ORLANDO – A novel small molecule agent improved hematologic parameters and was associated with significant reduction in sickling of red blood cells in patients with sickle cell disease.

The drug was shown to increase hemoglobin in both healthy volunteers and patients, reduce reticulocytosis, and improve biomarkers of hemolysis and inflammation.

In an interview, Dr. Claire Hemmaway of Queens Hospital in Romford, England, discusses early results from a phase I/II randomized, double-blind, placebo-controlled, parallel-group trial.

ORLANDO – A novel small molecule agent improved hematologic parameters and was associated with significant reduction in sickling of red blood cells in patients with sickle cell disease.

The drug was shown to increase hemoglobin in both healthy volunteers and patients, reduce reticulocytosis, and improve biomarkers of hemolysis and inflammation.

In an interview, Dr. Claire Hemmaway of Queens Hospital in Romford, England, discusses early results from a phase I/II randomized, double-blind, placebo-controlled, parallel-group trial.

ORLANDO – A novel small molecule agent improved hematologic parameters and was associated with significant reduction in sickling of red blood cells in patients with sickle cell disease.

The drug was shown to increase hemoglobin in both healthy volunteers and patients, reduce reticulocytosis, and improve biomarkers of hemolysis and inflammation.

In an interview, Dr. Claire Hemmaway of Queens Hospital in Romford, England, discusses early results from a phase I/II randomized, double-blind, placebo-controlled, parallel-group trial.

Chronic hemophilic arthropathy, a well-known complication of hemophilia, develops as a long-term consequence of recurrent joint bleeds resulting in synovial hypertrophy (chronic proliferative synovitis) and joint cartilage destruction. Hemophilic arthropathy mostly affects the knees, ankles, and elbows and causes chronic joint pain and functional impairment in relatively young patients who have not received adequate primary prophylactic replacement therapy with factor concentrates from early childhood.^1-3

In the late stages of hemophilic arthropathy of the knee, total knee arthroplasty (TKA) provides dramatic joint pain relief, improves knee functional status, and reduces rebleeding into the joint.^4-8 TKA performed on a patient with hemophilia was first reported in the mid-1970s.^9,10 In these cases, the surgical procedure itself is often complicated by severe fibrosis developing in the joint soft tissues, flexion joint contracture, and poor quality of the joint bone structures. Even though TKA significantly reduces joint pain in patients with chronic hemophilic arthropathy, some authors have achieved only modest functional outcomes and experienced a high rate of complications (infection, prosthetic loosening).^11-13 Data on TKA outcomes are still scarce, and most studies have enrolled a limited number of patients.

We retrospectively evaluated the outcomes of 88 primary TKAs performed on patients with severe hemophilia at a single institution. Clinical outcomes and complications were assessed with a special focus on prosthetic survival and infection.

Patients and Methods

Ninety-one primary TKAs were performed in 77 patients with severe hemophilia A and B (factor VIII [FVIII] and factor IX plasma concentration, <1% each) between January 1, 1999, and December 31, 2011, and the medical records of all these patients were thoroughly reviewed in 2013. The cases of 3 patients who died shortly after surgery were excluded from analysis. Thus, 88 TKAs and 74 patients (74 males) were finally available for evaluation. Fourteen patients underwent bilateral TKAs but none concurrently. The patients provided written informed consent for print and electronic publication of their outcomes.

We recorded demographic data, type and severity of hemophilia, human immunodeficiency virus (HIV) status, hepatitis C virus (HCV) status, and Knee Society Scale (KSS) scores.¹⁴ KSS scores include Knee score (pain, range of motion [ROM], stability) and Function score (walking, stairs), both of which range from 0 (normal knee) to 100 (most affected knee). Prosthetic infection was classified (Segawa and colleagues¹⁵) as early or late, depending on timing of symptom onset (4 weeks after replacement surgery was the threshold used).

Patients received an intravenous bolus infusion of the deficient factor concentrate followed by continuous infusion to reach a plasma factor level of 100% just before surgery and during the first 7 postoperative days and 50% over the next 7 days (Table 1). Patients with a circulating inhibitor (3 overall) received bypassing agents FEIBA (FVIII inhibitor bypassing agent) or rFVIIa (recombinant factor VII activated) (Table 2). Patients were not given any antifibrinolytic treatment or thromboprophylaxis.

Surgery was performed in a standard surgical room. Patients were placed on the operating table in decubitus supinus position. A parapatellar medial incision was made on a bloodless surgical field (achieved with tourniquet ischemia). The prosthesis model used was always the cemented (gentamicin bone cement) NexGen (Zimmer). Patellar resurfacing was done in all cases (Figures 1A–1D). All TKAs were performed by Dr. Rodríguez-Merchán. Intravenous antibiotic prophylaxis was administered at anesthetic induction and during the first 48 hours after surgery (3 further doses). Active exercises were started on postoperative day 1. Joint load aided with 2 crutches was allowed starting on postoperative day 2.

Mean patient age was 38.2 years (range, 24-73 years). Of the 74 patients, 55 had a diagnosis of severe hemophilia A, and 19 had a diagnosis of severe hemophilia B. During the follow-up period, 23 patients died (mean time, 6.4 years; range, 4-9 years). Causes of death were acquired immune deficiency syndrome (AIDS), liver cirrhosis, and intracranial bleeding. Mean follow-up for the full series of patients was 8 years (range, 1-13 years).

Descriptive statistical analysis was performed with SPSS Windows Version 18.0. Prosthetic failure was regarded as implant removal for any reason. Student t test was used to compare continuous variables, and either χ² test or Fisher exact test was used to compare categorical variables. P < .05 (2-sided) was considered significant.

Results

Prosthetic survival rates with implant removal for any reason regarded as final endpoint was 92%. Causes of failure were prosthetic infection (6 cases, 6.8%) and loosening (2 cases, 2.2%). Of the 6 prosthetic infections, 5 were regarded as late and 1 as early. Late infections were successfully sorted by performing 2-stage revision TKA with the Constrained Condylar Knee (Zimmer). Acute infections were managed by open joint débridement and polyethylene exchange. Both cases of aseptic loosening of the TKA were successfully managed with 1-stage revision TKA using the same implant model (Figures 2A–2D).

Mean KSS Knee score improved from 79 before surgery to 36 after surgery, and mean KSS Function score improved from 63 to 33. KSS Pain score, which is included in the Knee score, 0 (no pain) to 50 (most severe pain), improved from 47 to 8. Patients receiving inhibitors and patients who were HIV- or HCV-positive did not have poorer outcomes relative to those of patients not receiving inhibitors and patients who were HIV- or HCV-negative. Patients with liver cirrhosis had a lower prosthetic survival rate and lower Knee scores.

Discussion

The prosthetic survival rate found in this study compares well with other reported rates for patients with hemophilia and other bleeding disorders. However, evidence regarding long-term prosthesis survival in TKAs performed for patients with hemophilia is limited. Table 3 summarizes the main reported series of patients with hemophilia with 10-year prosthetic survival rates, number of TKAs performed, and mean follow-up period; in all these series, implant removal for any reason was regarded as the final endpoint.^5-8,16,17 Mean follow-up in our study was 8 years. Clinical outcomes of TKA in patients with severe hemophilia and related disorders are expected to be inferior to those achieved in patients without a bleeding condition. The overall 10-year prosthetic survival rate for cemented TKA implants, as reported by the Norwegian Arthroplasty Register, was on the order of 93%.¹⁸ Mean age of our patients at time of surgery was only 38.2 years. TKAs performed in younger patients without a bleeding disorder have been associated with shorter implant survival times relative to those of elderly patients.¹⁹ Thus, Diduch and colleagues²⁰ reported a prosthetic survival rate of 87% at 18 years in 108 TKAs performed on patients under age 55 years. Lonner and colleagues²¹ reported a better implant survival rate (90% at 8 years) in a series of patients under age 40 years (32 TKAs). In a study by Duffy and colleagues,²² the implant survival rate was 85% at 15 years in patients under age 55 years (74 TKAs). The results from our retrospective case assessment are quite similar to the overall prosthetic survival rates reported for TKAs performed on patients without hemophilia.

Rates of periprosthetic infection after primary TKA in patients with hemophilia and other bleeding conditions are much higher (up to 11%), with a mean infection rate of 6.2% (range, 1% to 11%), consistent with the rate found in our series of patients (6.8%)^{7,16,17,23,24} (Table 4). This rate is much higher than that reported after primary TKA in patients without hemophilia but is similar to some rates reported for patients with hemophilia. In our experience, most periprosthetic infections (5/6) were sorted as late.

Late infection is a major concern after TKA in patients with hemophilia, and various factors have been hypothesized as contributing to the high prevalence. An important factor is the high rate of HIV-positive patients among patients with hemophilia—which acts as a strong predisposing factor because of the often low CD4 counts and associated immune deficiency,²⁵ but different reports have provided conflicting results in this respect.^5,6,12 We found no relationship between HIV status and risk for periprosthetic infection, but conclusions are limited by the low number of HIV-positive patients in our series (14/74, 18.9%). Our patients’ late periprosthetic infections were diagnosed several years after TKA, suggesting hematogenous spread of infection. Most of these patients either were on regular prophylactic factor infusions or were being treated on demand, which might entail a risk for contamination of infusions by skin bacteria from the puncture site. Therefore, having an aseptic technique for administering coagulation factor concentrates is of paramount importance for patients with hemophilia and a knee implant.

Another important complication of TKA surgery is aseptic loosening of the prosthesis. Aseptic loosening occurred in 2.2% of our patients, but higher rates have been reported elsewhere.^11,26 Rates of this complication increase over follow-up, and some authors have linked this complication to TKA polyethylene wear.²⁷ Development of a reactive and destructive bone–cement interface and microhemorrhages into such interface might be implicated in the higher rate of loosening observed among patients with hemophilia.²⁸

In the present study, preoperative and postoperative functional outcomes differed significantly. A modest postoperative total ROM of 69º to 79º has been reported by several authors.^5,6 Postoperative ROM may vary—may be slightly increased, remain unchanged, or may even be reduced.^4,23,26 Even though little improvement in total ROM is achieved after TKA, many authors have reported reduced flexion contracture and hence an easier gait. However, along with functional improvement, dramatic pain relief after TKA is perhaps the most remarkable aspect, and it has a strong effect on patient satisfaction after surgery.^5,7,8,18,23

Our study had 2 main limitations. First, it was a retrospective case series evaluation with the usual issues of potential inaccuracy of medical records and information bias. Second, the study did not include a control group.

Conclusion

The primary TKAs performed in our patients with hemophilia have had a good prosthetic survival rate. Even though such a result is slightly inferior to results in patients without hemophilia, our prosthetic survival rate is not significantly different from the rates reported in other, younger patient subsets. Late periprosthetic infections are a major concern, and taking precautions to avoid hematogenous spread of infections during factor concentrate infusions is strongly encouraged.

Chronic hemophilic arthropathy, a well-known complication of hemophilia, develops as a long-term consequence of recurrent joint bleeds resulting in synovial hypertrophy (chronic proliferative synovitis) and joint cartilage destruction. Hemophilic arthropathy mostly affects the knees, ankles, and elbows and causes chronic joint pain and functional impairment in relatively young patients who have not received adequate primary prophylactic replacement therapy with factor concentrates from early childhood.^1-3

In the late stages of hemophilic arthropathy of the knee, total knee arthroplasty (TKA) provides dramatic joint pain relief, improves knee functional status, and reduces rebleeding into the joint.^4-8 TKA performed on a patient with hemophilia was first reported in the mid-1970s.^9,10 In these cases, the surgical procedure itself is often complicated by severe fibrosis developing in the joint soft tissues, flexion joint contracture, and poor quality of the joint bone structures. Even though TKA significantly reduces joint pain in patients with chronic hemophilic arthropathy, some authors have achieved only modest functional outcomes and experienced a high rate of complications (infection, prosthetic loosening).^11-13 Data on TKA outcomes are still scarce, and most studies have enrolled a limited number of patients.

We retrospectively evaluated the outcomes of 88 primary TKAs performed on patients with severe hemophilia at a single institution. Clinical outcomes and complications were assessed with a special focus on prosthetic survival and infection.

Patients and Methods

Ninety-one primary TKAs were performed in 77 patients with severe hemophilia A and B (factor VIII [FVIII] and factor IX plasma concentration, <1% each) between January 1, 1999, and December 31, 2011, and the medical records of all these patients were thoroughly reviewed in 2013. The cases of 3 patients who died shortly after surgery were excluded from analysis. Thus, 88 TKAs and 74 patients (74 males) were finally available for evaluation. Fourteen patients underwent bilateral TKAs but none concurrently. The patients provided written informed consent for print and electronic publication of their outcomes.

We recorded demographic data, type and severity of hemophilia, human immunodeficiency virus (HIV) status, hepatitis C virus (HCV) status, and Knee Society Scale (KSS) scores.¹⁴ KSS scores include Knee score (pain, range of motion [ROM], stability) and Function score (walking, stairs), both of which range from 0 (normal knee) to 100 (most affected knee). Prosthetic infection was classified (Segawa and colleagues¹⁵) as early or late, depending on timing of symptom onset (4 weeks after replacement surgery was the threshold used).

Patients received an intravenous bolus infusion of the deficient factor concentrate followed by continuous infusion to reach a plasma factor level of 100% just before surgery and during the first 7 postoperative days and 50% over the next 7 days (Table 1). Patients with a circulating inhibitor (3 overall) received bypassing agents FEIBA (FVIII inhibitor bypassing agent) or rFVIIa (recombinant factor VII activated) (Table 2). Patients were not given any antifibrinolytic treatment or thromboprophylaxis.

Surgery was performed in a standard surgical room. Patients were placed on the operating table in decubitus supinus position. A parapatellar medial incision was made on a bloodless surgical field (achieved with tourniquet ischemia). The prosthesis model used was always the cemented (gentamicin bone cement) NexGen (Zimmer). Patellar resurfacing was done in all cases (Figures 1A–1D). All TKAs were performed by Dr. Rodríguez-Merchán. Intravenous antibiotic prophylaxis was administered at anesthetic induction and during the first 48 hours after surgery (3 further doses). Active exercises were started on postoperative day 1. Joint load aided with 2 crutches was allowed starting on postoperative day 2.

Mean patient age was 38.2 years (range, 24-73 years). Of the 74 patients, 55 had a diagnosis of severe hemophilia A, and 19 had a diagnosis of severe hemophilia B. During the follow-up period, 23 patients died (mean time, 6.4 years; range, 4-9 years). Causes of death were acquired immune deficiency syndrome (AIDS), liver cirrhosis, and intracranial bleeding. Mean follow-up for the full series of patients was 8 years (range, 1-13 years).

Descriptive statistical analysis was performed with SPSS Windows Version 18.0. Prosthetic failure was regarded as implant removal for any reason. Student t test was used to compare continuous variables, and either χ² test or Fisher exact test was used to compare categorical variables. P < .05 (2-sided) was considered significant.

Results

Prosthetic survival rates with implant removal for any reason regarded as final endpoint was 92%. Causes of failure were prosthetic infection (6 cases, 6.8%) and loosening (2 cases, 2.2%). Of the 6 prosthetic infections, 5 were regarded as late and 1 as early. Late infections were successfully sorted by performing 2-stage revision TKA with the Constrained Condylar Knee (Zimmer). Acute infections were managed by open joint débridement and polyethylene exchange. Both cases of aseptic loosening of the TKA were successfully managed with 1-stage revision TKA using the same implant model (Figures 2A–2D).

Mean KSS Knee score improved from 79 before surgery to 36 after surgery, and mean KSS Function score improved from 63 to 33. KSS Pain score, which is included in the Knee score, 0 (no pain) to 50 (most severe pain), improved from 47 to 8. Patients receiving inhibitors and patients who were HIV- or HCV-positive did not have poorer outcomes relative to those of patients not receiving inhibitors and patients who were HIV- or HCV-negative. Patients with liver cirrhosis had a lower prosthetic survival rate and lower Knee scores.

Discussion

The prosthetic survival rate found in this study compares well with other reported rates for patients with hemophilia and other bleeding disorders. However, evidence regarding long-term prosthesis survival in TKAs performed for patients with hemophilia is limited. Table 3 summarizes the main reported series of patients with hemophilia with 10-year prosthetic survival rates, number of TKAs performed, and mean follow-up period; in all these series, implant removal for any reason was regarded as the final endpoint.^5-8,16,17 Mean follow-up in our study was 8 years. Clinical outcomes of TKA in patients with severe hemophilia and related disorders are expected to be inferior to those achieved in patients without a bleeding condition. The overall 10-year prosthetic survival rate for cemented TKA implants, as reported by the Norwegian Arthroplasty Register, was on the order of 93%.¹⁸ Mean age of our patients at time of surgery was only 38.2 years. TKAs performed in younger patients without a bleeding disorder have been associated with shorter implant survival times relative to those of elderly patients.¹⁹ Thus, Diduch and colleagues²⁰ reported a prosthetic survival rate of 87% at 18 years in 108 TKAs performed on patients under age 55 years. Lonner and colleagues²¹ reported a better implant survival rate (90% at 8 years) in a series of patients under age 40 years (32 TKAs). In a study by Duffy and colleagues,²² the implant survival rate was 85% at 15 years in patients under age 55 years (74 TKAs). The results from our retrospective case assessment are quite similar to the overall prosthetic survival rates reported for TKAs performed on patients without hemophilia.

Rates of periprosthetic infection after primary TKA in patients with hemophilia and other bleeding conditions are much higher (up to 11%), with a mean infection rate of 6.2% (range, 1% to 11%), consistent with the rate found in our series of patients (6.8%)^{7,16,17,23,24} (Table 4). This rate is much higher than that reported after primary TKA in patients without hemophilia but is similar to some rates reported for patients with hemophilia. In our experience, most periprosthetic infections (5/6) were sorted as late.

Late infection is a major concern after TKA in patients with hemophilia, and various factors have been hypothesized as contributing to the high prevalence. An important factor is the high rate of HIV-positive patients among patients with hemophilia—which acts as a strong predisposing factor because of the often low CD4 counts and associated immune deficiency,²⁵ but different reports have provided conflicting results in this respect.^5,6,12 We found no relationship between HIV status and risk for periprosthetic infection, but conclusions are limited by the low number of HIV-positive patients in our series (14/74, 18.9%). Our patients’ late periprosthetic infections were diagnosed several years after TKA, suggesting hematogenous spread of infection. Most of these patients either were on regular prophylactic factor infusions or were being treated on demand, which might entail a risk for contamination of infusions by skin bacteria from the puncture site. Therefore, having an aseptic technique for administering coagulation factor concentrates is of paramount importance for patients with hemophilia and a knee implant.

Another important complication of TKA surgery is aseptic loosening of the prosthesis. Aseptic loosening occurred in 2.2% of our patients, but higher rates have been reported elsewhere.^11,26 Rates of this complication increase over follow-up, and some authors have linked this complication to TKA polyethylene wear.²⁷ Development of a reactive and destructive bone–cement interface and microhemorrhages into such interface might be implicated in the higher rate of loosening observed among patients with hemophilia.²⁸

In the present study, preoperative and postoperative functional outcomes differed significantly. A modest postoperative total ROM of 69º to 79º has been reported by several authors.^5,6 Postoperative ROM may vary—may be slightly increased, remain unchanged, or may even be reduced.^4,23,26 Even though little improvement in total ROM is achieved after TKA, many authors have reported reduced flexion contracture and hence an easier gait. However, along with functional improvement, dramatic pain relief after TKA is perhaps the most remarkable aspect, and it has a strong effect on patient satisfaction after surgery.^5,7,8,18,23

Our study had 2 main limitations. First, it was a retrospective case series evaluation with the usual issues of potential inaccuracy of medical records and information bias. Second, the study did not include a control group.

Conclusion

The primary TKAs performed in our patients with hemophilia have had a good prosthetic survival rate. Even though such a result is slightly inferior to results in patients without hemophilia, our prosthetic survival rate is not significantly different from the rates reported in other, younger patient subsets. Late periprosthetic infections are a major concern, and taking precautions to avoid hematogenous spread of infections during factor concentrate infusions is strongly encouraged.

Chronic hemophilic arthropathy, a well-known complication of hemophilia, develops as a long-term consequence of recurrent joint bleeds resulting in synovial hypertrophy (chronic proliferative synovitis) and joint cartilage destruction. Hemophilic arthropathy mostly affects the knees, ankles, and elbows and causes chronic joint pain and functional impairment in relatively young patients who have not received adequate primary prophylactic replacement therapy with factor concentrates from early childhood.^1-3

In the late stages of hemophilic arthropathy of the knee, total knee arthroplasty (TKA) provides dramatic joint pain relief, improves knee functional status, and reduces rebleeding into the joint.^4-8 TKA performed on a patient with hemophilia was first reported in the mid-1970s.^9,10 In these cases, the surgical procedure itself is often complicated by severe fibrosis developing in the joint soft tissues, flexion joint contracture, and poor quality of the joint bone structures. Even though TKA significantly reduces joint pain in patients with chronic hemophilic arthropathy, some authors have achieved only modest functional outcomes and experienced a high rate of complications (infection, prosthetic loosening).^11-13 Data on TKA outcomes are still scarce, and most studies have enrolled a limited number of patients.

We retrospectively evaluated the outcomes of 88 primary TKAs performed on patients with severe hemophilia at a single institution. Clinical outcomes and complications were assessed with a special focus on prosthetic survival and infection.

Patients and Methods

Ninety-one primary TKAs were performed in 77 patients with severe hemophilia A and B (factor VIII [FVIII] and factor IX plasma concentration, <1% each) between January 1, 1999, and December 31, 2011, and the medical records of all these patients were thoroughly reviewed in 2013. The cases of 3 patients who died shortly after surgery were excluded from analysis. Thus, 88 TKAs and 74 patients (74 males) were finally available for evaluation. Fourteen patients underwent bilateral TKAs but none concurrently. The patients provided written informed consent for print and electronic publication of their outcomes.

We recorded demographic data, type and severity of hemophilia, human immunodeficiency virus (HIV) status, hepatitis C virus (HCV) status, and Knee Society Scale (KSS) scores.¹⁴ KSS scores include Knee score (pain, range of motion [ROM], stability) and Function score (walking, stairs), both of which range from 0 (normal knee) to 100 (most affected knee). Prosthetic infection was classified (Segawa and colleagues¹⁵) as early or late, depending on timing of symptom onset (4 weeks after replacement surgery was the threshold used).

Patients received an intravenous bolus infusion of the deficient factor concentrate followed by continuous infusion to reach a plasma factor level of 100% just before surgery and during the first 7 postoperative days and 50% over the next 7 days (Table 1). Patients with a circulating inhibitor (3 overall) received bypassing agents FEIBA (FVIII inhibitor bypassing agent) or rFVIIa (recombinant factor VII activated) (Table 2). Patients were not given any antifibrinolytic treatment or thromboprophylaxis.

Surgery was performed in a standard surgical room. Patients were placed on the operating table in decubitus supinus position. A parapatellar medial incision was made on a bloodless surgical field (achieved with tourniquet ischemia). The prosthesis model used was always the cemented (gentamicin bone cement) NexGen (Zimmer). Patellar resurfacing was done in all cases (Figures 1A–1D). All TKAs were performed by Dr. Rodríguez-Merchán. Intravenous antibiotic prophylaxis was administered at anesthetic induction and during the first 48 hours after surgery (3 further doses). Active exercises were started on postoperative day 1. Joint load aided with 2 crutches was allowed starting on postoperative day 2.

Mean patient age was 38.2 years (range, 24-73 years). Of the 74 patients, 55 had a diagnosis of severe hemophilia A, and 19 had a diagnosis of severe hemophilia B. During the follow-up period, 23 patients died (mean time, 6.4 years; range, 4-9 years). Causes of death were acquired immune deficiency syndrome (AIDS), liver cirrhosis, and intracranial bleeding. Mean follow-up for the full series of patients was 8 years (range, 1-13 years).

Descriptive statistical analysis was performed with SPSS Windows Version 18.0. Prosthetic failure was regarded as implant removal for any reason. Student t test was used to compare continuous variables, and either χ² test or Fisher exact test was used to compare categorical variables. P < .05 (2-sided) was considered significant.

Results

Prosthetic survival rates with implant removal for any reason regarded as final endpoint was 92%. Causes of failure were prosthetic infection (6 cases, 6.8%) and loosening (2 cases, 2.2%). Of the 6 prosthetic infections, 5 were regarded as late and 1 as early. Late infections were successfully sorted by performing 2-stage revision TKA with the Constrained Condylar Knee (Zimmer). Acute infections were managed by open joint débridement and polyethylene exchange. Both cases of aseptic loosening of the TKA were successfully managed with 1-stage revision TKA using the same implant model (Figures 2A–2D).

Mean KSS Knee score improved from 79 before surgery to 36 after surgery, and mean KSS Function score improved from 63 to 33. KSS Pain score, which is included in the Knee score, 0 (no pain) to 50 (most severe pain), improved from 47 to 8. Patients receiving inhibitors and patients who were HIV- or HCV-positive did not have poorer outcomes relative to those of patients not receiving inhibitors and patients who were HIV- or HCV-negative. Patients with liver cirrhosis had a lower prosthetic survival rate and lower Knee scores.

Discussion

The prosthetic survival rate found in this study compares well with other reported rates for patients with hemophilia and other bleeding disorders. However, evidence regarding long-term prosthesis survival in TKAs performed for patients with hemophilia is limited. Table 3 summarizes the main reported series of patients with hemophilia with 10-year prosthetic survival rates, number of TKAs performed, and mean follow-up period; in all these series, implant removal for any reason was regarded as the final endpoint.^5-8,16,17 Mean follow-up in our study was 8 years. Clinical outcomes of TKA in patients with severe hemophilia and related disorders are expected to be inferior to those achieved in patients without a bleeding condition. The overall 10-year prosthetic survival rate for cemented TKA implants, as reported by the Norwegian Arthroplasty Register, was on the order of 93%.¹⁸ Mean age of our patients at time of surgery was only 38.2 years. TKAs performed in younger patients without a bleeding disorder have been associated with shorter implant survival times relative to those of elderly patients.¹⁹ Thus, Diduch and colleagues²⁰ reported a prosthetic survival rate of 87% at 18 years in 108 TKAs performed on patients under age 55 years. Lonner and colleagues²¹ reported a better implant survival rate (90% at 8 years) in a series of patients under age 40 years (32 TKAs). In a study by Duffy and colleagues,²² the implant survival rate was 85% at 15 years in patients under age 55 years (74 TKAs). The results from our retrospective case assessment are quite similar to the overall prosthetic survival rates reported for TKAs performed on patients without hemophilia.

Rates of periprosthetic infection after primary TKA in patients with hemophilia and other bleeding conditions are much higher (up to 11%), with a mean infection rate of 6.2% (range, 1% to 11%), consistent with the rate found in our series of patients (6.8%)^{7,16,17,23,24} (Table 4). This rate is much higher than that reported after primary TKA in patients without hemophilia but is similar to some rates reported for patients with hemophilia. In our experience, most periprosthetic infections (5/6) were sorted as late.

Late infection is a major concern after TKA in patients with hemophilia, and various factors have been hypothesized as contributing to the high prevalence. An important factor is the high rate of HIV-positive patients among patients with hemophilia—which acts as a strong predisposing factor because of the often low CD4 counts and associated immune deficiency,²⁵ but different reports have provided conflicting results in this respect.^5,6,12 We found no relationship between HIV status and risk for periprosthetic infection, but conclusions are limited by the low number of HIV-positive patients in our series (14/74, 18.9%). Our patients’ late periprosthetic infections were diagnosed several years after TKA, suggesting hematogenous spread of infection. Most of these patients either were on regular prophylactic factor infusions or were being treated on demand, which might entail a risk for contamination of infusions by skin bacteria from the puncture site. Therefore, having an aseptic technique for administering coagulation factor concentrates is of paramount importance for patients with hemophilia and a knee implant.

Another important complication of TKA surgery is aseptic loosening of the prosthesis. Aseptic loosening occurred in 2.2% of our patients, but higher rates have been reported elsewhere.^11,26 Rates of this complication increase over follow-up, and some authors have linked this complication to TKA polyethylene wear.²⁷ Development of a reactive and destructive bone–cement interface and microhemorrhages into such interface might be implicated in the higher rate of loosening observed among patients with hemophilia.²⁸

In the present study, preoperative and postoperative functional outcomes differed significantly. A modest postoperative total ROM of 69º to 79º has been reported by several authors.^5,6 Postoperative ROM may vary—may be slightly increased, remain unchanged, or may even be reduced.^4,23,26 Even though little improvement in total ROM is achieved after TKA, many authors have reported reduced flexion contracture and hence an easier gait. However, along with functional improvement, dramatic pain relief after TKA is perhaps the most remarkable aspect, and it has a strong effect on patient satisfaction after surgery.^5,7,8,18,23

Our study had 2 main limitations. First, it was a retrospective case series evaluation with the usual issues of potential inaccuracy of medical records and information bias. Second, the study did not include a control group.

Conclusion

The primary TKAs performed in our patients with hemophilia have had a good prosthetic survival rate. Even though such a result is slightly inferior to results in patients without hemophilia, our prosthetic survival rate is not significantly different from the rates reported in other, younger patient subsets. Late periprosthetic infections are a major concern, and taking precautions to avoid hematogenous spread of infections during factor concentrate infusions is strongly encouraged.

Many organizations and work groups have issued recommendations regarding which patients should undergo bone densitometry. In 2004, the US Surgeon General recommended bone mineral density (BMD) evaluation for all women over age 65 years and for women and men with fragility fractures.¹ The Centers for Medicare & Medicaid Services recommended BMD assessment for estrogen-deficient patients, for patients with vertebral abnormalities or hyperparathyroidism, and for patients receiving either steroid therapy or osteoporosis medications approved by the US Food and Drug Administration.² The US Preventive Services Task Force and the National Osteoporosis Foundation each recommended screening for all women age 65 years or older and for postmenopausal women (age, 60-64 years) at high risk.^3,4 The International Society for Clinical Densitometry (ISCD) recommended screening for all women age 65 years or older, all men age 70 years or older, and high-risk women under age 65 years.⁵

These current recommendations for BMD evaluation focus on women over age 65 years. More recent studies of postmenopausal women with distal radius fractures (DRFs) have found that both younger women (age, 45-65 years) and older women (age, ≥65 years) can have lower BMD and increased risk for hip and spine fracture.^6,7 The authors of those studies recommended that all postmenopausal women with DRFs be evaluated for low BMD and that fracture prevention treatment be initiated. Earnshaw and colleagues⁸ and Oyen and colleagues⁹ found that men and women (age, ≥50 years) with DRFs had low BMD and elevated 10-year fracture rates. They concluded that BMD should be evaluated and treated in all DRF patients age 50 years or older. Other studies have shown low BMD in the contralateral distal radius of patients of all ages who presented with Colles fractures.^10,11 These 2 studies did not measure spine or hip BMD.

The literature on BMD of younger women with DRFs is limited, relying solely on data collected for the contralateral distal radius.^10,11 The ISCD recommended measuring both hip and spine BMD in premenopausal women. They also stated that z scores, not t scores, should be used for premenopausal women.⁵ The causes of low BMD in women over age 55 years are primarily nutritional deficiency and normal aging.¹ In younger females, low BMD results from secondary causes, such as diet, medications, medical conditions, and endocrine disorders. When the secondary cause of low BMD can be identified and treated, osteoporosis can be stopped and even reversed in younger patients.^12-14 Low BMD is more amenable to treatment in younger patients than in postmenopausal women. Younger patients with low BMD carry a higher lifetime fracture risk because they have more years of life with low BMD; therefore, early identification and treatment have a more significant impact on fracture prevention in these patients.

In the present study, we determined the prevalence of osteoporosis and osteopenia in younger women (age, 35-50 years) with DRFs and compared BMD measurements from younger women (age, 35-50 years) and older women (age, >50 years) with DRFs. The main goal was to determine which patients should be referred for bone densitometry and subsequent treatment.

Patients and Methods

This study received institutional review board approval. During a 5-year period (January 2005–August 2010), we prospectively collected dual-energy x-ray absorptiometry (DXA) scans for 128 women (age, >35 years) who presented with DRFs to our level I trauma center. Age ranged from 35 to 86 years. Data on mechanism of injury, treatment, and body mass index (BMI) were collected. The 128 patients were divided into a younger group (47 women; age range, 35-50 years; mean age, 44 years) and an older group (81 women; age, ≥51 years; mean age, 61 years). Mean BMI was 29.3 in the younger group and 28.8 in the older group (P = .88) (Table).

BMD was measured with a General Electric Lunar Prodigy Advance scanner that was tested annually for accuracy and precision. BMD of hips and lumbar spines was measured with a 76-Kv x-ray source. All DXA scans were analyzed by the same physician. BMD was omitted in cases of patients with a history of lumbar spine or hip fracture.

Two-sample Student t test was used to compare the 2 groups’ data. When multiple groups were being compared, analysis of variance was used. Spearman rank-order test was used to calculate a correlation coefficient for evaluation of the relationships between age and BMD.

Results

Mean lumbar spine (L1–L4) BMD was 1.12 in the younger group and 1.063 in the older group (P = .02); t scores were –0.63 and –1.132, respectively (P = .02); and mean z scores were –0.69 and –0.61, respectively (P = .81). Mean femoral neck BMD was 0.91 in the younger group and 0.80 in the older group (P < .05); t scores were –0.87 and –1.65, respectively (P < .01), and mean femoral neck z scores were –0.69 and –0.67, respectively (P = .92).

To further analyze BMD of specific age groups, we divided patients by decade: 35-39, 40-49, 50-59, 60-69, 70-79, 80-89 years. Among all 6 decades, there were no statistically significant differences between hip z scores (P = .83) (Figure 1). Spearman rank-order correlation test showed a moderate inverse correlation between age and femoral neck BMD (R = –0.42) and t score (R = –0.43). There was a weak correlation between increasing age and decreasing spine BMD, t score, and z score (Rs = –0.27, –0.31, 0.03). There was no correlation between age and femoral neck z score (R = –0.04).

According to the WHO classification system, 11 (23%) of the 47 women in the younger group were osteopenic, and 8 (17%) were osteoporotic, based on spine BMD. Hip BMD values indicated that 20 patients (43%) were osteopenic, and 3 (6%) were osteoporotic. One patient in the younger group had a hip z score of less than –2, and 14 patients (39%) had a hip z score between –2 and –1. Six patients (18%) had a spine z score of less than –2, and 6 patients (18%) had a spine z score between –2 and –1. Of the 81 older patients, 22 (27%) were osteopenic, and 21 (26%) were osteoporotic, according to spine measurements. The femoral neck data indicated that 39 (48%) of the older patients were osteopenic, and 22 (27%) were osteoporotic.

In both groups, mechanisms of injury were identified. Of the 47 younger patients, 26 fell from standing, 7 fell from a height of more than 6 feet, and 14 were injured in motor vehicle collisions (MVCs). Of the 81 older patients, 2 sustained a direct blow, 64 fell from standing, 4 fell from a height of more than 6 feet, and 11 were injured in MVCs. The differences in z scores based on mechanism of injury were not statistically significant (P = .22) (Figure 2).

Discussion

Several studies have shown that older women with DRFs have low BMD in the spine and femoral neck.^8,9 These studies focused on older women who sustained low-energy fractures caused by a fall from a standing height. Studies of younger women with DRFs focused on BMD of the contralateral distal radius, not the spine or femoral neck.^10,11 Those study groups also had low BMD. Findings from a multitude of studies have established that patients who are older than 50 years when they sustain distal radius fragility fractures should be referred for bone densitometry studies, and there is increasing evidence that younger patients with fragility fractures should undergo this evaluation as well.

The present study was designed to expand the range of patients and mechanisms of injury. Women in this study were 35 years or older. In addition to collecting data from patients injured in a fall from standing, we examined the medical records of women injured in MVCs, in falls from heights of more than 6 feet, and from direct trauma to the wrist. We measured the BMD of the spine and femoral neck and of the contralateral distal radius.

For this discussion, several key points should be made about BMD evaluation in younger versus older women. Most organizations caution against using spine BMD in older women. The ISCD, however, recommended measuring both hip and spine BMD; whereas BMD can be falsely elevated by spine osteoarthritis in older patients, spine BMD measurements are accurate in younger patients not affected by osteoarthritis. The ISCD also stipulated that z scores should be used in examining BMD in younger patients. The z score is a value of how many standard deviations BMD differs from a matched population of the same age, sex, ethnicity, and weight. The t score, which is useful in evaluating older patients, compares a patient’s BMD with that of an average 30-year-old.¹²

According to the WHO classification system (intended for older women), osteopenia is indicated by a t score between –1.0 and –2.5, and osteoporosis is indicated by a t score of less than –2.5. In the present study, about 43% of the younger patients (age, 35-50 years) with DRFs were osteopenic, and 6% of these patients were osteoporotic. In concert with previous studies,⁹ 48% of our older women (age, >50 years) with DRFs were osteopenic, and 27% were osteoporotic. The difference in mean spinal z scores between the younger and older groups was not statistically significant (P = .81).

As mentioned, when examining BMD of younger patients, it is imperative to use spine z scores. About 18% of our younger patients had a z score of less than –2, and 18% had a z score between –2 and –1. In our comparison of patients from 5 different age decades (range, 35-79 years), there was no statistically significant difference in z scores (P = .83). In addition, there was no correlation between increasing age and decreasing z score (R = –0.04).

Secondary causes of osteoporosis have been documented in 30% of premenopausal women and 55% of men with vertebral fractures.^13-15 Primary osteoporosis results from the normal aging process; secondary osteoporosis results from reversible causes, including medications, gastrointestinal disorders, renal disease, endocrine disorders, and sedentary lifestyle.^15,16 When a secondary cause of osteoporosis is identified, treatment can be initiated to increase BMD. As younger patients can reverse bone loss and even increase BMD, it is important to identify reversible causes of osteopenia and osteoporosis in this age group. It is well documented that both younger and older patients with DRFs are at increased risk for subsequent fractures.⁶ Preventing further bone loss at a younger age may drastically decrease lifetime fracture risk.^12,17

Most previous studies of BMD in women were limited to patients with DRFs caused by a low-energy mechanism or by a fall from standing. Current recommendations for BMD testing focus on postmenopausal women who have sustained a fragility or low-energy DRF. When an osteoporotic or osteopenic patient’s distal radius is subjected to a high-energy force, a fracture is likely. Therefore, we expanded our study to include high-energy mechanisms of injury. Our analysis of BMD in patients with DRFs sustained in MVCs indicated that 12% of this group were osteoporotic, and 44% were osteopenic. Forty-three percent of our younger patients with a DRF fractured in a MVC were osteopenic, and 6% were osteoporotic. Among 4 mechanisms of injury for DRFs, there was no statistically significant difference in z scores (P = .22) (Figure 2). This provides evidence that a significant portion of patients with DRFs from both high- and low-energy mechanisms are osteoporotic or osteopenic. Patients with DRFs sustained in MVCs or in falls from heights of more than 6 feet should be referred for BMD evaluation.         

Conclusion

A significant proportion of younger patients with DRFs are osteopenic or osteoporotic (43% and 6%, respectively), and their z scores are comparable to those of older patients with DRFs. There was no statistically significant difference in BMD z scores between younger and older patients and no difference in mechanisms of injury. This is evidence that younger patients with DRFs caused by a high- or low-energy mechanism of injury should undergo both DXA scan and BMD evaluation. If osteoporosis or osteopenia can be diagnosed at an earlier age, and if these patients can be properly treated, subsequent fractures could be prevented. The present study provides evidence supporting a simplification of the current recommendations for BMD evaluation: All women with DRFs should undergo bone densitometry.

Many organizations and work groups have issued recommendations regarding which patients should undergo bone densitometry. In 2004, the US Surgeon General recommended bone mineral density (BMD) evaluation for all women over age 65 years and for women and men with fragility fractures.¹ The Centers for Medicare & Medicaid Services recommended BMD assessment for estrogen-deficient patients, for patients with vertebral abnormalities or hyperparathyroidism, and for patients receiving either steroid therapy or osteoporosis medications approved by the US Food and Drug Administration.² The US Preventive Services Task Force and the National Osteoporosis Foundation each recommended screening for all women age 65 years or older and for postmenopausal women (age, 60-64 years) at high risk.^3,4 The International Society for Clinical Densitometry (ISCD) recommended screening for all women age 65 years or older, all men age 70 years or older, and high-risk women under age 65 years.⁵

These current recommendations for BMD evaluation focus on women over age 65 years. More recent studies of postmenopausal women with distal radius fractures (DRFs) have found that both younger women (age, 45-65 years) and older women (age, ≥65 years) can have lower BMD and increased risk for hip and spine fracture.^6,7 The authors of those studies recommended that all postmenopausal women with DRFs be evaluated for low BMD and that fracture prevention treatment be initiated. Earnshaw and colleagues⁸ and Oyen and colleagues⁹ found that men and women (age, ≥50 years) with DRFs had low BMD and elevated 10-year fracture rates. They concluded that BMD should be evaluated and treated in all DRF patients age 50 years or older. Other studies have shown low BMD in the contralateral distal radius of patients of all ages who presented with Colles fractures.^10,11 These 2 studies did not measure spine or hip BMD.

The literature on BMD of younger women with DRFs is limited, relying solely on data collected for the contralateral distal radius.^10,11 The ISCD recommended measuring both hip and spine BMD in premenopausal women. They also stated that z scores, not t scores, should be used for premenopausal women.⁵ The causes of low BMD in women over age 55 years are primarily nutritional deficiency and normal aging.¹ In younger females, low BMD results from secondary causes, such as diet, medications, medical conditions, and endocrine disorders. When the secondary cause of low BMD can be identified and treated, osteoporosis can be stopped and even reversed in younger patients.^12-14 Low BMD is more amenable to treatment in younger patients than in postmenopausal women. Younger patients with low BMD carry a higher lifetime fracture risk because they have more years of life with low BMD; therefore, early identification and treatment have a more significant impact on fracture prevention in these patients.

In the present study, we determined the prevalence of osteoporosis and osteopenia in younger women (age, 35-50 years) with DRFs and compared BMD measurements from younger women (age, 35-50 years) and older women (age, >50 years) with DRFs. The main goal was to determine which patients should be referred for bone densitometry and subsequent treatment.

Patients and Methods

This study received institutional review board approval. During a 5-year period (January 2005–August 2010), we prospectively collected dual-energy x-ray absorptiometry (DXA) scans for 128 women (age, >35 years) who presented with DRFs to our level I trauma center. Age ranged from 35 to 86 years. Data on mechanism of injury, treatment, and body mass index (BMI) were collected. The 128 patients were divided into a younger group (47 women; age range, 35-50 years; mean age, 44 years) and an older group (81 women; age, ≥51 years; mean age, 61 years). Mean BMI was 29.3 in the younger group and 28.8 in the older group (P = .88) (Table).

BMD was measured with a General Electric Lunar Prodigy Advance scanner that was tested annually for accuracy and precision. BMD of hips and lumbar spines was measured with a 76-Kv x-ray source. All DXA scans were analyzed by the same physician. BMD was omitted in cases of patients with a history of lumbar spine or hip fracture.

Two-sample Student t test was used to compare the 2 groups’ data. When multiple groups were being compared, analysis of variance was used. Spearman rank-order test was used to calculate a correlation coefficient for evaluation of the relationships between age and BMD.

Results

Mean lumbar spine (L1–L4) BMD was 1.12 in the younger group and 1.063 in the older group (P = .02); t scores were –0.63 and –1.132, respectively (P = .02); and mean z scores were –0.69 and –0.61, respectively (P = .81). Mean femoral neck BMD was 0.91 in the younger group and 0.80 in the older group (P < .05); t scores were –0.87 and –1.65, respectively (P < .01), and mean femoral neck z scores were –0.69 and –0.67, respectively (P = .92).

To further analyze BMD of specific age groups, we divided patients by decade: 35-39, 40-49, 50-59, 60-69, 70-79, 80-89 years. Among all 6 decades, there were no statistically significant differences between hip z scores (P = .83) (Figure 1). Spearman rank-order correlation test showed a moderate inverse correlation between age and femoral neck BMD (R = –0.42) and t score (R = –0.43). There was a weak correlation between increasing age and decreasing spine BMD, t score, and z score (Rs = –0.27, –0.31, 0.03). There was no correlation between age and femoral neck z score (R = –0.04).

According to the WHO classification system, 11 (23%) of the 47 women in the younger group were osteopenic, and 8 (17%) were osteoporotic, based on spine BMD. Hip BMD values indicated that 20 patients (43%) were osteopenic, and 3 (6%) were osteoporotic. One patient in the younger group had a hip z score of less than –2, and 14 patients (39%) had a hip z score between –2 and –1. Six patients (18%) had a spine z score of less than –2, and 6 patients (18%) had a spine z score between –2 and –1. Of the 81 older patients, 22 (27%) were osteopenic, and 21 (26%) were osteoporotic, according to spine measurements. The femoral neck data indicated that 39 (48%) of the older patients were osteopenic, and 22 (27%) were osteoporotic.

In both groups, mechanisms of injury were identified. Of the 47 younger patients, 26 fell from standing, 7 fell from a height of more than 6 feet, and 14 were injured in motor vehicle collisions (MVCs). Of the 81 older patients, 2 sustained a direct blow, 64 fell from standing, 4 fell from a height of more than 6 feet, and 11 were injured in MVCs. The differences in z scores based on mechanism of injury were not statistically significant (P = .22) (Figure 2).

Discussion

Several studies have shown that older women with DRFs have low BMD in the spine and femoral neck.^8,9 These studies focused on older women who sustained low-energy fractures caused by a fall from a standing height. Studies of younger women with DRFs focused on BMD of the contralateral distal radius, not the spine or femoral neck.^10,11 Those study groups also had low BMD. Findings from a multitude of studies have established that patients who are older than 50 years when they sustain distal radius fragility fractures should be referred for bone densitometry studies, and there is increasing evidence that younger patients with fragility fractures should undergo this evaluation as well.

The present study was designed to expand the range of patients and mechanisms of injury. Women in this study were 35 years or older. In addition to collecting data from patients injured in a fall from standing, we examined the medical records of women injured in MVCs, in falls from heights of more than 6 feet, and from direct trauma to the wrist. We measured the BMD of the spine and femoral neck and of the contralateral distal radius.

For this discussion, several key points should be made about BMD evaluation in younger versus older women. Most organizations caution against using spine BMD in older women. The ISCD, however, recommended measuring both hip and spine BMD; whereas BMD can be falsely elevated by spine osteoarthritis in older patients, spine BMD measurements are accurate in younger patients not affected by osteoarthritis. The ISCD also stipulated that z scores should be used in examining BMD in younger patients. The z score is a value of how many standard deviations BMD differs from a matched population of the same age, sex, ethnicity, and weight. The t score, which is useful in evaluating older patients, compares a patient’s BMD with that of an average 30-year-old.¹²

According to the WHO classification system (intended for older women), osteopenia is indicated by a t score between –1.0 and –2.5, and osteoporosis is indicated by a t score of less than –2.5. In the present study, about 43% of the younger patients (age, 35-50 years) with DRFs were osteopenic, and 6% of these patients were osteoporotic. In concert with previous studies,⁹ 48% of our older women (age, >50 years) with DRFs were osteopenic, and 27% were osteoporotic. The difference in mean spinal z scores between the younger and older groups was not statistically significant (P = .81).

As mentioned, when examining BMD of younger patients, it is imperative to use spine z scores. About 18% of our younger patients had a z score of less than –2, and 18% had a z score between –2 and –1. In our comparison of patients from 5 different age decades (range, 35-79 years), there was no statistically significant difference in z scores (P = .83). In addition, there was no correlation between increasing age and decreasing z score (R = –0.04).

Secondary causes of osteoporosis have been documented in 30% of premenopausal women and 55% of men with vertebral fractures.^13-15 Primary osteoporosis results from the normal aging process; secondary osteoporosis results from reversible causes, including medications, gastrointestinal disorders, renal disease, endocrine disorders, and sedentary lifestyle.^15,16 When a secondary cause of osteoporosis is identified, treatment can be initiated to increase BMD. As younger patients can reverse bone loss and even increase BMD, it is important to identify reversible causes of osteopenia and osteoporosis in this age group. It is well documented that both younger and older patients with DRFs are at increased risk for subsequent fractures.⁶ Preventing further bone loss at a younger age may drastically decrease lifetime fracture risk.^12,17

Most previous studies of BMD in women were limited to patients with DRFs caused by a low-energy mechanism or by a fall from standing. Current recommendations for BMD testing focus on postmenopausal women who have sustained a fragility or low-energy DRF. When an osteoporotic or osteopenic patient’s distal radius is subjected to a high-energy force, a fracture is likely. Therefore, we expanded our study to include high-energy mechanisms of injury. Our analysis of BMD in patients with DRFs sustained in MVCs indicated that 12% of this group were osteoporotic, and 44% were osteopenic. Forty-three percent of our younger patients with a DRF fractured in a MVC were osteopenic, and 6% were osteoporotic. Among 4 mechanisms of injury for DRFs, there was no statistically significant difference in z scores (P = .22) (Figure 2). This provides evidence that a significant portion of patients with DRFs from both high- and low-energy mechanisms are osteoporotic or osteopenic. Patients with DRFs sustained in MVCs or in falls from heights of more than 6 feet should be referred for BMD evaluation.         

Conclusion

A significant proportion of younger patients with DRFs are osteopenic or osteoporotic (43% and 6%, respectively), and their z scores are comparable to those of older patients with DRFs. There was no statistically significant difference in BMD z scores between younger and older patients and no difference in mechanisms of injury. This is evidence that younger patients with DRFs caused by a high- or low-energy mechanism of injury should undergo both DXA scan and BMD evaluation. If osteoporosis or osteopenia can be diagnosed at an earlier age, and if these patients can be properly treated, subsequent fractures could be prevented. The present study provides evidence supporting a simplification of the current recommendations for BMD evaluation: All women with DRFs should undergo bone densitometry.

Many organizations and work groups have issued recommendations regarding which patients should undergo bone densitometry. In 2004, the US Surgeon General recommended bone mineral density (BMD) evaluation for all women over age 65 years and for women and men with fragility fractures.¹ The Centers for Medicare & Medicaid Services recommended BMD assessment for estrogen-deficient patients, for patients with vertebral abnormalities or hyperparathyroidism, and for patients receiving either steroid therapy or osteoporosis medications approved by the US Food and Drug Administration.² The US Preventive Services Task Force and the National Osteoporosis Foundation each recommended screening for all women age 65 years or older and for postmenopausal women (age, 60-64 years) at high risk.^3,4 The International Society for Clinical Densitometry (ISCD) recommended screening for all women age 65 years or older, all men age 70 years or older, and high-risk women under age 65 years.⁵

These current recommendations for BMD evaluation focus on women over age 65 years. More recent studies of postmenopausal women with distal radius fractures (DRFs) have found that both younger women (age, 45-65 years) and older women (age, ≥65 years) can have lower BMD and increased risk for hip and spine fracture.^6,7 The authors of those studies recommended that all postmenopausal women with DRFs be evaluated for low BMD and that fracture prevention treatment be initiated. Earnshaw and colleagues⁸ and Oyen and colleagues⁹ found that men and women (age, ≥50 years) with DRFs had low BMD and elevated 10-year fracture rates. They concluded that BMD should be evaluated and treated in all DRF patients age 50 years or older. Other studies have shown low BMD in the contralateral distal radius of patients of all ages who presented with Colles fractures.^10,11 These 2 studies did not measure spine or hip BMD.

The literature on BMD of younger women with DRFs is limited, relying solely on data collected for the contralateral distal radius.^10,11 The ISCD recommended measuring both hip and spine BMD in premenopausal women. They also stated that z scores, not t scores, should be used for premenopausal women.⁵ The causes of low BMD in women over age 55 years are primarily nutritional deficiency and normal aging.¹ In younger females, low BMD results from secondary causes, such as diet, medications, medical conditions, and endocrine disorders. When the secondary cause of low BMD can be identified and treated, osteoporosis can be stopped and even reversed in younger patients.^12-14 Low BMD is more amenable to treatment in younger patients than in postmenopausal women. Younger patients with low BMD carry a higher lifetime fracture risk because they have more years of life with low BMD; therefore, early identification and treatment have a more significant impact on fracture prevention in these patients.

In the present study, we determined the prevalence of osteoporosis and osteopenia in younger women (age, 35-50 years) with DRFs and compared BMD measurements from younger women (age, 35-50 years) and older women (age, >50 years) with DRFs. The main goal was to determine which patients should be referred for bone densitometry and subsequent treatment.

Patients and Methods

This study received institutional review board approval. During a 5-year period (January 2005–August 2010), we prospectively collected dual-energy x-ray absorptiometry (DXA) scans for 128 women (age, >35 years) who presented with DRFs to our level I trauma center. Age ranged from 35 to 86 years. Data on mechanism of injury, treatment, and body mass index (BMI) were collected. The 128 patients were divided into a younger group (47 women; age range, 35-50 years; mean age, 44 years) and an older group (81 women; age, ≥51 years; mean age, 61 years). Mean BMI was 29.3 in the younger group and 28.8 in the older group (P = .88) (Table).

BMD was measured with a General Electric Lunar Prodigy Advance scanner that was tested annually for accuracy and precision. BMD of hips and lumbar spines was measured with a 76-Kv x-ray source. All DXA scans were analyzed by the same physician. BMD was omitted in cases of patients with a history of lumbar spine or hip fracture.

Two-sample Student t test was used to compare the 2 groups’ data. When multiple groups were being compared, analysis of variance was used. Spearman rank-order test was used to calculate a correlation coefficient for evaluation of the relationships between age and BMD.

Results

Mean lumbar spine (L1–L4) BMD was 1.12 in the younger group and 1.063 in the older group (P = .02); t scores were –0.63 and –1.132, respectively (P = .02); and mean z scores were –0.69 and –0.61, respectively (P = .81). Mean femoral neck BMD was 0.91 in the younger group and 0.80 in the older group (P < .05); t scores were –0.87 and –1.65, respectively (P < .01), and mean femoral neck z scores were –0.69 and –0.67, respectively (P = .92).

To further analyze BMD of specific age groups, we divided patients by decade: 35-39, 40-49, 50-59, 60-69, 70-79, 80-89 years. Among all 6 decades, there were no statistically significant differences between hip z scores (P = .83) (Figure 1). Spearman rank-order correlation test showed a moderate inverse correlation between age and femoral neck BMD (R = –0.42) and t score (R = –0.43). There was a weak correlation between increasing age and decreasing spine BMD, t score, and z score (Rs = –0.27, –0.31, 0.03). There was no correlation between age and femoral neck z score (R = –0.04).

According to the WHO classification system, 11 (23%) of the 47 women in the younger group were osteopenic, and 8 (17%) were osteoporotic, based on spine BMD. Hip BMD values indicated that 20 patients (43%) were osteopenic, and 3 (6%) were osteoporotic. One patient in the younger group had a hip z score of less than –2, and 14 patients (39%) had a hip z score between –2 and –1. Six patients (18%) had a spine z score of less than –2, and 6 patients (18%) had a spine z score between –2 and –1. Of the 81 older patients, 22 (27%) were osteopenic, and 21 (26%) were osteoporotic, according to spine measurements. The femoral neck data indicated that 39 (48%) of the older patients were osteopenic, and 22 (27%) were osteoporotic.

In both groups, mechanisms of injury were identified. Of the 47 younger patients, 26 fell from standing, 7 fell from a height of more than 6 feet, and 14 were injured in motor vehicle collisions (MVCs). Of the 81 older patients, 2 sustained a direct blow, 64 fell from standing, 4 fell from a height of more than 6 feet, and 11 were injured in MVCs. The differences in z scores based on mechanism of injury were not statistically significant (P = .22) (Figure 2).

Discussion

Several studies have shown that older women with DRFs have low BMD in the spine and femoral neck.^8,9 These studies focused on older women who sustained low-energy fractures caused by a fall from a standing height. Studies of younger women with DRFs focused on BMD of the contralateral distal radius, not the spine or femoral neck.^10,11 Those study groups also had low BMD. Findings from a multitude of studies have established that patients who are older than 50 years when they sustain distal radius fragility fractures should be referred for bone densitometry studies, and there is increasing evidence that younger patients with fragility fractures should undergo this evaluation as well.

The present study was designed to expand the range of patients and mechanisms of injury. Women in this study were 35 years or older. In addition to collecting data from patients injured in a fall from standing, we examined the medical records of women injured in MVCs, in falls from heights of more than 6 feet, and from direct trauma to the wrist. We measured the BMD of the spine and femoral neck and of the contralateral distal radius.

For this discussion, several key points should be made about BMD evaluation in younger versus older women. Most organizations caution against using spine BMD in older women. The ISCD, however, recommended measuring both hip and spine BMD; whereas BMD can be falsely elevated by spine osteoarthritis in older patients, spine BMD measurements are accurate in younger patients not affected by osteoarthritis. The ISCD also stipulated that z scores should be used in examining BMD in younger patients. The z score is a value of how many standard deviations BMD differs from a matched population of the same age, sex, ethnicity, and weight. The t score, which is useful in evaluating older patients, compares a patient’s BMD with that of an average 30-year-old.¹²

According to the WHO classification system (intended for older women), osteopenia is indicated by a t score between –1.0 and –2.5, and osteoporosis is indicated by a t score of less than –2.5. In the present study, about 43% of the younger patients (age, 35-50 years) with DRFs were osteopenic, and 6% of these patients were osteoporotic. In concert with previous studies,⁹ 48% of our older women (age, >50 years) with DRFs were osteopenic, and 27% were osteoporotic. The difference in mean spinal z scores between the younger and older groups was not statistically significant (P = .81).

As mentioned, when examining BMD of younger patients, it is imperative to use spine z scores. About 18% of our younger patients had a z score of less than –2, and 18% had a z score between –2 and –1. In our comparison of patients from 5 different age decades (range, 35-79 years), there was no statistically significant difference in z scores (P = .83). In addition, there was no correlation between increasing age and decreasing z score (R = –0.04).

Secondary causes of osteoporosis have been documented in 30% of premenopausal women and 55% of men with vertebral fractures.^13-15 Primary osteoporosis results from the normal aging process; secondary osteoporosis results from reversible causes, including medications, gastrointestinal disorders, renal disease, endocrine disorders, and sedentary lifestyle.^15,16 When a secondary cause of osteoporosis is identified, treatment can be initiated to increase BMD. As younger patients can reverse bone loss and even increase BMD, it is important to identify reversible causes of osteopenia and osteoporosis in this age group. It is well documented that both younger and older patients with DRFs are at increased risk for subsequent fractures.⁶ Preventing further bone loss at a younger age may drastically decrease lifetime fracture risk.^12,17

Most previous studies of BMD in women were limited to patients with DRFs caused by a low-energy mechanism or by a fall from standing. Current recommendations for BMD testing focus on postmenopausal women who have sustained a fragility or low-energy DRF. When an osteoporotic or osteopenic patient’s distal radius is subjected to a high-energy force, a fracture is likely. Therefore, we expanded our study to include high-energy mechanisms of injury. Our analysis of BMD in patients with DRFs sustained in MVCs indicated that 12% of this group were osteoporotic, and 44% were osteopenic. Forty-three percent of our younger patients with a DRF fractured in a MVC were osteopenic, and 6% were osteoporotic. Among 4 mechanisms of injury for DRFs, there was no statistically significant difference in z scores (P = .22) (Figure 2). This provides evidence that a significant portion of patients with DRFs from both high- and low-energy mechanisms are osteoporotic or osteopenic. Patients with DRFs sustained in MVCs or in falls from heights of more than 6 feet should be referred for BMD evaluation.         

Conclusion

A significant proportion of younger patients with DRFs are osteopenic or osteoporotic (43% and 6%, respectively), and their z scores are comparable to those of older patients with DRFs. There was no statistically significant difference in BMD z scores between younger and older patients and no difference in mechanisms of injury. This is evidence that younger patients with DRFs caused by a high- or low-energy mechanism of injury should undergo both DXA scan and BMD evaluation. If osteoporosis or osteopenia can be diagnosed at an earlier age, and if these patients can be properly treated, subsequent fractures could be prevented. The present study provides evidence supporting a simplification of the current recommendations for BMD evaluation: All women with DRFs should undergo bone densitometry.

In shoulder arthroplasty, it is not uncommon for patients to receive postoperative blood transfusions; rates range from 7% to 43%.^1-6 Allogeneic blood transfusions (ABTs) are costly and not entirely free of risks.⁷ The risk for infection has decreased because of improved screening and risk reduction strategies, but there are still significant risks associated with ABTs, such as clerical errors, acute and delayed hemolytic reactions, graft-versus-host reactions, transfusion-related acute lung injury, and anaphylaxis.^8-10 As use of shoulder arthroplasty continues to increase, the importance of minimizing unnecessary transfusions is growing as well.⁷

Predictive factors for ABT have been explored in other orthopedic settings, yet little has been done in shoulder arthroplasty.^1-6,11-15 Previous shoulder arthroplasty studies have shown that low preoperative hemoglobin (Hb) levels are independent risk factors for postoperative blood transfusion. However, there is debate over the significance of other variables, such as procedure type, age, sex, and medical comorbidities. Further, prior studies were limited by relatively small samples from single institutions; the largest series included fewer than 600 patients.^1-6

We conducted a study to determine predictors of ABT in a large cohort of patients admitted to US hospitals for shoulder arthroplasty. We also wanted to evaluate the effect of ABT on postoperative outcomes, including inpatient mortality, adverse events, prolonged hospital stay, and nonroutine discharge. According to the null hypothesis, in shoulder arthroplasty there will be no difference in risk factors between patients who require ABT and those who did not, after accounting for confounding variables.

Materials and Methods

This study was exempt from institutional review board approval, as all data were appropriately deidentified before use in this project. We used the Nationwide Inpatient Sample (NIS) to retrospectively study the period 2002–2011, from which all demographic, clinical, and resource use data were derived.¹⁶ NIS, an annual survey conducted by the Agency for Healthcare Research and Quality (AHRQ) since 1988, has generated a huge amount of data, forming the largest all-payer inpatient care database in the United States. Yearly samples contain discharge data from about 8 million hospital stays at more than 1000 hospitals across 46 states, approximating a 20% random sample of all hospital discharges at participating institutions.¹⁷ These data are then weighted to generate statistically valid national estimates.

The NIS database uses International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes to identify 15 medical diagnoses up to the year 2008 and a maximum of 25 medical diagnoses and 15 procedures thereafter. In addition, the database includes information on patient and hospital characteristics as well as inpatient outcomes such as length of stay, total hospitalization charges, and discharge disposition.^18,19 Given its large sample size and data volume, NIS is a powerful tool in the analysis of data associated with a multitude of medical diagnoses and procedures.²⁰

We used the NIS database to study a population of 422,371 patients (age, >18 years) who underwent total shoulder arthroplasty (TSA) or hemiarthroplasty (HSA) between 2002 and 2011. ICD-9-CM procedure codes for TSA (81.80, 81.88) and HSA (81.81) were used to identify this population. We also analyzed data for reverse TSA for the year 2011. Then we divided our target population into 2 different cohorts: patients who did not receive any blood transfusion products and patients who received a transfusion of allogeneic packed cells (ICD-9-CM code 99.04 was used to identify the latter cohort).

In this study, normal distribution of the dataset was assumed, given the large sample size. The 2 cohorts were evaluated through bivariate analysis using the Pearson χ² test for categorical data and the independent-samples t test for continuous data. The extent to which diagnosis, age, race, sex, and medical comorbidities were predictive of blood transfusion after TSA or HSA was evaluated through multivariate binary logistic regression analysis. Statistical significance was set at P < .05. All statistical analyses and data modeling were performed with SPSS Version 22.0.

Results

Using the NIS database, we stratified an estimated 422,371 patients who presented for shoulder arthroplasty between January 1, 2002, and December 31, 2011, into a TSA cohort (59.3%) and an HSA cohort (40.7%). Eight percent (33,889) of all patients received an ABT; the proportion of patients who received ABT was higher (P < .001) for the HSA cohort (55.6%) than the TSA cohort (39.4%). Further, the rate of ABT after shoulder arthroplasty showed an upward inclination (Figure).

Demographically, patients who received ABT tended (P < .001) to be older (74±11 years vs 68±11 years) and of a minority race (black or Hispanic) and to fall in either the lowest range of median household income (21.5% vs 20.7%; ≤$38,999) or the highest (27.3% vs 25.4%; ≥$63,000). Shoulder arthroplasty with ABT occurred more often (P < .001) at hospitals that were urban (13.3% vs 11.3%), medium in size (27.3% vs 23.4%), and nonteaching (56.2% vs 54.3%). In addition, ABT was used more often (P < .001) in patients with a primary diagnosis of fracture (43.1% vs 14.3%) or fracture nonunion (4.4% vs 2.1%). These groups also had a longer (P < .001) hospital stay (5.0±4.3 days vs 2.5±2.2 days). Table 1 summarizes these findings.

The 2 cohorts were then analyzed for presence of medical comorbidities (Table 2). Patients who required ABT during shoulder arthroplasty had a significantly (P < .001) higher prevalence of congestive heart failure, chronic lung disease, hypertension, uncomplicated and complicated diabetes mellitus, liver disease, renal failure, fluid and electrolyte disorders, pulmonary circulatory disease, weight loss, coagulopathy, and deficiency anemia.

In multivariate regression modeling (Table 3), demographic predictors of ABT (P < .001) included increasing age (odds ratio [OR], 1.03 per year; 95% confidence interval [95% CI], 1.03-1.03), female sex (OR, 1.55; 95% CI, 1.51-1.60), and minority race (black or Hispanic). Odds of requiring ABT were higher for patients with Medicare (OR, 1.25; 95% CI, 1.20-1.30) and patients with Medicaid (OR, 1.63; 95% CI, 1.51-1.77) than for patients with private insurance.

ABT was more likely to be required (P < .001) in patients with a primary diagnosis of fracture (OR, 4.49; 95% CI, 4.34-4.65), avascular necrosis (OR, 2.06; 95% CI, 1.91-2.22), rheumatoid arthritis (OR, 1.91; 95% CI, 1.72-2.12), fracture nonunion (OR, 3.55; 95% CI, 3.33-3.79), or rotator cuff arthropathy (OR, 1.47; 95% CI, 1.41-1.54) than for patients with osteoarthritis. Moreover, compared with patients having HSA, patients having TSA were more likely to require ABT (OR, 1.20; 95% CI, 1.17-1.24). According to the analysis restricted to the year 2011, compared with patients having anatomical TSAs, patients having reverse TSAs were 1.6 times more likely (P < .001) to require ABT (OR, 1.63; 95% CI, 1.50-1.79).

With the exception of obesity, all comorbidities were significant (P < .001) independent predictors of ABT after shoulder arthroplasty: deficiency anemia (OR, 3.42; 95% CI, 3.32-3.52), coagulopathy (OR, 2.54; 95% CI, 2.36-2.73), fluid and electrolyte disorders (OR, 1.91; 95% CI, 1.84-1.97), and weight loss (OR, 1.78; 95% CI, 1.58-2.00).

Patients who received ABT were more likely to experience adverse events (OR, 1.74; 95% CI, 1.68-1.81), prolonged hospital stay (OR, 3.21; 95% CI, 3.12-3.30), and nonroutine discharge (OR, 1.77; 95% CI, 1.72-1.82) (Table 4). There was no difference in mortality between the 2 cohorts.

Discussion

There is an abundance of literature on blood transfusions in hip and knee arthroplasty, but there are few articles on ABT in shoulder arthroplasty, and they all report data from single institutions with relatively low caseloads.^{1,2,11-13,15,21} In the present study, we investigated ABT in shoulder arthroplasty from the perspective of a multi-institutional database with a caseload of more than 400,000. Given the rapidly increasing rates of shoulder arthroplasty, it is important to further examine this issue to minimize unnecessary blood transfusion and its associated risks and costs.⁷

We found that 8% of patients who had shoulder arthroplasty received ABT, which is consistent with previously reported transfusion rates (range, 7%-43%).^1-6 Rates of ABT after shoulder arthroplasty have continued to rise. The exception, a decrease during the year 2010, can be explained by increased efforts to more rigidly follow transfusion indication guidelines to reduce the number of potentially unnecessary ABTs.^21-24 Our study also identified numerous significant independent predictors of ABT in shoulder arthroplasty: age, sex, race, insurance status, procedure type, primary diagnoses, and multiple medical comorbidities.

Demographics

According to our analysis, more than 80% of patients who received ABT were over age 65 years, which aligns with what several other studies have demonstrated: Increasing age is a predictor of ABT, despite higher rates of comorbidities and lower preoperative Hb levels in this population.^{1,2,4,5,25-27} Consistent with previous work, female sex was predictive of ABT.^2,5 It has been suggested that females are more likely predisposed to ABT because of lower preoperative Hb and smaller blood mass.^2,5,28 Interestingly, our study showed a higher likelihood of ABT in both black and Hispanic populations. Further, patients with Medicare or Medicaid were more likely to receive ABT.

Primary Diagnosis

Although patients with a primary diagnosis of osteoarthritis constitute the majority of patients who undergo shoulder arthroplasty, our analysis showed that patients with a diagnosis of proximal humerus fracture were more likely to receive ABT. This finding is reasonable given studies showing the high prevalence of proximal humerus fractures in elderly women.^29,30 Similarly, patients with a humerus fracture nonunion were more likely to receive a blood transfusion, which is unsurprising given the increased complexity associated with arthroplasty in this predominately elderly population.³¹ Interestingly, compared with patients with osteoarthritis, patients with any one of the other primary diagnoses were more likely to require a transfusion—proximal humerus fracture being the most significant, followed by humerus fracture nonunion, avascular necrosis, rheumatoid arthritis, and rotator cuff arthropathy.

Type of Arthroplasty

Bivariate analysis revealed that 55.6% of the patients who received ABT underwent HSA; the other 44.4% underwent TSA. The effect of primary diagnosis on procedure choice likely played a role in this finding. HSA indications include humerus fracture, which has been associated with increased ABT, whereas patients with osteoarthritis requiring TSA are significantly less likely to require ABT, as reflected in this analysis.^7,32-34 Previous studies have failed to show a difference in blood transfusion rates between TSA and HSA.^2,4-6,35 Conversely, with confounding factors controlled for, multivariate logistic regression analysis showed that TSA was 1.2 times more likely than HSA to require ABT, which could be explained by the increased operative time, case complexity, and blood loss that may be associated with the glenoid exposure.^36,37 With analysis restricted to the year 2011, patients with reverse TSAs were 1.6 times more likely than patients with anatomical TSAs to receive a blood transfusion (OR, 1.63; 95% CI, 1.50-1.79). Although this finding differs from what was previously reported, it fits given that patients having reverse TSAs are often older and may present with a more significant comorbidity profile.³ In addition, there are the increased technical surgical aspects associated with “salvage surgery” for challenging indications such as cuff arthropathy and failed previous arthroplasty.^38-41

Medical Comorbidities

Patients who received ABT were more likely to present with numerous medical comorbidities. Previous studies have indicated that the presence of multiple medical comorbidities significantly increased blood transfusion rates, possibly by working synergistically.⁴² All studies of blood transfusion in shoulder arthroplasty concluded that lower preoperative Hb was an independent predictor.^1-6 Schumer and colleagues⁴ reported a 4-fold increase in likelihood of blood transfusion in patients with a preoperative Hb level less than 12.5 g/dL. In addition, Millett and colleagues⁶ showed a 20-fold increase in likelihood of transfusion in patients with a preoperative Hb level less than 11.0 g/dL compared with patients with a level higher than 13.0 g/dL. Patients with a Hb level between 11.0 and 13.0 g/dL showed a 5-fold increase in likelihood of transfusion.⁶ We should note that correction of preoperative anemia through various pharmacologic methods (eg, erythropoietin, intravenous iron supplementation) has been shown to decrease postoperative transfusion rates.^43,44 Although we could not include preoperative Hb levels in the present study, given inherent limitations in using NIS, our multivariate analysis showed that preoperative deficiency anemia and coagulopathy were the most significant predictors of ABT.

In addition, the multivariate logistic regression model showed that both cardiac disease and diabetes were independent predictors of ABT, confirming data reported by Ahmadi and colleagues.¹ Although not as well characterized in other studies, in the current analysis multiple other medical comorbidities, including fluid and electrolyte abnormalities, weight loss, liver disease, renal failure, and chronic lung disease, had significant predictive value. Contrarily, obesity significantly decreased the odds of ABT, likely because of higher baseline blood volume in obese patients.

Patient Outcomes

Patients who undergo shoulder arthroplasty with ABT are more likely to experience adverse events or a prolonged hospital stay and are more often discharged to a nursing home or an extended-care facility. In this population, however, deaths did not occur at a significantly higher rate—similar to what was found for patients who underwent hip or knee arthroplasty with blood transfusions.⁴⁵

Little has been done to investigate the effect of pharmacologic agents on the need for perioperative ABT for orthopedic shoulder procedures. Aprotinin, tranexamic acid, epoetin-α, and aminocaproic acid have all been effective in limiting ABT during the perioperative period in various orthopedic hip, knee, and spine procedures.^9,46-53 Given the increased morbidity associated with ABT, it may be beneficial to use similar methods to limit blood loss in high-risk patients undergoing shoulder arthroplasty.

Study Limitations

NIS has intrinsic limitations. Given its massive volume, it is subject to errors in both data entry and clinical coding. Moreover, the database lacks data that would have been useful in our study: preoperative Hb levels, intraoperative course, number of units transfused, total blood loss, use of blood conservation techniques, transfusion protocols, and severity of comorbidities. Reverse TSA was given a unique ICD-9-CM code in October 2010, so 2011 was the only year we were able to examine the relationship between reverse TSA and transfusions. Further, our analysis was unable to identify any medications, including chronic anticoagulants or postoperative prophylaxis, that have been shown to significantly affect blood transfusion rates.⁵⁴ Yet, there are obvious advantages to using the NIS database, as previously outlined across the medical landscape.

Conclusion

Our results confirmed previous findings and identified new predictors of ABT in shoulder arthroplasty in a large cohort. We examined demographics and perioperative complications while identifying predictors of ABT use. Patients who received ABT were older, female, and nonwhite and were covered by Medicare or Medicaid insurance, and many had a primary diagnosis of proximal humerus fracture. The ABT cohort had numerous medical comorbidities, including deficiency anemia and coagulopathy. Identifying this patient population is a prerequisite to educating patients while minimizing unnecessary risks and costs.

Using NIS data on a population of 422,371 patients who underwent shoulder arthroplasty, we identified the 5 likeliest predictors of ABT: fracture, fracture nonunion, deficiency anemia, coagulopathy, and avascular necrosis. Of the identified variables associated with ABT, deficiency anemia may be the most amenable to treatment; therefore, there may be benefit in delaying elective shoulder arthroplasty in this cohort. Given these findings, it is important to identify at-risk patients before surgery, with the intent to provide education and minimize risk.

In shoulder arthroplasty, it is not uncommon for patients to receive postoperative blood transfusions; rates range from 7% to 43%.^1-6 Allogeneic blood transfusions (ABTs) are costly and not entirely free of risks.⁷ The risk for infection has decreased because of improved screening and risk reduction strategies, but there are still significant risks associated with ABTs, such as clerical errors, acute and delayed hemolytic reactions, graft-versus-host reactions, transfusion-related acute lung injury, and anaphylaxis.^8-10 As use of shoulder arthroplasty continues to increase, the importance of minimizing unnecessary transfusions is growing as well.⁷

Predictive factors for ABT have been explored in other orthopedic settings, yet little has been done in shoulder arthroplasty.^1-6,11-15 Previous shoulder arthroplasty studies have shown that low preoperative hemoglobin (Hb) levels are independent risk factors for postoperative blood transfusion. However, there is debate over the significance of other variables, such as procedure type, age, sex, and medical comorbidities. Further, prior studies were limited by relatively small samples from single institutions; the largest series included fewer than 600 patients.^1-6

We conducted a study to determine predictors of ABT in a large cohort of patients admitted to US hospitals for shoulder arthroplasty. We also wanted to evaluate the effect of ABT on postoperative outcomes, including inpatient mortality, adverse events, prolonged hospital stay, and nonroutine discharge. According to the null hypothesis, in shoulder arthroplasty there will be no difference in risk factors between patients who require ABT and those who did not, after accounting for confounding variables.

Materials and Methods

This study was exempt from institutional review board approval, as all data were appropriately deidentified before use in this project. We used the Nationwide Inpatient Sample (NIS) to retrospectively study the period 2002–2011, from which all demographic, clinical, and resource use data were derived.¹⁶ NIS, an annual survey conducted by the Agency for Healthcare Research and Quality (AHRQ) since 1988, has generated a huge amount of data, forming the largest all-payer inpatient care database in the United States. Yearly samples contain discharge data from about 8 million hospital stays at more than 1000 hospitals across 46 states, approximating a 20% random sample of all hospital discharges at participating institutions.¹⁷ These data are then weighted to generate statistically valid national estimates.

The NIS database uses International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes to identify 15 medical diagnoses up to the year 2008 and a maximum of 25 medical diagnoses and 15 procedures thereafter. In addition, the database includes information on patient and hospital characteristics as well as inpatient outcomes such as length of stay, total hospitalization charges, and discharge disposition.^18,19 Given its large sample size and data volume, NIS is a powerful tool in the analysis of data associated with a multitude of medical diagnoses and procedures.²⁰

We used the NIS database to study a population of 422,371 patients (age, >18 years) who underwent total shoulder arthroplasty (TSA) or hemiarthroplasty (HSA) between 2002 and 2011. ICD-9-CM procedure codes for TSA (81.80, 81.88) and HSA (81.81) were used to identify this population. We also analyzed data for reverse TSA for the year 2011. Then we divided our target population into 2 different cohorts: patients who did not receive any blood transfusion products and patients who received a transfusion of allogeneic packed cells (ICD-9-CM code 99.04 was used to identify the latter cohort).

In this study, normal distribution of the dataset was assumed, given the large sample size. The 2 cohorts were evaluated through bivariate analysis using the Pearson χ² test for categorical data and the independent-samples t test for continuous data. The extent to which diagnosis, age, race, sex, and medical comorbidities were predictive of blood transfusion after TSA or HSA was evaluated through multivariate binary logistic regression analysis. Statistical significance was set at P < .05. All statistical analyses and data modeling were performed with SPSS Version 22.0.

Results

Using the NIS database, we stratified an estimated 422,371 patients who presented for shoulder arthroplasty between January 1, 2002, and December 31, 2011, into a TSA cohort (59.3%) and an HSA cohort (40.7%). Eight percent (33,889) of all patients received an ABT; the proportion of patients who received ABT was higher (P < .001) for the HSA cohort (55.6%) than the TSA cohort (39.4%). Further, the rate of ABT after shoulder arthroplasty showed an upward inclination (Figure).

Demographically, patients who received ABT tended (P < .001) to be older (74±11 years vs 68±11 years) and of a minority race (black or Hispanic) and to fall in either the lowest range of median household income (21.5% vs 20.7%; ≤$38,999) or the highest (27.3% vs 25.4%; ≥$63,000). Shoulder arthroplasty with ABT occurred more often (P < .001) at hospitals that were urban (13.3% vs 11.3%), medium in size (27.3% vs 23.4%), and nonteaching (56.2% vs 54.3%). In addition, ABT was used more often (P < .001) in patients with a primary diagnosis of fracture (43.1% vs 14.3%) or fracture nonunion (4.4% vs 2.1%). These groups also had a longer (P < .001) hospital stay (5.0±4.3 days vs 2.5±2.2 days). Table 1 summarizes these findings.

The 2 cohorts were then analyzed for presence of medical comorbidities (Table 2). Patients who required ABT during shoulder arthroplasty had a significantly (P < .001) higher prevalence of congestive heart failure, chronic lung disease, hypertension, uncomplicated and complicated diabetes mellitus, liver disease, renal failure, fluid and electrolyte disorders, pulmonary circulatory disease, weight loss, coagulopathy, and deficiency anemia.

In multivariate regression modeling (Table 3), demographic predictors of ABT (P < .001) included increasing age (odds ratio [OR], 1.03 per year; 95% confidence interval [95% CI], 1.03-1.03), female sex (OR, 1.55; 95% CI, 1.51-1.60), and minority race (black or Hispanic). Odds of requiring ABT were higher for patients with Medicare (OR, 1.25; 95% CI, 1.20-1.30) and patients with Medicaid (OR, 1.63; 95% CI, 1.51-1.77) than for patients with private insurance.

ABT was more likely to be required (P < .001) in patients with a primary diagnosis of fracture (OR, 4.49; 95% CI, 4.34-4.65), avascular necrosis (OR, 2.06; 95% CI, 1.91-2.22), rheumatoid arthritis (OR, 1.91; 95% CI, 1.72-2.12), fracture nonunion (OR, 3.55; 95% CI, 3.33-3.79), or rotator cuff arthropathy (OR, 1.47; 95% CI, 1.41-1.54) than for patients with osteoarthritis. Moreover, compared with patients having HSA, patients having TSA were more likely to require ABT (OR, 1.20; 95% CI, 1.17-1.24). According to the analysis restricted to the year 2011, compared with patients having anatomical TSAs, patients having reverse TSAs were 1.6 times more likely (P < .001) to require ABT (OR, 1.63; 95% CI, 1.50-1.79).

With the exception of obesity, all comorbidities were significant (P < .001) independent predictors of ABT after shoulder arthroplasty: deficiency anemia (OR, 3.42; 95% CI, 3.32-3.52), coagulopathy (OR, 2.54; 95% CI, 2.36-2.73), fluid and electrolyte disorders (OR, 1.91; 95% CI, 1.84-1.97), and weight loss (OR, 1.78; 95% CI, 1.58-2.00).

Patients who received ABT were more likely to experience adverse events (OR, 1.74; 95% CI, 1.68-1.81), prolonged hospital stay (OR, 3.21; 95% CI, 3.12-3.30), and nonroutine discharge (OR, 1.77; 95% CI, 1.72-1.82) (Table 4). There was no difference in mortality between the 2 cohorts.

Discussion

There is an abundance of literature on blood transfusions in hip and knee arthroplasty, but there are few articles on ABT in shoulder arthroplasty, and they all report data from single institutions with relatively low caseloads.^{1,2,11-13,15,21} In the present study, we investigated ABT in shoulder arthroplasty from the perspective of a multi-institutional database with a caseload of more than 400,000. Given the rapidly increasing rates of shoulder arthroplasty, it is important to further examine this issue to minimize unnecessary blood transfusion and its associated risks and costs.⁷

We found that 8% of patients who had shoulder arthroplasty received ABT, which is consistent with previously reported transfusion rates (range, 7%-43%).^1-6 Rates of ABT after shoulder arthroplasty have continued to rise. The exception, a decrease during the year 2010, can be explained by increased efforts to more rigidly follow transfusion indication guidelines to reduce the number of potentially unnecessary ABTs.^21-24 Our study also identified numerous significant independent predictors of ABT in shoulder arthroplasty: age, sex, race, insurance status, procedure type, primary diagnoses, and multiple medical comorbidities.

Demographics

According to our analysis, more than 80% of patients who received ABT were over age 65 years, which aligns with what several other studies have demonstrated: Increasing age is a predictor of ABT, despite higher rates of comorbidities and lower preoperative Hb levels in this population.^{1,2,4,5,25-27} Consistent with previous work, female sex was predictive of ABT.^2,5 It has been suggested that females are more likely predisposed to ABT because of lower preoperative Hb and smaller blood mass.^2,5,28 Interestingly, our study showed a higher likelihood of ABT in both black and Hispanic populations. Further, patients with Medicare or Medicaid were more likely to receive ABT.

Primary Diagnosis

Although patients with a primary diagnosis of osteoarthritis constitute the majority of patients who undergo shoulder arthroplasty, our analysis showed that patients with a diagnosis of proximal humerus fracture were more likely to receive ABT. This finding is reasonable given studies showing the high prevalence of proximal humerus fractures in elderly women.^29,30 Similarly, patients with a humerus fracture nonunion were more likely to receive a blood transfusion, which is unsurprising given the increased complexity associated with arthroplasty in this predominately elderly population.³¹ Interestingly, compared with patients with osteoarthritis, patients with any one of the other primary diagnoses were more likely to require a transfusion—proximal humerus fracture being the most significant, followed by humerus fracture nonunion, avascular necrosis, rheumatoid arthritis, and rotator cuff arthropathy.

Type of Arthroplasty

Bivariate analysis revealed that 55.6% of the patients who received ABT underwent HSA; the other 44.4% underwent TSA. The effect of primary diagnosis on procedure choice likely played a role in this finding. HSA indications include humerus fracture, which has been associated with increased ABT, whereas patients with osteoarthritis requiring TSA are significantly less likely to require ABT, as reflected in this analysis.^7,32-34 Previous studies have failed to show a difference in blood transfusion rates between TSA and HSA.^2,4-6,35 Conversely, with confounding factors controlled for, multivariate logistic regression analysis showed that TSA was 1.2 times more likely than HSA to require ABT, which could be explained by the increased operative time, case complexity, and blood loss that may be associated with the glenoid exposure.^36,37 With analysis restricted to the year 2011, patients with reverse TSAs were 1.6 times more likely than patients with anatomical TSAs to receive a blood transfusion (OR, 1.63; 95% CI, 1.50-1.79). Although this finding differs from what was previously reported, it fits given that patients having reverse TSAs are often older and may present with a more significant comorbidity profile.³ In addition, there are the increased technical surgical aspects associated with “salvage surgery” for challenging indications such as cuff arthropathy and failed previous arthroplasty.^38-41

Medical Comorbidities

Patients who received ABT were more likely to present with numerous medical comorbidities. Previous studies have indicated that the presence of multiple medical comorbidities significantly increased blood transfusion rates, possibly by working synergistically.⁴² All studies of blood transfusion in shoulder arthroplasty concluded that lower preoperative Hb was an independent predictor.^1-6 Schumer and colleagues⁴ reported a 4-fold increase in likelihood of blood transfusion in patients with a preoperative Hb level less than 12.5 g/dL. In addition, Millett and colleagues⁶ showed a 20-fold increase in likelihood of transfusion in patients with a preoperative Hb level less than 11.0 g/dL compared with patients with a level higher than 13.0 g/dL. Patients with a Hb level between 11.0 and 13.0 g/dL showed a 5-fold increase in likelihood of transfusion.⁶ We should note that correction of preoperative anemia through various pharmacologic methods (eg, erythropoietin, intravenous iron supplementation) has been shown to decrease postoperative transfusion rates.^43,44 Although we could not include preoperative Hb levels in the present study, given inherent limitations in using NIS, our multivariate analysis showed that preoperative deficiency anemia and coagulopathy were the most significant predictors of ABT.

In addition, the multivariate logistic regression model showed that both cardiac disease and diabetes were independent predictors of ABT, confirming data reported by Ahmadi and colleagues.¹ Although not as well characterized in other studies, in the current analysis multiple other medical comorbidities, including fluid and electrolyte abnormalities, weight loss, liver disease, renal failure, and chronic lung disease, had significant predictive value. Contrarily, obesity significantly decreased the odds of ABT, likely because of higher baseline blood volume in obese patients.

Patient Outcomes

Patients who undergo shoulder arthroplasty with ABT are more likely to experience adverse events or a prolonged hospital stay and are more often discharged to a nursing home or an extended-care facility. In this population, however, deaths did not occur at a significantly higher rate—similar to what was found for patients who underwent hip or knee arthroplasty with blood transfusions.⁴⁵

Little has been done to investigate the effect of pharmacologic agents on the need for perioperative ABT for orthopedic shoulder procedures. Aprotinin, tranexamic acid, epoetin-α, and aminocaproic acid have all been effective in limiting ABT during the perioperative period in various orthopedic hip, knee, and spine procedures.^9,46-53 Given the increased morbidity associated with ABT, it may be beneficial to use similar methods to limit blood loss in high-risk patients undergoing shoulder arthroplasty.

Study Limitations

NIS has intrinsic limitations. Given its massive volume, it is subject to errors in both data entry and clinical coding. Moreover, the database lacks data that would have been useful in our study: preoperative Hb levels, intraoperative course, number of units transfused, total blood loss, use of blood conservation techniques, transfusion protocols, and severity of comorbidities. Reverse TSA was given a unique ICD-9-CM code in October 2010, so 2011 was the only year we were able to examine the relationship between reverse TSA and transfusions. Further, our analysis was unable to identify any medications, including chronic anticoagulants or postoperative prophylaxis, that have been shown to significantly affect blood transfusion rates.⁵⁴ Yet, there are obvious advantages to using the NIS database, as previously outlined across the medical landscape.

Conclusion

Our results confirmed previous findings and identified new predictors of ABT in shoulder arthroplasty in a large cohort. We examined demographics and perioperative complications while identifying predictors of ABT use. Patients who received ABT were older, female, and nonwhite and were covered by Medicare or Medicaid insurance, and many had a primary diagnosis of proximal humerus fracture. The ABT cohort had numerous medical comorbidities, including deficiency anemia and coagulopathy. Identifying this patient population is a prerequisite to educating patients while minimizing unnecessary risks and costs.

Using NIS data on a population of 422,371 patients who underwent shoulder arthroplasty, we identified the 5 likeliest predictors of ABT: fracture, fracture nonunion, deficiency anemia, coagulopathy, and avascular necrosis. Of the identified variables associated with ABT, deficiency anemia may be the most amenable to treatment; therefore, there may be benefit in delaying elective shoulder arthroplasty in this cohort. Given these findings, it is important to identify at-risk patients before surgery, with the intent to provide education and minimize risk.

In shoulder arthroplasty, it is not uncommon for patients to receive postoperative blood transfusions; rates range from 7% to 43%.^1-6 Allogeneic blood transfusions (ABTs) are costly and not entirely free of risks.⁷ The risk for infection has decreased because of improved screening and risk reduction strategies, but there are still significant risks associated with ABTs, such as clerical errors, acute and delayed hemolytic reactions, graft-versus-host reactions, transfusion-related acute lung injury, and anaphylaxis.^8-10 As use of shoulder arthroplasty continues to increase, the importance of minimizing unnecessary transfusions is growing as well.⁷

Predictive factors for ABT have been explored in other orthopedic settings, yet little has been done in shoulder arthroplasty.^1-6,11-15 Previous shoulder arthroplasty studies have shown that low preoperative hemoglobin (Hb) levels are independent risk factors for postoperative blood transfusion. However, there is debate over the significance of other variables, such as procedure type, age, sex, and medical comorbidities. Further, prior studies were limited by relatively small samples from single institutions; the largest series included fewer than 600 patients.^1-6

We conducted a study to determine predictors of ABT in a large cohort of patients admitted to US hospitals for shoulder arthroplasty. We also wanted to evaluate the effect of ABT on postoperative outcomes, including inpatient mortality, adverse events, prolonged hospital stay, and nonroutine discharge. According to the null hypothesis, in shoulder arthroplasty there will be no difference in risk factors between patients who require ABT and those who did not, after accounting for confounding variables.

Materials and Methods

This study was exempt from institutional review board approval, as all data were appropriately deidentified before use in this project. We used the Nationwide Inpatient Sample (NIS) to retrospectively study the period 2002–2011, from which all demographic, clinical, and resource use data were derived.¹⁶ NIS, an annual survey conducted by the Agency for Healthcare Research and Quality (AHRQ) since 1988, has generated a huge amount of data, forming the largest all-payer inpatient care database in the United States. Yearly samples contain discharge data from about 8 million hospital stays at more than 1000 hospitals across 46 states, approximating a 20% random sample of all hospital discharges at participating institutions.¹⁷ These data are then weighted to generate statistically valid national estimates.

The NIS database uses International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes to identify 15 medical diagnoses up to the year 2008 and a maximum of 25 medical diagnoses and 15 procedures thereafter. In addition, the database includes information on patient and hospital characteristics as well as inpatient outcomes such as length of stay, total hospitalization charges, and discharge disposition.^18,19 Given its large sample size and data volume, NIS is a powerful tool in the analysis of data associated with a multitude of medical diagnoses and procedures.²⁰

We used the NIS database to study a population of 422,371 patients (age, >18 years) who underwent total shoulder arthroplasty (TSA) or hemiarthroplasty (HSA) between 2002 and 2011. ICD-9-CM procedure codes for TSA (81.80, 81.88) and HSA (81.81) were used to identify this population. We also analyzed data for reverse TSA for the year 2011. Then we divided our target population into 2 different cohorts: patients who did not receive any blood transfusion products and patients who received a transfusion of allogeneic packed cells (ICD-9-CM code 99.04 was used to identify the latter cohort).

In this study, normal distribution of the dataset was assumed, given the large sample size. The 2 cohorts were evaluated through bivariate analysis using the Pearson χ² test for categorical data and the independent-samples t test for continuous data. The extent to which diagnosis, age, race, sex, and medical comorbidities were predictive of blood transfusion after TSA or HSA was evaluated through multivariate binary logistic regression analysis. Statistical significance was set at P < .05. All statistical analyses and data modeling were performed with SPSS Version 22.0.

Results

Using the NIS database, we stratified an estimated 422,371 patients who presented for shoulder arthroplasty between January 1, 2002, and December 31, 2011, into a TSA cohort (59.3%) and an HSA cohort (40.7%). Eight percent (33,889) of all patients received an ABT; the proportion of patients who received ABT was higher (P < .001) for the HSA cohort (55.6%) than the TSA cohort (39.4%). Further, the rate of ABT after shoulder arthroplasty showed an upward inclination (Figure).

Demographically, patients who received ABT tended (P < .001) to be older (74±11 years vs 68±11 years) and of a minority race (black or Hispanic) and to fall in either the lowest range of median household income (21.5% vs 20.7%; ≤$38,999) or the highest (27.3% vs 25.4%; ≥$63,000). Shoulder arthroplasty with ABT occurred more often (P < .001) at hospitals that were urban (13.3% vs 11.3%), medium in size (27.3% vs 23.4%), and nonteaching (56.2% vs 54.3%). In addition, ABT was used more often (P < .001) in patients with a primary diagnosis of fracture (43.1% vs 14.3%) or fracture nonunion (4.4% vs 2.1%). These groups also had a longer (P < .001) hospital stay (5.0±4.3 days vs 2.5±2.2 days). Table 1 summarizes these findings.

The 2 cohorts were then analyzed for presence of medical comorbidities (Table 2). Patients who required ABT during shoulder arthroplasty had a significantly (P < .001) higher prevalence of congestive heart failure, chronic lung disease, hypertension, uncomplicated and complicated diabetes mellitus, liver disease, renal failure, fluid and electrolyte disorders, pulmonary circulatory disease, weight loss, coagulopathy, and deficiency anemia.

In multivariate regression modeling (Table 3), demographic predictors of ABT (P < .001) included increasing age (odds ratio [OR], 1.03 per year; 95% confidence interval [95% CI], 1.03-1.03), female sex (OR, 1.55; 95% CI, 1.51-1.60), and minority race (black or Hispanic). Odds of requiring ABT were higher for patients with Medicare (OR, 1.25; 95% CI, 1.20-1.30) and patients with Medicaid (OR, 1.63; 95% CI, 1.51-1.77) than for patients with private insurance.

ABT was more likely to be required (P < .001) in patients with a primary diagnosis of fracture (OR, 4.49; 95% CI, 4.34-4.65), avascular necrosis (OR, 2.06; 95% CI, 1.91-2.22), rheumatoid arthritis (OR, 1.91; 95% CI, 1.72-2.12), fracture nonunion (OR, 3.55; 95% CI, 3.33-3.79), or rotator cuff arthropathy (OR, 1.47; 95% CI, 1.41-1.54) than for patients with osteoarthritis. Moreover, compared with patients having HSA, patients having TSA were more likely to require ABT (OR, 1.20; 95% CI, 1.17-1.24). According to the analysis restricted to the year 2011, compared with patients having anatomical TSAs, patients having reverse TSAs were 1.6 times more likely (P < .001) to require ABT (OR, 1.63; 95% CI, 1.50-1.79).

With the exception of obesity, all comorbidities were significant (P < .001) independent predictors of ABT after shoulder arthroplasty: deficiency anemia (OR, 3.42; 95% CI, 3.32-3.52), coagulopathy (OR, 2.54; 95% CI, 2.36-2.73), fluid and electrolyte disorders (OR, 1.91; 95% CI, 1.84-1.97), and weight loss (OR, 1.78; 95% CI, 1.58-2.00).

Patients who received ABT were more likely to experience adverse events (OR, 1.74; 95% CI, 1.68-1.81), prolonged hospital stay (OR, 3.21; 95% CI, 3.12-3.30), and nonroutine discharge (OR, 1.77; 95% CI, 1.72-1.82) (Table 4). There was no difference in mortality between the 2 cohorts.

Discussion

There is an abundance of literature on blood transfusions in hip and knee arthroplasty, but there are few articles on ABT in shoulder arthroplasty, and they all report data from single institutions with relatively low caseloads.^{1,2,11-13,15,21} In the present study, we investigated ABT in shoulder arthroplasty from the perspective of a multi-institutional database with a caseload of more than 400,000. Given the rapidly increasing rates of shoulder arthroplasty, it is important to further examine this issue to minimize unnecessary blood transfusion and its associated risks and costs.⁷

We found that 8% of patients who had shoulder arthroplasty received ABT, which is consistent with previously reported transfusion rates (range, 7%-43%).^1-6 Rates of ABT after shoulder arthroplasty have continued to rise. The exception, a decrease during the year 2010, can be explained by increased efforts to more rigidly follow transfusion indication guidelines to reduce the number of potentially unnecessary ABTs.^21-24 Our study also identified numerous significant independent predictors of ABT in shoulder arthroplasty: age, sex, race, insurance status, procedure type, primary diagnoses, and multiple medical comorbidities.

Demographics

According to our analysis, more than 80% of patients who received ABT were over age 65 years, which aligns with what several other studies have demonstrated: Increasing age is a predictor of ABT, despite higher rates of comorbidities and lower preoperative Hb levels in this population.^{1,2,4,5,25-27} Consistent with previous work, female sex was predictive of ABT.^2,5 It has been suggested that females are more likely predisposed to ABT because of lower preoperative Hb and smaller blood mass.^2,5,28 Interestingly, our study showed a higher likelihood of ABT in both black and Hispanic populations. Further, patients with Medicare or Medicaid were more likely to receive ABT.

Primary Diagnosis

Although patients with a primary diagnosis of osteoarthritis constitute the majority of patients who undergo shoulder arthroplasty, our analysis showed that patients with a diagnosis of proximal humerus fracture were more likely to receive ABT. This finding is reasonable given studies showing the high prevalence of proximal humerus fractures in elderly women.^29,30 Similarly, patients with a humerus fracture nonunion were more likely to receive a blood transfusion, which is unsurprising given the increased complexity associated with arthroplasty in this predominately elderly population.³¹ Interestingly, compared with patients with osteoarthritis, patients with any one of the other primary diagnoses were more likely to require a transfusion—proximal humerus fracture being the most significant, followed by humerus fracture nonunion, avascular necrosis, rheumatoid arthritis, and rotator cuff arthropathy.

Type of Arthroplasty

Bivariate analysis revealed that 55.6% of the patients who received ABT underwent HSA; the other 44.4% underwent TSA. The effect of primary diagnosis on procedure choice likely played a role in this finding. HSA indications include humerus fracture, which has been associated with increased ABT, whereas patients with osteoarthritis requiring TSA are significantly less likely to require ABT, as reflected in this analysis.^7,32-34 Previous studies have failed to show a difference in blood transfusion rates between TSA and HSA.^2,4-6,35 Conversely, with confounding factors controlled for, multivariate logistic regression analysis showed that TSA was 1.2 times more likely than HSA to require ABT, which could be explained by the increased operative time, case complexity, and blood loss that may be associated with the glenoid exposure.^36,37 With analysis restricted to the year 2011, patients with reverse TSAs were 1.6 times more likely than patients with anatomical TSAs to receive a blood transfusion (OR, 1.63; 95% CI, 1.50-1.79). Although this finding differs from what was previously reported, it fits given that patients having reverse TSAs are often older and may present with a more significant comorbidity profile.³ In addition, there are the increased technical surgical aspects associated with “salvage surgery” for challenging indications such as cuff arthropathy and failed previous arthroplasty.^38-41

Medical Comorbidities

Patients who received ABT were more likely to present with numerous medical comorbidities. Previous studies have indicated that the presence of multiple medical comorbidities significantly increased blood transfusion rates, possibly by working synergistically.⁴² All studies of blood transfusion in shoulder arthroplasty concluded that lower preoperative Hb was an independent predictor.^1-6 Schumer and colleagues⁴ reported a 4-fold increase in likelihood of blood transfusion in patients with a preoperative Hb level less than 12.5 g/dL. In addition, Millett and colleagues⁶ showed a 20-fold increase in likelihood of transfusion in patients with a preoperative Hb level less than 11.0 g/dL compared with patients with a level higher than 13.0 g/dL. Patients with a Hb level between 11.0 and 13.0 g/dL showed a 5-fold increase in likelihood of transfusion.⁶ We should note that correction of preoperative anemia through various pharmacologic methods (eg, erythropoietin, intravenous iron supplementation) has been shown to decrease postoperative transfusion rates.^43,44 Although we could not include preoperative Hb levels in the present study, given inherent limitations in using NIS, our multivariate analysis showed that preoperative deficiency anemia and coagulopathy were the most significant predictors of ABT.

In addition, the multivariate logistic regression model showed that both cardiac disease and diabetes were independent predictors of ABT, confirming data reported by Ahmadi and colleagues.¹ Although not as well characterized in other studies, in the current analysis multiple other medical comorbidities, including fluid and electrolyte abnormalities, weight loss, liver disease, renal failure, and chronic lung disease, had significant predictive value. Contrarily, obesity significantly decreased the odds of ABT, likely because of higher baseline blood volume in obese patients.

Patient Outcomes

Patients who undergo shoulder arthroplasty with ABT are more likely to experience adverse events or a prolonged hospital stay and are more often discharged to a nursing home or an extended-care facility. In this population, however, deaths did not occur at a significantly higher rate—similar to what was found for patients who underwent hip or knee arthroplasty with blood transfusions.⁴⁵

Little has been done to investigate the effect of pharmacologic agents on the need for perioperative ABT for orthopedic shoulder procedures. Aprotinin, tranexamic acid, epoetin-α, and aminocaproic acid have all been effective in limiting ABT during the perioperative period in various orthopedic hip, knee, and spine procedures.^9,46-53 Given the increased morbidity associated with ABT, it may be beneficial to use similar methods to limit blood loss in high-risk patients undergoing shoulder arthroplasty.

Study Limitations

NIS has intrinsic limitations. Given its massive volume, it is subject to errors in both data entry and clinical coding. Moreover, the database lacks data that would have been useful in our study: preoperative Hb levels, intraoperative course, number of units transfused, total blood loss, use of blood conservation techniques, transfusion protocols, and severity of comorbidities. Reverse TSA was given a unique ICD-9-CM code in October 2010, so 2011 was the only year we were able to examine the relationship between reverse TSA and transfusions. Further, our analysis was unable to identify any medications, including chronic anticoagulants or postoperative prophylaxis, that have been shown to significantly affect blood transfusion rates.⁵⁴ Yet, there are obvious advantages to using the NIS database, as previously outlined across the medical landscape.

Conclusion

Our results confirmed previous findings and identified new predictors of ABT in shoulder arthroplasty in a large cohort. We examined demographics and perioperative complications while identifying predictors of ABT use. Patients who received ABT were older, female, and nonwhite and were covered by Medicare or Medicaid insurance, and many had a primary diagnosis of proximal humerus fracture. The ABT cohort had numerous medical comorbidities, including deficiency anemia and coagulopathy. Identifying this patient population is a prerequisite to educating patients while minimizing unnecessary risks and costs.

Using NIS data on a population of 422,371 patients who underwent shoulder arthroplasty, we identified the 5 likeliest predictors of ABT: fracture, fracture nonunion, deficiency anemia, coagulopathy, and avascular necrosis. Of the identified variables associated with ABT, deficiency anemia may be the most amenable to treatment; therefore, there may be benefit in delaying elective shoulder arthroplasty in this cohort. Given these findings, it is important to identify at-risk patients before surgery, with the intent to provide education and minimize risk.

Highlights from the December 2015 issue of The Hospitalist include a look at ways hospitals can better care for unassigned or uninsured patients, how electronic health record implementation has contributed to physician burnout, and our key clinical question examines strategies for secondary stroke prevention.

Highlights from the December 2015 issue of The Hospitalist include a look at ways hospitals can better care for unassigned or uninsured patients, how electronic health record implementation has contributed to physician burnout, and our key clinical question examines strategies for secondary stroke prevention.

Highlights from the December 2015 issue of The Hospitalist include a look at ways hospitals can better care for unassigned or uninsured patients, how electronic health record implementation has contributed to physician burnout, and our key clinical question examines strategies for secondary stroke prevention.

National Hockey League (NHL), Major League Soccer (MLS), and US Olympic/World Cup Ski/Snowboard (Olympic) athletes receive orthopedic care from a select group of surgeons. There are 30 NHL teams, 19 MLS teams, 1 Olympic ski team, and 1 Olympic snowboard team, for a total of 51 teams and a rough total of 2229 athletes (1500 NHL, 570 MLS, 159 Olympic).¹

Studies have shown that MLS athletes and X-Game skiers and snowboarders have performed well on return to sport (RTS) after anterior cruciate ligament (ACL) reconstruction.^2,3 However, the techniques, graft choices, and rehabilitation protocols used to return these elite athletes to their preinjury level of performance have not been elucidated. It is unclear if the treatment given to these elite athletes differs from that given to recreational athletes and nonathletes. Bradley and colleagues⁴ examined how 32 NFL team orthopedists treated ACL tears, and Erickson and colleagues⁵ recently surveyed NFL and National Collegiate Athletic Association (NCAA) team physicians to determine practice patterns (eg, surgical techniques, graft choices, postoperative protocols) in treating ACL tears. Until now, however, no one has examined NHL, MLS, or Olympic team orthopedic surgeons’ practice patterns as they relate to ACL reconstruction.

We conducted an online survey of NHL, MLS, and Olympic team orthopedic surgeons to determine practice patterns relating to ACL reconstruction in elite athletes. Given the practice patterns of surgeons in our practice, we hypothesized that the surveyed surgeons treating these elite athletes would most commonly use bone–patellar tendon–bone (BPTB) autograft with a single-bundle technique. We also hypothesized that they would permit RTS without a brace at a minimum of 6 months after surgery, with a normal physical examination, and after successful completion of a structured battery of RTS tests.

Materials and Methods

On the SurveyMonkey website (http://www.surveymonkey.com), we created a 7-question base survey, with other questions added for the NHL and MLS surveys (Figure 1). We sent this survey to 94 team orthopedic surgeons (41 NHL, 26 MLS, 27 Olympic) identified through Internet searches and direct contact with team public relations departments. The survey was approved by MLS and NHL research committees. In 2013, each survey was sent out 5 times. The response rates for each round are shown in Figure 2. All responses remained confidential; we did not learn surgeons’ identities. Data were collected and analyzed through the SurveyMonkey website. Each surgeon was instructed to respond to all relevant questions in the survey. The survey was designed such that the participant could not submit the survey without answering all the questions. Descriptive statistics were calculated for each study and parameter analyzed. Continuous variable data are reported as means and standard deviations (weighted means where applicable). Categorical data are reported as frequencies with percentages.

Results

Of the 94 team orthopedic surgeons surveyed, 47 (50%) responded (NHL, 49%; MLS, 50%; Olympic, 52%). Mean (SD) experience as a team physician was 7.73 (5.33) years (range, 2-20 years) for NHL, 6.77 (6.64) years (range, 2-20 years) for MLS, and 1.14 (0.36) years (range, 1-10 years) for Olympic. Mean (SD) number of ACL reconstructions performed in 2012 was 101 (51) for NHL (range, 50-200), 78 (38) for MLS (range, 20-150), and 110 (105) for Olympic (range, 25-175) (Table 1). Of the 47 surgeons, 42 (89.4%) used autograft in the treatment of elite athletes, and 5 (10.6%) used allograft. Autograft choices were BPTB (n = 33; 70.2%), 4-strand semitendinosus (n = 7; 14.9%), and quadriceps (n = 2; 4.3%); allograft choices were 4-strand semitendinosus (n = 4; 8.5%) and BPTB (n = 1; 2.1%) (Table 2).

Of the 40 surgeons (85.1%) who indicated they would use autograft in 25-year-old recreational athletes, 25 (53.2%) would use BPTB, 13 (27.7%) would use 4-strand semitendinosus, and 2 (4.3%) would use quadriceps; of the 7 who indicated they would use allograft, 4 (8.5%) would use 4-strand semitendinosus, and 3 (6.4%) would use BPTB. In the NHL and MLS surveys, 19 surgeons (57.6%) indicated they would use autograft (6 would use BPTB, 13 would use 4-strand semitendinosus), and 14 (42.4%) would use allograft (7 would use BPTB, 5 would use Achilles, and 2 would use tibialis anterior) in 35-year-old recreational athletes.

Twenty-one surgeons (44.7%) were drilling the femoral tunnel through a transtibial portal, 36.2% through an anteromedial portal, and 12.8% using a 2-incision technique. All surgeons indicated they were using a single-bundle technique in ACL reconstruction. Thirty-three surgeons (70.2%) did not recommend a brace for their elite athletes on RTS. Olympic team surgeons had the highest rate of brace wear in RTS (50%, both skiers and snowboarders); NHL and MLS surgeons had significantly lower rates (25% and 15.4%, respectively) (Table 3).

Twenty (60.6%) of the NHL and MLS surgeons recommended waiting at least 6 months before RTS; 2 (6.1%) recommended waiting at least 9 months; no surgeon recommended waiting at least 12 months; and the others did not have a specific time frame for RTS. Twenty-seven surgeons (81.8%) recommended RTS after an athlete passed a series of RTS tests (eg, Vail, single-leg hop). Nineteen surgeons (57.6%) recommended waiting until the athlete had full range of motion, no pain, full strength, and subjective stability in the knee. Physicians could choose more than one answer for the previous question, allowing for a total percentage higher than 100%.

Discussion

The goal of this study was to determine how NHL, MLS, and Olympic team orthopedic surgeons manage ACL tears in elite and recreational athletes. Our study hypotheses were confirmed, as 70.2% of those surveyed used BPTB autograft for elite athletes, 100% used the single-bundle technique, 70.2% did not require a brace on RTS, 81.8% recommended RTS after the athlete passed a series of RTS tests (eg, Vail, single-leg hop), and 60.6% waited at least 6 months after surgery.

As soccer and skiing are the top 2 sports in which participants sustain ACL tears, it is necessary to report how surgeons obtain successful results in these patient populations.⁶ Using the US and Norwegian ACL reconstruction registries, Granan and colleagues⁶ found that, over a 7-year period, 5760 ACL tears occurred during soccer, and 2030 occurred during skiing. The scope of ACL injuries is broad, and treatment patterns must be elucidated. Although most surgeons do not treat elite athletes, many high school and college athletes compete at very high levels. Therefore, replicating the methods of the surgeons who treat elite athletes may be warranted.

In our survey, autograft (89.4%), particularly BPTB autograft (70.2%), was the most common graft choice for elite athletes. The rate of allograft use (42.4%) was higher for 35-year-old recreational athletes. As BPTB autograft produces reliable long-term results, this graft type is a reasonable choice.⁷ However, only 18% of our surveyed orthopedic surgeons indicated they would use BPTB autograft in older, recreational athletes. This stark difference is likely related to the more than 40% long-term side effects of anterior knee pain and graft harvest site morbidity with BPTB autograft as opposed to allograft and other types of autograft.^8,9 Younger patients may be more willing to accept some anterior knee pain to ensure bone-to-bone healing with BPTB autograft. This shift in graft choice may also reflect the desire to minimize skin incisions and their resulting scars, especially in female recreational athletes.

In a meta-analysis of more than 5000 patients, Kraeutler and colleagues⁷ found that BPTB autograft outperformed allograft according to several knee scores, including Lysholm and Tegner, and had a lower re-rupture rate (4.3% vs 12.7%). However, despite the superior performance of BPTB autograft, graft choice cannot overcome surgeon error in graft placement.¹⁰ BPTB autograft appears to remain the gold standard for ACL reconstruction for many reasons, including low failure rates and decreased costs.¹¹ Recently, investigators have tried to challenge the superiority of BPTB autograft. In a retrospective case–control study, Mascarenhas and colleagues¹² found that hamstring autograft afforded patients better extension and higher subjective outcome scores. Bourke and colleagues¹³ found a higher rate of contralateral ACL rupture in patients treated with BPTB autograft compared with hamstring autograft.

According to this survey, 44.7% of surgeons indicated they drilled the femoral tunnel through a transtibial portal, 36.2% used an anteromedial portal, and 12.8% used the 2-incision technique. These methods were recently evaluated to determine if any is superior to the others, but the study results were not definitive.¹⁴ Franceschi and colleagues¹⁵ found improved rotational and anterior stability of the knee with use of an anteromedial approach, but their findings were not clinically or functionally significant. Wang and colleagues¹⁶ found an extension loss in the late-stance phase of gait with the anteromedial approach; the transtibial approach was correlated with inferior anterior-posterior stability during the stance phase of gait. Therefore, our results parallel those in the current literature in that the surveyed population is split on which technique to use and likely bases its practice on comfort level and residency/fellowship training.

Limitations

This study had several limitations. First, it provided level V evidence of team physicians in 3 major sports. Although some of these physicians were also treating athletes in other sports, our survey targeted NHL, MLS, and Olympic athletes. It did not address all ages and both sexes—which is significant, given the higher rate of ACL tears in females. All NHL and MLS players are male, and there was a high rate of BPTB graft use in these sports. However, recreational athletes include both males and females, and the fact that some surgeons would choose a hamstring graft for a female for cosmetic reasons must not be overlooked. Conversely, that there was no difference in the number of BPTB autografts chosen between NHL and MLS surgeons versus Olympic surgeons, where females are included (all chose about 60% BPTB autografts for their elite athletes), disputes this limitation. Our survey response rate was 50%. Other studies have had similar rates in relation to ACL practices,¹⁷ especially elite team physicians’ practices,⁵ and recent literature has confirmed that lower response rates in surveys did not alter results and may in fact have improved results.^18,19 This percentage could be falsely low if some of our email addresses were incorrect. This rate also raises the possibility of selection bias, as surgeons who routinely used allograft in their athlete population may not have wanted to admit this. It is possible that some NHL, MLS, and Olympic athletes were treated by surgeons not included in this survey (in some cases, a non–team surgeon may have performed the athlete’s surgery). This survey did not address concomitant knee pathology or cover all possible technique variables.

Conclusion

Most of the NHL, MLS, and Olympic team orthopedic surgeons who were surveyed perform their ACL reconstructions using BPTB autograft, using a single-bundle technique, through a transtibial portal, and do not require bracing for their athletes returning to sport. Most required their athletes to complete a series of RTS tests before resuming competitive play.

National Hockey League (NHL), Major League Soccer (MLS), and US Olympic/World Cup Ski/Snowboard (Olympic) athletes receive orthopedic care from a select group of surgeons. There are 30 NHL teams, 19 MLS teams, 1 Olympic ski team, and 1 Olympic snowboard team, for a total of 51 teams and a rough total of 2229 athletes (1500 NHL, 570 MLS, 159 Olympic).¹

Studies have shown that MLS athletes and X-Game skiers and snowboarders have performed well on return to sport (RTS) after anterior cruciate ligament (ACL) reconstruction.^2,3 However, the techniques, graft choices, and rehabilitation protocols used to return these elite athletes to their preinjury level of performance have not been elucidated. It is unclear if the treatment given to these elite athletes differs from that given to recreational athletes and nonathletes. Bradley and colleagues⁴ examined how 32 NFL team orthopedists treated ACL tears, and Erickson and colleagues⁵ recently surveyed NFL and National Collegiate Athletic Association (NCAA) team physicians to determine practice patterns (eg, surgical techniques, graft choices, postoperative protocols) in treating ACL tears. Until now, however, no one has examined NHL, MLS, or Olympic team orthopedic surgeons’ practice patterns as they relate to ACL reconstruction.

We conducted an online survey of NHL, MLS, and Olympic team orthopedic surgeons to determine practice patterns relating to ACL reconstruction in elite athletes. Given the practice patterns of surgeons in our practice, we hypothesized that the surveyed surgeons treating these elite athletes would most commonly use bone–patellar tendon–bone (BPTB) autograft with a single-bundle technique. We also hypothesized that they would permit RTS without a brace at a minimum of 6 months after surgery, with a normal physical examination, and after successful completion of a structured battery of RTS tests.

Materials and Methods

On the SurveyMonkey website (http://www.surveymonkey.com), we created a 7-question base survey, with other questions added for the NHL and MLS surveys (Figure 1). We sent this survey to 94 team orthopedic surgeons (41 NHL, 26 MLS, 27 Olympic) identified through Internet searches and direct contact with team public relations departments. The survey was approved by MLS and NHL research committees. In 2013, each survey was sent out 5 times. The response rates for each round are shown in Figure 2. All responses remained confidential; we did not learn surgeons’ identities. Data were collected and analyzed through the SurveyMonkey website. Each surgeon was instructed to respond to all relevant questions in the survey. The survey was designed such that the participant could not submit the survey without answering all the questions. Descriptive statistics were calculated for each study and parameter analyzed. Continuous variable data are reported as means and standard deviations (weighted means where applicable). Categorical data are reported as frequencies with percentages.

Results

Of the 94 team orthopedic surgeons surveyed, 47 (50%) responded (NHL, 49%; MLS, 50%; Olympic, 52%). Mean (SD) experience as a team physician was 7.73 (5.33) years (range, 2-20 years) for NHL, 6.77 (6.64) years (range, 2-20 years) for MLS, and 1.14 (0.36) years (range, 1-10 years) for Olympic. Mean (SD) number of ACL reconstructions performed in 2012 was 101 (51) for NHL (range, 50-200), 78 (38) for MLS (range, 20-150), and 110 (105) for Olympic (range, 25-175) (Table 1). Of the 47 surgeons, 42 (89.4%) used autograft in the treatment of elite athletes, and 5 (10.6%) used allograft. Autograft choices were BPTB (n = 33; 70.2%), 4-strand semitendinosus (n = 7; 14.9%), and quadriceps (n = 2; 4.3%); allograft choices were 4-strand semitendinosus (n = 4; 8.5%) and BPTB (n = 1; 2.1%) (Table 2).

Of the 40 surgeons (85.1%) who indicated they would use autograft in 25-year-old recreational athletes, 25 (53.2%) would use BPTB, 13 (27.7%) would use 4-strand semitendinosus, and 2 (4.3%) would use quadriceps; of the 7 who indicated they would use allograft, 4 (8.5%) would use 4-strand semitendinosus, and 3 (6.4%) would use BPTB. In the NHL and MLS surveys, 19 surgeons (57.6%) indicated they would use autograft (6 would use BPTB, 13 would use 4-strand semitendinosus), and 14 (42.4%) would use allograft (7 would use BPTB, 5 would use Achilles, and 2 would use tibialis anterior) in 35-year-old recreational athletes.

Twenty-one surgeons (44.7%) were drilling the femoral tunnel through a transtibial portal, 36.2% through an anteromedial portal, and 12.8% using a 2-incision technique. All surgeons indicated they were using a single-bundle technique in ACL reconstruction. Thirty-three surgeons (70.2%) did not recommend a brace for their elite athletes on RTS. Olympic team surgeons had the highest rate of brace wear in RTS (50%, both skiers and snowboarders); NHL and MLS surgeons had significantly lower rates (25% and 15.4%, respectively) (Table 3).

Twenty (60.6%) of the NHL and MLS surgeons recommended waiting at least 6 months before RTS; 2 (6.1%) recommended waiting at least 9 months; no surgeon recommended waiting at least 12 months; and the others did not have a specific time frame for RTS. Twenty-seven surgeons (81.8%) recommended RTS after an athlete passed a series of RTS tests (eg, Vail, single-leg hop). Nineteen surgeons (57.6%) recommended waiting until the athlete had full range of motion, no pain, full strength, and subjective stability in the knee. Physicians could choose more than one answer for the previous question, allowing for a total percentage higher than 100%.

Discussion

The goal of this study was to determine how NHL, MLS, and Olympic team orthopedic surgeons manage ACL tears in elite and recreational athletes. Our study hypotheses were confirmed, as 70.2% of those surveyed used BPTB autograft for elite athletes, 100% used the single-bundle technique, 70.2% did not require a brace on RTS, 81.8% recommended RTS after the athlete passed a series of RTS tests (eg, Vail, single-leg hop), and 60.6% waited at least 6 months after surgery.

As soccer and skiing are the top 2 sports in which participants sustain ACL tears, it is necessary to report how surgeons obtain successful results in these patient populations.⁶ Using the US and Norwegian ACL reconstruction registries, Granan and colleagues⁶ found that, over a 7-year period, 5760 ACL tears occurred during soccer, and 2030 occurred during skiing. The scope of ACL injuries is broad, and treatment patterns must be elucidated. Although most surgeons do not treat elite athletes, many high school and college athletes compete at very high levels. Therefore, replicating the methods of the surgeons who treat elite athletes may be warranted.

In our survey, autograft (89.4%), particularly BPTB autograft (70.2%), was the most common graft choice for elite athletes. The rate of allograft use (42.4%) was higher for 35-year-old recreational athletes. As BPTB autograft produces reliable long-term results, this graft type is a reasonable choice.⁷ However, only 18% of our surveyed orthopedic surgeons indicated they would use BPTB autograft in older, recreational athletes. This stark difference is likely related to the more than 40% long-term side effects of anterior knee pain and graft harvest site morbidity with BPTB autograft as opposed to allograft and other types of autograft.^8,9 Younger patients may be more willing to accept some anterior knee pain to ensure bone-to-bone healing with BPTB autograft. This shift in graft choice may also reflect the desire to minimize skin incisions and their resulting scars, especially in female recreational athletes.

In a meta-analysis of more than 5000 patients, Kraeutler and colleagues⁷ found that BPTB autograft outperformed allograft according to several knee scores, including Lysholm and Tegner, and had a lower re-rupture rate (4.3% vs 12.7%). However, despite the superior performance of BPTB autograft, graft choice cannot overcome surgeon error in graft placement.¹⁰ BPTB autograft appears to remain the gold standard for ACL reconstruction for many reasons, including low failure rates and decreased costs.¹¹ Recently, investigators have tried to challenge the superiority of BPTB autograft. In a retrospective case–control study, Mascarenhas and colleagues¹² found that hamstring autograft afforded patients better extension and higher subjective outcome scores. Bourke and colleagues¹³ found a higher rate of contralateral ACL rupture in patients treated with BPTB autograft compared with hamstring autograft.

According to this survey, 44.7% of surgeons indicated they drilled the femoral tunnel through a transtibial portal, 36.2% used an anteromedial portal, and 12.8% used the 2-incision technique. These methods were recently evaluated to determine if any is superior to the others, but the study results were not definitive.¹⁴ Franceschi and colleagues¹⁵ found improved rotational and anterior stability of the knee with use of an anteromedial approach, but their findings were not clinically or functionally significant. Wang and colleagues¹⁶ found an extension loss in the late-stance phase of gait with the anteromedial approach; the transtibial approach was correlated with inferior anterior-posterior stability during the stance phase of gait. Therefore, our results parallel those in the current literature in that the surveyed population is split on which technique to use and likely bases its practice on comfort level and residency/fellowship training.

Limitations

This study had several limitations. First, it provided level V evidence of team physicians in 3 major sports. Although some of these physicians were also treating athletes in other sports, our survey targeted NHL, MLS, and Olympic athletes. It did not address all ages and both sexes—which is significant, given the higher rate of ACL tears in females. All NHL and MLS players are male, and there was a high rate of BPTB graft use in these sports. However, recreational athletes include both males and females, and the fact that some surgeons would choose a hamstring graft for a female for cosmetic reasons must not be overlooked. Conversely, that there was no difference in the number of BPTB autografts chosen between NHL and MLS surgeons versus Olympic surgeons, where females are included (all chose about 60% BPTB autografts for their elite athletes), disputes this limitation. Our survey response rate was 50%. Other studies have had similar rates in relation to ACL practices,¹⁷ especially elite team physicians’ practices,⁵ and recent literature has confirmed that lower response rates in surveys did not alter results and may in fact have improved results.^18,19 This percentage could be falsely low if some of our email addresses were incorrect. This rate also raises the possibility of selection bias, as surgeons who routinely used allograft in their athlete population may not have wanted to admit this. It is possible that some NHL, MLS, and Olympic athletes were treated by surgeons not included in this survey (in some cases, a non–team surgeon may have performed the athlete’s surgery). This survey did not address concomitant knee pathology or cover all possible technique variables.

Conclusion

Most of the NHL, MLS, and Olympic team orthopedic surgeons who were surveyed perform their ACL reconstructions using BPTB autograft, using a single-bundle technique, through a transtibial portal, and do not require bracing for their athletes returning to sport. Most required their athletes to complete a series of RTS tests before resuming competitive play.

National Hockey League (NHL), Major League Soccer (MLS), and US Olympic/World Cup Ski/Snowboard (Olympic) athletes receive orthopedic care from a select group of surgeons. There are 30 NHL teams, 19 MLS teams, 1 Olympic ski team, and 1 Olympic snowboard team, for a total of 51 teams and a rough total of 2229 athletes (1500 NHL, 570 MLS, 159 Olympic).¹

Studies have shown that MLS athletes and X-Game skiers and snowboarders have performed well on return to sport (RTS) after anterior cruciate ligament (ACL) reconstruction.^2,3 However, the techniques, graft choices, and rehabilitation protocols used to return these elite athletes to their preinjury level of performance have not been elucidated. It is unclear if the treatment given to these elite athletes differs from that given to recreational athletes and nonathletes. Bradley and colleagues⁴ examined how 32 NFL team orthopedists treated ACL tears, and Erickson and colleagues⁵ recently surveyed NFL and National Collegiate Athletic Association (NCAA) team physicians to determine practice patterns (eg, surgical techniques, graft choices, postoperative protocols) in treating ACL tears. Until now, however, no one has examined NHL, MLS, or Olympic team orthopedic surgeons’ practice patterns as they relate to ACL reconstruction.

We conducted an online survey of NHL, MLS, and Olympic team orthopedic surgeons to determine practice patterns relating to ACL reconstruction in elite athletes. Given the practice patterns of surgeons in our practice, we hypothesized that the surveyed surgeons treating these elite athletes would most commonly use bone–patellar tendon–bone (BPTB) autograft with a single-bundle technique. We also hypothesized that they would permit RTS without a brace at a minimum of 6 months after surgery, with a normal physical examination, and after successful completion of a structured battery of RTS tests.

Materials and Methods

On the SurveyMonkey website (http://www.surveymonkey.com), we created a 7-question base survey, with other questions added for the NHL and MLS surveys (Figure 1). We sent this survey to 94 team orthopedic surgeons (41 NHL, 26 MLS, 27 Olympic) identified through Internet searches and direct contact with team public relations departments. The survey was approved by MLS and NHL research committees. In 2013, each survey was sent out 5 times. The response rates for each round are shown in Figure 2. All responses remained confidential; we did not learn surgeons’ identities. Data were collected and analyzed through the SurveyMonkey website. Each surgeon was instructed to respond to all relevant questions in the survey. The survey was designed such that the participant could not submit the survey without answering all the questions. Descriptive statistics were calculated for each study and parameter analyzed. Continuous variable data are reported as means and standard deviations (weighted means where applicable). Categorical data are reported as frequencies with percentages.

Results

Of the 94 team orthopedic surgeons surveyed, 47 (50%) responded (NHL, 49%; MLS, 50%; Olympic, 52%). Mean (SD) experience as a team physician was 7.73 (5.33) years (range, 2-20 years) for NHL, 6.77 (6.64) years (range, 2-20 years) for MLS, and 1.14 (0.36) years (range, 1-10 years) for Olympic. Mean (SD) number of ACL reconstructions performed in 2012 was 101 (51) for NHL (range, 50-200), 78 (38) for MLS (range, 20-150), and 110 (105) for Olympic (range, 25-175) (Table 1). Of the 47 surgeons, 42 (89.4%) used autograft in the treatment of elite athletes, and 5 (10.6%) used allograft. Autograft choices were BPTB (n = 33; 70.2%), 4-strand semitendinosus (n = 7; 14.9%), and quadriceps (n = 2; 4.3%); allograft choices were 4-strand semitendinosus (n = 4; 8.5%) and BPTB (n = 1; 2.1%) (Table 2).

Of the 40 surgeons (85.1%) who indicated they would use autograft in 25-year-old recreational athletes, 25 (53.2%) would use BPTB, 13 (27.7%) would use 4-strand semitendinosus, and 2 (4.3%) would use quadriceps; of the 7 who indicated they would use allograft, 4 (8.5%) would use 4-strand semitendinosus, and 3 (6.4%) would use BPTB. In the NHL and MLS surveys, 19 surgeons (57.6%) indicated they would use autograft (6 would use BPTB, 13 would use 4-strand semitendinosus), and 14 (42.4%) would use allograft (7 would use BPTB, 5 would use Achilles, and 2 would use tibialis anterior) in 35-year-old recreational athletes.

Twenty-one surgeons (44.7%) were drilling the femoral tunnel through a transtibial portal, 36.2% through an anteromedial portal, and 12.8% using a 2-incision technique. All surgeons indicated they were using a single-bundle technique in ACL reconstruction. Thirty-three surgeons (70.2%) did not recommend a brace for their elite athletes on RTS. Olympic team surgeons had the highest rate of brace wear in RTS (50%, both skiers and snowboarders); NHL and MLS surgeons had significantly lower rates (25% and 15.4%, respectively) (Table 3).

Twenty (60.6%) of the NHL and MLS surgeons recommended waiting at least 6 months before RTS; 2 (6.1%) recommended waiting at least 9 months; no surgeon recommended waiting at least 12 months; and the others did not have a specific time frame for RTS. Twenty-seven surgeons (81.8%) recommended RTS after an athlete passed a series of RTS tests (eg, Vail, single-leg hop). Nineteen surgeons (57.6%) recommended waiting until the athlete had full range of motion, no pain, full strength, and subjective stability in the knee. Physicians could choose more than one answer for the previous question, allowing for a total percentage higher than 100%.

Discussion

The goal of this study was to determine how NHL, MLS, and Olympic team orthopedic surgeons manage ACL tears in elite and recreational athletes. Our study hypotheses were confirmed, as 70.2% of those surveyed used BPTB autograft for elite athletes, 100% used the single-bundle technique, 70.2% did not require a brace on RTS, 81.8% recommended RTS after the athlete passed a series of RTS tests (eg, Vail, single-leg hop), and 60.6% waited at least 6 months after surgery.

As soccer and skiing are the top 2 sports in which participants sustain ACL tears, it is necessary to report how surgeons obtain successful results in these patient populations.⁶ Using the US and Norwegian ACL reconstruction registries, Granan and colleagues⁶ found that, over a 7-year period, 5760 ACL tears occurred during soccer, and 2030 occurred during skiing. The scope of ACL injuries is broad, and treatment patterns must be elucidated. Although most surgeons do not treat elite athletes, many high school and college athletes compete at very high levels. Therefore, replicating the methods of the surgeons who treat elite athletes may be warranted.

In our survey, autograft (89.4%), particularly BPTB autograft (70.2%), was the most common graft choice for elite athletes. The rate of allograft use (42.4%) was higher for 35-year-old recreational athletes. As BPTB autograft produces reliable long-term results, this graft type is a reasonable choice.⁷ However, only 18% of our surveyed orthopedic surgeons indicated they would use BPTB autograft in older, recreational athletes. This stark difference is likely related to the more than 40% long-term side effects of anterior knee pain and graft harvest site morbidity with BPTB autograft as opposed to allograft and other types of autograft.^8,9 Younger patients may be more willing to accept some anterior knee pain to ensure bone-to-bone healing with BPTB autograft. This shift in graft choice may also reflect the desire to minimize skin incisions and their resulting scars, especially in female recreational athletes.

In a meta-analysis of more than 5000 patients, Kraeutler and colleagues⁷ found that BPTB autograft outperformed allograft according to several knee scores, including Lysholm and Tegner, and had a lower re-rupture rate (4.3% vs 12.7%). However, despite the superior performance of BPTB autograft, graft choice cannot overcome surgeon error in graft placement.¹⁰ BPTB autograft appears to remain the gold standard for ACL reconstruction for many reasons, including low failure rates and decreased costs.¹¹ Recently, investigators have tried to challenge the superiority of BPTB autograft. In a retrospective case–control study, Mascarenhas and colleagues¹² found that hamstring autograft afforded patients better extension and higher subjective outcome scores. Bourke and colleagues¹³ found a higher rate of contralateral ACL rupture in patients treated with BPTB autograft compared with hamstring autograft.

According to this survey, 44.7% of surgeons indicated they drilled the femoral tunnel through a transtibial portal, 36.2% used an anteromedial portal, and 12.8% used the 2-incision technique. These methods were recently evaluated to determine if any is superior to the others, but the study results were not definitive.¹⁴ Franceschi and colleagues¹⁵ found improved rotational and anterior stability of the knee with use of an anteromedial approach, but their findings were not clinically or functionally significant. Wang and colleagues¹⁶ found an extension loss in the late-stance phase of gait with the anteromedial approach; the transtibial approach was correlated with inferior anterior-posterior stability during the stance phase of gait. Therefore, our results parallel those in the current literature in that the surveyed population is split on which technique to use and likely bases its practice on comfort level and residency/fellowship training.

Limitations

This study had several limitations. First, it provided level V evidence of team physicians in 3 major sports. Although some of these physicians were also treating athletes in other sports, our survey targeted NHL, MLS, and Olympic athletes. It did not address all ages and both sexes—which is significant, given the higher rate of ACL tears in females. All NHL and MLS players are male, and there was a high rate of BPTB graft use in these sports. However, recreational athletes include both males and females, and the fact that some surgeons would choose a hamstring graft for a female for cosmetic reasons must not be overlooked. Conversely, that there was no difference in the number of BPTB autografts chosen between NHL and MLS surgeons versus Olympic surgeons, where females are included (all chose about 60% BPTB autografts for their elite athletes), disputes this limitation. Our survey response rate was 50%. Other studies have had similar rates in relation to ACL practices,¹⁷ especially elite team physicians’ practices,⁵ and recent literature has confirmed that lower response rates in surveys did not alter results and may in fact have improved results.^18,19 This percentage could be falsely low if some of our email addresses were incorrect. This rate also raises the possibility of selection bias, as surgeons who routinely used allograft in their athlete population may not have wanted to admit this. It is possible that some NHL, MLS, and Olympic athletes were treated by surgeons not included in this survey (in some cases, a non–team surgeon may have performed the athlete’s surgery). This survey did not address concomitant knee pathology or cover all possible technique variables.

Conclusion

Most of the NHL, MLS, and Olympic team orthopedic surgeons who were surveyed perform their ACL reconstructions using BPTB autograft, using a single-bundle technique, through a transtibial portal, and do not require bracing for their athletes returning to sport. Most required their athletes to complete a series of RTS tests before resuming competitive play.

ORLANDO – Monotherapy with ibrutinib (Imbruvica) prolonged survival longer than did standard chemotherapy using chlorambucil (Leukeran) in the front-line treatment of older patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the phase III RESONATE-2 study.

Co–drug developers Pharmacyclics and Janssen Biotech announced this summer that ibrutinib, an orally bioavailable, small-molecule inhibitor of Bruton’s tyrosine kinase, had achieved its primary and secondary endpoints.

Courtesy: Neil Osterweil

But the first full look at the data at the annual meeting of the American Society of Hematology showed ibrutinib reduced the risk of progression or death by 84% by independent review compared with chlorambucil, which has been a standard first-line therapy in older CLL patients.

The results were simultaneously published in the New England Journal of Medicine (doi: 10.1056/NEJMoa1509388).

With a median follow-up of 18.4 months, median progression-free survival (PFS) had not been reached with ibrutinib vs. 19 months with chlorambucil (hazard ratio, 0.16; P less than .001).

By investigator assessment, ibrutinib reduced the risk of progression by 91%, with an 18-month PFS rate of 94% vs. 45% with chlorambucil (HR, 0.09; P less than .001).

The PFS benefit with ibrutinib was consistent regardless of patient age, Rai stage, ECOG (Eastern Cooperative Oncology Group) status, bulky disease, and importantly, such high-risk markers as chromosome 11q deletion and unmutated immunoglobulin heavy chain variable (IGHV) mutation status, study author Dr. Alessandra Tedeschi, of Hospital Niguarda Cà Granda, Milan, , said at a press briefing highlighting the study (Ab. 485).

In addition, ibrutinib led to an 84% reduction in the risk of death compared with chlorambucil (HR, 0.16; P = .001). The 24-month overall survival rate was 98% with ibrutinib versus 85% with chlorambucil.

Single-agent ibrutinib was approved in 2014 for patients with CLL who had received at least one prior therapy and for all patients with the deleterious 17p deletion on the basis of the phase III RESONATE trial in relapsed or refractory CLL.

Three-year follow-up in the phase II PCYC-1102 study signaled a benefit with ibrutinib in treatment-naive CLL, showing an overall response rate of 84%, 30-month PFS of 96%, and overall survival rate of 97% in a subset of 31 patients at least 65 years old (Blood. 2015 Apr 16;125[16]:2497-506).

“The phase III RESONATE-2 trial confirms the efficacy of ibrutinib in treatment-naive CLL patients, leading to a 91% reduction in risk of progression and 84% reduction in risk of death when compared to chlorambucil,” Dr. Tedeschi said.

In all, 269 patients, median age of 73 years, were evenly randomized to once-daily ibrutinib 420 mg until progression or unacceptable toxicity or chlorambucil 0.5 mg/kg (up to a maximum of 0.8 mg/kg) on days 1 and 15 of a 28-day cycle for up to 12 cycles. Patients with the deleterious 17p deletion were excluded, as single-agent chlorambucil is not effective in this population.

Ibrutinib significantly improved bone marrow function, as reflected by a sustained increase in hemoglobin and platelets.

“This is very important in this category of elderly patients, in whom bone marrow failure is the most common cause of morbidity,” Dr. Tedeschi said.

There were 3 deaths on the ibrutinib arm and 17 on the chlorambucil arm.

The majority of patients (87%) in this older population with frequent comorbidities was able to continue on oral, once-daily ibrutinib with a median of 1.5 years of follow-up, she said.

The most common adverse events on ibrutinib were grade one diarrhea, fatigue, cough, and nausea that did not result in treatment discontinuation. On the chlorambucil arm, fatigue nausea, vomiting, and cytopenias occurred more frequently than with ibrutinib.

Grade 3 maculopapular rash occurred in 3% with ibrutinib and 2% with chlorambucil, she said.

Ibrutinib was associated with higher and not insignificant rates of atrial fibrillation and major hemorrhage compared with chlorambucil, said Dr. Brian T. Hill of the Taussig Cancer Institute at the Cleveland Clinic, who was not involved in the study. In our interview, Dr. Hill also questions the relevance today of chlorambucil monotherapy as the comparator arm in RESONATE-2.

Pharmacyclics, which is jointly developing ibrutinib with Janssen Biotech, sponsored the study. Dr. Tedeschi reported having nothing to disclose. Several coauthors reported relationships with Pharmacyclics and Janssen.

[email protected]

ORLANDO – Monotherapy with ibrutinib (Imbruvica) prolonged survival longer than did standard chemotherapy using chlorambucil (Leukeran) in the front-line treatment of older patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the phase III RESONATE-2 study.

Co–drug developers Pharmacyclics and Janssen Biotech announced this summer that ibrutinib, an orally bioavailable, small-molecule inhibitor of Bruton’s tyrosine kinase, had achieved its primary and secondary endpoints.

Courtesy: Neil Osterweil

But the first full look at the data at the annual meeting of the American Society of Hematology showed ibrutinib reduced the risk of progression or death by 84% by independent review compared with chlorambucil, which has been a standard first-line therapy in older CLL patients.

The results were simultaneously published in the New England Journal of Medicine (doi: 10.1056/NEJMoa1509388).

With a median follow-up of 18.4 months, median progression-free survival (PFS) had not been reached with ibrutinib vs. 19 months with chlorambucil (hazard ratio, 0.16; P less than .001).

By investigator assessment, ibrutinib reduced the risk of progression by 91%, with an 18-month PFS rate of 94% vs. 45% with chlorambucil (HR, 0.09; P less than .001).

The PFS benefit with ibrutinib was consistent regardless of patient age, Rai stage, ECOG (Eastern Cooperative Oncology Group) status, bulky disease, and importantly, such high-risk markers as chromosome 11q deletion and unmutated immunoglobulin heavy chain variable (IGHV) mutation status, study author Dr. Alessandra Tedeschi, of Hospital Niguarda Cà Granda, Milan, , said at a press briefing highlighting the study (Ab. 485).

In addition, ibrutinib led to an 84% reduction in the risk of death compared with chlorambucil (HR, 0.16; P = .001). The 24-month overall survival rate was 98% with ibrutinib versus 85% with chlorambucil.

Single-agent ibrutinib was approved in 2014 for patients with CLL who had received at least one prior therapy and for all patients with the deleterious 17p deletion on the basis of the phase III RESONATE trial in relapsed or refractory CLL.

Three-year follow-up in the phase II PCYC-1102 study signaled a benefit with ibrutinib in treatment-naive CLL, showing an overall response rate of 84%, 30-month PFS of 96%, and overall survival rate of 97% in a subset of 31 patients at least 65 years old (Blood. 2015 Apr 16;125[16]:2497-506).

“The phase III RESONATE-2 trial confirms the efficacy of ibrutinib in treatment-naive CLL patients, leading to a 91% reduction in risk of progression and 84% reduction in risk of death when compared to chlorambucil,” Dr. Tedeschi said.

In all, 269 patients, median age of 73 years, were evenly randomized to once-daily ibrutinib 420 mg until progression or unacceptable toxicity or chlorambucil 0.5 mg/kg (up to a maximum of 0.8 mg/kg) on days 1 and 15 of a 28-day cycle for up to 12 cycles. Patients with the deleterious 17p deletion were excluded, as single-agent chlorambucil is not effective in this population.

Ibrutinib significantly improved bone marrow function, as reflected by a sustained increase in hemoglobin and platelets.

“This is very important in this category of elderly patients, in whom bone marrow failure is the most common cause of morbidity,” Dr. Tedeschi said.

There were 3 deaths on the ibrutinib arm and 17 on the chlorambucil arm.

The majority of patients (87%) in this older population with frequent comorbidities was able to continue on oral, once-daily ibrutinib with a median of 1.5 years of follow-up, she said.

The most common adverse events on ibrutinib were grade one diarrhea, fatigue, cough, and nausea that did not result in treatment discontinuation. On the chlorambucil arm, fatigue nausea, vomiting, and cytopenias occurred more frequently than with ibrutinib.

Grade 3 maculopapular rash occurred in 3% with ibrutinib and 2% with chlorambucil, she said.

Ibrutinib was associated with higher and not insignificant rates of atrial fibrillation and major hemorrhage compared with chlorambucil, said Dr. Brian T. Hill of the Taussig Cancer Institute at the Cleveland Clinic, who was not involved in the study. In our interview, Dr. Hill also questions the relevance today of chlorambucil monotherapy as the comparator arm in RESONATE-2.

Pharmacyclics, which is jointly developing ibrutinib with Janssen Biotech, sponsored the study. Dr. Tedeschi reported having nothing to disclose. Several coauthors reported relationships with Pharmacyclics and Janssen.

[email protected]

ORLANDO – Monotherapy with ibrutinib (Imbruvica) prolonged survival longer than did standard chemotherapy using chlorambucil (Leukeran) in the front-line treatment of older patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the phase III RESONATE-2 study.

Co–drug developers Pharmacyclics and Janssen Biotech announced this summer that ibrutinib, an orally bioavailable, small-molecule inhibitor of Bruton’s tyrosine kinase, had achieved its primary and secondary endpoints.

Courtesy: Neil Osterweil

But the first full look at the data at the annual meeting of the American Society of Hematology showed ibrutinib reduced the risk of progression or death by 84% by independent review compared with chlorambucil, which has been a standard first-line therapy in older CLL patients.

The results were simultaneously published in the New England Journal of Medicine (doi: 10.1056/NEJMoa1509388).

With a median follow-up of 18.4 months, median progression-free survival (PFS) had not been reached with ibrutinib vs. 19 months with chlorambucil (hazard ratio, 0.16; P less than .001).

By investigator assessment, ibrutinib reduced the risk of progression by 91%, with an 18-month PFS rate of 94% vs. 45% with chlorambucil (HR, 0.09; P less than .001).

The PFS benefit with ibrutinib was consistent regardless of patient age, Rai stage, ECOG (Eastern Cooperative Oncology Group) status, bulky disease, and importantly, such high-risk markers as chromosome 11q deletion and unmutated immunoglobulin heavy chain variable (IGHV) mutation status, study author Dr. Alessandra Tedeschi, of Hospital Niguarda Cà Granda, Milan, , said at a press briefing highlighting the study (Ab. 485).

In addition, ibrutinib led to an 84% reduction in the risk of death compared with chlorambucil (HR, 0.16; P = .001). The 24-month overall survival rate was 98% with ibrutinib versus 85% with chlorambucil.

Single-agent ibrutinib was approved in 2014 for patients with CLL who had received at least one prior therapy and for all patients with the deleterious 17p deletion on the basis of the phase III RESONATE trial in relapsed or refractory CLL.

Three-year follow-up in the phase II PCYC-1102 study signaled a benefit with ibrutinib in treatment-naive CLL, showing an overall response rate of 84%, 30-month PFS of 96%, and overall survival rate of 97% in a subset of 31 patients at least 65 years old (Blood. 2015 Apr 16;125[16]:2497-506).

“The phase III RESONATE-2 trial confirms the efficacy of ibrutinib in treatment-naive CLL patients, leading to a 91% reduction in risk of progression and 84% reduction in risk of death when compared to chlorambucil,” Dr. Tedeschi said.

In all, 269 patients, median age of 73 years, were evenly randomized to once-daily ibrutinib 420 mg until progression or unacceptable toxicity or chlorambucil 0.5 mg/kg (up to a maximum of 0.8 mg/kg) on days 1 and 15 of a 28-day cycle for up to 12 cycles. Patients with the deleterious 17p deletion were excluded, as single-agent chlorambucil is not effective in this population.

Ibrutinib significantly improved bone marrow function, as reflected by a sustained increase in hemoglobin and platelets.

“This is very important in this category of elderly patients, in whom bone marrow failure is the most common cause of morbidity,” Dr. Tedeschi said.

There were 3 deaths on the ibrutinib arm and 17 on the chlorambucil arm.

The majority of patients (87%) in this older population with frequent comorbidities was able to continue on oral, once-daily ibrutinib with a median of 1.5 years of follow-up, she said.

The most common adverse events on ibrutinib were grade one diarrhea, fatigue, cough, and nausea that did not result in treatment discontinuation. On the chlorambucil arm, fatigue nausea, vomiting, and cytopenias occurred more frequently than with ibrutinib.

Grade 3 maculopapular rash occurred in 3% with ibrutinib and 2% with chlorambucil, she said.

Ibrutinib was associated with higher and not insignificant rates of atrial fibrillation and major hemorrhage compared with chlorambucil, said Dr. Brian T. Hill of the Taussig Cancer Institute at the Cleveland Clinic, who was not involved in the study. In our interview, Dr. Hill also questions the relevance today of chlorambucil monotherapy as the comparator arm in RESONATE-2.

Pharmacyclics, which is jointly developing ibrutinib with Janssen Biotech, sponsored the study. Dr. Tedeschi reported having nothing to disclose. Several coauthors reported relationships with Pharmacyclics and Janssen.

[email protected]

ORLANDO – The oral multikinase inhibitor midostaurin improved overall survival by 23% when added to standard chemotherapy and given as maintenance therapy for 1 year in newly diagnosed patients with FLT3-mutated acute myeloid leukemia (AML) in the global phase III CALGB 10603/RATIFY trial.

The results struck a chord at the annual meeting of the American Society of Hematology because the benefits of targeted therapy have so far eluded AML patients despite transforming the treatment of other blood cancers. Currently, there are no approved, targeted treatments for AML.

CALGB 10603/RATIFY is the first large, controlled trial to show an overall survival benefit in the roughly 30% of AML patients with a mutation in the FLT3 gene.

“This is exciting because we haven’t had a new treatment in AML for 30 years,” Dr. Robert Hromas of the University of Florida, Gainesville, said while moderating a press conference highlighting the plenary abstract.

The results were a decade in the making after midostaurin failed previously when used in all AML patients rather than the subset with the FLT3 mutation. But the persistence of researchers, the international collaboration, and funding in cancer research paid off, Dr. Hromas said.

Study author Dr. Richard M. Stone, chief of staff at Dana-Farber Cancer Institute in Boston, reviewed the results of CALGB 10603/RATIFY in an interview.

CALGB 10603/RATIFY was sponsored by the Cancer Therapy Evaluation Program. Dr. Stone reported financial relationships with several drug companies including Novartis, which provided the study drug and sponsored the trial outside North America. Dr. Hromas disclosed serving as an uncompensated advisory board member without equity for Cloud Pharmaceuticals.

[email protected]

ORLANDO – The oral multikinase inhibitor midostaurin improved overall survival by 23% when added to standard chemotherapy and given as maintenance therapy for 1 year in newly diagnosed patients with FLT3-mutated acute myeloid leukemia (AML) in the global phase III CALGB 10603/RATIFY trial.

The results struck a chord at the annual meeting of the American Society of Hematology because the benefits of targeted therapy have so far eluded AML patients despite transforming the treatment of other blood cancers. Currently, there are no approved, targeted treatments for AML.

CALGB 10603/RATIFY is the first large, controlled trial to show an overall survival benefit in the roughly 30% of AML patients with a mutation in the FLT3 gene.

“This is exciting because we haven’t had a new treatment in AML for 30 years,” Dr. Robert Hromas of the University of Florida, Gainesville, said while moderating a press conference highlighting the plenary abstract.

The results were a decade in the making after midostaurin failed previously when used in all AML patients rather than the subset with the FLT3 mutation. But the persistence of researchers, the international collaboration, and funding in cancer research paid off, Dr. Hromas said.

Study author Dr. Richard M. Stone, chief of staff at Dana-Farber Cancer Institute in Boston, reviewed the results of CALGB 10603/RATIFY in an interview.

CALGB 10603/RATIFY was sponsored by the Cancer Therapy Evaluation Program. Dr. Stone reported financial relationships with several drug companies including Novartis, which provided the study drug and sponsored the trial outside North America. Dr. Hromas disclosed serving as an uncompensated advisory board member without equity for Cloud Pharmaceuticals.

[email protected]

ORLANDO – The oral multikinase inhibitor midostaurin improved overall survival by 23% when added to standard chemotherapy and given as maintenance therapy for 1 year in newly diagnosed patients with FLT3-mutated acute myeloid leukemia (AML) in the global phase III CALGB 10603/RATIFY trial.

The results struck a chord at the annual meeting of the American Society of Hematology because the benefits of targeted therapy have so far eluded AML patients despite transforming the treatment of other blood cancers. Currently, there are no approved, targeted treatments for AML.

CALGB 10603/RATIFY is the first large, controlled trial to show an overall survival benefit in the roughly 30% of AML patients with a mutation in the FLT3 gene.

“This is exciting because we haven’t had a new treatment in AML for 30 years,” Dr. Robert Hromas of the University of Florida, Gainesville, said while moderating a press conference highlighting the plenary abstract.

The results were a decade in the making after midostaurin failed previously when used in all AML patients rather than the subset with the FLT3 mutation. But the persistence of researchers, the international collaboration, and funding in cancer research paid off, Dr. Hromas said.

Study author Dr. Richard M. Stone, chief of staff at Dana-Farber Cancer Institute in Boston, reviewed the results of CALGB 10603/RATIFY in an interview.

CALGB 10603/RATIFY was sponsored by the Cancer Therapy Evaluation Program. Dr. Stone reported financial relationships with several drug companies including Novartis, which provided the study drug and sponsored the trial outside North America. Dr. Hromas disclosed serving as an uncompensated advisory board member without equity for Cloud Pharmaceuticals.

[email protected]

NEW YORK - Intravascular ultrasound-guided (IVUS) stent implantation can lead to fewer adverse cardiac events compared with angiography-guided implantation, according to a new trial.

"Among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at one year," Dr. Myeong-Ki Hong of Severance Cardiovascular Hospital and Yonsei University College of Medicine in Seoul, Korea, and colleagues report.

"These differences were primarily due to lower risk of target lesion revascularization," they note in an article online November 10 in JAMA. They presented their findings simultaneously at the American Heart Association Scientific Sessions in Orlando, Fla.

Dr. Hong and colleagues conducted a trial involving 1,400 patients with long coronary lesions between 2010 and 2014 at 20 centers in Korea. They randomized 700 patients to IVUS-guided stent implantation and 700 to angiography-guided stent implantation. They had one-year follow-up results on 94.5%.

Patient mean age was 64 and 69% were men. The mean stented target length was 39.3 mm.

The composite endpoint of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction (MI), or ischemia-driven target lesion revascularization, occurred in 19 (2.9%) patients who underwent IVUS implantation and 39 (5.8%) patients who underwent angiography-guided implantation (hazard ratio, 0.48; p=0.007).

Cardiac death and target-related MI were not significantly different between the two groups. However, ischemia-driven target lesion revascularization occurred in 17 (2.5%) IVUS

patients and 33 (5%) angiography patients (HR 0.51, p=0.02).

Clinicians performed post-stent balloon dilation more frequently in IVUS patients than in angiography patients (76% vs. 57%, p<0.001), and the mean final balloon size was larger in IVUS patients.

Patients who met IVUS criteria for stent optimization (363, 54%) had significantly greater mean post-intervention minimal lumen area at the stented segment compared with patients who did not meet IVUS criteria.

"The clinical benefit of IVUS-guided (drug-eluting stent) implantation may be attributed to the larger minimal lumen diameter followed by the more frequent adjunct postdilation with a large-sized balloon in the IVUS-guided group," the researchers write.

"To our knowledge, the current study is the first demonstration of the clinical benefit of IVUS guidance in second generation (drug-eluting stent) implantation in an adequately powered randomized clinical trial," they note.

However, even though recent guidelines recommend IVUS-guided implantation for some patients, evidence for improved outcomes based on adequately powered trials remains inadequate, they caution.

Dr. Hong did not respond to a request for comments. Abbott Vascular funded this research. The authors reported no conflicts of interest.

NEW YORK - Intravascular ultrasound-guided (IVUS) stent implantation can lead to fewer adverse cardiac events compared with angiography-guided implantation, according to a new trial.

"Among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at one year," Dr. Myeong-Ki Hong of Severance Cardiovascular Hospital and Yonsei University College of Medicine in Seoul, Korea, and colleagues report.

"These differences were primarily due to lower risk of target lesion revascularization," they note in an article online November 10 in JAMA. They presented their findings simultaneously at the American Heart Association Scientific Sessions in Orlando, Fla.

Dr. Hong and colleagues conducted a trial involving 1,400 patients with long coronary lesions between 2010 and 2014 at 20 centers in Korea. They randomized 700 patients to IVUS-guided stent implantation and 700 to angiography-guided stent implantation. They had one-year follow-up results on 94.5%.

Patient mean age was 64 and 69% were men. The mean stented target length was 39.3 mm.

The composite endpoint of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction (MI), or ischemia-driven target lesion revascularization, occurred in 19 (2.9%) patients who underwent IVUS implantation and 39 (5.8%) patients who underwent angiography-guided implantation (hazard ratio, 0.48; p=0.007).

Cardiac death and target-related MI were not significantly different between the two groups. However, ischemia-driven target lesion revascularization occurred in 17 (2.5%) IVUS

patients and 33 (5%) angiography patients (HR 0.51, p=0.02).

Clinicians performed post-stent balloon dilation more frequently in IVUS patients than in angiography patients (76% vs. 57%, p<0.001), and the mean final balloon size was larger in IVUS patients.

Patients who met IVUS criteria for stent optimization (363, 54%) had significantly greater mean post-intervention minimal lumen area at the stented segment compared with patients who did not meet IVUS criteria.

"The clinical benefit of IVUS-guided (drug-eluting stent) implantation may be attributed to the larger minimal lumen diameter followed by the more frequent adjunct postdilation with a large-sized balloon in the IVUS-guided group," the researchers write.

"To our knowledge, the current study is the first demonstration of the clinical benefit of IVUS guidance in second generation (drug-eluting stent) implantation in an adequately powered randomized clinical trial," they note.

However, even though recent guidelines recommend IVUS-guided implantation for some patients, evidence for improved outcomes based on adequately powered trials remains inadequate, they caution.

Dr. Hong did not respond to a request for comments. Abbott Vascular funded this research. The authors reported no conflicts of interest.

NEW YORK - Intravascular ultrasound-guided (IVUS) stent implantation can lead to fewer adverse cardiac events compared with angiography-guided implantation, according to a new trial.

"Among patients requiring long coronary stent implantation, the use of IVUS-guided everolimus-eluting stent implantation, compared with angiography-guided stent implantation, resulted in a significantly lower rate of the composite of major adverse cardiac events at one year," Dr. Myeong-Ki Hong of Severance Cardiovascular Hospital and Yonsei University College of Medicine in Seoul, Korea, and colleagues report.

"These differences were primarily due to lower risk of target lesion revascularization," they note in an article online November 10 in JAMA. They presented their findings simultaneously at the American Heart Association Scientific Sessions in Orlando, Fla.

Dr. Hong and colleagues conducted a trial involving 1,400 patients with long coronary lesions between 2010 and 2014 at 20 centers in Korea. They randomized 700 patients to IVUS-guided stent implantation and 700 to angiography-guided stent implantation. They had one-year follow-up results on 94.5%.

Patient mean age was 64 and 69% were men. The mean stented target length was 39.3 mm.

The composite endpoint of major adverse cardiac events, including cardiac death, target lesion-related myocardial infarction (MI), or ischemia-driven target lesion revascularization, occurred in 19 (2.9%) patients who underwent IVUS implantation and 39 (5.8%) patients who underwent angiography-guided implantation (hazard ratio, 0.48; p=0.007).

Cardiac death and target-related MI were not significantly different between the two groups. However, ischemia-driven target lesion revascularization occurred in 17 (2.5%) IVUS

patients and 33 (5%) angiography patients (HR 0.51, p=0.02).

Clinicians performed post-stent balloon dilation more frequently in IVUS patients than in angiography patients (76% vs. 57%, p<0.001), and the mean final balloon size was larger in IVUS patients.

Patients who met IVUS criteria for stent optimization (363, 54%) had significantly greater mean post-intervention minimal lumen area at the stented segment compared with patients who did not meet IVUS criteria.

"The clinical benefit of IVUS-guided (drug-eluting stent) implantation may be attributed to the larger minimal lumen diameter followed by the more frequent adjunct postdilation with a large-sized balloon in the IVUS-guided group," the researchers write.

"To our knowledge, the current study is the first demonstration of the clinical benefit of IVUS guidance in second generation (drug-eluting stent) implantation in an adequately powered randomized clinical trial," they note.

However, even though recent guidelines recommend IVUS-guided implantation for some patients, evidence for improved outcomes based on adequately powered trials remains inadequate, they caution.

Dr. Hong did not respond to a request for comments. Abbott Vascular funded this research. The authors reported no conflicts of interest.

Two U.S. states experienced “moderate” activity of influenza-like illness for the week ending Nov. 28, 2015 – week 7 of the 2015-2016 flu season – the Centers for Disease Control and Prevention reported Dec. 4.

South Carolina had the highest (level 7) activity for the week, with Oklahoma joined by Puerto Rico at level 6. New Jersey was at the highest level (level 5) of “low” activity, while Arizona, Mississippi, and Virginia were a notch lower (level 4) but still in the “low” zone. All told, 20 states had flu activity of level 2 or higher, according to the CDC.

There were no influenza-associated pediatric deaths reported during the week, with two such deaths reported for the 2015-2016 season so far. For week 7 nationwide, 1.9% of patient visits reported through the U.S. Outpatient Influenza-like Illness Surveillance Network were the result of influenza-like illness – defined as a temperature of 100° F or greater and cough and/or sore throat – which is below the national baseline of 2.1%, the CDC said.

During week 7, 1.5% of the 11,288 specimens tested were positive for influenza, with 60% positive for influenza A and 40% positive for influenza B. For the season overall, 1.2% of the 102,675 specimens tested have been positive, with a 61/39 split for influenza A and B, the CDC noted.

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Two U.S. states experienced “moderate” activity of influenza-like illness for the week ending Nov. 28, 2015 – week 7 of the 2015-2016 flu season – the Centers for Disease Control and Prevention reported Dec. 4.

South Carolina had the highest (level 7) activity for the week, with Oklahoma joined by Puerto Rico at level 6. New Jersey was at the highest level (level 5) of “low” activity, while Arizona, Mississippi, and Virginia were a notch lower (level 4) but still in the “low” zone. All told, 20 states had flu activity of level 2 or higher, according to the CDC.

There were no influenza-associated pediatric deaths reported during the week, with two such deaths reported for the 2015-2016 season so far. For week 7 nationwide, 1.9% of patient visits reported through the U.S. Outpatient Influenza-like Illness Surveillance Network were the result of influenza-like illness – defined as a temperature of 100° F or greater and cough and/or sore throat – which is below the national baseline of 2.1%, the CDC said.

During week 7, 1.5% of the 11,288 specimens tested were positive for influenza, with 60% positive for influenza A and 40% positive for influenza B. For the season overall, 1.2% of the 102,675 specimens tested have been positive, with a 61/39 split for influenza A and B, the CDC noted.

[email protected]

Two U.S. states experienced “moderate” activity of influenza-like illness for the week ending Nov. 28, 2015 – week 7 of the 2015-2016 flu season – the Centers for Disease Control and Prevention reported Dec. 4.

South Carolina had the highest (level 7) activity for the week, with Oklahoma joined by Puerto Rico at level 6. New Jersey was at the highest level (level 5) of “low” activity, while Arizona, Mississippi, and Virginia were a notch lower (level 4) but still in the “low” zone. All told, 20 states had flu activity of level 2 or higher, according to the CDC.

There were no influenza-associated pediatric deaths reported during the week, with two such deaths reported for the 2015-2016 season so far. For week 7 nationwide, 1.9% of patient visits reported through the U.S. Outpatient Influenza-like Illness Surveillance Network were the result of influenza-like illness – defined as a temperature of 100° F or greater and cough and/or sore throat – which is below the national baseline of 2.1%, the CDC said.

During week 7, 1.5% of the 11,288 specimens tested were positive for influenza, with 60% positive for influenza A and 40% positive for influenza B. For the season overall, 1.2% of the 102,675 specimens tested have been positive, with a 61/39 split for influenza A and B, the CDC noted.

[email protected]