Facial symmetry plays a role in attractiveness, but a small degree of asymmetry is normal and more common than symmetry. Mild asymmetry has been noted in the general population, even in the absence of pathology such as trauma or craniosynostosis.^1,2 Asymmetry may be static or dynamic and is thought to arise from a multitude of developmental factors, including skeletal, neurologic, and soft tissue changes, as well as photoaging.^3-5 Cosmetic and reconstructive surgical procedures strive to achieve facial symmetry. Patients often are unaware of their preexisting facial asymmetry.⁶ Anecdotally, we have found patients tend to be more cognizant of preexisting facial asymmetry following a notable change in facial appearance (eg, surgery). In counseling patients who are considering reconstructive or cosmetic surgery, it is beneficial to identify any preexisting facial asymmetries and discuss if they are within normal limits. The current literature, however, lacks thresholds for what is considered normal in many cases. In this study, we reviewed 100 faces without unilateral or orbital pathology or diplopia to describe the occurrence of facial asymmetries, including larger hemiface and hemiface with greater excursion of motion upon smiling (interpreted to signify stronger seventh cranial nerve), hemiface with more rhytides at rest, higher globe, higher earlobe, and higher lip.

Methods

One hundred oculofacial surgery patients without unilateral or orbital pathology or diplopia were included in this retrospective evaluation of static and dynamic facial asymmetry via facial photography (100 participants). Three graders were provided standard frontal and frontal smiling photographs with overlying facial grids to aid in assessing larger hemiface and hemiface with stronger seventh cranial nerve, which was judged in smiling photographs by assessing the excursion and the vector of motion; more rhytides at rest; higher globe; higher earlobe; and higher lip. Difference in globe height was measured relative to interpupillary distance (IPD) and recorded as the ratio of difference in globe height to IPD. The data were analyzed to see if there were any correlations among the 6 variables. This study was approved by the Duke University Health System (Durham, North Carolina) institutional review board.

Results

One hundred photographs were analyzed including 82 women aged 42 to 85 years and 18 men aged 22 to 88 years (overall average age, 61.64 years). The average difference in globe height was 1.2% of IPD; the maximum was 4.4% of IPD. The difference in globe height was verified by 3 graders via 2 different methods. Fifty-four patients were found to have a larger right hemiface, 36 had a larger left hemiface, and 10 had symmetrically sized hemifaces. Nearly half of patients were judged to have greater seventh cranial nerve action on the left (n=47), approximately one-quarter had greater action on the right (n=28), and another quarter were judged to have equal action (n=25). Most patients had static facial asymmetry; 72 had rhytides more pronounced on one hemiface compared to the other, 79 with a difference in globe height, and 68 with a difference in lip height. In approximately 40% of photographs, the graders were unable to judge earlobe height difference; therefore, this data was not analyzed. There was no correlation among the 6 variables.

Discussion

Facial asymmetry has long been a topic of interest in the plastic and reconstructive surgery fields. Ercan et al⁷ used statistical shape analysis to study facial asymmetry in young healthy subjects and found the left hemiface to be larger than the right hemiface in both sexes. Smith⁴ evaluated facial asymmetry in healthy college students and found the left hemiface to be larger in males and the right hemiface to be larger in females. Our group was predominantly female, but we found the right hemiface to be larger in both females and males, similar to the findings of Lepich et al.⁸

We also found that most patients had static and dynamic facial asymmetry despite no known unilateral pathology. The present literature lacks normative values to help determine what degree of asymmetry should be considered pathologic. Vertical orbital dystopia is defined as an inequality in the horizontal levels of the whole orbits.⁹ It has been hypothesized that most vertical dystopia is caused by congenital malformations, but no threshold has been set for the difference in height that qualifies as dystopia.¹⁰ Regarding the difference we found in globe height relative to IPD, if one takes the mean IPD of 63.36 mm (based on a study of 3976 American adults aged 17–51 years)¹¹ and makes the assumption that our patients have this IPD, then one can extrapolate that on average there was a difference of 0.76 mm between the 2 globe heights. Likewise, nearly all patients (n=96) had less than a 2-mm difference (21 had symmetric globe heights, 46 had a difference in globe height of <1 mm, and 29 had a difference of >1 mm and <2 mm). Four patients had a difference greater than 2 mm, with the largest difference being 2.75 mm. A limitation of this retrospective study is the need to extrapolate these distances, as our patients were not photographed with rulers.

Hafezi et al¹² looked at the facial asymmetry in patients without history of trauma or nasal fracture who were seeking rhinoplasty. They noted vertical orbital dystopia in this patient population, but the degree of dystopia was not quantified.¹² We believe our data highlight the importance of counseling patients about preexisting facial asymmetry with normative values in mind. Patients may be dissatisfied by new or preexisting asymmetry following surgery, even if such asymmetries are less objectively apparent than in the patient’s preoperative appearance. Even when patients are already acutely aware of their facial asymmetries, they should learn that facial asymmetries, to varying degrees, are natural and not necessarily unattractive. In fact, a 2006 study of ocular adnexal asymmetry in 102 models with magazine photograph analysis found small amounts of asymmetry to be the norm. Specifically, the authors found an average difference in globe height of 1.2 mm, slightly greater than the average found among our patients.¹³ Our data will help to establish normative values for asymmetry in normal faces.

Facial symmetry plays a role in attractiveness, but a small degree of asymmetry is normal and more common than symmetry. Mild asymmetry has been noted in the general population, even in the absence of pathology such as trauma or craniosynostosis.^1,2 Asymmetry may be static or dynamic and is thought to arise from a multitude of developmental factors, including skeletal, neurologic, and soft tissue changes, as well as photoaging.^3-5 Cosmetic and reconstructive surgical procedures strive to achieve facial symmetry. Patients often are unaware of their preexisting facial asymmetry.⁶ Anecdotally, we have found patients tend to be more cognizant of preexisting facial asymmetry following a notable change in facial appearance (eg, surgery). In counseling patients who are considering reconstructive or cosmetic surgery, it is beneficial to identify any preexisting facial asymmetries and discuss if they are within normal limits. The current literature, however, lacks thresholds for what is considered normal in many cases. In this study, we reviewed 100 faces without unilateral or orbital pathology or diplopia to describe the occurrence of facial asymmetries, including larger hemiface and hemiface with greater excursion of motion upon smiling (interpreted to signify stronger seventh cranial nerve), hemiface with more rhytides at rest, higher globe, higher earlobe, and higher lip.

Methods

One hundred oculofacial surgery patients without unilateral or orbital pathology or diplopia were included in this retrospective evaluation of static and dynamic facial asymmetry via facial photography (100 participants). Three graders were provided standard frontal and frontal smiling photographs with overlying facial grids to aid in assessing larger hemiface and hemiface with stronger seventh cranial nerve, which was judged in smiling photographs by assessing the excursion and the vector of motion; more rhytides at rest; higher globe; higher earlobe; and higher lip. Difference in globe height was measured relative to interpupillary distance (IPD) and recorded as the ratio of difference in globe height to IPD. The data were analyzed to see if there were any correlations among the 6 variables. This study was approved by the Duke University Health System (Durham, North Carolina) institutional review board.

Results

One hundred photographs were analyzed including 82 women aged 42 to 85 years and 18 men aged 22 to 88 years (overall average age, 61.64 years). The average difference in globe height was 1.2% of IPD; the maximum was 4.4% of IPD. The difference in globe height was verified by 3 graders via 2 different methods. Fifty-four patients were found to have a larger right hemiface, 36 had a larger left hemiface, and 10 had symmetrically sized hemifaces. Nearly half of patients were judged to have greater seventh cranial nerve action on the left (n=47), approximately one-quarter had greater action on the right (n=28), and another quarter were judged to have equal action (n=25). Most patients had static facial asymmetry; 72 had rhytides more pronounced on one hemiface compared to the other, 79 with a difference in globe height, and 68 with a difference in lip height. In approximately 40% of photographs, the graders were unable to judge earlobe height difference; therefore, this data was not analyzed. There was no correlation among the 6 variables.

Discussion

Facial asymmetry has long been a topic of interest in the plastic and reconstructive surgery fields. Ercan et al⁷ used statistical shape analysis to study facial asymmetry in young healthy subjects and found the left hemiface to be larger than the right hemiface in both sexes. Smith⁴ evaluated facial asymmetry in healthy college students and found the left hemiface to be larger in males and the right hemiface to be larger in females. Our group was predominantly female, but we found the right hemiface to be larger in both females and males, similar to the findings of Lepich et al.⁸

We also found that most patients had static and dynamic facial asymmetry despite no known unilateral pathology. The present literature lacks normative values to help determine what degree of asymmetry should be considered pathologic. Vertical orbital dystopia is defined as an inequality in the horizontal levels of the whole orbits.⁹ It has been hypothesized that most vertical dystopia is caused by congenital malformations, but no threshold has been set for the difference in height that qualifies as dystopia.¹⁰ Regarding the difference we found in globe height relative to IPD, if one takes the mean IPD of 63.36 mm (based on a study of 3976 American adults aged 17–51 years)¹¹ and makes the assumption that our patients have this IPD, then one can extrapolate that on average there was a difference of 0.76 mm between the 2 globe heights. Likewise, nearly all patients (n=96) had less than a 2-mm difference (21 had symmetric globe heights, 46 had a difference in globe height of <1 mm, and 29 had a difference of >1 mm and <2 mm). Four patients had a difference greater than 2 mm, with the largest difference being 2.75 mm. A limitation of this retrospective study is the need to extrapolate these distances, as our patients were not photographed with rulers.

Hafezi et al¹² looked at the facial asymmetry in patients without history of trauma or nasal fracture who were seeking rhinoplasty. They noted vertical orbital dystopia in this patient population, but the degree of dystopia was not quantified.¹² We believe our data highlight the importance of counseling patients about preexisting facial asymmetry with normative values in mind. Patients may be dissatisfied by new or preexisting asymmetry following surgery, even if such asymmetries are less objectively apparent than in the patient’s preoperative appearance. Even when patients are already acutely aware of their facial asymmetries, they should learn that facial asymmetries, to varying degrees, are natural and not necessarily unattractive. In fact, a 2006 study of ocular adnexal asymmetry in 102 models with magazine photograph analysis found small amounts of asymmetry to be the norm. Specifically, the authors found an average difference in globe height of 1.2 mm, slightly greater than the average found among our patients.¹³ Our data will help to establish normative values for asymmetry in normal faces.

Facial symmetry plays a role in attractiveness, but a small degree of asymmetry is normal and more common than symmetry. Mild asymmetry has been noted in the general population, even in the absence of pathology such as trauma or craniosynostosis.^1,2 Asymmetry may be static or dynamic and is thought to arise from a multitude of developmental factors, including skeletal, neurologic, and soft tissue changes, as well as photoaging.^3-5 Cosmetic and reconstructive surgical procedures strive to achieve facial symmetry. Patients often are unaware of their preexisting facial asymmetry.⁶ Anecdotally, we have found patients tend to be more cognizant of preexisting facial asymmetry following a notable change in facial appearance (eg, surgery). In counseling patients who are considering reconstructive or cosmetic surgery, it is beneficial to identify any preexisting facial asymmetries and discuss if they are within normal limits. The current literature, however, lacks thresholds for what is considered normal in many cases. In this study, we reviewed 100 faces without unilateral or orbital pathology or diplopia to describe the occurrence of facial asymmetries, including larger hemiface and hemiface with greater excursion of motion upon smiling (interpreted to signify stronger seventh cranial nerve), hemiface with more rhytides at rest, higher globe, higher earlobe, and higher lip.

Methods

One hundred oculofacial surgery patients without unilateral or orbital pathology or diplopia were included in this retrospective evaluation of static and dynamic facial asymmetry via facial photography (100 participants). Three graders were provided standard frontal and frontal smiling photographs with overlying facial grids to aid in assessing larger hemiface and hemiface with stronger seventh cranial nerve, which was judged in smiling photographs by assessing the excursion and the vector of motion; more rhytides at rest; higher globe; higher earlobe; and higher lip. Difference in globe height was measured relative to interpupillary distance (IPD) and recorded as the ratio of difference in globe height to IPD. The data were analyzed to see if there were any correlations among the 6 variables. This study was approved by the Duke University Health System (Durham, North Carolina) institutional review board.

Results

One hundred photographs were analyzed including 82 women aged 42 to 85 years and 18 men aged 22 to 88 years (overall average age, 61.64 years). The average difference in globe height was 1.2% of IPD; the maximum was 4.4% of IPD. The difference in globe height was verified by 3 graders via 2 different methods. Fifty-four patients were found to have a larger right hemiface, 36 had a larger left hemiface, and 10 had symmetrically sized hemifaces. Nearly half of patients were judged to have greater seventh cranial nerve action on the left (n=47), approximately one-quarter had greater action on the right (n=28), and another quarter were judged to have equal action (n=25). Most patients had static facial asymmetry; 72 had rhytides more pronounced on one hemiface compared to the other, 79 with a difference in globe height, and 68 with a difference in lip height. In approximately 40% of photographs, the graders were unable to judge earlobe height difference; therefore, this data was not analyzed. There was no correlation among the 6 variables.

Discussion

Facial asymmetry has long been a topic of interest in the plastic and reconstructive surgery fields. Ercan et al⁷ used statistical shape analysis to study facial asymmetry in young healthy subjects and found the left hemiface to be larger than the right hemiface in both sexes. Smith⁴ evaluated facial asymmetry in healthy college students and found the left hemiface to be larger in males and the right hemiface to be larger in females. Our group was predominantly female, but we found the right hemiface to be larger in both females and males, similar to the findings of Lepich et al.⁸

We also found that most patients had static and dynamic facial asymmetry despite no known unilateral pathology. The present literature lacks normative values to help determine what degree of asymmetry should be considered pathologic. Vertical orbital dystopia is defined as an inequality in the horizontal levels of the whole orbits.⁹ It has been hypothesized that most vertical dystopia is caused by congenital malformations, but no threshold has been set for the difference in height that qualifies as dystopia.¹⁰ Regarding the difference we found in globe height relative to IPD, if one takes the mean IPD of 63.36 mm (based on a study of 3976 American adults aged 17–51 years)¹¹ and makes the assumption that our patients have this IPD, then one can extrapolate that on average there was a difference of 0.76 mm between the 2 globe heights. Likewise, nearly all patients (n=96) had less than a 2-mm difference (21 had symmetric globe heights, 46 had a difference in globe height of <1 mm, and 29 had a difference of >1 mm and <2 mm). Four patients had a difference greater than 2 mm, with the largest difference being 2.75 mm. A limitation of this retrospective study is the need to extrapolate these distances, as our patients were not photographed with rulers.

Hafezi et al¹² looked at the facial asymmetry in patients without history of trauma or nasal fracture who were seeking rhinoplasty. They noted vertical orbital dystopia in this patient population, but the degree of dystopia was not quantified.¹² We believe our data highlight the importance of counseling patients about preexisting facial asymmetry with normative values in mind. Patients may be dissatisfied by new or preexisting asymmetry following surgery, even if such asymmetries are less objectively apparent than in the patient’s preoperative appearance. Even when patients are already acutely aware of their facial asymmetries, they should learn that facial asymmetries, to varying degrees, are natural and not necessarily unattractive. In fact, a 2006 study of ocular adnexal asymmetry in 102 models with magazine photograph analysis found small amounts of asymmetry to be the norm. Specifically, the authors found an average difference in globe height of 1.2 mm, slightly greater than the average found among our patients.¹³ Our data will help to establish normative values for asymmetry in normal faces.

ORLANDO – Neither metformin nor insulin glargine followed by metformin improved beta cell function in adolescents with impaired glucose tolerance or early type 2 diabetes mellitus (T2DM) in the pediatric medication portion of the Restoring Insulin Secretion (RISE) study.

The treatments, including either metformin for 12 months in 47 participants or insulin glargine for 3 months followed by metformin for 9 months in 44 participants, were not associated with improvement in beta cell function at 12 months, compared with baseline, according to reports from members of the RISE Consortium at the annual scientific sessions of the American Diabetes Association.

Furthermore, measures of beta cell function worsened in both groups at 15-month follow-up, and the same was true for participants with impaired glucose tolerance only; the outcomes in that subset of patients were similar to the entire group, including patients with early T2DM.

“Beta cell failure progressed despite that intervention, and though both [metformin and insulin glargine] were effective for lowering glucose – and metformin for lowering weight ... it had nothing to do with the natural history of the disease, and that’s really quite disappointing,” John B. Buse, MD, said in a video interview.

But that’s not to say the findings weren’t of value.

“The exciting bit was our greater understanding of what’s different about diabetes in youth, and basically [the findings] showed that, both in the setting of impaired glucose tolerance and early diabetes, youth have more insulin resistance than adults, they have relatively more well-preserved beta cell function – they’re secreting more insulin at both impaired glucose tolerance and diabetes, and they have lesser hepatic insulin clearance,” said Dr. Buse, professor, chief of the division of endocrinology, and director of the Diabetes Center at the University of North Carolina, Chapel Hill.

Dr. Buse provided invited commentary on the findings at the ADA scientific sessions and elaborated on those comments in this interview, noting that, in addition to identifying important differences between children and adults with impaired glucose tolerance and diabetes, the RISE study demonstrated that the numerous challenges associated with conducting a major study involving children with impaired glucose tolerance or T2DM can be overcome.

“It’s a really heartwarming story,” he said of the efforts and successes of the RISE investigators in completing the pediatric medication portion of the study. “It at least gives us hope that, even if we haven’t found a cure for type 2 diabetes in children, we at least know we can do the studies.”

Dr. Buse also provided his take on what the future holds for both parts of the RISE study (findings from the adult medication and adult surgery portions are expected to be reported within the next year) and for other studies in children and youth with diabetes; he noted that the current findings and successes in enrolling and completing the pediatric portion of the study highlight multiple opportunities for future research.

Dr. Buse reported financial relationships with Adocia, AstraZeneca, Dexcom, Elcelyx, Eli Lilly, Fractyl Laboratories, Intarcia Therapeutics, Lexicon Pharmaceuticals, Metavention, NovaTarg Therapeutics, Novo Nordisk, Sanofi, VTV Therapeutics, Boehringer Ingelheim, Johnson & Johnson Services, Theracos, Shenzhen Hightide Biopharmaceutical, National Heart Lung and Blood Institute, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association, Patient-Centered Outcomes Research Institute, and the National Institute of Environmental Health Sciences.

[email protected]

ORLANDO – Neither metformin nor insulin glargine followed by metformin improved beta cell function in adolescents with impaired glucose tolerance or early type 2 diabetes mellitus (T2DM) in the pediatric medication portion of the Restoring Insulin Secretion (RISE) study.

The treatments, including either metformin for 12 months in 47 participants or insulin glargine for 3 months followed by metformin for 9 months in 44 participants, were not associated with improvement in beta cell function at 12 months, compared with baseline, according to reports from members of the RISE Consortium at the annual scientific sessions of the American Diabetes Association.

Furthermore, measures of beta cell function worsened in both groups at 15-month follow-up, and the same was true for participants with impaired glucose tolerance only; the outcomes in that subset of patients were similar to the entire group, including patients with early T2DM.

“Beta cell failure progressed despite that intervention, and though both [metformin and insulin glargine] were effective for lowering glucose – and metformin for lowering weight ... it had nothing to do with the natural history of the disease, and that’s really quite disappointing,” John B. Buse, MD, said in a video interview.

But that’s not to say the findings weren’t of value.

“The exciting bit was our greater understanding of what’s different about diabetes in youth, and basically [the findings] showed that, both in the setting of impaired glucose tolerance and early diabetes, youth have more insulin resistance than adults, they have relatively more well-preserved beta cell function – they’re secreting more insulin at both impaired glucose tolerance and diabetes, and they have lesser hepatic insulin clearance,” said Dr. Buse, professor, chief of the division of endocrinology, and director of the Diabetes Center at the University of North Carolina, Chapel Hill.

Dr. Buse provided invited commentary on the findings at the ADA scientific sessions and elaborated on those comments in this interview, noting that, in addition to identifying important differences between children and adults with impaired glucose tolerance and diabetes, the RISE study demonstrated that the numerous challenges associated with conducting a major study involving children with impaired glucose tolerance or T2DM can be overcome.

“It’s a really heartwarming story,” he said of the efforts and successes of the RISE investigators in completing the pediatric medication portion of the study. “It at least gives us hope that, even if we haven’t found a cure for type 2 diabetes in children, we at least know we can do the studies.”

Dr. Buse also provided his take on what the future holds for both parts of the RISE study (findings from the adult medication and adult surgery portions are expected to be reported within the next year) and for other studies in children and youth with diabetes; he noted that the current findings and successes in enrolling and completing the pediatric portion of the study highlight multiple opportunities for future research.

Dr. Buse reported financial relationships with Adocia, AstraZeneca, Dexcom, Elcelyx, Eli Lilly, Fractyl Laboratories, Intarcia Therapeutics, Lexicon Pharmaceuticals, Metavention, NovaTarg Therapeutics, Novo Nordisk, Sanofi, VTV Therapeutics, Boehringer Ingelheim, Johnson & Johnson Services, Theracos, Shenzhen Hightide Biopharmaceutical, National Heart Lung and Blood Institute, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association, Patient-Centered Outcomes Research Institute, and the National Institute of Environmental Health Sciences.

[email protected]

ORLANDO – Neither metformin nor insulin glargine followed by metformin improved beta cell function in adolescents with impaired glucose tolerance or early type 2 diabetes mellitus (T2DM) in the pediatric medication portion of the Restoring Insulin Secretion (RISE) study.

The treatments, including either metformin for 12 months in 47 participants or insulin glargine for 3 months followed by metformin for 9 months in 44 participants, were not associated with improvement in beta cell function at 12 months, compared with baseline, according to reports from members of the RISE Consortium at the annual scientific sessions of the American Diabetes Association.

Furthermore, measures of beta cell function worsened in both groups at 15-month follow-up, and the same was true for participants with impaired glucose tolerance only; the outcomes in that subset of patients were similar to the entire group, including patients with early T2DM.

“Beta cell failure progressed despite that intervention, and though both [metformin and insulin glargine] were effective for lowering glucose – and metformin for lowering weight ... it had nothing to do with the natural history of the disease, and that’s really quite disappointing,” John B. Buse, MD, said in a video interview.

But that’s not to say the findings weren’t of value.

“The exciting bit was our greater understanding of what’s different about diabetes in youth, and basically [the findings] showed that, both in the setting of impaired glucose tolerance and early diabetes, youth have more insulin resistance than adults, they have relatively more well-preserved beta cell function – they’re secreting more insulin at both impaired glucose tolerance and diabetes, and they have lesser hepatic insulin clearance,” said Dr. Buse, professor, chief of the division of endocrinology, and director of the Diabetes Center at the University of North Carolina, Chapel Hill.

Dr. Buse provided invited commentary on the findings at the ADA scientific sessions and elaborated on those comments in this interview, noting that, in addition to identifying important differences between children and adults with impaired glucose tolerance and diabetes, the RISE study demonstrated that the numerous challenges associated with conducting a major study involving children with impaired glucose tolerance or T2DM can be overcome.

“It’s a really heartwarming story,” he said of the efforts and successes of the RISE investigators in completing the pediatric medication portion of the study. “It at least gives us hope that, even if we haven’t found a cure for type 2 diabetes in children, we at least know we can do the studies.”

Dr. Buse also provided his take on what the future holds for both parts of the RISE study (findings from the adult medication and adult surgery portions are expected to be reported within the next year) and for other studies in children and youth with diabetes; he noted that the current findings and successes in enrolling and completing the pediatric portion of the study highlight multiple opportunities for future research.

Dr. Buse reported financial relationships with Adocia, AstraZeneca, Dexcom, Elcelyx, Eli Lilly, Fractyl Laboratories, Intarcia Therapeutics, Lexicon Pharmaceuticals, Metavention, NovaTarg Therapeutics, Novo Nordisk, Sanofi, VTV Therapeutics, Boehringer Ingelheim, Johnson & Johnson Services, Theracos, Shenzhen Hightide Biopharmaceutical, National Heart Lung and Blood Institute, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association, Patient-Centered Outcomes Research Institute, and the National Institute of Environmental Health Sciences.

[email protected]

ABSTRACT

Despite advancements in surgical technique and understanding of throwing mechanics, controversy persists regarding the treatment of grade III acromioclavicular (AC) joint separations, particularly in throwing athletes. Twenty-eight major league baseball (MLB) orthopedic team physicians were surveyed to determine their definitive management of a grade III AC separation in the dominant arm of a professional baseball pitcher and their experience treating AC joint separations in starting pitchers and position players. Return-to-play outcomes were also evaluated. Twenty (71.4%) team physicians recommended nonoperative intervention compared to 8 (28.6%) who would have operated acutely. Eighteen (64.3%) team physicians had treated at least 1 professional pitcher with a grade III AC separation; 51 (77.3%) pitchers had been treated nonoperatively compared to 15 (22.7%) operatively. No difference was observed in the proportion of pitchers who returned to the same level of play (P = .54), had full, unrestricted range of motion (P = .23), or had full pain relief (P = .19) between the operatively and nonoperatively treated MLB pitchers. The majority (53.6%) of physicians would not include an injection if the injury was treated nonoperatively. Open coracoclavicular reconstruction (65.2%) was preferred for operative cases; 66.7% of surgeons would also include distal clavicle excision as an adjunct procedure. About 90% of physicians would return pitchers to throwing >12 weeks after surgery compared to after 4 to 6 weeks in nonoperatively treated cases. In conclusion, MLB team physicians preferred nonoperative management for an acute grade III AC joint separation in professional pitchers. If operative intervention is required, ligament reconstruction with adjunct distal clavicle excision were the most commonly performed procedures.

Continue to: Despite advancements in surgucal technique...

Despite advancements in surgical technique and improved understanding of the physiology of throwing mechanics, controversy persists regarding the preferred treatment for grade III acromioclavicular (AC) joint separations.^1-6 Nonsurgical management has demonstrated return to prior function with fewer complications.⁷ However, there is a growing body of evidence demonstrating that surgical intervention is associated with more favorable outcomes⁸ and should be considered in patients who place high functional demands on their shoulders.⁹

The reported results on professional athletes in the literature remain ambivalent. Multiple small case reports/series have reported successful nonoperative treatment of elite athletes.^10-12 Not surprisingly, McFarland and colleagues¹³ reported in 1997 that 69% of major league baseball (MLB) team physicians preferred nonoperative treatment for a theoretical starting pitcher sustaining a grade III AC separation 1 week prior to the start of the season. In contrast, reports of an inability to throw at a pre-injury level are equally commonplace.^14,15 Nevertheless, all of these studies were limited to small cohorts, as the incidence of grade III AC separations in elite throwing athletes is relatively uncommon.^13,16

In this study, we re-evaluated the study performed by McFarland and colleagues¹³ in 1997 by surveying all active MLB team orthopedic surgeons. We asked them how they would treat a grade III AC separation in a starting professional baseball pitcher. The physicians were also asked about their personal experience evaluating outcomes in these elite athletes. Given our improved understanding of the anatomy, pathophysiology, and surgical techniques for treating grade III AC separations, we hypothesize that more MLB team physicians would favor operative intervention treatment in professional baseball pitchers, as their vocation places higher demands on their shoulders.

MATERIALS AND METHODS

A questionnaire (Appendix A) was distributed to the team physicians of all 30 MLB teams. In addition to surgeon demographics, including age, years in practice, and years of taking care of an MLB team, the initial section of the questionnaire asked orthopedic surgeons how they would treat a theoretical starting pitcher who sustained a grade III AC joint separation of the dominant throwing arm 1 week prior to the start of the season. Physicians who preferred nonoperative treatment were asked whether they would use an injection (and what type), as well as when they would allow the pitcher to start a progressive interval throwing program. Physicians who preferred operative treatment were asked to rank their indications for operating, what procedure they would use (eg, open vs arthroscopic or coracoclavicular ligament repair vs reconstruction), and whether the surgical intervention would include distal clavicle excision. Both groups of physicians were also asked if their preferred treatment would change if the injury were to occur at the end of the season.

The second portion of the questionnaire asked surgeons about their experience treating AC joint separations in both starting pitchers and position players, as well as to describe the long-term outcomes of their preferred treatment, including time to return to full clearance for pitching, whether their patients returned to their prior level of play, and whether these patients had full pain relief. Finally, physicians were asked if any of the nonoperatively treated players ultimately crossed over and required operative intervention.

Continue to: Statistics...

STATISTICS

Descriptive statistics were used for continuous variables, and frequencies were used for categorical variables. Linear regression was performed to determine the correlation between the physician’s training or experience in treating AC joint separations and their recommended treatment. Fischer’s exact test/chi-square analysis was used to compare categorical variables. All tests were conducted using 2-sided hypothesis testing with statistical significance set at P < .05. All statistical analyses were conducted with SPSS 21.0 software (IBM Corporation).

RESULTS

A total of 28 MLB team physicians completed the questionnaires from 18 of the 30 MLB teams. The average age of the responders was 50.5 years (range, 34-60 years), with an average of 18.2 years in practice (range, 2-30 years) and 10.8 years (range, 1-24 years) taking care of their current professional baseball team. About 82% of the team physicians completed a sports medicine fellowship. On average, physicians saw 16.6 (range, 5-50) grade III or higher AC joint separations per year, and operated on 4.6 (range, 0-10) per year.

Nonoperative treatment was the preferred treatment for a grade III AC joint separation in a starting professional baseball pitcher for the majority of team physicians (20/28). No correlation was observed between the physician’s age (P = .881), years in practice (P = .915), years taking care of their professional team (P = .989), percentage of practice focused on shoulders (P = .986), number of AC joint injuries seen (P = .325), or number of surgeries performed per year (P = .807) with the team physician’s preferred treatment. Compared to the proportion reported originally by McFarland and colleagues¹³ in 1997 (69%), there was no difference in the proportion of team physicians that recommended nonoperative treatment (P = 1).

If treating this injury nonoperatively, 46.4% of physicians would also use an injection, with orthobiologics (eg, platelet-rich plasma) as the most popular choice (Table 1). No consensus was provided on the timeframe to return pitchers back to a progressive interval throwing program; however, 46.67% of physicians would return pitchers 4 to 6 weeks after a nonoperatively treated injury, while 35.7% would return pitchers 7 to 12 weeks after the initial injury.

Table 1. Treatment Preferences of Grade III AC Separation by MLB Team Physicians

^aRespondents were allowed to choose more than 1 treatment in each category. ^bChosen as an adjunct treatment.

Abbreviations: AC, acromioclavicular; MLB, major league baseball.

Most physicians (64.3%) cited functional limitations as the most important reason for indicating operative treatment, followed by pain (21.4%), and a deformity (14.3%). About 65% preferred open coracoclavicular ligament reconstruction. No physician recommended the Weaver-Dunn procedure or use of hardware (eg, hook plate). Of those who preferred an operative intervention, 66.7% would also include a distal clavicle excision, which is significantly higher than the proportion reported by McFarland and colleagues¹³ (23%, P = .0170). About 90% of physicians would return pitchers to play >12 weeks after operative treatment.

Continue to: If the injury occurred at the end ...

If the injury occurred at the end of the season, 7 of the 20 orthopedists (35%) who recommended nonoperative treatment said they would change to an operative intervention. Eighteen of 28 responders would have the same algorithm for MLB position players. Team physicians were less likely to recommend operative intervention in position players due to less demand on the arm and increased ability to accommodate the injury by altering their throwing mechanics.

Eighteen (64%) of the team physicians had treated at least 1 professional pitcher with a grade III AC separation in his dominant arm, and 11 (39.3%) had treated >1. Collectively, team physicians had treated 15 professional pitchers operatively, and 51 nonoperatively; only 3 patients converted to operative intervention after a failed nonoperative treatment.

Of the pitchers treated operatively, 93.3% (14) of pitchers returned to their prior level of pitching. The 1 patient who failed to return to the same level of pitching retired instead of returning to play. About 80% (12) of the pitchers had full pain relief, and 93.3% (14) had full range of motion (ROM). The pitcher who failed to regain full ROM also had a concomitant rotator cuff repair. The only complication reported from an operative intervention was a pitcher who sustained a coracoid fracture 10 months postoperatively while throwing 100 mph. Of the pitchers treated nonoperatively, 96% returned to their prior level of pitching, 92.2% (47) had full complete pain relief when throwing, and 100% had full ROM. No differences were observed between the proportion of pitchers who returned to their prior level of pitching, regained full ROM, or had full pain relief in the operative and nonoperative groups (Table 2).

Table 2. Outcomes of Treatment of Grade III AC Separation in 58 Professional Baseball Players

Abbreviations: AC, acromioclavicular; ROM, range of motion.

DISCUSSION 

Controversy persists regarding the optimal management of acute grade III AC separations, with the current available evidence potentially suggesting better cosmetic and radiological results but no definite differences in clinical results.^1-6,17,18 In the absence of formal clinical practice guidelines, surgeons rely on their own experience or defer to the anecdotal experience of experts in the field. Our initial hypothesis was false in this survey of MLB team physicians taking care of overhead throwing athletes at the highest level. Our results demonstrate that despite improved techniques and an increased understanding of the pathophysiology of AC joint separations, conservative management is still the preferred treatment for acute grade III AC joint separations in professional baseball pitchers. The proportion of team physicians recommending nonoperative treatment in our series was essentially equivalent to the results reported by McFarland and colleagues¹³ in 1997, suggesting that the pendulum continues to favor conservative management initially. This status quo likely reflects both the dearth of literature suggesting a substantial benefit of acute operative repair, as well as the ability to accommodate with conservative measures after most grade III AC injuries, even at the highest level of athletic competition.

These results are also consistent with trends from the last few decades. In the 1970s, the overwhelming preference for treating an acute complete AC joint separation was surgical repair, with Powers and Bach¹⁰ reporting in a 1974 survey of 163 chairmen of orthopedic programs around the country that 91.5% advocated surgical treatment. However, surgical preference had reversed by the 1990s. Of the 187 chairmen and 59 team physicians surveyed by Cox¹⁹ in 1992, 72% and 86% respectively preferred nonoperative treatment in a theoretical 21-year-old athlete with a grade III AC separation. Nissen and Chatterjee²⁰ reported in 2007 on a survey of all American Orthopaedic Society for Sports Medicine surgeons (N = 577) and Accreditation Council for Graduate Medical Education orthopedic program residency directors (N = 87) that >80% of responders preferred conservative measures for this acute injury. The reversal of trends has also been corroborated by recent multicenter trials demonstrating no difference in clinical outcomes between operative and nonoperative treatment of high grade AC joint dislocations, albeit these patients were not all high level overhead throwing athletes.^17,18

Continue to: The trends in surgical interventions are notable...

The trends in surgical interventions are notable within the smaller subset of patients who are indicated for operative repair. Use of hardware and primary ligament repair, while popular in the surveys conducted in the 1970s¹⁰ and 1990s¹³ and even present in Nissen and Chatterjee’s²⁰ 2007 survey, were noticeably absent from our survey results, with the majority of respondents preferring open coracoclavicular ligament reconstruction. The role of distal clavicle excision has also expanded, from 23% of team physicians recommending it in 1997¹³ to 57% to 59% in Nissen and Chatterjee’s²⁰ 2007 survey, to 66.7% in our series. This trend is not surprising as several recent cadaveric biomechanical studies have demonstrated that not only do peak graft forces not increase significantly,²¹ the anterior-posterior and superior-inferior motion at the AC joint following ligament reconstruction is maintained despite resection of the lateral clavicle.²² Additionally, primary distal clavicle excision may prevent the development of post-traumatic arthritis at the AC joint and osteolysis of the distal clavicle as a possible pain generator in the future.²³ However, some respondents cautioned against performing a concomitant distal clavicle excision, as some biomechanical data demonstrate that resecting the distal clavicle may lead to increased horizontal translation at the AC joint despite intact superior and posterior AC capsules.²⁴ Professional baseball pitchers may also be more lax and thus prone to more instability. Primary repair or reconstruction may not always lead to complete pre-injury stability in these individuals. This subtle unrecognized instability is hard to diagnosis and may be a persistent source of pain; thus, adding a distal clavicle excision may actually exacerbate the instability.

The nuanced indications for operative intervention, such as the presence of associated lesions were not captured by our survey.²⁵ While most team physicians cited functional limitations as their most common reason for offering surgery, several MLB orthopedic surgeons also commented on evaluating the stability of the AC joint after a grade III injury, akin to the consensus statement from the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) Upper Extremity Committee²⁶ in 2014 that diversified the Rockwood Grade III AC joint separation into its IIIA and IIIB classifications. The ISAKOS recommendations include initial conservative management and a second evaluation (both clinical and radiographic) for grade III lesions 3 to 6 weeks after the injury. However, as professional baseball is an incredibly profitable sport with an annual revenue approaching $9.5 billion²⁷ and pitching salaries up to $32.5 million in 2015, serious financial considerations must be given to players who wish to avoid undergoing delayed surgery.

This study has shortcomings typical of expert opinion papers. The retrospective nature of this study places the data at risk of recall bias. Objective data (eg, terminal ROM, pain relief, and return to play) were obtained from a retrospective chart review; however, no standard documentation or collection method was used given the number of surgeons involved and, thus, conclusions based on treatment outcomes are imperfect. Another major weakness of this survey is the relatively small number of patients and respondents. An a priori power analysis was not available, as this was a retrospective review. A comparative trial will be necessary to definitively support one treatment over another. Assuming a 95% return to play in the nonoperatively treated group, approximately 300 patients would be needed in a prospective 2-armed study with 80% power to detect a 10% reduction in the incidence of return to play using an alpha level of 0.05 and assuming no loss to follow-up. This sample size would be difficult to achieve in this patient population.

However, compared to past series,¹³ the number of professional baseball players treated by the collective experience of these MLB team physicians is the largest reported to date. As suggested above, the rarity of this condition in elite athletes precludes the ability to have matched controls to definitively determine the optimal treatment, which may explain the lack of difference in the return to play, ROM, and pain relief outcomes. Instead, we can only extrapolate based on the collective anecdotal experience of the MLB team physicians.

CONCLUSION

Despite advances in surgical technique and understanding of throwing mechanics, the majority of MLB team physicians preferred nonoperative management for an acute grade III AC joint separation in a professional baseball pitcher. Open coracoclavicular ligament reconstruction was preferred for those who preferred operative intervention. An increasing number of orthopedic surgeons now consider a distal clavicle excision as an adjunct procedure.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

Despite advancements in surgical technique and understanding of throwing mechanics, controversy persists regarding the treatment of grade III acromioclavicular (AC) joint separations, particularly in throwing athletes. Twenty-eight major league baseball (MLB) orthopedic team physicians were surveyed to determine their definitive management of a grade III AC separation in the dominant arm of a professional baseball pitcher and their experience treating AC joint separations in starting pitchers and position players. Return-to-play outcomes were also evaluated. Twenty (71.4%) team physicians recommended nonoperative intervention compared to 8 (28.6%) who would have operated acutely. Eighteen (64.3%) team physicians had treated at least 1 professional pitcher with a grade III AC separation; 51 (77.3%) pitchers had been treated nonoperatively compared to 15 (22.7%) operatively. No difference was observed in the proportion of pitchers who returned to the same level of play (P = .54), had full, unrestricted range of motion (P = .23), or had full pain relief (P = .19) between the operatively and nonoperatively treated MLB pitchers. The majority (53.6%) of physicians would not include an injection if the injury was treated nonoperatively. Open coracoclavicular reconstruction (65.2%) was preferred for operative cases; 66.7% of surgeons would also include distal clavicle excision as an adjunct procedure. About 90% of physicians would return pitchers to throwing >12 weeks after surgery compared to after 4 to 6 weeks in nonoperatively treated cases. In conclusion, MLB team physicians preferred nonoperative management for an acute grade III AC joint separation in professional pitchers. If operative intervention is required, ligament reconstruction with adjunct distal clavicle excision were the most commonly performed procedures.

Continue to: Despite advancements in surgucal technique...

Despite advancements in surgical technique and improved understanding of the physiology of throwing mechanics, controversy persists regarding the preferred treatment for grade III acromioclavicular (AC) joint separations.^1-6 Nonsurgical management has demonstrated return to prior function with fewer complications.⁷ However, there is a growing body of evidence demonstrating that surgical intervention is associated with more favorable outcomes⁸ and should be considered in patients who place high functional demands on their shoulders.⁹

The reported results on professional athletes in the literature remain ambivalent. Multiple small case reports/series have reported successful nonoperative treatment of elite athletes.^10-12 Not surprisingly, McFarland and colleagues¹³ reported in 1997 that 69% of major league baseball (MLB) team physicians preferred nonoperative treatment for a theoretical starting pitcher sustaining a grade III AC separation 1 week prior to the start of the season. In contrast, reports of an inability to throw at a pre-injury level are equally commonplace.^14,15 Nevertheless, all of these studies were limited to small cohorts, as the incidence of grade III AC separations in elite throwing athletes is relatively uncommon.^13,16

In this study, we re-evaluated the study performed by McFarland and colleagues¹³ in 1997 by surveying all active MLB team orthopedic surgeons. We asked them how they would treat a grade III AC separation in a starting professional baseball pitcher. The physicians were also asked about their personal experience evaluating outcomes in these elite athletes. Given our improved understanding of the anatomy, pathophysiology, and surgical techniques for treating grade III AC separations, we hypothesize that more MLB team physicians would favor operative intervention treatment in professional baseball pitchers, as their vocation places higher demands on their shoulders.

MATERIALS AND METHODS

A questionnaire (Appendix A) was distributed to the team physicians of all 30 MLB teams. In addition to surgeon demographics, including age, years in practice, and years of taking care of an MLB team, the initial section of the questionnaire asked orthopedic surgeons how they would treat a theoretical starting pitcher who sustained a grade III AC joint separation of the dominant throwing arm 1 week prior to the start of the season. Physicians who preferred nonoperative treatment were asked whether they would use an injection (and what type), as well as when they would allow the pitcher to start a progressive interval throwing program. Physicians who preferred operative treatment were asked to rank their indications for operating, what procedure they would use (eg, open vs arthroscopic or coracoclavicular ligament repair vs reconstruction), and whether the surgical intervention would include distal clavicle excision. Both groups of physicians were also asked if their preferred treatment would change if the injury were to occur at the end of the season.

The second portion of the questionnaire asked surgeons about their experience treating AC joint separations in both starting pitchers and position players, as well as to describe the long-term outcomes of their preferred treatment, including time to return to full clearance for pitching, whether their patients returned to their prior level of play, and whether these patients had full pain relief. Finally, physicians were asked if any of the nonoperatively treated players ultimately crossed over and required operative intervention.

Continue to: Statistics...

STATISTICS

Descriptive statistics were used for continuous variables, and frequencies were used for categorical variables. Linear regression was performed to determine the correlation between the physician’s training or experience in treating AC joint separations and their recommended treatment. Fischer’s exact test/chi-square analysis was used to compare categorical variables. All tests were conducted using 2-sided hypothesis testing with statistical significance set at P < .05. All statistical analyses were conducted with SPSS 21.0 software (IBM Corporation).

RESULTS

A total of 28 MLB team physicians completed the questionnaires from 18 of the 30 MLB teams. The average age of the responders was 50.5 years (range, 34-60 years), with an average of 18.2 years in practice (range, 2-30 years) and 10.8 years (range, 1-24 years) taking care of their current professional baseball team. About 82% of the team physicians completed a sports medicine fellowship. On average, physicians saw 16.6 (range, 5-50) grade III or higher AC joint separations per year, and operated on 4.6 (range, 0-10) per year.

Nonoperative treatment was the preferred treatment for a grade III AC joint separation in a starting professional baseball pitcher for the majority of team physicians (20/28). No correlation was observed between the physician’s age (P = .881), years in practice (P = .915), years taking care of their professional team (P = .989), percentage of practice focused on shoulders (P = .986), number of AC joint injuries seen (P = .325), or number of surgeries performed per year (P = .807) with the team physician’s preferred treatment. Compared to the proportion reported originally by McFarland and colleagues¹³ in 1997 (69%), there was no difference in the proportion of team physicians that recommended nonoperative treatment (P = 1).

If treating this injury nonoperatively, 46.4% of physicians would also use an injection, with orthobiologics (eg, platelet-rich plasma) as the most popular choice (Table 1). No consensus was provided on the timeframe to return pitchers back to a progressive interval throwing program; however, 46.67% of physicians would return pitchers 4 to 6 weeks after a nonoperatively treated injury, while 35.7% would return pitchers 7 to 12 weeks after the initial injury.

Table 1. Treatment Preferences of Grade III AC Separation by MLB Team Physicians

^aRespondents were allowed to choose more than 1 treatment in each category. ^bChosen as an adjunct treatment.

Abbreviations: AC, acromioclavicular; MLB, major league baseball.

Most physicians (64.3%) cited functional limitations as the most important reason for indicating operative treatment, followed by pain (21.4%), and a deformity (14.3%). About 65% preferred open coracoclavicular ligament reconstruction. No physician recommended the Weaver-Dunn procedure or use of hardware (eg, hook plate). Of those who preferred an operative intervention, 66.7% would also include a distal clavicle excision, which is significantly higher than the proportion reported by McFarland and colleagues¹³ (23%, P = .0170). About 90% of physicians would return pitchers to play >12 weeks after operative treatment.

Continue to: If the injury occurred at the end ...

If the injury occurred at the end of the season, 7 of the 20 orthopedists (35%) who recommended nonoperative treatment said they would change to an operative intervention. Eighteen of 28 responders would have the same algorithm for MLB position players. Team physicians were less likely to recommend operative intervention in position players due to less demand on the arm and increased ability to accommodate the injury by altering their throwing mechanics.

Eighteen (64%) of the team physicians had treated at least 1 professional pitcher with a grade III AC separation in his dominant arm, and 11 (39.3%) had treated >1. Collectively, team physicians had treated 15 professional pitchers operatively, and 51 nonoperatively; only 3 patients converted to operative intervention after a failed nonoperative treatment.

Of the pitchers treated operatively, 93.3% (14) of pitchers returned to their prior level of pitching. The 1 patient who failed to return to the same level of pitching retired instead of returning to play. About 80% (12) of the pitchers had full pain relief, and 93.3% (14) had full range of motion (ROM). The pitcher who failed to regain full ROM also had a concomitant rotator cuff repair. The only complication reported from an operative intervention was a pitcher who sustained a coracoid fracture 10 months postoperatively while throwing 100 mph. Of the pitchers treated nonoperatively, 96% returned to their prior level of pitching, 92.2% (47) had full complete pain relief when throwing, and 100% had full ROM. No differences were observed between the proportion of pitchers who returned to their prior level of pitching, regained full ROM, or had full pain relief in the operative and nonoperative groups (Table 2).

Table 2. Outcomes of Treatment of Grade III AC Separation in 58 Professional Baseball Players

Abbreviations: AC, acromioclavicular; ROM, range of motion.

DISCUSSION 

Controversy persists regarding the optimal management of acute grade III AC separations, with the current available evidence potentially suggesting better cosmetic and radiological results but no definite differences in clinical results.^1-6,17,18 In the absence of formal clinical practice guidelines, surgeons rely on their own experience or defer to the anecdotal experience of experts in the field. Our initial hypothesis was false in this survey of MLB team physicians taking care of overhead throwing athletes at the highest level. Our results demonstrate that despite improved techniques and an increased understanding of the pathophysiology of AC joint separations, conservative management is still the preferred treatment for acute grade III AC joint separations in professional baseball pitchers. The proportion of team physicians recommending nonoperative treatment in our series was essentially equivalent to the results reported by McFarland and colleagues¹³ in 1997, suggesting that the pendulum continues to favor conservative management initially. This status quo likely reflects both the dearth of literature suggesting a substantial benefit of acute operative repair, as well as the ability to accommodate with conservative measures after most grade III AC injuries, even at the highest level of athletic competition.

These results are also consistent with trends from the last few decades. In the 1970s, the overwhelming preference for treating an acute complete AC joint separation was surgical repair, with Powers and Bach¹⁰ reporting in a 1974 survey of 163 chairmen of orthopedic programs around the country that 91.5% advocated surgical treatment. However, surgical preference had reversed by the 1990s. Of the 187 chairmen and 59 team physicians surveyed by Cox¹⁹ in 1992, 72% and 86% respectively preferred nonoperative treatment in a theoretical 21-year-old athlete with a grade III AC separation. Nissen and Chatterjee²⁰ reported in 2007 on a survey of all American Orthopaedic Society for Sports Medicine surgeons (N = 577) and Accreditation Council for Graduate Medical Education orthopedic program residency directors (N = 87) that >80% of responders preferred conservative measures for this acute injury. The reversal of trends has also been corroborated by recent multicenter trials demonstrating no difference in clinical outcomes between operative and nonoperative treatment of high grade AC joint dislocations, albeit these patients were not all high level overhead throwing athletes.^17,18

Continue to: The trends in surgical interventions are notable...

The trends in surgical interventions are notable within the smaller subset of patients who are indicated for operative repair. Use of hardware and primary ligament repair, while popular in the surveys conducted in the 1970s¹⁰ and 1990s¹³ and even present in Nissen and Chatterjee’s²⁰ 2007 survey, were noticeably absent from our survey results, with the majority of respondents preferring open coracoclavicular ligament reconstruction. The role of distal clavicle excision has also expanded, from 23% of team physicians recommending it in 1997¹³ to 57% to 59% in Nissen and Chatterjee’s²⁰ 2007 survey, to 66.7% in our series. This trend is not surprising as several recent cadaveric biomechanical studies have demonstrated that not only do peak graft forces not increase significantly,²¹ the anterior-posterior and superior-inferior motion at the AC joint following ligament reconstruction is maintained despite resection of the lateral clavicle.²² Additionally, primary distal clavicle excision may prevent the development of post-traumatic arthritis at the AC joint and osteolysis of the distal clavicle as a possible pain generator in the future.²³ However, some respondents cautioned against performing a concomitant distal clavicle excision, as some biomechanical data demonstrate that resecting the distal clavicle may lead to increased horizontal translation at the AC joint despite intact superior and posterior AC capsules.²⁴ Professional baseball pitchers may also be more lax and thus prone to more instability. Primary repair or reconstruction may not always lead to complete pre-injury stability in these individuals. This subtle unrecognized instability is hard to diagnosis and may be a persistent source of pain; thus, adding a distal clavicle excision may actually exacerbate the instability.

The nuanced indications for operative intervention, such as the presence of associated lesions were not captured by our survey.²⁵ While most team physicians cited functional limitations as their most common reason for offering surgery, several MLB orthopedic surgeons also commented on evaluating the stability of the AC joint after a grade III injury, akin to the consensus statement from the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) Upper Extremity Committee²⁶ in 2014 that diversified the Rockwood Grade III AC joint separation into its IIIA and IIIB classifications. The ISAKOS recommendations include initial conservative management and a second evaluation (both clinical and radiographic) for grade III lesions 3 to 6 weeks after the injury. However, as professional baseball is an incredibly profitable sport with an annual revenue approaching $9.5 billion²⁷ and pitching salaries up to $32.5 million in 2015, serious financial considerations must be given to players who wish to avoid undergoing delayed surgery.

This study has shortcomings typical of expert opinion papers. The retrospective nature of this study places the data at risk of recall bias. Objective data (eg, terminal ROM, pain relief, and return to play) were obtained from a retrospective chart review; however, no standard documentation or collection method was used given the number of surgeons involved and, thus, conclusions based on treatment outcomes are imperfect. Another major weakness of this survey is the relatively small number of patients and respondents. An a priori power analysis was not available, as this was a retrospective review. A comparative trial will be necessary to definitively support one treatment over another. Assuming a 95% return to play in the nonoperatively treated group, approximately 300 patients would be needed in a prospective 2-armed study with 80% power to detect a 10% reduction in the incidence of return to play using an alpha level of 0.05 and assuming no loss to follow-up. This sample size would be difficult to achieve in this patient population.

However, compared to past series,¹³ the number of professional baseball players treated by the collective experience of these MLB team physicians is the largest reported to date. As suggested above, the rarity of this condition in elite athletes precludes the ability to have matched controls to definitively determine the optimal treatment, which may explain the lack of difference in the return to play, ROM, and pain relief outcomes. Instead, we can only extrapolate based on the collective anecdotal experience of the MLB team physicians.

CONCLUSION

Despite advances in surgical technique and understanding of throwing mechanics, the majority of MLB team physicians preferred nonoperative management for an acute grade III AC joint separation in a professional baseball pitcher. Open coracoclavicular ligament reconstruction was preferred for those who preferred operative intervention. An increasing number of orthopedic surgeons now consider a distal clavicle excision as an adjunct procedure.

This paper will be judged for the Resident Writer’s Award.

ABSTRACT

Despite advancements in surgical technique and understanding of throwing mechanics, controversy persists regarding the treatment of grade III acromioclavicular (AC) joint separations, particularly in throwing athletes. Twenty-eight major league baseball (MLB) orthopedic team physicians were surveyed to determine their definitive management of a grade III AC separation in the dominant arm of a professional baseball pitcher and their experience treating AC joint separations in starting pitchers and position players. Return-to-play outcomes were also evaluated. Twenty (71.4%) team physicians recommended nonoperative intervention compared to 8 (28.6%) who would have operated acutely. Eighteen (64.3%) team physicians had treated at least 1 professional pitcher with a grade III AC separation; 51 (77.3%) pitchers had been treated nonoperatively compared to 15 (22.7%) operatively. No difference was observed in the proportion of pitchers who returned to the same level of play (P = .54), had full, unrestricted range of motion (P = .23), or had full pain relief (P = .19) between the operatively and nonoperatively treated MLB pitchers. The majority (53.6%) of physicians would not include an injection if the injury was treated nonoperatively. Open coracoclavicular reconstruction (65.2%) was preferred for operative cases; 66.7% of surgeons would also include distal clavicle excision as an adjunct procedure. About 90% of physicians would return pitchers to throwing >12 weeks after surgery compared to after 4 to 6 weeks in nonoperatively treated cases. In conclusion, MLB team physicians preferred nonoperative management for an acute grade III AC joint separation in professional pitchers. If operative intervention is required, ligament reconstruction with adjunct distal clavicle excision were the most commonly performed procedures.

Continue to: Despite advancements in surgucal technique...

Despite advancements in surgical technique and improved understanding of the physiology of throwing mechanics, controversy persists regarding the preferred treatment for grade III acromioclavicular (AC) joint separations.^1-6 Nonsurgical management has demonstrated return to prior function with fewer complications.⁷ However, there is a growing body of evidence demonstrating that surgical intervention is associated with more favorable outcomes⁸ and should be considered in patients who place high functional demands on their shoulders.⁹

The reported results on professional athletes in the literature remain ambivalent. Multiple small case reports/series have reported successful nonoperative treatment of elite athletes.^10-12 Not surprisingly, McFarland and colleagues¹³ reported in 1997 that 69% of major league baseball (MLB) team physicians preferred nonoperative treatment for a theoretical starting pitcher sustaining a grade III AC separation 1 week prior to the start of the season. In contrast, reports of an inability to throw at a pre-injury level are equally commonplace.^14,15 Nevertheless, all of these studies were limited to small cohorts, as the incidence of grade III AC separations in elite throwing athletes is relatively uncommon.^13,16

In this study, we re-evaluated the study performed by McFarland and colleagues¹³ in 1997 by surveying all active MLB team orthopedic surgeons. We asked them how they would treat a grade III AC separation in a starting professional baseball pitcher. The physicians were also asked about their personal experience evaluating outcomes in these elite athletes. Given our improved understanding of the anatomy, pathophysiology, and surgical techniques for treating grade III AC separations, we hypothesize that more MLB team physicians would favor operative intervention treatment in professional baseball pitchers, as their vocation places higher demands on their shoulders.

MATERIALS AND METHODS

A questionnaire (Appendix A) was distributed to the team physicians of all 30 MLB teams. In addition to surgeon demographics, including age, years in practice, and years of taking care of an MLB team, the initial section of the questionnaire asked orthopedic surgeons how they would treat a theoretical starting pitcher who sustained a grade III AC joint separation of the dominant throwing arm 1 week prior to the start of the season. Physicians who preferred nonoperative treatment were asked whether they would use an injection (and what type), as well as when they would allow the pitcher to start a progressive interval throwing program. Physicians who preferred operative treatment were asked to rank their indications for operating, what procedure they would use (eg, open vs arthroscopic or coracoclavicular ligament repair vs reconstruction), and whether the surgical intervention would include distal clavicle excision. Both groups of physicians were also asked if their preferred treatment would change if the injury were to occur at the end of the season.

The second portion of the questionnaire asked surgeons about their experience treating AC joint separations in both starting pitchers and position players, as well as to describe the long-term outcomes of their preferred treatment, including time to return to full clearance for pitching, whether their patients returned to their prior level of play, and whether these patients had full pain relief. Finally, physicians were asked if any of the nonoperatively treated players ultimately crossed over and required operative intervention.

Continue to: Statistics...

STATISTICS

Descriptive statistics were used for continuous variables, and frequencies were used for categorical variables. Linear regression was performed to determine the correlation between the physician’s training or experience in treating AC joint separations and their recommended treatment. Fischer’s exact test/chi-square analysis was used to compare categorical variables. All tests were conducted using 2-sided hypothesis testing with statistical significance set at P < .05. All statistical analyses were conducted with SPSS 21.0 software (IBM Corporation).

RESULTS

A total of 28 MLB team physicians completed the questionnaires from 18 of the 30 MLB teams. The average age of the responders was 50.5 years (range, 34-60 years), with an average of 18.2 years in practice (range, 2-30 years) and 10.8 years (range, 1-24 years) taking care of their current professional baseball team. About 82% of the team physicians completed a sports medicine fellowship. On average, physicians saw 16.6 (range, 5-50) grade III or higher AC joint separations per year, and operated on 4.6 (range, 0-10) per year.

Nonoperative treatment was the preferred treatment for a grade III AC joint separation in a starting professional baseball pitcher for the majority of team physicians (20/28). No correlation was observed between the physician’s age (P = .881), years in practice (P = .915), years taking care of their professional team (P = .989), percentage of practice focused on shoulders (P = .986), number of AC joint injuries seen (P = .325), or number of surgeries performed per year (P = .807) with the team physician’s preferred treatment. Compared to the proportion reported originally by McFarland and colleagues¹³ in 1997 (69%), there was no difference in the proportion of team physicians that recommended nonoperative treatment (P = 1).

If treating this injury nonoperatively, 46.4% of physicians would also use an injection, with orthobiologics (eg, platelet-rich plasma) as the most popular choice (Table 1). No consensus was provided on the timeframe to return pitchers back to a progressive interval throwing program; however, 46.67% of physicians would return pitchers 4 to 6 weeks after a nonoperatively treated injury, while 35.7% would return pitchers 7 to 12 weeks after the initial injury.

Table 1. Treatment Preferences of Grade III AC Separation by MLB Team Physicians

^aRespondents were allowed to choose more than 1 treatment in each category. ^bChosen as an adjunct treatment.

Abbreviations: AC, acromioclavicular; MLB, major league baseball.

Most physicians (64.3%) cited functional limitations as the most important reason for indicating operative treatment, followed by pain (21.4%), and a deformity (14.3%). About 65% preferred open coracoclavicular ligament reconstruction. No physician recommended the Weaver-Dunn procedure or use of hardware (eg, hook plate). Of those who preferred an operative intervention, 66.7% would also include a distal clavicle excision, which is significantly higher than the proportion reported by McFarland and colleagues¹³ (23%, P = .0170). About 90% of physicians would return pitchers to play >12 weeks after operative treatment.

Continue to: If the injury occurred at the end ...

If the injury occurred at the end of the season, 7 of the 20 orthopedists (35%) who recommended nonoperative treatment said they would change to an operative intervention. Eighteen of 28 responders would have the same algorithm for MLB position players. Team physicians were less likely to recommend operative intervention in position players due to less demand on the arm and increased ability to accommodate the injury by altering their throwing mechanics.

Eighteen (64%) of the team physicians had treated at least 1 professional pitcher with a grade III AC separation in his dominant arm, and 11 (39.3%) had treated >1. Collectively, team physicians had treated 15 professional pitchers operatively, and 51 nonoperatively; only 3 patients converted to operative intervention after a failed nonoperative treatment.

Of the pitchers treated operatively, 93.3% (14) of pitchers returned to their prior level of pitching. The 1 patient who failed to return to the same level of pitching retired instead of returning to play. About 80% (12) of the pitchers had full pain relief, and 93.3% (14) had full range of motion (ROM). The pitcher who failed to regain full ROM also had a concomitant rotator cuff repair. The only complication reported from an operative intervention was a pitcher who sustained a coracoid fracture 10 months postoperatively while throwing 100 mph. Of the pitchers treated nonoperatively, 96% returned to their prior level of pitching, 92.2% (47) had full complete pain relief when throwing, and 100% had full ROM. No differences were observed between the proportion of pitchers who returned to their prior level of pitching, regained full ROM, or had full pain relief in the operative and nonoperative groups (Table 2).

Table 2. Outcomes of Treatment of Grade III AC Separation in 58 Professional Baseball Players

Abbreviations: AC, acromioclavicular; ROM, range of motion.

DISCUSSION 

Controversy persists regarding the optimal management of acute grade III AC separations, with the current available evidence potentially suggesting better cosmetic and radiological results but no definite differences in clinical results.^1-6,17,18 In the absence of formal clinical practice guidelines, surgeons rely on their own experience or defer to the anecdotal experience of experts in the field. Our initial hypothesis was false in this survey of MLB team physicians taking care of overhead throwing athletes at the highest level. Our results demonstrate that despite improved techniques and an increased understanding of the pathophysiology of AC joint separations, conservative management is still the preferred treatment for acute grade III AC joint separations in professional baseball pitchers. The proportion of team physicians recommending nonoperative treatment in our series was essentially equivalent to the results reported by McFarland and colleagues¹³ in 1997, suggesting that the pendulum continues to favor conservative management initially. This status quo likely reflects both the dearth of literature suggesting a substantial benefit of acute operative repair, as well as the ability to accommodate with conservative measures after most grade III AC injuries, even at the highest level of athletic competition.

These results are also consistent with trends from the last few decades. In the 1970s, the overwhelming preference for treating an acute complete AC joint separation was surgical repair, with Powers and Bach¹⁰ reporting in a 1974 survey of 163 chairmen of orthopedic programs around the country that 91.5% advocated surgical treatment. However, surgical preference had reversed by the 1990s. Of the 187 chairmen and 59 team physicians surveyed by Cox¹⁹ in 1992, 72% and 86% respectively preferred nonoperative treatment in a theoretical 21-year-old athlete with a grade III AC separation. Nissen and Chatterjee²⁰ reported in 2007 on a survey of all American Orthopaedic Society for Sports Medicine surgeons (N = 577) and Accreditation Council for Graduate Medical Education orthopedic program residency directors (N = 87) that >80% of responders preferred conservative measures for this acute injury. The reversal of trends has also been corroborated by recent multicenter trials demonstrating no difference in clinical outcomes between operative and nonoperative treatment of high grade AC joint dislocations, albeit these patients were not all high level overhead throwing athletes.^17,18

Continue to: The trends in surgical interventions are notable...

The trends in surgical interventions are notable within the smaller subset of patients who are indicated for operative repair. Use of hardware and primary ligament repair, while popular in the surveys conducted in the 1970s¹⁰ and 1990s¹³ and even present in Nissen and Chatterjee’s²⁰ 2007 survey, were noticeably absent from our survey results, with the majority of respondents preferring open coracoclavicular ligament reconstruction. The role of distal clavicle excision has also expanded, from 23% of team physicians recommending it in 1997¹³ to 57% to 59% in Nissen and Chatterjee’s²⁰ 2007 survey, to 66.7% in our series. This trend is not surprising as several recent cadaveric biomechanical studies have demonstrated that not only do peak graft forces not increase significantly,²¹ the anterior-posterior and superior-inferior motion at the AC joint following ligament reconstruction is maintained despite resection of the lateral clavicle.²² Additionally, primary distal clavicle excision may prevent the development of post-traumatic arthritis at the AC joint and osteolysis of the distal clavicle as a possible pain generator in the future.²³ However, some respondents cautioned against performing a concomitant distal clavicle excision, as some biomechanical data demonstrate that resecting the distal clavicle may lead to increased horizontal translation at the AC joint despite intact superior and posterior AC capsules.²⁴ Professional baseball pitchers may also be more lax and thus prone to more instability. Primary repair or reconstruction may not always lead to complete pre-injury stability in these individuals. This subtle unrecognized instability is hard to diagnosis and may be a persistent source of pain; thus, adding a distal clavicle excision may actually exacerbate the instability.

The nuanced indications for operative intervention, such as the presence of associated lesions were not captured by our survey.²⁵ While most team physicians cited functional limitations as their most common reason for offering surgery, several MLB orthopedic surgeons also commented on evaluating the stability of the AC joint after a grade III injury, akin to the consensus statement from the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) Upper Extremity Committee²⁶ in 2014 that diversified the Rockwood Grade III AC joint separation into its IIIA and IIIB classifications. The ISAKOS recommendations include initial conservative management and a second evaluation (both clinical and radiographic) for grade III lesions 3 to 6 weeks after the injury. However, as professional baseball is an incredibly profitable sport with an annual revenue approaching $9.5 billion²⁷ and pitching salaries up to $32.5 million in 2015, serious financial considerations must be given to players who wish to avoid undergoing delayed surgery.

This study has shortcomings typical of expert opinion papers. The retrospective nature of this study places the data at risk of recall bias. Objective data (eg, terminal ROM, pain relief, and return to play) were obtained from a retrospective chart review; however, no standard documentation or collection method was used given the number of surgeons involved and, thus, conclusions based on treatment outcomes are imperfect. Another major weakness of this survey is the relatively small number of patients and respondents. An a priori power analysis was not available, as this was a retrospective review. A comparative trial will be necessary to definitively support one treatment over another. Assuming a 95% return to play in the nonoperatively treated group, approximately 300 patients would be needed in a prospective 2-armed study with 80% power to detect a 10% reduction in the incidence of return to play using an alpha level of 0.05 and assuming no loss to follow-up. This sample size would be difficult to achieve in this patient population.

However, compared to past series,¹³ the number of professional baseball players treated by the collective experience of these MLB team physicians is the largest reported to date. As suggested above, the rarity of this condition in elite athletes precludes the ability to have matched controls to definitively determine the optimal treatment, which may explain the lack of difference in the return to play, ROM, and pain relief outcomes. Instead, we can only extrapolate based on the collective anecdotal experience of the MLB team physicians.

CONCLUSION

Despite advances in surgical technique and understanding of throwing mechanics, the majority of MLB team physicians preferred nonoperative management for an acute grade III AC joint separation in a professional baseball pitcher. Open coracoclavicular ligament reconstruction was preferred for those who preferred operative intervention. An increasing number of orthopedic surgeons now consider a distal clavicle excision as an adjunct procedure.

This paper will be judged for the Resident Writer’s Award.

STOCKHOLM – A chemotherapy-free regimen of ibrutinib plus venetoclax was generally safe and showed promising early efficacy in patients with relapsed or refractory chronic lymphocytic leukemia, investigators reported.

A planned interim analysis performed after the first 15 patients who had received two cycles of ibrutinib plus one of ibrutinib and venetoclax showed no treatment-related deaths or treatment interruptions, and all patients had clinical responses, including 8 with complete clinical remission (CR), reported Carsten U. Niemann, MD, PhD, from Rigshospitalet in Copenhagen, and his colleagues.

Neil Osterweil/MDedge News

The goal of the ongoing VISION/HOVEN 141 study is to evaluate whether minimal residual disease (MRD)–guided therapy with the Bruton tyrosine kinase inhibitor ibrutinib and the BCL2 inhibitor venetoclax could lead to MRD negativity and allow select patients to stop treatment, Dr. Niemann said in an interview at the annual congress of the European Hematology Association.

“It’s a 100% clinical response rate and 53% CR. Obviously these are clinical responses, so we don’t have the CT scans, we don’t have the bone marrow biopsies, but we’re very happy to see even in the relapsed/refractory setting such good response rates,” he said.

The investigators are enrolling patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic leukemia requiring treatment and starting all patients on ibrutinib 420 mg daily for the first 2 cycles, with venetoclax added in a 5-week ramp-up from 20 mg beginning with cycle 3 to a final dose of 400 mg daily for 15 total treatment cycles.

At the end of the induction phase, patients who are determined to be MRD-negative by flow cytometry at cycles 12 and 15, and by bone marrow at cycle 15, are randomized on a 1:2 basis to ibrutinib maintenance until disease progression or intolerable toxicity, or to observation until progression or loss of MRD negativity, at which time they start maintenance with ibrutinib until progression or toxicity, plus 12 months of venetoclax.

All 15 patients who were followed for 3 months had clinical responses, including 8 CRs (53%), 6 partial remissions (40%), and 1 partial remission with lymphocytosis (7%).

Three patients had ibrutinib dose reductions and two had venetoclax dose reductions, but no patients stopped treatment. Three patients had grade 2 adverse events (AEs), three had grade 3 AEs, and two had grade 4 AEs. There were no grade 5 AEs.

Two patients had serious AEs during the first two cycles with ibrutinib alone, one of which was a case of febrile neutropenia and one which was an adenocarcinoma of the lung. There were no serious AEs reported during venetoclax ramp-up. To date, there have been no cases of tumor lysis syndrome, atrial fibrillation, or bleeding events reported.

The results suggest that treatment with ibrutinib and venetoclax ramp-up is manageable in this patient population, and the study is ongoing, with further results expected to be reported at either the 2018 annual meeting of the American Society of Hematology or the 2019 annual meeting of the American Society of Clinical Oncology, Dr. Niemann said.

The study is supported by AbbVie and Janssen, which supplied the drugs and had the right to comment on the presentation. Dr. Niemann has previously disclosed consultancy fees from those companies and others.

SOURCE: Niemann CU et al. EHA Congress, Abstract PF346.


 

STOCKHOLM – A chemotherapy-free regimen of ibrutinib plus venetoclax was generally safe and showed promising early efficacy in patients with relapsed or refractory chronic lymphocytic leukemia, investigators reported.

A planned interim analysis performed after the first 15 patients who had received two cycles of ibrutinib plus one of ibrutinib and venetoclax showed no treatment-related deaths or treatment interruptions, and all patients had clinical responses, including 8 with complete clinical remission (CR), reported Carsten U. Niemann, MD, PhD, from Rigshospitalet in Copenhagen, and his colleagues.

Neil Osterweil/MDedge News

The goal of the ongoing VISION/HOVEN 141 study is to evaluate whether minimal residual disease (MRD)–guided therapy with the Bruton tyrosine kinase inhibitor ibrutinib and the BCL2 inhibitor venetoclax could lead to MRD negativity and allow select patients to stop treatment, Dr. Niemann said in an interview at the annual congress of the European Hematology Association.

“It’s a 100% clinical response rate and 53% CR. Obviously these are clinical responses, so we don’t have the CT scans, we don’t have the bone marrow biopsies, but we’re very happy to see even in the relapsed/refractory setting such good response rates,” he said.

The investigators are enrolling patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic leukemia requiring treatment and starting all patients on ibrutinib 420 mg daily for the first 2 cycles, with venetoclax added in a 5-week ramp-up from 20 mg beginning with cycle 3 to a final dose of 400 mg daily for 15 total treatment cycles.

At the end of the induction phase, patients who are determined to be MRD-negative by flow cytometry at cycles 12 and 15, and by bone marrow at cycle 15, are randomized on a 1:2 basis to ibrutinib maintenance until disease progression or intolerable toxicity, or to observation until progression or loss of MRD negativity, at which time they start maintenance with ibrutinib until progression or toxicity, plus 12 months of venetoclax.

All 15 patients who were followed for 3 months had clinical responses, including 8 CRs (53%), 6 partial remissions (40%), and 1 partial remission with lymphocytosis (7%).

Three patients had ibrutinib dose reductions and two had venetoclax dose reductions, but no patients stopped treatment. Three patients had grade 2 adverse events (AEs), three had grade 3 AEs, and two had grade 4 AEs. There were no grade 5 AEs.

Two patients had serious AEs during the first two cycles with ibrutinib alone, one of which was a case of febrile neutropenia and one which was an adenocarcinoma of the lung. There were no serious AEs reported during venetoclax ramp-up. To date, there have been no cases of tumor lysis syndrome, atrial fibrillation, or bleeding events reported.

The results suggest that treatment with ibrutinib and venetoclax ramp-up is manageable in this patient population, and the study is ongoing, with further results expected to be reported at either the 2018 annual meeting of the American Society of Hematology or the 2019 annual meeting of the American Society of Clinical Oncology, Dr. Niemann said.

The study is supported by AbbVie and Janssen, which supplied the drugs and had the right to comment on the presentation. Dr. Niemann has previously disclosed consultancy fees from those companies and others.

SOURCE: Niemann CU et al. EHA Congress, Abstract PF346.


 

STOCKHOLM – A chemotherapy-free regimen of ibrutinib plus venetoclax was generally safe and showed promising early efficacy in patients with relapsed or refractory chronic lymphocytic leukemia, investigators reported.

A planned interim analysis performed after the first 15 patients who had received two cycles of ibrutinib plus one of ibrutinib and venetoclax showed no treatment-related deaths or treatment interruptions, and all patients had clinical responses, including 8 with complete clinical remission (CR), reported Carsten U. Niemann, MD, PhD, from Rigshospitalet in Copenhagen, and his colleagues.

Neil Osterweil/MDedge News

The goal of the ongoing VISION/HOVEN 141 study is to evaluate whether minimal residual disease (MRD)–guided therapy with the Bruton tyrosine kinase inhibitor ibrutinib and the BCL2 inhibitor venetoclax could lead to MRD negativity and allow select patients to stop treatment, Dr. Niemann said in an interview at the annual congress of the European Hematology Association.

“It’s a 100% clinical response rate and 53% CR. Obviously these are clinical responses, so we don’t have the CT scans, we don’t have the bone marrow biopsies, but we’re very happy to see even in the relapsed/refractory setting such good response rates,” he said.

The investigators are enrolling patients with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic leukemia requiring treatment and starting all patients on ibrutinib 420 mg daily for the first 2 cycles, with venetoclax added in a 5-week ramp-up from 20 mg beginning with cycle 3 to a final dose of 400 mg daily for 15 total treatment cycles.

At the end of the induction phase, patients who are determined to be MRD-negative by flow cytometry at cycles 12 and 15, and by bone marrow at cycle 15, are randomized on a 1:2 basis to ibrutinib maintenance until disease progression or intolerable toxicity, or to observation until progression or loss of MRD negativity, at which time they start maintenance with ibrutinib until progression or toxicity, plus 12 months of venetoclax.

All 15 patients who were followed for 3 months had clinical responses, including 8 CRs (53%), 6 partial remissions (40%), and 1 partial remission with lymphocytosis (7%).

Three patients had ibrutinib dose reductions and two had venetoclax dose reductions, but no patients stopped treatment. Three patients had grade 2 adverse events (AEs), three had grade 3 AEs, and two had grade 4 AEs. There were no grade 5 AEs.

Two patients had serious AEs during the first two cycles with ibrutinib alone, one of which was a case of febrile neutropenia and one which was an adenocarcinoma of the lung. There were no serious AEs reported during venetoclax ramp-up. To date, there have been no cases of tumor lysis syndrome, atrial fibrillation, or bleeding events reported.

The results suggest that treatment with ibrutinib and venetoclax ramp-up is manageable in this patient population, and the study is ongoing, with further results expected to be reported at either the 2018 annual meeting of the American Society of Hematology or the 2019 annual meeting of the American Society of Clinical Oncology, Dr. Niemann said.

The study is supported by AbbVie and Janssen, which supplied the drugs and had the right to comment on the presentation. Dr. Niemann has previously disclosed consultancy fees from those companies and others.

SOURCE: Niemann CU et al. EHA Congress, Abstract PF346.


 

Henrique Orlandi Mourao

Researchers say they have found ways to identify patients with a high risk of developing acute myeloid leukemia (AML).

The researchers used basic clinical and laboratory data to identify patients 6 to 12 months before AML presentation.

Using genetic information, the researchers were able to identify high-risk patients several years before AML presentation.

“This long time window gives us the first opportunity to think about how to prevent AML,” said John Dick, PhD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada.

However, Dr Dick and his colleagues noted that neither the genetic method nor the clinical data method were entirely accurate in identifying patients who would develop AML.

The researchers described both methods in Nature.

The team’s work began with the goal of distinguishing patients who will develop AML from patients who simply develop age-related clonal hematopoiesis.

“We wanted to know if there was any difference between these 2 groups in the genetics of their ‘normal’ blood samples taken at enrollment,” Dr Dick said. “To find out, we developed a gene-sequencing tool that captured the most common genes that get altered in AML and sequenced all the 500 blood samples.”

The researchers analyzed samples from 95 patients who ultimately developed AML and 414 age- and gender-matched controls. The samples from AML patients were obtained an average of 6.3 years before AML diagnosis.

The researchers found that pre-AML cases had more mutations per sample, higher variant allele frequencies, and a higher frequency of certain mutations than controls. Specifically, pre-AML cases had a significantly greater frequency of DNMT3A, TET2, SRSF2, ASXL1, TP53, U2AF1, JAK2, RUNX1, and IDH2 mutations.

The researchers used these findings to develop a model for predicting AML. They tested the model in a validation cohort of 29 pre-AML cases and 262 controls, as well as in a cohort combining the validation and discovery cohorts. The model predicted AML development with 41.9% sensitivity and 95.7% specificity.

However, the researchers said widespread use of this model would not be practical because AML is so rare. The team said millions of people would need to undergo screening to identify a few pre-AML cases, and there would be “many” false-positives.

Therefore, the researchers developed a model using clinical information from electronic health records—particularly blood counts. This model was able to predict AML development 6 to 12 months before diagnosis with a sensitivity of 25.7% and specificity of 98.2%.

The researchers said these results suggest clinical data can be used to identify patients with a high risk of AML who may benefit from targeted genetic screening. And combining clinical and genetic information in a single model could improve predictive accuracy.

“Our study provides, for the first time, evidence that we can identify people at risk of developing AML many years before they actually develop this life-threatening disease,” said study author George Vassiliou, PhD, of the Wellcome Trust Sanger Institute in Hinxton, UK.

“We hope to build on these findings to develop robust screening tests for identifying those at risk and drive research into how to prevent or stall progression towards AML. Our aspiration is that, one day, AML prevention would provide a compelling alternative to treatment.”

Henrique Orlandi Mourao

Researchers say they have found ways to identify patients with a high risk of developing acute myeloid leukemia (AML).

The researchers used basic clinical and laboratory data to identify patients 6 to 12 months before AML presentation.

Using genetic information, the researchers were able to identify high-risk patients several years before AML presentation.

“This long time window gives us the first opportunity to think about how to prevent AML,” said John Dick, PhD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada.

However, Dr Dick and his colleagues noted that neither the genetic method nor the clinical data method were entirely accurate in identifying patients who would develop AML.

The researchers described both methods in Nature.

The team’s work began with the goal of distinguishing patients who will develop AML from patients who simply develop age-related clonal hematopoiesis.

“We wanted to know if there was any difference between these 2 groups in the genetics of their ‘normal’ blood samples taken at enrollment,” Dr Dick said. “To find out, we developed a gene-sequencing tool that captured the most common genes that get altered in AML and sequenced all the 500 blood samples.”

The researchers analyzed samples from 95 patients who ultimately developed AML and 414 age- and gender-matched controls. The samples from AML patients were obtained an average of 6.3 years before AML diagnosis.

The researchers found that pre-AML cases had more mutations per sample, higher variant allele frequencies, and a higher frequency of certain mutations than controls. Specifically, pre-AML cases had a significantly greater frequency of DNMT3A, TET2, SRSF2, ASXL1, TP53, U2AF1, JAK2, RUNX1, and IDH2 mutations.

The researchers used these findings to develop a model for predicting AML. They tested the model in a validation cohort of 29 pre-AML cases and 262 controls, as well as in a cohort combining the validation and discovery cohorts. The model predicted AML development with 41.9% sensitivity and 95.7% specificity.

However, the researchers said widespread use of this model would not be practical because AML is so rare. The team said millions of people would need to undergo screening to identify a few pre-AML cases, and there would be “many” false-positives.

Therefore, the researchers developed a model using clinical information from electronic health records—particularly blood counts. This model was able to predict AML development 6 to 12 months before diagnosis with a sensitivity of 25.7% and specificity of 98.2%.

The researchers said these results suggest clinical data can be used to identify patients with a high risk of AML who may benefit from targeted genetic screening. And combining clinical and genetic information in a single model could improve predictive accuracy.

“Our study provides, for the first time, evidence that we can identify people at risk of developing AML many years before they actually develop this life-threatening disease,” said study author George Vassiliou, PhD, of the Wellcome Trust Sanger Institute in Hinxton, UK.

“We hope to build on these findings to develop robust screening tests for identifying those at risk and drive research into how to prevent or stall progression towards AML. Our aspiration is that, one day, AML prevention would provide a compelling alternative to treatment.”

Henrique Orlandi Mourao

Researchers say they have found ways to identify patients with a high risk of developing acute myeloid leukemia (AML).

The researchers used basic clinical and laboratory data to identify patients 6 to 12 months before AML presentation.

Using genetic information, the researchers were able to identify high-risk patients several years before AML presentation.

“This long time window gives us the first opportunity to think about how to prevent AML,” said John Dick, PhD, of Princess Margaret Cancer Centre in Toronto, Ontario, Canada.

However, Dr Dick and his colleagues noted that neither the genetic method nor the clinical data method were entirely accurate in identifying patients who would develop AML.

The researchers described both methods in Nature.

The team’s work began with the goal of distinguishing patients who will develop AML from patients who simply develop age-related clonal hematopoiesis.

“We wanted to know if there was any difference between these 2 groups in the genetics of their ‘normal’ blood samples taken at enrollment,” Dr Dick said. “To find out, we developed a gene-sequencing tool that captured the most common genes that get altered in AML and sequenced all the 500 blood samples.”

The researchers analyzed samples from 95 patients who ultimately developed AML and 414 age- and gender-matched controls. The samples from AML patients were obtained an average of 6.3 years before AML diagnosis.

The researchers found that pre-AML cases had more mutations per sample, higher variant allele frequencies, and a higher frequency of certain mutations than controls. Specifically, pre-AML cases had a significantly greater frequency of DNMT3A, TET2, SRSF2, ASXL1, TP53, U2AF1, JAK2, RUNX1, and IDH2 mutations.

The researchers used these findings to develop a model for predicting AML. They tested the model in a validation cohort of 29 pre-AML cases and 262 controls, as well as in a cohort combining the validation and discovery cohorts. The model predicted AML development with 41.9% sensitivity and 95.7% specificity.

However, the researchers said widespread use of this model would not be practical because AML is so rare. The team said millions of people would need to undergo screening to identify a few pre-AML cases, and there would be “many” false-positives.

Therefore, the researchers developed a model using clinical information from electronic health records—particularly blood counts. This model was able to predict AML development 6 to 12 months before diagnosis with a sensitivity of 25.7% and specificity of 98.2%.

The researchers said these results suggest clinical data can be used to identify patients with a high risk of AML who may benefit from targeted genetic screening. And combining clinical and genetic information in a single model could improve predictive accuracy.

“Our study provides, for the first time, evidence that we can identify people at risk of developing AML many years before they actually develop this life-threatening disease,” said study author George Vassiliou, PhD, of the Wellcome Trust Sanger Institute in Hinxton, UK.

“We hope to build on these findings to develop robust screening tests for identifying those at risk and drive research into how to prevent or stall progression towards AML. Our aspiration is that, one day, AML prevention would provide a compelling alternative to treatment.”

Photo by Kyle Davis

The US Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for a freeze-dried plasma product to be used by the military.

The product is Pathogen-Reduced Leukocyte-Depleted Freeze-Dried Plasma manufactured by the Centre de Transfusion Sanguine des Armées, referred to in the EUA as “French FDP.”

Under the EUA, French FDP is authorized for the treatment of hemorrhage or coagulopathy in US military personnel during an emergency involving agents of military combat (eg, firearms, projectiles, and explosive devices) when plasma is not available or when the use of plasma is not practical.

The use of plasma in combat settings is severely limited by logistical and operational challenges, such as the need for refrigeration and, in the case of frozen plasma, a long thawing period.

French FDP is a powdered, freeze-dried product that can be used following reconstitution in settings where refrigeration is not available, thus enabling the rapid availability of plasma for use at the point of injury.

The FDA issued the EUA for French FDP in response to a request from the US Department of Defense (DoD) and after receiving the required determination by DoD and a declaration by the Secretary of the Department of Health and Human Services.

This action is the result of a collaboration between the FDA and the DoD to prioritize development of medical products intended to help save the lives of American military personnel. The FDA outlined its approach to advancing the development of such products in a work plan developed with DoD.

“Earlier this year, we reaffirmed our commitment to the Department of Defense and to the dedicated men and women protecting our country by expediting the development and availability of safe and effective priority medical products that are essential to the health of our military service members,” said FDA Commissioner Scott Gottlieb, MD.

“Through our collaborative program with the DoD, they’ve made clear the importance of access to freeze-dried plasma in initial efforts to control hemorrhage from battlefield trauma. Granting this authorization will support access to this important product in the event it’s needed. The FDA remains deeply committed to implementing an enduring pathway to ensure that these potentially life-saving medical products are made available in the most expeditious, safe, and effective manner possible.”

Photo by Kyle Davis

The US Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for a freeze-dried plasma product to be used by the military.

The product is Pathogen-Reduced Leukocyte-Depleted Freeze-Dried Plasma manufactured by the Centre de Transfusion Sanguine des Armées, referred to in the EUA as “French FDP.”

Under the EUA, French FDP is authorized for the treatment of hemorrhage or coagulopathy in US military personnel during an emergency involving agents of military combat (eg, firearms, projectiles, and explosive devices) when plasma is not available or when the use of plasma is not practical.

The use of plasma in combat settings is severely limited by logistical and operational challenges, such as the need for refrigeration and, in the case of frozen plasma, a long thawing period.

French FDP is a powdered, freeze-dried product that can be used following reconstitution in settings where refrigeration is not available, thus enabling the rapid availability of plasma for use at the point of injury.

The FDA issued the EUA for French FDP in response to a request from the US Department of Defense (DoD) and after receiving the required determination by DoD and a declaration by the Secretary of the Department of Health and Human Services.

This action is the result of a collaboration between the FDA and the DoD to prioritize development of medical products intended to help save the lives of American military personnel. The FDA outlined its approach to advancing the development of such products in a work plan developed with DoD.

“Earlier this year, we reaffirmed our commitment to the Department of Defense and to the dedicated men and women protecting our country by expediting the development and availability of safe and effective priority medical products that are essential to the health of our military service members,” said FDA Commissioner Scott Gottlieb, MD.

“Through our collaborative program with the DoD, they’ve made clear the importance of access to freeze-dried plasma in initial efforts to control hemorrhage from battlefield trauma. Granting this authorization will support access to this important product in the event it’s needed. The FDA remains deeply committed to implementing an enduring pathway to ensure that these potentially life-saving medical products are made available in the most expeditious, safe, and effective manner possible.”

Photo by Kyle Davis

The US Food and Drug Administration (FDA) has granted emergency use authorization (EUA) for a freeze-dried plasma product to be used by the military.

The product is Pathogen-Reduced Leukocyte-Depleted Freeze-Dried Plasma manufactured by the Centre de Transfusion Sanguine des Armées, referred to in the EUA as “French FDP.”

Under the EUA, French FDP is authorized for the treatment of hemorrhage or coagulopathy in US military personnel during an emergency involving agents of military combat (eg, firearms, projectiles, and explosive devices) when plasma is not available or when the use of plasma is not practical.

The use of plasma in combat settings is severely limited by logistical and operational challenges, such as the need for refrigeration and, in the case of frozen plasma, a long thawing period.

French FDP is a powdered, freeze-dried product that can be used following reconstitution in settings where refrigeration is not available, thus enabling the rapid availability of plasma for use at the point of injury.

The FDA issued the EUA for French FDP in response to a request from the US Department of Defense (DoD) and after receiving the required determination by DoD and a declaration by the Secretary of the Department of Health and Human Services.

This action is the result of a collaboration between the FDA and the DoD to prioritize development of medical products intended to help save the lives of American military personnel. The FDA outlined its approach to advancing the development of such products in a work plan developed with DoD.

“Earlier this year, we reaffirmed our commitment to the Department of Defense and to the dedicated men and women protecting our country by expediting the development and availability of safe and effective priority medical products that are essential to the health of our military service members,” said FDA Commissioner Scott Gottlieb, MD.

“Through our collaborative program with the DoD, they’ve made clear the importance of access to freeze-dried plasma in initial efforts to control hemorrhage from battlefield trauma. Granting this authorization will support access to this important product in the event it’s needed. The FDA remains deeply committed to implementing an enduring pathway to ensure that these potentially life-saving medical products are made available in the most expeditious, safe, and effective manner possible.”

Photo courtesy of NIH

A group of experts has called for improvements in reporting adverse events (AEs) that occur in patients with hematologic malignancies.

The group highlighted deficiencies in capturing chronic, cumulative, and late AEs; collecting patient-reported outcomes (PROs); reporting AEs associated with hematopoietic stem cell transplant (HSCT); assessing long-term toxicity in survivors; reporting AEs to regulatory agencies; and tracking AEs that occur in routine clinical practice.

The experts discussed these problems and made recommendations for fixing them in The Lancet Haematology.

“The success in outcomes and survival in many hematological malignancies is historically unparalleled and fueled by scientific discovery and implementation,” said author Gita Thanarajasingam, MD, of the Mayo Clinic in Rochester, Minnesota.

“Patients are now living with the challenge of managing not just their hematological malignancy but also managing chronic therapy for their illness, with new types of acute, chronic, cumulative, and late toxicities. Measures to address the broad facets of toxicity assessment must be prioritized and further developed to ultimately enhance accurate, comprehensive, patient-centered toxicity reporting that will meaningfully inform the care of patients with blood cancers.”

Dr Thanarajasingam and a group of clinicians, investigators, regulators, biostatisticians, and patient advocates analyzed the evidence on AEs and proposed recommendations to policy makers, researchers, industry, and regulators.

First, the group noted that chronic, delayed, and cumulative AEs may go unreported in patients with hematologic malignancies. Therefore, longitudinal methods for AE analysis are needed, and phase 1 trials should have longer periods for evaluating dose-limiting toxicity.

The experts also said PROs are often overlooked, but it should be standard to assess PROs in clinical trials of patients with hematologic malignancies.

Another of the group’s concerns is the “cumbersome” reporting of AEs associated with HSCT acting as a barrier to clinical trials. The experts recommended using registry data to develop a consensus on expected AEs after HSCT.

The group also highlighted deficiencies in the “description and management” of cumulative and late toxicities in survivors of hematologic malignancies. Potential solutions to this problem include developing infrastructure to collect data for adult survivors and standardizing the use and content of survivorship care plans.

The experts said “meaningful” AEs are often underreported to regulatory agencies, so better systems are needed for collecting and analyzing AE data, and the electronic submission of AEs should be simplified.

Finally, the group said AEs occurring in routine clinical practice are difficult to capture and analyze on a large scale. This suggests a need to optimize the systematic, objective collection of toxicity data at multiple points in real-world databases, according to the experts.

Additional details and recommendations are available in the full report.

Photo courtesy of NIH

A group of experts has called for improvements in reporting adverse events (AEs) that occur in patients with hematologic malignancies.

The group highlighted deficiencies in capturing chronic, cumulative, and late AEs; collecting patient-reported outcomes (PROs); reporting AEs associated with hematopoietic stem cell transplant (HSCT); assessing long-term toxicity in survivors; reporting AEs to regulatory agencies; and tracking AEs that occur in routine clinical practice.

The experts discussed these problems and made recommendations for fixing them in The Lancet Haematology.

“The success in outcomes and survival in many hematological malignancies is historically unparalleled and fueled by scientific discovery and implementation,” said author Gita Thanarajasingam, MD, of the Mayo Clinic in Rochester, Minnesota.

“Patients are now living with the challenge of managing not just their hematological malignancy but also managing chronic therapy for their illness, with new types of acute, chronic, cumulative, and late toxicities. Measures to address the broad facets of toxicity assessment must be prioritized and further developed to ultimately enhance accurate, comprehensive, patient-centered toxicity reporting that will meaningfully inform the care of patients with blood cancers.”

Dr Thanarajasingam and a group of clinicians, investigators, regulators, biostatisticians, and patient advocates analyzed the evidence on AEs and proposed recommendations to policy makers, researchers, industry, and regulators.

First, the group noted that chronic, delayed, and cumulative AEs may go unreported in patients with hematologic malignancies. Therefore, longitudinal methods for AE analysis are needed, and phase 1 trials should have longer periods for evaluating dose-limiting toxicity.

The experts also said PROs are often overlooked, but it should be standard to assess PROs in clinical trials of patients with hematologic malignancies.

Another of the group’s concerns is the “cumbersome” reporting of AEs associated with HSCT acting as a barrier to clinical trials. The experts recommended using registry data to develop a consensus on expected AEs after HSCT.

The group also highlighted deficiencies in the “description and management” of cumulative and late toxicities in survivors of hematologic malignancies. Potential solutions to this problem include developing infrastructure to collect data for adult survivors and standardizing the use and content of survivorship care plans.

The experts said “meaningful” AEs are often underreported to regulatory agencies, so better systems are needed for collecting and analyzing AE data, and the electronic submission of AEs should be simplified.

Finally, the group said AEs occurring in routine clinical practice are difficult to capture and analyze on a large scale. This suggests a need to optimize the systematic, objective collection of toxicity data at multiple points in real-world databases, according to the experts.

Additional details and recommendations are available in the full report.

Photo courtesy of NIH

A group of experts has called for improvements in reporting adverse events (AEs) that occur in patients with hematologic malignancies.

The group highlighted deficiencies in capturing chronic, cumulative, and late AEs; collecting patient-reported outcomes (PROs); reporting AEs associated with hematopoietic stem cell transplant (HSCT); assessing long-term toxicity in survivors; reporting AEs to regulatory agencies; and tracking AEs that occur in routine clinical practice.

The experts discussed these problems and made recommendations for fixing them in The Lancet Haematology.

“The success in outcomes and survival in many hematological malignancies is historically unparalleled and fueled by scientific discovery and implementation,” said author Gita Thanarajasingam, MD, of the Mayo Clinic in Rochester, Minnesota.

“Patients are now living with the challenge of managing not just their hematological malignancy but also managing chronic therapy for their illness, with new types of acute, chronic, cumulative, and late toxicities. Measures to address the broad facets of toxicity assessment must be prioritized and further developed to ultimately enhance accurate, comprehensive, patient-centered toxicity reporting that will meaningfully inform the care of patients with blood cancers.”

Dr Thanarajasingam and a group of clinicians, investigators, regulators, biostatisticians, and patient advocates analyzed the evidence on AEs and proposed recommendations to policy makers, researchers, industry, and regulators.

First, the group noted that chronic, delayed, and cumulative AEs may go unreported in patients with hematologic malignancies. Therefore, longitudinal methods for AE analysis are needed, and phase 1 trials should have longer periods for evaluating dose-limiting toxicity.

The experts also said PROs are often overlooked, but it should be standard to assess PROs in clinical trials of patients with hematologic malignancies.

Another of the group’s concerns is the “cumbersome” reporting of AEs associated with HSCT acting as a barrier to clinical trials. The experts recommended using registry data to develop a consensus on expected AEs after HSCT.

The group also highlighted deficiencies in the “description and management” of cumulative and late toxicities in survivors of hematologic malignancies. Potential solutions to this problem include developing infrastructure to collect data for adult survivors and standardizing the use and content of survivorship care plans.

The experts said “meaningful” AEs are often underreported to regulatory agencies, so better systems are needed for collecting and analyzing AE data, and the electronic submission of AEs should be simplified.

Finally, the group said AEs occurring in routine clinical practice are difficult to capture and analyze on a large scale. This suggests a need to optimize the systematic, objective collection of toxicity data at multiple points in real-world databases, according to the experts.

Additional details and recommendations are available in the full report.

ANSWER

This ECG shows evidence of an acute anterior ST-elevation myocardial infarction (STEMI) and inferolateral ischemia.

STEMI criteria include a new ST-elevation in the anterior chest leads (V₂–V₄) at the J point (the junction of the termination of the QRS complex and the beginning of the ST segment). The American College of Cardiology/American Heart Association guidelines define cut-points for STEMI as follows: in women, 1.5 mm in leads V₂ and V₃ and 1 mm in all other leads; in men, 2 mm (those 40 and older) or 2.5 mm (those younger than 40) in leads V₂ and V₃ and 1 mm in all other leads. In this ECG, the classic “tombstone” pattern can be seen in the T wave in leads V₃ and V₄.

Inferolateral ischemia is evidenced by the ST elevation and T-wave flattening in the inferior leads II, III, and aVF, as well as in lateral chest leads V₅ and V₆.

The patient was transferred via ACLS ambulance to a tertiary care hospital for cardiac intervention.

ANSWER

This ECG shows evidence of an acute anterior ST-elevation myocardial infarction (STEMI) and inferolateral ischemia.

STEMI criteria include a new ST-elevation in the anterior chest leads (V₂–V₄) at the J point (the junction of the termination of the QRS complex and the beginning of the ST segment). The American College of Cardiology/American Heart Association guidelines define cut-points for STEMI as follows: in women, 1.5 mm in leads V₂ and V₃ and 1 mm in all other leads; in men, 2 mm (those 40 and older) or 2.5 mm (those younger than 40) in leads V₂ and V₃ and 1 mm in all other leads. In this ECG, the classic “tombstone” pattern can be seen in the T wave in leads V₃ and V₄.

Inferolateral ischemia is evidenced by the ST elevation and T-wave flattening in the inferior leads II, III, and aVF, as well as in lateral chest leads V₅ and V₆.

The patient was transferred via ACLS ambulance to a tertiary care hospital for cardiac intervention.

ANSWER

This ECG shows evidence of an acute anterior ST-elevation myocardial infarction (STEMI) and inferolateral ischemia.

STEMI criteria include a new ST-elevation in the anterior chest leads (V₂–V₄) at the J point (the junction of the termination of the QRS complex and the beginning of the ST segment). The American College of Cardiology/American Heart Association guidelines define cut-points for STEMI as follows: in women, 1.5 mm in leads V₂ and V₃ and 1 mm in all other leads; in men, 2 mm (those 40 and older) or 2.5 mm (those younger than 40) in leads V₂ and V₃ and 1 mm in all other leads. In this ECG, the classic “tombstone” pattern can be seen in the T wave in leads V₃ and V₄.

Inferolateral ischemia is evidenced by the ST elevation and T-wave flattening in the inferior leads II, III, and aVF, as well as in lateral chest leads V₅ and V₆.

The patient was transferred via ACLS ambulance to a tertiary care hospital for cardiac intervention.

Clinical question: Is there a difference in lower GI rebleeding risk in patients on antiplatelet medications versus those on anticoagulation medications?

Background: It is estimated that 29%-37% of patient with GI bleeds are also on antiplatelet or anticoagulation medications. Minimal research has looked at outcomes for these populations and the comparative risk of rebleeding.

Study design: A retrospective study.

Setting: Multicenter study in the United Kingdom.

Synopsis: The study followed 2,528 patients with lower GI bleeds, 917 of whom were on antiplatelet or anticoagulation medications. Of these, 504 were on single-antiplatelet therapy, 79 on dual-antiplatelet therapy, 232 on warfarin, and 102 on direct-acting oral anticoagulants (DOACs). Patients on single-antiplatelet agents had a threefold increased risk of rebleeding (hazard ratio, 3.57), those on dual-antiplatelet agents had a fivefold increased risk of rebleeding (HR, 5.38), and patients taking warfarin or DOACs had no increased risk of rebleeding.

In addition, the authors concluded that there was no significant difference in rebleeding risk if antiplatelet medications were held for less than 5 days during hospitalization versus if they were continued. The risk of rebleeding with antiplatelet agents is likely caused by the relatively long half-lives of these therapies. In contrast, warfarin and DOACs have available reversal agents, and DOACs have comparatively shorter half-lives.

Bottom line: The risk of rebleeding from a lower-GI bleed is higher in patients on antiplatelet medications than it is in patients on warfarin or DOACs.

Citation: Oakland K et al. Rebleeding and mortality after lower gastrointestinal bleeding in patients taking antiplatelets or anticoagulants. Clin Gastroent Hepatol. 2017 Dec 23. doi: 10.1016/j.cgh.2017.12.032.

Dr. Thota is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.

Clinical question: Is there a difference in lower GI rebleeding risk in patients on antiplatelet medications versus those on anticoagulation medications?

Background: It is estimated that 29%-37% of patient with GI bleeds are also on antiplatelet or anticoagulation medications. Minimal research has looked at outcomes for these populations and the comparative risk of rebleeding.

Study design: A retrospective study.

Setting: Multicenter study in the United Kingdom.

Synopsis: The study followed 2,528 patients with lower GI bleeds, 917 of whom were on antiplatelet or anticoagulation medications. Of these, 504 were on single-antiplatelet therapy, 79 on dual-antiplatelet therapy, 232 on warfarin, and 102 on direct-acting oral anticoagulants (DOACs). Patients on single-antiplatelet agents had a threefold increased risk of rebleeding (hazard ratio, 3.57), those on dual-antiplatelet agents had a fivefold increased risk of rebleeding (HR, 5.38), and patients taking warfarin or DOACs had no increased risk of rebleeding.

In addition, the authors concluded that there was no significant difference in rebleeding risk if antiplatelet medications were held for less than 5 days during hospitalization versus if they were continued. The risk of rebleeding with antiplatelet agents is likely caused by the relatively long half-lives of these therapies. In contrast, warfarin and DOACs have available reversal agents, and DOACs have comparatively shorter half-lives.

Bottom line: The risk of rebleeding from a lower-GI bleed is higher in patients on antiplatelet medications than it is in patients on warfarin or DOACs.

Citation: Oakland K et al. Rebleeding and mortality after lower gastrointestinal bleeding in patients taking antiplatelets or anticoagulants. Clin Gastroent Hepatol. 2017 Dec 23. doi: 10.1016/j.cgh.2017.12.032.

Dr. Thota is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.

Clinical question: Is there a difference in lower GI rebleeding risk in patients on antiplatelet medications versus those on anticoagulation medications?

Background: It is estimated that 29%-37% of patient with GI bleeds are also on antiplatelet or anticoagulation medications. Minimal research has looked at outcomes for these populations and the comparative risk of rebleeding.

Study design: A retrospective study.

Setting: Multicenter study in the United Kingdom.

Synopsis: The study followed 2,528 patients with lower GI bleeds, 917 of whom were on antiplatelet or anticoagulation medications. Of these, 504 were on single-antiplatelet therapy, 79 on dual-antiplatelet therapy, 232 on warfarin, and 102 on direct-acting oral anticoagulants (DOACs). Patients on single-antiplatelet agents had a threefold increased risk of rebleeding (hazard ratio, 3.57), those on dual-antiplatelet agents had a fivefold increased risk of rebleeding (HR, 5.38), and patients taking warfarin or DOACs had no increased risk of rebleeding.

In addition, the authors concluded that there was no significant difference in rebleeding risk if antiplatelet medications were held for less than 5 days during hospitalization versus if they were continued. The risk of rebleeding with antiplatelet agents is likely caused by the relatively long half-lives of these therapies. In contrast, warfarin and DOACs have available reversal agents, and DOACs have comparatively shorter half-lives.

Bottom line: The risk of rebleeding from a lower-GI bleed is higher in patients on antiplatelet medications than it is in patients on warfarin or DOACs.

Citation: Oakland K et al. Rebleeding and mortality after lower gastrointestinal bleeding in patients taking antiplatelets or anticoagulants. Clin Gastroent Hepatol. 2017 Dec 23. doi: 10.1016/j.cgh.2017.12.032.

Dr. Thota is a hospitalist at UC San Diego Health and an assistant clinical professor at the University of California, San Diego.

There’s not enough evidence to recommend – or not recommend – routine ankle-brachial index screening for peripheral artery disease in asymptomatic adults without known cardiovascular or chronic kidney disease, according to the U.S. Preventive Services Task Force.

“A substantial number of asymptomatic persons with low ABI may never develop clinical signs or symptoms of CVD or PAD but would still be subjected to the harms of testing,” including false positives, exposure to gadolinium or contrast dye with subsequent imaging, and others, the Task Force wrote in JAMA.

In short, it found “inadequate evidence to assess whether screening for and treatment of PAD in asymptomatic patients leads to clinically important benefits in either preventing the progression of PAD or preventing CVD events. ... The current evidence is insufficient to assess the balance of benefits and harms of screening for PAD and CVD risk with the ABI in asymptomatic adults.”

The group made no recommendation, and issued an I statement, for insufficient evidence, July 10. The new work replaces the Task Force’s last visitation in 2013, which was also an “I statement.”

ABI is systolic blood pressure at the ankle divided by the systolic blood pressure in the arm while the patient is lying down. A ratio below 1 is considered abnormal.

ABI is low in perhaps about 6% of adults over 40 years old but “the natural history of screen-detected PAD, including the development of morbidity and mortality directly related to atherosclerosis in the lower limbs, is not well known. ... Large, population-based, randomized trials of screening [versus] no screening are needed to determine whether screening for PAD with the ABI improves clinical outcomes,” the task force said.

Among the many studies it reviewed were two large trials of asymptomatic women with low ABI treated with aspirin 100 mg/d for several years. Neither study showed any significant difference in CVD events, mortality, or development of intermittent claudication.

Even in high-risk people – diabetes, high blood pressure, high cholesterol, current tobacco use – there was “no compelling evidence” to support routine screening, so long as they have no symptoms.

The new review is broader than the group’s 2013 effort, and includes a broader population and range of interventions. Even so, “the recommendation remains an I statement,” it said.

The USPSTF is supported by the U.S. Agency for Healthcare Research and Quality.

[email protected]

SOURCE: JAMA. 2018 Jul 10;320(2):177-83

There’s not enough evidence to recommend – or not recommend – routine ankle-brachial index screening for peripheral artery disease in asymptomatic adults without known cardiovascular or chronic kidney disease, according to the U.S. Preventive Services Task Force.

“A substantial number of asymptomatic persons with low ABI may never develop clinical signs or symptoms of CVD or PAD but would still be subjected to the harms of testing,” including false positives, exposure to gadolinium or contrast dye with subsequent imaging, and others, the Task Force wrote in JAMA.

In short, it found “inadequate evidence to assess whether screening for and treatment of PAD in asymptomatic patients leads to clinically important benefits in either preventing the progression of PAD or preventing CVD events. ... The current evidence is insufficient to assess the balance of benefits and harms of screening for PAD and CVD risk with the ABI in asymptomatic adults.”

The group made no recommendation, and issued an I statement, for insufficient evidence, July 10. The new work replaces the Task Force’s last visitation in 2013, which was also an “I statement.”

ABI is systolic blood pressure at the ankle divided by the systolic blood pressure in the arm while the patient is lying down. A ratio below 1 is considered abnormal.

ABI is low in perhaps about 6% of adults over 40 years old but “the natural history of screen-detected PAD, including the development of morbidity and mortality directly related to atherosclerosis in the lower limbs, is not well known. ... Large, population-based, randomized trials of screening [versus] no screening are needed to determine whether screening for PAD with the ABI improves clinical outcomes,” the task force said.

Among the many studies it reviewed were two large trials of asymptomatic women with low ABI treated with aspirin 100 mg/d for several years. Neither study showed any significant difference in CVD events, mortality, or development of intermittent claudication.

Even in high-risk people – diabetes, high blood pressure, high cholesterol, current tobacco use – there was “no compelling evidence” to support routine screening, so long as they have no symptoms.

The new review is broader than the group’s 2013 effort, and includes a broader population and range of interventions. Even so, “the recommendation remains an I statement,” it said.

The USPSTF is supported by the U.S. Agency for Healthcare Research and Quality.

[email protected]

SOURCE: JAMA. 2018 Jul 10;320(2):177-83

There’s not enough evidence to recommend – or not recommend – routine ankle-brachial index screening for peripheral artery disease in asymptomatic adults without known cardiovascular or chronic kidney disease, according to the U.S. Preventive Services Task Force.

“A substantial number of asymptomatic persons with low ABI may never develop clinical signs or symptoms of CVD or PAD but would still be subjected to the harms of testing,” including false positives, exposure to gadolinium or contrast dye with subsequent imaging, and others, the Task Force wrote in JAMA.

In short, it found “inadequate evidence to assess whether screening for and treatment of PAD in asymptomatic patients leads to clinically important benefits in either preventing the progression of PAD or preventing CVD events. ... The current evidence is insufficient to assess the balance of benefits and harms of screening for PAD and CVD risk with the ABI in asymptomatic adults.”

The group made no recommendation, and issued an I statement, for insufficient evidence, July 10. The new work replaces the Task Force’s last visitation in 2013, which was also an “I statement.”

ABI is systolic blood pressure at the ankle divided by the systolic blood pressure in the arm while the patient is lying down. A ratio below 1 is considered abnormal.

ABI is low in perhaps about 6% of adults over 40 years old but “the natural history of screen-detected PAD, including the development of morbidity and mortality directly related to atherosclerosis in the lower limbs, is not well known. ... Large, population-based, randomized trials of screening [versus] no screening are needed to determine whether screening for PAD with the ABI improves clinical outcomes,” the task force said.

Among the many studies it reviewed were two large trials of asymptomatic women with low ABI treated with aspirin 100 mg/d for several years. Neither study showed any significant difference in CVD events, mortality, or development of intermittent claudication.

Even in high-risk people – diabetes, high blood pressure, high cholesterol, current tobacco use – there was “no compelling evidence” to support routine screening, so long as they have no symptoms.

The new review is broader than the group’s 2013 effort, and includes a broader population and range of interventions. Even so, “the recommendation remains an I statement,” it said.

The USPSTF is supported by the U.S. Agency for Healthcare Research and Quality.

[email protected]

SOURCE: JAMA. 2018 Jul 10;320(2):177-83