The annual number of total shoulder arthroplasties (TSAs) is rising with the growing elderly population and development of new technologies such as reverse shoulder arthroplasty.¹ In 2008, 47,000 shoulder arthroplasties were performed in the US compared with 19,000 in 1998.¹ As of 2011, there were 53,000 shoulder arthroplasties performed annually.² Pain control after shoulder procedures, particularly TSA, is challenging. ³

Several modalities exist to manage pain after shoulder arthroplasty. The interscalene brachial plexus nerve block is considered the “gold standard” for shoulder analgesia. A new approach is the periarticular injection method, in which the surgeon administers a local anesthetic intraoperatively. Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals, Inc.) is a nonopioid anesthetic that has been shown to improve pain control, shorten hospital stays, and decrease costs for total knee and hip arthroplasty compared with nerve blocks.^4-6 Patients who were treated with liposomal bupivacaine consumed less opioid medication than a placebo group.⁷

Our purpose was to compare intraoperative local liposomal bupivacaine injection with preoperative single-shot interscalene nerve block (ISNB) in terms of pain control, opioid use, and length of hospital stay (LOS) after shoulder arthroplasty. We hypothesized that patients in the liposomal bupivacaine group would have lower pain scores, less opioid use, and shorter LOS compared with patients in the ISNB group.

Methods

A retrospective cohort analysis was conducted with 58 patients who underwent shoulder arthroplasty by 1 surgeon at our academically affiliated community hospital from January 2012 through January 2015. ISNBs were the standard at the beginning of the study period and were used until Exparel became available on the hospital formulary in 2013. We began using Exparel for all shoulder arthroplasties in November 2013. No other changes were made in the perioperative management of our arthroplasty patients during this period. Patients who underwent TSA, reverse TSA, or hemiarthroplasty of the shoulder were included. Patients who underwent revision TSA were excluded. Twenty-one patients received ISNBs and 37 received liposomal bupivacaine injections. This study was approved by our Institutional Review Board.

Baseline data for each patient were age, sex, body mass index, and the American Society of Anesthesiologists (ASA) Physical Status Classification. The primary outcome measure was the numeric rating scale (NRS) pain score at 4 post-operative time intervals. The NRS pain score has a range of 0 to 10, with 10 representing severe pain. Data were gathered from nursing and physical therapy notes in patient charts. The postoperative time intervals were 0 to 1 hour, 8 to 14 hours, 18 to 24 hours, and 27 to 36 hours. Available NRS scores for these time intervals were averaged. Patients were included if they had pain scores for at least 3 of the postoperative time intervals documented in their charts. Secondary outcome measures were LOS and opioid consumption during hospital admission. Intravenous acetaminophen use was also measured in both groups. All data on opioids were converted to oral morphine equivalents using the method described by Schneider and colleagues.⁸

A board-certified, fellowship-trained anesthesiologist, experienced in regional anesthesia, administered the single-shot ISNB before surgery. The block was administered under ultrasound guidance using a 44-mm, 22-gauge needle with the patient in the supine position. No indwelling catheter was used. The medication consisted of 30 mL of 5% ropivacaine (5 mg/mL). The surgeon injected liposomal bupivacaine (266 mg diluted into 40 mL of injectable saline) near the end of the procedure throughout the pericapsular area and multiple layers of the wound, per manufacturer guidelines.⁹ A 60-mL syringe with a 20-gauge needle was used. All operations were performed by 1 board-certified, fellowship-trained surgeon using a standard deltopectoral approach with the same surgical equipment. The same postoperative pain protocol was used for all patients, including intravenous acetaminophen and patient-controlled analgesia. Additional oral pain medication was provided as needed for all patients. Physical therapy protocols were identical between groups.

Statistical Analysis

Mean patient ages in the 2 treatment groups were compared using the Student t test. Sex distribution and the ASA scores were compared using a χ² test and a Fisher exact test, respectively. Arthroplasty types were compared using a Fisher exact test. The medians and interquartile ranges of the NRS scores at each time point measured were tabulated by treatment group, and at each time point the difference between groups was tested using nonparametric rank sum tests.

We tested the longitudinal trajectory of NRS scores over time, accounting for repeated measurements in the same patients using linear mixed model analysis. Treatment group, time period as a categorical variable, and the interaction between treatment and time period were included as fixed effects, and patient identification number was included as the random effect. An initial omnibus test was performed for all treatment and treatment-by-time interaction effects. Subsequently, the treatment-by-time interaction was tested for each of the time periods. The association of day of discharge (as a categorical variable) with treatment was tested using the Fisher exact test. All analyses were conducted using Stata, version 13, software (StataCorp LP). P values <.05 were considered significant.

Sample Size Analysis

We calculated the minimum detectable effect size with 80% power at an alpha level of 0.05 for the nonparametric rank sum test in terms of the proportion of every possible pair of patients treated with the 2 treatments, where the patient treated with liposomal bupivacaine has a lower pain score than the patient treated with ISNB. For pain score at 18 to 24 hours, the sample sizes of 33 patients treated with liposomal bupivacaine and 20 treated with ISNB, the minimum detectable effect size is 73%.

Results

Fifty-eight patient charts (21 in the ISNB group and 37 in the liposomal bupivacaine group) were reviewed for the study. Patient sex distribution, mean age, mean body mass index, and mean baseline ASA scores were not statistically different (Table 1).

The primary outcome measure, NRS pain score, showed no significant differences between groups at 0 to 1 hour after surgery (P = .99) or 8 to 14 hours after surgery (P = .208).

Discussion

Postoperative pain control after shoulder arthroplasty can be challenging, and several modalities have been tried in various combinations to minimize pain and decrease adverse effects of opioid medications. The most common method for pain relief after shoulder arthroplasty is the ISNB. Several studies of ISNBs have shown improved pain control after shoulder arthroplasty with associated decreased opioid consumption and related side effects.¹⁰ Patient rehabilitation and satisfaction have improved with the increasing use of peripheral nerve blocks.¹¹

Despite the well-established benefits of ISNBs, several limitations exist. Although the superior portion of the shoulder is well covered by an ISNB, the inferior portion of the brachial plexus can remain uncovered or only partially covered.¹² Complications of ISNBs include hemidiaphragmatic paresis, rebound pain 24 hours after surgery,¹³ chronic neurologic complications,¹⁴ and substantial respiratory and cardiovascular events.¹⁵ Nerve blocks also require additional time and resources in the perioperative period, including an anesthesiologist with specialized training, assistants, and ultrasonography or nerve stimulation equipment contraindicated in patients taking blood thinners.¹⁶

Periarticular injections of local anesthetics have also shown promise in reducing pain after arthroplasty.⁴ Benefits include an enhanced safety profile because local injection avoids the concurrent blockade of the phrenic nerve and recurrent laryngeal nerve and has not been associated with the risk of peripheral neuropathies. Further, local injection is a simple technique that can be performed during surgery without additional personnel or expertise. A limitation of this approach is the relatively short duration of effectiveness of the local anesthetic and uncertainty regarding the best agent and the ideal volume of injection.⁶ Liposomal bupivacaine is a new agent (approved by the US Food and Drug Administration in 2011¹⁷) with a sustained release over 72 to 96 hours.¹⁸ The most common adverse effects of liposomal bupivacaine are nausea, vomiting, constipation, pyrexia, dizziness, and headache.¹⁹ Chondrotoxicity and granulomatous inflammation are more serious, yet rare, complications of liposomal bupivacaine.²⁰

We found that liposomal bupivacaine injections were associated with lower pain scores compared with ISNB at 18 to 24 hours after surgery. This correlated with less opioid consumption in the liposomal bupivacaine group than in the ISNB group on the second postoperative day. These differences in pain values are consistent with the known pharmacokinetics of liposomal bupivacaine.¹⁸ Peak plasma levels normally occur approximately 24 hours after injection, leaving the early postoperative period relatively uncovered by anesthetic agent. This finding of relatively poor pain control early after surgery has also been noted in patients undergoing knee arthroplasty.⁵ On the basis of the findings of this study, we have added standard bupivacaine injections to our separate liposomal bupivacaine injection to cover early postoperative pain. Opioid consumption was significantly lower in the liposomal bupivacaine group than in the ISNB group on postoperative days 2 and 3. We did not measure adverse events related to opioid consumption, so we cannot comment on whether the decreased opioid consumption was associated with the rate of adverse events. However, other studies^21,22 have established this relationship.

We found the liposomal bupivacaine group to have earlier discharges to home. Sixteen of 37 patients in the liposomal bupivacaine group compared with 2 of 21 patients in the ISNB group were discharged on the day after surgery. A mean reduction in LOS of 18 hours for the liposomal bupivacaine group was statistically significant (P = .012). This reduction in LOS has important implications for hospitals and value analysis committees considering whether to keep a new, more expensive local anesthetic on formulary. Savings from reduced LOS and improvements in patient satisfaction may justify the expense (approximately $300 per 266-mg vial) of Exparel.

From a societal cost perspective, liposomal bupivacaine is more economical compared with ISNB, which adds approximately $1500 to the cost of anesthesia per patient.²³ Eliminating the costs associated with ISNB administration in shoulder arthroplasties could result in substantial savings to our healthcare system. More research examining time savings and exact costs of each procedure is needed to determine the true cost effectiveness of each approach.

Limitations of our study include the retrospective design, relatively small numbers of patients in each group, missing data for some patients at various time points, variation in the types of procedures in each group, and lack of long-term outcome measures. It is important to note that we did not confirm the success of the nerve block after administration. However, this study reflects the effectiveness of each of the modalities in actual clinical conditions (as opposed to a controlled experimental setting). The actual effectiveness of a nerve block varies, even when performed by an experienced anesthesiologist with ultrasound guidance. Furthermore, immediate postoperative pain scores in the nerve block group are consistent with those of prior research reporting pain values ranging from 4 to 5 and a mean duration of effect ranging from 9 to 14 hours.^23,24 Additionally, the patients, surgeon, and nursing team were not blinded to the treatment group. Although we did note a significant difference in the types of procedures between groups, this finding is related to the greater number of hemiarthroplasties performed in the ISNB group (N = 5) compared with the liposomal group (N = 1). Because of this variation and the decreased invasiveness of hemiarthroplasties, the bias is against the liposomal group. Finally, our primary outcome variable was pain, which is a subjective, self-reported measure. However, our opioid consumption data and LOS data corroborate the improved pain scores in the liposomal bupivacaine group.

Limiting the study to a single surgeon may limit external validity. Another limitation is the lack of data on adverse events related to opioid medication use. There was no additional experimental group to determine whether less expensive local anesthetics injected locally would perform similarly to liposomal bupivacaine. In total knee arthroplasty, periarticular injections of liposomal bupivacaine were not as effective as less expensive periarticular injections.²⁵ It is unclear which agents (and in what doses or combinations) should be used for periarticular injections. Finally, we acknowledge that our retrospective study design cannot account for all potential factors affecting discharge time.

This is the first comparative study of liposomal bupivacaine and ISNB in TSA. The study design allowed us to control for variables such as surgical technique, postoperative protocols (including use and type of sling), and use of other pain modalities such as patient-controlled analgesia and intravenous acetaminophen that are likely to affect postoperative pain and LOS. This study provides preliminary data that confirm relative equipoise between liposomal bupivacaine and ISNB, which is needed for the ethical conduct of a randomized controlled trial. Such a trial would allow for a more robust comparison, and this retrospective study provides appropriate pilot data on which to base this design and the clinical information needed to counsel patients during enrollment.

Our results suggest that liposomal bupivacaine may provide superior or similar pain relief compared with ISNB after shoulder arthroplasty. Additionally, the use of liposomal bupivacaine was associated with decreased opioid consumption and earlier discharge to home compared with ISNB. These findings have important implications for pain control after TSA because pain represents a major concern for patients and providers after surgery. In addition to clinical improvements, use of liposomal bupivacaine may save time and eliminate costs associated with administering nerve blocks. Local injection may also be used in patients who are contraindicated for ISNB such as those with obesity, pulmonary disease, or peripheral neuropathy. Although we cannot definitively suggest that liposomal bupivacaine is superior to the current gold standard ISNB for pain control after shoulder arthroplasty, our results suggest a relative clinical equipoise between these modalities. Larger analytical studies, including randomized trials, should be performed to explore the potential benefits of liposomal bupivacaine injections for pain control after shoulder arthroplasty.

Am J Orthop. 2016;45(7):424-430. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

The annual number of total shoulder arthroplasties (TSAs) is rising with the growing elderly population and development of new technologies such as reverse shoulder arthroplasty.¹ In 2008, 47,000 shoulder arthroplasties were performed in the US compared with 19,000 in 1998.¹ As of 2011, there were 53,000 shoulder arthroplasties performed annually.² Pain control after shoulder procedures, particularly TSA, is challenging. ³

Several modalities exist to manage pain after shoulder arthroplasty. The interscalene brachial plexus nerve block is considered the “gold standard” for shoulder analgesia. A new approach is the periarticular injection method, in which the surgeon administers a local anesthetic intraoperatively. Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals, Inc.) is a nonopioid anesthetic that has been shown to improve pain control, shorten hospital stays, and decrease costs for total knee and hip arthroplasty compared with nerve blocks.^4-6 Patients who were treated with liposomal bupivacaine consumed less opioid medication than a placebo group.⁷

Our purpose was to compare intraoperative local liposomal bupivacaine injection with preoperative single-shot interscalene nerve block (ISNB) in terms of pain control, opioid use, and length of hospital stay (LOS) after shoulder arthroplasty. We hypothesized that patients in the liposomal bupivacaine group would have lower pain scores, less opioid use, and shorter LOS compared with patients in the ISNB group.

Methods

A retrospective cohort analysis was conducted with 58 patients who underwent shoulder arthroplasty by 1 surgeon at our academically affiliated community hospital from January 2012 through January 2015. ISNBs were the standard at the beginning of the study period and were used until Exparel became available on the hospital formulary in 2013. We began using Exparel for all shoulder arthroplasties in November 2013. No other changes were made in the perioperative management of our arthroplasty patients during this period. Patients who underwent TSA, reverse TSA, or hemiarthroplasty of the shoulder were included. Patients who underwent revision TSA were excluded. Twenty-one patients received ISNBs and 37 received liposomal bupivacaine injections. This study was approved by our Institutional Review Board.

Baseline data for each patient were age, sex, body mass index, and the American Society of Anesthesiologists (ASA) Physical Status Classification. The primary outcome measure was the numeric rating scale (NRS) pain score at 4 post-operative time intervals. The NRS pain score has a range of 0 to 10, with 10 representing severe pain. Data were gathered from nursing and physical therapy notes in patient charts. The postoperative time intervals were 0 to 1 hour, 8 to 14 hours, 18 to 24 hours, and 27 to 36 hours. Available NRS scores for these time intervals were averaged. Patients were included if they had pain scores for at least 3 of the postoperative time intervals documented in their charts. Secondary outcome measures were LOS and opioid consumption during hospital admission. Intravenous acetaminophen use was also measured in both groups. All data on opioids were converted to oral morphine equivalents using the method described by Schneider and colleagues.⁸

A board-certified, fellowship-trained anesthesiologist, experienced in regional anesthesia, administered the single-shot ISNB before surgery. The block was administered under ultrasound guidance using a 44-mm, 22-gauge needle with the patient in the supine position. No indwelling catheter was used. The medication consisted of 30 mL of 5% ropivacaine (5 mg/mL). The surgeon injected liposomal bupivacaine (266 mg diluted into 40 mL of injectable saline) near the end of the procedure throughout the pericapsular area and multiple layers of the wound, per manufacturer guidelines.⁹ A 60-mL syringe with a 20-gauge needle was used. All operations were performed by 1 board-certified, fellowship-trained surgeon using a standard deltopectoral approach with the same surgical equipment. The same postoperative pain protocol was used for all patients, including intravenous acetaminophen and patient-controlled analgesia. Additional oral pain medication was provided as needed for all patients. Physical therapy protocols were identical between groups.

Statistical Analysis

Mean patient ages in the 2 treatment groups were compared using the Student t test. Sex distribution and the ASA scores were compared using a χ² test and a Fisher exact test, respectively. Arthroplasty types were compared using a Fisher exact test. The medians and interquartile ranges of the NRS scores at each time point measured were tabulated by treatment group, and at each time point the difference between groups was tested using nonparametric rank sum tests.

We tested the longitudinal trajectory of NRS scores over time, accounting for repeated measurements in the same patients using linear mixed model analysis. Treatment group, time period as a categorical variable, and the interaction between treatment and time period were included as fixed effects, and patient identification number was included as the random effect. An initial omnibus test was performed for all treatment and treatment-by-time interaction effects. Subsequently, the treatment-by-time interaction was tested for each of the time periods. The association of day of discharge (as a categorical variable) with treatment was tested using the Fisher exact test. All analyses were conducted using Stata, version 13, software (StataCorp LP). P values <.05 were considered significant.

Sample Size Analysis

We calculated the minimum detectable effect size with 80% power at an alpha level of 0.05 for the nonparametric rank sum test in terms of the proportion of every possible pair of patients treated with the 2 treatments, where the patient treated with liposomal bupivacaine has a lower pain score than the patient treated with ISNB. For pain score at 18 to 24 hours, the sample sizes of 33 patients treated with liposomal bupivacaine and 20 treated with ISNB, the minimum detectable effect size is 73%.

Results

Fifty-eight patient charts (21 in the ISNB group and 37 in the liposomal bupivacaine group) were reviewed for the study. Patient sex distribution, mean age, mean body mass index, and mean baseline ASA scores were not statistically different (Table 1).

The primary outcome measure, NRS pain score, showed no significant differences between groups at 0 to 1 hour after surgery (P = .99) or 8 to 14 hours after surgery (P = .208).

Discussion

Postoperative pain control after shoulder arthroplasty can be challenging, and several modalities have been tried in various combinations to minimize pain and decrease adverse effects of opioid medications. The most common method for pain relief after shoulder arthroplasty is the ISNB. Several studies of ISNBs have shown improved pain control after shoulder arthroplasty with associated decreased opioid consumption and related side effects.¹⁰ Patient rehabilitation and satisfaction have improved with the increasing use of peripheral nerve blocks.¹¹

Despite the well-established benefits of ISNBs, several limitations exist. Although the superior portion of the shoulder is well covered by an ISNB, the inferior portion of the brachial plexus can remain uncovered or only partially covered.¹² Complications of ISNBs include hemidiaphragmatic paresis, rebound pain 24 hours after surgery,¹³ chronic neurologic complications,¹⁴ and substantial respiratory and cardiovascular events.¹⁵ Nerve blocks also require additional time and resources in the perioperative period, including an anesthesiologist with specialized training, assistants, and ultrasonography or nerve stimulation equipment contraindicated in patients taking blood thinners.¹⁶

Periarticular injections of local anesthetics have also shown promise in reducing pain after arthroplasty.⁴ Benefits include an enhanced safety profile because local injection avoids the concurrent blockade of the phrenic nerve and recurrent laryngeal nerve and has not been associated with the risk of peripheral neuropathies. Further, local injection is a simple technique that can be performed during surgery without additional personnel or expertise. A limitation of this approach is the relatively short duration of effectiveness of the local anesthetic and uncertainty regarding the best agent and the ideal volume of injection.⁶ Liposomal bupivacaine is a new agent (approved by the US Food and Drug Administration in 2011¹⁷) with a sustained release over 72 to 96 hours.¹⁸ The most common adverse effects of liposomal bupivacaine are nausea, vomiting, constipation, pyrexia, dizziness, and headache.¹⁹ Chondrotoxicity and granulomatous inflammation are more serious, yet rare, complications of liposomal bupivacaine.²⁰

We found that liposomal bupivacaine injections were associated with lower pain scores compared with ISNB at 18 to 24 hours after surgery. This correlated with less opioid consumption in the liposomal bupivacaine group than in the ISNB group on the second postoperative day. These differences in pain values are consistent with the known pharmacokinetics of liposomal bupivacaine.¹⁸ Peak plasma levels normally occur approximately 24 hours after injection, leaving the early postoperative period relatively uncovered by anesthetic agent. This finding of relatively poor pain control early after surgery has also been noted in patients undergoing knee arthroplasty.⁵ On the basis of the findings of this study, we have added standard bupivacaine injections to our separate liposomal bupivacaine injection to cover early postoperative pain. Opioid consumption was significantly lower in the liposomal bupivacaine group than in the ISNB group on postoperative days 2 and 3. We did not measure adverse events related to opioid consumption, so we cannot comment on whether the decreased opioid consumption was associated with the rate of adverse events. However, other studies^21,22 have established this relationship.

We found the liposomal bupivacaine group to have earlier discharges to home. Sixteen of 37 patients in the liposomal bupivacaine group compared with 2 of 21 patients in the ISNB group were discharged on the day after surgery. A mean reduction in LOS of 18 hours for the liposomal bupivacaine group was statistically significant (P = .012). This reduction in LOS has important implications for hospitals and value analysis committees considering whether to keep a new, more expensive local anesthetic on formulary. Savings from reduced LOS and improvements in patient satisfaction may justify the expense (approximately $300 per 266-mg vial) of Exparel.

From a societal cost perspective, liposomal bupivacaine is more economical compared with ISNB, which adds approximately $1500 to the cost of anesthesia per patient.²³ Eliminating the costs associated with ISNB administration in shoulder arthroplasties could result in substantial savings to our healthcare system. More research examining time savings and exact costs of each procedure is needed to determine the true cost effectiveness of each approach.

Limitations of our study include the retrospective design, relatively small numbers of patients in each group, missing data for some patients at various time points, variation in the types of procedures in each group, and lack of long-term outcome measures. It is important to note that we did not confirm the success of the nerve block after administration. However, this study reflects the effectiveness of each of the modalities in actual clinical conditions (as opposed to a controlled experimental setting). The actual effectiveness of a nerve block varies, even when performed by an experienced anesthesiologist with ultrasound guidance. Furthermore, immediate postoperative pain scores in the nerve block group are consistent with those of prior research reporting pain values ranging from 4 to 5 and a mean duration of effect ranging from 9 to 14 hours.^23,24 Additionally, the patients, surgeon, and nursing team were not blinded to the treatment group. Although we did note a significant difference in the types of procedures between groups, this finding is related to the greater number of hemiarthroplasties performed in the ISNB group (N = 5) compared with the liposomal group (N = 1). Because of this variation and the decreased invasiveness of hemiarthroplasties, the bias is against the liposomal group. Finally, our primary outcome variable was pain, which is a subjective, self-reported measure. However, our opioid consumption data and LOS data corroborate the improved pain scores in the liposomal bupivacaine group.

Limiting the study to a single surgeon may limit external validity. Another limitation is the lack of data on adverse events related to opioid medication use. There was no additional experimental group to determine whether less expensive local anesthetics injected locally would perform similarly to liposomal bupivacaine. In total knee arthroplasty, periarticular injections of liposomal bupivacaine were not as effective as less expensive periarticular injections.²⁵ It is unclear which agents (and in what doses or combinations) should be used for periarticular injections. Finally, we acknowledge that our retrospective study design cannot account for all potential factors affecting discharge time.

This is the first comparative study of liposomal bupivacaine and ISNB in TSA. The study design allowed us to control for variables such as surgical technique, postoperative protocols (including use and type of sling), and use of other pain modalities such as patient-controlled analgesia and intravenous acetaminophen that are likely to affect postoperative pain and LOS. This study provides preliminary data that confirm relative equipoise between liposomal bupivacaine and ISNB, which is needed for the ethical conduct of a randomized controlled trial. Such a trial would allow for a more robust comparison, and this retrospective study provides appropriate pilot data on which to base this design and the clinical information needed to counsel patients during enrollment.

Our results suggest that liposomal bupivacaine may provide superior or similar pain relief compared with ISNB after shoulder arthroplasty. Additionally, the use of liposomal bupivacaine was associated with decreased opioid consumption and earlier discharge to home compared with ISNB. These findings have important implications for pain control after TSA because pain represents a major concern for patients and providers after surgery. In addition to clinical improvements, use of liposomal bupivacaine may save time and eliminate costs associated with administering nerve blocks. Local injection may also be used in patients who are contraindicated for ISNB such as those with obesity, pulmonary disease, or peripheral neuropathy. Although we cannot definitively suggest that liposomal bupivacaine is superior to the current gold standard ISNB for pain control after shoulder arthroplasty, our results suggest a relative clinical equipoise between these modalities. Larger analytical studies, including randomized trials, should be performed to explore the potential benefits of liposomal bupivacaine injections for pain control after shoulder arthroplasty.

Am J Orthop. 2016;45(7):424-430. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

The annual number of total shoulder arthroplasties (TSAs) is rising with the growing elderly population and development of new technologies such as reverse shoulder arthroplasty.¹ In 2008, 47,000 shoulder arthroplasties were performed in the US compared with 19,000 in 1998.¹ As of 2011, there were 53,000 shoulder arthroplasties performed annually.² Pain control after shoulder procedures, particularly TSA, is challenging. ³

Several modalities exist to manage pain after shoulder arthroplasty. The interscalene brachial plexus nerve block is considered the “gold standard” for shoulder analgesia. A new approach is the periarticular injection method, in which the surgeon administers a local anesthetic intraoperatively. Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals, Inc.) is a nonopioid anesthetic that has been shown to improve pain control, shorten hospital stays, and decrease costs for total knee and hip arthroplasty compared with nerve blocks.^4-6 Patients who were treated with liposomal bupivacaine consumed less opioid medication than a placebo group.⁷

Our purpose was to compare intraoperative local liposomal bupivacaine injection with preoperative single-shot interscalene nerve block (ISNB) in terms of pain control, opioid use, and length of hospital stay (LOS) after shoulder arthroplasty. We hypothesized that patients in the liposomal bupivacaine group would have lower pain scores, less opioid use, and shorter LOS compared with patients in the ISNB group.

Methods

A retrospective cohort analysis was conducted with 58 patients who underwent shoulder arthroplasty by 1 surgeon at our academically affiliated community hospital from January 2012 through January 2015. ISNBs were the standard at the beginning of the study period and were used until Exparel became available on the hospital formulary in 2013. We began using Exparel for all shoulder arthroplasties in November 2013. No other changes were made in the perioperative management of our arthroplasty patients during this period. Patients who underwent TSA, reverse TSA, or hemiarthroplasty of the shoulder were included. Patients who underwent revision TSA were excluded. Twenty-one patients received ISNBs and 37 received liposomal bupivacaine injections. This study was approved by our Institutional Review Board.

Baseline data for each patient were age, sex, body mass index, and the American Society of Anesthesiologists (ASA) Physical Status Classification. The primary outcome measure was the numeric rating scale (NRS) pain score at 4 post-operative time intervals. The NRS pain score has a range of 0 to 10, with 10 representing severe pain. Data were gathered from nursing and physical therapy notes in patient charts. The postoperative time intervals were 0 to 1 hour, 8 to 14 hours, 18 to 24 hours, and 27 to 36 hours. Available NRS scores for these time intervals were averaged. Patients were included if they had pain scores for at least 3 of the postoperative time intervals documented in their charts. Secondary outcome measures were LOS and opioid consumption during hospital admission. Intravenous acetaminophen use was also measured in both groups. All data on opioids were converted to oral morphine equivalents using the method described by Schneider and colleagues.⁸

A board-certified, fellowship-trained anesthesiologist, experienced in regional anesthesia, administered the single-shot ISNB before surgery. The block was administered under ultrasound guidance using a 44-mm, 22-gauge needle with the patient in the supine position. No indwelling catheter was used. The medication consisted of 30 mL of 5% ropivacaine (5 mg/mL). The surgeon injected liposomal bupivacaine (266 mg diluted into 40 mL of injectable saline) near the end of the procedure throughout the pericapsular area and multiple layers of the wound, per manufacturer guidelines.⁹ A 60-mL syringe with a 20-gauge needle was used. All operations were performed by 1 board-certified, fellowship-trained surgeon using a standard deltopectoral approach with the same surgical equipment. The same postoperative pain protocol was used for all patients, including intravenous acetaminophen and patient-controlled analgesia. Additional oral pain medication was provided as needed for all patients. Physical therapy protocols were identical between groups.

Statistical Analysis

Mean patient ages in the 2 treatment groups were compared using the Student t test. Sex distribution and the ASA scores were compared using a χ² test and a Fisher exact test, respectively. Arthroplasty types were compared using a Fisher exact test. The medians and interquartile ranges of the NRS scores at each time point measured were tabulated by treatment group, and at each time point the difference between groups was tested using nonparametric rank sum tests.

We tested the longitudinal trajectory of NRS scores over time, accounting for repeated measurements in the same patients using linear mixed model analysis. Treatment group, time period as a categorical variable, and the interaction between treatment and time period were included as fixed effects, and patient identification number was included as the random effect. An initial omnibus test was performed for all treatment and treatment-by-time interaction effects. Subsequently, the treatment-by-time interaction was tested for each of the time periods. The association of day of discharge (as a categorical variable) with treatment was tested using the Fisher exact test. All analyses were conducted using Stata, version 13, software (StataCorp LP). P values <.05 were considered significant.

Sample Size Analysis

We calculated the minimum detectable effect size with 80% power at an alpha level of 0.05 for the nonparametric rank sum test in terms of the proportion of every possible pair of patients treated with the 2 treatments, where the patient treated with liposomal bupivacaine has a lower pain score than the patient treated with ISNB. For pain score at 18 to 24 hours, the sample sizes of 33 patients treated with liposomal bupivacaine and 20 treated with ISNB, the minimum detectable effect size is 73%.

Results

Fifty-eight patient charts (21 in the ISNB group and 37 in the liposomal bupivacaine group) were reviewed for the study. Patient sex distribution, mean age, mean body mass index, and mean baseline ASA scores were not statistically different (Table 1).

The primary outcome measure, NRS pain score, showed no significant differences between groups at 0 to 1 hour after surgery (P = .99) or 8 to 14 hours after surgery (P = .208).

Discussion

Postoperative pain control after shoulder arthroplasty can be challenging, and several modalities have been tried in various combinations to minimize pain and decrease adverse effects of opioid medications. The most common method for pain relief after shoulder arthroplasty is the ISNB. Several studies of ISNBs have shown improved pain control after shoulder arthroplasty with associated decreased opioid consumption and related side effects.¹⁰ Patient rehabilitation and satisfaction have improved with the increasing use of peripheral nerve blocks.¹¹

Despite the well-established benefits of ISNBs, several limitations exist. Although the superior portion of the shoulder is well covered by an ISNB, the inferior portion of the brachial plexus can remain uncovered or only partially covered.¹² Complications of ISNBs include hemidiaphragmatic paresis, rebound pain 24 hours after surgery,¹³ chronic neurologic complications,¹⁴ and substantial respiratory and cardiovascular events.¹⁵ Nerve blocks also require additional time and resources in the perioperative period, including an anesthesiologist with specialized training, assistants, and ultrasonography or nerve stimulation equipment contraindicated in patients taking blood thinners.¹⁶

Periarticular injections of local anesthetics have also shown promise in reducing pain after arthroplasty.⁴ Benefits include an enhanced safety profile because local injection avoids the concurrent blockade of the phrenic nerve and recurrent laryngeal nerve and has not been associated with the risk of peripheral neuropathies. Further, local injection is a simple technique that can be performed during surgery without additional personnel or expertise. A limitation of this approach is the relatively short duration of effectiveness of the local anesthetic and uncertainty regarding the best agent and the ideal volume of injection.⁶ Liposomal bupivacaine is a new agent (approved by the US Food and Drug Administration in 2011¹⁷) with a sustained release over 72 to 96 hours.¹⁸ The most common adverse effects of liposomal bupivacaine are nausea, vomiting, constipation, pyrexia, dizziness, and headache.¹⁹ Chondrotoxicity and granulomatous inflammation are more serious, yet rare, complications of liposomal bupivacaine.²⁰

We found that liposomal bupivacaine injections were associated with lower pain scores compared with ISNB at 18 to 24 hours after surgery. This correlated with less opioid consumption in the liposomal bupivacaine group than in the ISNB group on the second postoperative day. These differences in pain values are consistent with the known pharmacokinetics of liposomal bupivacaine.¹⁸ Peak plasma levels normally occur approximately 24 hours after injection, leaving the early postoperative period relatively uncovered by anesthetic agent. This finding of relatively poor pain control early after surgery has also been noted in patients undergoing knee arthroplasty.⁵ On the basis of the findings of this study, we have added standard bupivacaine injections to our separate liposomal bupivacaine injection to cover early postoperative pain. Opioid consumption was significantly lower in the liposomal bupivacaine group than in the ISNB group on postoperative days 2 and 3. We did not measure adverse events related to opioid consumption, so we cannot comment on whether the decreased opioid consumption was associated with the rate of adverse events. However, other studies^21,22 have established this relationship.

We found the liposomal bupivacaine group to have earlier discharges to home. Sixteen of 37 patients in the liposomal bupivacaine group compared with 2 of 21 patients in the ISNB group were discharged on the day after surgery. A mean reduction in LOS of 18 hours for the liposomal bupivacaine group was statistically significant (P = .012). This reduction in LOS has important implications for hospitals and value analysis committees considering whether to keep a new, more expensive local anesthetic on formulary. Savings from reduced LOS and improvements in patient satisfaction may justify the expense (approximately $300 per 266-mg vial) of Exparel.

From a societal cost perspective, liposomal bupivacaine is more economical compared with ISNB, which adds approximately $1500 to the cost of anesthesia per patient.²³ Eliminating the costs associated with ISNB administration in shoulder arthroplasties could result in substantial savings to our healthcare system. More research examining time savings and exact costs of each procedure is needed to determine the true cost effectiveness of each approach.

Limitations of our study include the retrospective design, relatively small numbers of patients in each group, missing data for some patients at various time points, variation in the types of procedures in each group, and lack of long-term outcome measures. It is important to note that we did not confirm the success of the nerve block after administration. However, this study reflects the effectiveness of each of the modalities in actual clinical conditions (as opposed to a controlled experimental setting). The actual effectiveness of a nerve block varies, even when performed by an experienced anesthesiologist with ultrasound guidance. Furthermore, immediate postoperative pain scores in the nerve block group are consistent with those of prior research reporting pain values ranging from 4 to 5 and a mean duration of effect ranging from 9 to 14 hours.^23,24 Additionally, the patients, surgeon, and nursing team were not blinded to the treatment group. Although we did note a significant difference in the types of procedures between groups, this finding is related to the greater number of hemiarthroplasties performed in the ISNB group (N = 5) compared with the liposomal group (N = 1). Because of this variation and the decreased invasiveness of hemiarthroplasties, the bias is against the liposomal group. Finally, our primary outcome variable was pain, which is a subjective, self-reported measure. However, our opioid consumption data and LOS data corroborate the improved pain scores in the liposomal bupivacaine group.

Limiting the study to a single surgeon may limit external validity. Another limitation is the lack of data on adverse events related to opioid medication use. There was no additional experimental group to determine whether less expensive local anesthetics injected locally would perform similarly to liposomal bupivacaine. In total knee arthroplasty, periarticular injections of liposomal bupivacaine were not as effective as less expensive periarticular injections.²⁵ It is unclear which agents (and in what doses or combinations) should be used for periarticular injections. Finally, we acknowledge that our retrospective study design cannot account for all potential factors affecting discharge time.

This is the first comparative study of liposomal bupivacaine and ISNB in TSA. The study design allowed us to control for variables such as surgical technique, postoperative protocols (including use and type of sling), and use of other pain modalities such as patient-controlled analgesia and intravenous acetaminophen that are likely to affect postoperative pain and LOS. This study provides preliminary data that confirm relative equipoise between liposomal bupivacaine and ISNB, which is needed for the ethical conduct of a randomized controlled trial. Such a trial would allow for a more robust comparison, and this retrospective study provides appropriate pilot data on which to base this design and the clinical information needed to counsel patients during enrollment.

Our results suggest that liposomal bupivacaine may provide superior or similar pain relief compared with ISNB after shoulder arthroplasty. Additionally, the use of liposomal bupivacaine was associated with decreased opioid consumption and earlier discharge to home compared with ISNB. These findings have important implications for pain control after TSA because pain represents a major concern for patients and providers after surgery. In addition to clinical improvements, use of liposomal bupivacaine may save time and eliminate costs associated with administering nerve blocks. Local injection may also be used in patients who are contraindicated for ISNB such as those with obesity, pulmonary disease, or peripheral neuropathy. Although we cannot definitively suggest that liposomal bupivacaine is superior to the current gold standard ISNB for pain control after shoulder arthroplasty, our results suggest a relative clinical equipoise between these modalities. Larger analytical studies, including randomized trials, should be performed to explore the potential benefits of liposomal bupivacaine injections for pain control after shoulder arthroplasty.

Am J Orthop. 2016;45(7):424-430. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Ultrasound has classically been marketed and used as a diagnostic tool. Radiologists, emergency physicians, and sports physicians used ultrasound units to rapidly and appropriately diagnose numerous injuries and disorders, in a timely and cost effective manner. Part 1¹ and Part 2² of this series showed how to use ultrasound in the shoulder for diagnosis and how to code and get reimbursed for its use.Ultrasound can also be used to help guide procedures and interventions performed to treat patients. Currently, more physicians are beginning to recognize the utility of this modality as an aid to interventional procedures.

First-generation procedures use ultrasound to improve accuracy of joint, bursal, tendon, and muscular injections.³ Recent studies have shown a significant improvement in accuracy, outcomes, and patient satisfaction using ultrasound guidance for injections.^3-12 Within the limitation of using a needle, second-generation procedures—hydrodissection of peripherally entrapped nerves, capsular distention, mechanical disruption of neovascularization, and needle fenestration or barbotage in chronic tendinopathy—try to simulate surgical objectives while minimizing tissue burden and other complications of surgery.³ More advanced procedures include needle fenestration/release of the carpal ligament in carpal tunnel syndrome and A1 pulley needle release in the setting of trigger finger.³ Innovative third-generation procedures involve the use of surgical tools such as hook blades under ultrasound guidance to perform surgical procedures. Surgeons are now improving already established percutaneous, arthroscopic, and open surgical procedures with ultrasound assistance.³ Aside from better guidance, reducing cost and improving surgeon comfort may be additional benefits of ultrasound assisted surgery.

Image-Guided Treatment Options

Prior to image guidance, palpation of surface anatomy helped physicians determine the anatomic placement of injections, incisions, or portals. Joints and bursas that do not have any inflammation or fluid can sometimes be difficult to identify or locate by palpation alone. Palpation-guided joint injections often miss their target and cause significant pain when the therapeutic agent is injected into a muscle, tendon, ligament, fat, or other tissue. Ultrasound-guided injections have proven to be more accurate and have better patient satisfaction when compared to blind injections.^3-12

X-ray fluoroscopy has been the primary option for surgeons to assist in surgery. This is a natural modality for orthopedic surgeons; their primary use is for bone to help with fracture reduction and fixation as the bone, instrumentation, and fixation methods are usually radio-opaque. With the advancement in technology, many orthopedic surgeons are regularly using radiolucent fixation devices and working with soft tissue as opposed to bone. Fixation of tendons, ligaments, and muscles would be done using a large incision, palpation of the anatomy, then fixation or repair. Many surgeons began looking for ways to minimize the incisions. Turning to fluoroscopy, a traditional and well-used modality, was a natural progression. Guides and methods were developed to isolate insertions and drill placements. However, fluoroscopy is limited by its difficulty in changing planes and the large equipment required. Also, it is limited in its ability to image soft tissue.

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are far better at imaging soft tissue but cannot be taken for use into the office or surgical suite. These modalities are also far more expensive and take up significant space.

Ultrasound Procedural Basics

Appropriate use of ultrasound still remains highly technician-dependent. Unlike other imaging modalities, ultrasound requires a higher skill level by the physician to implement the use of ultrasound and identification of pathology to treat these disease processes. However, this is no different from the use of arthroscopy or fluoroscopy to treat patients. Training is required, as well as an understanding of the ultrasound machine, anatomy, and sono-anatomy—identification of anatomy and pathology as shown by the ultrasound machine.²

In ultrasound, the long axis refers to looking at a structure along its length, as in longitudinal. The short axis refers to evaluating a structure in cross-section, transverse, or along its shortest length. “In plane” refers to performing a procedure where the needle or object being used enters the ultrasound field along the plane of the transducer, allowing visualization of the majority of the needle as it crosses tissue planes. “Out of plane” has the needle entering perpendicular to the plane of the transducer, showing the needle on the monitor as a bright, hyperechoic dot. Some studies have suggested that novice ultrasonographers should start in a long axis view and use the in plane technique when injecting, as doing so may decrease time to identify the target and improve mean imaging quality during needle advancement.¹³

Anisotropy is the property of being directionally dependent. The ultrasound beam needs to be perpendicular to the structure being imaged to give the optimal image. When the beam hits a longitudinal structure like a needle at an angle <90°, the linear structure might reflect most of the beam away from the transducer. So when using a needle to localize or inject a specific area, maintaining the probe as close to perpendicular as possible with the needle will give a better image. New technology exists to better visualize needles even at high acuity angles by using a multi-beam processing algorithm, which can significantly aid the physician without the need for specialized needles.

Despite better technology, advance planning is key to a successful procedure. Positioning the patient and ultrasound machine in a manner that is comfortable and makes the desired target accessible while being able to visualize the ultrasound monitor comes first. Identifying the target, mapping the needle trajectory using depth markings, and scanning for nerves, vessels, and other structures that may be damaged along the needle path comes next. Using the in plane ultrasound technique with color Doppler and the nerve contrast setting can ensure that the physician has placed the therapeutic agent to the proper location while avoiding any nerves, arteries, or veins. Marking the borders of the ultrasound probe and needle entry site can be helpful to return to the same area after sterile preparation is done. As in any procedure, sterile technique is paramount. Sterile technique considerations may include using sterile gloves and a probe cover with sterile gel, cleaning the area thoroughly, planning the needle entry point 3 cm to 5 cm away from the probe, and maintaining a dry and gel-free needle entry.^14-15 The probe should be sterilized between patients to avoid cross-contamination; note that certain solutions like alcohol or ethyl chloride can damage the transducer.^14-15 However, simple injections do not require such stringent standards when simple sterile technique is observed by cleaning and then never touching the cleaned area again except with the needle to avoid contamination. Also, ethyl chloride has been found to not contaminate a sterile site and can be used safely to anesthetize the skin.

Ultrasound-Guided Procedures

Many injectable therapeutic options exist as interventions. Cortisone, hyaluronic acid, platelet-rich plasma (PRP), stem cells/bone marrow concentrate (BMC), amniotic fluid, prolotherapy, and saline are now commonly used.^16-17 A meta-analysis of the literature assessing the accuracy of ultrasound-guided shoulder girdle injections vs a landmark-guided injection was done in 2015.¹⁸ It showed that for the acromioclavicular joint, accuracy was 93.6% vs 68.2% (P < .0001), based on single studies. The accuracy of ultrasound vs a landmark-guided injection was 65% vs 70% for the subacromial space (P > .05); 86.7% vs 26.7% for the biceps tendon sheath (P < .05); and 92.5% vs 72.5% for the glenohumeral joint (P = .025).¹⁸ 

With cortisone, injecting into muscle, ligament, or tendons could potentially harm the tissue or cause worsening of the disease process.^19-20 With the advent of orthobiologics, injecting into these structures is now desirable, instead of a potential complication.^19-20 Ultrasound has become even more important to the accurate delivery of these therapies to the disease locations. Multiple studies using leukocyte-poor PRP for osteoarthritis show significant differences in pain scores.^21-23 Peerbooms and colleagues^24,25 also showed that PRP reduced pain and increased function compared to cortisone injections for lateral epicondylitis in 1- and 2-year double-blind randomized controlled trials. Centeno and colleagues²⁶ performed a prospective, multi-site registry study on 102 patients with symptomatic osteoarthritis and/or rotator cuff tears that were injected with bone marrow concentrate. There was a statistically significant improvement in Disabilities of the Arm, Shoulder and Hand (DASH) scores from 36.1 to 17.1 (P < .001) and numeric pain scores improved from 4.3 to 2.4 (P < .001).

By being able to see the pathology, like a hypoechoic region in a tendon, ligament, or muscle, the physician can reliably place the therapeutic agent into the precise location. Also, adjacent para-tendon or para-ligament injections allow for in-season athletes to get some relief from symptoms while allowing to return to play quickly; injections into muscle, ligament, or tendon can damage the structure and require days or weeks of rest, while para-tendon and para-ligament injections are far less painful.

Second-generation techniques have provided patients with great options that can help avoid surgery. Calcific tendonitis appears brightly hyperechoic on ultrasound and is easily identified. The physician can attempt to break up the calcium by fenestration or barbotage of the calcium. The same can be accomplished by injecting the density with PRP or stem cells. If the calcium is soft or “toothpaste-like,” the negative pressure will make it easy to aspirate it into the syringe. A 2-year, longitudinal prospective study of 121 patients demonstrated that visual analog score (VAS) pain scores and size of calcium significantly decreased with ultrasound-guided percutaneous needle lavage; 89% of patients were pain-free at 1-year follow-up.²⁷ Moreover, a randomized controlled trial of 48 patients comparing needle lavage vs subacromial steroid injection showed statistically significant radiographic and clinically better outcomes with the needle lavage group at the 1-year mark.²⁸

The Tenex procedure is a novel technique that uses ultrasonic energy to fenestrate diseased tendon tissue. It also can be used to break up calcific deposits. After the Tenex probe is guided to the diseased tendon/calcium, the TX-1 tip oscillates at the speed of sound, fenestrating/cutting through the tendon or calcium while lavaging the tendon with saline. Multiple prospective, noncontrolled studies done in common extensor, patellar, and rotator cuff tendinopathy have demonstrated good to excellent improvements in pain scores with the Tenex procedure.^29-31

Ultrasound is extremely useful in the treatment of adhesive capsulitis.³² The posterior glenohumeral capsule can be distended using a large volume (60 cc) of saline to loosen adhesions in preparation for manipulation. Because the manipulation can be an extremely painful procedure, ultrasound can be used to perform an inter-scalene block for regional anesthesia prior to the procedure. In 2014, Park and colleagues³³ performed a randomized prospective trial that showed that capsular distension followed by manipulation was more effective than cortisone injection alone for the treatment of adhesive capsulitis.Ultrasound guidance was found to be just as efficacious as fluoroscopy in a randomized controlled trial in 2014; the authors noted that ultrasound does not expose the patient or clinician to radiation and can be done in office.³⁴

Currently, techniques to perform ultrasound-guided percutaneous tenotomies of the long head of the biceps tendon using hook blades are being studied.³⁵

Ultrasound-Assisted Surgery

Ultrasound has been a boon to surgeons who perform minimally invasive procedures. It is far less cumbersome than classic fluoroscopy. Fluoroscopy requires the use of heavy lead aprons by the surgeons. Combining this with the impervious gowns and hot lights, the surgeons’ comfort level is severely sacrificed. When having to do many long surgeries in a row, this situation can take a toll on the surgeons’ endurance and strength. Improving the comfort of the surgeon is not the primary goal of surgery, but can significantly help our ability to do a better job.

Ultrasound allows the surgeon to localize any superficial foreign objects, especially with radiolucent objects like fragments of glass. Small glass fragments or pieces of wood have always been extremely difficult to remove. X-rays cannot localize these objects, so getting a proper orientation is difficult. MRI and CT scans easily identify these types of foreign objects, but cannot be used intraoperatively (Figure 1A). Often, these objects cannot be felt and therefore require a large dissection. The objects may encapsulate and be easily confused with other soft tissues.

Conclusion

Ultrasound is quickly becoming a popular imaging modality due to its simplicity, portability, and cost efficiency. Its use as a diagnostic tool is widely known. As an adjunct for procedures and interventions, its advantages over larger, more expensive modalities such as fluoroscopy, CT, or MRI make it stand out. Ultrasound is not the perfect solution to all problems, but it is clearly a technology that is gaining traction. Ultrasound is another imaging modality and tool that physicians and surgeons can use to improve their patients’ treatment.

Ultrasound has classically been marketed and used as a diagnostic tool. Radiologists, emergency physicians, and sports physicians used ultrasound units to rapidly and appropriately diagnose numerous injuries and disorders, in a timely and cost effective manner. Part 1¹ and Part 2² of this series showed how to use ultrasound in the shoulder for diagnosis and how to code and get reimbursed for its use.Ultrasound can also be used to help guide procedures and interventions performed to treat patients. Currently, more physicians are beginning to recognize the utility of this modality as an aid to interventional procedures.

First-generation procedures use ultrasound to improve accuracy of joint, bursal, tendon, and muscular injections.³ Recent studies have shown a significant improvement in accuracy, outcomes, and patient satisfaction using ultrasound guidance for injections.^3-12 Within the limitation of using a needle, second-generation procedures—hydrodissection of peripherally entrapped nerves, capsular distention, mechanical disruption of neovascularization, and needle fenestration or barbotage in chronic tendinopathy—try to simulate surgical objectives while minimizing tissue burden and other complications of surgery.³ More advanced procedures include needle fenestration/release of the carpal ligament in carpal tunnel syndrome and A1 pulley needle release in the setting of trigger finger.³ Innovative third-generation procedures involve the use of surgical tools such as hook blades under ultrasound guidance to perform surgical procedures. Surgeons are now improving already established percutaneous, arthroscopic, and open surgical procedures with ultrasound assistance.³ Aside from better guidance, reducing cost and improving surgeon comfort may be additional benefits of ultrasound assisted surgery.

Image-Guided Treatment Options

Prior to image guidance, palpation of surface anatomy helped physicians determine the anatomic placement of injections, incisions, or portals. Joints and bursas that do not have any inflammation or fluid can sometimes be difficult to identify or locate by palpation alone. Palpation-guided joint injections often miss their target and cause significant pain when the therapeutic agent is injected into a muscle, tendon, ligament, fat, or other tissue. Ultrasound-guided injections have proven to be more accurate and have better patient satisfaction when compared to blind injections.^3-12

X-ray fluoroscopy has been the primary option for surgeons to assist in surgery. This is a natural modality for orthopedic surgeons; their primary use is for bone to help with fracture reduction and fixation as the bone, instrumentation, and fixation methods are usually radio-opaque. With the advancement in technology, many orthopedic surgeons are regularly using radiolucent fixation devices and working with soft tissue as opposed to bone. Fixation of tendons, ligaments, and muscles would be done using a large incision, palpation of the anatomy, then fixation or repair. Many surgeons began looking for ways to minimize the incisions. Turning to fluoroscopy, a traditional and well-used modality, was a natural progression. Guides and methods were developed to isolate insertions and drill placements. However, fluoroscopy is limited by its difficulty in changing planes and the large equipment required. Also, it is limited in its ability to image soft tissue.

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are far better at imaging soft tissue but cannot be taken for use into the office or surgical suite. These modalities are also far more expensive and take up significant space.

Ultrasound Procedural Basics

Appropriate use of ultrasound still remains highly technician-dependent. Unlike other imaging modalities, ultrasound requires a higher skill level by the physician to implement the use of ultrasound and identification of pathology to treat these disease processes. However, this is no different from the use of arthroscopy or fluoroscopy to treat patients. Training is required, as well as an understanding of the ultrasound machine, anatomy, and sono-anatomy—identification of anatomy and pathology as shown by the ultrasound machine.²

In ultrasound, the long axis refers to looking at a structure along its length, as in longitudinal. The short axis refers to evaluating a structure in cross-section, transverse, or along its shortest length. “In plane” refers to performing a procedure where the needle or object being used enters the ultrasound field along the plane of the transducer, allowing visualization of the majority of the needle as it crosses tissue planes. “Out of plane” has the needle entering perpendicular to the plane of the transducer, showing the needle on the monitor as a bright, hyperechoic dot. Some studies have suggested that novice ultrasonographers should start in a long axis view and use the in plane technique when injecting, as doing so may decrease time to identify the target and improve mean imaging quality during needle advancement.¹³

Anisotropy is the property of being directionally dependent. The ultrasound beam needs to be perpendicular to the structure being imaged to give the optimal image. When the beam hits a longitudinal structure like a needle at an angle <90°, the linear structure might reflect most of the beam away from the transducer. So when using a needle to localize or inject a specific area, maintaining the probe as close to perpendicular as possible with the needle will give a better image. New technology exists to better visualize needles even at high acuity angles by using a multi-beam processing algorithm, which can significantly aid the physician without the need for specialized needles.

Despite better technology, advance planning is key to a successful procedure. Positioning the patient and ultrasound machine in a manner that is comfortable and makes the desired target accessible while being able to visualize the ultrasound monitor comes first. Identifying the target, mapping the needle trajectory using depth markings, and scanning for nerves, vessels, and other structures that may be damaged along the needle path comes next. Using the in plane ultrasound technique with color Doppler and the nerve contrast setting can ensure that the physician has placed the therapeutic agent to the proper location while avoiding any nerves, arteries, or veins. Marking the borders of the ultrasound probe and needle entry site can be helpful to return to the same area after sterile preparation is done. As in any procedure, sterile technique is paramount. Sterile technique considerations may include using sterile gloves and a probe cover with sterile gel, cleaning the area thoroughly, planning the needle entry point 3 cm to 5 cm away from the probe, and maintaining a dry and gel-free needle entry.^14-15 The probe should be sterilized between patients to avoid cross-contamination; note that certain solutions like alcohol or ethyl chloride can damage the transducer.^14-15 However, simple injections do not require such stringent standards when simple sterile technique is observed by cleaning and then never touching the cleaned area again except with the needle to avoid contamination. Also, ethyl chloride has been found to not contaminate a sterile site and can be used safely to anesthetize the skin.

Ultrasound-Guided Procedures

Many injectable therapeutic options exist as interventions. Cortisone, hyaluronic acid, platelet-rich plasma (PRP), stem cells/bone marrow concentrate (BMC), amniotic fluid, prolotherapy, and saline are now commonly used.^16-17 A meta-analysis of the literature assessing the accuracy of ultrasound-guided shoulder girdle injections vs a landmark-guided injection was done in 2015.¹⁸ It showed that for the acromioclavicular joint, accuracy was 93.6% vs 68.2% (P < .0001), based on single studies. The accuracy of ultrasound vs a landmark-guided injection was 65% vs 70% for the subacromial space (P > .05); 86.7% vs 26.7% for the biceps tendon sheath (P < .05); and 92.5% vs 72.5% for the glenohumeral joint (P = .025).¹⁸ 

With cortisone, injecting into muscle, ligament, or tendons could potentially harm the tissue or cause worsening of the disease process.^19-20 With the advent of orthobiologics, injecting into these structures is now desirable, instead of a potential complication.^19-20 Ultrasound has become even more important to the accurate delivery of these therapies to the disease locations. Multiple studies using leukocyte-poor PRP for osteoarthritis show significant differences in pain scores.^21-23 Peerbooms and colleagues^24,25 also showed that PRP reduced pain and increased function compared to cortisone injections for lateral epicondylitis in 1- and 2-year double-blind randomized controlled trials. Centeno and colleagues²⁶ performed a prospective, multi-site registry study on 102 patients with symptomatic osteoarthritis and/or rotator cuff tears that were injected with bone marrow concentrate. There was a statistically significant improvement in Disabilities of the Arm, Shoulder and Hand (DASH) scores from 36.1 to 17.1 (P < .001) and numeric pain scores improved from 4.3 to 2.4 (P < .001).

By being able to see the pathology, like a hypoechoic region in a tendon, ligament, or muscle, the physician can reliably place the therapeutic agent into the precise location. Also, adjacent para-tendon or para-ligament injections allow for in-season athletes to get some relief from symptoms while allowing to return to play quickly; injections into muscle, ligament, or tendon can damage the structure and require days or weeks of rest, while para-tendon and para-ligament injections are far less painful.

Second-generation techniques have provided patients with great options that can help avoid surgery. Calcific tendonitis appears brightly hyperechoic on ultrasound and is easily identified. The physician can attempt to break up the calcium by fenestration or barbotage of the calcium. The same can be accomplished by injecting the density with PRP or stem cells. If the calcium is soft or “toothpaste-like,” the negative pressure will make it easy to aspirate it into the syringe. A 2-year, longitudinal prospective study of 121 patients demonstrated that visual analog score (VAS) pain scores and size of calcium significantly decreased with ultrasound-guided percutaneous needle lavage; 89% of patients were pain-free at 1-year follow-up.²⁷ Moreover, a randomized controlled trial of 48 patients comparing needle lavage vs subacromial steroid injection showed statistically significant radiographic and clinically better outcomes with the needle lavage group at the 1-year mark.²⁸

The Tenex procedure is a novel technique that uses ultrasonic energy to fenestrate diseased tendon tissue. It also can be used to break up calcific deposits. After the Tenex probe is guided to the diseased tendon/calcium, the TX-1 tip oscillates at the speed of sound, fenestrating/cutting through the tendon or calcium while lavaging the tendon with saline. Multiple prospective, noncontrolled studies done in common extensor, patellar, and rotator cuff tendinopathy have demonstrated good to excellent improvements in pain scores with the Tenex procedure.^29-31

Ultrasound is extremely useful in the treatment of adhesive capsulitis.³² The posterior glenohumeral capsule can be distended using a large volume (60 cc) of saline to loosen adhesions in preparation for manipulation. Because the manipulation can be an extremely painful procedure, ultrasound can be used to perform an inter-scalene block for regional anesthesia prior to the procedure. In 2014, Park and colleagues³³ performed a randomized prospective trial that showed that capsular distension followed by manipulation was more effective than cortisone injection alone for the treatment of adhesive capsulitis.Ultrasound guidance was found to be just as efficacious as fluoroscopy in a randomized controlled trial in 2014; the authors noted that ultrasound does not expose the patient or clinician to radiation and can be done in office.³⁴

Currently, techniques to perform ultrasound-guided percutaneous tenotomies of the long head of the biceps tendon using hook blades are being studied.³⁵

Ultrasound-Assisted Surgery

Ultrasound has been a boon to surgeons who perform minimally invasive procedures. It is far less cumbersome than classic fluoroscopy. Fluoroscopy requires the use of heavy lead aprons by the surgeons. Combining this with the impervious gowns and hot lights, the surgeons’ comfort level is severely sacrificed. When having to do many long surgeries in a row, this situation can take a toll on the surgeons’ endurance and strength. Improving the comfort of the surgeon is not the primary goal of surgery, but can significantly help our ability to do a better job.

Ultrasound allows the surgeon to localize any superficial foreign objects, especially with radiolucent objects like fragments of glass. Small glass fragments or pieces of wood have always been extremely difficult to remove. X-rays cannot localize these objects, so getting a proper orientation is difficult. MRI and CT scans easily identify these types of foreign objects, but cannot be used intraoperatively (Figure 1A). Often, these objects cannot be felt and therefore require a large dissection. The objects may encapsulate and be easily confused with other soft tissues.

Conclusion

Ultrasound is quickly becoming a popular imaging modality due to its simplicity, portability, and cost efficiency. Its use as a diagnostic tool is widely known. As an adjunct for procedures and interventions, its advantages over larger, more expensive modalities such as fluoroscopy, CT, or MRI make it stand out. Ultrasound is not the perfect solution to all problems, but it is clearly a technology that is gaining traction. Ultrasound is another imaging modality and tool that physicians and surgeons can use to improve their patients’ treatment.

Ultrasound has classically been marketed and used as a diagnostic tool. Radiologists, emergency physicians, and sports physicians used ultrasound units to rapidly and appropriately diagnose numerous injuries and disorders, in a timely and cost effective manner. Part 1¹ and Part 2² of this series showed how to use ultrasound in the shoulder for diagnosis and how to code and get reimbursed for its use.Ultrasound can also be used to help guide procedures and interventions performed to treat patients. Currently, more physicians are beginning to recognize the utility of this modality as an aid to interventional procedures.

First-generation procedures use ultrasound to improve accuracy of joint, bursal, tendon, and muscular injections.³ Recent studies have shown a significant improvement in accuracy, outcomes, and patient satisfaction using ultrasound guidance for injections.^3-12 Within the limitation of using a needle, second-generation procedures—hydrodissection of peripherally entrapped nerves, capsular distention, mechanical disruption of neovascularization, and needle fenestration or barbotage in chronic tendinopathy—try to simulate surgical objectives while minimizing tissue burden and other complications of surgery.³ More advanced procedures include needle fenestration/release of the carpal ligament in carpal tunnel syndrome and A1 pulley needle release in the setting of trigger finger.³ Innovative third-generation procedures involve the use of surgical tools such as hook blades under ultrasound guidance to perform surgical procedures. Surgeons are now improving already established percutaneous, arthroscopic, and open surgical procedures with ultrasound assistance.³ Aside from better guidance, reducing cost and improving surgeon comfort may be additional benefits of ultrasound assisted surgery.

Image-Guided Treatment Options

Prior to image guidance, palpation of surface anatomy helped physicians determine the anatomic placement of injections, incisions, or portals. Joints and bursas that do not have any inflammation or fluid can sometimes be difficult to identify or locate by palpation alone. Palpation-guided joint injections often miss their target and cause significant pain when the therapeutic agent is injected into a muscle, tendon, ligament, fat, or other tissue. Ultrasound-guided injections have proven to be more accurate and have better patient satisfaction when compared to blind injections.^3-12

X-ray fluoroscopy has been the primary option for surgeons to assist in surgery. This is a natural modality for orthopedic surgeons; their primary use is for bone to help with fracture reduction and fixation as the bone, instrumentation, and fixation methods are usually radio-opaque. With the advancement in technology, many orthopedic surgeons are regularly using radiolucent fixation devices and working with soft tissue as opposed to bone. Fixation of tendons, ligaments, and muscles would be done using a large incision, palpation of the anatomy, then fixation or repair. Many surgeons began looking for ways to minimize the incisions. Turning to fluoroscopy, a traditional and well-used modality, was a natural progression. Guides and methods were developed to isolate insertions and drill placements. However, fluoroscopy is limited by its difficulty in changing planes and the large equipment required. Also, it is limited in its ability to image soft tissue.

Computed tomography (CT) scans and magnetic resonance imaging (MRI) are far better at imaging soft tissue but cannot be taken for use into the office or surgical suite. These modalities are also far more expensive and take up significant space.

Ultrasound Procedural Basics

Appropriate use of ultrasound still remains highly technician-dependent. Unlike other imaging modalities, ultrasound requires a higher skill level by the physician to implement the use of ultrasound and identification of pathology to treat these disease processes. However, this is no different from the use of arthroscopy or fluoroscopy to treat patients. Training is required, as well as an understanding of the ultrasound machine, anatomy, and sono-anatomy—identification of anatomy and pathology as shown by the ultrasound machine.²

In ultrasound, the long axis refers to looking at a structure along its length, as in longitudinal. The short axis refers to evaluating a structure in cross-section, transverse, or along its shortest length. “In plane” refers to performing a procedure where the needle or object being used enters the ultrasound field along the plane of the transducer, allowing visualization of the majority of the needle as it crosses tissue planes. “Out of plane” has the needle entering perpendicular to the plane of the transducer, showing the needle on the monitor as a bright, hyperechoic dot. Some studies have suggested that novice ultrasonographers should start in a long axis view and use the in plane technique when injecting, as doing so may decrease time to identify the target and improve mean imaging quality during needle advancement.¹³

Anisotropy is the property of being directionally dependent. The ultrasound beam needs to be perpendicular to the structure being imaged to give the optimal image. When the beam hits a longitudinal structure like a needle at an angle <90°, the linear structure might reflect most of the beam away from the transducer. So when using a needle to localize or inject a specific area, maintaining the probe as close to perpendicular as possible with the needle will give a better image. New technology exists to better visualize needles even at high acuity angles by using a multi-beam processing algorithm, which can significantly aid the physician without the need for specialized needles.

Despite better technology, advance planning is key to a successful procedure. Positioning the patient and ultrasound machine in a manner that is comfortable and makes the desired target accessible while being able to visualize the ultrasound monitor comes first. Identifying the target, mapping the needle trajectory using depth markings, and scanning for nerves, vessels, and other structures that may be damaged along the needle path comes next. Using the in plane ultrasound technique with color Doppler and the nerve contrast setting can ensure that the physician has placed the therapeutic agent to the proper location while avoiding any nerves, arteries, or veins. Marking the borders of the ultrasound probe and needle entry site can be helpful to return to the same area after sterile preparation is done. As in any procedure, sterile technique is paramount. Sterile technique considerations may include using sterile gloves and a probe cover with sterile gel, cleaning the area thoroughly, planning the needle entry point 3 cm to 5 cm away from the probe, and maintaining a dry and gel-free needle entry.^14-15 The probe should be sterilized between patients to avoid cross-contamination; note that certain solutions like alcohol or ethyl chloride can damage the transducer.^14-15 However, simple injections do not require such stringent standards when simple sterile technique is observed by cleaning and then never touching the cleaned area again except with the needle to avoid contamination. Also, ethyl chloride has been found to not contaminate a sterile site and can be used safely to anesthetize the skin.

Ultrasound-Guided Procedures

Many injectable therapeutic options exist as interventions. Cortisone, hyaluronic acid, platelet-rich plasma (PRP), stem cells/bone marrow concentrate (BMC), amniotic fluid, prolotherapy, and saline are now commonly used.^16-17 A meta-analysis of the literature assessing the accuracy of ultrasound-guided shoulder girdle injections vs a landmark-guided injection was done in 2015.¹⁸ It showed that for the acromioclavicular joint, accuracy was 93.6% vs 68.2% (P < .0001), based on single studies. The accuracy of ultrasound vs a landmark-guided injection was 65% vs 70% for the subacromial space (P > .05); 86.7% vs 26.7% for the biceps tendon sheath (P < .05); and 92.5% vs 72.5% for the glenohumeral joint (P = .025).¹⁸ 

With cortisone, injecting into muscle, ligament, or tendons could potentially harm the tissue or cause worsening of the disease process.^19-20 With the advent of orthobiologics, injecting into these structures is now desirable, instead of a potential complication.^19-20 Ultrasound has become even more important to the accurate delivery of these therapies to the disease locations. Multiple studies using leukocyte-poor PRP for osteoarthritis show significant differences in pain scores.^21-23 Peerbooms and colleagues^24,25 also showed that PRP reduced pain and increased function compared to cortisone injections for lateral epicondylitis in 1- and 2-year double-blind randomized controlled trials. Centeno and colleagues²⁶ performed a prospective, multi-site registry study on 102 patients with symptomatic osteoarthritis and/or rotator cuff tears that were injected with bone marrow concentrate. There was a statistically significant improvement in Disabilities of the Arm, Shoulder and Hand (DASH) scores from 36.1 to 17.1 (P < .001) and numeric pain scores improved from 4.3 to 2.4 (P < .001).

By being able to see the pathology, like a hypoechoic region in a tendon, ligament, or muscle, the physician can reliably place the therapeutic agent into the precise location. Also, adjacent para-tendon or para-ligament injections allow for in-season athletes to get some relief from symptoms while allowing to return to play quickly; injections into muscle, ligament, or tendon can damage the structure and require days or weeks of rest, while para-tendon and para-ligament injections are far less painful.

Second-generation techniques have provided patients with great options that can help avoid surgery. Calcific tendonitis appears brightly hyperechoic on ultrasound and is easily identified. The physician can attempt to break up the calcium by fenestration or barbotage of the calcium. The same can be accomplished by injecting the density with PRP or stem cells. If the calcium is soft or “toothpaste-like,” the negative pressure will make it easy to aspirate it into the syringe. A 2-year, longitudinal prospective study of 121 patients demonstrated that visual analog score (VAS) pain scores and size of calcium significantly decreased with ultrasound-guided percutaneous needle lavage; 89% of patients were pain-free at 1-year follow-up.²⁷ Moreover, a randomized controlled trial of 48 patients comparing needle lavage vs subacromial steroid injection showed statistically significant radiographic and clinically better outcomes with the needle lavage group at the 1-year mark.²⁸

The Tenex procedure is a novel technique that uses ultrasonic energy to fenestrate diseased tendon tissue. It also can be used to break up calcific deposits. After the Tenex probe is guided to the diseased tendon/calcium, the TX-1 tip oscillates at the speed of sound, fenestrating/cutting through the tendon or calcium while lavaging the tendon with saline. Multiple prospective, noncontrolled studies done in common extensor, patellar, and rotator cuff tendinopathy have demonstrated good to excellent improvements in pain scores with the Tenex procedure.^29-31

Ultrasound is extremely useful in the treatment of adhesive capsulitis.³² The posterior glenohumeral capsule can be distended using a large volume (60 cc) of saline to loosen adhesions in preparation for manipulation. Because the manipulation can be an extremely painful procedure, ultrasound can be used to perform an inter-scalene block for regional anesthesia prior to the procedure. In 2014, Park and colleagues³³ performed a randomized prospective trial that showed that capsular distension followed by manipulation was more effective than cortisone injection alone for the treatment of adhesive capsulitis.Ultrasound guidance was found to be just as efficacious as fluoroscopy in a randomized controlled trial in 2014; the authors noted that ultrasound does not expose the patient or clinician to radiation and can be done in office.³⁴

Currently, techniques to perform ultrasound-guided percutaneous tenotomies of the long head of the biceps tendon using hook blades are being studied.³⁵

Ultrasound-Assisted Surgery

Ultrasound has been a boon to surgeons who perform minimally invasive procedures. It is far less cumbersome than classic fluoroscopy. Fluoroscopy requires the use of heavy lead aprons by the surgeons. Combining this with the impervious gowns and hot lights, the surgeons’ comfort level is severely sacrificed. When having to do many long surgeries in a row, this situation can take a toll on the surgeons’ endurance and strength. Improving the comfort of the surgeon is not the primary goal of surgery, but can significantly help our ability to do a better job.

Ultrasound allows the surgeon to localize any superficial foreign objects, especially with radiolucent objects like fragments of glass. Small glass fragments or pieces of wood have always been extremely difficult to remove. X-rays cannot localize these objects, so getting a proper orientation is difficult. MRI and CT scans easily identify these types of foreign objects, but cannot be used intraoperatively (Figure 1A). Often, these objects cannot be felt and therefore require a large dissection. The objects may encapsulate and be easily confused with other soft tissues.

Conclusion

Ultrasound is quickly becoming a popular imaging modality due to its simplicity, portability, and cost efficiency. Its use as a diagnostic tool is widely known. As an adjunct for procedures and interventions, its advantages over larger, more expensive modalities such as fluoroscopy, CT, or MRI make it stand out. Ultrasound is not the perfect solution to all problems, but it is clearly a technology that is gaining traction. Ultrasound is another imaging modality and tool that physicians and surgeons can use to improve their patients’ treatment.

Restoring native kinematics of the knee has been a primary goal of anterior cruciate ligament (ACL) procedures. Double-bundle ACL reconstruction, compared to single-bundle, has been hypothesized to more effectively re-establish rotational stability by re-creating the anatomic ACL, but has not yet proven to result in better clinical outcomes.¹

In 1879, Dr. Paul Segond described a “fibrous, pearly band” at the lateral aspect of the knee that avulsed off the anterolateral proximal tibia during many ACL injuries.² The role of the lateral tissues in knee stability and their relationship with ACL pathology has attracted noteworthy attention in recent time. There have been multiple studies presenting an anatomical description of a structure at the anterolateral portion of the knee with definitive femoral, meniscal, and tibial attachments, which helps control internal rotational forces.^3-7 Claes and colleagues⁴ later found that band of tissue to be the anterolateral ligament (ALL) and determined its injury to be pathognomonic with ACL ruptures.

The ALL is a vital static stabilizer of the tibio-femoral joint, especially during internal tibial rotation.^8-10 In their report on ALL and ACL reconstruction, Helito and colleagues¹¹ acknowledge the necessity of accurate assessment of the lateral structures through imaging to determine the presence of extra-articular injury. Musculoskeletal diagnostic ultrasound has been established as an appropriate means to identify the ALL.¹²

Ultrasound can accurately determine the exact anatomic location of the origin and insertion of the ALL. Reconstruction of the ALL could yield better patient outcomes for those who experience concurrent ACL/ALL injury. Here we present an innovative technique for an ultrasound-guided percutaneous method for reconstruction of the ALL and report on a patient who had underwent ALL reconstruction.

Surgical Indications

All patients undergo an ultrasound evaluation preoperatively to determine if the ALL is intact or injured. Our experience has shown that when ultrasound evaluation reveals an intact ALL, the pivot shift has never been a grade III.

Surgical Technique

For a demonstration of this technique, see the video that accompanies this article.

The pivot shift test is conducted under anesthesia to determine whether an ALL reconstruction is required. The patient is placed in a supine position with the knee flexed at 30^o, at neutral rotation, and without any varus or valgus stress.

Rehabilitation

Rehabilitation following an ALL procedure is similar to traditional ACL rehabilitation with an added emphasis on minimizing rotational torque of the tibia in the early stages.

Case Report

In January 2013, a 17-year-old male soccer player suffered an ACL rupture of his right knee. Later that spring, he had an ACL reconstruction with an allograft. Twelve months postoperatively, the patient returned, saying that he felt much better; however, anytime he tried to plant his foot and rotate over that fixed foot, his knee felt unstable. The physical examination revealed both negative Lachman and anterior drawer tests but a I+ pivot shift test. A magnetic resonance imaging (MRI) examination revealed an intact ACL graft. A diagnostic ultrasound evaluation revealed a distal ALL injury. After discussing the risks, benefits, and goals with the patient, we opted for a diagnostic arthroscopy and a percutaneous, ultrasound-guided reconstruction of the ALL.

Postoperatively, the patient did very well. One week after surgery, he returned, saying he felt completely stable and demonstrated by repeating the rotation of his knee. The patient continued to have no issues until he returned 13 months post-ALL surgery, complaining of a recent injury that had caused the return of his feelings of instability. An MRI evaluation showed an intact ACL graft and the possibility of a ruptured ALL. Fifteen months after the initial ALL reconstruction, we proceeded with surgery. At arthroscopy, the patient was found to have a pivot shift of I+ and an intact ACL graft. The ALL was reconstructed again using an allograft, internal brace, and bone marrow concentrate. At 13 months post-ALL reconstruction revision, the patient had no complaints.

Discussion

Reconstruction of the ALL is aimed to restore anatomic rotational kinematics. Sonnery-Cottet and colleagues¹⁴ have reported promising initial results in their 2-year follow-up study of combined ACL and ALL reconstruction outcomes. This surgical technique includes use of an internal brace, which negates the necessity for external support devices and allows for earlier mobilization of the joint. A reconstruction of the ALL, performed concurrently with the ACL, does not add recovery time, but could prevent postsurgical complications and improve rehabilitation by eliminating rotational instability that presents in some ACL-reconstructed patients.

Sonnery-Cottet and colleagues¹⁵ state that their arthroscopic identification of the ALL can help to cultivate a “less invasive and more anatomic” reconstruction. The use of musculoskeletal ultrasound allows our technique to utilize a completely noninvasive imaging tool that allows proper establishment of ALL anatomy prior to the procedure. The entirety of the ALL is easily identifiable,^4,12 which has proven to be shortcoming of MRI evaluation.^15-17 Accurate preoperative assessment of the lateral structures is necessary in ACL-deficient individuals.^11,15 Sonography also provides a means of accurate guidance and socket creation, without generating large incisions.

If the ALL is responsible for internal rotatory stability as asserted, the structure should exhibit biomechanical properties during movement. In their study on the function of the ligament, Parsons and colleagues⁹ established the inverse relationship between the ALL and ACL during internal rotation. As their cadaveric knees were subjected to an internal rotatory force through increasing angles of flexion, the contribution of the ALL towards stability significantly increased while the ACL declined. Helito and colleagues⁸ and Zens and colleagues¹⁰ have demonstrated length changes of the ligament through varying degrees of flexion and internal rotation. Their reports indicate greater tension during knee movements, coinciding with the description of increasing ALL stability contribution by Parsons and colleagues.⁹ Kennedy and colleagues⁷ conducted a pull-to-failure test on the ALL. The average failure load was 175 N with a stiffness of 20 N/mm, illustrating the structure is a candidate for most traditional soft tissue grafts. The biomechanical evidence of the structural properties of the ALL confirms its importance in knee function and the necessity for its reconstruction.

With the understanding that ACL contributes to rotatory stability to some extent, the notion begs the question of how a centrally located ligament is able to prevent excessive rotation in a structure with a large relative radius. Biomechanically, with such a small moment arm, the ACL would experience tremendous stress when a rotatory force is applied. The same torque applied to a more superficial structure, with a greater moment, would sustain a large reduction in the applied force. The concept of a wheel and an axle should be considered. The equation is F₁ × R₁ = F₂ × R₂. We measured on a cadaveric knee the distance from the center of rotation to the ACL and the ALL, finding the radii were 5 mm and 30 mm, respectively. Taking these measurements, we would then expect the force experienced on the axle (ACL) to be 6 times greater than what would be experienced on the periphery of the wheel (ALL). The ALL (wheel) has a significant biomechanical advantage over the ACL (axle) in controlling and enduring internal rotatory forces of the knee. This would imply that if the ALL were damaged and not re-established, the ACL would experience a 6 times greater force trying to control internal rotation, which would result in a significantly increased chance of failure and rupture.

While there is a degree of dissent on the presence of the ALL, a number of studies have classified the tissue as an independent ligamentous structure.^3-7 While there is disagreement on the precise location of the femoral attachment, there is a consensus on the location of the tibial and meniscal attachments. Claes and colleagues⁴ originally outlined the femoral attachment as anterior and distal to the origin of the fibular collateral ligament (FCL), which is the description this technique follows. Since Claes and colleagues’⁴ report, many have investigated the ligament’s femoral origin with delineations ranging from posterior and proximal^3,5,7 to anterior and distal.^6,16-18

The accurate, noninvasive nature of the musculoskeletal ultrasound prior to any incisions being made makes this technique innovative and superior to other open surgical techniques or those that require fluoroscopy.

Conclusion

The ALL has been determined to play an integral role in the rotational stability of the knee. In the setting of instability and insufficiency, reconstruction will lead to better patient outcomes for concurrent ACL/ALL injuries and postsurgical rotatory instability following ACL procedures. This innovative technique utilizes ultrasound to ascertain the precise anatomical attachments of the ALL prior to the operation. The novel nature of this ultrasound-guided reconstruction has the potential to be applicable in many other surgical procedures.

Restoring native kinematics of the knee has been a primary goal of anterior cruciate ligament (ACL) procedures. Double-bundle ACL reconstruction, compared to single-bundle, has been hypothesized to more effectively re-establish rotational stability by re-creating the anatomic ACL, but has not yet proven to result in better clinical outcomes.¹

In 1879, Dr. Paul Segond described a “fibrous, pearly band” at the lateral aspect of the knee that avulsed off the anterolateral proximal tibia during many ACL injuries.² The role of the lateral tissues in knee stability and their relationship with ACL pathology has attracted noteworthy attention in recent time. There have been multiple studies presenting an anatomical description of a structure at the anterolateral portion of the knee with definitive femoral, meniscal, and tibial attachments, which helps control internal rotational forces.^3-7 Claes and colleagues⁴ later found that band of tissue to be the anterolateral ligament (ALL) and determined its injury to be pathognomonic with ACL ruptures.

The ALL is a vital static stabilizer of the tibio-femoral joint, especially during internal tibial rotation.^8-10 In their report on ALL and ACL reconstruction, Helito and colleagues¹¹ acknowledge the necessity of accurate assessment of the lateral structures through imaging to determine the presence of extra-articular injury. Musculoskeletal diagnostic ultrasound has been established as an appropriate means to identify the ALL.¹²

Ultrasound can accurately determine the exact anatomic location of the origin and insertion of the ALL. Reconstruction of the ALL could yield better patient outcomes for those who experience concurrent ACL/ALL injury. Here we present an innovative technique for an ultrasound-guided percutaneous method for reconstruction of the ALL and report on a patient who had underwent ALL reconstruction.

Surgical Indications

All patients undergo an ultrasound evaluation preoperatively to determine if the ALL is intact or injured. Our experience has shown that when ultrasound evaluation reveals an intact ALL, the pivot shift has never been a grade III.

Surgical Technique

For a demonstration of this technique, see the video that accompanies this article.

The pivot shift test is conducted under anesthesia to determine whether an ALL reconstruction is required. The patient is placed in a supine position with the knee flexed at 30^o, at neutral rotation, and without any varus or valgus stress.

Rehabilitation

Rehabilitation following an ALL procedure is similar to traditional ACL rehabilitation with an added emphasis on minimizing rotational torque of the tibia in the early stages.

Case Report

In January 2013, a 17-year-old male soccer player suffered an ACL rupture of his right knee. Later that spring, he had an ACL reconstruction with an allograft. Twelve months postoperatively, the patient returned, saying that he felt much better; however, anytime he tried to plant his foot and rotate over that fixed foot, his knee felt unstable. The physical examination revealed both negative Lachman and anterior drawer tests but a I+ pivot shift test. A magnetic resonance imaging (MRI) examination revealed an intact ACL graft. A diagnostic ultrasound evaluation revealed a distal ALL injury. After discussing the risks, benefits, and goals with the patient, we opted for a diagnostic arthroscopy and a percutaneous, ultrasound-guided reconstruction of the ALL.

Postoperatively, the patient did very well. One week after surgery, he returned, saying he felt completely stable and demonstrated by repeating the rotation of his knee. The patient continued to have no issues until he returned 13 months post-ALL surgery, complaining of a recent injury that had caused the return of his feelings of instability. An MRI evaluation showed an intact ACL graft and the possibility of a ruptured ALL. Fifteen months after the initial ALL reconstruction, we proceeded with surgery. At arthroscopy, the patient was found to have a pivot shift of I+ and an intact ACL graft. The ALL was reconstructed again using an allograft, internal brace, and bone marrow concentrate. At 13 months post-ALL reconstruction revision, the patient had no complaints.

Discussion

Reconstruction of the ALL is aimed to restore anatomic rotational kinematics. Sonnery-Cottet and colleagues¹⁴ have reported promising initial results in their 2-year follow-up study of combined ACL and ALL reconstruction outcomes. This surgical technique includes use of an internal brace, which negates the necessity for external support devices and allows for earlier mobilization of the joint. A reconstruction of the ALL, performed concurrently with the ACL, does not add recovery time, but could prevent postsurgical complications and improve rehabilitation by eliminating rotational instability that presents in some ACL-reconstructed patients.

Sonnery-Cottet and colleagues¹⁵ state that their arthroscopic identification of the ALL can help to cultivate a “less invasive and more anatomic” reconstruction. The use of musculoskeletal ultrasound allows our technique to utilize a completely noninvasive imaging tool that allows proper establishment of ALL anatomy prior to the procedure. The entirety of the ALL is easily identifiable,^4,12 which has proven to be shortcoming of MRI evaluation.^15-17 Accurate preoperative assessment of the lateral structures is necessary in ACL-deficient individuals.^11,15 Sonography also provides a means of accurate guidance and socket creation, without generating large incisions.

If the ALL is responsible for internal rotatory stability as asserted, the structure should exhibit biomechanical properties during movement. In their study on the function of the ligament, Parsons and colleagues⁹ established the inverse relationship between the ALL and ACL during internal rotation. As their cadaveric knees were subjected to an internal rotatory force through increasing angles of flexion, the contribution of the ALL towards stability significantly increased while the ACL declined. Helito and colleagues⁸ and Zens and colleagues¹⁰ have demonstrated length changes of the ligament through varying degrees of flexion and internal rotation. Their reports indicate greater tension during knee movements, coinciding with the description of increasing ALL stability contribution by Parsons and colleagues.⁹ Kennedy and colleagues⁷ conducted a pull-to-failure test on the ALL. The average failure load was 175 N with a stiffness of 20 N/mm, illustrating the structure is a candidate for most traditional soft tissue grafts. The biomechanical evidence of the structural properties of the ALL confirms its importance in knee function and the necessity for its reconstruction.

With the understanding that ACL contributes to rotatory stability to some extent, the notion begs the question of how a centrally located ligament is able to prevent excessive rotation in a structure with a large relative radius. Biomechanically, with such a small moment arm, the ACL would experience tremendous stress when a rotatory force is applied. The same torque applied to a more superficial structure, with a greater moment, would sustain a large reduction in the applied force. The concept of a wheel and an axle should be considered. The equation is F₁ × R₁ = F₂ × R₂. We measured on a cadaveric knee the distance from the center of rotation to the ACL and the ALL, finding the radii were 5 mm and 30 mm, respectively. Taking these measurements, we would then expect the force experienced on the axle (ACL) to be 6 times greater than what would be experienced on the periphery of the wheel (ALL). The ALL (wheel) has a significant biomechanical advantage over the ACL (axle) in controlling and enduring internal rotatory forces of the knee. This would imply that if the ALL were damaged and not re-established, the ACL would experience a 6 times greater force trying to control internal rotation, which would result in a significantly increased chance of failure and rupture.

While there is a degree of dissent on the presence of the ALL, a number of studies have classified the tissue as an independent ligamentous structure.^3-7 While there is disagreement on the precise location of the femoral attachment, there is a consensus on the location of the tibial and meniscal attachments. Claes and colleagues⁴ originally outlined the femoral attachment as anterior and distal to the origin of the fibular collateral ligament (FCL), which is the description this technique follows. Since Claes and colleagues’⁴ report, many have investigated the ligament’s femoral origin with delineations ranging from posterior and proximal^3,5,7 to anterior and distal.^6,16-18

The accurate, noninvasive nature of the musculoskeletal ultrasound prior to any incisions being made makes this technique innovative and superior to other open surgical techniques or those that require fluoroscopy.

Conclusion

The ALL has been determined to play an integral role in the rotational stability of the knee. In the setting of instability and insufficiency, reconstruction will lead to better patient outcomes for concurrent ACL/ALL injuries and postsurgical rotatory instability following ACL procedures. This innovative technique utilizes ultrasound to ascertain the precise anatomical attachments of the ALL prior to the operation. The novel nature of this ultrasound-guided reconstruction has the potential to be applicable in many other surgical procedures.

Restoring native kinematics of the knee has been a primary goal of anterior cruciate ligament (ACL) procedures. Double-bundle ACL reconstruction, compared to single-bundle, has been hypothesized to more effectively re-establish rotational stability by re-creating the anatomic ACL, but has not yet proven to result in better clinical outcomes.¹

In 1879, Dr. Paul Segond described a “fibrous, pearly band” at the lateral aspect of the knee that avulsed off the anterolateral proximal tibia during many ACL injuries.² The role of the lateral tissues in knee stability and their relationship with ACL pathology has attracted noteworthy attention in recent time. There have been multiple studies presenting an anatomical description of a structure at the anterolateral portion of the knee with definitive femoral, meniscal, and tibial attachments, which helps control internal rotational forces.^3-7 Claes and colleagues⁴ later found that band of tissue to be the anterolateral ligament (ALL) and determined its injury to be pathognomonic with ACL ruptures.

The ALL is a vital static stabilizer of the tibio-femoral joint, especially during internal tibial rotation.^8-10 In their report on ALL and ACL reconstruction, Helito and colleagues¹¹ acknowledge the necessity of accurate assessment of the lateral structures through imaging to determine the presence of extra-articular injury. Musculoskeletal diagnostic ultrasound has been established as an appropriate means to identify the ALL.¹²

Ultrasound can accurately determine the exact anatomic location of the origin and insertion of the ALL. Reconstruction of the ALL could yield better patient outcomes for those who experience concurrent ACL/ALL injury. Here we present an innovative technique for an ultrasound-guided percutaneous method for reconstruction of the ALL and report on a patient who had underwent ALL reconstruction.

Surgical Indications

All patients undergo an ultrasound evaluation preoperatively to determine if the ALL is intact or injured. Our experience has shown that when ultrasound evaluation reveals an intact ALL, the pivot shift has never been a grade III.

Surgical Technique

For a demonstration of this technique, see the video that accompanies this article.

The pivot shift test is conducted under anesthesia to determine whether an ALL reconstruction is required. The patient is placed in a supine position with the knee flexed at 30^o, at neutral rotation, and without any varus or valgus stress.

Rehabilitation

Rehabilitation following an ALL procedure is similar to traditional ACL rehabilitation with an added emphasis on minimizing rotational torque of the tibia in the early stages.

Case Report

In January 2013, a 17-year-old male soccer player suffered an ACL rupture of his right knee. Later that spring, he had an ACL reconstruction with an allograft. Twelve months postoperatively, the patient returned, saying that he felt much better; however, anytime he tried to plant his foot and rotate over that fixed foot, his knee felt unstable. The physical examination revealed both negative Lachman and anterior drawer tests but a I+ pivot shift test. A magnetic resonance imaging (MRI) examination revealed an intact ACL graft. A diagnostic ultrasound evaluation revealed a distal ALL injury. After discussing the risks, benefits, and goals with the patient, we opted for a diagnostic arthroscopy and a percutaneous, ultrasound-guided reconstruction of the ALL.

Postoperatively, the patient did very well. One week after surgery, he returned, saying he felt completely stable and demonstrated by repeating the rotation of his knee. The patient continued to have no issues until he returned 13 months post-ALL surgery, complaining of a recent injury that had caused the return of his feelings of instability. An MRI evaluation showed an intact ACL graft and the possibility of a ruptured ALL. Fifteen months after the initial ALL reconstruction, we proceeded with surgery. At arthroscopy, the patient was found to have a pivot shift of I+ and an intact ACL graft. The ALL was reconstructed again using an allograft, internal brace, and bone marrow concentrate. At 13 months post-ALL reconstruction revision, the patient had no complaints.

Discussion

Reconstruction of the ALL is aimed to restore anatomic rotational kinematics. Sonnery-Cottet and colleagues¹⁴ have reported promising initial results in their 2-year follow-up study of combined ACL and ALL reconstruction outcomes. This surgical technique includes use of an internal brace, which negates the necessity for external support devices and allows for earlier mobilization of the joint. A reconstruction of the ALL, performed concurrently with the ACL, does not add recovery time, but could prevent postsurgical complications and improve rehabilitation by eliminating rotational instability that presents in some ACL-reconstructed patients.

Sonnery-Cottet and colleagues¹⁵ state that their arthroscopic identification of the ALL can help to cultivate a “less invasive and more anatomic” reconstruction. The use of musculoskeletal ultrasound allows our technique to utilize a completely noninvasive imaging tool that allows proper establishment of ALL anatomy prior to the procedure. The entirety of the ALL is easily identifiable,^4,12 which has proven to be shortcoming of MRI evaluation.^15-17 Accurate preoperative assessment of the lateral structures is necessary in ACL-deficient individuals.^11,15 Sonography also provides a means of accurate guidance and socket creation, without generating large incisions.

If the ALL is responsible for internal rotatory stability as asserted, the structure should exhibit biomechanical properties during movement. In their study on the function of the ligament, Parsons and colleagues⁹ established the inverse relationship between the ALL and ACL during internal rotation. As their cadaveric knees were subjected to an internal rotatory force through increasing angles of flexion, the contribution of the ALL towards stability significantly increased while the ACL declined. Helito and colleagues⁸ and Zens and colleagues¹⁰ have demonstrated length changes of the ligament through varying degrees of flexion and internal rotation. Their reports indicate greater tension during knee movements, coinciding with the description of increasing ALL stability contribution by Parsons and colleagues.⁹ Kennedy and colleagues⁷ conducted a pull-to-failure test on the ALL. The average failure load was 175 N with a stiffness of 20 N/mm, illustrating the structure is a candidate for most traditional soft tissue grafts. The biomechanical evidence of the structural properties of the ALL confirms its importance in knee function and the necessity for its reconstruction.

With the understanding that ACL contributes to rotatory stability to some extent, the notion begs the question of how a centrally located ligament is able to prevent excessive rotation in a structure with a large relative radius. Biomechanically, with such a small moment arm, the ACL would experience tremendous stress when a rotatory force is applied. The same torque applied to a more superficial structure, with a greater moment, would sustain a large reduction in the applied force. The concept of a wheel and an axle should be considered. The equation is F₁ × R₁ = F₂ × R₂. We measured on a cadaveric knee the distance from the center of rotation to the ACL and the ALL, finding the radii were 5 mm and 30 mm, respectively. Taking these measurements, we would then expect the force experienced on the axle (ACL) to be 6 times greater than what would be experienced on the periphery of the wheel (ALL). The ALL (wheel) has a significant biomechanical advantage over the ACL (axle) in controlling and enduring internal rotatory forces of the knee. This would imply that if the ALL were damaged and not re-established, the ACL would experience a 6 times greater force trying to control internal rotation, which would result in a significantly increased chance of failure and rupture.

While there is a degree of dissent on the presence of the ALL, a number of studies have classified the tissue as an independent ligamentous structure.^3-7 While there is disagreement on the precise location of the femoral attachment, there is a consensus on the location of the tibial and meniscal attachments. Claes and colleagues⁴ originally outlined the femoral attachment as anterior and distal to the origin of the fibular collateral ligament (FCL), which is the description this technique follows. Since Claes and colleagues’⁴ report, many have investigated the ligament’s femoral origin with delineations ranging from posterior and proximal^3,5,7 to anterior and distal.^6,16-18

The accurate, noninvasive nature of the musculoskeletal ultrasound prior to any incisions being made makes this technique innovative and superior to other open surgical techniques or those that require fluoroscopy.

Conclusion

The ALL has been determined to play an integral role in the rotational stability of the knee. In the setting of instability and insufficiency, reconstruction will lead to better patient outcomes for concurrent ACL/ALL injuries and postsurgical rotatory instability following ACL procedures. This innovative technique utilizes ultrasound to ascertain the precise anatomical attachments of the ALL prior to the operation. The novel nature of this ultrasound-guided reconstruction has the potential to be applicable in many other surgical procedures.

Those who cannot remember the past are condemned to repeat it.

—George Santayana (Life of Reason, 1905)

Zero. That’s the number I put on the screen when I start the lecture I give to residents about the future of orthopedics. It represents the number of cases I still do exactly the same way now as I did when I graduated from my residency program. It represents the commitment to lifelong learning that we’ve made as orthopedists. Surgical techniques innovate so rapidly that they often outpace our research, leaving us performing new techniques based solely on industry and key opinion leader recommendation, and not on randomized controlled studies. Sometimes we’re led down the wrong path (remember when the meniscus was thought to be vestigial?) and other times new techniques lead to disappointing long-term results (the transtibial anterior cruciate ligament’s (ACL’s) failure to prevent arthritis). Sometimes, the old way is just as good as the new (there is no evidence to suggest that results from arthroscopic cuff repair are better than open in the long term). If we’ve been in practice long enough, we see the same ideas come around again (meniscal spacers, ACL repair, anterolateral ligament [ALL]). Most often, these new variations offer a slightly different twist and supporting literature.

So it seems “everything old is new again.” That’s why this issue of AJO is called The Throwback Issue. In this issue, we revisit ideas whose time has come and gone and now come again.

Our lead article this month focuses on ACL repair. Once abandoned after a landmark paper by Feagin and Curl¹ showed poor mid-term results, new and innovative techniques and instrumentation for knee surgery have made this possible. Investigators such as Murray² and DiFelice³ have done outstanding work showing the feasibility of ACL repair. In this issue we offer a comprehensive review and surgical technique for adding ACL repair to your portfolio of surgical offerings (see pages 408 and 454). Expanded versions of both of these articles are available at amjorthopedics.com.

Our second feature article discusses the reemergence of the ALL, an idea so hot in the public domain that it has been featured as a Jeopardy question. Described originally by Müller⁴ as the missing link in persistent rotational instability, the ALL might offer the key to improved long-term outcomes for patients undergoing ACL surgery. Read the article on page 418 and learn how to identify which patients are candidates for ALL reconstruction, and a simple surgical technique you can apply to your practice. Scan the provided QR code to watch the accompanying surgical technique video.

The Throwback Issue marks the fifth edition of the “new AJO.” It’s time to let us know how we are doing. Please email us at ajo@frontlinemedcom.com to suggest future themes, articles you’d like to read, or suggestions for improvement.

Recently, based on the work of the authors mentioned above, I’ve begun offering ACL repair to select patients in my practice. I wouldn’t be able to do this if we as orthopedists weren’t constantly looking to improve, and weren’t willing to revisit old ideas to do it. Our goal at AJO is to present something in every article that can be immediately applied to your practice. Take a look at the articles presented this month, as we go “Back to the Future” to see what discarded ideas from our recent past can be applied to improve outcomes for your patients in the future.

Those who cannot remember the past are condemned to repeat it.

—George Santayana (Life of Reason, 1905)

Zero. That’s the number I put on the screen when I start the lecture I give to residents about the future of orthopedics. It represents the number of cases I still do exactly the same way now as I did when I graduated from my residency program. It represents the commitment to lifelong learning that we’ve made as orthopedists. Surgical techniques innovate so rapidly that they often outpace our research, leaving us performing new techniques based solely on industry and key opinion leader recommendation, and not on randomized controlled studies. Sometimes we’re led down the wrong path (remember when the meniscus was thought to be vestigial?) and other times new techniques lead to disappointing long-term results (the transtibial anterior cruciate ligament’s (ACL’s) failure to prevent arthritis). Sometimes, the old way is just as good as the new (there is no evidence to suggest that results from arthroscopic cuff repair are better than open in the long term). If we’ve been in practice long enough, we see the same ideas come around again (meniscal spacers, ACL repair, anterolateral ligament [ALL]). Most often, these new variations offer a slightly different twist and supporting literature.

So it seems “everything old is new again.” That’s why this issue of AJO is called The Throwback Issue. In this issue, we revisit ideas whose time has come and gone and now come again.

Our lead article this month focuses on ACL repair. Once abandoned after a landmark paper by Feagin and Curl¹ showed poor mid-term results, new and innovative techniques and instrumentation for knee surgery have made this possible. Investigators such as Murray² and DiFelice³ have done outstanding work showing the feasibility of ACL repair. In this issue we offer a comprehensive review and surgical technique for adding ACL repair to your portfolio of surgical offerings (see pages 408 and 454). Expanded versions of both of these articles are available at amjorthopedics.com.

Our second feature article discusses the reemergence of the ALL, an idea so hot in the public domain that it has been featured as a Jeopardy question. Described originally by Müller⁴ as the missing link in persistent rotational instability, the ALL might offer the key to improved long-term outcomes for patients undergoing ACL surgery. Read the article on page 418 and learn how to identify which patients are candidates for ALL reconstruction, and a simple surgical technique you can apply to your practice. Scan the provided QR code to watch the accompanying surgical technique video.

The Throwback Issue marks the fifth edition of the “new AJO.” It’s time to let us know how we are doing. Please email us at ajo@frontlinemedcom.com to suggest future themes, articles you’d like to read, or suggestions for improvement.

Recently, based on the work of the authors mentioned above, I’ve begun offering ACL repair to select patients in my practice. I wouldn’t be able to do this if we as orthopedists weren’t constantly looking to improve, and weren’t willing to revisit old ideas to do it. Our goal at AJO is to present something in every article that can be immediately applied to your practice. Take a look at the articles presented this month, as we go “Back to the Future” to see what discarded ideas from our recent past can be applied to improve outcomes for your patients in the future.

Those who cannot remember the past are condemned to repeat it.

—George Santayana (Life of Reason, 1905)

Zero. That’s the number I put on the screen when I start the lecture I give to residents about the future of orthopedics. It represents the number of cases I still do exactly the same way now as I did when I graduated from my residency program. It represents the commitment to lifelong learning that we’ve made as orthopedists. Surgical techniques innovate so rapidly that they often outpace our research, leaving us performing new techniques based solely on industry and key opinion leader recommendation, and not on randomized controlled studies. Sometimes we’re led down the wrong path (remember when the meniscus was thought to be vestigial?) and other times new techniques lead to disappointing long-term results (the transtibial anterior cruciate ligament’s (ACL’s) failure to prevent arthritis). Sometimes, the old way is just as good as the new (there is no evidence to suggest that results from arthroscopic cuff repair are better than open in the long term). If we’ve been in practice long enough, we see the same ideas come around again (meniscal spacers, ACL repair, anterolateral ligament [ALL]). Most often, these new variations offer a slightly different twist and supporting literature.

So it seems “everything old is new again.” That’s why this issue of AJO is called The Throwback Issue. In this issue, we revisit ideas whose time has come and gone and now come again.

Our lead article this month focuses on ACL repair. Once abandoned after a landmark paper by Feagin and Curl¹ showed poor mid-term results, new and innovative techniques and instrumentation for knee surgery have made this possible. Investigators such as Murray² and DiFelice³ have done outstanding work showing the feasibility of ACL repair. In this issue we offer a comprehensive review and surgical technique for adding ACL repair to your portfolio of surgical offerings (see pages 408 and 454). Expanded versions of both of these articles are available at amjorthopedics.com.

Our second feature article discusses the reemergence of the ALL, an idea so hot in the public domain that it has been featured as a Jeopardy question. Described originally by Müller⁴ as the missing link in persistent rotational instability, the ALL might offer the key to improved long-term outcomes for patients undergoing ACL surgery. Read the article on page 418 and learn how to identify which patients are candidates for ALL reconstruction, and a simple surgical technique you can apply to your practice. Scan the provided QR code to watch the accompanying surgical technique video.

The Throwback Issue marks the fifth edition of the “new AJO.” It’s time to let us know how we are doing. Please email us at ajo@frontlinemedcom.com to suggest future themes, articles you’d like to read, or suggestions for improvement.

Recently, based on the work of the authors mentioned above, I’ve begun offering ACL repair to select patients in my practice. I wouldn’t be able to do this if we as orthopedists weren’t constantly looking to improve, and weren’t willing to revisit old ideas to do it. Our goal at AJO is to present something in every article that can be immediately applied to your practice. Take a look at the articles presented this month, as we go “Back to the Future” to see what discarded ideas from our recent past can be applied to improve outcomes for your patients in the future.

Research flock at US

Sheep Experiment Station

Research conducted in sheep indicates that pretreating red blood cells (RBCs) with nitric oxide (NO) may make it safer to transfuse blood nearing its expiration date.

Past studies have suggested that RBCs stored for more than 30 days are less likely than “fresher” RBCs to survive after transfusion, and receiving a transfusion of RBCs nearing their expiration date of 42 days may increase the risk of pulmonary hypertension.

However, a new study published in Anesthesiology suggests that pretreating older RBCs with NO may increase their likelihood of survival after transfusion and reduce the risk of pulmonary hypertension in the recipient.

“Extended storage of RBCs makes them rigid and decreases their ability to change shape, which is necessary as they travel through small blood vessels,” said study author Warren M. Zapol, MD, of Massachusetts General Hospital in Boston.

“We found that pretreatment with nitric oxide actually rejuvenates RBCs, making them more flexible so they can more easily travel through blood vessels. This can further reduce the risk of pulmonary hypertension.”

Dr Zapol and his colleagues performed their experiments on RBCs derived from lambs. The team treated RBCs with NO gas, a short-lived NO donor, or gas without NO (control).

The RBCs were then stored for either 2 days (hereafter referred to as “fresh” RBCs) or 40 days (referred to as “stored” RBCs) and transfused back into the original lambs.

RBC survival

The researchers found that treatment with NO gas improved the early post-transfusion survival of stored RBCs.

At 1 hour after transfusion, 75.3 ± 5.8% of the control-treated stored RBCs remained in the circulation, compared to 86.8 ± 8.1% of the NO-treated stored RBCs and 94.2 ± 4.6% of the fresh RBCs.

At 24 hours after transfusion, 73.4 ± 3.8% of the control-treated stored RBCs remained in the circulation, compared to 78.3 ± 6.3% of the NO-treated stored RBCs, 90.8 ± 4.1% of control-treated fresh RBCs, and 91.4 ± 1.4% of NO-treated fresh RBCs.

The differences between stored RBCs that were treated with NO gas and stored control RBCs was statistically significant at both 1 hour and 24 hours, with P values of 0.002 and 0.046, respectively.

Seven days after transfusion, there was no significant difference in the percentage of NO-treated and control-treated RBCs in the circulation.

Pulmonary hypertension

The researchers found that pretreating RBCs with NO prevented transfusion-associated pulmonary hypertension in the lambs.

Lambs that received control-treated stored RBCs had an increase in pulmonary arterial pressure (PAP) during and after transfusion—from 13.4 ± 0.8 mmHg at baseline to a maximum of 22.7 ± 2.2 mmHg.

However, lambs that received stored RBCs treated with NO gas did not have an increase in PAP when compared to lambs that received fresh RBCs.

At 20 minutes, PAP was 14.5 ± 1.4 mmHg for NO-treated stored RBCs, 13.9 ± 0.6 mmHg for control-treated fresh RBCs, and 14 ± 1.2 mmHg for NO-treated fresh RBCs.

The researchers also found that transfusion of stored RBCs caused a transient increase in the pulmonary vascular resistance index (PVRI) from 10 minutes to 30 minutes after transfusion, but pretreatment with NO gas prevented this increase.

At 20 minutes, the PVRI was 211.1 ± 44.4 dyn·sec·cm⁻⁵·m⁻² for control-treated stored RBCs and 114.6 ± 18.9 dyn·sec·cm⁻⁵·m⁻² for NO-treated stored RBCs (P<0.0001).

Transfusion of fresh RBCs, with or without prior NO exposure, did not alter the PVRI.

Finally, the researchers found that treating stored RBCs with the NO donor compound MAHMA NONOate prevented transfusion-associated pulmonary hypertension and pulmonary vasoconstriction in awake lambs.

The team said studies with human RBCs are required to confirm the beneficial effects of NO exposure observed in this study.

Research flock at US

Sheep Experiment Station

Research conducted in sheep indicates that pretreating red blood cells (RBCs) with nitric oxide (NO) may make it safer to transfuse blood nearing its expiration date.

Past studies have suggested that RBCs stored for more than 30 days are less likely than “fresher” RBCs to survive after transfusion, and receiving a transfusion of RBCs nearing their expiration date of 42 days may increase the risk of pulmonary hypertension.

However, a new study published in Anesthesiology suggests that pretreating older RBCs with NO may increase their likelihood of survival after transfusion and reduce the risk of pulmonary hypertension in the recipient.

“Extended storage of RBCs makes them rigid and decreases their ability to change shape, which is necessary as they travel through small blood vessels,” said study author Warren M. Zapol, MD, of Massachusetts General Hospital in Boston.

“We found that pretreatment with nitric oxide actually rejuvenates RBCs, making them more flexible so they can more easily travel through blood vessels. This can further reduce the risk of pulmonary hypertension.”

Dr Zapol and his colleagues performed their experiments on RBCs derived from lambs. The team treated RBCs with NO gas, a short-lived NO donor, or gas without NO (control).

The RBCs were then stored for either 2 days (hereafter referred to as “fresh” RBCs) or 40 days (referred to as “stored” RBCs) and transfused back into the original lambs.

RBC survival

The researchers found that treatment with NO gas improved the early post-transfusion survival of stored RBCs.

At 1 hour after transfusion, 75.3 ± 5.8% of the control-treated stored RBCs remained in the circulation, compared to 86.8 ± 8.1% of the NO-treated stored RBCs and 94.2 ± 4.6% of the fresh RBCs.

At 24 hours after transfusion, 73.4 ± 3.8% of the control-treated stored RBCs remained in the circulation, compared to 78.3 ± 6.3% of the NO-treated stored RBCs, 90.8 ± 4.1% of control-treated fresh RBCs, and 91.4 ± 1.4% of NO-treated fresh RBCs.

The differences between stored RBCs that were treated with NO gas and stored control RBCs was statistically significant at both 1 hour and 24 hours, with P values of 0.002 and 0.046, respectively.

Seven days after transfusion, there was no significant difference in the percentage of NO-treated and control-treated RBCs in the circulation.

Pulmonary hypertension

The researchers found that pretreating RBCs with NO prevented transfusion-associated pulmonary hypertension in the lambs.

Lambs that received control-treated stored RBCs had an increase in pulmonary arterial pressure (PAP) during and after transfusion—from 13.4 ± 0.8 mmHg at baseline to a maximum of 22.7 ± 2.2 mmHg.

However, lambs that received stored RBCs treated with NO gas did not have an increase in PAP when compared to lambs that received fresh RBCs.

At 20 minutes, PAP was 14.5 ± 1.4 mmHg for NO-treated stored RBCs, 13.9 ± 0.6 mmHg for control-treated fresh RBCs, and 14 ± 1.2 mmHg for NO-treated fresh RBCs.

The researchers also found that transfusion of stored RBCs caused a transient increase in the pulmonary vascular resistance index (PVRI) from 10 minutes to 30 minutes after transfusion, but pretreatment with NO gas prevented this increase.

At 20 minutes, the PVRI was 211.1 ± 44.4 dyn·sec·cm⁻⁵·m⁻² for control-treated stored RBCs and 114.6 ± 18.9 dyn·sec·cm⁻⁵·m⁻² for NO-treated stored RBCs (P<0.0001).

Transfusion of fresh RBCs, with or without prior NO exposure, did not alter the PVRI.

Finally, the researchers found that treating stored RBCs with the NO donor compound MAHMA NONOate prevented transfusion-associated pulmonary hypertension and pulmonary vasoconstriction in awake lambs.

The team said studies with human RBCs are required to confirm the beneficial effects of NO exposure observed in this study.

Research flock at US

Sheep Experiment Station

Research conducted in sheep indicates that pretreating red blood cells (RBCs) with nitric oxide (NO) may make it safer to transfuse blood nearing its expiration date.

Past studies have suggested that RBCs stored for more than 30 days are less likely than “fresher” RBCs to survive after transfusion, and receiving a transfusion of RBCs nearing their expiration date of 42 days may increase the risk of pulmonary hypertension.

However, a new study published in Anesthesiology suggests that pretreating older RBCs with NO may increase their likelihood of survival after transfusion and reduce the risk of pulmonary hypertension in the recipient.

“Extended storage of RBCs makes them rigid and decreases their ability to change shape, which is necessary as they travel through small blood vessels,” said study author Warren M. Zapol, MD, of Massachusetts General Hospital in Boston.

“We found that pretreatment with nitric oxide actually rejuvenates RBCs, making them more flexible so they can more easily travel through blood vessels. This can further reduce the risk of pulmonary hypertension.”

Dr Zapol and his colleagues performed their experiments on RBCs derived from lambs. The team treated RBCs with NO gas, a short-lived NO donor, or gas without NO (control).

The RBCs were then stored for either 2 days (hereafter referred to as “fresh” RBCs) or 40 days (referred to as “stored” RBCs) and transfused back into the original lambs.

RBC survival

The researchers found that treatment with NO gas improved the early post-transfusion survival of stored RBCs.

At 1 hour after transfusion, 75.3 ± 5.8% of the control-treated stored RBCs remained in the circulation, compared to 86.8 ± 8.1% of the NO-treated stored RBCs and 94.2 ± 4.6% of the fresh RBCs.

At 24 hours after transfusion, 73.4 ± 3.8% of the control-treated stored RBCs remained in the circulation, compared to 78.3 ± 6.3% of the NO-treated stored RBCs, 90.8 ± 4.1% of control-treated fresh RBCs, and 91.4 ± 1.4% of NO-treated fresh RBCs.

The differences between stored RBCs that were treated with NO gas and stored control RBCs was statistically significant at both 1 hour and 24 hours, with P values of 0.002 and 0.046, respectively.

Seven days after transfusion, there was no significant difference in the percentage of NO-treated and control-treated RBCs in the circulation.

Pulmonary hypertension

The researchers found that pretreating RBCs with NO prevented transfusion-associated pulmonary hypertension in the lambs.

Lambs that received control-treated stored RBCs had an increase in pulmonary arterial pressure (PAP) during and after transfusion—from 13.4 ± 0.8 mmHg at baseline to a maximum of 22.7 ± 2.2 mmHg.

However, lambs that received stored RBCs treated with NO gas did not have an increase in PAP when compared to lambs that received fresh RBCs.

At 20 minutes, PAP was 14.5 ± 1.4 mmHg for NO-treated stored RBCs, 13.9 ± 0.6 mmHg for control-treated fresh RBCs, and 14 ± 1.2 mmHg for NO-treated fresh RBCs.

The researchers also found that transfusion of stored RBCs caused a transient increase in the pulmonary vascular resistance index (PVRI) from 10 minutes to 30 minutes after transfusion, but pretreatment with NO gas prevented this increase.

At 20 minutes, the PVRI was 211.1 ± 44.4 dyn·sec·cm⁻⁵·m⁻² for control-treated stored RBCs and 114.6 ± 18.9 dyn·sec·cm⁻⁵·m⁻² for NO-treated stored RBCs (P<0.0001).

Transfusion of fresh RBCs, with or without prior NO exposure, did not alter the PVRI.

Finally, the researchers found that treating stored RBCs with the NO donor compound MAHMA NONOate prevented transfusion-associated pulmonary hypertension and pulmonary vasoconstriction in awake lambs.

The team said studies with human RBCs are required to confirm the beneficial effects of NO exposure observed in this study.

Cancer patient

receiving treatment

Photo by Rhoda Baer

The American Cancer Society and National Cancer Institute have launched an online tool for cancer patients and survivors.

The tool, Springboard Beyond Cancer, was designed to help these individuals address medical, psychosocial, and wellness needs during and after treatment.

Springboard Beyond Cancer provides information to help cancer patients and survivors manage ongoing cancer-related symptoms, deal with stress, ensure healthy behavior, communicate better with healthcare teams, and seek support from friends and family.

“With Springboard Beyond Cancer, we want to empower cancer survivors by giving them the information they need to help identify issues, set goals, and create a plan to more smoothly navigate the cancer journey and take control of their health,” said Corinne Leach, PhD, a behavioral scientist and strategic director in the Behavioral Research Center at the American Cancer Society.

“We hope that Springboard Beyond Cancer, along with the close collaboration of their medical team, can help cancer survivors reduce their disease burden and improve their overall wellbeing,” added Erik Augustson, PhD, program director at the National Cancer Institute.

Cancer patient

receiving treatment

Photo by Rhoda Baer

The American Cancer Society and National Cancer Institute have launched an online tool for cancer patients and survivors.

The tool, Springboard Beyond Cancer, was designed to help these individuals address medical, psychosocial, and wellness needs during and after treatment.

Springboard Beyond Cancer provides information to help cancer patients and survivors manage ongoing cancer-related symptoms, deal with stress, ensure healthy behavior, communicate better with healthcare teams, and seek support from friends and family.

“With Springboard Beyond Cancer, we want to empower cancer survivors by giving them the information they need to help identify issues, set goals, and create a plan to more smoothly navigate the cancer journey and take control of their health,” said Corinne Leach, PhD, a behavioral scientist and strategic director in the Behavioral Research Center at the American Cancer Society.

“We hope that Springboard Beyond Cancer, along with the close collaboration of their medical team, can help cancer survivors reduce their disease burden and improve their overall wellbeing,” added Erik Augustson, PhD, program director at the National Cancer Institute.

Cancer patient

receiving treatment

Photo by Rhoda Baer

The American Cancer Society and National Cancer Institute have launched an online tool for cancer patients and survivors.

The tool, Springboard Beyond Cancer, was designed to help these individuals address medical, psychosocial, and wellness needs during and after treatment.

Springboard Beyond Cancer provides information to help cancer patients and survivors manage ongoing cancer-related symptoms, deal with stress, ensure healthy behavior, communicate better with healthcare teams, and seek support from friends and family.

“With Springboard Beyond Cancer, we want to empower cancer survivors by giving them the information they need to help identify issues, set goals, and create a plan to more smoothly navigate the cancer journey and take control of their health,” said Corinne Leach, PhD, a behavioral scientist and strategic director in the Behavioral Research Center at the American Cancer Society.

“We hope that Springboard Beyond Cancer, along with the close collaboration of their medical team, can help cancer survivors reduce their disease burden and improve their overall wellbeing,” added Erik Augustson, PhD, program director at the National Cancer Institute.

 

 

Blood sample collection

Photo by Juan D. Alfonso

 

A blood test can reveal genetic features linked to outcomes in patients with diffuse large B-cell lymphoma (DLBCL), according to research published in Science Translational Medicine.

Investigators used targeted sequencing to analyze circulating tumor DNA (ctDNA) in blood samples from DLBCL patients.

This allowed the team to identify the cell of origin, detect minimal residual disease (MRD), and predict progression-free survival (PFS) in these patients.

Florian Scherer, MD, of Stanford University in California, and his colleagues conducted this research.

They used cancer personalized profiling by deep sequencing (CAPP-Seq) to analyze tumor biopsies and cell-free DNA samples from 92 patients with DLBCL and 24 healthy controls.

The investigators found that CAPP-Seq could effectively detect somatic mutations in DLBCL plasma samples as well as tumor biopsies. They said their results suggest ctDNA is a “robust surrogate for direct assessment of primary tumor genotypes” in most DLBCL patients.

In addition, ctDNA profiling with CAPP-Seq revealed mutations associated with resistance to the BTK inhibitor ibrutinib.

The investigators also said their results suggest ctDNA profiling can be used to classify DLBCL subtypes. The overall concordance in cell of origin predictions between tumor tissue and plasma genotyping was 88%.

Another key finding of this study is that the amount of ctDNA at DLBCL diagnosis was predictive of PFS. The investigators said higher ctDNA levels at diagnosis were “continuously and independently” correlated with inferior PFS.

Dr Scherer and his colleagues also discovered that ctDNA profiling could detect MRD with greater accuracy than immunoglobulin sequencing and radiographic imaging. And patients with ctDNA in their plasma had significantly worse PFS than patients with undetectable ctDNA.

Finally, the investigators found evidence to suggest that ctDNA profiling could provide early detection of disease transformation. They identified “distinct patterns of clonal evolution” by which they could distinguish indolent follicular lymphomas from follicular lymphomas that transformed into DLBCL.

 

 

Blood sample collection

Photo by Juan D. Alfonso

 

A blood test can reveal genetic features linked to outcomes in patients with diffuse large B-cell lymphoma (DLBCL), according to research published in Science Translational Medicine.

Investigators used targeted sequencing to analyze circulating tumor DNA (ctDNA) in blood samples from DLBCL patients.

This allowed the team to identify the cell of origin, detect minimal residual disease (MRD), and predict progression-free survival (PFS) in these patients.

Florian Scherer, MD, of Stanford University in California, and his colleagues conducted this research.

They used cancer personalized profiling by deep sequencing (CAPP-Seq) to analyze tumor biopsies and cell-free DNA samples from 92 patients with DLBCL and 24 healthy controls.

The investigators found that CAPP-Seq could effectively detect somatic mutations in DLBCL plasma samples as well as tumor biopsies. They said their results suggest ctDNA is a “robust surrogate for direct assessment of primary tumor genotypes” in most DLBCL patients.

In addition, ctDNA profiling with CAPP-Seq revealed mutations associated with resistance to the BTK inhibitor ibrutinib.

The investigators also said their results suggest ctDNA profiling can be used to classify DLBCL subtypes. The overall concordance in cell of origin predictions between tumor tissue and plasma genotyping was 88%.

Another key finding of this study is that the amount of ctDNA at DLBCL diagnosis was predictive of PFS. The investigators said higher ctDNA levels at diagnosis were “continuously and independently” correlated with inferior PFS.

Dr Scherer and his colleagues also discovered that ctDNA profiling could detect MRD with greater accuracy than immunoglobulin sequencing and radiographic imaging. And patients with ctDNA in their plasma had significantly worse PFS than patients with undetectable ctDNA.

Finally, the investigators found evidence to suggest that ctDNA profiling could provide early detection of disease transformation. They identified “distinct patterns of clonal evolution” by which they could distinguish indolent follicular lymphomas from follicular lymphomas that transformed into DLBCL.

 

 

Blood sample collection

Photo by Juan D. Alfonso

 

A blood test can reveal genetic features linked to outcomes in patients with diffuse large B-cell lymphoma (DLBCL), according to research published in Science Translational Medicine.

Investigators used targeted sequencing to analyze circulating tumor DNA (ctDNA) in blood samples from DLBCL patients.

This allowed the team to identify the cell of origin, detect minimal residual disease (MRD), and predict progression-free survival (PFS) in these patients.

Florian Scherer, MD, of Stanford University in California, and his colleagues conducted this research.

They used cancer personalized profiling by deep sequencing (CAPP-Seq) to analyze tumor biopsies and cell-free DNA samples from 92 patients with DLBCL and 24 healthy controls.

The investigators found that CAPP-Seq could effectively detect somatic mutations in DLBCL plasma samples as well as tumor biopsies. They said their results suggest ctDNA is a “robust surrogate for direct assessment of primary tumor genotypes” in most DLBCL patients.

In addition, ctDNA profiling with CAPP-Seq revealed mutations associated with resistance to the BTK inhibitor ibrutinib.

The investigators also said their results suggest ctDNA profiling can be used to classify DLBCL subtypes. The overall concordance in cell of origin predictions between tumor tissue and plasma genotyping was 88%.

Another key finding of this study is that the amount of ctDNA at DLBCL diagnosis was predictive of PFS. The investigators said higher ctDNA levels at diagnosis were “continuously and independently” correlated with inferior PFS.

Dr Scherer and his colleagues also discovered that ctDNA profiling could detect MRD with greater accuracy than immunoglobulin sequencing and radiographic imaging. And patients with ctDNA in their plasma had significantly worse PFS than patients with undetectable ctDNA.

Finally, the investigators found evidence to suggest that ctDNA profiling could provide early detection of disease transformation. They identified “distinct patterns of clonal evolution” by which they could distinguish indolent follicular lymphomas from follicular lymphomas that transformed into DLBCL.

The experimental Ebola treatment ZMapp, which is composed of 3 different monoclonal antibodies, prevents progression of Ebola virus disease by targeting the main surface protein of the virus. According to findings from the clinical trial PREVAIL II, ZMapp is safe and well tolerated. But because the Ebola epidemic is “waning,” NIH says, the study enrolled too few people to determine definitively whether it is a better treatment than the best available standard of care.

Related: Novel Treatment for Ebola Virus

The study involved 72 men and women with confirmed infection. However, the researchers closed the study early because they could not enroll the target number of 200 participants due to the decline in cases. All patients received the optimized standard of care—IV fluids, electrolyte balance, maintaining oxygen and blood pressure levels—and half also received 3 IV infusions of ZMapp 3 days apart.

At 28 days, 13 of the 35 patients (37%) in the standard care group had died, compared with 8 of 36 (22%) in the ZMapp group. That difference, a 40% lower risk of death with ZMapp, still did not reach statistical significance.

Related: Ebola Virus Persists in Semen Long Term

The findings are “promising and provide valuable scientific data,” says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases. Moreover, he adds, “Importantly, the study establishes that it is feasible to conduct a randomized, controlled trial during a major public health emergency in a scientifically and ethically sound manner.”

The experimental Ebola treatment ZMapp, which is composed of 3 different monoclonal antibodies, prevents progression of Ebola virus disease by targeting the main surface protein of the virus. According to findings from the clinical trial PREVAIL II, ZMapp is safe and well tolerated. But because the Ebola epidemic is “waning,” NIH says, the study enrolled too few people to determine definitively whether it is a better treatment than the best available standard of care.

Related: Novel Treatment for Ebola Virus

The study involved 72 men and women with confirmed infection. However, the researchers closed the study early because they could not enroll the target number of 200 participants due to the decline in cases. All patients received the optimized standard of care—IV fluids, electrolyte balance, maintaining oxygen and blood pressure levels—and half also received 3 IV infusions of ZMapp 3 days apart.

At 28 days, 13 of the 35 patients (37%) in the standard care group had died, compared with 8 of 36 (22%) in the ZMapp group. That difference, a 40% lower risk of death with ZMapp, still did not reach statistical significance.

Related: Ebola Virus Persists in Semen Long Term

The findings are “promising and provide valuable scientific data,” says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases. Moreover, he adds, “Importantly, the study establishes that it is feasible to conduct a randomized, controlled trial during a major public health emergency in a scientifically and ethically sound manner.”

The experimental Ebola treatment ZMapp, which is composed of 3 different monoclonal antibodies, prevents progression of Ebola virus disease by targeting the main surface protein of the virus. According to findings from the clinical trial PREVAIL II, ZMapp is safe and well tolerated. But because the Ebola epidemic is “waning,” NIH says, the study enrolled too few people to determine definitively whether it is a better treatment than the best available standard of care.

Related: Novel Treatment for Ebola Virus

The study involved 72 men and women with confirmed infection. However, the researchers closed the study early because they could not enroll the target number of 200 participants due to the decline in cases. All patients received the optimized standard of care—IV fluids, electrolyte balance, maintaining oxygen and blood pressure levels—and half also received 3 IV infusions of ZMapp 3 days apart.

At 28 days, 13 of the 35 patients (37%) in the standard care group had died, compared with 8 of 36 (22%) in the ZMapp group. That difference, a 40% lower risk of death with ZMapp, still did not reach statistical significance.

Related: Ebola Virus Persists in Semen Long Term

The findings are “promising and provide valuable scientific data,” says Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases. Moreover, he adds, “Importantly, the study establishes that it is feasible to conduct a randomized, controlled trial during a major public health emergency in a scientifically and ethically sound manner.”

Based on the pattern of the rash and the patient’s history, the family physician (FP) considered tinea corporis and cruris, but the history of failing treatment seemed unusual. The FP also considered a diagnosis of pityriasis rubra pilaris because he observed a “skip” area on the left thigh.

The FP performed a potassium hydroxide (KOH) preparation using a fungal stain and found branching septate hyphae. (See video on how to perform a KOH preparation here.) He also wondered if the failed treatment was secondary to inadequate dosing or duration of the oral medicines previously used, given that the patient was 6 feet, 5 inches tall and weighed more than 250 pounds. The patient didn’t have liver disease and rarely drank alcohol. Baseline liver function tests (LFTs) were within normal limits.

The FP told the patient to use oral terbinafine for one month rather than the recommended 2 weeks. One month later, there was less erythema and scaling, but the rash had not completely resolved. At that time, the FP and patient decided together to do a punch biopsy to make sure the diagnosis was correct. The punch biopsy supported the diagnosis of tinea with a positive periodic acid–Schiff stain for fungal elements; no other pathology was noted.

Since the LFTs were still normal, the FP and patient discussed a second month of treatment. The FP also performed a fungal culture and requested that the lab test the fungus for identification and sensitivities. Two weeks later, the results showed Trichophyton rubrum that was sensitive to all oral antifungal medications tested, including terbinafine.

At this point, the FP became concerned about the patient’s immune system, so he ordered a complete blood count (CBC) and human immunodeficiency virus (HIV) test. The CBC came back normal and the HIV test was negative. At the end of the second month, the fungal infection was still present clinically and the KOH preparation was still positive.

The FP offered oral itraconazole 100 mg/d and the patient was happy to try another therapy. The LFTs remained normal and after one month of itraconazole, the tinea was still present. At this point, the patient decided that he could live with the condition and would use a topical antifungal when the rash was itchy.

This case demonstrates a situation in which the patient’s immune system is “blind” to the foreign fungus. This has been known to happen with human papillomavirus, when patients have warts that do not resolve even with the most aggressive therapies.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Smith M. Tinea cruris. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:795-798.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Based on the pattern of the rash and the patient’s history, the family physician (FP) considered tinea corporis and cruris, but the history of failing treatment seemed unusual. The FP also considered a diagnosis of pityriasis rubra pilaris because he observed a “skip” area on the left thigh.

The FP performed a potassium hydroxide (KOH) preparation using a fungal stain and found branching septate hyphae. (See video on how to perform a KOH preparation here.) He also wondered if the failed treatment was secondary to inadequate dosing or duration of the oral medicines previously used, given that the patient was 6 feet, 5 inches tall and weighed more than 250 pounds. The patient didn’t have liver disease and rarely drank alcohol. Baseline liver function tests (LFTs) were within normal limits.

The FP told the patient to use oral terbinafine for one month rather than the recommended 2 weeks. One month later, there was less erythema and scaling, but the rash had not completely resolved. At that time, the FP and patient decided together to do a punch biopsy to make sure the diagnosis was correct. The punch biopsy supported the diagnosis of tinea with a positive periodic acid–Schiff stain for fungal elements; no other pathology was noted.

Since the LFTs were still normal, the FP and patient discussed a second month of treatment. The FP also performed a fungal culture and requested that the lab test the fungus for identification and sensitivities. Two weeks later, the results showed Trichophyton rubrum that was sensitive to all oral antifungal medications tested, including terbinafine.

At this point, the FP became concerned about the patient’s immune system, so he ordered a complete blood count (CBC) and human immunodeficiency virus (HIV) test. The CBC came back normal and the HIV test was negative. At the end of the second month, the fungal infection was still present clinically and the KOH preparation was still positive.

The FP offered oral itraconazole 100 mg/d and the patient was happy to try another therapy. The LFTs remained normal and after one month of itraconazole, the tinea was still present. At this point, the patient decided that he could live with the condition and would use a topical antifungal when the rash was itchy.

This case demonstrates a situation in which the patient’s immune system is “blind” to the foreign fungus. This has been known to happen with human papillomavirus, when patients have warts that do not resolve even with the most aggressive therapies.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Smith M. Tinea cruris. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:795-798.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Based on the pattern of the rash and the patient’s history, the family physician (FP) considered tinea corporis and cruris, but the history of failing treatment seemed unusual. The FP also considered a diagnosis of pityriasis rubra pilaris because he observed a “skip” area on the left thigh.

The FP performed a potassium hydroxide (KOH) preparation using a fungal stain and found branching septate hyphae. (See video on how to perform a KOH preparation here.) He also wondered if the failed treatment was secondary to inadequate dosing or duration of the oral medicines previously used, given that the patient was 6 feet, 5 inches tall and weighed more than 250 pounds. The patient didn’t have liver disease and rarely drank alcohol. Baseline liver function tests (LFTs) were within normal limits.

The FP told the patient to use oral terbinafine for one month rather than the recommended 2 weeks. One month later, there was less erythema and scaling, but the rash had not completely resolved. At that time, the FP and patient decided together to do a punch biopsy to make sure the diagnosis was correct. The punch biopsy supported the diagnosis of tinea with a positive periodic acid–Schiff stain for fungal elements; no other pathology was noted.

Since the LFTs were still normal, the FP and patient discussed a second month of treatment. The FP also performed a fungal culture and requested that the lab test the fungus for identification and sensitivities. Two weeks later, the results showed Trichophyton rubrum that was sensitive to all oral antifungal medications tested, including terbinafine.

At this point, the FP became concerned about the patient’s immune system, so he ordered a complete blood count (CBC) and human immunodeficiency virus (HIV) test. The CBC came back normal and the HIV test was negative. At the end of the second month, the fungal infection was still present clinically and the KOH preparation was still positive.

The FP offered oral itraconazole 100 mg/d and the patient was happy to try another therapy. The LFTs remained normal and after one month of itraconazole, the tinea was still present. At this point, the patient decided that he could live with the condition and would use a topical antifungal when the rash was itchy.

This case demonstrates a situation in which the patient’s immune system is “blind” to the foreign fungus. This has been known to happen with human papillomavirus, when patients have warts that do not resolve even with the most aggressive therapies.

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R, Smith M. Tinea cruris. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:795-798.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

ANSWER

The correct diagnosis in this case is juvenile xanthogranuloma (JXG; choice “d”).

Anderson-Fabry disease (choice “a”) is a rare inherited disorder characterized by widespread red papules; these lesions, however, are much smaller and far more widespread than those of JXG.

Considered a possibility at initial presentation, molluscum contagiosum (choice “b”) was quickly ruled out upon further inspection. This patient’s condition lacked the typical features of molluscum: umbilicated, white, firm papules caused by a pox virus. 

Eruptive xanthomata (choice “c”) is a collection of lipid-laden macrophages caused by hypertriglyceridemia. They present as papules and nodules under, rather than on, the skin.

DISCUSSION

Solitary JXG lesions are fairly common, developing on the trunk, face, or extremities as smooth, reddish brown to cream papules. Typically, they cause no problems—but when multiple lesions manifest at birth, the condition can affect the eye (especially the iris, as in this case).

JXG is considered a form of histiocytosis, specifically classified as a type II non-Langerhans cell-mediated lesion. It is believed to result from a disordered macrophage response to a nonspecific tissue injury, which leads to a distinct variety of granulomatous change. These lesions are part of a spectrum of related conditions that also includes Langerhans cell histiocytosis.

No perfect treatment exists for this patient’s multitudinous skin lesions, because her darker skin could easily be permanently changed by burning, freezing, laser, or other destructive modality. Fair or not, in many cases, insurance coverage (or lack thereof) ultimately dictates what treatment is used.

Once the biopsy confirmed the diagnosis and effectively ruled out the other items in the differential, she was referred to ophthalmology for ongoing care of her eyes. Beyond that, she’ll need an annual physical with labs, because JXG is known to affect internal organs as well.

ANSWER

The correct diagnosis in this case is juvenile xanthogranuloma (JXG; choice “d”).

Anderson-Fabry disease (choice “a”) is a rare inherited disorder characterized by widespread red papules; these lesions, however, are much smaller and far more widespread than those of JXG.

Considered a possibility at initial presentation, molluscum contagiosum (choice “b”) was quickly ruled out upon further inspection. This patient’s condition lacked the typical features of molluscum: umbilicated, white, firm papules caused by a pox virus. 

Eruptive xanthomata (choice “c”) is a collection of lipid-laden macrophages caused by hypertriglyceridemia. They present as papules and nodules under, rather than on, the skin.

DISCUSSION

Solitary JXG lesions are fairly common, developing on the trunk, face, or extremities as smooth, reddish brown to cream papules. Typically, they cause no problems—but when multiple lesions manifest at birth, the condition can affect the eye (especially the iris, as in this case).

JXG is considered a form of histiocytosis, specifically classified as a type II non-Langerhans cell-mediated lesion. It is believed to result from a disordered macrophage response to a nonspecific tissue injury, which leads to a distinct variety of granulomatous change. These lesions are part of a spectrum of related conditions that also includes Langerhans cell histiocytosis.

No perfect treatment exists for this patient’s multitudinous skin lesions, because her darker skin could easily be permanently changed by burning, freezing, laser, or other destructive modality. Fair or not, in many cases, insurance coverage (or lack thereof) ultimately dictates what treatment is used.

Once the biopsy confirmed the diagnosis and effectively ruled out the other items in the differential, she was referred to ophthalmology for ongoing care of her eyes. Beyond that, she’ll need an annual physical with labs, because JXG is known to affect internal organs as well.

ANSWER

The correct diagnosis in this case is juvenile xanthogranuloma (JXG; choice “d”).

Anderson-Fabry disease (choice “a”) is a rare inherited disorder characterized by widespread red papules; these lesions, however, are much smaller and far more widespread than those of JXG.

Considered a possibility at initial presentation, molluscum contagiosum (choice “b”) was quickly ruled out upon further inspection. This patient’s condition lacked the typical features of molluscum: umbilicated, white, firm papules caused by a pox virus. 

Eruptive xanthomata (choice “c”) is a collection of lipid-laden macrophages caused by hypertriglyceridemia. They present as papules and nodules under, rather than on, the skin.

DISCUSSION

Solitary JXG lesions are fairly common, developing on the trunk, face, or extremities as smooth, reddish brown to cream papules. Typically, they cause no problems—but when multiple lesions manifest at birth, the condition can affect the eye (especially the iris, as in this case).

JXG is considered a form of histiocytosis, specifically classified as a type II non-Langerhans cell-mediated lesion. It is believed to result from a disordered macrophage response to a nonspecific tissue injury, which leads to a distinct variety of granulomatous change. These lesions are part of a spectrum of related conditions that also includes Langerhans cell histiocytosis.

No perfect treatment exists for this patient’s multitudinous skin lesions, because her darker skin could easily be permanently changed by burning, freezing, laser, or other destructive modality. Fair or not, in many cases, insurance coverage (or lack thereof) ultimately dictates what treatment is used.

Once the biopsy confirmed the diagnosis and effectively ruled out the other items in the differential, she was referred to ophthalmology for ongoing care of her eyes. Beyond that, she’ll need an annual physical with labs, because JXG is known to affect internal organs as well.