Infection and infection sites have been found to be associated with a significant increased risk of venous thromboembolism, according to results of a population-based, matched, case-control analysis of medical records covering the 13-year period 1988-2000.

Dr. Kevin P. Cohoon and his colleagues at the Mayo Clinic, Rochester, Minn., developed models using conditional logistic regression analysis to stratify the risk associated with specific infections and infection sites.

Courtesy Wikimedia Commons/Walter Serra, Giuseppe De Iaco, Claudio Reverberi, and Tiziano Gherli/Creative Commons License

Infection and infection sites have been found to be associated with a significant increased risk of venous thromboembolism, according to results of a population-based, matched, case-control analysis of medical records covering the 13-year period 1988-2000.

Dr. Kevin P. Cohoon and his colleagues at the Mayo Clinic, Rochester, Minn., developed models using conditional logistic regression analysis to stratify the risk associated with specific infections and infection sites.

Courtesy Wikimedia Commons/Walter Serra, Giuseppe De Iaco, Claudio Reverberi, and Tiziano Gherli/Creative Commons License

Infection and infection sites have been found to be associated with a significant increased risk of venous thromboembolism, according to results of a population-based, matched, case-control analysis of medical records covering the 13-year period 1988-2000.

Dr. Kevin P. Cohoon and his colleagues at the Mayo Clinic, Rochester, Minn., developed models using conditional logistic regression analysis to stratify the risk associated with specific infections and infection sites.

Courtesy Wikimedia Commons/Walter Serra, Giuseppe De Iaco, Claudio Reverberi, and Tiziano Gherli/Creative Commons License

In any given year, < 10% of people diagnosed with alcohol use disorder receive treatment, and many do not receive the type of care that best fits their needs. Two reasons may be that they don’t know where to turn for help, or they may not know that they have more treatment options beyond a mutual help group or long-term residential rehabilitation facility.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has developed a new online tool that may help. The “comprehensive, yet easy-to-use” Alcohol Treatment Navigator was developed “to help address the alcohol ‘treatment gap,’” said NIAAA Director George Koob, PhD. It’s based on decades of scientific research into clinical interventions and health services with input from patients, providers, and researchers.

The Navigator includes an overview of alcohol use disorder and a description of professionally led treatment options. It also gives step-by-step instructions for searching online directories of treatment providers, 10 questions to ask a provider, and signs of quality to listen for. A downloadable tool kit helps organize and simplify the search process.

In any given year, < 10% of people diagnosed with alcohol use disorder receive treatment, and many do not receive the type of care that best fits their needs. Two reasons may be that they don’t know where to turn for help, or they may not know that they have more treatment options beyond a mutual help group or long-term residential rehabilitation facility.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has developed a new online tool that may help. The “comprehensive, yet easy-to-use” Alcohol Treatment Navigator was developed “to help address the alcohol ‘treatment gap,’” said NIAAA Director George Koob, PhD. It’s based on decades of scientific research into clinical interventions and health services with input from patients, providers, and researchers.

The Navigator includes an overview of alcohol use disorder and a description of professionally led treatment options. It also gives step-by-step instructions for searching online directories of treatment providers, 10 questions to ask a provider, and signs of quality to listen for. A downloadable tool kit helps organize and simplify the search process.

In any given year, < 10% of people diagnosed with alcohol use disorder receive treatment, and many do not receive the type of care that best fits their needs. Two reasons may be that they don’t know where to turn for help, or they may not know that they have more treatment options beyond a mutual help group or long-term residential rehabilitation facility.

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has developed a new online tool that may help. The “comprehensive, yet easy-to-use” Alcohol Treatment Navigator was developed “to help address the alcohol ‘treatment gap,’” said NIAAA Director George Koob, PhD. It’s based on decades of scientific research into clinical interventions and health services with input from patients, providers, and researchers.

The Navigator includes an overview of alcohol use disorder and a description of professionally led treatment options. It also gives step-by-step instructions for searching online directories of treatment providers, 10 questions to ask a provider, and signs of quality to listen for. A downloadable tool kit helps organize and simplify the search process.

Photo courtesy of NIH

NEW YORK, NY—Speakers faced off over the issue of minimal residual disease (MRD) testing in multiple myeloma (MM) at Lymphoma & Myeloma 2017.

Ola Landgren, MD, PhD, of Weill Cornell Medicine in New York, New York, said, “it’s really a necessary and logical step forward to look at MRD.”

On the other hand, Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, took the clinicians’ perspective and suggested that, at this point, “we’re not yet ready to apply it to everyday practice.”

“[P]atients who have a complete response (CR) and are MRD negative have longer progression-free survival (PFS),” Dr Landgren pointed out, “and there are indications that their overall survival (OS) is better than in those patients who are just CR and MRD positive.”

“My position on this is that MRD testing is absolutely ready for prime time in the research and regulatory arena,” Dr Richardson contended. “The question for me, as a clinician, in my clinic, is ‘Do I apply it to everyday practice?’ And I would simply suggest to you, at this point, we’re not ready for that.”

Yes—MRD is ready for prime time

Dr Landgren based his argument on 2 meta-analyses published in 2016 and 2017 that outline the importance of MRD status in newly diagnosed MM patients.

The first analysis (Landgren et al 2016) showed that MRD negativity was associated with better PFS (hazard ratio [HR]=0.35] and OS (HR=0.48) than MRD positivity.

“So using more simple language,” Dr Landgren said, “this means that MRD negativity reduces the risk of progression by 65%, and it also reduces the risk of dying by 52%.”

The second analysis (Munshi et al 2017) also associated MRD-negative status with superior survival outcomes for both PFS (HR=0.41) and OS (HR=0.57).

As further confirmation of the importance of MRD status, the International Myeloma Working Group last year published response definitions that include MRD negativity at a sensitivity of 1 in 10⁵ cells or higher as the deepest level of treatment response in MM.

Dr Landgren drew on additional studies to support routine MRD testing in patient care.

The IFM Study Group found that, in newly diagnosed patients treated with lenalidomide, bortezomib, and dexamethasone followed by 1 year of lenalidomide maintenance, patients who received a subsequent transplant achieved superior outcomes compared to non-transplanted patients, in terms of CR (58% vs 46%) and 3-year PFS (61% vs 48%).

However, in patients who were MRD negative in both arms, the PFS rates were very similar, Dr Landgren said. And in terms of 3-year OS, there was no difference, at 88% in both arms.

The experience with daratumumab in relapsed/refractory patients exhibited a similar pattern.

The phase 3 POLLUX trial first showed that adding daratumumab to lenalidomide and dexamethasone was superior to lenalidomide and dexamethasone only, with a PFS at 18 months of 78% and 52%, respectively. This amounted to a 63% reduction in the risk of disease progression.

Investigators then took one more step forward, Dr Landgren said, and looked at MRD.

At a sensitivity of 10^-5, almost 25% of patients on the 3-drug regimen were MRD negative, “which is kind of amazing,” Dr Landgren said. “This is a very big step forward.”

“If you break down the results by MRD status, which is not the primary endpoint of the study, you see very similar patterns for PFS for MRD negative patients in each of the 2 arms,” he continued.

This raises the question of whether attaining MRD negativity is more important than the treatment modality.

MRD negativity has implications for speeding drug approvals, developing more sensitive assays, and future treatment management, Dr Landgren said.

No—MRD is not ready for prime time

Dr Richardson acknowledged that MRD assessment is important. However, he pointed out a number of caveats regarding how MRD assessment would be applied in clinical practice to support his position.

“I’d simply suggest to you that, in day-to-day practice, the definition [of MRD] is somewhat fluid,” he said. “And it varies, obviously, between diseases and technology used.”

For most malignancies, Dr Richardson said, 10⁹ to 10¹⁰ malignant cells are undetectable with conventional methods. These may or may not lead to a full clinical relapse within months or even years.

Using a sensitive technique to determine the presence of MRD could permit analysis of treatments that induce a greater depth of response or identify patients at risk of early relapse who need further treatment.

Dr Richardson enumerated hematologic malignancies that utilize MRD as secondary endpoints—acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma.

In chronic myeloid leukemia, MRD is used as a primary endpoint that dictates practice.

“And I would applaud the field in that area because, obviously, molecular response accepted as an endpoint by FDA for second-generation TKIs has been a bedrock of that approval process, and it now applies in clinical practice,” Dr Richardson said.

“Obviously, that’s where we’d like to be, but I’d suggest to you, just again, with a certain amount of moderation and a certain amount of caution, that we may not be quite there yet.”

Dr Richardson suggested that MRD assessment in MM is less advanced than in leukemia and lymphoma.

“[W]e are currently at the point where MRD assessments are clearly secondary endpoints, an important research tool,” he said.

Some “remarkable combination therapies,” he added, have abrogated some of the “extraordinary genetic complexity” in MM.

“The critical point here, though, is that, while we’re more successful in terms of these triplets and quadruplets and now with the introduction of monoclonal antibodies and similar approaches, we’re able to throw a bigger net around the disease,” Dr Richardson said.

“We’re not able to eradicate it completely, and cure remains, in myeloma, frankly, evasive. And I think that’s a critical point.”

Dr Richardson reviewed various strategies for molecular response monitoring, from flow cytometry to polymerase chain reaction and next-generation sequencing, noting that there is variance in applicability and sensitivity.

For example, the limits of detection among 91 labs ranged from 0.10% to 0.001%.

Dr Richardson returned to the “very robust” meta-analysis by Munshi and colleagues discussed by Dr Landgren.

While the authors’ analysis demonstrated that MRD is predictive of both longer PFS and OS, they concluded that the evidence supported MRD as an endpoint and research tool in clinical trials.

“So I would humbly suggest perhaps it’s not ready for clinical prime time yet,” Dr Richardson said.

He also referred to the IFM Study Group trial described by Dr Landgren, calling it a “critical forward effort.”

“[W]hat’s so interesting is that there was no difference in overall survival,” Dr Richardson said. “Now, that’s a very important point as we soberly look at these data and judge what they mean for each patient.”

And so Dr Richardson stood by his assessment that MRD is not yet a standard of care but may be one day. 

Photo courtesy of NIH

NEW YORK, NY—Speakers faced off over the issue of minimal residual disease (MRD) testing in multiple myeloma (MM) at Lymphoma & Myeloma 2017.

Ola Landgren, MD, PhD, of Weill Cornell Medicine in New York, New York, said, “it’s really a necessary and logical step forward to look at MRD.”

On the other hand, Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, took the clinicians’ perspective and suggested that, at this point, “we’re not yet ready to apply it to everyday practice.”

“[P]atients who have a complete response (CR) and are MRD negative have longer progression-free survival (PFS),” Dr Landgren pointed out, “and there are indications that their overall survival (OS) is better than in those patients who are just CR and MRD positive.”

“My position on this is that MRD testing is absolutely ready for prime time in the research and regulatory arena,” Dr Richardson contended. “The question for me, as a clinician, in my clinic, is ‘Do I apply it to everyday practice?’ And I would simply suggest to you, at this point, we’re not ready for that.”

Yes—MRD is ready for prime time

Dr Landgren based his argument on 2 meta-analyses published in 2016 and 2017 that outline the importance of MRD status in newly diagnosed MM patients.

The first analysis (Landgren et al 2016) showed that MRD negativity was associated with better PFS (hazard ratio [HR]=0.35] and OS (HR=0.48) than MRD positivity.

“So using more simple language,” Dr Landgren said, “this means that MRD negativity reduces the risk of progression by 65%, and it also reduces the risk of dying by 52%.”

The second analysis (Munshi et al 2017) also associated MRD-negative status with superior survival outcomes for both PFS (HR=0.41) and OS (HR=0.57).

As further confirmation of the importance of MRD status, the International Myeloma Working Group last year published response definitions that include MRD negativity at a sensitivity of 1 in 10⁵ cells or higher as the deepest level of treatment response in MM.

Dr Landgren drew on additional studies to support routine MRD testing in patient care.

The IFM Study Group found that, in newly diagnosed patients treated with lenalidomide, bortezomib, and dexamethasone followed by 1 year of lenalidomide maintenance, patients who received a subsequent transplant achieved superior outcomes compared to non-transplanted patients, in terms of CR (58% vs 46%) and 3-year PFS (61% vs 48%).

However, in patients who were MRD negative in both arms, the PFS rates were very similar, Dr Landgren said. And in terms of 3-year OS, there was no difference, at 88% in both arms.

The experience with daratumumab in relapsed/refractory patients exhibited a similar pattern.

The phase 3 POLLUX trial first showed that adding daratumumab to lenalidomide and dexamethasone was superior to lenalidomide and dexamethasone only, with a PFS at 18 months of 78% and 52%, respectively. This amounted to a 63% reduction in the risk of disease progression.

Investigators then took one more step forward, Dr Landgren said, and looked at MRD.

At a sensitivity of 10^-5, almost 25% of patients on the 3-drug regimen were MRD negative, “which is kind of amazing,” Dr Landgren said. “This is a very big step forward.”

“If you break down the results by MRD status, which is not the primary endpoint of the study, you see very similar patterns for PFS for MRD negative patients in each of the 2 arms,” he continued.

This raises the question of whether attaining MRD negativity is more important than the treatment modality.

MRD negativity has implications for speeding drug approvals, developing more sensitive assays, and future treatment management, Dr Landgren said.

No—MRD is not ready for prime time

Dr Richardson acknowledged that MRD assessment is important. However, he pointed out a number of caveats regarding how MRD assessment would be applied in clinical practice to support his position.

“I’d simply suggest to you that, in day-to-day practice, the definition [of MRD] is somewhat fluid,” he said. “And it varies, obviously, between diseases and technology used.”

For most malignancies, Dr Richardson said, 10⁹ to 10¹⁰ malignant cells are undetectable with conventional methods. These may or may not lead to a full clinical relapse within months or even years.

Using a sensitive technique to determine the presence of MRD could permit analysis of treatments that induce a greater depth of response or identify patients at risk of early relapse who need further treatment.

Dr Richardson enumerated hematologic malignancies that utilize MRD as secondary endpoints—acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma.

In chronic myeloid leukemia, MRD is used as a primary endpoint that dictates practice.

“And I would applaud the field in that area because, obviously, molecular response accepted as an endpoint by FDA for second-generation TKIs has been a bedrock of that approval process, and it now applies in clinical practice,” Dr Richardson said.

“Obviously, that’s where we’d like to be, but I’d suggest to you, just again, with a certain amount of moderation and a certain amount of caution, that we may not be quite there yet.”

Dr Richardson suggested that MRD assessment in MM is less advanced than in leukemia and lymphoma.

“[W]e are currently at the point where MRD assessments are clearly secondary endpoints, an important research tool,” he said.

Some “remarkable combination therapies,” he added, have abrogated some of the “extraordinary genetic complexity” in MM.

“The critical point here, though, is that, while we’re more successful in terms of these triplets and quadruplets and now with the introduction of monoclonal antibodies and similar approaches, we’re able to throw a bigger net around the disease,” Dr Richardson said.

“We’re not able to eradicate it completely, and cure remains, in myeloma, frankly, evasive. And I think that’s a critical point.”

Dr Richardson reviewed various strategies for molecular response monitoring, from flow cytometry to polymerase chain reaction and next-generation sequencing, noting that there is variance in applicability and sensitivity.

For example, the limits of detection among 91 labs ranged from 0.10% to 0.001%.

Dr Richardson returned to the “very robust” meta-analysis by Munshi and colleagues discussed by Dr Landgren.

While the authors’ analysis demonstrated that MRD is predictive of both longer PFS and OS, they concluded that the evidence supported MRD as an endpoint and research tool in clinical trials.

“So I would humbly suggest perhaps it’s not ready for clinical prime time yet,” Dr Richardson said.

He also referred to the IFM Study Group trial described by Dr Landgren, calling it a “critical forward effort.”

“[W]hat’s so interesting is that there was no difference in overall survival,” Dr Richardson said. “Now, that’s a very important point as we soberly look at these data and judge what they mean for each patient.”

And so Dr Richardson stood by his assessment that MRD is not yet a standard of care but may be one day. 

Photo courtesy of NIH

NEW YORK, NY—Speakers faced off over the issue of minimal residual disease (MRD) testing in multiple myeloma (MM) at Lymphoma & Myeloma 2017.

Ola Landgren, MD, PhD, of Weill Cornell Medicine in New York, New York, said, “it’s really a necessary and logical step forward to look at MRD.”

On the other hand, Paul Richardson, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, took the clinicians’ perspective and suggested that, at this point, “we’re not yet ready to apply it to everyday practice.”

“[P]atients who have a complete response (CR) and are MRD negative have longer progression-free survival (PFS),” Dr Landgren pointed out, “and there are indications that their overall survival (OS) is better than in those patients who are just CR and MRD positive.”

“My position on this is that MRD testing is absolutely ready for prime time in the research and regulatory arena,” Dr Richardson contended. “The question for me, as a clinician, in my clinic, is ‘Do I apply it to everyday practice?’ And I would simply suggest to you, at this point, we’re not ready for that.”

Yes—MRD is ready for prime time

Dr Landgren based his argument on 2 meta-analyses published in 2016 and 2017 that outline the importance of MRD status in newly diagnosed MM patients.

The first analysis (Landgren et al 2016) showed that MRD negativity was associated with better PFS (hazard ratio [HR]=0.35] and OS (HR=0.48) than MRD positivity.

“So using more simple language,” Dr Landgren said, “this means that MRD negativity reduces the risk of progression by 65%, and it also reduces the risk of dying by 52%.”

The second analysis (Munshi et al 2017) also associated MRD-negative status with superior survival outcomes for both PFS (HR=0.41) and OS (HR=0.57).

As further confirmation of the importance of MRD status, the International Myeloma Working Group last year published response definitions that include MRD negativity at a sensitivity of 1 in 10⁵ cells or higher as the deepest level of treatment response in MM.

Dr Landgren drew on additional studies to support routine MRD testing in patient care.

The IFM Study Group found that, in newly diagnosed patients treated with lenalidomide, bortezomib, and dexamethasone followed by 1 year of lenalidomide maintenance, patients who received a subsequent transplant achieved superior outcomes compared to non-transplanted patients, in terms of CR (58% vs 46%) and 3-year PFS (61% vs 48%).

However, in patients who were MRD negative in both arms, the PFS rates were very similar, Dr Landgren said. And in terms of 3-year OS, there was no difference, at 88% in both arms.

The experience with daratumumab in relapsed/refractory patients exhibited a similar pattern.

The phase 3 POLLUX trial first showed that adding daratumumab to lenalidomide and dexamethasone was superior to lenalidomide and dexamethasone only, with a PFS at 18 months of 78% and 52%, respectively. This amounted to a 63% reduction in the risk of disease progression.

Investigators then took one more step forward, Dr Landgren said, and looked at MRD.

At a sensitivity of 10^-5, almost 25% of patients on the 3-drug regimen were MRD negative, “which is kind of amazing,” Dr Landgren said. “This is a very big step forward.”

“If you break down the results by MRD status, which is not the primary endpoint of the study, you see very similar patterns for PFS for MRD negative patients in each of the 2 arms,” he continued.

This raises the question of whether attaining MRD negativity is more important than the treatment modality.

MRD negativity has implications for speeding drug approvals, developing more sensitive assays, and future treatment management, Dr Landgren said.

No—MRD is not ready for prime time

Dr Richardson acknowledged that MRD assessment is important. However, he pointed out a number of caveats regarding how MRD assessment would be applied in clinical practice to support his position.

“I’d simply suggest to you that, in day-to-day practice, the definition [of MRD] is somewhat fluid,” he said. “And it varies, obviously, between diseases and technology used.”

For most malignancies, Dr Richardson said, 10⁹ to 10¹⁰ malignant cells are undetectable with conventional methods. These may or may not lead to a full clinical relapse within months or even years.

Using a sensitive technique to determine the presence of MRD could permit analysis of treatments that induce a greater depth of response or identify patients at risk of early relapse who need further treatment.

Dr Richardson enumerated hematologic malignancies that utilize MRD as secondary endpoints—acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, follicular lymphoma, and mantle cell lymphoma.

In chronic myeloid leukemia, MRD is used as a primary endpoint that dictates practice.

“And I would applaud the field in that area because, obviously, molecular response accepted as an endpoint by FDA for second-generation TKIs has been a bedrock of that approval process, and it now applies in clinical practice,” Dr Richardson said.

“Obviously, that’s where we’d like to be, but I’d suggest to you, just again, with a certain amount of moderation and a certain amount of caution, that we may not be quite there yet.”

Dr Richardson suggested that MRD assessment in MM is less advanced than in leukemia and lymphoma.

“[W]e are currently at the point where MRD assessments are clearly secondary endpoints, an important research tool,” he said.

Some “remarkable combination therapies,” he added, have abrogated some of the “extraordinary genetic complexity” in MM.

“The critical point here, though, is that, while we’re more successful in terms of these triplets and quadruplets and now with the introduction of monoclonal antibodies and similar approaches, we’re able to throw a bigger net around the disease,” Dr Richardson said.

“We’re not able to eradicate it completely, and cure remains, in myeloma, frankly, evasive. And I think that’s a critical point.”

Dr Richardson reviewed various strategies for molecular response monitoring, from flow cytometry to polymerase chain reaction and next-generation sequencing, noting that there is variance in applicability and sensitivity.

For example, the limits of detection among 91 labs ranged from 0.10% to 0.001%.

Dr Richardson returned to the “very robust” meta-analysis by Munshi and colleagues discussed by Dr Landgren.

While the authors’ analysis demonstrated that MRD is predictive of both longer PFS and OS, they concluded that the evidence supported MRD as an endpoint and research tool in clinical trials.

“So I would humbly suggest perhaps it’s not ready for clinical prime time yet,” Dr Richardson said.

He also referred to the IFM Study Group trial described by Dr Landgren, calling it a “critical forward effort.”

“[W]hat’s so interesting is that there was no difference in overall survival,” Dr Richardson said. “Now, that’s a very important point as we soberly look at these data and judge what they mean for each patient.”

And so Dr Richardson stood by his assessment that MRD is not yet a standard of care but may be one day. 

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Red blood cells

The US Food and Drug Administration (FDA) has approved ferric citrate (Auryxia) to treat iron-deficiency anemia in adults with chronic kidney disease (CKD) who are not on dialysis.

Ferric citrate was originally approved by the FDA in September 2014 for the control of serum phosphorus levels in patients with CKD who require dialysis.

The full prescribing information for the drug is available at www.Auryxia.com.

“We are pleased with the broad indication permitted by the FDA, as a first-line treatment option for adults with iron-deficiency anemia and chronic kidney disease not on dialysis,” said John Neylan, MD, senior vice president and chief medical officer of Keryx Biopharmaceuticals, Inc., the company marketing ferric citrate.

“Physicians and their patients now have a new treatment option to help manage a serious complication of this complex disease.”

The new approval of ferric citrate was based on results from a 24-week, placebo-controlled, phase 3  trial. Results from this trial were published in the Journal of the American Society of Nephrology in January.

The trial enrolled 234 adults with stage 3-5, non-dialysis-dependent CKD and iron-deficiency anemia. Patients had hemoglobin levels between 9.0 g/dL and 11.5 g/dL and were intolerant to or had an inadequate response to prior treatment with oral iron supplements.

The starting dose of ferric citrate was 3 tablets per day, taken with meals. The mean dose was 5 tablets per day. Patients were not allowed to receive any intravenous or oral iron or erythropoiesis-stimulating agents.

Significantly more patients in the ferric citrate arm than the placebo arm had increases in hemoglobin levels of at least 1 g/dL at any point during the trial’s 16-week efficacy period—52.1% (61/117) and 19.1% (22/115), respectively (P<0.001).

Likewise, significantly more patients in the ferric citrate arm than the placebo arm had a sustained increase in hemoglobin of at least 0.75 g/dL over any 4-week period during the trial—48.7% (n=57) and 14.8% (n=17), respectively (P<0.001).

Serious adverse events occurred in 12.0% of patients in the ferric citrate arm and 11.2% of patients in the placebo arm. There were 2 treatment-emergent deaths in the ferric citrate arm (and none in the placebo arm), but they were not considered drug-related.

The most common (≥5%) treatment-emergent adverse events in patients who received ferric citrate were diarrhea (20.5%), constipation (18.8%), discolored feces (14.5%), nausea (11.1%), abdominal pain (6.0%), and hyperkalemia (6.8%).

Image from NIAID

The US Food and Drug Administration (FDA) has lifted the full clinical hold on 2 phase 1 studies of UCART123, an allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD123.

One of these studies was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The hold meant no new subjects could be enrolled in either trial, and there could be no further dosing of subjects who were already enrolled.

The hold was placed in September because the first patient treated in the BPDCN trial died. The patient developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection. This was followed by grade 4 capillary leak syndrome and grade 5 CRS.

The first patient treated in the AML trial also developed grade 4 capillary leak syndrome and grade 3 CRS, but both resolved.

Now, the FDA has lifted the hold on the trials because Cellectis, the company developing UCART123, agreed to implement the following main revisions to phase 1 UCART123 protocols:

• Decrease the cohort dose level to 6.25 x 10⁴ UCART123 cells/kg
• Decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m²/day over 3 days, with a maximum daily dose of 1.33 grams
• Include specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening
• Ensure the next 3 patients to be treated in each protocol will be under the age of 65
• Ensure that enrollment will be staggered across the UCART123 protocols; at least 28 days should elapse between the enrollments of 2 patients across the 2 studies.

Cellectis is currently working with investigators and clinical sites to obtain internal review board approval on the revised protocols and resume patient enrollment.

Image from NIAID

The US Food and Drug Administration (FDA) has lifted the full clinical hold on 2 phase 1 studies of UCART123, an allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD123.

One of these studies was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The hold meant no new subjects could be enrolled in either trial, and there could be no further dosing of subjects who were already enrolled.

The hold was placed in September because the first patient treated in the BPDCN trial died. The patient developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection. This was followed by grade 4 capillary leak syndrome and grade 5 CRS.

The first patient treated in the AML trial also developed grade 4 capillary leak syndrome and grade 3 CRS, but both resolved.

Now, the FDA has lifted the hold on the trials because Cellectis, the company developing UCART123, agreed to implement the following main revisions to phase 1 UCART123 protocols:

• Decrease the cohort dose level to 6.25 x 10⁴ UCART123 cells/kg
• Decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m²/day over 3 days, with a maximum daily dose of 1.33 grams
• Include specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening
• Ensure the next 3 patients to be treated in each protocol will be under the age of 65
• Ensure that enrollment will be staggered across the UCART123 protocols; at least 28 days should elapse between the enrollments of 2 patients across the 2 studies.

Cellectis is currently working with investigators and clinical sites to obtain internal review board approval on the revised protocols and resume patient enrollment.

Image from NIAID

The US Food and Drug Administration (FDA) has lifted the full clinical hold on 2 phase 1 studies of UCART123, an allogeneic chimeric antigen receptor (CAR) T-cell therapy targeting CD123.

One of these studies was designed for patients with acute myeloid leukemia (AML), and the other was designed for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The hold meant no new subjects could be enrolled in either trial, and there could be no further dosing of subjects who were already enrolled.

The hold was placed in September because the first patient treated in the BPDCN trial died. The patient developed grade 2 cytokine release syndrome (CRS) and a grade 3 lung infection. This was followed by grade 4 capillary leak syndrome and grade 5 CRS.

The first patient treated in the AML trial also developed grade 4 capillary leak syndrome and grade 3 CRS, but both resolved.

Now, the FDA has lifted the hold on the trials because Cellectis, the company developing UCART123, agreed to implement the following main revisions to phase 1 UCART123 protocols:

• Decrease the cohort dose level to 6.25 x 10⁴ UCART123 cells/kg
• Decrease the cyclophosphamide dose of the lymphodepleting regimen to 750 mg/m²/day over 3 days, with a maximum daily dose of 1.33 grams
• Include specific criteria at Day 0, the day of UCART123 infusion, such as no new uncontrolled infection after receipt of lymphodepletion, afebrile, off all but replacement dose of corticosteroids, and no organ dysfunction since eligibility screening
• Ensure the next 3 patients to be treated in each protocol will be under the age of 65
• Ensure that enrollment will be staggered across the UCART123 protocols; at least 28 days should elapse between the enrollments of 2 patients across the 2 studies.

Cellectis is currently working with investigators and clinical sites to obtain internal review board approval on the revised protocols and resume patient enrollment.

ANSWER

The correct interpretation includes sinus tachycardia with complete heart block and an idioventricular rhythm. Careful review of this ECG confirms complete atrioventricular dissociation, which is indicative of complete heart block.

Sinus tachycardia is indicated by a consistent P-P interval at a rate of 110 beats/min, idioventricular rhythm with a regular (but not normal) rate, and prolonged QRS interval of 148 ms. In this patient’s case, the tachycardia was presumed to be due to his upper respiratory infection. He underwent permanent pacemaker placement and resumed his normal activities without restriction.

ANSWER

The correct interpretation includes sinus tachycardia with complete heart block and an idioventricular rhythm. Careful review of this ECG confirms complete atrioventricular dissociation, which is indicative of complete heart block.

Sinus tachycardia is indicated by a consistent P-P interval at a rate of 110 beats/min, idioventricular rhythm with a regular (but not normal) rate, and prolonged QRS interval of 148 ms. In this patient’s case, the tachycardia was presumed to be due to his upper respiratory infection. He underwent permanent pacemaker placement and resumed his normal activities without restriction.

ANSWER

The correct interpretation includes sinus tachycardia with complete heart block and an idioventricular rhythm. Careful review of this ECG confirms complete atrioventricular dissociation, which is indicative of complete heart block.

Sinus tachycardia is indicated by a consistent P-P interval at a rate of 110 beats/min, idioventricular rhythm with a regular (but not normal) rate, and prolonged QRS interval of 148 ms. In this patient’s case, the tachycardia was presumed to be due to his upper respiratory infection. He underwent permanent pacemaker placement and resumed his normal activities without restriction.

How do you feel about apple pie? Is it a concept that evokes a positive feeling for you? Even if you prefer pumpkin or blueberry? Although your attitude toward apple pie may be relevant as we approach the holidays, is it a topic worthy of discussion in a publication devoted to pediatrics?

Certainly not, but what about motherhood? How do you feel about motherhood? As someone who is devoting his or her professional energies to the health of children, you must have formed some opinions about motherhood. Although your patients are children, it is their parents – and more often their mothers – with whom you communicate, particularly in the first several years of life. The interaction between a child and his or her mother can provide the child critical emotional support.

BananaStock/Thinkstock

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

Email him at [email protected].

How do you feel about apple pie? Is it a concept that evokes a positive feeling for you? Even if you prefer pumpkin or blueberry? Although your attitude toward apple pie may be relevant as we approach the holidays, is it a topic worthy of discussion in a publication devoted to pediatrics?

Certainly not, but what about motherhood? How do you feel about motherhood? As someone who is devoting his or her professional energies to the health of children, you must have formed some opinions about motherhood. Although your patients are children, it is their parents – and more often their mothers – with whom you communicate, particularly in the first several years of life. The interaction between a child and his or her mother can provide the child critical emotional support.

BananaStock/Thinkstock

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

Email him at [email protected].

How do you feel about apple pie? Is it a concept that evokes a positive feeling for you? Even if you prefer pumpkin or blueberry? Although your attitude toward apple pie may be relevant as we approach the holidays, is it a topic worthy of discussion in a publication devoted to pediatrics?

Certainly not, but what about motherhood? How do you feel about motherhood? As someone who is devoting his or her professional energies to the health of children, you must have formed some opinions about motherhood. Although your patients are children, it is their parents – and more often their mothers – with whom you communicate, particularly in the first several years of life. The interaction between a child and his or her mother can provide the child critical emotional support.

BananaStock/Thinkstock

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”

Email him at [email protected].

SAN DIEGO – The use of selective serotonin reuptake inhibitors and opioids was associated with an increased osteoporotic fracture risk in patients with rheumatoid arthritis, results from an analysis of national data showed.

“Osteoporotic fractures are one of the important causes of disability, health-related costs, and mortality in RA, with substantially higher complication and mortality rates than the general population,” study author Gulsen Ozen, MD, said in an interview prior to the annual meeting of the American College of Rheumatology. “Given the burden of osteoporotic fractures and the suboptimal osteoporosis care, identifying the factors associated with fracture risk in RA patients is of paramount importance.”

[email protected]

SAN DIEGO – The use of selective serotonin reuptake inhibitors and opioids was associated with an increased osteoporotic fracture risk in patients with rheumatoid arthritis, results from an analysis of national data showed.

“Osteoporotic fractures are one of the important causes of disability, health-related costs, and mortality in RA, with substantially higher complication and mortality rates than the general population,” study author Gulsen Ozen, MD, said in an interview prior to the annual meeting of the American College of Rheumatology. “Given the burden of osteoporotic fractures and the suboptimal osteoporosis care, identifying the factors associated with fracture risk in RA patients is of paramount importance.”

[email protected]

SAN DIEGO – The use of selective serotonin reuptake inhibitors and opioids was associated with an increased osteoporotic fracture risk in patients with rheumatoid arthritis, results from an analysis of national data showed.

“Osteoporotic fractures are one of the important causes of disability, health-related costs, and mortality in RA, with substantially higher complication and mortality rates than the general population,” study author Gulsen Ozen, MD, said in an interview prior to the annual meeting of the American College of Rheumatology. “Given the burden of osteoporotic fractures and the suboptimal osteoporosis care, identifying the factors associated with fracture risk in RA patients is of paramount importance.”

[email protected]

Take-Home Points

• The authors have developed a total shoulder glenoid prosthesis that conforms with the humeral head in its center and is nonconforming on its peripheral edge.
• All clinical survey and range of motion parameters demonstrated statistically significant improvements at final follow-up.
• Only 3 shoulders (1.7%) required revision surgery.
• Eighty-six (63%) of 136 shoulders demonstrated no radiographic evidence of glenoid loosening.
• This is the first and largest study that evaluates the clinical and radiographic outcomes of this hybrid shoulder prosthesis.

Fixation of the glenoid component is the limiting factor in modern total shoulder arthroplasty (TSA). Glenoid loosening, the most common long-term complication, necessitates revision in up to 12% of patients.^1-4 By contrast, humeral component loosening is relatively uncommon, affecting as few as 0.34% of patients.⁵ Multiple long-term studies have found consistently high rates (45%-93%) of radiolucencies around the glenoid component.^3,6,7 Although their clinical significance has been debated, radiolucencies around the glenoid component raise concern about progressive loss of fixation.

Since TSA was introduced in the 1970s, complications with the glenoid component have been addressed with 2 different designs: conforming (congruent) and nonconforming. In a congruent articulation, the radii of curvature of the glenoid and humeral head components are identical, whereas they differ in a nonconforming model. Joint conformity is inversely related to glenohumeral translation.⁸ Neer’s original TSA was made congruent in order to limit translation and maximize the contact area. However, this design results in edge loading and a so-called rocking-horse phenomenon, which may lead to glenoid loosening.^9-13 Surgeons therefore have increasingly turned to nonconforming implants. In the nonconforming design, the radius of curvature of the humeral head is smaller than that of the glenoid. Although this design may reduce edge loading,¹⁴ it allows more translation and reduces the relative contact area of the glenohumeral joint. As a result, more contact stress is transmitted to the glenoid component, leading to polyethylene deformation and wear.^15,16

Dual radii of curvature are designed to augment joint stability without increasing component wear. Biomechanical data have indicated that edge loading is not increased by having a central conforming region added to a nonconforming model.¹⁷ The clinical value of this prosthesis, however, has not been determined. Therefore, we conducted a study to describe the intermediate-term clinical and radiographic outcomes of TSAs that use a novel hybrid glenoid component.

Materials and Methods

This study was approved (protocol AAAD3473) by the Institutional Review Board of Columbia University and was conducted in compliance with Health Insurance Portability and Accountability Act (HIPAA) regulations.

Patient Selection

At Columbia University Medical Center, Dr. Bigliani performed 196 TSAs with a hybrid glenoid component (Bigliani-Flatow; Zimmer Biomet) in 169 patients between September 1998 and November 2007. All patients had received a diagnosis of primary glenohumeral arthritis as defined by Neer.¹⁸ Patients with previous surgery such as rotator cuff repair or subacromial decompression were included in our review, and patients with a nonprimary form of arthritis, such as rheumatoid, posttraumatic, or post-capsulorrhaphy arthritis, were excluded.

Operative Technique

For all surgeries, Dr. Bigliani performed a subscapularis tenotomy with regional anesthesia and a standard deltopectoral approach. A partial anterior capsulectomy was performed to increase the glenoid’s visibility. The inferior labrum was removed with a needle-tip bovie while the axillary nerve was being protected with a metal finger or narrow Darrach retractor. After reaming and trialing, the final glenoid component was cemented into place. Cement was placed only in the peg or keel holes and pressurized twice before final implantation. Of the 196 glenoid components, 168 (86%) were pegged and 28 (14%) keeled; in addition,190 of these components were all-polyethylene, whereas 6 had trabecular-metal backing. All glenoid components incorporated the hybrid design of dual radii of curvature. After the glenoid was cemented, the final humeral component was placed in 30° of retroversion. Whenever posterior wear was found, retroversion was reduced by 5° to 10°. The humeral prosthesis was cemented in cases (104/196, 53%) of poor bone quality or a large canal.

After surgery, the patient’s sling was fitted with an abduction pillow and a swathe, to be worn the first 24 hours, and the arm was passively ranged. Patients typically were discharged on postoperative day 2. Then, for 2 weeks, they followed an assisted passive range of motion (ROM) protocol, with limited external rotation, for promotion of subscapularis healing.

Clinical Outcomes

Dr. Bigliani assessed preoperative ROM in all planes. During initial evaluation, patients completed a questionnaire that consisted of the 36-Item Short Form Health Survey^19,20 (SF-36) and the American Shoulder and Elbow Surgeons²¹ (ASES) and Simple Shoulder Test²² (SST) surveys. Postoperative clinical data were collected from office follow-up visits, survey questionnaires, or both. Postoperative office data included ROM, subscapularis integrity testing (belly-press or lift-off), and any complications. Patients with <1 year of office follow-up were excluded. In addition, the same survey questionnaire that was used before surgery was mailed to all patients after surgery; then, for anyone who did not respond by mail, we attempted contact by telephone. Neer criteria were based on patients’ subjective assessment of each arm on a 3-point Likert scale (1 = very satisfied, 2 = satisfied, 3 = dissatisfied). Patients were also asked about any specific complications or revision operations since their index procedure.

Physical examination and office follow-up data were obtained for 129 patients (148/196 shoulders, 76% follow-up) at a mean of 3.7 years (range 1.0-10.2 years) after surgery. Surveys were completed by 117 patients (139/196 shoulders, 71% follow-up) at a mean of 5.1 years (range, 1.6-11.2 years) after surgery. Only 15 patients had neither 1 year of office follow-up nor a completed questionnaire. The remaining 154 patients (178/196 shoulders, 91% follow-up) had clinical follow-up with office, mail, or telephone questionnaire at a mean of 4.8 years (range, 1.0-11.2 years) after surgery. This cohort of patients was used to determine rates of surgical revisions, subscapularis tears, dislocations, and other complications.

Radiographic Outcomes

Patients were included in the radiographic analysis if they had a shoulder radiograph at least 1 year after surgery. One hundred nineteen patients (136/196 shoulders, 69% follow-up) had radiographic follow-up at a mean of 3.7 years (range, 1.0-9.4 years) after surgery.

Statistical Analysis

Statistical analysis was performed with Stata Version 10.0. Paired t tests were used to compare preoperative and postoperative numerical data, including ROM and survey scores. We calculated 95% confidence intervals (CIs) and set statistical significance at P < .05. For qualitative measures, the Fisher exact test was used. Survivorship analysis was performed according to the Kaplan-Meier method, with right-censored data for no event or missing data.²⁵

Results

Clinical Analysis of Demographics

In demographics, the clinical and radiographic patient subgroups were similar to each other and to the overall study population (Table 2). Of 196 patients overall, 16 (8%) had a concomitant rotator cuff repair, and 27 (14%) underwent staged bilateral shoulder arthroplasties.

Clinical Analysis of ROM and Survey Scores

Operative shoulder ROM in forward elevation, external rotation at side, external rotation in abduction, and internal rotation all showed statistically significant (P < .001) improvement from before surgery to after surgery. Over 3.7 years, mean (SD) forward elevation improved from 107.3° (34.8°) to 159.0° (29.4°), external rotation at side improved from 20.4° (16.7°) to 49.4° (11.3°), and external rotation in abduction improved from 53.7° (24.3°) to 84.7° (9.1°). Internal rotation improved from a mean (SD) vertebral level of S1 (6.0 levels) to T9 (3.7 levels).

All validated survey scores also showed statistically significant (P < .001) improvement from before surgery to after surgery. Over 5.1 years, mean (SD) SF-36 scores improved from 64.9 (13.4) to 73.6 (17.1), ASES scores improved from 41.1 (22.5) to 82.7 (17.7), SST scores improved from 3.9 (2.8) to 9.7 (2.2), and visual analog scale pain scores improved from 5.6 (3.2) to 1.4 (2.1). Of 139 patients with follow-up, 130 (93.5%) were either satisfied or very satisfied with their TSA, and only 119 (86%) were either satisfied or very satisfied with the nonoperative shoulder.

Clinical Analysis of Postoperative Complications

Of the 178 shoulders evaluated for complications, 3 (1.7%) underwent revision surgery. Mean time to revision was 2.3 years (range, 1.5-3.9 years). Two revisions involved the glenoid component, and the third involved the humerus. In one of the glenoid cases, a 77-year-old woman fell and sustained a fracture at the base of the trabecular metal glenoid pegs; her component was revised to an all-polyethylene component, and she had no further complications. In the other glenoid case, a 73-year-old man’s all-polyethylene component loosened after 2 years and was revised to a trabecular metal implant, which loosened as well and was later converted to a hemiarthroplasty. In the humeral case, a 33-year-old man had his 4-year-old index TSA revised to a cemented stem and had no further complications.

Table 4 compares the clinical and radiographic outcomes of patients who required subscapularis repair, capsular shift, or implant revision with the outcomes of all other study patients, and Figure 3 shows Kaplan-Meier survivorship.

Postoperative Radiographic Analysis

Glenoid Component. At a mean of 3.7 years (minimum, 1 year) after surgery, 86 (63%) of 136 radiographically evaluated shoulders showed no glenoid lucencies; the other 50 (37%) showed ≥1 lucency. Of the 136 shoulders, 33 (24%) had a Lazarus score of 1, 15 (11%) had a score of 2, and only 2 (2%) had a score of 3. None of the shoulders had a score of 4 or 5.

Humeral Component. Of the 136 shoulders, 91 (67%) showed no lucencies in any of the 8 humeral stem zones; the other 45 (33%) showed 1 to 3 lucencies. Thirty (22%) of the 136 shoulders had 1 stem lucency zone, 8 (6%) had 2, and 3 (2%) had 3. None of the shoulders had >3 periprosthetic zones with lucent lines.

Discussion

In this article, we describe a hybrid glenoid TSA component with dual radii of curvature. Its central portion is congruent with the humeral head, and its peripheral portion is noncongruent and larger. The most significant finding of our study is the low rate (1.1%) of glenoid component revision 4.8 years after surgery. This rate is the lowest that has been reported in a study of ≥100 patients. Overall implant survival appeared as an almost flat Kaplan-Meir curve. We attribute this low revision rate to improved biomechanics with the hybrid glenoid design. 

Symptomatic glenoid component loosening is the most common TSA complication.^1,26-28 In a review of 73 Neer TSAs, Cofield7 found glenoid radiolucencies in 71% of patients 3.8 years after surgery. Radiographic evidence of loosening, defined as component migration, or tilt, or a circumferential lucency 1.5 mm thick, was present in another 11% of patients, and 4.1% developed symptomatic loosening that required glenoid revision. In a study with 12.2-year follow-up, Torchia and colleagues³ found rates of 84% for glenoid radiolucencies, 44% for radiographic loosening, and 5.6% for symptomatic loosening that required revision. In a systematic review of studies with follow-up of ≥10 years, Bohsali and colleagues²⁷ found similar lucency and radiographic loosening rates and a 7% glenoid revision rate. These data suggest glenoid radiolucencies may progress to component loosening.

Degree of joint congruence is a key factor in glenoid loosening. Neer’s congruent design increases the contact area with concentric loading and reduces glenohumeral translation, which leads to reduced polyethylene wear and improved joint stability. In extreme arm positions, however, humeral head subluxation results in edge loading and a glenoid rocking-horse effect.^{9-13,17,29-31} Conversely, nonconforming implants allow increased glenohumeral translation without edge loading,¹⁴ though they also reduce the relative glenohumeral contact area and thus transmit more contact stress to the glenoid.^16,17 A hybrid glenoid component with central conforming and peripheral nonconforming zones may reduce the rocking-horse effect while maximizing ROM and joint stability. Wang and colleagues32 studied the biomechanical properties of this glenoid design and found that the addition of a central conforming region did not increase edge loading.

Additional results from our study support the efficacy of a hybrid glenoid component. Patients’ clinical outcomes improved significantly. At 5.1 years after surgery, 93.5% of patients were satisfied or very satisfied with their procedure and reported less satisfaction (86%) with the nonoperative shoulder. Also significant was the reduced number of radiolucencies. At 3.7 years after surgery, the overall percentage of shoulders with ≥1 glenoid radiolucency was 37%, considerably lower than the 82% reported by Cofield7 and the rates in more recent studies.^3,16,33-36 Of the 178 shoulders in our study, 10 (5.6%) had subscapularis tears, and 6 (3.4%) of 178 had these tears surgically repaired. This 3.4% compares favorably with the 5.9% (of 119 patients) found by Miller and colleagues37 28 months after surgery. Of our 178 shoulders, 27 (15.2%) had clinically significant postoperative complications; 18 (10.1%) of the 178 had these complications surgically treated, and 9 (5.1%) had them managed nonoperatively. Bohsali and colleagues²⁷ systematically reviewed 33 TSA studies and found a slightly higher complication rate (16.3%) 5.3 years after surgery. Furthermore, in our study, the 11 patients who underwent revision, capsular shift, or subscapularis repair had final outcomes comparable to those of the rest of our study population.

Our study had several potential weaknesses. First, its minimum clinical and radiographic follow-up was 1 year, whereas most long-term TSA series set a minimum of 2 years. We used 1 year because this was the first clinical study of the hybrid glenoid component design, and we wanted to maximize its sample size by reporting on intermediate-length outcomes. Even so, 93% (166/178) of our clinical patients and 83% (113/136) of our radiographic patients have had ≥2 years of follow-up, and we continue to follow all study patients for long-term outcomes. Another weakness of the study was its lack of a uniform group of patients with all the office, survey, complications, and radiographic data. Our retrospective study design made it difficult to obtain such a group without significantly reducing the sample size, so we divided patients into 4 data groups. A third potential weakness was the study’s variable method for collecting complications data. Rates of complications in the 178 shoulders were calculated from either office evaluation or patient self-report by mail or telephone. This data collection method is subject to recall bias, but mail and telephone contact was needed so the study would capture the large number of patients who had traveled to our institution for their surgery or had since moved away. Fourth, belly-press and lift-off tests were used in part to assess subscapularis function, but recent literature suggests post-TSA subscapularis assessment can be unreliable.³⁸ These tests may be positive in up to two-thirds of patients after 2 years.³⁹ Fifth, the generalizability of our findings to diagnoses such as rheumatoid and posttraumatic arthritis is limited. We had to restrict the study to patients with primary glenohumeral arthritis in order to minimize confounders.

This study’s main strength is its description of the clinical and radiographic outcomes of using a single prosthetic system in operations performed by a single surgeon in a large number of patients. This was the first and largest study evaluating the clinical and radiographic outcomes of this hybrid glenoid implant. Excluding patients with nonprimary arthritis allowed us to minimize potential confounding factors that affect patient outcomes. In conclusion, our study results showed the favorable clinical and radiographic outcomes of TSAs that have a hybrid glenoid component with dual radii of curvature. At a mean of 3.7 years after surgery, 63% of patients had no glenoid lucencies, and, at a mean of 4.8 years, only 1.7% of patients required revision. We continue to follow these patients to obtain long-term results of this innovative prosthesis.

Take-Home Points

• The authors have developed a total shoulder glenoid prosthesis that conforms with the humeral head in its center and is nonconforming on its peripheral edge.
• All clinical survey and range of motion parameters demonstrated statistically significant improvements at final follow-up.
• Only 3 shoulders (1.7%) required revision surgery.
• Eighty-six (63%) of 136 shoulders demonstrated no radiographic evidence of glenoid loosening.
• This is the first and largest study that evaluates the clinical and radiographic outcomes of this hybrid shoulder prosthesis.

Fixation of the glenoid component is the limiting factor in modern total shoulder arthroplasty (TSA). Glenoid loosening, the most common long-term complication, necessitates revision in up to 12% of patients.^1-4 By contrast, humeral component loosening is relatively uncommon, affecting as few as 0.34% of patients.⁵ Multiple long-term studies have found consistently high rates (45%-93%) of radiolucencies around the glenoid component.^3,6,7 Although their clinical significance has been debated, radiolucencies around the glenoid component raise concern about progressive loss of fixation.

Since TSA was introduced in the 1970s, complications with the glenoid component have been addressed with 2 different designs: conforming (congruent) and nonconforming. In a congruent articulation, the radii of curvature of the glenoid and humeral head components are identical, whereas they differ in a nonconforming model. Joint conformity is inversely related to glenohumeral translation.⁸ Neer’s original TSA was made congruent in order to limit translation and maximize the contact area. However, this design results in edge loading and a so-called rocking-horse phenomenon, which may lead to glenoid loosening.^9-13 Surgeons therefore have increasingly turned to nonconforming implants. In the nonconforming design, the radius of curvature of the humeral head is smaller than that of the glenoid. Although this design may reduce edge loading,¹⁴ it allows more translation and reduces the relative contact area of the glenohumeral joint. As a result, more contact stress is transmitted to the glenoid component, leading to polyethylene deformation and wear.^15,16

Dual radii of curvature are designed to augment joint stability without increasing component wear. Biomechanical data have indicated that edge loading is not increased by having a central conforming region added to a nonconforming model.¹⁷ The clinical value of this prosthesis, however, has not been determined. Therefore, we conducted a study to describe the intermediate-term clinical and radiographic outcomes of TSAs that use a novel hybrid glenoid component.

Materials and Methods

This study was approved (protocol AAAD3473) by the Institutional Review Board of Columbia University and was conducted in compliance with Health Insurance Portability and Accountability Act (HIPAA) regulations.

Patient Selection

At Columbia University Medical Center, Dr. Bigliani performed 196 TSAs with a hybrid glenoid component (Bigliani-Flatow; Zimmer Biomet) in 169 patients between September 1998 and November 2007. All patients had received a diagnosis of primary glenohumeral arthritis as defined by Neer.¹⁸ Patients with previous surgery such as rotator cuff repair or subacromial decompression were included in our review, and patients with a nonprimary form of arthritis, such as rheumatoid, posttraumatic, or post-capsulorrhaphy arthritis, were excluded.

Operative Technique

For all surgeries, Dr. Bigliani performed a subscapularis tenotomy with regional anesthesia and a standard deltopectoral approach. A partial anterior capsulectomy was performed to increase the glenoid’s visibility. The inferior labrum was removed with a needle-tip bovie while the axillary nerve was being protected with a metal finger or narrow Darrach retractor. After reaming and trialing, the final glenoid component was cemented into place. Cement was placed only in the peg or keel holes and pressurized twice before final implantation. Of the 196 glenoid components, 168 (86%) were pegged and 28 (14%) keeled; in addition,190 of these components were all-polyethylene, whereas 6 had trabecular-metal backing. All glenoid components incorporated the hybrid design of dual radii of curvature. After the glenoid was cemented, the final humeral component was placed in 30° of retroversion. Whenever posterior wear was found, retroversion was reduced by 5° to 10°. The humeral prosthesis was cemented in cases (104/196, 53%) of poor bone quality or a large canal.

After surgery, the patient’s sling was fitted with an abduction pillow and a swathe, to be worn the first 24 hours, and the arm was passively ranged. Patients typically were discharged on postoperative day 2. Then, for 2 weeks, they followed an assisted passive range of motion (ROM) protocol, with limited external rotation, for promotion of subscapularis healing.

Clinical Outcomes

Dr. Bigliani assessed preoperative ROM in all planes. During initial evaluation, patients completed a questionnaire that consisted of the 36-Item Short Form Health Survey^19,20 (SF-36) and the American Shoulder and Elbow Surgeons²¹ (ASES) and Simple Shoulder Test²² (SST) surveys. Postoperative clinical data were collected from office follow-up visits, survey questionnaires, or both. Postoperative office data included ROM, subscapularis integrity testing (belly-press or lift-off), and any complications. Patients with <1 year of office follow-up were excluded. In addition, the same survey questionnaire that was used before surgery was mailed to all patients after surgery; then, for anyone who did not respond by mail, we attempted contact by telephone. Neer criteria were based on patients’ subjective assessment of each arm on a 3-point Likert scale (1 = very satisfied, 2 = satisfied, 3 = dissatisfied). Patients were also asked about any specific complications or revision operations since their index procedure.

Physical examination and office follow-up data were obtained for 129 patients (148/196 shoulders, 76% follow-up) at a mean of 3.7 years (range 1.0-10.2 years) after surgery. Surveys were completed by 117 patients (139/196 shoulders, 71% follow-up) at a mean of 5.1 years (range, 1.6-11.2 years) after surgery. Only 15 patients had neither 1 year of office follow-up nor a completed questionnaire. The remaining 154 patients (178/196 shoulders, 91% follow-up) had clinical follow-up with office, mail, or telephone questionnaire at a mean of 4.8 years (range, 1.0-11.2 years) after surgery. This cohort of patients was used to determine rates of surgical revisions, subscapularis tears, dislocations, and other complications.

Radiographic Outcomes

Patients were included in the radiographic analysis if they had a shoulder radiograph at least 1 year after surgery. One hundred nineteen patients (136/196 shoulders, 69% follow-up) had radiographic follow-up at a mean of 3.7 years (range, 1.0-9.4 years) after surgery.

Statistical Analysis

Statistical analysis was performed with Stata Version 10.0. Paired t tests were used to compare preoperative and postoperative numerical data, including ROM and survey scores. We calculated 95% confidence intervals (CIs) and set statistical significance at P < .05. For qualitative measures, the Fisher exact test was used. Survivorship analysis was performed according to the Kaplan-Meier method, with right-censored data for no event or missing data.²⁵

Results

Clinical Analysis of Demographics

In demographics, the clinical and radiographic patient subgroups were similar to each other and to the overall study population (Table 2). Of 196 patients overall, 16 (8%) had a concomitant rotator cuff repair, and 27 (14%) underwent staged bilateral shoulder arthroplasties.

Clinical Analysis of ROM and Survey Scores

Operative shoulder ROM in forward elevation, external rotation at side, external rotation in abduction, and internal rotation all showed statistically significant (P < .001) improvement from before surgery to after surgery. Over 3.7 years, mean (SD) forward elevation improved from 107.3° (34.8°) to 159.0° (29.4°), external rotation at side improved from 20.4° (16.7°) to 49.4° (11.3°), and external rotation in abduction improved from 53.7° (24.3°) to 84.7° (9.1°). Internal rotation improved from a mean (SD) vertebral level of S1 (6.0 levels) to T9 (3.7 levels).

All validated survey scores also showed statistically significant (P < .001) improvement from before surgery to after surgery. Over 5.1 years, mean (SD) SF-36 scores improved from 64.9 (13.4) to 73.6 (17.1), ASES scores improved from 41.1 (22.5) to 82.7 (17.7), SST scores improved from 3.9 (2.8) to 9.7 (2.2), and visual analog scale pain scores improved from 5.6 (3.2) to 1.4 (2.1). Of 139 patients with follow-up, 130 (93.5%) were either satisfied or very satisfied with their TSA, and only 119 (86%) were either satisfied or very satisfied with the nonoperative shoulder.

Clinical Analysis of Postoperative Complications

Of the 178 shoulders evaluated for complications, 3 (1.7%) underwent revision surgery. Mean time to revision was 2.3 years (range, 1.5-3.9 years). Two revisions involved the glenoid component, and the third involved the humerus. In one of the glenoid cases, a 77-year-old woman fell and sustained a fracture at the base of the trabecular metal glenoid pegs; her component was revised to an all-polyethylene component, and she had no further complications. In the other glenoid case, a 73-year-old man’s all-polyethylene component loosened after 2 years and was revised to a trabecular metal implant, which loosened as well and was later converted to a hemiarthroplasty. In the humeral case, a 33-year-old man had his 4-year-old index TSA revised to a cemented stem and had no further complications.

Table 4 compares the clinical and radiographic outcomes of patients who required subscapularis repair, capsular shift, or implant revision with the outcomes of all other study patients, and Figure 3 shows Kaplan-Meier survivorship.

Postoperative Radiographic Analysis

Glenoid Component. At a mean of 3.7 years (minimum, 1 year) after surgery, 86 (63%) of 136 radiographically evaluated shoulders showed no glenoid lucencies; the other 50 (37%) showed ≥1 lucency. Of the 136 shoulders, 33 (24%) had a Lazarus score of 1, 15 (11%) had a score of 2, and only 2 (2%) had a score of 3. None of the shoulders had a score of 4 or 5.

Humeral Component. Of the 136 shoulders, 91 (67%) showed no lucencies in any of the 8 humeral stem zones; the other 45 (33%) showed 1 to 3 lucencies. Thirty (22%) of the 136 shoulders had 1 stem lucency zone, 8 (6%) had 2, and 3 (2%) had 3. None of the shoulders had >3 periprosthetic zones with lucent lines.

Discussion

In this article, we describe a hybrid glenoid TSA component with dual radii of curvature. Its central portion is congruent with the humeral head, and its peripheral portion is noncongruent and larger. The most significant finding of our study is the low rate (1.1%) of glenoid component revision 4.8 years after surgery. This rate is the lowest that has been reported in a study of ≥100 patients. Overall implant survival appeared as an almost flat Kaplan-Meir curve. We attribute this low revision rate to improved biomechanics with the hybrid glenoid design. 

Symptomatic glenoid component loosening is the most common TSA complication.^1,26-28 In a review of 73 Neer TSAs, Cofield7 found glenoid radiolucencies in 71% of patients 3.8 years after surgery. Radiographic evidence of loosening, defined as component migration, or tilt, or a circumferential lucency 1.5 mm thick, was present in another 11% of patients, and 4.1% developed symptomatic loosening that required glenoid revision. In a study with 12.2-year follow-up, Torchia and colleagues³ found rates of 84% for glenoid radiolucencies, 44% for radiographic loosening, and 5.6% for symptomatic loosening that required revision. In a systematic review of studies with follow-up of ≥10 years, Bohsali and colleagues²⁷ found similar lucency and radiographic loosening rates and a 7% glenoid revision rate. These data suggest glenoid radiolucencies may progress to component loosening.

Degree of joint congruence is a key factor in glenoid loosening. Neer’s congruent design increases the contact area with concentric loading and reduces glenohumeral translation, which leads to reduced polyethylene wear and improved joint stability. In extreme arm positions, however, humeral head subluxation results in edge loading and a glenoid rocking-horse effect.^{9-13,17,29-31} Conversely, nonconforming implants allow increased glenohumeral translation without edge loading,¹⁴ though they also reduce the relative glenohumeral contact area and thus transmit more contact stress to the glenoid.^16,17 A hybrid glenoid component with central conforming and peripheral nonconforming zones may reduce the rocking-horse effect while maximizing ROM and joint stability. Wang and colleagues32 studied the biomechanical properties of this glenoid design and found that the addition of a central conforming region did not increase edge loading.

Additional results from our study support the efficacy of a hybrid glenoid component. Patients’ clinical outcomes improved significantly. At 5.1 years after surgery, 93.5% of patients were satisfied or very satisfied with their procedure and reported less satisfaction (86%) with the nonoperative shoulder. Also significant was the reduced number of radiolucencies. At 3.7 years after surgery, the overall percentage of shoulders with ≥1 glenoid radiolucency was 37%, considerably lower than the 82% reported by Cofield7 and the rates in more recent studies.^3,16,33-36 Of the 178 shoulders in our study, 10 (5.6%) had subscapularis tears, and 6 (3.4%) of 178 had these tears surgically repaired. This 3.4% compares favorably with the 5.9% (of 119 patients) found by Miller and colleagues37 28 months after surgery. Of our 178 shoulders, 27 (15.2%) had clinically significant postoperative complications; 18 (10.1%) of the 178 had these complications surgically treated, and 9 (5.1%) had them managed nonoperatively. Bohsali and colleagues²⁷ systematically reviewed 33 TSA studies and found a slightly higher complication rate (16.3%) 5.3 years after surgery. Furthermore, in our study, the 11 patients who underwent revision, capsular shift, or subscapularis repair had final outcomes comparable to those of the rest of our study population.

Our study had several potential weaknesses. First, its minimum clinical and radiographic follow-up was 1 year, whereas most long-term TSA series set a minimum of 2 years. We used 1 year because this was the first clinical study of the hybrid glenoid component design, and we wanted to maximize its sample size by reporting on intermediate-length outcomes. Even so, 93% (166/178) of our clinical patients and 83% (113/136) of our radiographic patients have had ≥2 years of follow-up, and we continue to follow all study patients for long-term outcomes. Another weakness of the study was its lack of a uniform group of patients with all the office, survey, complications, and radiographic data. Our retrospective study design made it difficult to obtain such a group without significantly reducing the sample size, so we divided patients into 4 data groups. A third potential weakness was the study’s variable method for collecting complications data. Rates of complications in the 178 shoulders were calculated from either office evaluation or patient self-report by mail or telephone. This data collection method is subject to recall bias, but mail and telephone contact was needed so the study would capture the large number of patients who had traveled to our institution for their surgery or had since moved away. Fourth, belly-press and lift-off tests were used in part to assess subscapularis function, but recent literature suggests post-TSA subscapularis assessment can be unreliable.³⁸ These tests may be positive in up to two-thirds of patients after 2 years.³⁹ Fifth, the generalizability of our findings to diagnoses such as rheumatoid and posttraumatic arthritis is limited. We had to restrict the study to patients with primary glenohumeral arthritis in order to minimize confounders.

This study’s main strength is its description of the clinical and radiographic outcomes of using a single prosthetic system in operations performed by a single surgeon in a large number of patients. This was the first and largest study evaluating the clinical and radiographic outcomes of this hybrid glenoid implant. Excluding patients with nonprimary arthritis allowed us to minimize potential confounding factors that affect patient outcomes. In conclusion, our study results showed the favorable clinical and radiographic outcomes of TSAs that have a hybrid glenoid component with dual radii of curvature. At a mean of 3.7 years after surgery, 63% of patients had no glenoid lucencies, and, at a mean of 4.8 years, only 1.7% of patients required revision. We continue to follow these patients to obtain long-term results of this innovative prosthesis.

Take-Home Points

• The authors have developed a total shoulder glenoid prosthesis that conforms with the humeral head in its center and is nonconforming on its peripheral edge.
• All clinical survey and range of motion parameters demonstrated statistically significant improvements at final follow-up.
• Only 3 shoulders (1.7%) required revision surgery.
• Eighty-six (63%) of 136 shoulders demonstrated no radiographic evidence of glenoid loosening.
• This is the first and largest study that evaluates the clinical and radiographic outcomes of this hybrid shoulder prosthesis.

Fixation of the glenoid component is the limiting factor in modern total shoulder arthroplasty (TSA). Glenoid loosening, the most common long-term complication, necessitates revision in up to 12% of patients.^1-4 By contrast, humeral component loosening is relatively uncommon, affecting as few as 0.34% of patients.⁵ Multiple long-term studies have found consistently high rates (45%-93%) of radiolucencies around the glenoid component.^3,6,7 Although their clinical significance has been debated, radiolucencies around the glenoid component raise concern about progressive loss of fixation.

Since TSA was introduced in the 1970s, complications with the glenoid component have been addressed with 2 different designs: conforming (congruent) and nonconforming. In a congruent articulation, the radii of curvature of the glenoid and humeral head components are identical, whereas they differ in a nonconforming model. Joint conformity is inversely related to glenohumeral translation.⁸ Neer’s original TSA was made congruent in order to limit translation and maximize the contact area. However, this design results in edge loading and a so-called rocking-horse phenomenon, which may lead to glenoid loosening.^9-13 Surgeons therefore have increasingly turned to nonconforming implants. In the nonconforming design, the radius of curvature of the humeral head is smaller than that of the glenoid. Although this design may reduce edge loading,¹⁴ it allows more translation and reduces the relative contact area of the glenohumeral joint. As a result, more contact stress is transmitted to the glenoid component, leading to polyethylene deformation and wear.^15,16

Dual radii of curvature are designed to augment joint stability without increasing component wear. Biomechanical data have indicated that edge loading is not increased by having a central conforming region added to a nonconforming model.¹⁷ The clinical value of this prosthesis, however, has not been determined. Therefore, we conducted a study to describe the intermediate-term clinical and radiographic outcomes of TSAs that use a novel hybrid glenoid component.

Materials and Methods

This study was approved (protocol AAAD3473) by the Institutional Review Board of Columbia University and was conducted in compliance with Health Insurance Portability and Accountability Act (HIPAA) regulations.

Patient Selection

At Columbia University Medical Center, Dr. Bigliani performed 196 TSAs with a hybrid glenoid component (Bigliani-Flatow; Zimmer Biomet) in 169 patients between September 1998 and November 2007. All patients had received a diagnosis of primary glenohumeral arthritis as defined by Neer.¹⁸ Patients with previous surgery such as rotator cuff repair or subacromial decompression were included in our review, and patients with a nonprimary form of arthritis, such as rheumatoid, posttraumatic, or post-capsulorrhaphy arthritis, were excluded.

Operative Technique

For all surgeries, Dr. Bigliani performed a subscapularis tenotomy with regional anesthesia and a standard deltopectoral approach. A partial anterior capsulectomy was performed to increase the glenoid’s visibility. The inferior labrum was removed with a needle-tip bovie while the axillary nerve was being protected with a metal finger or narrow Darrach retractor. After reaming and trialing, the final glenoid component was cemented into place. Cement was placed only in the peg or keel holes and pressurized twice before final implantation. Of the 196 glenoid components, 168 (86%) were pegged and 28 (14%) keeled; in addition,190 of these components were all-polyethylene, whereas 6 had trabecular-metal backing. All glenoid components incorporated the hybrid design of dual radii of curvature. After the glenoid was cemented, the final humeral component was placed in 30° of retroversion. Whenever posterior wear was found, retroversion was reduced by 5° to 10°. The humeral prosthesis was cemented in cases (104/196, 53%) of poor bone quality or a large canal.

After surgery, the patient’s sling was fitted with an abduction pillow and a swathe, to be worn the first 24 hours, and the arm was passively ranged. Patients typically were discharged on postoperative day 2. Then, for 2 weeks, they followed an assisted passive range of motion (ROM) protocol, with limited external rotation, for promotion of subscapularis healing.

Clinical Outcomes

Dr. Bigliani assessed preoperative ROM in all planes. During initial evaluation, patients completed a questionnaire that consisted of the 36-Item Short Form Health Survey^19,20 (SF-36) and the American Shoulder and Elbow Surgeons²¹ (ASES) and Simple Shoulder Test²² (SST) surveys. Postoperative clinical data were collected from office follow-up visits, survey questionnaires, or both. Postoperative office data included ROM, subscapularis integrity testing (belly-press or lift-off), and any complications. Patients with <1 year of office follow-up were excluded. In addition, the same survey questionnaire that was used before surgery was mailed to all patients after surgery; then, for anyone who did not respond by mail, we attempted contact by telephone. Neer criteria were based on patients’ subjective assessment of each arm on a 3-point Likert scale (1 = very satisfied, 2 = satisfied, 3 = dissatisfied). Patients were also asked about any specific complications or revision operations since their index procedure.

Physical examination and office follow-up data were obtained for 129 patients (148/196 shoulders, 76% follow-up) at a mean of 3.7 years (range 1.0-10.2 years) after surgery. Surveys were completed by 117 patients (139/196 shoulders, 71% follow-up) at a mean of 5.1 years (range, 1.6-11.2 years) after surgery. Only 15 patients had neither 1 year of office follow-up nor a completed questionnaire. The remaining 154 patients (178/196 shoulders, 91% follow-up) had clinical follow-up with office, mail, or telephone questionnaire at a mean of 4.8 years (range, 1.0-11.2 years) after surgery. This cohort of patients was used to determine rates of surgical revisions, subscapularis tears, dislocations, and other complications.

Radiographic Outcomes

Patients were included in the radiographic analysis if they had a shoulder radiograph at least 1 year after surgery. One hundred nineteen patients (136/196 shoulders, 69% follow-up) had radiographic follow-up at a mean of 3.7 years (range, 1.0-9.4 years) after surgery.

Statistical Analysis

Statistical analysis was performed with Stata Version 10.0. Paired t tests were used to compare preoperative and postoperative numerical data, including ROM and survey scores. We calculated 95% confidence intervals (CIs) and set statistical significance at P < .05. For qualitative measures, the Fisher exact test was used. Survivorship analysis was performed according to the Kaplan-Meier method, with right-censored data for no event or missing data.²⁵

Results

Clinical Analysis of Demographics

In demographics, the clinical and radiographic patient subgroups were similar to each other and to the overall study population (Table 2). Of 196 patients overall, 16 (8%) had a concomitant rotator cuff repair, and 27 (14%) underwent staged bilateral shoulder arthroplasties.

Clinical Analysis of ROM and Survey Scores

Operative shoulder ROM in forward elevation, external rotation at side, external rotation in abduction, and internal rotation all showed statistically significant (P < .001) improvement from before surgery to after surgery. Over 3.7 years, mean (SD) forward elevation improved from 107.3° (34.8°) to 159.0° (29.4°), external rotation at side improved from 20.4° (16.7°) to 49.4° (11.3°), and external rotation in abduction improved from 53.7° (24.3°) to 84.7° (9.1°). Internal rotation improved from a mean (SD) vertebral level of S1 (6.0 levels) to T9 (3.7 levels).

All validated survey scores also showed statistically significant (P < .001) improvement from before surgery to after surgery. Over 5.1 years, mean (SD) SF-36 scores improved from 64.9 (13.4) to 73.6 (17.1), ASES scores improved from 41.1 (22.5) to 82.7 (17.7), SST scores improved from 3.9 (2.8) to 9.7 (2.2), and visual analog scale pain scores improved from 5.6 (3.2) to 1.4 (2.1). Of 139 patients with follow-up, 130 (93.5%) were either satisfied or very satisfied with their TSA, and only 119 (86%) were either satisfied or very satisfied with the nonoperative shoulder.

Clinical Analysis of Postoperative Complications

Of the 178 shoulders evaluated for complications, 3 (1.7%) underwent revision surgery. Mean time to revision was 2.3 years (range, 1.5-3.9 years). Two revisions involved the glenoid component, and the third involved the humerus. In one of the glenoid cases, a 77-year-old woman fell and sustained a fracture at the base of the trabecular metal glenoid pegs; her component was revised to an all-polyethylene component, and she had no further complications. In the other glenoid case, a 73-year-old man’s all-polyethylene component loosened after 2 years and was revised to a trabecular metal implant, which loosened as well and was later converted to a hemiarthroplasty. In the humeral case, a 33-year-old man had his 4-year-old index TSA revised to a cemented stem and had no further complications.

Table 4 compares the clinical and radiographic outcomes of patients who required subscapularis repair, capsular shift, or implant revision with the outcomes of all other study patients, and Figure 3 shows Kaplan-Meier survivorship.

Postoperative Radiographic Analysis

Glenoid Component. At a mean of 3.7 years (minimum, 1 year) after surgery, 86 (63%) of 136 radiographically evaluated shoulders showed no glenoid lucencies; the other 50 (37%) showed ≥1 lucency. Of the 136 shoulders, 33 (24%) had a Lazarus score of 1, 15 (11%) had a score of 2, and only 2 (2%) had a score of 3. None of the shoulders had a score of 4 or 5.

Humeral Component. Of the 136 shoulders, 91 (67%) showed no lucencies in any of the 8 humeral stem zones; the other 45 (33%) showed 1 to 3 lucencies. Thirty (22%) of the 136 shoulders had 1 stem lucency zone, 8 (6%) had 2, and 3 (2%) had 3. None of the shoulders had >3 periprosthetic zones with lucent lines.

Discussion

In this article, we describe a hybrid glenoid TSA component with dual radii of curvature. Its central portion is congruent with the humeral head, and its peripheral portion is noncongruent and larger. The most significant finding of our study is the low rate (1.1%) of glenoid component revision 4.8 years after surgery. This rate is the lowest that has been reported in a study of ≥100 patients. Overall implant survival appeared as an almost flat Kaplan-Meir curve. We attribute this low revision rate to improved biomechanics with the hybrid glenoid design. 

Symptomatic glenoid component loosening is the most common TSA complication.^1,26-28 In a review of 73 Neer TSAs, Cofield7 found glenoid radiolucencies in 71% of patients 3.8 years after surgery. Radiographic evidence of loosening, defined as component migration, or tilt, or a circumferential lucency 1.5 mm thick, was present in another 11% of patients, and 4.1% developed symptomatic loosening that required glenoid revision. In a study with 12.2-year follow-up, Torchia and colleagues³ found rates of 84% for glenoid radiolucencies, 44% for radiographic loosening, and 5.6% for symptomatic loosening that required revision. In a systematic review of studies with follow-up of ≥10 years, Bohsali and colleagues²⁷ found similar lucency and radiographic loosening rates and a 7% glenoid revision rate. These data suggest glenoid radiolucencies may progress to component loosening.

Degree of joint congruence is a key factor in glenoid loosening. Neer’s congruent design increases the contact area with concentric loading and reduces glenohumeral translation, which leads to reduced polyethylene wear and improved joint stability. In extreme arm positions, however, humeral head subluxation results in edge loading and a glenoid rocking-horse effect.^{9-13,17,29-31} Conversely, nonconforming implants allow increased glenohumeral translation without edge loading,¹⁴ though they also reduce the relative glenohumeral contact area and thus transmit more contact stress to the glenoid.^16,17 A hybrid glenoid component with central conforming and peripheral nonconforming zones may reduce the rocking-horse effect while maximizing ROM and joint stability. Wang and colleagues32 studied the biomechanical properties of this glenoid design and found that the addition of a central conforming region did not increase edge loading.

Additional results from our study support the efficacy of a hybrid glenoid component. Patients’ clinical outcomes improved significantly. At 5.1 years after surgery, 93.5% of patients were satisfied or very satisfied with their procedure and reported less satisfaction (86%) with the nonoperative shoulder. Also significant was the reduced number of radiolucencies. At 3.7 years after surgery, the overall percentage of shoulders with ≥1 glenoid radiolucency was 37%, considerably lower than the 82% reported by Cofield7 and the rates in more recent studies.^3,16,33-36 Of the 178 shoulders in our study, 10 (5.6%) had subscapularis tears, and 6 (3.4%) of 178 had these tears surgically repaired. This 3.4% compares favorably with the 5.9% (of 119 patients) found by Miller and colleagues37 28 months after surgery. Of our 178 shoulders, 27 (15.2%) had clinically significant postoperative complications; 18 (10.1%) of the 178 had these complications surgically treated, and 9 (5.1%) had them managed nonoperatively. Bohsali and colleagues²⁷ systematically reviewed 33 TSA studies and found a slightly higher complication rate (16.3%) 5.3 years after surgery. Furthermore, in our study, the 11 patients who underwent revision, capsular shift, or subscapularis repair had final outcomes comparable to those of the rest of our study population.

Our study had several potential weaknesses. First, its minimum clinical and radiographic follow-up was 1 year, whereas most long-term TSA series set a minimum of 2 years. We used 1 year because this was the first clinical study of the hybrid glenoid component design, and we wanted to maximize its sample size by reporting on intermediate-length outcomes. Even so, 93% (166/178) of our clinical patients and 83% (113/136) of our radiographic patients have had ≥2 years of follow-up, and we continue to follow all study patients for long-term outcomes. Another weakness of the study was its lack of a uniform group of patients with all the office, survey, complications, and radiographic data. Our retrospective study design made it difficult to obtain such a group without significantly reducing the sample size, so we divided patients into 4 data groups. A third potential weakness was the study’s variable method for collecting complications data. Rates of complications in the 178 shoulders were calculated from either office evaluation or patient self-report by mail or telephone. This data collection method is subject to recall bias, but mail and telephone contact was needed so the study would capture the large number of patients who had traveled to our institution for their surgery or had since moved away. Fourth, belly-press and lift-off tests were used in part to assess subscapularis function, but recent literature suggests post-TSA subscapularis assessment can be unreliable.³⁸ These tests may be positive in up to two-thirds of patients after 2 years.³⁹ Fifth, the generalizability of our findings to diagnoses such as rheumatoid and posttraumatic arthritis is limited. We had to restrict the study to patients with primary glenohumeral arthritis in order to minimize confounders.

This study’s main strength is its description of the clinical and radiographic outcomes of using a single prosthetic system in operations performed by a single surgeon in a large number of patients. This was the first and largest study evaluating the clinical and radiographic outcomes of this hybrid glenoid implant. Excluding patients with nonprimary arthritis allowed us to minimize potential confounding factors that affect patient outcomes. In conclusion, our study results showed the favorable clinical and radiographic outcomes of TSAs that have a hybrid glenoid component with dual radii of curvature. At a mean of 3.7 years after surgery, 63% of patients had no glenoid lucencies, and, at a mean of 4.8 years, only 1.7% of patients required revision. We continue to follow these patients to obtain long-term results of this innovative prosthesis.

From 2013 to 2016, all U.S. immunization information systems showed progress in bidirectional information exchange with EHRs, said Neil Murthy, MD, and his associates at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.

Across all 55 jurisdictions in 49 states and six cities in the United States using immunization information systems (IIS), 106% of U.S. births were registered in IIS in 2016, which is an increase from 102% in 2013; percentages may exceed 100%, because a child who is born in one state but who lives in a different state might be recorded in both IISs.

FotoMaximum/Thinkstock

From 2013 to 2016, all U.S. immunization information systems showed progress in bidirectional information exchange with EHRs, said Neil Murthy, MD, and his associates at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.

Across all 55 jurisdictions in 49 states and six cities in the United States using immunization information systems (IIS), 106% of U.S. births were registered in IIS in 2016, which is an increase from 102% in 2013; percentages may exceed 100%, because a child who is born in one state but who lives in a different state might be recorded in both IISs.

FotoMaximum/Thinkstock

From 2013 to 2016, all U.S. immunization information systems showed progress in bidirectional information exchange with EHRs, said Neil Murthy, MD, and his associates at the National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta.

Across all 55 jurisdictions in 49 states and six cities in the United States using immunization information systems (IIS), 106% of U.S. births were registered in IIS in 2016, which is an increase from 102% in 2013; percentages may exceed 100%, because a child who is born in one state but who lives in a different state might be recorded in both IISs.

FotoMaximum/Thinkstock