The FDA’s MedWatch program safety labeling changes for boxed warnings are compiled quarterly for drugs and therapeutic biologics where important changes have been made to the safety information. These and other label changes are searchable in the Drug Safety Labeling Changes (SLC) database, where data are available to the public in downloadable and searchable formats. Boxed warnings are ordinarily used to highlight either adverse reactions so serious in proportion to the potential benefit from the drug that it is essential that it be considered in assessing the risks and benefits of using the drug; or serious adverse reactions that can be prevented/reduced in frequency or severity by appropriate use of the drug; or FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted. For complete FDA Drug Safety Labeling changes, please visit http://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges.

CODEINE SULFATE: EPIVIR-HBV (LAMIVUDINE)

• Added to warning September 2017

WARNING: LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, EXACERBATIONS OF HEPATITIS B, and RISK OF HIV-1 RESISTANCE IF EPIVIR-HBV IS USED IN PATIENTS WITH UNRECOGNIZED OR UNTREATED HIV-1 INFECTION

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue EPIVIR-HBV if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.

Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy (including EPIVIR-HBV). Hepatic function should be monitored closely with both clinical and laboratory followup for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

EPIVIR-HBV is not approved for the treatment of HIV-1 infection because the lamivudine dosage in EPIVIR-HBV is subtherapeutic and monotherapy is inappropriate for the treatment of HIV-1 infection. HIV-1 resistance may emerge in chronic hepatitis B-infected patients with unrecognized or untreated HIV-1 infection. HIV counseling and testing should be offered to all patients before beginning treatment with EPIVIR-HBV and periodically during treatment.

INVOKANA (CANAGLIFLOZIN)

• Added section to warning July 2017

WARNING: LOWER LIMB AMPUTATION

• An approximately 2-fold increased risk of lower limb amputations associated with INVOKANA use was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
• Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
• Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.

Monitor patients receiving INVOKANA for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.

INVOKAMET (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)

• Edited warning August 2017

WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION

Lactic Acidosis

• Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

Risk of Lower Limb Amputation

• In patients with type 2 diabetes who have established cardiovascular disease (CVD) or at risk for CVD, canagliflozin, a component of INVOKAMET, has been associated with lower limb amputations, most frequently of the toe and midfoot; some also involved the leg.

INVOKAMET XR (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)

• Edited warning August 2017

WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION

Lactic Acidosis

• Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as
  malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/ pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.
• Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, cationic drugs such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
• Steps to reduce the risk of and manage metforminassociated lactic acidosis in these high risk groups are provided in the full prescribing information.
• If metformin-associated lactic acidosis is suspected, immediately discontinue INVOKAMET and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

Risk of Lower Limb Amputation

• An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin, a component of INVOKAMET, was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
• Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
• Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.
• Monitor patients receiving INVOKAMET for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.

JEVTANA KIT (CABAZITAXEL)

• Edited warning September 2017

WARNING: NEUTROPENIA AND HYPERSENSITIVITY

Neutropenia: Neutropenic deaths have been reported. Monitor for neutropenia with frequent blood cell counts. JEVTANA is contraindicated in patients with neutrophil counts of less than or equal to 1,500 cells/mm3. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features.

THYRO-TABS (LEVOTHYROXINE SODIUM)

• Added section to warning August 2017

WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS

Thyroid hormones, including THYRO-TABS, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss.

In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction.

Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

REGLAN (METOCLOPRAMIDE HYDROCHLORIDE)

• Edited warning August 2017

WARNING: TARDIVE DYSKINESIA

• Reglan can cause tardive dyskinesia (TD), a serious movement disorder that is often irreversible. There is no known treatment for TD. The risk of developing TD increases with duration of treatment and total cumulative dosage.
• Discontinue Reglan in patients who develop signs or symptoms of TD. In some patients, symptoms may lessen or resolve after Reglan is stopped.
• Avoid treatment with Reglan for longer than 12 weeks because of the increased risk of developing TD with longer-term use.

The FDA’s MedWatch program safety labeling changes for boxed warnings are compiled quarterly for drugs and therapeutic biologics where important changes have been made to the safety information. These and other label changes are searchable in the Drug Safety Labeling Changes (SLC) database, where data are available to the public in downloadable and searchable formats. Boxed warnings are ordinarily used to highlight either adverse reactions so serious in proportion to the potential benefit from the drug that it is essential that it be considered in assessing the risks and benefits of using the drug; or serious adverse reactions that can be prevented/reduced in frequency or severity by appropriate use of the drug; or FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted. For complete FDA Drug Safety Labeling changes, please visit http://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges.

CODEINE SULFATE: EPIVIR-HBV (LAMIVUDINE)

• Added to warning September 2017

WARNING: LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, EXACERBATIONS OF HEPATITIS B, and RISK OF HIV-1 RESISTANCE IF EPIVIR-HBV IS USED IN PATIENTS WITH UNRECOGNIZED OR UNTREATED HIV-1 INFECTION

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue EPIVIR-HBV if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.

Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy (including EPIVIR-HBV). Hepatic function should be monitored closely with both clinical and laboratory followup for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

EPIVIR-HBV is not approved for the treatment of HIV-1 infection because the lamivudine dosage in EPIVIR-HBV is subtherapeutic and monotherapy is inappropriate for the treatment of HIV-1 infection. HIV-1 resistance may emerge in chronic hepatitis B-infected patients with unrecognized or untreated HIV-1 infection. HIV counseling and testing should be offered to all patients before beginning treatment with EPIVIR-HBV and periodically during treatment.

INVOKANA (CANAGLIFLOZIN)

• Added section to warning July 2017

WARNING: LOWER LIMB AMPUTATION

• An approximately 2-fold increased risk of lower limb amputations associated with INVOKANA use was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
• Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
• Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.

Monitor patients receiving INVOKANA for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.

INVOKAMET (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)

• Edited warning August 2017

WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION

Lactic Acidosis

• Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

Risk of Lower Limb Amputation

• In patients with type 2 diabetes who have established cardiovascular disease (CVD) or at risk for CVD, canagliflozin, a component of INVOKAMET, has been associated with lower limb amputations, most frequently of the toe and midfoot; some also involved the leg.

INVOKAMET XR (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)

• Edited warning August 2017

WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION

Lactic Acidosis

• Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as
  malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/ pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.
• Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, cationic drugs such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
• Steps to reduce the risk of and manage metforminassociated lactic acidosis in these high risk groups are provided in the full prescribing information.
• If metformin-associated lactic acidosis is suspected, immediately discontinue INVOKAMET and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

Risk of Lower Limb Amputation

• An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin, a component of INVOKAMET, was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
• Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
• Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.
• Monitor patients receiving INVOKAMET for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.

JEVTANA KIT (CABAZITAXEL)

• Edited warning September 2017

WARNING: NEUTROPENIA AND HYPERSENSITIVITY

Neutropenia: Neutropenic deaths have been reported. Monitor for neutropenia with frequent blood cell counts. JEVTANA is contraindicated in patients with neutrophil counts of less than or equal to 1,500 cells/mm3. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features.

THYRO-TABS (LEVOTHYROXINE SODIUM)

• Added section to warning August 2017

WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS

Thyroid hormones, including THYRO-TABS, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss.

In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction.

Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

REGLAN (METOCLOPRAMIDE HYDROCHLORIDE)

• Edited warning August 2017

WARNING: TARDIVE DYSKINESIA

• Reglan can cause tardive dyskinesia (TD), a serious movement disorder that is often irreversible. There is no known treatment for TD. The risk of developing TD increases with duration of treatment and total cumulative dosage.
• Discontinue Reglan in patients who develop signs or symptoms of TD. In some patients, symptoms may lessen or resolve after Reglan is stopped.
• Avoid treatment with Reglan for longer than 12 weeks because of the increased risk of developing TD with longer-term use.

The FDA’s MedWatch program safety labeling changes for boxed warnings are compiled quarterly for drugs and therapeutic biologics where important changes have been made to the safety information. These and other label changes are searchable in the Drug Safety Labeling Changes (SLC) database, where data are available to the public in downloadable and searchable formats. Boxed warnings are ordinarily used to highlight either adverse reactions so serious in proportion to the potential benefit from the drug that it is essential that it be considered in assessing the risks and benefits of using the drug; or serious adverse reactions that can be prevented/reduced in frequency or severity by appropriate use of the drug; or FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted. For complete FDA Drug Safety Labeling changes, please visit http://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges.

CODEINE SULFATE: EPIVIR-HBV (LAMIVUDINE)

• Added to warning September 2017

WARNING: LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, EXACERBATIONS OF HEPATITIS B, and RISK OF HIV-1 RESISTANCE IF EPIVIR-HBV IS USED IN PATIENTS WITH UNRECOGNIZED OR UNTREATED HIV-1 INFECTION

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue EPIVIR-HBV if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.

Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued anti-hepatitis B therapy (including EPIVIR-HBV). Hepatic function should be monitored closely with both clinical and laboratory followup for at least several months in patients who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

EPIVIR-HBV is not approved for the treatment of HIV-1 infection because the lamivudine dosage in EPIVIR-HBV is subtherapeutic and monotherapy is inappropriate for the treatment of HIV-1 infection. HIV-1 resistance may emerge in chronic hepatitis B-infected patients with unrecognized or untreated HIV-1 infection. HIV counseling and testing should be offered to all patients before beginning treatment with EPIVIR-HBV and periodically during treatment.

INVOKANA (CANAGLIFLOZIN)

• Added section to warning July 2017

WARNING: LOWER LIMB AMPUTATION

• An approximately 2-fold increased risk of lower limb amputations associated with INVOKANA use was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
• Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
• Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.

Monitor patients receiving INVOKANA for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.

INVOKAMET (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)

• Edited warning August 2017

WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION

Lactic Acidosis

• Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

Risk of Lower Limb Amputation

• In patients with type 2 diabetes who have established cardiovascular disease (CVD) or at risk for CVD, canagliflozin, a component of INVOKAMET, has been associated with lower limb amputations, most frequently of the toe and midfoot; some also involved the leg.

INVOKAMET XR (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE)

• Edited warning August 2017

WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION

Lactic Acidosis

• Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as
  malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/ pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.
• Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (eg, cationic drugs such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (eg, acute congestive heart failure), excessive alcohol intake, and hepatic impairment.
• Steps to reduce the risk of and manage metforminassociated lactic acidosis in these high risk groups are provided in the full prescribing information.
• If metformin-associated lactic acidosis is suspected, immediately discontinue INVOKAMET and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended.

Risk of Lower Limb Amputation

• An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin, a component of INVOKAMET, was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
• Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also observed. Some patients had multiple amputations, some involving both limbs.
• Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers.
• Monitor patients receiving INVOKAMET for infection, new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue if these complications occur.

JEVTANA KIT (CABAZITAXEL)

• Edited warning September 2017

WARNING: NEUTROPENIA AND HYPERSENSITIVITY

Neutropenia: Neutropenic deaths have been reported. Monitor for neutropenia with frequent blood cell counts. JEVTANA is contraindicated in patients with neutrophil counts of less than or equal to 1,500 cells/mm3. Primary prophylaxis with G-CSF is recommended in patients with high-risk clinical features.

THYRO-TABS (LEVOTHYROXINE SODIUM)

• Added section to warning August 2017

WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS

Thyroid hormones, including THYRO-TABS, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss.

In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction.

Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

REGLAN (METOCLOPRAMIDE HYDROCHLORIDE)

• Edited warning August 2017

WARNING: TARDIVE DYSKINESIA

• Reglan can cause tardive dyskinesia (TD), a serious movement disorder that is often irreversible. There is no known treatment for TD. The risk of developing TD increases with duration of treatment and total cumulative dosage.
• Discontinue Reglan in patients who develop signs or symptoms of TD. In some patients, symptoms may lessen or resolve after Reglan is stopped.
• Avoid treatment with Reglan for longer than 12 weeks because of the increased risk of developing TD with longer-term use.

LOS ANGELES – The benefits seen early after placement of stem cells near the damaged brain site of chronic stroke patients continued during 2 years of follow-up, Gary K. Steinberg, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

Seeing sustained benefit out to 2 years was “quite surprising. We thought we’d lose the benefit,” Dr. Steinberg said in a video interview.

The findings “change our notion of what happens after a stroke. The damaged circuits can be resurrected,” said Dr. Steinberg, professor and chair of neurosurgery at Stanford (Calif.) University.

He reported long-term follow-up data for 18 chronic stroke patients who had received transplantation of allogeneic bone marrow–derived stem cells. The study’s primary efficacy endpoint, at 6 months after treatment, showed clinically meaningful improvements in several measures of stroke disability and function in 13 of the 18 patients (72%), including a rise of at least 10 points in the Fugl-Meyer total motor function score.

His new report on 2-year follow-up showed that these 6-month improvements continued. The average increase in Fugl-Meyer score over baseline was about 18 points at 6, 12, and 24 months of follow-up.

Based on the promise shown in this pilot study, Dr. Steinberg and his associates are running a randomized study with 156 patients. Enrollment recently completed, and the results should be available during the second half of 2019, Dr. Steinberg said.

SanBio funded the study. Dr. Steinberg has been a consultant or advisor to Qool Therapeutics, Peter Lazic US, and NeuroSave.

[email protected]

SOURCE: Steinberg K et al. International Stroke Conference 2018, Abstract LB14.

LOS ANGELES – The benefits seen early after placement of stem cells near the damaged brain site of chronic stroke patients continued during 2 years of follow-up, Gary K. Steinberg, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

Seeing sustained benefit out to 2 years was “quite surprising. We thought we’d lose the benefit,” Dr. Steinberg said in a video interview.

The findings “change our notion of what happens after a stroke. The damaged circuits can be resurrected,” said Dr. Steinberg, professor and chair of neurosurgery at Stanford (Calif.) University.

He reported long-term follow-up data for 18 chronic stroke patients who had received transplantation of allogeneic bone marrow–derived stem cells. The study’s primary efficacy endpoint, at 6 months after treatment, showed clinically meaningful improvements in several measures of stroke disability and function in 13 of the 18 patients (72%), including a rise of at least 10 points in the Fugl-Meyer total motor function score.

His new report on 2-year follow-up showed that these 6-month improvements continued. The average increase in Fugl-Meyer score over baseline was about 18 points at 6, 12, and 24 months of follow-up.

Based on the promise shown in this pilot study, Dr. Steinberg and his associates are running a randomized study with 156 patients. Enrollment recently completed, and the results should be available during the second half of 2019, Dr. Steinberg said.

SanBio funded the study. Dr. Steinberg has been a consultant or advisor to Qool Therapeutics, Peter Lazic US, and NeuroSave.

[email protected]

SOURCE: Steinberg K et al. International Stroke Conference 2018, Abstract LB14.

LOS ANGELES – The benefits seen early after placement of stem cells near the damaged brain site of chronic stroke patients continued during 2 years of follow-up, Gary K. Steinberg, MD, said at the International Stroke Conference, sponsored by the American Heart Association.

Seeing sustained benefit out to 2 years was “quite surprising. We thought we’d lose the benefit,” Dr. Steinberg said in a video interview.

The findings “change our notion of what happens after a stroke. The damaged circuits can be resurrected,” said Dr. Steinberg, professor and chair of neurosurgery at Stanford (Calif.) University.

He reported long-term follow-up data for 18 chronic stroke patients who had received transplantation of allogeneic bone marrow–derived stem cells. The study’s primary efficacy endpoint, at 6 months after treatment, showed clinically meaningful improvements in several measures of stroke disability and function in 13 of the 18 patients (72%), including a rise of at least 10 points in the Fugl-Meyer total motor function score.

His new report on 2-year follow-up showed that these 6-month improvements continued. The average increase in Fugl-Meyer score over baseline was about 18 points at 6, 12, and 24 months of follow-up.

Based on the promise shown in this pilot study, Dr. Steinberg and his associates are running a randomized study with 156 patients. Enrollment recently completed, and the results should be available during the second half of 2019, Dr. Steinberg said.

SanBio funded the study. Dr. Steinberg has been a consultant or advisor to Qool Therapeutics, Peter Lazic US, and NeuroSave.

[email protected]

SOURCE: Steinberg K et al. International Stroke Conference 2018, Abstract LB14.

Adding metronomic oral cyclophosphamide to trastuzumab and pertuzumab in frail elderly women with human epidermal growth factor receptor 2–positive metastatic breast cancer improved median progression-free survival by 7 months – with acceptable toxicity – vs. dual HER2 blockade alone in a randomized, open-label, phase 2 trial.

After a median follow-up of 20.7 months, the median progression-free survival (PFS) among 41 women who received trastuzumab and pertuzumab plus metronomic oral cyclophosphamide was 12.7 months, compared with 5.6 months among 39 women who received only trastuzumab and pertuzumab. Estimated PFS at 6 months was 73.4% and 46.2% in the groups, respectively (hazard ratio, 0.65), Hans Wildiers, MD, PhD, of University Hospitals Leuven, Belgium, and his colleagues reported in Lancet Oncology.

The most frequent grade 3-4 adverse events occurring in each group, respectively, were hypertension (12% and 15%), diarrhea (12% and 10%), dyspnea (10% and 5%), fatigue (5% and 8%), and pain (5% in each group). Thromboembolic events occurred in four patients (10%) receiving cyclophosphamide, while none occurred in the dual HER2 blockade-only group. Severe cardiac toxicities were occasionally observed in both groups.

Study subjects were women aged at least 70 years, or at least 60 years with confirmed functional restrictions. All had confirmed HER2-positive metastatic breast cancer and no prior chemotherapy for metastatic disease. They received either intravenous trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks, and intravenous pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks (median of 6 cycles), or those same doses of trastuzumab and pertuzumab plus metronomic oral cyclophosphamide at a dose of 50 mg daily (median of 13 cycles). Subsequent treatment with trastuzumab emtansine in 29 patients who progressed during the study was active and well tolerated; the overall PFS at 6 months in this group of patients was 49.5% and median PFS was 5 months after starting trastuzumab emtansine.

“The results of this study indicate that the benefit of avoiding the side effects of chemotherapy with the use of dual anti–HER2 blockade only does not compensate for an important loss of activity in the metastatic setting,” the investigators wrote, concluding that “trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, potentially followed by trastuzumab emtansine after progression, might delay the need for, or supersede, the use of taxane-based chemotherapy in this population.”

Further evaluation of this combination in a randomized phase 3 study is warranted, as the phase 2 findings do not provide “robust justification for a change in practice.” They do, however, provide a scientific framework for supporting more specific trials in older patients, who compromise nearly a third of breast cancer patients worldwide, and up to 50% in high-income countries, they said.

This study was funded by F Hoffmann-La Roche. Dr. Wildiers has received research grants from Roche, and personal fees to his institute from Roche, Amgen, Novartis, Pfizer, Puma, and Celldex. Other authors also reported receiving research or other support from Roche Products, Eisai, Novartis Pharmaceuticals UK, Astellas/Medivation, Astra Zeneca, Celgene, Daiichi-Sankyo, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck Sharp & Dohme, Merus BV, Mylan, Novartis, Pfizer, Pierre Fabre, Sanofi, and Teva.

[email protected]

SOURCE: Wildiers H et al. Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30083-4.

Adding metronomic oral cyclophosphamide to trastuzumab and pertuzumab in frail elderly women with human epidermal growth factor receptor 2–positive metastatic breast cancer improved median progression-free survival by 7 months – with acceptable toxicity – vs. dual HER2 blockade alone in a randomized, open-label, phase 2 trial.

After a median follow-up of 20.7 months, the median progression-free survival (PFS) among 41 women who received trastuzumab and pertuzumab plus metronomic oral cyclophosphamide was 12.7 months, compared with 5.6 months among 39 women who received only trastuzumab and pertuzumab. Estimated PFS at 6 months was 73.4% and 46.2% in the groups, respectively (hazard ratio, 0.65), Hans Wildiers, MD, PhD, of University Hospitals Leuven, Belgium, and his colleagues reported in Lancet Oncology.

The most frequent grade 3-4 adverse events occurring in each group, respectively, were hypertension (12% and 15%), diarrhea (12% and 10%), dyspnea (10% and 5%), fatigue (5% and 8%), and pain (5% in each group). Thromboembolic events occurred in four patients (10%) receiving cyclophosphamide, while none occurred in the dual HER2 blockade-only group. Severe cardiac toxicities were occasionally observed in both groups.

Study subjects were women aged at least 70 years, or at least 60 years with confirmed functional restrictions. All had confirmed HER2-positive metastatic breast cancer and no prior chemotherapy for metastatic disease. They received either intravenous trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks, and intravenous pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks (median of 6 cycles), or those same doses of trastuzumab and pertuzumab plus metronomic oral cyclophosphamide at a dose of 50 mg daily (median of 13 cycles). Subsequent treatment with trastuzumab emtansine in 29 patients who progressed during the study was active and well tolerated; the overall PFS at 6 months in this group of patients was 49.5% and median PFS was 5 months after starting trastuzumab emtansine.

“The results of this study indicate that the benefit of avoiding the side effects of chemotherapy with the use of dual anti–HER2 blockade only does not compensate for an important loss of activity in the metastatic setting,” the investigators wrote, concluding that “trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, potentially followed by trastuzumab emtansine after progression, might delay the need for, or supersede, the use of taxane-based chemotherapy in this population.”

Further evaluation of this combination in a randomized phase 3 study is warranted, as the phase 2 findings do not provide “robust justification for a change in practice.” They do, however, provide a scientific framework for supporting more specific trials in older patients, who compromise nearly a third of breast cancer patients worldwide, and up to 50% in high-income countries, they said.

This study was funded by F Hoffmann-La Roche. Dr. Wildiers has received research grants from Roche, and personal fees to his institute from Roche, Amgen, Novartis, Pfizer, Puma, and Celldex. Other authors also reported receiving research or other support from Roche Products, Eisai, Novartis Pharmaceuticals UK, Astellas/Medivation, Astra Zeneca, Celgene, Daiichi-Sankyo, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck Sharp & Dohme, Merus BV, Mylan, Novartis, Pfizer, Pierre Fabre, Sanofi, and Teva.

[email protected]

SOURCE: Wildiers H et al. Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30083-4.

Adding metronomic oral cyclophosphamide to trastuzumab and pertuzumab in frail elderly women with human epidermal growth factor receptor 2–positive metastatic breast cancer improved median progression-free survival by 7 months – with acceptable toxicity – vs. dual HER2 blockade alone in a randomized, open-label, phase 2 trial.

After a median follow-up of 20.7 months, the median progression-free survival (PFS) among 41 women who received trastuzumab and pertuzumab plus metronomic oral cyclophosphamide was 12.7 months, compared with 5.6 months among 39 women who received only trastuzumab and pertuzumab. Estimated PFS at 6 months was 73.4% and 46.2% in the groups, respectively (hazard ratio, 0.65), Hans Wildiers, MD, PhD, of University Hospitals Leuven, Belgium, and his colleagues reported in Lancet Oncology.

The most frequent grade 3-4 adverse events occurring in each group, respectively, were hypertension (12% and 15%), diarrhea (12% and 10%), dyspnea (10% and 5%), fatigue (5% and 8%), and pain (5% in each group). Thromboembolic events occurred in four patients (10%) receiving cyclophosphamide, while none occurred in the dual HER2 blockade-only group. Severe cardiac toxicities were occasionally observed in both groups.

Study subjects were women aged at least 70 years, or at least 60 years with confirmed functional restrictions. All had confirmed HER2-positive metastatic breast cancer and no prior chemotherapy for metastatic disease. They received either intravenous trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks, and intravenous pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks (median of 6 cycles), or those same doses of trastuzumab and pertuzumab plus metronomic oral cyclophosphamide at a dose of 50 mg daily (median of 13 cycles). Subsequent treatment with trastuzumab emtansine in 29 patients who progressed during the study was active and well tolerated; the overall PFS at 6 months in this group of patients was 49.5% and median PFS was 5 months after starting trastuzumab emtansine.

“The results of this study indicate that the benefit of avoiding the side effects of chemotherapy with the use of dual anti–HER2 blockade only does not compensate for an important loss of activity in the metastatic setting,” the investigators wrote, concluding that “trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, potentially followed by trastuzumab emtansine after progression, might delay the need for, or supersede, the use of taxane-based chemotherapy in this population.”

Further evaluation of this combination in a randomized phase 3 study is warranted, as the phase 2 findings do not provide “robust justification for a change in practice.” They do, however, provide a scientific framework for supporting more specific trials in older patients, who compromise nearly a third of breast cancer patients worldwide, and up to 50% in high-income countries, they said.

This study was funded by F Hoffmann-La Roche. Dr. Wildiers has received research grants from Roche, and personal fees to his institute from Roche, Amgen, Novartis, Pfizer, Puma, and Celldex. Other authors also reported receiving research or other support from Roche Products, Eisai, Novartis Pharmaceuticals UK, Astellas/Medivation, Astra Zeneca, Celgene, Daiichi-Sankyo, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck Sharp & Dohme, Merus BV, Mylan, Novartis, Pfizer, Pierre Fabre, Sanofi, and Teva.

[email protected]

SOURCE: Wildiers H et al. Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30083-4.

How much is $9 worth? Not much. Probably less than most people spend on coffee in a given week.

And yet, that $9 is really irritating to me.

For the last few weeks, when signing into Allscripts to send and refill prescriptions, I’ve encountered this:

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

How much is $9 worth? Not much. Probably less than most people spend on coffee in a given week.

And yet, that $9 is really irritating to me.

For the last few weeks, when signing into Allscripts to send and refill prescriptions, I’ve encountered this:

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

How much is $9 worth? Not much. Probably less than most people spend on coffee in a given week.

And yet, that $9 is really irritating to me.

For the last few weeks, when signing into Allscripts to send and refill prescriptions, I’ve encountered this:

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The Food and Drug Administration approved a new blood test on Feb. 14 – the Banyan Brain Trauma Indicator – for assessing patients with mild traumatic brain injuries, also known as concussions.

Most traumatic brain injuries are classified as “mild,” and the majority of patients have negative CT scans, according to an FDA announcement. Within a matter of hours, this test can help predict which patients will have negative scans by measuring certain proteins released by brain tissue, thereby potentially eliminating unnecessary imaging – and the costs and radiation exposure that would go along with it.

[email protected]

The Food and Drug Administration approved a new blood test on Feb. 14 – the Banyan Brain Trauma Indicator – for assessing patients with mild traumatic brain injuries, also known as concussions.

Most traumatic brain injuries are classified as “mild,” and the majority of patients have negative CT scans, according to an FDA announcement. Within a matter of hours, this test can help predict which patients will have negative scans by measuring certain proteins released by brain tissue, thereby potentially eliminating unnecessary imaging – and the costs and radiation exposure that would go along with it.

[email protected]

The Food and Drug Administration approved a new blood test on Feb. 14 – the Banyan Brain Trauma Indicator – for assessing patients with mild traumatic brain injuries, also known as concussions.

Most traumatic brain injuries are classified as “mild,” and the majority of patients have negative CT scans, according to an FDA announcement. Within a matter of hours, this test can help predict which patients will have negative scans by measuring certain proteins released by brain tissue, thereby potentially eliminating unnecessary imaging – and the costs and radiation exposure that would go along with it.

[email protected]

The influenza vaccine is only about 36% effective this year, preventing infections in just over a third of people who receive it, according to the Feb. 16 issue of Morbidity and Mortality Weekly Report.

The elderly are not among them. Although the vaccine was somewhat protective in children and adults up to 49 years old, “no statistically significant protection was observed in other age groups,” including people 65 years and older, reported investigators led by Brendan Flannery, PhD, of the Centers for Disease Control and Prevention influenza division.

Pradit_Ph/thinkstock

On a related note, on Feb. 18, Senators Edward J. Markey (D-Mass.), Richard Blumenthal (D-Conn.), and Amy Klobuchar (D-Minn.) held a press conference to announce they were introducing the Flu Vaccine Bill to dedicate $1 billion over a 5-year period in order to develop a flu vaccine that could provide lifetime protection. 

The investigators had no conflicts of interest.

[email protected]

SOURCE: Flannery B. et al. MMWR. 2018 Feb 16;67(6):180-5; Budd A. et al. MMWR. 2018 Feb 16;67(6):169-79.

The influenza vaccine is only about 36% effective this year, preventing infections in just over a third of people who receive it, according to the Feb. 16 issue of Morbidity and Mortality Weekly Report.

The elderly are not among them. Although the vaccine was somewhat protective in children and adults up to 49 years old, “no statistically significant protection was observed in other age groups,” including people 65 years and older, reported investigators led by Brendan Flannery, PhD, of the Centers for Disease Control and Prevention influenza division.

Pradit_Ph/thinkstock

On a related note, on Feb. 18, Senators Edward J. Markey (D-Mass.), Richard Blumenthal (D-Conn.), and Amy Klobuchar (D-Minn.) held a press conference to announce they were introducing the Flu Vaccine Bill to dedicate $1 billion over a 5-year period in order to develop a flu vaccine that could provide lifetime protection. 

The investigators had no conflicts of interest.

[email protected]

SOURCE: Flannery B. et al. MMWR. 2018 Feb 16;67(6):180-5; Budd A. et al. MMWR. 2018 Feb 16;67(6):169-79.

The influenza vaccine is only about 36% effective this year, preventing infections in just over a third of people who receive it, according to the Feb. 16 issue of Morbidity and Mortality Weekly Report.

The elderly are not among them. Although the vaccine was somewhat protective in children and adults up to 49 years old, “no statistically significant protection was observed in other age groups,” including people 65 years and older, reported investigators led by Brendan Flannery, PhD, of the Centers for Disease Control and Prevention influenza division.

Pradit_Ph/thinkstock

On a related note, on Feb. 18, Senators Edward J. Markey (D-Mass.), Richard Blumenthal (D-Conn.), and Amy Klobuchar (D-Minn.) held a press conference to announce they were introducing the Flu Vaccine Bill to dedicate $1 billion over a 5-year period in order to develop a flu vaccine that could provide lifetime protection. 

The investigators had no conflicts of interest.

[email protected]

SOURCE: Flannery B. et al. MMWR. 2018 Feb 16;67(6):180-5; Budd A. et al. MMWR. 2018 Feb 16;67(6):169-79.

I recently attended a local Charleston (S.C.) Medical Society meeting, the theme of which was the opioid crisis. Although at the time I did not see a perfect relevance of this crisis to hospital medicine, I attended anyway, hoping to gain some pearls of wisdom regarding what my role in this epidemic could be.

I was already certainly aware of the extent of the opioid epidemic, including some startling statistics. For example, the burden of the crisis totaled $95 billion in the United States in 2016 from lost productivity and health care and criminal justice system expenses.¹ But I was still not certain what my specific role could be in doing something about it.

The main speaker at the meeting was Nanci Steadman Shipman, the mother of a 19-year-old college student who had accidentally overdosed on heroin the year prior. She told the story of his upbringing, which was in an upper-middle-class suburban neighborhood, full of family, friends, and loving support. When her son was 15 years old, he suffered a leg injury during his lacrosse season, which led to a hospital stay, a surgery, and a prolonged recovery. It was during this period of time that, unbeknownst to his family, he became addicted to opioids.

Over the years, Nanci’s son found ever more creative mechanisms to procure various opioids, eventually resorting to heroin, which was remarkably cheap and easy to find. All the while in high school, he maintained good grades, remained active in sports, and had a normal social circle of friends. It was not until his first year of college that his mother started to worry that something might be wrong. In less than a year, her son quit sports, and his grades spiraled. Despite ongoing family support and extensive rehab, he suffered more than one setback and accidentally overdosed.

After her son’s death, Nanci started a nonprofit organization, Wake Up Carolina.² Its mission is to fight drug abuse among adolescents and young adults. They use a combination of education, awareness, prevention, and recovery tactics to achieve their task. In the meantime, they try to diminish the shame and secrecy among families suffering from opioid addiction. During Nanci’s presentation at the medical society meeting, the message she conveyed to us – an audience full of physicians – was simple: We can either be part of the problem or part of the solution; we all have a duty to help and a role to play in this crisis. Whether a patient is exposed first inside the hospital or outside of it, for a short period of time or for a long one, every opioid exposure comes with a risk. Nanci’s story was incredibly affecting and made me rethink my personal role in this epidemic; how might I have contributed to this, and what could I do differently?

Shortly after her son died, her younger son suffered a femur fracture during a football game. You can imagine the horror her family felt knowing that he would need some pain medication for his acute injury. Nanci and her family were able to work with the medical and surgical teams, and through multimodal pain regimens, her son received little to no opioids during the hospital stay and was able to recover from the fracture with reasonable pain levels. She expressed gratitude that the hospital teams were willing to listen to her and her family’s concerns and offer both pharmacological and nonpharmacological therapies for her son’s recovery, which allayed their fears about opioids.

From this incredibly powerful and moving story of one family’s experience, I was able to gather some very meaningful, evidence-based, and tangible practices that I could implement in my own organization. These might even help other hospitalists take an active role in stemming this sadly growing epidemic.



As hospitalists, we should work on the following:

• Improve our personal knowledge of and skills in utilizing multimodal pain therapies regardless of the etiology of the pain. These should include both pharmacologic and nonpharmacologic interventions.
• Use consultants to assist us with difficult cases. Depending on our practice setting, we should utilize consultants who can give us good advice on nonopioid pain management regimens, such as palliative care.
• Try to influence the practice of surgeons and other specialties that consult us, to help shape prescribing patterns that include nonopioid medical regimens, and to get doctors used to entertaining nonpharmacologic pain-reducing interventions.
• Limit the volume of prescription opioids written to our patients at the time of hospital discharge. There is mounting literature that suggests leftover prescriptions can be the start of an opioid addiction for a family member.
• Educate ourselves and our patients about any local “take back” programs that allow for safe, secure, and anonymous drops of prescription medications. This may reduce opioids getting into the hands of someone who might later become addicted.
• Find out whether our hospitals or health systems have a pain or opioid oversight group or team, and if not, see whether there is interest in starting one.
• Look into local community activist programs to partner with for education, awareness, prevention, or treatment options (such as Wake Up Carolina).
• Work with local resources (for example, case management, social workers, psychiatrists) to learn about and utilize local options for rehabilitation. We should actively and openly discuss these options with any patients known or suspected to be addicted.
• Make a valiant attempt to remove any unconscious bias against people who have become addicted to opioids. Continuing the social stigma of addiction only spurs the shame and secrecy.

Please share other ideas or suggestions you may have regarding the role hospitalists can have in curbing this growing epidemic.
 

References

1. “Burden of opioid crisis reached $95 billion in 2016; private sector hit hardest.” Altarum press release. Nov 16, 2017.

2. Wake Up Carolina website.








 

I recently attended a local Charleston (S.C.) Medical Society meeting, the theme of which was the opioid crisis. Although at the time I did not see a perfect relevance of this crisis to hospital medicine, I attended anyway, hoping to gain some pearls of wisdom regarding what my role in this epidemic could be.

I was already certainly aware of the extent of the opioid epidemic, including some startling statistics. For example, the burden of the crisis totaled $95 billion in the United States in 2016 from lost productivity and health care and criminal justice system expenses.¹ But I was still not certain what my specific role could be in doing something about it.

The main speaker at the meeting was Nanci Steadman Shipman, the mother of a 19-year-old college student who had accidentally overdosed on heroin the year prior. She told the story of his upbringing, which was in an upper-middle-class suburban neighborhood, full of family, friends, and loving support. When her son was 15 years old, he suffered a leg injury during his lacrosse season, which led to a hospital stay, a surgery, and a prolonged recovery. It was during this period of time that, unbeknownst to his family, he became addicted to opioids.

Over the years, Nanci’s son found ever more creative mechanisms to procure various opioids, eventually resorting to heroin, which was remarkably cheap and easy to find. All the while in high school, he maintained good grades, remained active in sports, and had a normal social circle of friends. It was not until his first year of college that his mother started to worry that something might be wrong. In less than a year, her son quit sports, and his grades spiraled. Despite ongoing family support and extensive rehab, he suffered more than one setback and accidentally overdosed.

After her son’s death, Nanci started a nonprofit organization, Wake Up Carolina.² Its mission is to fight drug abuse among adolescents and young adults. They use a combination of education, awareness, prevention, and recovery tactics to achieve their task. In the meantime, they try to diminish the shame and secrecy among families suffering from opioid addiction. During Nanci’s presentation at the medical society meeting, the message she conveyed to us – an audience full of physicians – was simple: We can either be part of the problem or part of the solution; we all have a duty to help and a role to play in this crisis. Whether a patient is exposed first inside the hospital or outside of it, for a short period of time or for a long one, every opioid exposure comes with a risk. Nanci’s story was incredibly affecting and made me rethink my personal role in this epidemic; how might I have contributed to this, and what could I do differently?

Shortly after her son died, her younger son suffered a femur fracture during a football game. You can imagine the horror her family felt knowing that he would need some pain medication for his acute injury. Nanci and her family were able to work with the medical and surgical teams, and through multimodal pain regimens, her son received little to no opioids during the hospital stay and was able to recover from the fracture with reasonable pain levels. She expressed gratitude that the hospital teams were willing to listen to her and her family’s concerns and offer both pharmacological and nonpharmacological therapies for her son’s recovery, which allayed their fears about opioids.

From this incredibly powerful and moving story of one family’s experience, I was able to gather some very meaningful, evidence-based, and tangible practices that I could implement in my own organization. These might even help other hospitalists take an active role in stemming this sadly growing epidemic.



As hospitalists, we should work on the following:

• Improve our personal knowledge of and skills in utilizing multimodal pain therapies regardless of the etiology of the pain. These should include both pharmacologic and nonpharmacologic interventions.
• Use consultants to assist us with difficult cases. Depending on our practice setting, we should utilize consultants who can give us good advice on nonopioid pain management regimens, such as palliative care.
• Try to influence the practice of surgeons and other specialties that consult us, to help shape prescribing patterns that include nonopioid medical regimens, and to get doctors used to entertaining nonpharmacologic pain-reducing interventions.
• Limit the volume of prescription opioids written to our patients at the time of hospital discharge. There is mounting literature that suggests leftover prescriptions can be the start of an opioid addiction for a family member.
• Educate ourselves and our patients about any local “take back” programs that allow for safe, secure, and anonymous drops of prescription medications. This may reduce opioids getting into the hands of someone who might later become addicted.
• Find out whether our hospitals or health systems have a pain or opioid oversight group or team, and if not, see whether there is interest in starting one.
• Look into local community activist programs to partner with for education, awareness, prevention, or treatment options (such as Wake Up Carolina).
• Work with local resources (for example, case management, social workers, psychiatrists) to learn about and utilize local options for rehabilitation. We should actively and openly discuss these options with any patients known or suspected to be addicted.
• Make a valiant attempt to remove any unconscious bias against people who have become addicted to opioids. Continuing the social stigma of addiction only spurs the shame and secrecy.

Please share other ideas or suggestions you may have regarding the role hospitalists can have in curbing this growing epidemic.
 

References

1. “Burden of opioid crisis reached $95 billion in 2016; private sector hit hardest.” Altarum press release. Nov 16, 2017.

2. Wake Up Carolina website.








 

I recently attended a local Charleston (S.C.) Medical Society meeting, the theme of which was the opioid crisis. Although at the time I did not see a perfect relevance of this crisis to hospital medicine, I attended anyway, hoping to gain some pearls of wisdom regarding what my role in this epidemic could be.

I was already certainly aware of the extent of the opioid epidemic, including some startling statistics. For example, the burden of the crisis totaled $95 billion in the United States in 2016 from lost productivity and health care and criminal justice system expenses.¹ But I was still not certain what my specific role could be in doing something about it.

The main speaker at the meeting was Nanci Steadman Shipman, the mother of a 19-year-old college student who had accidentally overdosed on heroin the year prior. She told the story of his upbringing, which was in an upper-middle-class suburban neighborhood, full of family, friends, and loving support. When her son was 15 years old, he suffered a leg injury during his lacrosse season, which led to a hospital stay, a surgery, and a prolonged recovery. It was during this period of time that, unbeknownst to his family, he became addicted to opioids.

Over the years, Nanci’s son found ever more creative mechanisms to procure various opioids, eventually resorting to heroin, which was remarkably cheap and easy to find. All the while in high school, he maintained good grades, remained active in sports, and had a normal social circle of friends. It was not until his first year of college that his mother started to worry that something might be wrong. In less than a year, her son quit sports, and his grades spiraled. Despite ongoing family support and extensive rehab, he suffered more than one setback and accidentally overdosed.

After her son’s death, Nanci started a nonprofit organization, Wake Up Carolina.² Its mission is to fight drug abuse among adolescents and young adults. They use a combination of education, awareness, prevention, and recovery tactics to achieve their task. In the meantime, they try to diminish the shame and secrecy among families suffering from opioid addiction. During Nanci’s presentation at the medical society meeting, the message she conveyed to us – an audience full of physicians – was simple: We can either be part of the problem or part of the solution; we all have a duty to help and a role to play in this crisis. Whether a patient is exposed first inside the hospital or outside of it, for a short period of time or for a long one, every opioid exposure comes with a risk. Nanci’s story was incredibly affecting and made me rethink my personal role in this epidemic; how might I have contributed to this, and what could I do differently?

Shortly after her son died, her younger son suffered a femur fracture during a football game. You can imagine the horror her family felt knowing that he would need some pain medication for his acute injury. Nanci and her family were able to work with the medical and surgical teams, and through multimodal pain regimens, her son received little to no opioids during the hospital stay and was able to recover from the fracture with reasonable pain levels. She expressed gratitude that the hospital teams were willing to listen to her and her family’s concerns and offer both pharmacological and nonpharmacological therapies for her son’s recovery, which allayed their fears about opioids.

From this incredibly powerful and moving story of one family’s experience, I was able to gather some very meaningful, evidence-based, and tangible practices that I could implement in my own organization. These might even help other hospitalists take an active role in stemming this sadly growing epidemic.



As hospitalists, we should work on the following:

• Improve our personal knowledge of and skills in utilizing multimodal pain therapies regardless of the etiology of the pain. These should include both pharmacologic and nonpharmacologic interventions.
• Use consultants to assist us with difficult cases. Depending on our practice setting, we should utilize consultants who can give us good advice on nonopioid pain management regimens, such as palliative care.
• Try to influence the practice of surgeons and other specialties that consult us, to help shape prescribing patterns that include nonopioid medical regimens, and to get doctors used to entertaining nonpharmacologic pain-reducing interventions.
• Limit the volume of prescription opioids written to our patients at the time of hospital discharge. There is mounting literature that suggests leftover prescriptions can be the start of an opioid addiction for a family member.
• Educate ourselves and our patients about any local “take back” programs that allow for safe, secure, and anonymous drops of prescription medications. This may reduce opioids getting into the hands of someone who might later become addicted.
• Find out whether our hospitals or health systems have a pain or opioid oversight group or team, and if not, see whether there is interest in starting one.
• Look into local community activist programs to partner with for education, awareness, prevention, or treatment options (such as Wake Up Carolina).
• Work with local resources (for example, case management, social workers, psychiatrists) to learn about and utilize local options for rehabilitation. We should actively and openly discuss these options with any patients known or suspected to be addicted.
• Make a valiant attempt to remove any unconscious bias against people who have become addicted to opioids. Continuing the social stigma of addiction only spurs the shame and secrecy.

Please share other ideas or suggestions you may have regarding the role hospitalists can have in curbing this growing epidemic.
 

References

1. “Burden of opioid crisis reached $95 billion in 2016; private sector hit hardest.” Altarum press release. Nov 16, 2017.

2. Wake Up Carolina website.








 

The American College of Surgeons (ACS) Division of Education is offering fellowships in surgical ethics with the MacLean Center for Clinical Medical Ethics, University of Chicago, IL. The MacLean Center will prepare two surgeons for careers that combine clinical surgery with scholarly studies in surgical ethics, beginning with a five-week, full-time course in Chicago in July and August 2018. From September 2018 to June 2019, fellowship recipients will meet weekly for a structured ethics curriculum. In addition, fellows will participate in an ethics consultation service and complete a research project.

For additional information about this fellowship, contact Patrice Gabler Blair, MPH, Associate Director, ACS Division of Education, at [email protected]. Application materials are now due March 15.

The American College of Surgeons (ACS) Division of Education is offering fellowships in surgical ethics with the MacLean Center for Clinical Medical Ethics, University of Chicago, IL. The MacLean Center will prepare two surgeons for careers that combine clinical surgery with scholarly studies in surgical ethics, beginning with a five-week, full-time course in Chicago in July and August 2018. From September 2018 to June 2019, fellowship recipients will meet weekly for a structured ethics curriculum. In addition, fellows will participate in an ethics consultation service and complete a research project.

For additional information about this fellowship, contact Patrice Gabler Blair, MPH, Associate Director, ACS Division of Education, at [email protected]. Application materials are now due March 15.

The American College of Surgeons (ACS) Division of Education is offering fellowships in surgical ethics with the MacLean Center for Clinical Medical Ethics, University of Chicago, IL. The MacLean Center will prepare two surgeons for careers that combine clinical surgery with scholarly studies in surgical ethics, beginning with a five-week, full-time course in Chicago in July and August 2018. From September 2018 to June 2019, fellowship recipients will meet weekly for a structured ethics curriculum. In addition, fellows will participate in an ethics consultation service and complete a research project.

For additional information about this fellowship, contact Patrice Gabler Blair, MPH, Associate Director, ACS Division of Education, at [email protected]. Application materials are now due March 15.

Registration is open for the 12th annual Residents as Teachers and Leaders Course hosted by the American College of Surgeons (ACS) Division of Education. The 2018 program, April 13−15 at the ACS headquarters in Chicago, IL, is designed specifically for surgery residents and will address the essential nonclinical skills—teaching and leading—that are required for success as surgeons and members of the health care team.

The course faculty, all experts in resident education, will provide an interactive learning environment. Residents will learn to lead a team more effectively, resolve conflict, be better teachers, give constructive feedback, and apply these skills during and after residency. The number of participants is limited to allow ample interaction with faculty and to facilitate networking. This course is targeted at mid- to senior-level residents, but all are welcome to attend.

Registration information and a brochure are available on the course web page at www.facs.org/education/division-of-education/courses/residents-as-teachers; the advance registration discount ends March 16. Note that last year’s course was oversubscribed, so register soon if you are interested in attending. Contact Kim Echert at [email protected] or at 312-202-5488 with any questions.








 

Registration is open for the 12th annual Residents as Teachers and Leaders Course hosted by the American College of Surgeons (ACS) Division of Education. The 2018 program, April 13−15 at the ACS headquarters in Chicago, IL, is designed specifically for surgery residents and will address the essential nonclinical skills—teaching and leading—that are required for success as surgeons and members of the health care team.

The course faculty, all experts in resident education, will provide an interactive learning environment. Residents will learn to lead a team more effectively, resolve conflict, be better teachers, give constructive feedback, and apply these skills during and after residency. The number of participants is limited to allow ample interaction with faculty and to facilitate networking. This course is targeted at mid- to senior-level residents, but all are welcome to attend.

Registration information and a brochure are available on the course web page at www.facs.org/education/division-of-education/courses/residents-as-teachers; the advance registration discount ends March 16. Note that last year’s course was oversubscribed, so register soon if you are interested in attending. Contact Kim Echert at [email protected] or at 312-202-5488 with any questions.








 

Registration is open for the 12th annual Residents as Teachers and Leaders Course hosted by the American College of Surgeons (ACS) Division of Education. The 2018 program, April 13−15 at the ACS headquarters in Chicago, IL, is designed specifically for surgery residents and will address the essential nonclinical skills—teaching and leading—that are required for success as surgeons and members of the health care team.

The course faculty, all experts in resident education, will provide an interactive learning environment. Residents will learn to lead a team more effectively, resolve conflict, be better teachers, give constructive feedback, and apply these skills during and after residency. The number of participants is limited to allow ample interaction with faculty and to facilitate networking. This course is targeted at mid- to senior-level residents, but all are welcome to attend.

Registration information and a brochure are available on the course web page at www.facs.org/education/division-of-education/courses/residents-as-teachers; the advance registration discount ends March 16. Note that last year’s course was oversubscribed, so register soon if you are interested in attending. Contact Kim Echert at [email protected] or at 312-202-5488 with any questions.








 

ABSTRACT

Revision shoulder arthroplasty is becoming more prevalent as the rate of primary shoulder arthroplasty in the US continues to increase. The management of proximal humeral bone loss in the revision setting presents a difficult problem without a clear solution. Different preoperative diagnoses often lead to distinctly different patterns of bone loss. Successful management of these cases requires a clear understanding of the normal anatomy of the proximal humerus, as well as structural limitations imposed by significant bone loss and the effect this loss has on component fixation. Our preferred technique differs depending on the pattern of bone loss encountered. The use of allograft-prosthetic composites, the cement-within-cement technique, and combinations of these strategies comprise the mainstay of our treatment algorithm. This article focuses on indications, surgical techniques, and some of the published outcomes using these strategies in the management of proximal humeral bone loss.

Continue to: The demand for shoulder arthroplasty...

The demand for shoulder arthroplasty (SA) has increased significantly over the past decade, with a 200% increase witnessed from 2011 to 2015.¹ SA performed in patients younger than 55 years is expected to increase 333% between 2011 to 2030.² With increasing rates of SA being performed in younger patient populations, rates of revision SA also can be expected to climb. Revision to reverse shoulder arthroplasty (RSA) has arisen as a viable option in these patients, and multiple studies demonstrate excellent outcomes that can be obtained with RSA.^3-11

Despite significant improvements obtained in revision SA since the mainstream acceptance of RSA, bone loss remains a problematic issue. Loss of humeral bone stock, in particular, can be a challenging problem to solve with multiple clinical implications. Biomechanical studies have demonstrated that if bone loss is left unaddressed, increased bending and torsional forces on the prosthesis result, which ultimately contribute to increased micromotion and eventual component failure.¹² In addition, existing challenges are associated with the lack of attachment sites for both multiple muscles and tendons. Also, there is a loss of the normal lateralized pull of the deltoid, which results in a decreased amount of force generated by this muscle.^13,14 Ultimately, the increased loss of bone can lead to a devastating situation where there is not enough bone to provide adequate fixation while maintaining the appropriate humeral length necessary to achieve stability of the articulation, which will inevitably lead to instability.^4,15 Therefore, techniques are needed to address proximal humeral bone loss while maintaining as much native humeral bone as possible.

PROXIMAL HUMERUS: ANATOMICAL CONSIDERATIONS

The anatomy of the proximal humerus has been studied in great detail and reported in a number of different studies.^16-23 The average humeral head thickness (24 mm in men and 19 mm in women) and offset relative to the humeral shaft (2.1 mm posterior and 6.6 mm medial) act to tension the rotator cuff musculature appropriately and contribute to a wrapping effect that allows the deltoid to function more effectively.^13,14 Knowledge regarding the rotator cuff footprint has advanced over the past 10 years, specifically with regard to the supraspinatus and infraspinatus.²⁴ The current belief is that the supraspinatus has a triangular insertion onto the most anterior aspect of the greater tuberosity, with a maximum medial-to-lateral length of 6.9 mm and a maximum anterior-to-posterior width of 12.6 mm. The infraspinatus insertion has a trapezoidal insertion, with a maximum medial-to-lateral length of 10.2 mm and anterior-to-posterior width of 32.7 mm. The subscapularis, by far the largest of all the rotator cuff muscles, has a complex geometry with regard to its insertion on the lesser tuberosity, with 4 different insertion points and an overall lateral footprint measuring 37.6 mm and a medial footprint measuring 40.7 mm.²⁵ Finally, the teres minor, with the smallest volume of all the rotator cuff muscles, inserts immediately inferior to the infraspinatus along the inferior facet of the greater tuberosity.²⁶

Aside from the rotator cuff, there are various other muscles and tendons that insert about the proximal humerus and are essential for normal function. The deltoid, which inserts at a point approximately 6 cm from the greater tuberosity along the length of the humerus, with an insertion length between 5 cm to 7 cm,^13,27 is the primary mover of the shoulder and essential for proper function after RSA.^28,29 The pectoralis major tendon, which begins inserting at a point approximately 5.6 cm from the humeral head and spans a distance of 7.7 cm along the length of the humerus,^30-32 is important not only for function but as an anatomical landmark in reconstruction. Lastly, the latissimus dorsi and teres major, which share a role in extension, adduction, and internal rotation of the glenohumeral joint, insert along the floor and medial lip of the intertubercular groove of the humerus, respectively.^33,34 In addition to their role in tendon transfer procedures because of treating irreparable posterosuperior cuff and subscapularis tears,^35,36 it has been suggested that these tendons may play some role in glenohumeral joint stability.³⁷

            In addition to the loss of muscular attachments, the absence of proximal humeral bone stock, in and of itself, can have deleterious effects on fixation of the humeral component. RSA is a semiconstrained device, which results in increased transmission of forces to the interface between the humeral implant and its surrounding structures, including cement (when present) and the bone itself. When there is the absence of significant amounts of bone, the remaining bone must now account for an even higher proportion of these forces. A previous biomechanical study showed that cemented humeral stems demonstrated significantly increased micromotion in the presence of proximal humeral bone loss, particularly when a modular humeral component was used.¹²

Continue to: TYPES OF BONE LOSS

There are a variety of different etiologies of proximal humeral bone loss that result in distinctly different clinical presentations. These can be fairly mild, as is the case of isolated resorption of the greater tuberosity in a non-united proximal humerus fracture (Figure 1). Alternatively, they can be severe, as seen in a grossly loose cemented long-stemmed component that is freely mobile, creating a windshield-wiper effect throughout the length of the humerus (Figure 2). This can be somewhat deceiving, however, as the amount of bone loss, as well as the pathophysiologic process that led to the bone loss, are important factors to determine ideal reconstructive methods. In the case of a failed open reduction internal fixation, where the tuberosity has failed to unite or has been resected, there is much less of a biologic response in comparison with implant loosening associated with osteolysis. This latter condition will be associated with a much more destructive inflammatory response resulting in poor tissue quality and often dramatic thinning of the cortex. If one simply measured the distance from the most proximal remaining bone stock to the area where the greater tuberosity should be, a loose stem with subsidence and ballooning of the cortices may appear to have a similar amount of bone loss as a failed hemiarthroplasty for fracture with a well-fixed stem. However, intraoperatively, one will find that the bone that appeared to be present radiographically in the case of the loose stem is of such poor quality that it cannot reasonably provide any beneficial fixation. In light of this, different treatment modalities are recommended for different types of bone loss, and the revision surgeon must be able to anticipate this and possess a full armamentarium of options to treat these challenging cases successfully.

INDICATIONS

Our technique to manage proximal humeral bone loss is dependent on both the quantity of bone loss, which can be measured radiographically, as well as the anticipated inflammatory response described above. As both the destructive process and the amount of bone loss increase, the importance of more advanced reconstructive procedures that will sustain implant security and soft-tissue management becomes apparent. In the least destructive cases with <5 cm of bone loss, successful revision can typically be accomplished with stem removal and placement of a new monoblock humeral stem. In cases where more advanced destructive pathology is present, and bone loss is >5 cm, an allograft-prosthetic composite (APC) is typically used. In both scenarios, if the stem being revised is cemented and the cement mantle remains intact, and of reasonable length, consideration is given to the cement-within-cement technique. Finally, in the most destructive cases where bone loss exceeds 10 cm and a large biological response is anticipated (eg, periprosthetic fractures with humeral loosening), the use of a longer diaphyseal-incorporating APC is often necessary. This prosthetic composite can be combined with a cement-within-cement technique as well.

It is important to comment on the implications of using modular stems in this setting. With advanced bone loss, a situation is often encountered where the newly implanted stem geometry and working length may be insufficient to acquire adequate rotational stability. In this setting, if a modular junction is positioned close to the stem and cement/bone interface, it will be exposed to very high stress concentrations which can lead to component fracture³⁸ as well as taper corrosion, also referred to as trunnionosis. This latter phenomenon, which has been well studied in the total hip arthroplasty literature with the use of modular components,³⁹ is especially relevant given the high torsional loads imparted at the modular junction. Ultimately, high torsional loads lead to micromotion and electrochemical ion release via degradation of the passivation layer, initiating the process of mechanically assisted crevice corrosion.⁴⁰ For these reasons, when a modular stem must be used in the presence of mild to moderate bone loss, using a proximal humeral allograft to protect the junction or to provide additional fixation may be implemented with a lower threshold than when using a monoblock stem.

SURGICAL TECHNIQUE: ALLOGRAFT-PROSTHETIC COMPOSITES

A standard deltopectoral approach is used, taking care to preserve all viable muscular attachments to the proximal humerus. After removal of the prosthetic humeral head, the decision to proceed with removal of the stem at this juncture is based on several factors. If the remaining proximal humeral bone is so compromised that it might not be able to withstand the forces exerted upon it during retraction for glenoid exposure, the component is left in place. Additionally, if there is consideration that the glenoid-sided bone loss may be so severe that a glenoid baseplate cannot be implanted, and the stem remains well fixed, it is retained so that it can be converted to a hemiarthroplasty.

If neither of the above issues is present, the humeral stem is removed. If a well-fixed press-fit stem is in place, it is typically removed using a combination of burrs and osteotomes to disrupt the bone-implant interface, and the stem is then carefully removed using an impactor and mallet. If a cemented stem is present, the stem is removed in a similar manner, and the cement mantle is left in place if stable, in anticipation of a cement-within-cement technique. If the mantle is disrupted, standard cement removal instruments are used to remove all cement from the canal meticulously.

Continue to: Management of the glenoid...

Management of the glenoid can have significant implications with regard to the humerus. Most notably, the size of the glenosphere has direct implications on the fixation of the humeral component. Use of larger diameter glenospheres result in increased contact area between the glenosphere and humerosocket, adding constraint to the articulation and further increasing the stresses at the implant-bone interface. As such, the use of larger glenospheres to prevent instability must be balanced with the resulting implications on humeral component fixation, especially in cases of severe bone loss.

After implanting the appropriate glenosphere, attention is then turned back to the humerus. Trial implants are sequentially used to obtain adequate humeral length and stability. Once this is accomplished, the amount of humeral bone loss is quantified by measuring the distance from the superior aspect of the medial humeral tray to the medial humeral shaft. If this number is >5 cm (Figure 3), the decision is made to proceed with an APC. The allograft humeral head is cut, cancellous bone is removed, and a step-cut is performed, with the medial portion of the allograft measuring the same length as that of bone loss and the lateral plate extending an additional several centimeters distally (Figure 4). Additional soft tissue is removed from the allograft, leaving the subscapularis stump intact for later repair with the patient’s native tissue. The allograft is secured to the patient’s proximal humerus using multiple cerclage wires, and the humeral stem is cemented into place. The final construct is shown in Figure 5.

ADDITIONAL CONSIDERATIONS: CASES OF ADVANCED BONE LOSS

In cases of advanced humeral bone loss, as is often seen when revising loose humeral stems, larger allografts that span a significant length of the diaphysis are often required. This type of bone loss has implications with regard to how the deltoid insertion is managed. Interestingly, even in situations when the vast majority of the remaining diaphysis consists of ectatic egg-shell bone, the deltoid tuberosity remains of fairly substantial quality due to the continued pull of the muscular insertion on this area. This fragment is isolated, carefully mobilized, and subsequently repaired back on top of the allograft using cables.

POSTOPERATIVE CARE

Patients are kept in a shoulder immobilizer for 6 weeks after surgery to facilitate allograft incorporation and subscapularis tendon healing. During this time, pendulum exercises are initiated. Active assisted range of motion (ROM) exercises begin after 6 weeks, consisting of supine forward elevation. A sling is given to be used in public. Light strengthening exercises begin at 3 months postoperatively.

DISCUSSION

In cases of mild to moderate proximal humeral bone loss, RSA using a long-stem humeral component without allograft augmentation is a viable option. Budge and colleagues³⁸ demonstrated excellent results in a population of 15 patients with an average of 38 mm of proximal humeral bone loss without use of allografts. Interestingly, they noted 1 case of component fracture in a modular prosthesis and therefore concluded that monoblock humeral stems should be used in the absence of allograft augmentation.

Continue to: In more advanced cases of bone loss...

In more advanced cases of bone loss, our data shows that use of APCs can result in equally satisfactory results. In a series of 25 patients with an average bone loss of 54 mm, patients were able to achieve statistically significant improvements in pain, ROM, and function with high rates of allograft incorporation.⁹ Overall, a low rate of complications was noted, including 1 infection. This finding is consistent with an additional study looking specifically at factors associated with infection in revision SA, which found that the use of allografts was not associated with increased risk of infection.⁴¹

As stated previously, the size of allograft needed for the APC construct is related to the distinct pathology encountered. In our experience, we have noted that well-fixed stems can be treated with short metaphyseal APCs in 85% of cases. On the other hand, loose stems require long allografts measuring >10 cm in 90% of cases. As such, these cases typically require mobilization of the deltoid insertion as described above, and therefore it is important that the surgeon is prepared for this aspect of the procedure preoperatively.

Finally, the cement-within-cement technique, originally popularized for use in revision total hip arthroplasty, has demonstrated reliable results when utilized in revision SA.⁴² To date, there are no recommendations regarding the minimal length of existing cement mantle that is needed to perform this technique. In situations in which the length of the cement mantle is questionable, our preference is to combine the cement-within-cement technique with an APC when possible.

ABSTRACT

Revision shoulder arthroplasty is becoming more prevalent as the rate of primary shoulder arthroplasty in the US continues to increase. The management of proximal humeral bone loss in the revision setting presents a difficult problem without a clear solution. Different preoperative diagnoses often lead to distinctly different patterns of bone loss. Successful management of these cases requires a clear understanding of the normal anatomy of the proximal humerus, as well as structural limitations imposed by significant bone loss and the effect this loss has on component fixation. Our preferred technique differs depending on the pattern of bone loss encountered. The use of allograft-prosthetic composites, the cement-within-cement technique, and combinations of these strategies comprise the mainstay of our treatment algorithm. This article focuses on indications, surgical techniques, and some of the published outcomes using these strategies in the management of proximal humeral bone loss.

Continue to: The demand for shoulder arthroplasty...

The demand for shoulder arthroplasty (SA) has increased significantly over the past decade, with a 200% increase witnessed from 2011 to 2015.¹ SA performed in patients younger than 55 years is expected to increase 333% between 2011 to 2030.² With increasing rates of SA being performed in younger patient populations, rates of revision SA also can be expected to climb. Revision to reverse shoulder arthroplasty (RSA) has arisen as a viable option in these patients, and multiple studies demonstrate excellent outcomes that can be obtained with RSA.^3-11

Despite significant improvements obtained in revision SA since the mainstream acceptance of RSA, bone loss remains a problematic issue. Loss of humeral bone stock, in particular, can be a challenging problem to solve with multiple clinical implications. Biomechanical studies have demonstrated that if bone loss is left unaddressed, increased bending and torsional forces on the prosthesis result, which ultimately contribute to increased micromotion and eventual component failure.¹² In addition, existing challenges are associated with the lack of attachment sites for both multiple muscles and tendons. Also, there is a loss of the normal lateralized pull of the deltoid, which results in a decreased amount of force generated by this muscle.^13,14 Ultimately, the increased loss of bone can lead to a devastating situation where there is not enough bone to provide adequate fixation while maintaining the appropriate humeral length necessary to achieve stability of the articulation, which will inevitably lead to instability.^4,15 Therefore, techniques are needed to address proximal humeral bone loss while maintaining as much native humeral bone as possible.

PROXIMAL HUMERUS: ANATOMICAL CONSIDERATIONS

The anatomy of the proximal humerus has been studied in great detail and reported in a number of different studies.^16-23 The average humeral head thickness (24 mm in men and 19 mm in women) and offset relative to the humeral shaft (2.1 mm posterior and 6.6 mm medial) act to tension the rotator cuff musculature appropriately and contribute to a wrapping effect that allows the deltoid to function more effectively.^13,14 Knowledge regarding the rotator cuff footprint has advanced over the past 10 years, specifically with regard to the supraspinatus and infraspinatus.²⁴ The current belief is that the supraspinatus has a triangular insertion onto the most anterior aspect of the greater tuberosity, with a maximum medial-to-lateral length of 6.9 mm and a maximum anterior-to-posterior width of 12.6 mm. The infraspinatus insertion has a trapezoidal insertion, with a maximum medial-to-lateral length of 10.2 mm and anterior-to-posterior width of 32.7 mm. The subscapularis, by far the largest of all the rotator cuff muscles, has a complex geometry with regard to its insertion on the lesser tuberosity, with 4 different insertion points and an overall lateral footprint measuring 37.6 mm and a medial footprint measuring 40.7 mm.²⁵ Finally, the teres minor, with the smallest volume of all the rotator cuff muscles, inserts immediately inferior to the infraspinatus along the inferior facet of the greater tuberosity.²⁶

Aside from the rotator cuff, there are various other muscles and tendons that insert about the proximal humerus and are essential for normal function. The deltoid, which inserts at a point approximately 6 cm from the greater tuberosity along the length of the humerus, with an insertion length between 5 cm to 7 cm,^13,27 is the primary mover of the shoulder and essential for proper function after RSA.^28,29 The pectoralis major tendon, which begins inserting at a point approximately 5.6 cm from the humeral head and spans a distance of 7.7 cm along the length of the humerus,^30-32 is important not only for function but as an anatomical landmark in reconstruction. Lastly, the latissimus dorsi and teres major, which share a role in extension, adduction, and internal rotation of the glenohumeral joint, insert along the floor and medial lip of the intertubercular groove of the humerus, respectively.^33,34 In addition to their role in tendon transfer procedures because of treating irreparable posterosuperior cuff and subscapularis tears,^35,36 it has been suggested that these tendons may play some role in glenohumeral joint stability.³⁷

            In addition to the loss of muscular attachments, the absence of proximal humeral bone stock, in and of itself, can have deleterious effects on fixation of the humeral component. RSA is a semiconstrained device, which results in increased transmission of forces to the interface between the humeral implant and its surrounding structures, including cement (when present) and the bone itself. When there is the absence of significant amounts of bone, the remaining bone must now account for an even higher proportion of these forces. A previous biomechanical study showed that cemented humeral stems demonstrated significantly increased micromotion in the presence of proximal humeral bone loss, particularly when a modular humeral component was used.¹²

Continue to: TYPES OF BONE LOSS

There are a variety of different etiologies of proximal humeral bone loss that result in distinctly different clinical presentations. These can be fairly mild, as is the case of isolated resorption of the greater tuberosity in a non-united proximal humerus fracture (Figure 1). Alternatively, they can be severe, as seen in a grossly loose cemented long-stemmed component that is freely mobile, creating a windshield-wiper effect throughout the length of the humerus (Figure 2). This can be somewhat deceiving, however, as the amount of bone loss, as well as the pathophysiologic process that led to the bone loss, are important factors to determine ideal reconstructive methods. In the case of a failed open reduction internal fixation, where the tuberosity has failed to unite or has been resected, there is much less of a biologic response in comparison with implant loosening associated with osteolysis. This latter condition will be associated with a much more destructive inflammatory response resulting in poor tissue quality and often dramatic thinning of the cortex. If one simply measured the distance from the most proximal remaining bone stock to the area where the greater tuberosity should be, a loose stem with subsidence and ballooning of the cortices may appear to have a similar amount of bone loss as a failed hemiarthroplasty for fracture with a well-fixed stem. However, intraoperatively, one will find that the bone that appeared to be present radiographically in the case of the loose stem is of such poor quality that it cannot reasonably provide any beneficial fixation. In light of this, different treatment modalities are recommended for different types of bone loss, and the revision surgeon must be able to anticipate this and possess a full armamentarium of options to treat these challenging cases successfully.

INDICATIONS

Our technique to manage proximal humeral bone loss is dependent on both the quantity of bone loss, which can be measured radiographically, as well as the anticipated inflammatory response described above. As both the destructive process and the amount of bone loss increase, the importance of more advanced reconstructive procedures that will sustain implant security and soft-tissue management becomes apparent. In the least destructive cases with <5 cm of bone loss, successful revision can typically be accomplished with stem removal and placement of a new monoblock humeral stem. In cases where more advanced destructive pathology is present, and bone loss is >5 cm, an allograft-prosthetic composite (APC) is typically used. In both scenarios, if the stem being revised is cemented and the cement mantle remains intact, and of reasonable length, consideration is given to the cement-within-cement technique. Finally, in the most destructive cases where bone loss exceeds 10 cm and a large biological response is anticipated (eg, periprosthetic fractures with humeral loosening), the use of a longer diaphyseal-incorporating APC is often necessary. This prosthetic composite can be combined with a cement-within-cement technique as well.

It is important to comment on the implications of using modular stems in this setting. With advanced bone loss, a situation is often encountered where the newly implanted stem geometry and working length may be insufficient to acquire adequate rotational stability. In this setting, if a modular junction is positioned close to the stem and cement/bone interface, it will be exposed to very high stress concentrations which can lead to component fracture³⁸ as well as taper corrosion, also referred to as trunnionosis. This latter phenomenon, which has been well studied in the total hip arthroplasty literature with the use of modular components,³⁹ is especially relevant given the high torsional loads imparted at the modular junction. Ultimately, high torsional loads lead to micromotion and electrochemical ion release via degradation of the passivation layer, initiating the process of mechanically assisted crevice corrosion.⁴⁰ For these reasons, when a modular stem must be used in the presence of mild to moderate bone loss, using a proximal humeral allograft to protect the junction or to provide additional fixation may be implemented with a lower threshold than when using a monoblock stem.

SURGICAL TECHNIQUE: ALLOGRAFT-PROSTHETIC COMPOSITES

A standard deltopectoral approach is used, taking care to preserve all viable muscular attachments to the proximal humerus. After removal of the prosthetic humeral head, the decision to proceed with removal of the stem at this juncture is based on several factors. If the remaining proximal humeral bone is so compromised that it might not be able to withstand the forces exerted upon it during retraction for glenoid exposure, the component is left in place. Additionally, if there is consideration that the glenoid-sided bone loss may be so severe that a glenoid baseplate cannot be implanted, and the stem remains well fixed, it is retained so that it can be converted to a hemiarthroplasty.

If neither of the above issues is present, the humeral stem is removed. If a well-fixed press-fit stem is in place, it is typically removed using a combination of burrs and osteotomes to disrupt the bone-implant interface, and the stem is then carefully removed using an impactor and mallet. If a cemented stem is present, the stem is removed in a similar manner, and the cement mantle is left in place if stable, in anticipation of a cement-within-cement technique. If the mantle is disrupted, standard cement removal instruments are used to remove all cement from the canal meticulously.

Continue to: Management of the glenoid...

Management of the glenoid can have significant implications with regard to the humerus. Most notably, the size of the glenosphere has direct implications on the fixation of the humeral component. Use of larger diameter glenospheres result in increased contact area between the glenosphere and humerosocket, adding constraint to the articulation and further increasing the stresses at the implant-bone interface. As such, the use of larger glenospheres to prevent instability must be balanced with the resulting implications on humeral component fixation, especially in cases of severe bone loss.

After implanting the appropriate glenosphere, attention is then turned back to the humerus. Trial implants are sequentially used to obtain adequate humeral length and stability. Once this is accomplished, the amount of humeral bone loss is quantified by measuring the distance from the superior aspect of the medial humeral tray to the medial humeral shaft. If this number is >5 cm (Figure 3), the decision is made to proceed with an APC. The allograft humeral head is cut, cancellous bone is removed, and a step-cut is performed, with the medial portion of the allograft measuring the same length as that of bone loss and the lateral plate extending an additional several centimeters distally (Figure 4). Additional soft tissue is removed from the allograft, leaving the subscapularis stump intact for later repair with the patient’s native tissue. The allograft is secured to the patient’s proximal humerus using multiple cerclage wires, and the humeral stem is cemented into place. The final construct is shown in Figure 5.

ADDITIONAL CONSIDERATIONS: CASES OF ADVANCED BONE LOSS

In cases of advanced humeral bone loss, as is often seen when revising loose humeral stems, larger allografts that span a significant length of the diaphysis are often required. This type of bone loss has implications with regard to how the deltoid insertion is managed. Interestingly, even in situations when the vast majority of the remaining diaphysis consists of ectatic egg-shell bone, the deltoid tuberosity remains of fairly substantial quality due to the continued pull of the muscular insertion on this area. This fragment is isolated, carefully mobilized, and subsequently repaired back on top of the allograft using cables.

POSTOPERATIVE CARE

Patients are kept in a shoulder immobilizer for 6 weeks after surgery to facilitate allograft incorporation and subscapularis tendon healing. During this time, pendulum exercises are initiated. Active assisted range of motion (ROM) exercises begin after 6 weeks, consisting of supine forward elevation. A sling is given to be used in public. Light strengthening exercises begin at 3 months postoperatively.

DISCUSSION

In cases of mild to moderate proximal humeral bone loss, RSA using a long-stem humeral component without allograft augmentation is a viable option. Budge and colleagues³⁸ demonstrated excellent results in a population of 15 patients with an average of 38 mm of proximal humeral bone loss without use of allografts. Interestingly, they noted 1 case of component fracture in a modular prosthesis and therefore concluded that monoblock humeral stems should be used in the absence of allograft augmentation.

Continue to: In more advanced cases of bone loss...

In more advanced cases of bone loss, our data shows that use of APCs can result in equally satisfactory results. In a series of 25 patients with an average bone loss of 54 mm, patients were able to achieve statistically significant improvements in pain, ROM, and function with high rates of allograft incorporation.⁹ Overall, a low rate of complications was noted, including 1 infection. This finding is consistent with an additional study looking specifically at factors associated with infection in revision SA, which found that the use of allografts was not associated with increased risk of infection.⁴¹

As stated previously, the size of allograft needed for the APC construct is related to the distinct pathology encountered. In our experience, we have noted that well-fixed stems can be treated with short metaphyseal APCs in 85% of cases. On the other hand, loose stems require long allografts measuring >10 cm in 90% of cases. As such, these cases typically require mobilization of the deltoid insertion as described above, and therefore it is important that the surgeon is prepared for this aspect of the procedure preoperatively.

Finally, the cement-within-cement technique, originally popularized for use in revision total hip arthroplasty, has demonstrated reliable results when utilized in revision SA.⁴² To date, there are no recommendations regarding the minimal length of existing cement mantle that is needed to perform this technique. In situations in which the length of the cement mantle is questionable, our preference is to combine the cement-within-cement technique with an APC when possible.

ABSTRACT

Revision shoulder arthroplasty is becoming more prevalent as the rate of primary shoulder arthroplasty in the US continues to increase. The management of proximal humeral bone loss in the revision setting presents a difficult problem without a clear solution. Different preoperative diagnoses often lead to distinctly different patterns of bone loss. Successful management of these cases requires a clear understanding of the normal anatomy of the proximal humerus, as well as structural limitations imposed by significant bone loss and the effect this loss has on component fixation. Our preferred technique differs depending on the pattern of bone loss encountered. The use of allograft-prosthetic composites, the cement-within-cement technique, and combinations of these strategies comprise the mainstay of our treatment algorithm. This article focuses on indications, surgical techniques, and some of the published outcomes using these strategies in the management of proximal humeral bone loss.

Continue to: The demand for shoulder arthroplasty...

The demand for shoulder arthroplasty (SA) has increased significantly over the past decade, with a 200% increase witnessed from 2011 to 2015.¹ SA performed in patients younger than 55 years is expected to increase 333% between 2011 to 2030.² With increasing rates of SA being performed in younger patient populations, rates of revision SA also can be expected to climb. Revision to reverse shoulder arthroplasty (RSA) has arisen as a viable option in these patients, and multiple studies demonstrate excellent outcomes that can be obtained with RSA.^3-11

Despite significant improvements obtained in revision SA since the mainstream acceptance of RSA, bone loss remains a problematic issue. Loss of humeral bone stock, in particular, can be a challenging problem to solve with multiple clinical implications. Biomechanical studies have demonstrated that if bone loss is left unaddressed, increased bending and torsional forces on the prosthesis result, which ultimately contribute to increased micromotion and eventual component failure.¹² In addition, existing challenges are associated with the lack of attachment sites for both multiple muscles and tendons. Also, there is a loss of the normal lateralized pull of the deltoid, which results in a decreased amount of force generated by this muscle.^13,14 Ultimately, the increased loss of bone can lead to a devastating situation where there is not enough bone to provide adequate fixation while maintaining the appropriate humeral length necessary to achieve stability of the articulation, which will inevitably lead to instability.^4,15 Therefore, techniques are needed to address proximal humeral bone loss while maintaining as much native humeral bone as possible.

PROXIMAL HUMERUS: ANATOMICAL CONSIDERATIONS

The anatomy of the proximal humerus has been studied in great detail and reported in a number of different studies.^16-23 The average humeral head thickness (24 mm in men and 19 mm in women) and offset relative to the humeral shaft (2.1 mm posterior and 6.6 mm medial) act to tension the rotator cuff musculature appropriately and contribute to a wrapping effect that allows the deltoid to function more effectively.^13,14 Knowledge regarding the rotator cuff footprint has advanced over the past 10 years, specifically with regard to the supraspinatus and infraspinatus.²⁴ The current belief is that the supraspinatus has a triangular insertion onto the most anterior aspect of the greater tuberosity, with a maximum medial-to-lateral length of 6.9 mm and a maximum anterior-to-posterior width of 12.6 mm. The infraspinatus insertion has a trapezoidal insertion, with a maximum medial-to-lateral length of 10.2 mm and anterior-to-posterior width of 32.7 mm. The subscapularis, by far the largest of all the rotator cuff muscles, has a complex geometry with regard to its insertion on the lesser tuberosity, with 4 different insertion points and an overall lateral footprint measuring 37.6 mm and a medial footprint measuring 40.7 mm.²⁵ Finally, the teres minor, with the smallest volume of all the rotator cuff muscles, inserts immediately inferior to the infraspinatus along the inferior facet of the greater tuberosity.²⁶

Aside from the rotator cuff, there are various other muscles and tendons that insert about the proximal humerus and are essential for normal function. The deltoid, which inserts at a point approximately 6 cm from the greater tuberosity along the length of the humerus, with an insertion length between 5 cm to 7 cm,^13,27 is the primary mover of the shoulder and essential for proper function after RSA.^28,29 The pectoralis major tendon, which begins inserting at a point approximately 5.6 cm from the humeral head and spans a distance of 7.7 cm along the length of the humerus,^30-32 is important not only for function but as an anatomical landmark in reconstruction. Lastly, the latissimus dorsi and teres major, which share a role in extension, adduction, and internal rotation of the glenohumeral joint, insert along the floor and medial lip of the intertubercular groove of the humerus, respectively.^33,34 In addition to their role in tendon transfer procedures because of treating irreparable posterosuperior cuff and subscapularis tears,^35,36 it has been suggested that these tendons may play some role in glenohumeral joint stability.³⁷

            In addition to the loss of muscular attachments, the absence of proximal humeral bone stock, in and of itself, can have deleterious effects on fixation of the humeral component. RSA is a semiconstrained device, which results in increased transmission of forces to the interface between the humeral implant and its surrounding structures, including cement (when present) and the bone itself. When there is the absence of significant amounts of bone, the remaining bone must now account for an even higher proportion of these forces. A previous biomechanical study showed that cemented humeral stems demonstrated significantly increased micromotion in the presence of proximal humeral bone loss, particularly when a modular humeral component was used.¹²

Continue to: TYPES OF BONE LOSS

There are a variety of different etiologies of proximal humeral bone loss that result in distinctly different clinical presentations. These can be fairly mild, as is the case of isolated resorption of the greater tuberosity in a non-united proximal humerus fracture (Figure 1). Alternatively, they can be severe, as seen in a grossly loose cemented long-stemmed component that is freely mobile, creating a windshield-wiper effect throughout the length of the humerus (Figure 2). This can be somewhat deceiving, however, as the amount of bone loss, as well as the pathophysiologic process that led to the bone loss, are important factors to determine ideal reconstructive methods. In the case of a failed open reduction internal fixation, where the tuberosity has failed to unite or has been resected, there is much less of a biologic response in comparison with implant loosening associated with osteolysis. This latter condition will be associated with a much more destructive inflammatory response resulting in poor tissue quality and often dramatic thinning of the cortex. If one simply measured the distance from the most proximal remaining bone stock to the area where the greater tuberosity should be, a loose stem with subsidence and ballooning of the cortices may appear to have a similar amount of bone loss as a failed hemiarthroplasty for fracture with a well-fixed stem. However, intraoperatively, one will find that the bone that appeared to be present radiographically in the case of the loose stem is of such poor quality that it cannot reasonably provide any beneficial fixation. In light of this, different treatment modalities are recommended for different types of bone loss, and the revision surgeon must be able to anticipate this and possess a full armamentarium of options to treat these challenging cases successfully.

INDICATIONS

Our technique to manage proximal humeral bone loss is dependent on both the quantity of bone loss, which can be measured radiographically, as well as the anticipated inflammatory response described above. As both the destructive process and the amount of bone loss increase, the importance of more advanced reconstructive procedures that will sustain implant security and soft-tissue management becomes apparent. In the least destructive cases with <5 cm of bone loss, successful revision can typically be accomplished with stem removal and placement of a new monoblock humeral stem. In cases where more advanced destructive pathology is present, and bone loss is >5 cm, an allograft-prosthetic composite (APC) is typically used. In both scenarios, if the stem being revised is cemented and the cement mantle remains intact, and of reasonable length, consideration is given to the cement-within-cement technique. Finally, in the most destructive cases where bone loss exceeds 10 cm and a large biological response is anticipated (eg, periprosthetic fractures with humeral loosening), the use of a longer diaphyseal-incorporating APC is often necessary. This prosthetic composite can be combined with a cement-within-cement technique as well.

It is important to comment on the implications of using modular stems in this setting. With advanced bone loss, a situation is often encountered where the newly implanted stem geometry and working length may be insufficient to acquire adequate rotational stability. In this setting, if a modular junction is positioned close to the stem and cement/bone interface, it will be exposed to very high stress concentrations which can lead to component fracture³⁸ as well as taper corrosion, also referred to as trunnionosis. This latter phenomenon, which has been well studied in the total hip arthroplasty literature with the use of modular components,³⁹ is especially relevant given the high torsional loads imparted at the modular junction. Ultimately, high torsional loads lead to micromotion and electrochemical ion release via degradation of the passivation layer, initiating the process of mechanically assisted crevice corrosion.⁴⁰ For these reasons, when a modular stem must be used in the presence of mild to moderate bone loss, using a proximal humeral allograft to protect the junction or to provide additional fixation may be implemented with a lower threshold than when using a monoblock stem.

SURGICAL TECHNIQUE: ALLOGRAFT-PROSTHETIC COMPOSITES

A standard deltopectoral approach is used, taking care to preserve all viable muscular attachments to the proximal humerus. After removal of the prosthetic humeral head, the decision to proceed with removal of the stem at this juncture is based on several factors. If the remaining proximal humeral bone is so compromised that it might not be able to withstand the forces exerted upon it during retraction for glenoid exposure, the component is left in place. Additionally, if there is consideration that the glenoid-sided bone loss may be so severe that a glenoid baseplate cannot be implanted, and the stem remains well fixed, it is retained so that it can be converted to a hemiarthroplasty.

If neither of the above issues is present, the humeral stem is removed. If a well-fixed press-fit stem is in place, it is typically removed using a combination of burrs and osteotomes to disrupt the bone-implant interface, and the stem is then carefully removed using an impactor and mallet. If a cemented stem is present, the stem is removed in a similar manner, and the cement mantle is left in place if stable, in anticipation of a cement-within-cement technique. If the mantle is disrupted, standard cement removal instruments are used to remove all cement from the canal meticulously.

Continue to: Management of the glenoid...

Management of the glenoid can have significant implications with regard to the humerus. Most notably, the size of the glenosphere has direct implications on the fixation of the humeral component. Use of larger diameter glenospheres result in increased contact area between the glenosphere and humerosocket, adding constraint to the articulation and further increasing the stresses at the implant-bone interface. As such, the use of larger glenospheres to prevent instability must be balanced with the resulting implications on humeral component fixation, especially in cases of severe bone loss.

After implanting the appropriate glenosphere, attention is then turned back to the humerus. Trial implants are sequentially used to obtain adequate humeral length and stability. Once this is accomplished, the amount of humeral bone loss is quantified by measuring the distance from the superior aspect of the medial humeral tray to the medial humeral shaft. If this number is >5 cm (Figure 3), the decision is made to proceed with an APC. The allograft humeral head is cut, cancellous bone is removed, and a step-cut is performed, with the medial portion of the allograft measuring the same length as that of bone loss and the lateral plate extending an additional several centimeters distally (Figure 4). Additional soft tissue is removed from the allograft, leaving the subscapularis stump intact for later repair with the patient’s native tissue. The allograft is secured to the patient’s proximal humerus using multiple cerclage wires, and the humeral stem is cemented into place. The final construct is shown in Figure 5.

ADDITIONAL CONSIDERATIONS: CASES OF ADVANCED BONE LOSS

In cases of advanced humeral bone loss, as is often seen when revising loose humeral stems, larger allografts that span a significant length of the diaphysis are often required. This type of bone loss has implications with regard to how the deltoid insertion is managed. Interestingly, even in situations when the vast majority of the remaining diaphysis consists of ectatic egg-shell bone, the deltoid tuberosity remains of fairly substantial quality due to the continued pull of the muscular insertion on this area. This fragment is isolated, carefully mobilized, and subsequently repaired back on top of the allograft using cables.

POSTOPERATIVE CARE

Patients are kept in a shoulder immobilizer for 6 weeks after surgery to facilitate allograft incorporation and subscapularis tendon healing. During this time, pendulum exercises are initiated. Active assisted range of motion (ROM) exercises begin after 6 weeks, consisting of supine forward elevation. A sling is given to be used in public. Light strengthening exercises begin at 3 months postoperatively.

DISCUSSION

In cases of mild to moderate proximal humeral bone loss, RSA using a long-stem humeral component without allograft augmentation is a viable option. Budge and colleagues³⁸ demonstrated excellent results in a population of 15 patients with an average of 38 mm of proximal humeral bone loss without use of allografts. Interestingly, they noted 1 case of component fracture in a modular prosthesis and therefore concluded that monoblock humeral stems should be used in the absence of allograft augmentation.

Continue to: In more advanced cases of bone loss...

In more advanced cases of bone loss, our data shows that use of APCs can result in equally satisfactory results. In a series of 25 patients with an average bone loss of 54 mm, patients were able to achieve statistically significant improvements in pain, ROM, and function with high rates of allograft incorporation.⁹ Overall, a low rate of complications was noted, including 1 infection. This finding is consistent with an additional study looking specifically at factors associated with infection in revision SA, which found that the use of allografts was not associated with increased risk of infection.⁴¹

As stated previously, the size of allograft needed for the APC construct is related to the distinct pathology encountered. In our experience, we have noted that well-fixed stems can be treated with short metaphyseal APCs in 85% of cases. On the other hand, loose stems require long allografts measuring >10 cm in 90% of cases. As such, these cases typically require mobilization of the deltoid insertion as described above, and therefore it is important that the surgeon is prepared for this aspect of the procedure preoperatively.

Finally, the cement-within-cement technique, originally popularized for use in revision total hip arthroplasty, has demonstrated reliable results when utilized in revision SA.⁴² To date, there are no recommendations regarding the minimal length of existing cement mantle that is needed to perform this technique. In situations in which the length of the cement mantle is questionable, our preference is to combine the cement-within-cement technique with an APC when possible.