA, et al. Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial. Nephrol Dial Transplant. 2016; 31(2):255-261.
3. Gonclaves A, Khwaja A, Ahmed A, et al. Stopping renin-angiotensin system inhibitors in chronic kidney disease: predictors of response. Nephron Clin Pract. 2011;119(4):348-354.
4. Zuber K, Gilmartin C, Davis J. Managing hypertension in patients with chronic kidney disease. JAAPA. 2014;27(9):37-46.
5. Shen JI, Saxena AB, Montez-Rath ME, et al. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis. Nephrol Dial Transplant. 2016 Apr 13. [Epub ahead of print]
6. Hou F, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354(2):131-140.
7. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month’s responses were authored by Cynthia Smith, DNP, CNN-NP, APRN, FNP-BC, who practices at Renal Consultants, PLLC, in South Charleston, West Virginia, Rebecca V. Rokosky, MSN, APRN, FNP-BC, who is Sub Investigator in the Clinical Advancement Center, PPLC, in San Antonio, Texas, and Shannon M. Rice, MS, PA-C, who is in the Division of Nephrology and Hypertension, Department of Medicine, at the University of California, San Diego.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month’s responses were authored by Cynthia Smith, DNP, CNN-NP, APRN, FNP-BC, who practices at Renal Consultants, PLLC, in South Charleston, West Virginia, Rebecca V. Rokosky, MSN, APRN, FNP-BC, who is Sub Investigator in the Clinical Advancement Center, PPLC, in San Antonio, Texas, and Shannon M. Rice, MS, PA-C, who is in the Division of Nephrology and Hypertension, Department of Medicine, at the University of California, San Diego.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month’s responses were authored by Cynthia Smith, DNP, CNN-NP, APRN, FNP-BC, who practices at Renal Consultants, PLLC, in South Charleston, West Virginia, Rebecca V. Rokosky, MSN, APRN, FNP-BC, who is Sub Investigator in the Clinical Advancement Center, PPLC, in San Antonio, Texas, and Shannon M. Rice, MS, PA-C, who is in the Division of Nephrology and Hypertension, Department of Medicine, at the University of California, San Diego.
Q) A speaker at a meeting I attended said that ACEis/ARBs can be used in all stages of CKD. But locally, our nephrologists discontinue use when the GFR falls below 20 mL/min. Who is correct?
Definitive data on whether to continue use of ACE inhibitors (ACEis) and angiotensin-II receptor blockers (ARBs) in patients with chronic kidney disease (CKD) is lacking.¹ At this time, it is difficult to prove that the renoprotective effects of renin-angiotensin-aldosterone system (RAAS) inhibitors are separate from their antihypertensive effects. Few studies have investigated the effects of RAAS therapy on patients with advanced CKD at baseline (CKD stage 4 or 5; glomerular filtration rate [GFR], < 30 mL/min).2
ACEis and ARBs are indicated for use in CKD patients with hypertension, proteinuria/albuminuria, heart failure with reduced ejection fraction, and left ventricle dysfunction post–myocardial infarction.3 While these medications are the main pharmacologic therapy for reducing albuminuria in CKD patients, they increase serum creatinine by 20% to 30% and thereby decrease GFR.2,4
The decision to continue or discontinue ACEi/ARB use when patients reach CKD stage 4 or 5 is controversial. On one hand, risks associated with continuation include hyperkalemia, metabolic acidosis, and possible reduction in GFR. The decision to discontinue these medications may result in increased GFR, improved kidney function, and delayed onset of kidney failure or need for dialysis.3,4 In a 2011 study examining outcomes in patients with stage 4 CKD two years after stopping their ACEis/ARBs, the researchers found that patients who were alive without renal replacement therapy were hypertensive but had the highest GFRs.3
On the other hand, ACEis/ARBs have been shown to reduce incidence of cardiovascular disease (CVD) in patients without CKD. It is widely known that patients with CKD have increased risk for CVD, though there is little data examining the effects of RAAS inhibitors on CVD in this population.¹ A recent study found a reduced risk for fatal CVD in peritoneal dialysis patients treated with ACEis.5 Another study reported improved renal outcomes in nondiabetic patients with advanced CKD who were treated with ACEis.6 The National Kidney Foundation/Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines on Hypertension currently state that with careful monitoring, most patients with advanced CKD can continue taking ACEis/ARBs.7
More studies are needed to confidently close this controversial debate. Fortunately, the STOP-ACEi study, a three-year trial that began in 2014 in the UK, is examining the effects of ACEi/ARB use in patients with advanced CKD. It aims to determine whether discontinuation of ACEis/ARBs in these patients can help to stabilize or improve renal function, compared to continued use. By maintaining good blood pressure control in these patients, the researchers hope to distinguish the antihypertensive effects from other potential benefits of the RAAS inhibitors.2 The results of this trial may provide additional clarity for making decisions about ACEi/ARB treatment in our patients with advanced CKD. —RVR, SMR
Rebecca V. Rokosky, MSN, APRN, FNP-BC
Sub Investigator in the Clinical Advancement Center, PPLC, San Antonio, Texas
Shannon M. Rice, MS, PA-C
Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego
Q) A speaker at a meeting I attended said that ACEis/ARBs can be used in all stages of CKD. But locally, our nephrologists discontinue use when the GFR falls below 20 mL/min. Who is correct?
Definitive data on whether to continue use of ACE inhibitors (ACEis) and angiotensin-II receptor blockers (ARBs) in patients with chronic kidney disease (CKD) is lacking.¹ At this time, it is difficult to prove that the renoprotective effects of renin-angiotensin-aldosterone system (RAAS) inhibitors are separate from their antihypertensive effects. Few studies have investigated the effects of RAAS therapy on patients with advanced CKD at baseline (CKD stage 4 or 5; glomerular filtration rate [GFR], < 30 mL/min).2
ACEis and ARBs are indicated for use in CKD patients with hypertension, proteinuria/albuminuria, heart failure with reduced ejection fraction, and left ventricle dysfunction post–myocardial infarction.3 While these medications are the main pharmacologic therapy for reducing albuminuria in CKD patients, they increase serum creatinine by 20% to 30% and thereby decrease GFR.2,4
The decision to continue or discontinue ACEi/ARB use when patients reach CKD stage 4 or 5 is controversial. On one hand, risks associated with continuation include hyperkalemia, metabolic acidosis, and possible reduction in GFR. The decision to discontinue these medications may result in increased GFR, improved kidney function, and delayed onset of kidney failure or need for dialysis.3,4 In a 2011 study examining outcomes in patients with stage 4 CKD two years after stopping their ACEis/ARBs, the researchers found that patients who were alive without renal replacement therapy were hypertensive but had the highest GFRs.3
On the other hand, ACEis/ARBs have been shown to reduce incidence of cardiovascular disease (CVD) in patients without CKD. It is widely known that patients with CKD have increased risk for CVD, though there is little data examining the effects of RAAS inhibitors on CVD in this population.¹ A recent study found a reduced risk for fatal CVD in peritoneal dialysis patients treated with ACEis.5 Another study reported improved renal outcomes in nondiabetic patients with advanced CKD who were treated with ACEis.6 The National Kidney Foundation/Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines on Hypertension currently state that with careful monitoring, most patients with advanced CKD can continue taking ACEis/ARBs.7
More studies are needed to confidently close this controversial debate. Fortunately, the STOP-ACEi study, a three-year trial that began in 2014 in the UK, is examining the effects of ACEi/ARB use in patients with advanced CKD. It aims to determine whether discontinuation of ACEis/ARBs in these patients can help to stabilize or improve renal function, compared to continued use. By maintaining good blood pressure control in these patients, the researchers hope to distinguish the antihypertensive effects from other potential benefits of the RAAS inhibitors.2 The results of this trial may provide additional clarity for making decisions about ACEi/ARB treatment in our patients with advanced CKD. —RVR, SMR
Rebecca V. Rokosky, MSN, APRN, FNP-BC
Sub Investigator in the Clinical Advancement Center, PPLC, San Antonio, Texas
Shannon M. Rice, MS, PA-C
Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego
1. Ahmed A, Jorna T, Bhandari S. Should we STOP angiotensin converting enzyme inhibitors/angiotensin receptor blockers in advanced kidney disease? Nephron. 2016; 133(3):147-158.
2. Bhandari S, Ives N, Brettell EA, et al. Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial. Nephrol Dial Transplant. 2016; 31(2):255-261.
3. Gonclaves A, Khwaja A, Ahmed A, et al. Stopping renin-angiotensin system inhibitors in chronic kidney disease: predictors of response. Nephron Clin Pract. 2011;119(4):348-354.
4. Zuber K, Gilmartin C, Davis J. Managing hypertension in patients with chronic kidney disease. JAAPA. 2014;27(9):37-46.
5. Shen JI, Saxena AB, Montez-Rath ME, et al. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis. Nephrol Dial Transplant. 2016 Apr 13. [Epub ahead of print]
6. Hou F, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354(2):131-140.
7. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.
1. Ahmed A, Jorna T, Bhandari S. Should we STOP angiotensin converting enzyme inhibitors/angiotensin receptor blockers in advanced kidney disease? Nephron. 2016; 133(3):147-158.
2. Bhandari S, Ives N, Brettell EA, et al. Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial. Nephrol Dial Transplant. 2016; 31(2):255-261.
3. Gonclaves A, Khwaja A, Ahmed A, et al. Stopping renin-angiotensin system inhibitors in chronic kidney disease: predictors of response. Nephron Clin Pract. 2011;119(4):348-354.
4. Zuber K, Gilmartin C, Davis J. Managing hypertension in patients with chronic kidney disease. JAAPA. 2014;27(9):37-46.
5. Shen JI, Saxena AB, Montez-Rath ME, et al. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use and cardiovascular outcomes in patients initiating peritoneal dialysis. Nephrol Dial Transplant. 2016 Apr 13. [Epub ahead of print]
6. Hou F, Zhang X, Zhang GH, et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354(2):131-140.
7. Kidney Disease Outcomes Quality Initiative (K/DOQI). K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290.
FDA issues EUA for test to detect Zika virus RNA
The US Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for Nanobiosym Diagnostics Inc.’s Gene-RADAR® Zika Virus Test.
The Gene-RADAR® Zika Virus Test is authorized for the qualitative detection of RNA from Zika virus in human serum.
The test should be used on serum samples collected from individuals meeting the US Centers for Disease Control and Prevention’s (CDC) criteria for Zika virus testing.
This includes clinical criteria—such as a history of clinical signs and symptoms associated with Zika virus infection—and/or epidemiological criteria—such as a history of residence in or travel to a geographic region with active Zika transmission.
The Gene-RADAR® Zika Virus Test is intended for use in US laboratories that are certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high-complexity tests, or by similarly qualified non-US laboratories, pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 360bbb-3).
The Gene-RADAR® Zika Virus Test should be performed according to the CDC’s algorithm for Zika testing (see http://www.cdc.gov/zika/laboratories/lab-guidance.html).
According to the CDC, Zika virus RNA has been detected in serum up to 13 days post-symptom onset in non-pregnant patients, up to 62 days post-symptom onset in pregnant patients, and up to 53 days after the last known possible exposure in an asymptomatic pregnant woman.
About the EUA
The EUA does not mean the Gene-RADAR® Zika Virus Test is FDA cleared or approved.
An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
The EUA for the Gene-RADAR® Zika Virus Test means the test is only authorized as long as circumstances exist to justify the emergency use of in vitro diagnostics for the detection of Zika virus, unless the authorization is terminated or revoked sooner.
More information on the Gene-RADAR® Zika Virus Test and other Zika tests granted EUAs can be found on the FDA’s EUA page.
The US Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for Nanobiosym Diagnostics Inc.’s Gene-RADAR® Zika Virus Test.
The Gene-RADAR® Zika Virus Test is authorized for the qualitative detection of RNA from Zika virus in human serum.
The test should be used on serum samples collected from individuals meeting the US Centers for Disease Control and Prevention’s (CDC) criteria for Zika virus testing.
This includes clinical criteria—such as a history of clinical signs and symptoms associated with Zika virus infection—and/or epidemiological criteria—such as a history of residence in or travel to a geographic region with active Zika transmission.
The Gene-RADAR® Zika Virus Test is intended for use in US laboratories that are certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high-complexity tests, or by similarly qualified non-US laboratories, pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 360bbb-3).
The Gene-RADAR® Zika Virus Test should be performed according to the CDC’s algorithm for Zika testing (see http://www.cdc.gov/zika/laboratories/lab-guidance.html).
According to the CDC, Zika virus RNA has been detected in serum up to 13 days post-symptom onset in non-pregnant patients, up to 62 days post-symptom onset in pregnant patients, and up to 53 days after the last known possible exposure in an asymptomatic pregnant woman.
About the EUA
The EUA does not mean the Gene-RADAR® Zika Virus Test is FDA cleared or approved.
An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
The EUA for the Gene-RADAR® Zika Virus Test means the test is only authorized as long as circumstances exist to justify the emergency use of in vitro diagnostics for the detection of Zika virus, unless the authorization is terminated or revoked sooner.
More information on the Gene-RADAR® Zika Virus Test and other Zika tests granted EUAs can be found on the FDA’s EUA page.
The US Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for Nanobiosym Diagnostics Inc.’s Gene-RADAR® Zika Virus Test.
The Gene-RADAR® Zika Virus Test is authorized for the qualitative detection of RNA from Zika virus in human serum.
The test should be used on serum samples collected from individuals meeting the US Centers for Disease Control and Prevention’s (CDC) criteria for Zika virus testing.
This includes clinical criteria—such as a history of clinical signs and symptoms associated with Zika virus infection—and/or epidemiological criteria—such as a history of residence in or travel to a geographic region with active Zika transmission.
The Gene-RADAR® Zika Virus Test is intended for use in US laboratories that are certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. §263a, to perform high-complexity tests, or by similarly qualified non-US laboratories, pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 360bbb-3).
The Gene-RADAR® Zika Virus Test should be performed according to the CDC’s algorithm for Zika testing (see http://www.cdc.gov/zika/laboratories/lab-guidance.html).
According to the CDC, Zika virus RNA has been detected in serum up to 13 days post-symptom onset in non-pregnant patients, up to 62 days post-symptom onset in pregnant patients, and up to 53 days after the last known possible exposure in an asymptomatic pregnant woman.
About the EUA
The EUA does not mean the Gene-RADAR® Zika Virus Test is FDA cleared or approved.
An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.
The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.
The EUA for the Gene-RADAR® Zika Virus Test means the test is only authorized as long as circumstances exist to justify the emergency use of in vitro diagnostics for the detection of Zika virus, unless the authorization is terminated or revoked sooner.
More information on the Gene-RADAR® Zika Virus Test and other Zika tests granted EUAs can be found on the FDA’s EUA page.
Treatment of Unstable Trochanteric Femur Fractures: Proximal Femur Nail Versus Proximal Femur Locking Compression Plate
Take-Home Points
- Both PFN and PFLCP are effective treatments for unstable trochanteric femur fractures.
- PFN is superior to PFLCP only in terms of shorter incisions and shorter time to full weight-bearing.
- Both devices have good long-term functional outcomes.
- Complication rates in unstable trochanteric fractures treated with both implants are comparable.
- Larger randomized controlled multicenter studies are needed to further evaluate and compare both implants in displaced unstable trochanteric femur fractures.
Trochanteric fractures are among the most widely treated orthopedic injuries, occurring mainly as low-energy injuries in elderly patients and high-energy injuries in younger patients.1,2 About half of these injuries are unstable.3 According to the AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) system, trochanteric fractures can be classified stable (AO/OTA 31.A1-1 to 31.A2-1) or unstable (AO/OTA 31.A2-2 to 31.A3.3).4,5 For surgical fixation of trochanteric femur fractures, various internal fixation devices have been used, either extramedullary (EM) or intramedullary (IM).6 The dynamic hip screw (DHS) is the implant of choice in the treatment of stable trochanteric femur fractures (AO/OTA 31-A1), as it provides secure fixation and controlled impaction.7 Mechanical and technical failures continue to occur in up to 6% to 18% of cases of unstable trochanteric fractures treated with DHS.8 Excessive sliding of the lag screw within the plate barrel results in limb shortening and distal fragment medialization, which are the main causes of these failures.9,10 Dissatisfaction with DHS use in unstable fractures led to the use of IM nails. The various IM devices available are condylocephalic (Ender) nails and cephalomedullary nails, such as gamma nails; IM hip screws; trochanteric antegrade nails; proximal femoral nails (PFNs); and trochanteric fixation nails.11,12 Unstable trochanteric fractures treated with these IM fixation devices have had good results.12-14 Because of their central location and shorter lever arm, IM nails decrease the tensile strain on the implant and thereby reduce the risk of implant failure and provide more efficient load transfer while maintaining the advantage of controlled fracture impaction, as in DHS.15,16 According to some authors, IM nail insertion theoretically requires less operative time and less soft-tissue dissection, potentially resulting in decreased overall morbidity.15,16 PFN is one of the most effective fixation methods used to treat unstable trochanteric femur fractures.17 However, it is associated with various technical problems and failures, such as anterior femoral cortex penetration (caused by mismatch of nail curvature and intact femur), lag screw prominence in the lateral thigh, creation of a large hole in the greater trochanter (leading to abductors weakness), and potential for the Z-effect.18,19 Studies have compared PFN with the Less Invasive Stabilization System-Distal Femur (LISS-DF) in the treatment of proximal femur fracture, and the clinical results are encouraging.20,21 Recently, the proximal femoral locking compression plate (PFLCP) was introduced as a new implant that allows for angular-stable plating in the treatment of complex comminuted and osteoporotic intertrochanteric fractures.22,23
To our knowledge, our study is the first to compare functional outcomes and complications of unstable trochanteric fractures treated with PFN and those treated with PFLCP. We hypothesized that both PFN and PFLCP would provide good functional outcomes with acceptable and comparable complications in the treatment of unstable trochanteric fractures.
Materials and Methods
The protocol for this prospective comparative study was approved by the Institutional Review Board at Mayo Institute of Medical Sciences. Informed consent was provided by all patients. A power analysis with power of 90% to detect a Harris Hip Score (HHS) difference of 10 as being significant at the 5% level, and with a 10% to 15% dropout rate, determined that a sample size of 50 patients was needed. Each group (PFN, PFLCP) required at least 25 participants. From April 2009 to June 2011, 74 patients with unilateral closed unstable trochanteric fractures were admitted to our hospital. Of these patients, 48 met our inclusion criteria and were included in the study. A sealed envelope method was used to randomly assign 24 of these patients to PFN treatment and the other 24 to PFLCP treatment. One patient died of causes unrelated to an implant during the study, and 2 were lost to follow-up (telephone numbers changed). The remaining 45 patients (23 PFN, 22 PFLCP) reached 2-year follow-up.
Inclusion criteria were unilateral, closed unstable trochanteric fractures, and age over 18 years. Exclusion criteria were bilateral fractures, polytrauma, pathologic fractures, open fractures (American Society of Anesthesiologists [ASA] grade 4 or 5),24 and associated hip osteoarthritis (Kellgren-Lawrence grade 3 or 4).25 We collected data on demographics, operative time, incision length, intraoperative blood loss (measured by gravimetric method), hospital length of stay (LOS), and time to full weight-bearing. Mean (SD) age was 58.3 (9.3) years for the PFN group (range, 19-82 years) and 60.5 (8.1) years for the PFLCP group (range, 20-84 years). 
Before surgery, each patient’s standard plain radiographs (1 anteroposterior [AP], 1 lateral) were evaluated. Patients underwent surgery as soon as their general medical condition allowed. Surgery was performed through a lateral approach with the patient supine and in traction on a fracture table. PFN patients received 2 femoral neck screws (DePuy Synthes) (Figures A-D), and PFLCP patients received PFLCP (DePuy Synthes) in a fashion similar to that described in AO internal fixation manuals. 
Absolute values of differences were used for statistical analysis. For categorical outcome variables (eg, reoperation reason and type), Pearson χ2 test was used; for continuous variables (eg, pain, HHS), Student t test was used. Statistical significance was set at P = .05 (2-sided).
Results
Intraoperative blood loss (P = .02) and incision length (P = .008) were significantly less in the PFN group than in the PFLCP group. No significant difference was found between the groups in terms of operative time (P = .08), reduction quality (P = .82), radiologic exposure time (P = .18), LOS (P = .32), union rate (P = .42), and time to union (P = .68). 
Two PFN patients and 3 PFLCP patients developed a superficial infection (P = .36); all 5 infections were controlled with oral antibiotics. There was 1 nonunion in the PFN group but none in the PFLCP group (P = .28). The nonunion patient, who also had a broken implant without any history of fresh trauma, was treated with implant removal and bipolar hemiarthroplasty. 
There was no significant difference between the groups in terms of functional outcome (HHS) at final follow-up (P = .48). 
Discussion
The goal in managing proximal femoral fractures is to achieve near anatomical reduction with stable fracture fixation. Over the years, EM and IM devices have been used to treat trochanteric fractures; each has its merits and demerits.29,30 However, unstable trochanteric fractures treated with EM devices (eg, DHS, dynamic condylar screw) have high complication rates (6%-18%).8,31 Excessive sliding of the lag screw within the plate barrel may result in limb shortening and distal fragment medialization. EM devices cannot adequately prevent secondary limb shortening after weight-bearing, owing to medialization of the distal fragment.32,33 Varus collapse and implant failure (eg, cut-out of the femoral head screw) are also common.29 These complications led to the development of IM hip screw devices, such as PFN, which has several potential advantages, including a shorter lever arm (decreases tensile strain on implant) and efficient load transfer capacity. PFN has been found to have increased fracture stability, with no difference in operative time or intraoperative complication rates, but some studies have reported implant failure and other complications (3%-17%) in PFN-treated unstable trochanteric fractures.29,34,35
We conducted the present study to compare PFN and PFLCP, new treatment options for unstable and highly comminuted trochanteric fractures. The characteristics of the patients in this study are very different from those in most hip fracture studies. Our PFN and PFLCP groups’ mean ages were lower relative to other studies.14,15,36 In addition, time from injury to surgery was longer for both our groups than for groups in other studies, though some studies36 have reported comparable times. Moreover, our groups showed no statistically significant differences in operative time, radiologic exposure time, LOS, union rate, or time to union. Our PFN patients had significantly shorter incisions and less time to full weight-bearing.
Wang and colleagues37 compared the clinical outcomes of DHS, IM fixation (IMF), and PFLCP in the treatment of trochanteric fractures in elderly patients. Incision length and operative time were shorter for the IMF group than for DHS and PFLCP, but there were no significant differences between DHS and PFLCP. Intraoperative blood loss, rehabilitation, and time to healing were less for the IMF and PFLCP groups than for DHS, but there were no significant differences between IMF and PFLCP. Functional recovery was better for the IMF and PFLCP groups than for DHS, and there were significant differences among the 3 groups. There were fewer complications in the PFLCP group than in IMF and DHS.
Yao and colleagues38 compared reverse LISS and PFN treatment of intertrochanteric fractures and reported no significant differences in operative time, intraoperative blood loss, or functional outcome. Regarding complications, the PFN group had none, and the LISS group had 3 (1 nonunion with locking screw breakage, 2 varus unions).
Haq and colleagues39 compared PFN and contralateral reverse distal femoral locking compression plate (reverse DFLCP) in the management of unstable intertrochanteric fractures with compromised lateral wall and reported better intraoperative variables, better functional outcomes, and lower failure rates in the PFN group than in the reverse DFLCP group.
Zha and colleagues22 followed up 110 patients with intertrochanteric and subtrochanteric fractures treated with PFLCP fixation and reported a 100% union rate at 1-year follow-up. Mean operative time was 35.5minutes, and mean bleeding amount was 150mL, which included operative blood loss and wound drainage. Mean radiologic exposure time was 5minutes, and mean incision length was 9cm. There was 1 case of implant breakage.
Strohm and colleagues40 reported good results in children with trochanteric fractures treated with conventional locking compression plate.
Brett and colleagues41 compared blade plate and PFLCP with and without a kickstand screw in a composite femur subtrochanteric fracture gap model. In their biomechanical study, the PFLCP with a kickstand screw provided higher axial but less torsional stiffness than the blade plate. The authors concluded that, though the devices are biomechanically equivalent, PFLCP may allow percutaneous insertion that avoids the potential morbidity associated with the blade plate’s extensile approach.
Our PFN group’s mean (SD) time to healing was 4.2 (1.3) months. In other studies, mean healing time for IMF-treated unstable trochanteric fractures was 3 to 4 months. Some authors have reported even longer healing times, up to 17 months,42 for PFN-treated trochanteric fractures. Many of the studies indicated that gradual weight-bearing was allowed around 6 weeks, when callus formation was adequate.43 Our treatment protocol differed in that its protected weight-bearing period was prolonged, and controlled weight-bearing was delayed until around 6 weeks, when callus formation was adequate.
The better PFLCP outcomes in our study, relative to most other studies, can be attributed to the relatively younger age of our PFN and PFLCP groups. In a study of 19 patients with trochanteric fractures treated with open reduction and internal fixation using PFLCP, Wirtz and colleagues44 reported 4 cases of secondary varus collapse, 2 cut-outs of the proximal fragment, and 1 implant failure caused by a broken proximal screw. Eight patients experienced persistent trochanteric pain, and 3 underwent hardware removal.
Streubel and colleagues45 retrospectively analyzed 29 patients with 30 OTA 31.A3 fractures treated with PFLCP and reported 11 failures (37%) at 20-month follow-up. The most frequent failure mode (5 cases) was varus collapse with screw cut-out. Presence of a kickstand screw and medial cortical reduction were not significantly different between cases that failed and those that did not.
Glassner and Tejwani46 retrospectively studied 10 patients with trochanteric fractures treated with open reduction and internal fixation with PFLCP. Failure modes were implant fracture (4 cases) and fixation loss (3 cases) resulting from varus collapse and implant cutout.
One of our PFN patients had a lower neck screw back out by 9-month follow-up. As the fracture had consolidated well, the patient underwent screw removal. Another PFN patient had a broken implant and fracture nonunion at 1-year follow-up. Various complications have been reported in the literature,13,14,47,48 but none occurred in our study. There were no implant-related complications in our PFLCP group, possibly because of the mechanical advantage of 3-dimensional and angular-stable fixation with PFLCP in unstable trochanteric fractures.
Gadegone and Salphale49 analyzed 100 cases of PFN-treated trochanteric fractures and reported femoral head cut-through (4.8%), intraoperative femoral shaft fracture (0.8%), implant breakage (0.8%), wound-healing impairment (9.7%), and false placement of osteosynthesis materials (0.8%). The 19% reoperation rate in their study mainly involved cephalic screw removal for lateral protrusion at the proximal thigh. Our PFN reoperation rate was 8.7%; none of our PFLCP patients required revision surgery.
Tyllianakis and colleagues50 analyzed 45 cases of PFN-treated unstable trochanteric fractures and concluded technical or mechanical complications were related more to fracture type, surgical technique, and time to weight-bearing than to the implant itself. Our postoperative wound complication rate was similar to that of other studies.14,47,51 Regarding functional outcomes, our groups’ HHSs were good and comparable at final follow-up, as were their PPM scores.
This study was limited in that it was a small prospective comparative single-center study with a small number of patients. Larger randomized controlled multicenter studies are needed to evaluate and compare both implants in displaced unstable trochanteric femur fractures.
This study found that both PFN and PFLCP were effective treatments for unstable trochanteric femur fractures. PFN is superior to PFLCP only in terms of shorter incisions and shorter time to full weight-bearing. Both devices can be used in unstable trochanteric fractures, and both have good functional outcomes and acceptable complication rates.
Am J Orthop. 2017;46(2):E116-E123. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.
1. Cummings SR, Rubin SM, Black D. The future of hip fractures in the United States. Numbers, costs, and potential effects of postmenopausal estrogen. Clin Orthop Relat Res. 1990;(252):163-166.
2. Kyle RF, Cabanela ME, Russell TA, et al. Fractures of the proximal part of the femur. Instr Course Lect. 1995;44:227-253.
3. Koval KJ, Aharonoff GB, Rokito AS, Lyon T, Zuckerman JD. Patients with femoral neck and intertrochanteric fractures. Are they the same? Clin Orthop Relat Res. 1996;(330):166-172.
4. Marsh JL, Slongo TF, Agel J, et al. Fracture and dislocation classification compendium - 2007: Orthopaedic Trauma Association classification, database and outcomes committee. J Orthop Trauma. 2007;21(10 suppl):S1-S133.
5. Lindskog D, Baumgaertner MR. Unstable intertrochanteric hip fractures in the elderly. J Am Acad Orthop Surg. 2004;12(3):179-190.
6. Kokoroghiannis C, Aktselis I, Deligeorgis A, Fragkomichalos E, Papadimas D, Pappadas I. Evolving concepts of stability and intramedullary fixation of intertrochanteric fractures—a review. Injury. 2012;43(6):686-693.
7. Larsson S, Friberg S, Hansson LI. Trochanteric fractures. Influence of reduction and implant position on impaction and complications. Clin Orthop Relat Res. 1990;(259):130-139.
8. Simpson AH, Varty K, Dodd CA. Sliding hip screws: modes of failure. Injury. 1989;20(4):227-231.
9. Rha JD, Kim YH, Yoon SI, Park TS, Lee MH. Factors affecting sliding of the lag screw in intertrochanteric fractures. Int Orthop. 1993;17(5):320-324.
10. Baixauli F, Vicent V, Baixauli E, et al. A reinforced rigid fixation device for unstable intertrochanteric fractures. Clin Orthop Relat Res. 1999;(361):205-215.
11. Harrington P, Nihal A, Singhania AK, Howell FR. Intramedullary hip screw versus sliding hip screw for unstable intertrochanteric femoral fractures in the elderly. Injury. 2002;33(1):23-28.
12. Parker MJ, Handoll HH. Gamma and other cephalocondylic intramedullary nails versus extramedullary implants for extracapsular hip fractures in adults. Cochrane Database Syst Rev. 2010;(9):CD000093.
13. Pajarinen J, Lindahl J, Michelsson O, Savolainen V, Hirvensalo E. Pertrochanteric femoral fractures treated with a dynamic hip screw or a proximal femoral nail. A randomised study comparing postoperative rehabilitation. J Bone Joint Surg Br. 2005;87(1):76-81.
14. Papasimos S, Koutsojannis CM, Panagopoulos A, Megas P, Lambiris E. A randomised comparison of AMBI, TGN and PFN for treatment of unstable trochanteric fractures. Arch Orthop Trauma Surg. 2005;125(7):462-468.
15. Saudan M, Lübbeke A, Sadowski C, Riand N, Stern R, Hoffmeyer P. Pertrochanteric fractures: is there an advantage to an intramedullary nail? A randomized, prospective study of 206 patients comparing the dynamic hip screw and proximal femoral nail. J Orthop Trauma. 2002;16(6):386-393.
16. Schipper IB, Steyerberg EW, Castelein RM, et al. Treatment of unstable trochanteric fractures. Randomised comparison of the gamma nail and the proximal femoral nail. J Bone Joint Surg Br. 2004;86(1):86-94.
17. Gardenbroek TJ, Segers MJ, Simmermacher RK, Hammacher ER. The proximal femur nail antirotation: an identifiable improvement in the treatment of unstable pertrochanteric fractures? J Trauma. 2011;71(1):169-174.
18. Egol KA, Chang EY, Cvitkovic J, Kummer FJ, Koval KJ. Mismatch of current intramedullary nails with the anterior bow of the femur. J Orthop Trauma. 2004;18(7):410-415.
19. Werner-Tutschku W, Lajtai G, Schmiedhuber G, Lang T, Pirkl C, Orthner E. Intra- and perioperative complications in the stabilization of per- and subtrochanteric femoral fractures by means of PFN [in German]. Unfallchirurg. 2002;105(10):881-885.
20. Ma CH, Tu YK, Yu SW, Yen CY, Yeh JH, Wu CH. Reverse LISS plates for unstable proximal femoral fractures. Injury. 2010;41(8):827-833.
21. Pryce Lewis JR, Ashcroft GP. Reverse LISS plating for proximal segmental femoral fractures in the polytrauma patient: a case report. Injury. 2007;38(2):235-239.
22. Zha GC, Chen ZL, Qi XB, Sun JY. Treatment of pertrochanteric fractures with a proximal femur locking compression plate. Injury. 2011;42(11):1294-1299.
23. Oh CW, Kim JJ, Byun YS, et al. Minimally invasive plate osteosynthesis of subtrochanteric femur fractures with a locking plate: a prospective series of 20 fractures. Arch Orthop Trauma Surg. 2009;129(12):1659-1665.
24. American Society of Anesthesiologists new classification of physical status. Anesthesiology. 1963;24:111-114.
25. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16(4):494-502.
26. Vidyadhara S, Rao SK. One and two femoral neck screws with intramedullary nails for unstable trochanteric fractures of femur in the elderly—randomised clinical trial. Injury. 2007;38(7):806-814.
27. Parker MJ, Palmer CR. A new mobility score for predicting mortality after hip fracture. J Bone Joint Surg Br. 1993;75(5):797-798.
28. Harris WH. Traumatic arthritis of the hip after dislocation and acetabular fractures: treatment by mold arthroplasty. An end-result study using a new method of result evaluation. J Bone Joint Surg Am. 1969;51(4):737-755.
29. Sadowski C, Lübbeke A, Saudan M, Riand N, Stern R, Hoffmeyer P. Treatment of reverse oblique and transverse intertrochanteric fractures with use of an intramedullary nail or a 95 degrees screw-plate: a prospective, randomized study. J Bone Joint Surg Am. 2002;84(3):372-381.
30. Suckel AA, Dietz K, Wuelker N, Helwig P. Evaluation of complications of three different types of proximal extra-articular femur fractures: differences in complications, age, sex and surviving rates. Int Orthop. 2007;31(5):689-695.
31. Nuber S, Schönweiss T, Rüter A. Stabilisation of unstable trochanteric femoral fractures. Dynamic hip screw (DHS) with trochanteric stabilisation plate vs. proximal femur nail (PFN) [in German]. Unfallchirurg. 2003;106(1):39-47.
32. Klinger HM, Baums MH, Eckert M, Neugebauer R. A comparative study of unstable per- and intertrochanteric femoral fractures treated with dynamic hip screw (DHS) and trochanteric butt-press plate vs. proximal femoral nail (PFN) [in German]. Zentralbl Chir. 2005;130(4):301-306.
33. Bridle SH, Patel AD, Bircher M, Calvert PT. Fixation of intertrochanteric fractures of the femur. A randomised prospective comparison of the gamma nail and the dynamic hip screw. J Bone Joint Surg Br. 1991;73(2):330-334.
34. Utrilla AL, Reig JS, Muñoz FM, Tufanisco CB. Trochanteric gamma nail and compression hip screw for trochanteric fractures: a randomized, prospective, comparative study in 210 elderly patients with a new design of the gamma nail. J Orthop Trauma. 2005;19(4):229-233.
35. Lenich A, Mayr E, Rüter A, Möckl CH, Füchtmeier B. First results with the trochanter fixation nail (TFN): a report on 120 cases. Arch Orthop Trauma Surg. 2006;126(10):706-712.
36. Tao R, Lu Y, Xu H, Zhou ZY, Wang YH, Liu F. Internal fixation of intertrochanteric hip fractures: a clinical comparison of two implant designs. ScientificWorldJournal. 2013;2013:834825.
37. Wang Y, Yang YY, Yu ZH, Li CQ, Wu YS, Zheng XX. Comparative study of intertrochanteric fractures treated with proximal femur locking compress plate in aged [in Chinese]. Zhongguo Gu Shang. 2011;24(5):370-373.
38. Yao C, Zhang CQ, Jin DX, Chen YF. Early results of reverse less invasive stabilization system plating in treating elderly intertrochanteric fractures: a prospective study compared to proximal femoral nail. Chin Med J (Engl). 2011;124(14):2150-2157.
39. Haq RU, Manhas V, Pankaj A, Srivastava A, Dhammi IK, Jain AK. Proximal femoral nails compared with reverse distal femoral locking plates in intertrochanteric fractures with a compromised lateral wall; a randomised controlled trial. Int Orthop. 2014;38(7):1443-1449.
40. Strohm PC, Schmal H, Kuminack K, Reising K, Südkamp NP. Intertrochanteric femoral fractures in children [in German]. Unfallchirurg. 2006;109(5):425-430.
41. Brett CD, Lee MA, Khalafi AK, Hazelwood SJ. A comparison of percutaneous versus traditional open plate fixation in a subtrochanteric fracture gap model. In: Proceedings of the Annual Meeting of the Orthopaedic Trauma Association (OTA); October 5-7, 2006; Phoenix, AZ. Basic science poster 71 (abstract).
42. Park SY, Yang KH, Yoo JH, Yoon HK, Park HW. The treatment of reverse obliquity intertrochanteric fractures with the intramedullary hip nail. J Trauma. 2008;65(4):852-857.
43. Habernek H, Wallner T, Aschauer E, Schmid L. Comparison of Ender nails, dynamic hip screws, and gamma nails in the treatment of peritrochanteric femoral fractures. Orthopedics. 2000;23(2):121-127.
44. Wirtz C, Abbassi F, Evangelopoulos DS, Kohl S, Siebenrock KA, Krüger A. High failure rate of trochanteric fracture osteosynthesis with proximal femoral locking compression plate. Injury. 2013;44(6):751-756.
45. Streubel PN, Moustoukas MJ, Obremskey WT. Mechanical failure after locking plate fixation of unstable intertrochanteric femur fractures. J Orthop Trauma. 2013;27(1):22-28.
46. Glassner PJ, Tejwani NC. Failure of proximal femoral locking compression plate: a case series. J Orthop Trauma. 2011;25(2):76-83.
47. Ekström W, Karlsson-Thur C, Larsson S, Ragnarsson B, Alberts KA. Functional outcome in treatment of unstable trochanteric and subtrochanteric fractures with the proximal femoral nail and the Medoff sliding plate. J Orthop Trauma. 2007;21(1):18-25.
48. Boldin C, Seibert FJ, Fankhauser F, Peicha G, Grechenig W, Szyszkowitz R. The proximal femoral nail (PFN)—a minimal invasive treatment of unstable proximal femoral fractures: a prospective study of 55 patients with a follow-up of 15 months. Acta Orthop Scand. 2003;74(1):53-58.
49. Gadegone WM, Salphale YS. Proximal femoral nail—an analysis of 100 cases of proximal femoral fractures with an average follow up of 1 year. Int Orthop. 2007;31(3):403-408.
50. Tyllianakis M, Panagopoulos A, Papadopoulos A, Papasimos S, Mousafiris K. Treatment of extracapsular hip fractures with the proximal femoral nail (PFN): long term results in 45 patients. Acta Orthop Belg. 2004;70(5):444-454.
51. Morihara T, Arai Y, Tokugawa S, Fujita S, Chatani K, Kubo T. Proximal femoral nail for treatment of trochanteric femoral fractures. J Orthop Surg (Hong Kong). 2007;15(3):273-277.
Take-Home Points
- Both PFN and PFLCP are effective treatments for unstable trochanteric femur fractures.
- PFN is superior to PFLCP only in terms of shorter incisions and shorter time to full weight-bearing.
- Both devices have good long-term functional outcomes.
- Complication rates in unstable trochanteric fractures treated with both implants are comparable.
- Larger randomized controlled multicenter studies are needed to further evaluate and compare both implants in displaced unstable trochanteric femur fractures.
Trochanteric fractures are among the most widely treated orthopedic injuries, occurring mainly as low-energy injuries in elderly patients and high-energy injuries in younger patients.1,2 About half of these injuries are unstable.3 According to the AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) system, trochanteric fractures can be classified stable (AO/OTA 31.A1-1 to 31.A2-1) or unstable (AO/OTA 31.A2-2 to 31.A3.3).4,5 For surgical fixation of trochanteric femur fractures, various internal fixation devices have been used, either extramedullary (EM) or intramedullary (IM).6 The dynamic hip screw (DHS) is the implant of choice in the treatment of stable trochanteric femur fractures (AO/OTA 31-A1), as it provides secure fixation and controlled impaction.7 Mechanical and technical failures continue to occur in up to 6% to 18% of cases of unstable trochanteric fractures treated with DHS.8 Excessive sliding of the lag screw within the plate barrel results in limb shortening and distal fragment medialization, which are the main causes of these failures.9,10 Dissatisfaction with DHS use in unstable fractures led to the use of IM nails. The various IM devices available are condylocephalic (Ender) nails and cephalomedullary nails, such as gamma nails; IM hip screws; trochanteric antegrade nails; proximal femoral nails (PFNs); and trochanteric fixation nails.11,12 Unstable trochanteric fractures treated with these IM fixation devices have had good results.12-14 Because of their central location and shorter lever arm, IM nails decrease the tensile strain on the implant and thereby reduce the risk of implant failure and provide more efficient load transfer while maintaining the advantage of controlled fracture impaction, as in DHS.15,16 According to some authors, IM nail insertion theoretically requires less operative time and less soft-tissue dissection, potentially resulting in decreased overall morbidity.15,16 PFN is one of the most effective fixation methods used to treat unstable trochanteric femur fractures.17 However, it is associated with various technical problems and failures, such as anterior femoral cortex penetration (caused by mismatch of nail curvature and intact femur), lag screw prominence in the lateral thigh, creation of a large hole in the greater trochanter (leading to abductors weakness), and potential for the Z-effect.18,19 Studies have compared PFN with the Less Invasive Stabilization System-Distal Femur (LISS-DF) in the treatment of proximal femur fracture, and the clinical results are encouraging.20,21 Recently, the proximal femoral locking compression plate (PFLCP) was introduced as a new implant that allows for angular-stable plating in the treatment of complex comminuted and osteoporotic intertrochanteric fractures.22,23
To our knowledge, our study is the first to compare functional outcomes and complications of unstable trochanteric fractures treated with PFN and those treated with PFLCP. We hypothesized that both PFN and PFLCP would provide good functional outcomes with acceptable and comparable complications in the treatment of unstable trochanteric fractures.
Materials and Methods
The protocol for this prospective comparative study was approved by the Institutional Review Board at Mayo Institute of Medical Sciences. Informed consent was provided by all patients. A power analysis with power of 90% to detect a Harris Hip Score (HHS) difference of 10 as being significant at the 5% level, and with a 10% to 15% dropout rate, determined that a sample size of 50 patients was needed. Each group (PFN, PFLCP) required at least 25 participants. From April 2009 to June 2011, 74 patients with unilateral closed unstable trochanteric fractures were admitted to our hospital. Of these patients, 48 met our inclusion criteria and were included in the study. A sealed envelope method was used to randomly assign 24 of these patients to PFN treatment and the other 24 to PFLCP treatment. One patient died of causes unrelated to an implant during the study, and 2 were lost to follow-up (telephone numbers changed). The remaining 45 patients (23 PFN, 22 PFLCP) reached 2-year follow-up.
Inclusion criteria were unilateral, closed unstable trochanteric fractures, and age over 18 years. Exclusion criteria were bilateral fractures, polytrauma, pathologic fractures, open fractures (American Society of Anesthesiologists [ASA] grade 4 or 5),24 and associated hip osteoarthritis (Kellgren-Lawrence grade 3 or 4).25 We collected data on demographics, operative time, incision length, intraoperative blood loss (measured by gravimetric method), hospital length of stay (LOS), and time to full weight-bearing. Mean (SD) age was 58.3 (9.3) years for the PFN group (range, 19-82 years) and 60.5 (8.1) years for the PFLCP group (range, 20-84 years).
Before surgery, each patient’s standard plain radiographs (1 anteroposterior [AP], 1 lateral) were evaluated. Patients underwent surgery as soon as their general medical condition allowed. Surgery was performed through a lateral approach with the patient supine and in traction on a fracture table. PFN patients received 2 femoral neck screws (DePuy Synthes) (Figures A-D), and PFLCP patients received PFLCP (DePuy Synthes) in a fashion similar to that described in AO internal fixation manuals.
Absolute values of differences were used for statistical analysis. For categorical outcome variables (eg, reoperation reason and type), Pearson χ2 test was used; for continuous variables (eg, pain, HHS), Student t test was used. Statistical significance was set at P = .05 (2-sided).
Results
Intraoperative blood loss (P = .02) and incision length (P = .008) were significantly less in the PFN group than in the PFLCP group. No significant difference was found between the groups in terms of operative time (P = .08), reduction quality (P = .82), radiologic exposure time (P = .18), LOS (P = .32), union rate (P = .42), and time to union (P = .68).
Two PFN patients and 3 PFLCP patients developed a superficial infection (P = .36); all 5 infections were controlled with oral antibiotics. There was 1 nonunion in the PFN group but none in the PFLCP group (P = .28). The nonunion patient, who also had a broken implant without any history of fresh trauma, was treated with implant removal and bipolar hemiarthroplasty.
There was no significant difference between the groups in terms of functional outcome (HHS) at final follow-up (P = .48).
Discussion
The goal in managing proximal femoral fractures is to achieve near anatomical reduction with stable fracture fixation. Over the years, EM and IM devices have been used to treat trochanteric fractures; each has its merits and demerits.29,30 However, unstable trochanteric fractures treated with EM devices (eg, DHS, dynamic condylar screw) have high complication rates (6%-18%).8,31 Excessive sliding of the lag screw within the plate barrel may result in limb shortening and distal fragment medialization. EM devices cannot adequately prevent secondary limb shortening after weight-bearing, owing to medialization of the distal fragment.32,33 Varus collapse and implant failure (eg, cut-out of the femoral head screw) are also common.29 These complications led to the development of IM hip screw devices, such as PFN, which has several potential advantages, including a shorter lever arm (decreases tensile strain on implant) and efficient load transfer capacity. PFN has been found to have increased fracture stability, with no difference in operative time or intraoperative complication rates, but some studies have reported implant failure and other complications (3%-17%) in PFN-treated unstable trochanteric fractures.29,34,35
We conducted the present study to compare PFN and PFLCP, new treatment options for unstable and highly comminuted trochanteric fractures. The characteristics of the patients in this study are very different from those in most hip fracture studies. Our PFN and PFLCP groups’ mean ages were lower relative to other studies.14,15,36 In addition, time from injury to surgery was longer for both our groups than for groups in other studies, though some studies36 have reported comparable times. Moreover, our groups showed no statistically significant differences in operative time, radiologic exposure time, LOS, union rate, or time to union. Our PFN patients had significantly shorter incisions and less time to full weight-bearing.
Wang and colleagues37 compared the clinical outcomes of DHS, IM fixation (IMF), and PFLCP in the treatment of trochanteric fractures in elderly patients. Incision length and operative time were shorter for the IMF group than for DHS and PFLCP, but there were no significant differences between DHS and PFLCP. Intraoperative blood loss, rehabilitation, and time to healing were less for the IMF and PFLCP groups than for DHS, but there were no significant differences between IMF and PFLCP. Functional recovery was better for the IMF and PFLCP groups than for DHS, and there were significant differences among the 3 groups. There were fewer complications in the PFLCP group than in IMF and DHS.
Yao and colleagues38 compared reverse LISS and PFN treatment of intertrochanteric fractures and reported no significant differences in operative time, intraoperative blood loss, or functional outcome. Regarding complications, the PFN group had none, and the LISS group had 3 (1 nonunion with locking screw breakage, 2 varus unions).
Haq and colleagues39 compared PFN and contralateral reverse distal femoral locking compression plate (reverse DFLCP) in the management of unstable intertrochanteric fractures with compromised lateral wall and reported better intraoperative variables, better functional outcomes, and lower failure rates in the PFN group than in the reverse DFLCP group.
Zha and colleagues22 followed up 110 patients with intertrochanteric and subtrochanteric fractures treated with PFLCP fixation and reported a 100% union rate at 1-year follow-up. Mean operative time was 35.5minutes, and mean bleeding amount was 150mL, which included operative blood loss and wound drainage. Mean radiologic exposure time was 5minutes, and mean incision length was 9cm. There was 1 case of implant breakage.
Strohm and colleagues40 reported good results in children with trochanteric fractures treated with conventional locking compression plate.
Brett and colleagues41 compared blade plate and PFLCP with and without a kickstand screw in a composite femur subtrochanteric fracture gap model. In their biomechanical study, the PFLCP with a kickstand screw provided higher axial but less torsional stiffness than the blade plate. The authors concluded that, though the devices are biomechanically equivalent, PFLCP may allow percutaneous insertion that avoids the potential morbidity associated with the blade plate’s extensile approach.
Our PFN group’s mean (SD) time to healing was 4.2 (1.3) months. In other studies, mean healing time for IMF-treated unstable trochanteric fractures was 3 to 4 months. Some authors have reported even longer healing times, up to 17 months,42 for PFN-treated trochanteric fractures. Many of the studies indicated that gradual weight-bearing was allowed around 6 weeks, when callus formation was adequate.43 Our treatment protocol differed in that its protected weight-bearing period was prolonged, and controlled weight-bearing was delayed until around 6 weeks, when callus formation was adequate.
The better PFLCP outcomes in our study, relative to most other studies, can be attributed to the relatively younger age of our PFN and PFLCP groups. In a study of 19 patients with trochanteric fractures treated with open reduction and internal fixation using PFLCP, Wirtz and colleagues44 reported 4 cases of secondary varus collapse, 2 cut-outs of the proximal fragment, and 1 implant failure caused by a broken proximal screw. Eight patients experienced persistent trochanteric pain, and 3 underwent hardware removal.
Streubel and colleagues45 retrospectively analyzed 29 patients with 30 OTA 31.A3 fractures treated with PFLCP and reported 11 failures (37%) at 20-month follow-up. The most frequent failure mode (5 cases) was varus collapse with screw cut-out. Presence of a kickstand screw and medial cortical reduction were not significantly different between cases that failed and those that did not.
Glassner and Tejwani46 retrospectively studied 10 patients with trochanteric fractures treated with open reduction and internal fixation with PFLCP. Failure modes were implant fracture (4 cases) and fixation loss (3 cases) resulting from varus collapse and implant cutout.
One of our PFN patients had a lower neck screw back out by 9-month follow-up. As the fracture had consolidated well, the patient underwent screw removal. Another PFN patient had a broken implant and fracture nonunion at 1-year follow-up. Various complications have been reported in the literature,13,14,47,48 but none occurred in our study. There were no implant-related complications in our PFLCP group, possibly because of the mechanical advantage of 3-dimensional and angular-stable fixation with PFLCP in unstable trochanteric fractures.
Gadegone and Salphale49 analyzed 100 cases of PFN-treated trochanteric fractures and reported femoral head cut-through (4.8%), intraoperative femoral shaft fracture (0.8%), implant breakage (0.8%), wound-healing impairment (9.7%), and false placement of osteosynthesis materials (0.8%). The 19% reoperation rate in their study mainly involved cephalic screw removal for lateral protrusion at the proximal thigh. Our PFN reoperation rate was 8.7%; none of our PFLCP patients required revision surgery.
Tyllianakis and colleagues50 analyzed 45 cases of PFN-treated unstable trochanteric fractures and concluded technical or mechanical complications were related more to fracture type, surgical technique, and time to weight-bearing than to the implant itself. Our postoperative wound complication rate was similar to that of other studies.14,47,51 Regarding functional outcomes, our groups’ HHSs were good and comparable at final follow-up, as were their PPM scores.
This study was limited in that it was a small prospective comparative single-center study with a small number of patients. Larger randomized controlled multicenter studies are needed to evaluate and compare both implants in displaced unstable trochanteric femur fractures.
This study found that both PFN and PFLCP were effective treatments for unstable trochanteric femur fractures. PFN is superior to PFLCP only in terms of shorter incisions and shorter time to full weight-bearing. Both devices can be used in unstable trochanteric fractures, and both have good functional outcomes and acceptable complication rates.
Am J Orthop. 2017;46(2):E116-E123. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.
Take-Home Points
- Both PFN and PFLCP are effective treatments for unstable trochanteric femur fractures.
- PFN is superior to PFLCP only in terms of shorter incisions and shorter time to full weight-bearing.
- Both devices have good long-term functional outcomes.
- Complication rates in unstable trochanteric fractures treated with both implants are comparable.
- Larger randomized controlled multicenter studies are needed to further evaluate and compare both implants in displaced unstable trochanteric femur fractures.
Trochanteric fractures are among the most widely treated orthopedic injuries, occurring mainly as low-energy injuries in elderly patients and high-energy injuries in younger patients.1,2 About half of these injuries are unstable.3 According to the AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association) system, trochanteric fractures can be classified stable (AO/OTA 31.A1-1 to 31.A2-1) or unstable (AO/OTA 31.A2-2 to 31.A3.3).4,5 For surgical fixation of trochanteric femur fractures, various internal fixation devices have been used, either extramedullary (EM) or intramedullary (IM).6 The dynamic hip screw (DHS) is the implant of choice in the treatment of stable trochanteric femur fractures (AO/OTA 31-A1), as it provides secure fixation and controlled impaction.7 Mechanical and technical failures continue to occur in up to 6% to 18% of cases of unstable trochanteric fractures treated with DHS.8 Excessive sliding of the lag screw within the plate barrel results in limb shortening and distal fragment medialization, which are the main causes of these failures.9,10 Dissatisfaction with DHS use in unstable fractures led to the use of IM nails. The various IM devices available are condylocephalic (Ender) nails and cephalomedullary nails, such as gamma nails; IM hip screws; trochanteric antegrade nails; proximal femoral nails (PFNs); and trochanteric fixation nails.11,12 Unstable trochanteric fractures treated with these IM fixation devices have had good results.12-14 Because of their central location and shorter lever arm, IM nails decrease the tensile strain on the implant and thereby reduce the risk of implant failure and provide more efficient load transfer while maintaining the advantage of controlled fracture impaction, as in DHS.15,16 According to some authors, IM nail insertion theoretically requires less operative time and less soft-tissue dissection, potentially resulting in decreased overall morbidity.15,16 PFN is one of the most effective fixation methods used to treat unstable trochanteric femur fractures.17 However, it is associated with various technical problems and failures, such as anterior femoral cortex penetration (caused by mismatch of nail curvature and intact femur), lag screw prominence in the lateral thigh, creation of a large hole in the greater trochanter (leading to abductors weakness), and potential for the Z-effect.18,19 Studies have compared PFN with the Less Invasive Stabilization System-Distal Femur (LISS-DF) in the treatment of proximal femur fracture, and the clinical results are encouraging.20,21 Recently, the proximal femoral locking compression plate (PFLCP) was introduced as a new implant that allows for angular-stable plating in the treatment of complex comminuted and osteoporotic intertrochanteric fractures.22,23
To our knowledge, our study is the first to compare functional outcomes and complications of unstable trochanteric fractures treated with PFN and those treated with PFLCP. We hypothesized that both PFN and PFLCP would provide good functional outcomes with acceptable and comparable complications in the treatment of unstable trochanteric fractures.
Materials and Methods
The protocol for this prospective comparative study was approved by the Institutional Review Board at Mayo Institute of Medical Sciences. Informed consent was provided by all patients. A power analysis with power of 90% to detect a Harris Hip Score (HHS) difference of 10 as being significant at the 5% level, and with a 10% to 15% dropout rate, determined that a sample size of 50 patients was needed. Each group (PFN, PFLCP) required at least 25 participants. From April 2009 to June 2011, 74 patients with unilateral closed unstable trochanteric fractures were admitted to our hospital. Of these patients, 48 met our inclusion criteria and were included in the study. A sealed envelope method was used to randomly assign 24 of these patients to PFN treatment and the other 24 to PFLCP treatment. One patient died of causes unrelated to an implant during the study, and 2 were lost to follow-up (telephone numbers changed). The remaining 45 patients (23 PFN, 22 PFLCP) reached 2-year follow-up.
Inclusion criteria were unilateral, closed unstable trochanteric fractures, and age over 18 years. Exclusion criteria were bilateral fractures, polytrauma, pathologic fractures, open fractures (American Society of Anesthesiologists [ASA] grade 4 or 5),24 and associated hip osteoarthritis (Kellgren-Lawrence grade 3 or 4).25 We collected data on demographics, operative time, incision length, intraoperative blood loss (measured by gravimetric method), hospital length of stay (LOS), and time to full weight-bearing. Mean (SD) age was 58.3 (9.3) years for the PFN group (range, 19-82 years) and 60.5 (8.1) years for the PFLCP group (range, 20-84 years).
Before surgery, each patient’s standard plain radiographs (1 anteroposterior [AP], 1 lateral) were evaluated. Patients underwent surgery as soon as their general medical condition allowed. Surgery was performed through a lateral approach with the patient supine and in traction on a fracture table. PFN patients received 2 femoral neck screws (DePuy Synthes) (Figures A-D), and PFLCP patients received PFLCP (DePuy Synthes) in a fashion similar to that described in AO internal fixation manuals.
Absolute values of differences were used for statistical analysis. For categorical outcome variables (eg, reoperation reason and type), Pearson χ2 test was used; for continuous variables (eg, pain, HHS), Student t test was used. Statistical significance was set at P = .05 (2-sided).
Results
Intraoperative blood loss (P = .02) and incision length (P = .008) were significantly less in the PFN group than in the PFLCP group. No significant difference was found between the groups in terms of operative time (P = .08), reduction quality (P = .82), radiologic exposure time (P = .18), LOS (P = .32), union rate (P = .42), and time to union (P = .68).
Two PFN patients and 3 PFLCP patients developed a superficial infection (P = .36); all 5 infections were controlled with oral antibiotics. There was 1 nonunion in the PFN group but none in the PFLCP group (P = .28). The nonunion patient, who also had a broken implant without any history of fresh trauma, was treated with implant removal and bipolar hemiarthroplasty.
There was no significant difference between the groups in terms of functional outcome (HHS) at final follow-up (P = .48).
Discussion
The goal in managing proximal femoral fractures is to achieve near anatomical reduction with stable fracture fixation. Over the years, EM and IM devices have been used to treat trochanteric fractures; each has its merits and demerits.29,30 However, unstable trochanteric fractures treated with EM devices (eg, DHS, dynamic condylar screw) have high complication rates (6%-18%).8,31 Excessive sliding of the lag screw within the plate barrel may result in limb shortening and distal fragment medialization. EM devices cannot adequately prevent secondary limb shortening after weight-bearing, owing to medialization of the distal fragment.32,33 Varus collapse and implant failure (eg, cut-out of the femoral head screw) are also common.29 These complications led to the development of IM hip screw devices, such as PFN, which has several potential advantages, including a shorter lever arm (decreases tensile strain on implant) and efficient load transfer capacity. PFN has been found to have increased fracture stability, with no difference in operative time or intraoperative complication rates, but some studies have reported implant failure and other complications (3%-17%) in PFN-treated unstable trochanteric fractures.29,34,35
We conducted the present study to compare PFN and PFLCP, new treatment options for unstable and highly comminuted trochanteric fractures. The characteristics of the patients in this study are very different from those in most hip fracture studies. Our PFN and PFLCP groups’ mean ages were lower relative to other studies.14,15,36 In addition, time from injury to surgery was longer for both our groups than for groups in other studies, though some studies36 have reported comparable times. Moreover, our groups showed no statistically significant differences in operative time, radiologic exposure time, LOS, union rate, or time to union. Our PFN patients had significantly shorter incisions and less time to full weight-bearing.
Wang and colleagues37 compared the clinical outcomes of DHS, IM fixation (IMF), and PFLCP in the treatment of trochanteric fractures in elderly patients. Incision length and operative time were shorter for the IMF group than for DHS and PFLCP, but there were no significant differences between DHS and PFLCP. Intraoperative blood loss, rehabilitation, and time to healing were less for the IMF and PFLCP groups than for DHS, but there were no significant differences between IMF and PFLCP. Functional recovery was better for the IMF and PFLCP groups than for DHS, and there were significant differences among the 3 groups. There were fewer complications in the PFLCP group than in IMF and DHS.
Yao and colleagues38 compared reverse LISS and PFN treatment of intertrochanteric fractures and reported no significant differences in operative time, intraoperative blood loss, or functional outcome. Regarding complications, the PFN group had none, and the LISS group had 3 (1 nonunion with locking screw breakage, 2 varus unions).
Haq and colleagues39 compared PFN and contralateral reverse distal femoral locking compression plate (reverse DFLCP) in the management of unstable intertrochanteric fractures with compromised lateral wall and reported better intraoperative variables, better functional outcomes, and lower failure rates in the PFN group than in the reverse DFLCP group.
Zha and colleagues22 followed up 110 patients with intertrochanteric and subtrochanteric fractures treated with PFLCP fixation and reported a 100% union rate at 1-year follow-up. Mean operative time was 35.5minutes, and mean bleeding amount was 150mL, which included operative blood loss and wound drainage. Mean radiologic exposure time was 5minutes, and mean incision length was 9cm. There was 1 case of implant breakage.
Strohm and colleagues40 reported good results in children with trochanteric fractures treated with conventional locking compression plate.
Brett and colleagues41 compared blade plate and PFLCP with and without a kickstand screw in a composite femur subtrochanteric fracture gap model. In their biomechanical study, the PFLCP with a kickstand screw provided higher axial but less torsional stiffness than the blade plate. The authors concluded that, though the devices are biomechanically equivalent, PFLCP may allow percutaneous insertion that avoids the potential morbidity associated with the blade plate’s extensile approach.
Our PFN group’s mean (SD) time to healing was 4.2 (1.3) months. In other studies, mean healing time for IMF-treated unstable trochanteric fractures was 3 to 4 months. Some authors have reported even longer healing times, up to 17 months,42 for PFN-treated trochanteric fractures. Many of the studies indicated that gradual weight-bearing was allowed around 6 weeks, when callus formation was adequate.43 Our treatment protocol differed in that its protected weight-bearing period was prolonged, and controlled weight-bearing was delayed until around 6 weeks, when callus formation was adequate.
The better PFLCP outcomes in our study, relative to most other studies, can be attributed to the relatively younger age of our PFN and PFLCP groups. In a study of 19 patients with trochanteric fractures treated with open reduction and internal fixation using PFLCP, Wirtz and colleagues44 reported 4 cases of secondary varus collapse, 2 cut-outs of the proximal fragment, and 1 implant failure caused by a broken proximal screw. Eight patients experienced persistent trochanteric pain, and 3 underwent hardware removal.
Streubel and colleagues45 retrospectively analyzed 29 patients with 30 OTA 31.A3 fractures treated with PFLCP and reported 11 failures (37%) at 20-month follow-up. The most frequent failure mode (5 cases) was varus collapse with screw cut-out. Presence of a kickstand screw and medial cortical reduction were not significantly different between cases that failed and those that did not.
Glassner and Tejwani46 retrospectively studied 10 patients with trochanteric fractures treated with open reduction and internal fixation with PFLCP. Failure modes were implant fracture (4 cases) and fixation loss (3 cases) resulting from varus collapse and implant cutout.
One of our PFN patients had a lower neck screw back out by 9-month follow-up. As the fracture had consolidated well, the patient underwent screw removal. Another PFN patient had a broken implant and fracture nonunion at 1-year follow-up. Various complications have been reported in the literature,13,14,47,48 but none occurred in our study. There were no implant-related complications in our PFLCP group, possibly because of the mechanical advantage of 3-dimensional and angular-stable fixation with PFLCP in unstable trochanteric fractures.
Gadegone and Salphale49 analyzed 100 cases of PFN-treated trochanteric fractures and reported femoral head cut-through (4.8%), intraoperative femoral shaft fracture (0.8%), implant breakage (0.8%), wound-healing impairment (9.7%), and false placement of osteosynthesis materials (0.8%). The 19% reoperation rate in their study mainly involved cephalic screw removal for lateral protrusion at the proximal thigh. Our PFN reoperation rate was 8.7%; none of our PFLCP patients required revision surgery.
Tyllianakis and colleagues50 analyzed 45 cases of PFN-treated unstable trochanteric fractures and concluded technical or mechanical complications were related more to fracture type, surgical technique, and time to weight-bearing than to the implant itself. Our postoperative wound complication rate was similar to that of other studies.14,47,51 Regarding functional outcomes, our groups’ HHSs were good and comparable at final follow-up, as were their PPM scores.
This study was limited in that it was a small prospective comparative single-center study with a small number of patients. Larger randomized controlled multicenter studies are needed to evaluate and compare both implants in displaced unstable trochanteric femur fractures.
This study found that both PFN and PFLCP were effective treatments for unstable trochanteric femur fractures. PFN is superior to PFLCP only in terms of shorter incisions and shorter time to full weight-bearing. Both devices can be used in unstable trochanteric fractures, and both have good functional outcomes and acceptable complication rates.
Am J Orthop. 2017;46(2):E116-E123. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.
1. Cummings SR, Rubin SM, Black D. The future of hip fractures in the United States. Numbers, costs, and potential effects of postmenopausal estrogen. Clin Orthop Relat Res. 1990;(252):163-166.
2. Kyle RF, Cabanela ME, Russell TA, et al. Fractures of the proximal part of the femur. Instr Course Lect. 1995;44:227-253.
3. Koval KJ, Aharonoff GB, Rokito AS, Lyon T, Zuckerman JD. Patients with femoral neck and intertrochanteric fractures. Are they the same? Clin Orthop Relat Res. 1996;(330):166-172.
4. Marsh JL, Slongo TF, Agel J, et al. Fracture and dislocation classification compendium - 2007: Orthopaedic Trauma Association classification, database and outcomes committee. J Orthop Trauma. 2007;21(10 suppl):S1-S133.
5. Lindskog D, Baumgaertner MR. Unstable intertrochanteric hip fractures in the elderly. J Am Acad Orthop Surg. 2004;12(3):179-190.
6. Kokoroghiannis C, Aktselis I, Deligeorgis A, Fragkomichalos E, Papadimas D, Pappadas I. Evolving concepts of stability and intramedullary fixation of intertrochanteric fractures—a review. Injury. 2012;43(6):686-693.
7. Larsson S, Friberg S, Hansson LI. Trochanteric fractures. Influence of reduction and implant position on impaction and complications. Clin Orthop Relat Res. 1990;(259):130-139.
8. Simpson AH, Varty K, Dodd CA. Sliding hip screws: modes of failure. Injury. 1989;20(4):227-231.
9. Rha JD, Kim YH, Yoon SI, Park TS, Lee MH. Factors affecting sliding of the lag screw in intertrochanteric fractures. Int Orthop. 1993;17(5):320-324.
10. Baixauli F, Vicent V, Baixauli E, et al. A reinforced rigid fixation device for unstable intertrochanteric fractures. Clin Orthop Relat Res. 1999;(361):205-215.
11. Harrington P, Nihal A, Singhania AK, Howell FR. Intramedullary hip screw versus sliding hip screw for unstable intertrochanteric femoral fractures in the elderly. Injury. 2002;33(1):23-28.
12. Parker MJ, Handoll HH. Gamma and other cephalocondylic intramedullary nails versus extramedullary implants for extracapsular hip fractures in adults. Cochrane Database Syst Rev. 2010;(9):CD000093.
13. Pajarinen J, Lindahl J, Michelsson O, Savolainen V, Hirvensalo E. Pertrochanteric femoral fractures treated with a dynamic hip screw or a proximal femoral nail. A randomised study comparing postoperative rehabilitation. J Bone Joint Surg Br. 2005;87(1):76-81.
14. Papasimos S, Koutsojannis CM, Panagopoulos A, Megas P, Lambiris E. A randomised comparison of AMBI, TGN and PFN for treatment of unstable trochanteric fractures. Arch Orthop Trauma Surg. 2005;125(7):462-468.
15. Saudan M, Lübbeke A, Sadowski C, Riand N, Stern R, Hoffmeyer P. Pertrochanteric fractures: is there an advantage to an intramedullary nail? A randomized, prospective study of 206 patients comparing the dynamic hip screw and proximal femoral nail. J Orthop Trauma. 2002;16(6):386-393.
16. Schipper IB, Steyerberg EW, Castelein RM, et al. Treatment of unstable trochanteric fractures. Randomised comparison of the gamma nail and the proximal femoral nail. J Bone Joint Surg Br. 2004;86(1):86-94.
17. Gardenbroek TJ, Segers MJ, Simmermacher RK, Hammacher ER. The proximal femur nail antirotation: an identifiable improvement in the treatment of unstable pertrochanteric fractures? J Trauma. 2011;71(1):169-174.
18. Egol KA, Chang EY, Cvitkovic J, Kummer FJ, Koval KJ. Mismatch of current intramedullary nails with the anterior bow of the femur. J Orthop Trauma. 2004;18(7):410-415.
19. Werner-Tutschku W, Lajtai G, Schmiedhuber G, Lang T, Pirkl C, Orthner E. Intra- and perioperative complications in the stabilization of per- and subtrochanteric femoral fractures by means of PFN [in German]. Unfallchirurg. 2002;105(10):881-885.
20. Ma CH, Tu YK, Yu SW, Yen CY, Yeh JH, Wu CH. Reverse LISS plates for unstable proximal femoral fractures. Injury. 2010;41(8):827-833.
21. Pryce Lewis JR, Ashcroft GP. Reverse LISS plating for proximal segmental femoral fractures in the polytrauma patient: a case report. Injury. 2007;38(2):235-239.
22. Zha GC, Chen ZL, Qi XB, Sun JY. Treatment of pertrochanteric fractures with a proximal femur locking compression plate. Injury. 2011;42(11):1294-1299.
23. Oh CW, Kim JJ, Byun YS, et al. Minimally invasive plate osteosynthesis of subtrochanteric femur fractures with a locking plate: a prospective series of 20 fractures. Arch Orthop Trauma Surg. 2009;129(12):1659-1665.
24. American Society of Anesthesiologists new classification of physical status. Anesthesiology. 1963;24:111-114.
25. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16(4):494-502.
26. Vidyadhara S, Rao SK. One and two femoral neck screws with intramedullary nails for unstable trochanteric fractures of femur in the elderly—randomised clinical trial. Injury. 2007;38(7):806-814.
27. Parker MJ, Palmer CR. A new mobility score for predicting mortality after hip fracture. J Bone Joint Surg Br. 1993;75(5):797-798.
28. Harris WH. Traumatic arthritis of the hip after dislocation and acetabular fractures: treatment by mold arthroplasty. An end-result study using a new method of result evaluation. J Bone Joint Surg Am. 1969;51(4):737-755.
29. Sadowski C, Lübbeke A, Saudan M, Riand N, Stern R, Hoffmeyer P. Treatment of reverse oblique and transverse intertrochanteric fractures with use of an intramedullary nail or a 95 degrees screw-plate: a prospective, randomized study. J Bone Joint Surg Am. 2002;84(3):372-381.
30. Suckel AA, Dietz K, Wuelker N, Helwig P. Evaluation of complications of three different types of proximal extra-articular femur fractures: differences in complications, age, sex and surviving rates. Int Orthop. 2007;31(5):689-695.
31. Nuber S, Schönweiss T, Rüter A. Stabilisation of unstable trochanteric femoral fractures. Dynamic hip screw (DHS) with trochanteric stabilisation plate vs. proximal femur nail (PFN) [in German]. Unfallchirurg. 2003;106(1):39-47.
32. Klinger HM, Baums MH, Eckert M, Neugebauer R. A comparative study of unstable per- and intertrochanteric femoral fractures treated with dynamic hip screw (DHS) and trochanteric butt-press plate vs. proximal femoral nail (PFN) [in German]. Zentralbl Chir. 2005;130(4):301-306.
33. Bridle SH, Patel AD, Bircher M, Calvert PT. Fixation of intertrochanteric fractures of the femur. A randomised prospective comparison of the gamma nail and the dynamic hip screw. J Bone Joint Surg Br. 1991;73(2):330-334.
34. Utrilla AL, Reig JS, Muñoz FM, Tufanisco CB. Trochanteric gamma nail and compression hip screw for trochanteric fractures: a randomized, prospective, comparative study in 210 elderly patients with a new design of the gamma nail. J Orthop Trauma. 2005;19(4):229-233.
35. Lenich A, Mayr E, Rüter A, Möckl CH, Füchtmeier B. First results with the trochanter fixation nail (TFN): a report on 120 cases. Arch Orthop Trauma Surg. 2006;126(10):706-712.
36. Tao R, Lu Y, Xu H, Zhou ZY, Wang YH, Liu F. Internal fixation of intertrochanteric hip fractures: a clinical comparison of two implant designs. ScientificWorldJournal. 2013;2013:834825.
37. Wang Y, Yang YY, Yu ZH, Li CQ, Wu YS, Zheng XX. Comparative study of intertrochanteric fractures treated with proximal femur locking compress plate in aged [in Chinese]. Zhongguo Gu Shang. 2011;24(5):370-373.
38. Yao C, Zhang CQ, Jin DX, Chen YF. Early results of reverse less invasive stabilization system plating in treating elderly intertrochanteric fractures: a prospective study compared to proximal femoral nail. Chin Med J (Engl). 2011;124(14):2150-2157.
39. Haq RU, Manhas V, Pankaj A, Srivastava A, Dhammi IK, Jain AK. Proximal femoral nails compared with reverse distal femoral locking plates in intertrochanteric fractures with a compromised lateral wall; a randomised controlled trial. Int Orthop. 2014;38(7):1443-1449.
40. Strohm PC, Schmal H, Kuminack K, Reising K, Südkamp NP. Intertrochanteric femoral fractures in children [in German]. Unfallchirurg. 2006;109(5):425-430.
41. Brett CD, Lee MA, Khalafi AK, Hazelwood SJ. A comparison of percutaneous versus traditional open plate fixation in a subtrochanteric fracture gap model. In: Proceedings of the Annual Meeting of the Orthopaedic Trauma Association (OTA); October 5-7, 2006; Phoenix, AZ. Basic science poster 71 (abstract).
42. Park SY, Yang KH, Yoo JH, Yoon HK, Park HW. The treatment of reverse obliquity intertrochanteric fractures with the intramedullary hip nail. J Trauma. 2008;65(4):852-857.
43. Habernek H, Wallner T, Aschauer E, Schmid L. Comparison of Ender nails, dynamic hip screws, and gamma nails in the treatment of peritrochanteric femoral fractures. Orthopedics. 2000;23(2):121-127.
44. Wirtz C, Abbassi F, Evangelopoulos DS, Kohl S, Siebenrock KA, Krüger A. High failure rate of trochanteric fracture osteosynthesis with proximal femoral locking compression plate. Injury. 2013;44(6):751-756.
45. Streubel PN, Moustoukas MJ, Obremskey WT. Mechanical failure after locking plate fixation of unstable intertrochanteric femur fractures. J Orthop Trauma. 2013;27(1):22-28.
46. Glassner PJ, Tejwani NC. Failure of proximal femoral locking compression plate: a case series. J Orthop Trauma. 2011;25(2):76-83.
47. Ekström W, Karlsson-Thur C, Larsson S, Ragnarsson B, Alberts KA. Functional outcome in treatment of unstable trochanteric and subtrochanteric fractures with the proximal femoral nail and the Medoff sliding plate. J Orthop Trauma. 2007;21(1):18-25.
48. Boldin C, Seibert FJ, Fankhauser F, Peicha G, Grechenig W, Szyszkowitz R. The proximal femoral nail (PFN)—a minimal invasive treatment of unstable proximal femoral fractures: a prospective study of 55 patients with a follow-up of 15 months. Acta Orthop Scand. 2003;74(1):53-58.
49. Gadegone WM, Salphale YS. Proximal femoral nail—an analysis of 100 cases of proximal femoral fractures with an average follow up of 1 year. Int Orthop. 2007;31(3):403-408.
50. Tyllianakis M, Panagopoulos A, Papadopoulos A, Papasimos S, Mousafiris K. Treatment of extracapsular hip fractures with the proximal femoral nail (PFN): long term results in 45 patients. Acta Orthop Belg. 2004;70(5):444-454.
51. Morihara T, Arai Y, Tokugawa S, Fujita S, Chatani K, Kubo T. Proximal femoral nail for treatment of trochanteric femoral fractures. J Orthop Surg (Hong Kong). 2007;15(3):273-277.
1. Cummings SR, Rubin SM, Black D. The future of hip fractures in the United States. Numbers, costs, and potential effects of postmenopausal estrogen. Clin Orthop Relat Res. 1990;(252):163-166.
2. Kyle RF, Cabanela ME, Russell TA, et al. Fractures of the proximal part of the femur. Instr Course Lect. 1995;44:227-253.
3. Koval KJ, Aharonoff GB, Rokito AS, Lyon T, Zuckerman JD. Patients with femoral neck and intertrochanteric fractures. Are they the same? Clin Orthop Relat Res. 1996;(330):166-172.
4. Marsh JL, Slongo TF, Agel J, et al. Fracture and dislocation classification compendium - 2007: Orthopaedic Trauma Association classification, database and outcomes committee. J Orthop Trauma. 2007;21(10 suppl):S1-S133.
5. Lindskog D, Baumgaertner MR. Unstable intertrochanteric hip fractures in the elderly. J Am Acad Orthop Surg. 2004;12(3):179-190.
6. Kokoroghiannis C, Aktselis I, Deligeorgis A, Fragkomichalos E, Papadimas D, Pappadas I. Evolving concepts of stability and intramedullary fixation of intertrochanteric fractures—a review. Injury. 2012;43(6):686-693.
7. Larsson S, Friberg S, Hansson LI. Trochanteric fractures. Influence of reduction and implant position on impaction and complications. Clin Orthop Relat Res. 1990;(259):130-139.
8. Simpson AH, Varty K, Dodd CA. Sliding hip screws: modes of failure. Injury. 1989;20(4):227-231.
9. Rha JD, Kim YH, Yoon SI, Park TS, Lee MH. Factors affecting sliding of the lag screw in intertrochanteric fractures. Int Orthop. 1993;17(5):320-324.
10. Baixauli F, Vicent V, Baixauli E, et al. A reinforced rigid fixation device for unstable intertrochanteric fractures. Clin Orthop Relat Res. 1999;(361):205-215.
11. Harrington P, Nihal A, Singhania AK, Howell FR. Intramedullary hip screw versus sliding hip screw for unstable intertrochanteric femoral fractures in the elderly. Injury. 2002;33(1):23-28.
12. Parker MJ, Handoll HH. Gamma and other cephalocondylic intramedullary nails versus extramedullary implants for extracapsular hip fractures in adults. Cochrane Database Syst Rev. 2010;(9):CD000093.
13. Pajarinen J, Lindahl J, Michelsson O, Savolainen V, Hirvensalo E. Pertrochanteric femoral fractures treated with a dynamic hip screw or a proximal femoral nail. A randomised study comparing postoperative rehabilitation. J Bone Joint Surg Br. 2005;87(1):76-81.
14. Papasimos S, Koutsojannis CM, Panagopoulos A, Megas P, Lambiris E. A randomised comparison of AMBI, TGN and PFN for treatment of unstable trochanteric fractures. Arch Orthop Trauma Surg. 2005;125(7):462-468.
15. Saudan M, Lübbeke A, Sadowski C, Riand N, Stern R, Hoffmeyer P. Pertrochanteric fractures: is there an advantage to an intramedullary nail? A randomized, prospective study of 206 patients comparing the dynamic hip screw and proximal femoral nail. J Orthop Trauma. 2002;16(6):386-393.
16. Schipper IB, Steyerberg EW, Castelein RM, et al. Treatment of unstable trochanteric fractures. Randomised comparison of the gamma nail and the proximal femoral nail. J Bone Joint Surg Br. 2004;86(1):86-94.
17. Gardenbroek TJ, Segers MJ, Simmermacher RK, Hammacher ER. The proximal femur nail antirotation: an identifiable improvement in the treatment of unstable pertrochanteric fractures? J Trauma. 2011;71(1):169-174.
18. Egol KA, Chang EY, Cvitkovic J, Kummer FJ, Koval KJ. Mismatch of current intramedullary nails with the anterior bow of the femur. J Orthop Trauma. 2004;18(7):410-415.
19. Werner-Tutschku W, Lajtai G, Schmiedhuber G, Lang T, Pirkl C, Orthner E. Intra- and perioperative complications in the stabilization of per- and subtrochanteric femoral fractures by means of PFN [in German]. Unfallchirurg. 2002;105(10):881-885.
20. Ma CH, Tu YK, Yu SW, Yen CY, Yeh JH, Wu CH. Reverse LISS plates for unstable proximal femoral fractures. Injury. 2010;41(8):827-833.
21. Pryce Lewis JR, Ashcroft GP. Reverse LISS plating for proximal segmental femoral fractures in the polytrauma patient: a case report. Injury. 2007;38(2):235-239.
22. Zha GC, Chen ZL, Qi XB, Sun JY. Treatment of pertrochanteric fractures with a proximal femur locking compression plate. Injury. 2011;42(11):1294-1299.
23. Oh CW, Kim JJ, Byun YS, et al. Minimally invasive plate osteosynthesis of subtrochanteric femur fractures with a locking plate: a prospective series of 20 fractures. Arch Orthop Trauma Surg. 2009;129(12):1659-1665.
24. American Society of Anesthesiologists new classification of physical status. Anesthesiology. 1963;24:111-114.
25. Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis. 1957;16(4):494-502.
26. Vidyadhara S, Rao SK. One and two femoral neck screws with intramedullary nails for unstable trochanteric fractures of femur in the elderly—randomised clinical trial. Injury. 2007;38(7):806-814.
27. Parker MJ, Palmer CR. A new mobility score for predicting mortality after hip fracture. J Bone Joint Surg Br. 1993;75(5):797-798.
28. Harris WH. Traumatic arthritis of the hip after dislocation and acetabular fractures: treatment by mold arthroplasty. An end-result study using a new method of result evaluation. J Bone Joint Surg Am. 1969;51(4):737-755.
29. Sadowski C, Lübbeke A, Saudan M, Riand N, Stern R, Hoffmeyer P. Treatment of reverse oblique and transverse intertrochanteric fractures with use of an intramedullary nail or a 95 degrees screw-plate: a prospective, randomized study. J Bone Joint Surg Am. 2002;84(3):372-381.
30. Suckel AA, Dietz K, Wuelker N, Helwig P. Evaluation of complications of three different types of proximal extra-articular femur fractures: differences in complications, age, sex and surviving rates. Int Orthop. 2007;31(5):689-695.
31. Nuber S, Schönweiss T, Rüter A. Stabilisation of unstable trochanteric femoral fractures. Dynamic hip screw (DHS) with trochanteric stabilisation plate vs. proximal femur nail (PFN) [in German]. Unfallchirurg. 2003;106(1):39-47.
32. Klinger HM, Baums MH, Eckert M, Neugebauer R. A comparative study of unstable per- and intertrochanteric femoral fractures treated with dynamic hip screw (DHS) and trochanteric butt-press plate vs. proximal femoral nail (PFN) [in German]. Zentralbl Chir. 2005;130(4):301-306.
33. Bridle SH, Patel AD, Bircher M, Calvert PT. Fixation of intertrochanteric fractures of the femur. A randomised prospective comparison of the gamma nail and the dynamic hip screw. J Bone Joint Surg Br. 1991;73(2):330-334.
34. Utrilla AL, Reig JS, Muñoz FM, Tufanisco CB. Trochanteric gamma nail and compression hip screw for trochanteric fractures: a randomized, prospective, comparative study in 210 elderly patients with a new design of the gamma nail. J Orthop Trauma. 2005;19(4):229-233.
35. Lenich A, Mayr E, Rüter A, Möckl CH, Füchtmeier B. First results with the trochanter fixation nail (TFN): a report on 120 cases. Arch Orthop Trauma Surg. 2006;126(10):706-712.
36. Tao R, Lu Y, Xu H, Zhou ZY, Wang YH, Liu F. Internal fixation of intertrochanteric hip fractures: a clinical comparison of two implant designs. ScientificWorldJournal. 2013;2013:834825.
37. Wang Y, Yang YY, Yu ZH, Li CQ, Wu YS, Zheng XX. Comparative study of intertrochanteric fractures treated with proximal femur locking compress plate in aged [in Chinese]. Zhongguo Gu Shang. 2011;24(5):370-373.
38. Yao C, Zhang CQ, Jin DX, Chen YF. Early results of reverse less invasive stabilization system plating in treating elderly intertrochanteric fractures: a prospective study compared to proximal femoral nail. Chin Med J (Engl). 2011;124(14):2150-2157.
39. Haq RU, Manhas V, Pankaj A, Srivastava A, Dhammi IK, Jain AK. Proximal femoral nails compared with reverse distal femoral locking plates in intertrochanteric fractures with a compromised lateral wall; a randomised controlled trial. Int Orthop. 2014;38(7):1443-1449.
40. Strohm PC, Schmal H, Kuminack K, Reising K, Südkamp NP. Intertrochanteric femoral fractures in children [in German]. Unfallchirurg. 2006;109(5):425-430.
41. Brett CD, Lee MA, Khalafi AK, Hazelwood SJ. A comparison of percutaneous versus traditional open plate fixation in a subtrochanteric fracture gap model. In: Proceedings of the Annual Meeting of the Orthopaedic Trauma Association (OTA); October 5-7, 2006; Phoenix, AZ. Basic science poster 71 (abstract).
42. Park SY, Yang KH, Yoo JH, Yoon HK, Park HW. The treatment of reverse obliquity intertrochanteric fractures with the intramedullary hip nail. J Trauma. 2008;65(4):852-857.
43. Habernek H, Wallner T, Aschauer E, Schmid L. Comparison of Ender nails, dynamic hip screws, and gamma nails in the treatment of peritrochanteric femoral fractures. Orthopedics. 2000;23(2):121-127.
44. Wirtz C, Abbassi F, Evangelopoulos DS, Kohl S, Siebenrock KA, Krüger A. High failure rate of trochanteric fracture osteosynthesis with proximal femoral locking compression plate. Injury. 2013;44(6):751-756.
45. Streubel PN, Moustoukas MJ, Obremskey WT. Mechanical failure after locking plate fixation of unstable intertrochanteric femur fractures. J Orthop Trauma. 2013;27(1):22-28.
46. Glassner PJ, Tejwani NC. Failure of proximal femoral locking compression plate: a case series. J Orthop Trauma. 2011;25(2):76-83.
47. Ekström W, Karlsson-Thur C, Larsson S, Ragnarsson B, Alberts KA. Functional outcome in treatment of unstable trochanteric and subtrochanteric fractures with the proximal femoral nail and the Medoff sliding plate. J Orthop Trauma. 2007;21(1):18-25.
48. Boldin C, Seibert FJ, Fankhauser F, Peicha G, Grechenig W, Szyszkowitz R. The proximal femoral nail (PFN)—a minimal invasive treatment of unstable proximal femoral fractures: a prospective study of 55 patients with a follow-up of 15 months. Acta Orthop Scand. 2003;74(1):53-58.
49. Gadegone WM, Salphale YS. Proximal femoral nail—an analysis of 100 cases of proximal femoral fractures with an average follow up of 1 year. Int Orthop. 2007;31(3):403-408.
50. Tyllianakis M, Panagopoulos A, Papadopoulos A, Papasimos S, Mousafiris K. Treatment of extracapsular hip fractures with the proximal femoral nail (PFN): long term results in 45 patients. Acta Orthop Belg. 2004;70(5):444-454.
51. Morihara T, Arai Y, Tokugawa S, Fujita S, Chatani K, Kubo T. Proximal femoral nail for treatment of trochanteric femoral fractures. J Orthop Surg (Hong Kong). 2007;15(3):273-277.
Flesh-Colored Nodule With Underlying Sclerotic Plaque
The Diagnosis: Collision Tumor
Excisional biopsy and histopathological examination demonstrated a collision tumor composed of a benign intradermal melanocytic nevus, tumor of follicular infundibulum, and an underlying sclerosing epithelial neoplasm, with a differential diagnosis of desmoplastic trichoepithelioma, morpheaform basal cell carcinoma, and microcystic adnexal carcinoma (Figure).
Common acquired melanocytic nevus presents clinically as a macule, papule, or nodule with smooth regular borders. The pigmented variant displays an evenly distributed pigment on the lesion. Intradermal melanocytic nevus often presents as a flesh-colored nodule, as in our case. Histopathologically, benign intradermal nevus typically is composed of a proliferation of melanocytes that exhibit dispersion as they go deeper in the dermis and maturation that manifests as melanocytes becoming smaller and more spindled in the deeper portions of the lesion.1 These 2 characteristics plus the bland cytology seen in the present case confirm the benign characteristic of this lesion (Figure, B).
In addition to the benign intradermal melanocytic nevus, an adjacent tumor of follicular infundibulum was noted. Tumor of follicular infundibulum is a rare adnexal tumor. It occurs frequently on the head and neck and shows some female predominance.2,3 Multiple lesions and eruptive lesions are rare forms that also have been reported.4 Histopathologically, the tumor demonstrates an epithelial plate that is present in the papillary dermis and is connected to the epidermis at multiple points with attachment to the follicular outer root sheath. Peripheral palisading is characteristically present above an eosinophilic basement membrane (Figure, A). Rare reports have documented sebaceous and eccrine differentiation.5,6
Tumor of follicular infundibulum has been reported to be associated with other tumors. Organoid nevus (nevus sebaceous), trichilemmal tumor, and fibroma have been reported to occur as a collision tumor with tumor of follicular infundibulum. An association with Cowden disease also has been described.7 Biopsies that represent partial samples should be interpreted cautiously, as step sections can reveal basal cell carcinoma.
The term sclerosing epithelial neoplasm describes tumors that share a paisley tielike epithelial pattern and sclerotic stroma. Small specimens often require clinicopathologic correlation (Figure, C). The differential diagnosis includes morpheaform basal cell carcinoma, desmoplastic trichoepithelioma, and microcystic adnexal carcinoma. A panel of stains using Ber-EP4, PHLDA1, cytokeratin 15, and cytokeratin 19 has been proposed to help differentiate these entities.8 CD34 and cytokeratin 20 also have been used with varying success in small specimens.9,10
- Ferringer T, Peckham S, Ko CJ, et al. Melanocytic neoplasms. In: Elston DM, Ferringer T, eds. Dermatopathology. 2nd ed. Philadelphia, PA: Elsevier Saunders; 2014:105-109.
- Headington JT. Tumors of the hair follicle. Am J Pathol. 1976;85:480-505.
- Davis DA, Cohen PR. Hair follicle nevus: case report and review of the literature. Pediatr Dermatol. 1996;13:135-138.
- Ikeda S, Kawada J, Yaguchi H, et al. A case of unilateral, systematized linear hair follicle nevi associated with epidermal nevus-like lesions. Dermatology. 2003;206:172-174.
- Mehregan AH. Hair follicle tumors of the skin. J Cutan Pathol. 1985;12:189-195.
- Mahalingam M, Bhawan J, Finn R, et al. Tumor of the follicular infundibulum with sebaceous differentiation. J Cutan Pathol. 2001;28:314-317.
- Cribier B, Grosshans E. Tumor of the follicular infundibulum: a clinicopathologic study. J Am Acad Dermatol. 1995;33:979-984.
- Sellheyer K, Nelson P, Kutzner H, et al. The immunohistochemical differential diagnosis of microcystic adnexal carcinoma, desmoplastic trichoepithelioma and morpheaform basal cell carcinoma using BerEP4 and stem cell markers. J Cutan Pathol. 2013;40:363-370.
- Abesamis-Cubillan E, El-Shabrawi-Caelen L, LeBoit PE. Merkel cells and sclerosing epithelial neoplasms. Am J Dermatopathol. 2000;22:311-315.
- Smith KJ, Williams J, Corbett D, et al. Microcystic adnexal carcinoma: an immunohistochemical study including markers of proliferation and apoptosis. Am J Surg Pathol. 2001;25:464-471.
The Diagnosis: Collision Tumor
Excisional biopsy and histopathological examination demonstrated a collision tumor composed of a benign intradermal melanocytic nevus, tumor of follicular infundibulum, and an underlying sclerosing epithelial neoplasm, with a differential diagnosis of desmoplastic trichoepithelioma, morpheaform basal cell carcinoma, and microcystic adnexal carcinoma (Figure).
Common acquired melanocytic nevus presents clinically as a macule, papule, or nodule with smooth regular borders. The pigmented variant displays an evenly distributed pigment on the lesion. Intradermal melanocytic nevus often presents as a flesh-colored nodule, as in our case. Histopathologically, benign intradermal nevus typically is composed of a proliferation of melanocytes that exhibit dispersion as they go deeper in the dermis and maturation that manifests as melanocytes becoming smaller and more spindled in the deeper portions of the lesion.1 These 2 characteristics plus the bland cytology seen in the present case confirm the benign characteristic of this lesion (Figure, B).
In addition to the benign intradermal melanocytic nevus, an adjacent tumor of follicular infundibulum was noted. Tumor of follicular infundibulum is a rare adnexal tumor. It occurs frequently on the head and neck and shows some female predominance.2,3 Multiple lesions and eruptive lesions are rare forms that also have been reported.4 Histopathologically, the tumor demonstrates an epithelial plate that is present in the papillary dermis and is connected to the epidermis at multiple points with attachment to the follicular outer root sheath. Peripheral palisading is characteristically present above an eosinophilic basement membrane (Figure, A). Rare reports have documented sebaceous and eccrine differentiation.5,6
Tumor of follicular infundibulum has been reported to be associated with other tumors. Organoid nevus (nevus sebaceous), trichilemmal tumor, and fibroma have been reported to occur as a collision tumor with tumor of follicular infundibulum. An association with Cowden disease also has been described.7 Biopsies that represent partial samples should be interpreted cautiously, as step sections can reveal basal cell carcinoma.
The term sclerosing epithelial neoplasm describes tumors that share a paisley tielike epithelial pattern and sclerotic stroma. Small specimens often require clinicopathologic correlation (Figure, C). The differential diagnosis includes morpheaform basal cell carcinoma, desmoplastic trichoepithelioma, and microcystic adnexal carcinoma. A panel of stains using Ber-EP4, PHLDA1, cytokeratin 15, and cytokeratin 19 has been proposed to help differentiate these entities.8 CD34 and cytokeratin 20 also have been used with varying success in small specimens.9,10
The Diagnosis: Collision Tumor
Excisional biopsy and histopathological examination demonstrated a collision tumor composed of a benign intradermal melanocytic nevus, tumor of follicular infundibulum, and an underlying sclerosing epithelial neoplasm, with a differential diagnosis of desmoplastic trichoepithelioma, morpheaform basal cell carcinoma, and microcystic adnexal carcinoma (Figure).
Common acquired melanocytic nevus presents clinically as a macule, papule, or nodule with smooth regular borders. The pigmented variant displays an evenly distributed pigment on the lesion. Intradermal melanocytic nevus often presents as a flesh-colored nodule, as in our case. Histopathologically, benign intradermal nevus typically is composed of a proliferation of melanocytes that exhibit dispersion as they go deeper in the dermis and maturation that manifests as melanocytes becoming smaller and more spindled in the deeper portions of the lesion.1 These 2 characteristics plus the bland cytology seen in the present case confirm the benign characteristic of this lesion (Figure, B).
In addition to the benign intradermal melanocytic nevus, an adjacent tumor of follicular infundibulum was noted. Tumor of follicular infundibulum is a rare adnexal tumor. It occurs frequently on the head and neck and shows some female predominance.2,3 Multiple lesions and eruptive lesions are rare forms that also have been reported.4 Histopathologically, the tumor demonstrates an epithelial plate that is present in the papillary dermis and is connected to the epidermis at multiple points with attachment to the follicular outer root sheath. Peripheral palisading is characteristically present above an eosinophilic basement membrane (Figure, A). Rare reports have documented sebaceous and eccrine differentiation.5,6
Tumor of follicular infundibulum has been reported to be associated with other tumors. Organoid nevus (nevus sebaceous), trichilemmal tumor, and fibroma have been reported to occur as a collision tumor with tumor of follicular infundibulum. An association with Cowden disease also has been described.7 Biopsies that represent partial samples should be interpreted cautiously, as step sections can reveal basal cell carcinoma.
The term sclerosing epithelial neoplasm describes tumors that share a paisley tielike epithelial pattern and sclerotic stroma. Small specimens often require clinicopathologic correlation (Figure, C). The differential diagnosis includes morpheaform basal cell carcinoma, desmoplastic trichoepithelioma, and microcystic adnexal carcinoma. A panel of stains using Ber-EP4, PHLDA1, cytokeratin 15, and cytokeratin 19 has been proposed to help differentiate these entities.8 CD34 and cytokeratin 20 also have been used with varying success in small specimens.9,10
- Ferringer T, Peckham S, Ko CJ, et al. Melanocytic neoplasms. In: Elston DM, Ferringer T, eds. Dermatopathology. 2nd ed. Philadelphia, PA: Elsevier Saunders; 2014:105-109.
- Headington JT. Tumors of the hair follicle. Am J Pathol. 1976;85:480-505.
- Davis DA, Cohen PR. Hair follicle nevus: case report and review of the literature. Pediatr Dermatol. 1996;13:135-138.
- Ikeda S, Kawada J, Yaguchi H, et al. A case of unilateral, systematized linear hair follicle nevi associated with epidermal nevus-like lesions. Dermatology. 2003;206:172-174.
- Mehregan AH. Hair follicle tumors of the skin. J Cutan Pathol. 1985;12:189-195.
- Mahalingam M, Bhawan J, Finn R, et al. Tumor of the follicular infundibulum with sebaceous differentiation. J Cutan Pathol. 2001;28:314-317.
- Cribier B, Grosshans E. Tumor of the follicular infundibulum: a clinicopathologic study. J Am Acad Dermatol. 1995;33:979-984.
- Sellheyer K, Nelson P, Kutzner H, et al. The immunohistochemical differential diagnosis of microcystic adnexal carcinoma, desmoplastic trichoepithelioma and morpheaform basal cell carcinoma using BerEP4 and stem cell markers. J Cutan Pathol. 2013;40:363-370.
- Abesamis-Cubillan E, El-Shabrawi-Caelen L, LeBoit PE. Merkel cells and sclerosing epithelial neoplasms. Am J Dermatopathol. 2000;22:311-315.
- Smith KJ, Williams J, Corbett D, et al. Microcystic adnexal carcinoma: an immunohistochemical study including markers of proliferation and apoptosis. Am J Surg Pathol. 2001;25:464-471.
- Ferringer T, Peckham S, Ko CJ, et al. Melanocytic neoplasms. In: Elston DM, Ferringer T, eds. Dermatopathology. 2nd ed. Philadelphia, PA: Elsevier Saunders; 2014:105-109.
- Headington JT. Tumors of the hair follicle. Am J Pathol. 1976;85:480-505.
- Davis DA, Cohen PR. Hair follicle nevus: case report and review of the literature. Pediatr Dermatol. 1996;13:135-138.
- Ikeda S, Kawada J, Yaguchi H, et al. A case of unilateral, systematized linear hair follicle nevi associated with epidermal nevus-like lesions. Dermatology. 2003;206:172-174.
- Mehregan AH. Hair follicle tumors of the skin. J Cutan Pathol. 1985;12:189-195.
- Mahalingam M, Bhawan J, Finn R, et al. Tumor of the follicular infundibulum with sebaceous differentiation. J Cutan Pathol. 2001;28:314-317.
- Cribier B, Grosshans E. Tumor of the follicular infundibulum: a clinicopathologic study. J Am Acad Dermatol. 1995;33:979-984.
- Sellheyer K, Nelson P, Kutzner H, et al. The immunohistochemical differential diagnosis of microcystic adnexal carcinoma, desmoplastic trichoepithelioma and morpheaform basal cell carcinoma using BerEP4 and stem cell markers. J Cutan Pathol. 2013;40:363-370.
- Abesamis-Cubillan E, El-Shabrawi-Caelen L, LeBoit PE. Merkel cells and sclerosing epithelial neoplasms. Am J Dermatopathol. 2000;22:311-315.
- Smith KJ, Williams J, Corbett D, et al. Microcystic adnexal carcinoma: an immunohistochemical study including markers of proliferation and apoptosis. Am J Surg Pathol. 2001;25:464-471.
A 54-year-old man presented with a flesh-colored lesion on the chin. The nodule measured 0.6 cm in diameter. There was an underlying sclerotic plaque with indistinct borders.
Bevy of monoclonal antibody migraine prevention trials awaits attendees
Calcitonin gene–related peptide (CGRP) monoclonal antibodies for migraine prevention will take center stage at the upcoming annual meeting of the American Academy of Neurology in Boston in a variety of talks aimed at describing the latest clinical trial findings.
Amaal J. Starling, MD, of the Mayo Clinic, Phoenix, Ariz., will lead off on the topic in the Contemporary Clinical Issues Plenary Session on April 24 by discussing in her presentation, “The Era of Targeted Preventive Treatment for Migraine: CGRP Monoclonal Antibodies,” the impact that CGRP monoclonal antibodies may have on migraine treatment
In the first of two presentations on the primary results of two phase III migraine prevention trials for the CGRP monoclonal antibody erenumab, also known as AMG 334, Peter Goadsby, MD, PhD, of the University of California, San Francisco, will report on the STRIVE trial in the Clinical Trials Plenary Session on April 25.
STRIVE is investigating two doses of erenumab against placebo in a 24-week trial examining the primary outcome of a change from baseline in mean monthly migraine days among 955 patients with a 1-year history of episodic migraine who are currently, have previously, or have never received migraine prophylactic medication. Patients will then be randomized after this initial double-blind treatment phase to 28 weeks of open-label active treatment with either dose of erenumab.
Later on April 25 in the Emerging Science Platform Session, David W. Dodick, MD, of the Mayo Clinic in Phoenix is set to describe the results of the phase III ARISE trial. Investigators in ARISE tested 12 weeks of one dosing regimen of erenumab versus placebo on the change from baseline in mean monthly migraine days in 577 patients with episodic migraine, followed by a 28-week open-label treatment phase.
Phase II study results of erenumab in the prevention of chronic migraine can be viewed April 28 in the “Headache: Clinical Trials and Disease Burden” platform session. The trial tested two doses of erenumab against placebo to detect differences in the change in monthly migraine days from baseline in the last 4 weeks of the trial’s 12-week double-blind treatment phase. The phase II trial results of a different CGRP monoclonal antibody known as eptinezumab or ALD403 in the prevention of chronic migraine will also be reported in the same platform session. The study evaluated a variety of doses of the drug for superiority against placebo in reducing the number of migraine days by 75% over 12 weeks.
Calcitonin gene–related peptide (CGRP) monoclonal antibodies for migraine prevention will take center stage at the upcoming annual meeting of the American Academy of Neurology in Boston in a variety of talks aimed at describing the latest clinical trial findings.
Amaal J. Starling, MD, of the Mayo Clinic, Phoenix, Ariz., will lead off on the topic in the Contemporary Clinical Issues Plenary Session on April 24 by discussing in her presentation, “The Era of Targeted Preventive Treatment for Migraine: CGRP Monoclonal Antibodies,” the impact that CGRP monoclonal antibodies may have on migraine treatment
In the first of two presentations on the primary results of two phase III migraine prevention trials for the CGRP monoclonal antibody erenumab, also known as AMG 334, Peter Goadsby, MD, PhD, of the University of California, San Francisco, will report on the STRIVE trial in the Clinical Trials Plenary Session on April 25.
STRIVE is investigating two doses of erenumab against placebo in a 24-week trial examining the primary outcome of a change from baseline in mean monthly migraine days among 955 patients with a 1-year history of episodic migraine who are currently, have previously, or have never received migraine prophylactic medication. Patients will then be randomized after this initial double-blind treatment phase to 28 weeks of open-label active treatment with either dose of erenumab.
Later on April 25 in the Emerging Science Platform Session, David W. Dodick, MD, of the Mayo Clinic in Phoenix is set to describe the results of the phase III ARISE trial. Investigators in ARISE tested 12 weeks of one dosing regimen of erenumab versus placebo on the change from baseline in mean monthly migraine days in 577 patients with episodic migraine, followed by a 28-week open-label treatment phase.
Phase II study results of erenumab in the prevention of chronic migraine can be viewed April 28 in the “Headache: Clinical Trials and Disease Burden” platform session. The trial tested two doses of erenumab against placebo to detect differences in the change in monthly migraine days from baseline in the last 4 weeks of the trial’s 12-week double-blind treatment phase. The phase II trial results of a different CGRP monoclonal antibody known as eptinezumab or ALD403 in the prevention of chronic migraine will also be reported in the same platform session. The study evaluated a variety of doses of the drug for superiority against placebo in reducing the number of migraine days by 75% over 12 weeks.
Calcitonin gene–related peptide (CGRP) monoclonal antibodies for migraine prevention will take center stage at the upcoming annual meeting of the American Academy of Neurology in Boston in a variety of talks aimed at describing the latest clinical trial findings.
Amaal J. Starling, MD, of the Mayo Clinic, Phoenix, Ariz., will lead off on the topic in the Contemporary Clinical Issues Plenary Session on April 24 by discussing in her presentation, “The Era of Targeted Preventive Treatment for Migraine: CGRP Monoclonal Antibodies,” the impact that CGRP monoclonal antibodies may have on migraine treatment
In the first of two presentations on the primary results of two phase III migraine prevention trials for the CGRP monoclonal antibody erenumab, also known as AMG 334, Peter Goadsby, MD, PhD, of the University of California, San Francisco, will report on the STRIVE trial in the Clinical Trials Plenary Session on April 25.
STRIVE is investigating two doses of erenumab against placebo in a 24-week trial examining the primary outcome of a change from baseline in mean monthly migraine days among 955 patients with a 1-year history of episodic migraine who are currently, have previously, or have never received migraine prophylactic medication. Patients will then be randomized after this initial double-blind treatment phase to 28 weeks of open-label active treatment with either dose of erenumab.
Later on April 25 in the Emerging Science Platform Session, David W. Dodick, MD, of the Mayo Clinic in Phoenix is set to describe the results of the phase III ARISE trial. Investigators in ARISE tested 12 weeks of one dosing regimen of erenumab versus placebo on the change from baseline in mean monthly migraine days in 577 patients with episodic migraine, followed by a 28-week open-label treatment phase.
Phase II study results of erenumab in the prevention of chronic migraine can be viewed April 28 in the “Headache: Clinical Trials and Disease Burden” platform session. The trial tested two doses of erenumab against placebo to detect differences in the change in monthly migraine days from baseline in the last 4 weeks of the trial’s 12-week double-blind treatment phase. The phase II trial results of a different CGRP monoclonal antibody known as eptinezumab or ALD403 in the prevention of chronic migraine will also be reported in the same platform session. The study evaluated a variety of doses of the drug for superiority against placebo in reducing the number of migraine days by 75% over 12 weeks.
AAN spotlights spinal muscular atrophy clinical research
A variety of plenary and emerging science sessions at this year’s annual meeting of the American Academy of Neurology in Boston will highlight clinical research efforts to treat children with spinal muscular atrophy.
At the Hot Topics Plenary Session on April 22, Claudia A. Chiriboga, MD, of Columbia University, New York, will discuss the results of clinical trials involving antisense oligonucleotide treatments for spinal muscular atrophy (SMA), including the recently approved nusinersen (Spinraza), which promotes transcription of the full-length survival motor neuron (SMN) protein from the SMN2 gene.
In the first of two reports on new clinical research about nusinersen, Nancy L. Kuntz, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago will present the initial interim efficacy and safety findings from the phase III international ENDEAR study on April 24 at the Contemporary Clinical Issues Plenary Session. The study of 122 infants with SMA is comparing intrathecal administration of nusinersen against a sham procedure of a small needle prick on the lower back to look for differences at day 402 in the primary outcome of the percentage of patients who attain motor milestones as assessed by section 2 of the Hammersmith Infant Neurological Examination or the time to death or need for respiratory intervention. Charlotte J. Sumner, MD, of Johns Hopkins University, Baltimore, will discuss the study following Dr. Kuntz’s presentation.
The second nusinersen trial to be reported at the meeting will describe interim results of the drug’s efficacy and safety in children with later-onset SMA in the phase III CHERISH study. At the Emerging Science Platform Session on April 25, Richard S. Finkel, MD, of Nemours Children’s Hospital in Orlando, Fla., will discuss how the primary outcome of the Hammersmith Functional Motor Scale–Expanded score changed from baseline to 15 months following intrathecal injection or a sham procedure in children aged 2-12 years.
An investigational SMA type 1 treatment just beginning testing in clinical trials will also receive attention in a plenary session and a platform session. In the Clinical Trials Plenary Session on April 25, Jerry R. Mendell, MD, of Nationwide Children’s Hospital, Columbus, Ohio, will report on the first gene therapy trial for SMA type 1, a phase I trial of AVXS-101, which delivers the SMN gene in a AAV9 viral vector that is able to cross the blood-brain barrier. The primary objective of the trial is to assess safety of a single intravenous dose. The secondary objectives include survival (avoidance of death/permanent-ventilation) and the ability to sit unassisted. Other analyses of data from the phase I trial will be reported during the “Motor Neuron Diseases: Biomarkers, Outcome Measures, and Therapeutics,” platform session on April 24, including the evaluation of preexisting anti-AAV9 antibodies and the proportion of patients who achieve CHOP-INTEND scores of 50 and above and sit unassisted.
A variety of plenary and emerging science sessions at this year’s annual meeting of the American Academy of Neurology in Boston will highlight clinical research efforts to treat children with spinal muscular atrophy.
At the Hot Topics Plenary Session on April 22, Claudia A. Chiriboga, MD, of Columbia University, New York, will discuss the results of clinical trials involving antisense oligonucleotide treatments for spinal muscular atrophy (SMA), including the recently approved nusinersen (Spinraza), which promotes transcription of the full-length survival motor neuron (SMN) protein from the SMN2 gene.
In the first of two reports on new clinical research about nusinersen, Nancy L. Kuntz, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago will present the initial interim efficacy and safety findings from the phase III international ENDEAR study on April 24 at the Contemporary Clinical Issues Plenary Session. The study of 122 infants with SMA is comparing intrathecal administration of nusinersen against a sham procedure of a small needle prick on the lower back to look for differences at day 402 in the primary outcome of the percentage of patients who attain motor milestones as assessed by section 2 of the Hammersmith Infant Neurological Examination or the time to death or need for respiratory intervention. Charlotte J. Sumner, MD, of Johns Hopkins University, Baltimore, will discuss the study following Dr. Kuntz’s presentation.
The second nusinersen trial to be reported at the meeting will describe interim results of the drug’s efficacy and safety in children with later-onset SMA in the phase III CHERISH study. At the Emerging Science Platform Session on April 25, Richard S. Finkel, MD, of Nemours Children’s Hospital in Orlando, Fla., will discuss how the primary outcome of the Hammersmith Functional Motor Scale–Expanded score changed from baseline to 15 months following intrathecal injection or a sham procedure in children aged 2-12 years.
An investigational SMA type 1 treatment just beginning testing in clinical trials will also receive attention in a plenary session and a platform session. In the Clinical Trials Plenary Session on April 25, Jerry R. Mendell, MD, of Nationwide Children’s Hospital, Columbus, Ohio, will report on the first gene therapy trial for SMA type 1, a phase I trial of AVXS-101, which delivers the SMN gene in a AAV9 viral vector that is able to cross the blood-brain barrier. The primary objective of the trial is to assess safety of a single intravenous dose. The secondary objectives include survival (avoidance of death/permanent-ventilation) and the ability to sit unassisted. Other analyses of data from the phase I trial will be reported during the “Motor Neuron Diseases: Biomarkers, Outcome Measures, and Therapeutics,” platform session on April 24, including the evaluation of preexisting anti-AAV9 antibodies and the proportion of patients who achieve CHOP-INTEND scores of 50 and above and sit unassisted.
A variety of plenary and emerging science sessions at this year’s annual meeting of the American Academy of Neurology in Boston will highlight clinical research efforts to treat children with spinal muscular atrophy.
At the Hot Topics Plenary Session on April 22, Claudia A. Chiriboga, MD, of Columbia University, New York, will discuss the results of clinical trials involving antisense oligonucleotide treatments for spinal muscular atrophy (SMA), including the recently approved nusinersen (Spinraza), which promotes transcription of the full-length survival motor neuron (SMN) protein from the SMN2 gene.
In the first of two reports on new clinical research about nusinersen, Nancy L. Kuntz, MD, of Ann & Robert H. Lurie Children’s Hospital of Chicago will present the initial interim efficacy and safety findings from the phase III international ENDEAR study on April 24 at the Contemporary Clinical Issues Plenary Session. The study of 122 infants with SMA is comparing intrathecal administration of nusinersen against a sham procedure of a small needle prick on the lower back to look for differences at day 402 in the primary outcome of the percentage of patients who attain motor milestones as assessed by section 2 of the Hammersmith Infant Neurological Examination or the time to death or need for respiratory intervention. Charlotte J. Sumner, MD, of Johns Hopkins University, Baltimore, will discuss the study following Dr. Kuntz’s presentation.
The second nusinersen trial to be reported at the meeting will describe interim results of the drug’s efficacy and safety in children with later-onset SMA in the phase III CHERISH study. At the Emerging Science Platform Session on April 25, Richard S. Finkel, MD, of Nemours Children’s Hospital in Orlando, Fla., will discuss how the primary outcome of the Hammersmith Functional Motor Scale–Expanded score changed from baseline to 15 months following intrathecal injection or a sham procedure in children aged 2-12 years.
An investigational SMA type 1 treatment just beginning testing in clinical trials will also receive attention in a plenary session and a platform session. In the Clinical Trials Plenary Session on April 25, Jerry R. Mendell, MD, of Nationwide Children’s Hospital, Columbus, Ohio, will report on the first gene therapy trial for SMA type 1, a phase I trial of AVXS-101, which delivers the SMN gene in a AAV9 viral vector that is able to cross the blood-brain barrier. The primary objective of the trial is to assess safety of a single intravenous dose. The secondary objectives include survival (avoidance of death/permanent-ventilation) and the ability to sit unassisted. Other analyses of data from the phase I trial will be reported during the “Motor Neuron Diseases: Biomarkers, Outcome Measures, and Therapeutics,” platform session on April 24, including the evaluation of preexisting anti-AAV9 antibodies and the proportion of patients who achieve CHOP-INTEND scores of 50 and above and sit unassisted.
CCP status doesn’t influence tocilizumab’s effectiveness in RA
Among adults with rheumatoid arthritis, serologic status regarding anti–cyclic citrullinated peptide (CCP) antibodies doesn’t appear to influence the effectiveness of tocilizumab therapy, according to a report published in Seminars in Arthritis and Rheumatism.
Compared with patients who have anti-CCP antibodies, those who don’t show differences in immune activation that may affect their response to various therapies. In particular, some experts have hypothesized that monoclonal antibodies such as tocilizumab that target the interleukin-6 receptor would be more effective in patients who are seronegative for anti-CCP antibodies than in those who are seropositive. Being able to predict patient response based on easily available biomarkers like CCP status would greatly assist treatment selection, said Laura C. Cappelli, MD, of the division of rheumatology at Johns Hopkins University, Baltimore, and her associates.
All but one of these eight measures of disease activity (the mHAQ) improved significantly with tocilizumab, regardless of patient anti-CCP status. In addition, the magnitude of change did not differ by anti-CCP status. These results persisted across several sensitivity analyses, Dr. Cappelli and her associates said (Semin Arthritis Rheum. 2017 Apr 1. doi: 10.1016/j.semarthrit.2017.03.024).
The findings indicate that CCP seronegativity does not improve the response to tocilizumab in this population derived from real-world patients at diverse clinical sites, the investigators noted.
This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Cappelli and her associates reported having no relevant financial disclosures.
Among adults with rheumatoid arthritis, serologic status regarding anti–cyclic citrullinated peptide (CCP) antibodies doesn’t appear to influence the effectiveness of tocilizumab therapy, according to a report published in Seminars in Arthritis and Rheumatism.
Compared with patients who have anti-CCP antibodies, those who don’t show differences in immune activation that may affect their response to various therapies. In particular, some experts have hypothesized that monoclonal antibodies such as tocilizumab that target the interleukin-6 receptor would be more effective in patients who are seronegative for anti-CCP antibodies than in those who are seropositive. Being able to predict patient response based on easily available biomarkers like CCP status would greatly assist treatment selection, said Laura C. Cappelli, MD, of the division of rheumatology at Johns Hopkins University, Baltimore, and her associates.
All but one of these eight measures of disease activity (the mHAQ) improved significantly with tocilizumab, regardless of patient anti-CCP status. In addition, the magnitude of change did not differ by anti-CCP status. These results persisted across several sensitivity analyses, Dr. Cappelli and her associates said (Semin Arthritis Rheum. 2017 Apr 1. doi: 10.1016/j.semarthrit.2017.03.024).
The findings indicate that CCP seronegativity does not improve the response to tocilizumab in this population derived from real-world patients at diverse clinical sites, the investigators noted.
This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Cappelli and her associates reported having no relevant financial disclosures.
Among adults with rheumatoid arthritis, serologic status regarding anti–cyclic citrullinated peptide (CCP) antibodies doesn’t appear to influence the effectiveness of tocilizumab therapy, according to a report published in Seminars in Arthritis and Rheumatism.
Compared with patients who have anti-CCP antibodies, those who don’t show differences in immune activation that may affect their response to various therapies. In particular, some experts have hypothesized that monoclonal antibodies such as tocilizumab that target the interleukin-6 receptor would be more effective in patients who are seronegative for anti-CCP antibodies than in those who are seropositive. Being able to predict patient response based on easily available biomarkers like CCP status would greatly assist treatment selection, said Laura C. Cappelli, MD, of the division of rheumatology at Johns Hopkins University, Baltimore, and her associates.
All but one of these eight measures of disease activity (the mHAQ) improved significantly with tocilizumab, regardless of patient anti-CCP status. In addition, the magnitude of change did not differ by anti-CCP status. These results persisted across several sensitivity analyses, Dr. Cappelli and her associates said (Semin Arthritis Rheum. 2017 Apr 1. doi: 10.1016/j.semarthrit.2017.03.024).
The findings indicate that CCP seronegativity does not improve the response to tocilizumab in this population derived from real-world patients at diverse clinical sites, the investigators noted.
This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Cappelli and her associates reported having no relevant financial disclosures.
FROM SEMINARS IN ARTHRITIS AND RHEUMATISM
Key clinical point: In adults with RA, serologic status regarding anti–cyclic citrullinated peptide antibodies doesn’t appear to influence the effectiveness of tocilizumab therapy.
Major finding: Seven of eight measures of disease activity improved significantly with tocilizumab, regardless of the patients’ CCP status.
Data source: A secondary analysis of data from a patient registry regarding 316 adults who initiated tocilizumab in a 6-year period.
Disclosures: This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Cappelli and her associates reported having no relevant financial disclosures.