Photo by Esther Dyson

New research has revealed a lack of public information regarding protocols for industry-sponsored, randomized drug trials in Denmark.

First, researchers found it difficult to obtain protocols for commercially sponsored trials, with some sponsors taking legal action in an attempt to keep protocols private.

When the researchers did receive protocols, many had widespread redactions.

The researchers reported these findings in the Journal of the Royal Society of Medicine.

“We wished to compare the information in the protocols with the information provided to the patients in order to evaluate whether the trials were ethical and necessary and whether essential information about the benefits and the harms of the drugs had been hidden from the patients,” said study author Peter Gøtzsche, MD, director of the Nordic Cochrane Centre in Copenhagen, Denmark.

To that end, Dr Gøtzsche and his colleagues used the Danish Freedom of Information Act to request access to 78 protocols for randomized trials that were approved by a research ethics committee from October 2012 to March 2013.

The researchers said several companies refused to provide protocols and involved their lawyers. In fact, Sanofi-Aventis sued the National Committee on Health Research Ethics but lost.

Three years after this project was started, the researchers were able to obtain all the protocols they had requested. Eight protocols were excluded from analysis because they did not meet the research inclusion criteria.

Seventeen of 34 protocols for commercially sponsored trials were unredacted, compared to 34 of 36 non-commercially sponsored trials.

The researchers said the redactions “were most widespread in those sections of the protocol where there is empirical evidence of substantial problems with the trustworthiness of published drug trials.”

This includes data analysis, the handling of missing data, the detection/analysis of adverse events, the definition of patient outcomes, interim analyses and premature study termination, the sponsor’s access to incoming data while the study is ongoing, ownership of the data, and investigators’ publication rights.

“The amount of redactions in the protocols we received was so vast that it made them rather useless for assessing the ethical justification for the studies and to identify discrepancies with subsequent publications,” Dr Gøtzsche said.

“We could not identify any legitimate rationale for the redactions. The current mistrust in industry-sponsored drug trials can only change if the industry offers unconditional access to its trial protocols and other relevant documents and data.”

Photo by Esther Dyson

New research has revealed a lack of public information regarding protocols for industry-sponsored, randomized drug trials in Denmark.

First, researchers found it difficult to obtain protocols for commercially sponsored trials, with some sponsors taking legal action in an attempt to keep protocols private.

When the researchers did receive protocols, many had widespread redactions.

The researchers reported these findings in the Journal of the Royal Society of Medicine.

“We wished to compare the information in the protocols with the information provided to the patients in order to evaluate whether the trials were ethical and necessary and whether essential information about the benefits and the harms of the drugs had been hidden from the patients,” said study author Peter Gøtzsche, MD, director of the Nordic Cochrane Centre in Copenhagen, Denmark.

To that end, Dr Gøtzsche and his colleagues used the Danish Freedom of Information Act to request access to 78 protocols for randomized trials that were approved by a research ethics committee from October 2012 to March 2013.

The researchers said several companies refused to provide protocols and involved their lawyers. In fact, Sanofi-Aventis sued the National Committee on Health Research Ethics but lost.

Three years after this project was started, the researchers were able to obtain all the protocols they had requested. Eight protocols were excluded from analysis because they did not meet the research inclusion criteria.

Seventeen of 34 protocols for commercially sponsored trials were unredacted, compared to 34 of 36 non-commercially sponsored trials.

The researchers said the redactions “were most widespread in those sections of the protocol where there is empirical evidence of substantial problems with the trustworthiness of published drug trials.”

This includes data analysis, the handling of missing data, the detection/analysis of adverse events, the definition of patient outcomes, interim analyses and premature study termination, the sponsor’s access to incoming data while the study is ongoing, ownership of the data, and investigators’ publication rights.

“The amount of redactions in the protocols we received was so vast that it made them rather useless for assessing the ethical justification for the studies and to identify discrepancies with subsequent publications,” Dr Gøtzsche said.

“We could not identify any legitimate rationale for the redactions. The current mistrust in industry-sponsored drug trials can only change if the industry offers unconditional access to its trial protocols and other relevant documents and data.”

Photo by Esther Dyson

New research has revealed a lack of public information regarding protocols for industry-sponsored, randomized drug trials in Denmark.

First, researchers found it difficult to obtain protocols for commercially sponsored trials, with some sponsors taking legal action in an attempt to keep protocols private.

When the researchers did receive protocols, many had widespread redactions.

The researchers reported these findings in the Journal of the Royal Society of Medicine.

“We wished to compare the information in the protocols with the information provided to the patients in order to evaluate whether the trials were ethical and necessary and whether essential information about the benefits and the harms of the drugs had been hidden from the patients,” said study author Peter Gøtzsche, MD, director of the Nordic Cochrane Centre in Copenhagen, Denmark.

To that end, Dr Gøtzsche and his colleagues used the Danish Freedom of Information Act to request access to 78 protocols for randomized trials that were approved by a research ethics committee from October 2012 to March 2013.

The researchers said several companies refused to provide protocols and involved their lawyers. In fact, Sanofi-Aventis sued the National Committee on Health Research Ethics but lost.

Three years after this project was started, the researchers were able to obtain all the protocols they had requested. Eight protocols were excluded from analysis because they did not meet the research inclusion criteria.

Seventeen of 34 protocols for commercially sponsored trials were unredacted, compared to 34 of 36 non-commercially sponsored trials.

The researchers said the redactions “were most widespread in those sections of the protocol where there is empirical evidence of substantial problems with the trustworthiness of published drug trials.”

This includes data analysis, the handling of missing data, the detection/analysis of adverse events, the definition of patient outcomes, interim analyses and premature study termination, the sponsor’s access to incoming data while the study is ongoing, ownership of the data, and investigators’ publication rights.

“The amount of redactions in the protocols we received was so vast that it made them rather useless for assessing the ethical justification for the studies and to identify discrepancies with subsequent publications,” Dr Gøtzsche said.

“We could not identify any legitimate rationale for the redactions. The current mistrust in industry-sponsored drug trials can only change if the industry offers unconditional access to its trial protocols and other relevant documents and data.”

Tsodikov, A., et al, Ann Intern Med 167(7):449, October 3, 2017

BACKGROUND: In 2012 the U.S. Preventive Services Task Force recommended against routine prostate cancer screening because its lack of effect on long-term mortality. Their recommendations (which are being updated) were based mainly on the ERSPC (European Randomized Study of Screening for Prostate Cancer) and PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) trials. However, these two trials are substantially different in terms of design, settings, screening intensity, baseline risk and screening effect on mortality (a relative reduction of 21% vs. no reduction, respectively).

METHODS: To evaluate whether the mortality difference persisted after accounting for implementation and practice setting differences, these multinational authors combined data from both trials to conduct a traditional statistical analysis that adjusted for participant age and trial setting, and extended analyses that overcame variability in screening intensity by considering mean lead times, which indicated increased prostate cancer incidence and earlier diagnosis with vs. without screening. Follow-up was restricted to eleven years for both trials.

RESULTS: The traditional analysis demonstrated a marginally different screening effect on mortality between trials (p=0.087), and an overall relative risk reduction of 16% (p=0.010). Extended analyses indicated no difference in screening effect on mortality between trials (p=0.37 to 0.47), and an overall association of longer mean lead times with a lower risk of prostate cancer specific death (p=0.0027 to 0.0032). Screening was estimated to lead to a 25-31% and a 27-32% relative reduction in risk of prostate cancer death in the two trials, respectively, vs. no screening (NNT = ~ 1,111 for 11 years of regular screening).

CONCLUSIONS: This analysis of data from two large prostate cancer-screening trials found that screening significantly reduced prostate cancer mortality risk compared with no screening. 18 references ([email protected] for reprints)

Tsodikov, A., et al, Ann Intern Med 167(7):449, October 3, 2017

BACKGROUND: In 2012 the U.S. Preventive Services Task Force recommended against routine prostate cancer screening because its lack of effect on long-term mortality. Their recommendations (which are being updated) were based mainly on the ERSPC (European Randomized Study of Screening for Prostate Cancer) and PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) trials. However, these two trials are substantially different in terms of design, settings, screening intensity, baseline risk and screening effect on mortality (a relative reduction of 21% vs. no reduction, respectively).

METHODS: To evaluate whether the mortality difference persisted after accounting for implementation and practice setting differences, these multinational authors combined data from both trials to conduct a traditional statistical analysis that adjusted for participant age and trial setting, and extended analyses that overcame variability in screening intensity by considering mean lead times, which indicated increased prostate cancer incidence and earlier diagnosis with vs. without screening. Follow-up was restricted to eleven years for both trials.

RESULTS: The traditional analysis demonstrated a marginally different screening effect on mortality between trials (p=0.087), and an overall relative risk reduction of 16% (p=0.010). Extended analyses indicated no difference in screening effect on mortality between trials (p=0.37 to 0.47), and an overall association of longer mean lead times with a lower risk of prostate cancer specific death (p=0.0027 to 0.0032). Screening was estimated to lead to a 25-31% and a 27-32% relative reduction in risk of prostate cancer death in the two trials, respectively, vs. no screening (NNT = ~ 1,111 for 11 years of regular screening).

CONCLUSIONS: This analysis of data from two large prostate cancer-screening trials found that screening significantly reduced prostate cancer mortality risk compared with no screening. 18 references ([email protected] for reprints)

Tsodikov, A., et al, Ann Intern Med 167(7):449, October 3, 2017

BACKGROUND: In 2012 the U.S. Preventive Services Task Force recommended against routine prostate cancer screening because its lack of effect on long-term mortality. Their recommendations (which are being updated) were based mainly on the ERSPC (European Randomized Study of Screening for Prostate Cancer) and PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) trials. However, these two trials are substantially different in terms of design, settings, screening intensity, baseline risk and screening effect on mortality (a relative reduction of 21% vs. no reduction, respectively).

METHODS: To evaluate whether the mortality difference persisted after accounting for implementation and practice setting differences, these multinational authors combined data from both trials to conduct a traditional statistical analysis that adjusted for participant age and trial setting, and extended analyses that overcame variability in screening intensity by considering mean lead times, which indicated increased prostate cancer incidence and earlier diagnosis with vs. without screening. Follow-up was restricted to eleven years for both trials.

RESULTS: The traditional analysis demonstrated a marginally different screening effect on mortality between trials (p=0.087), and an overall relative risk reduction of 16% (p=0.010). Extended analyses indicated no difference in screening effect on mortality between trials (p=0.37 to 0.47), and an overall association of longer mean lead times with a lower risk of prostate cancer specific death (p=0.0027 to 0.0032). Screening was estimated to lead to a 25-31% and a 27-32% relative reduction in risk of prostate cancer death in the two trials, respectively, vs. no screening (NNT = ~ 1,111 for 11 years of regular screening).

CONCLUSIONS: This analysis of data from two large prostate cancer-screening trials found that screening significantly reduced prostate cancer mortality risk compared with no screening. 18 references ([email protected] for reprints)

NEW YORK – About 25% of preadolescent children with attention-deficit/hyperactivity disorder have impulsive reactive aggression, a common but so far unnamed comorbidity that deserves attention and therapy, according to Robert L. Findling, MD.

Emphasizing the reactive component to this behavioral problem, he said: “They look okay until someone bumps into them at school. They do not have a mood disorder. They have a disorder of reactivity.”

Thinglass/Thinkstock

Dr. Findling reported financial ties with numerous pharmaceutical companies.

[email protected]

SOURCE: Findling RL. Psychopharmacology Update Institute

NEW YORK – About 25% of preadolescent children with attention-deficit/hyperactivity disorder have impulsive reactive aggression, a common but so far unnamed comorbidity that deserves attention and therapy, according to Robert L. Findling, MD.

Emphasizing the reactive component to this behavioral problem, he said: “They look okay until someone bumps into them at school. They do not have a mood disorder. They have a disorder of reactivity.”

Thinglass/Thinkstock

Dr. Findling reported financial ties with numerous pharmaceutical companies.

[email protected]

SOURCE: Findling RL. Psychopharmacology Update Institute

NEW YORK – About 25% of preadolescent children with attention-deficit/hyperactivity disorder have impulsive reactive aggression, a common but so far unnamed comorbidity that deserves attention and therapy, according to Robert L. Findling, MD.

Emphasizing the reactive component to this behavioral problem, he said: “They look okay until someone bumps into them at school. They do not have a mood disorder. They have a disorder of reactivity.”

Thinglass/Thinkstock

Dr. Findling reported financial ties with numerous pharmaceutical companies.

[email protected]

SOURCE: Findling RL. Psychopharmacology Update Institute

LAKE BUENA VISTA, FLA. – Every year brings new studies, updates, and trials, and it can be a challenge to keep up.

Christian Jones, MD, FACS, a general surgeon in the division of acute care surgery at Johns Hopkins University, Baltimore, ranked some of the more notable trauma studies published in the past year and presented his perspective on them at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Day 2 is the “sweet spot” for cholecystectomy

When it comes to cholecystectomy, acute cholecystitis (AC) patients appear to fare the best when operations are conducted on day 2 after admission, according to a study of patients registered in the Swedish Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks).

The retrospective study of 15,760 AC patients found that the rate of 30-day mortality of AC patients was significantly higher for patients who underwent a cholecystectomy on day of (odds ratio = .42) 3 days after (OR = .34), and 4 days after admission (OR = 1.0), compared with those who were operated on between 1 day after (OR = .23), and 2 days after (OR = .29) admission.

Lead author My Blohm, MD, of the department of clinical sciences, intervention, and technology at the Karolinska Institutet, Stockholm, and fellow investigators hypothesized that waiting allows patients to be medically optimized for surgery (J Gastrointest Surg. 2017;21[1]: 33-40).

With 90-day mortality rates showing nearly identical results for day 1 and day 2, holding off on surgery may be the best move for the patient, even if it is not the ideal situation for a provider.

“Sure, as we all know by now, delayed cholecystectomy is seldom necessary, later surgery is more difficult, and more likely to be associated with complications at least with an equal conversion to an open procedure, but even more surprising is the higher mortality on the admissions day,” said Dr. Jones.

Antibiotics for abscess drainage patients

For patients requiring abscess drainage, antibiotics may be the best bet to keep infection at bay, according to a study published in the New England Journal of Medicine in June 2017.

The prospective, randomized, placebo-controlled, double-blind, study of 786 simple skin abscess drainage patients found clindamycin and Bactrim (sulfamethoxazole and trimethoprim) outperformed a placebo in an evaluation of symptoms of true ongoing infection in patients even 30 days after the procedure (N Engl J Med. 2017 Jun 29;376[26]:2545-55).

Patients studied had Staphylococcus aureus (527) or methicillin-resistant S. aureus (388).

After 10 days of therapy, cure rate of infection for the clindamycin and Bactrim groups were 83% and 82% respectively, compared with 70% in the placebo group, according to Robert S. Daum, MD, principal investigator at the MRSA Research Center, University of Chicago. After 30 days, cure rate for both antibiotic groups remained superior to that of the placebo group.

While these treatments were successful, concern of drug resistance is notable and should be taken into consideration when deciding on treatment options.

“This does get to our typical concern with increased antibiotic usage, and that’s the concern of the health of the community versus the health of the individual patient,” said Dr. Jones. “Is the increased rate of [antibiotic] resistance important enough to have a lower cure rate of simple abscess drainage? We don’t know the answer to that.”

Loop ileostomies look good for C. diff patients

This minimally invasive procedure has been the subject of some well-received studies with findings that indicate it is a promising choice for patients with a Clostridium difficile–associated disease (CDAD) over total colectomy, Dr. Jones said.

In a study published in the Journal of Trauma and Acute Care Surgery, a study group of patients with CDAD who had loop ileostomy had no statistical difference in almost any recorded characteristic compared with those who underwent a total colectomy, except mortality rate. The retrospective, multicenter study of 98 CDAD patients found the mortality rate of the loop ileostomy group to be 17.2%, compared with 39.7% in the total colectomy group (J Trauma Acute Care Surg. 2017 Jul;83[1]:36-40).

“The outcomes all favored loop ileostomy in a statistically significant fashion,” said Dr. Jones. “Unsurprisingly, estimated blood loss and need for transfusions were all significantly less in the loop ileostomy patients, and the adjusted overall mortality, even if requiring a reoperation, still favored doing the loop ileostomy first.”

The one difference between LI and colectomy patients was a longer time from initial diagnosis to operation among LI patients, with about 12 hours from diagnosis for the colectomy versus 24 hours for LI patients, according to lead author Paula Ferrada, MD, FACS, director of the surgical and trauma intensive care unit at Virginia Commonwealth University, Richmond, and her fellow investigators,

Contrary to previous findings, the study found that LI can be performed on sick patients as well, according to the researchers, and failure of the procedure is not associated with increased mortality.

While these findings are encouraging, “there are things that the individual patient may reveal to you on your examination that tell you they are not a candidate and that you should go to total colectomy,” said Dr. Jones. “Keep in mind that perhaps we can be a bit more aggressive in this less invasive procedure.”
 

The skin vac actually works

A study published in Annals of Surgery found prophylactic negative-pressure dressings are associated with a decreased rate of surgical site infections in laparotomy wounds.

“The biggest surprise to me out of all of these studies is that a new piece of technology actually seems to work,” said Dr. Jones.

The randomized study included 50 laparotomy patients with a stapled wound, half of whom received a skin vac over their incision while the other half had a standard OpSite occlusive dressing (Ann Surg. 2017 Jun;265[6]:1082-6).

Patients in both arms had the same type of wound and had their dressings on for 4 days before being switched.

Rate of surgical site infections for the skin vac group was 8.3% over 30 days from operation, compared with 32% in the OpSite group. Average length of stay for patients with the pressure dressing was 6.1 days, while patients with an OpSite dressing had a length of 14.7 days, more than double, according to lead author Donal Peter O’Leary, MD, surgeon at Cork University Hospital, Ireland.

The difference in length of stay does become insignificant if six OpSite patients who stayed longer than 20 days are discounted, only two of whom were delayed because of wound complications as opposed to placement issues or unassociated infections.

“But a surgical site infection difference of 50% or more using a skin vac instead of a standard dressing, whether you’re talking about clean, clean-contaminated, or contaminated cases with a skin closure, seems to be worthy of notice,” explained Dr. Jones.

[email protected]

LAKE BUENA VISTA, FLA. – Every year brings new studies, updates, and trials, and it can be a challenge to keep up.

Christian Jones, MD, FACS, a general surgeon in the division of acute care surgery at Johns Hopkins University, Baltimore, ranked some of the more notable trauma studies published in the past year and presented his perspective on them at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Day 2 is the “sweet spot” for cholecystectomy

When it comes to cholecystectomy, acute cholecystitis (AC) patients appear to fare the best when operations are conducted on day 2 after admission, according to a study of patients registered in the Swedish Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks).

The retrospective study of 15,760 AC patients found that the rate of 30-day mortality of AC patients was significantly higher for patients who underwent a cholecystectomy on day of (odds ratio = .42) 3 days after (OR = .34), and 4 days after admission (OR = 1.0), compared with those who were operated on between 1 day after (OR = .23), and 2 days after (OR = .29) admission.

Lead author My Blohm, MD, of the department of clinical sciences, intervention, and technology at the Karolinska Institutet, Stockholm, and fellow investigators hypothesized that waiting allows patients to be medically optimized for surgery (J Gastrointest Surg. 2017;21[1]: 33-40).

With 90-day mortality rates showing nearly identical results for day 1 and day 2, holding off on surgery may be the best move for the patient, even if it is not the ideal situation for a provider.

“Sure, as we all know by now, delayed cholecystectomy is seldom necessary, later surgery is more difficult, and more likely to be associated with complications at least with an equal conversion to an open procedure, but even more surprising is the higher mortality on the admissions day,” said Dr. Jones.

Antibiotics for abscess drainage patients

For patients requiring abscess drainage, antibiotics may be the best bet to keep infection at bay, according to a study published in the New England Journal of Medicine in June 2017.

The prospective, randomized, placebo-controlled, double-blind, study of 786 simple skin abscess drainage patients found clindamycin and Bactrim (sulfamethoxazole and trimethoprim) outperformed a placebo in an evaluation of symptoms of true ongoing infection in patients even 30 days after the procedure (N Engl J Med. 2017 Jun 29;376[26]:2545-55).

Patients studied had Staphylococcus aureus (527) or methicillin-resistant S. aureus (388).

After 10 days of therapy, cure rate of infection for the clindamycin and Bactrim groups were 83% and 82% respectively, compared with 70% in the placebo group, according to Robert S. Daum, MD, principal investigator at the MRSA Research Center, University of Chicago. After 30 days, cure rate for both antibiotic groups remained superior to that of the placebo group.

While these treatments were successful, concern of drug resistance is notable and should be taken into consideration when deciding on treatment options.

“This does get to our typical concern with increased antibiotic usage, and that’s the concern of the health of the community versus the health of the individual patient,” said Dr. Jones. “Is the increased rate of [antibiotic] resistance important enough to have a lower cure rate of simple abscess drainage? We don’t know the answer to that.”

Loop ileostomies look good for C. diff patients

This minimally invasive procedure has been the subject of some well-received studies with findings that indicate it is a promising choice for patients with a Clostridium difficile–associated disease (CDAD) over total colectomy, Dr. Jones said.

In a study published in the Journal of Trauma and Acute Care Surgery, a study group of patients with CDAD who had loop ileostomy had no statistical difference in almost any recorded characteristic compared with those who underwent a total colectomy, except mortality rate. The retrospective, multicenter study of 98 CDAD patients found the mortality rate of the loop ileostomy group to be 17.2%, compared with 39.7% in the total colectomy group (J Trauma Acute Care Surg. 2017 Jul;83[1]:36-40).

“The outcomes all favored loop ileostomy in a statistically significant fashion,” said Dr. Jones. “Unsurprisingly, estimated blood loss and need for transfusions were all significantly less in the loop ileostomy patients, and the adjusted overall mortality, even if requiring a reoperation, still favored doing the loop ileostomy first.”

The one difference between LI and colectomy patients was a longer time from initial diagnosis to operation among LI patients, with about 12 hours from diagnosis for the colectomy versus 24 hours for LI patients, according to lead author Paula Ferrada, MD, FACS, director of the surgical and trauma intensive care unit at Virginia Commonwealth University, Richmond, and her fellow investigators,

Contrary to previous findings, the study found that LI can be performed on sick patients as well, according to the researchers, and failure of the procedure is not associated with increased mortality.

While these findings are encouraging, “there are things that the individual patient may reveal to you on your examination that tell you they are not a candidate and that you should go to total colectomy,” said Dr. Jones. “Keep in mind that perhaps we can be a bit more aggressive in this less invasive procedure.”
 

The skin vac actually works

A study published in Annals of Surgery found prophylactic negative-pressure dressings are associated with a decreased rate of surgical site infections in laparotomy wounds.

“The biggest surprise to me out of all of these studies is that a new piece of technology actually seems to work,” said Dr. Jones.

The randomized study included 50 laparotomy patients with a stapled wound, half of whom received a skin vac over their incision while the other half had a standard OpSite occlusive dressing (Ann Surg. 2017 Jun;265[6]:1082-6).

Patients in both arms had the same type of wound and had their dressings on for 4 days before being switched.

Rate of surgical site infections for the skin vac group was 8.3% over 30 days from operation, compared with 32% in the OpSite group. Average length of stay for patients with the pressure dressing was 6.1 days, while patients with an OpSite dressing had a length of 14.7 days, more than double, according to lead author Donal Peter O’Leary, MD, surgeon at Cork University Hospital, Ireland.

The difference in length of stay does become insignificant if six OpSite patients who stayed longer than 20 days are discounted, only two of whom were delayed because of wound complications as opposed to placement issues or unassociated infections.

“But a surgical site infection difference of 50% or more using a skin vac instead of a standard dressing, whether you’re talking about clean, clean-contaminated, or contaminated cases with a skin closure, seems to be worthy of notice,” explained Dr. Jones.

[email protected]

LAKE BUENA VISTA, FLA. – Every year brings new studies, updates, and trials, and it can be a challenge to keep up.

Christian Jones, MD, FACS, a general surgeon in the division of acute care surgery at Johns Hopkins University, Baltimore, ranked some of the more notable trauma studies published in the past year and presented his perspective on them at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Day 2 is the “sweet spot” for cholecystectomy

When it comes to cholecystectomy, acute cholecystitis (AC) patients appear to fare the best when operations are conducted on day 2 after admission, according to a study of patients registered in the Swedish Registry of Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (GallRiks).

The retrospective study of 15,760 AC patients found that the rate of 30-day mortality of AC patients was significantly higher for patients who underwent a cholecystectomy on day of (odds ratio = .42) 3 days after (OR = .34), and 4 days after admission (OR = 1.0), compared with those who were operated on between 1 day after (OR = .23), and 2 days after (OR = .29) admission.

Lead author My Blohm, MD, of the department of clinical sciences, intervention, and technology at the Karolinska Institutet, Stockholm, and fellow investigators hypothesized that waiting allows patients to be medically optimized for surgery (J Gastrointest Surg. 2017;21[1]: 33-40).

With 90-day mortality rates showing nearly identical results for day 1 and day 2, holding off on surgery may be the best move for the patient, even if it is not the ideal situation for a provider.

“Sure, as we all know by now, delayed cholecystectomy is seldom necessary, later surgery is more difficult, and more likely to be associated with complications at least with an equal conversion to an open procedure, but even more surprising is the higher mortality on the admissions day,” said Dr. Jones.

Antibiotics for abscess drainage patients

For patients requiring abscess drainage, antibiotics may be the best bet to keep infection at bay, according to a study published in the New England Journal of Medicine in June 2017.

The prospective, randomized, placebo-controlled, double-blind, study of 786 simple skin abscess drainage patients found clindamycin and Bactrim (sulfamethoxazole and trimethoprim) outperformed a placebo in an evaluation of symptoms of true ongoing infection in patients even 30 days after the procedure (N Engl J Med. 2017 Jun 29;376[26]:2545-55).

Patients studied had Staphylococcus aureus (527) or methicillin-resistant S. aureus (388).

After 10 days of therapy, cure rate of infection for the clindamycin and Bactrim groups were 83% and 82% respectively, compared with 70% in the placebo group, according to Robert S. Daum, MD, principal investigator at the MRSA Research Center, University of Chicago. After 30 days, cure rate for both antibiotic groups remained superior to that of the placebo group.

While these treatments were successful, concern of drug resistance is notable and should be taken into consideration when deciding on treatment options.

“This does get to our typical concern with increased antibiotic usage, and that’s the concern of the health of the community versus the health of the individual patient,” said Dr. Jones. “Is the increased rate of [antibiotic] resistance important enough to have a lower cure rate of simple abscess drainage? We don’t know the answer to that.”

Loop ileostomies look good for C. diff patients

This minimally invasive procedure has been the subject of some well-received studies with findings that indicate it is a promising choice for patients with a Clostridium difficile–associated disease (CDAD) over total colectomy, Dr. Jones said.

In a study published in the Journal of Trauma and Acute Care Surgery, a study group of patients with CDAD who had loop ileostomy had no statistical difference in almost any recorded characteristic compared with those who underwent a total colectomy, except mortality rate. The retrospective, multicenter study of 98 CDAD patients found the mortality rate of the loop ileostomy group to be 17.2%, compared with 39.7% in the total colectomy group (J Trauma Acute Care Surg. 2017 Jul;83[1]:36-40).

“The outcomes all favored loop ileostomy in a statistically significant fashion,” said Dr. Jones. “Unsurprisingly, estimated blood loss and need for transfusions were all significantly less in the loop ileostomy patients, and the adjusted overall mortality, even if requiring a reoperation, still favored doing the loop ileostomy first.”

The one difference between LI and colectomy patients was a longer time from initial diagnosis to operation among LI patients, with about 12 hours from diagnosis for the colectomy versus 24 hours for LI patients, according to lead author Paula Ferrada, MD, FACS, director of the surgical and trauma intensive care unit at Virginia Commonwealth University, Richmond, and her fellow investigators,

Contrary to previous findings, the study found that LI can be performed on sick patients as well, according to the researchers, and failure of the procedure is not associated with increased mortality.

While these findings are encouraging, “there are things that the individual patient may reveal to you on your examination that tell you they are not a candidate and that you should go to total colectomy,” said Dr. Jones. “Keep in mind that perhaps we can be a bit more aggressive in this less invasive procedure.”
 

The skin vac actually works

A study published in Annals of Surgery found prophylactic negative-pressure dressings are associated with a decreased rate of surgical site infections in laparotomy wounds.

“The biggest surprise to me out of all of these studies is that a new piece of technology actually seems to work,” said Dr. Jones.

The randomized study included 50 laparotomy patients with a stapled wound, half of whom received a skin vac over their incision while the other half had a standard OpSite occlusive dressing (Ann Surg. 2017 Jun;265[6]:1082-6).

Patients in both arms had the same type of wound and had their dressings on for 4 days before being switched.

Rate of surgical site infections for the skin vac group was 8.3% over 30 days from operation, compared with 32% in the OpSite group. Average length of stay for patients with the pressure dressing was 6.1 days, while patients with an OpSite dressing had a length of 14.7 days, more than double, according to lead author Donal Peter O’Leary, MD, surgeon at Cork University Hospital, Ireland.

The difference in length of stay does become insignificant if six OpSite patients who stayed longer than 20 days are discounted, only two of whom were delayed because of wound complications as opposed to placement issues or unassociated infections.

“But a surgical site infection difference of 50% or more using a skin vac instead of a standard dressing, whether you’re talking about clean, clean-contaminated, or contaminated cases with a skin closure, seems to be worthy of notice,” explained Dr. Jones.

[email protected]

A salmon-colored background and prominent serpentine blood vessels are two characteristic features of primary cutaneous B-cell lymphoma (PCBCL) that can be identified dermoscopically and may aid diagnosis, researchers say.

In the January issue of the Journal of the European Academy of Dermatology and Venereology, researchers reported the results of a retrospective observational study using the dermoscopic images of 58 biopsy-confirmed primary cutaneous B-cell lymphoma lesions in 51 patients.

While all the lesions were nonpigmented, 46 (79.3%) of them showed salmon- or yellow- to orange- colored background areas. More than three-quarters of the lesions also featured prominent blood vessels (77.6%), the majority of which were serpentine in nature.

Just over half of the PCBCL lesions (55%) featured both a salmon-colored background and serpentine blood vessels, while only 8.6% of the lesions showed neither feature.

Of the 58 lesions, the authors selected 17 to be evaluated by two dermoscopy experts who were blinded to the diagnosis. In 70.6% of these cases they included cutaneous B-cell lymphoma in the differential diagnosis, while other diagnoses included spider bite (58.8%), basal cell carcinoma (52.9%), amelanotic melanoma (47.1%), and scar/keloid (47.1%). Overall, the two experts did not agree on almost 30% of the suggested differential diagnoses.

“The presentation of cutaneous lymphomas in general and of PCBCLs in particular can be nonspecific, and a biopsy is essential for a definitive diagnosis,” wrote Shamir Geller, MD, of the dermatology service at Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

The 58 PCBCLs analyzed were among 172 biopsy-proven PCBCL lesions in the study, which were newly diagnosed and whose pathology reports included the clinical differential diagnosis in the pathology requisition slip, in patients referred to the cancer center between 1992 and 2016. In only 16.3% of these cases, the clinician suspected cutaneous lymphoma. Skin malignancies were suspected in 54.7% of cases, with the leading diagnosis being basal cell carcinoma in 17.4% of cases. Basal cell carcinoma was considered in nearly one-third of lesions, particularly those on the head and neck.

Nonneoplastic conditions suspected by clinicians included cyst in 21.5% of cases, granulomatous processes in 15.7%, and infectious disease in 4.7%.

The authors commented that a low index of suspicion for skin lymphoma was seen regardless of the subtype or site.

“While dermoscopy offers a bridge between the naked eye examination and the histopathological appearance, cutaneous lymphoma is diagnosed on a cellular level using histopathology, immunohistochemistry and molecular studies,” they wrote. “Therefore, dermoscopy may serve as an ancillary tool in PCBCL; however, it cannot be diagnostic.”

The study was supported in part by the National Institutes of Health/National Cancer Institute Cancer Center. Dr. Geller is a recipient of a grant from the American Physicians and Friends For Medicine in Israel. No conflicts of interest were declared.

SOURCE: Geller S et al. J Eur Acad Dermatol Venereol. 2018 Jan;32(1):53-6.

A salmon-colored background and prominent serpentine blood vessels are two characteristic features of primary cutaneous B-cell lymphoma (PCBCL) that can be identified dermoscopically and may aid diagnosis, researchers say.

In the January issue of the Journal of the European Academy of Dermatology and Venereology, researchers reported the results of a retrospective observational study using the dermoscopic images of 58 biopsy-confirmed primary cutaneous B-cell lymphoma lesions in 51 patients.

While all the lesions were nonpigmented, 46 (79.3%) of them showed salmon- or yellow- to orange- colored background areas. More than three-quarters of the lesions also featured prominent blood vessels (77.6%), the majority of which were serpentine in nature.

Just over half of the PCBCL lesions (55%) featured both a salmon-colored background and serpentine blood vessels, while only 8.6% of the lesions showed neither feature.

Of the 58 lesions, the authors selected 17 to be evaluated by two dermoscopy experts who were blinded to the diagnosis. In 70.6% of these cases they included cutaneous B-cell lymphoma in the differential diagnosis, while other diagnoses included spider bite (58.8%), basal cell carcinoma (52.9%), amelanotic melanoma (47.1%), and scar/keloid (47.1%). Overall, the two experts did not agree on almost 30% of the suggested differential diagnoses.

“The presentation of cutaneous lymphomas in general and of PCBCLs in particular can be nonspecific, and a biopsy is essential for a definitive diagnosis,” wrote Shamir Geller, MD, of the dermatology service at Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

The 58 PCBCLs analyzed were among 172 biopsy-proven PCBCL lesions in the study, which were newly diagnosed and whose pathology reports included the clinical differential diagnosis in the pathology requisition slip, in patients referred to the cancer center between 1992 and 2016. In only 16.3% of these cases, the clinician suspected cutaneous lymphoma. Skin malignancies were suspected in 54.7% of cases, with the leading diagnosis being basal cell carcinoma in 17.4% of cases. Basal cell carcinoma was considered in nearly one-third of lesions, particularly those on the head and neck.

Nonneoplastic conditions suspected by clinicians included cyst in 21.5% of cases, granulomatous processes in 15.7%, and infectious disease in 4.7%.

The authors commented that a low index of suspicion for skin lymphoma was seen regardless of the subtype or site.

“While dermoscopy offers a bridge between the naked eye examination and the histopathological appearance, cutaneous lymphoma is diagnosed on a cellular level using histopathology, immunohistochemistry and molecular studies,” they wrote. “Therefore, dermoscopy may serve as an ancillary tool in PCBCL; however, it cannot be diagnostic.”

The study was supported in part by the National Institutes of Health/National Cancer Institute Cancer Center. Dr. Geller is a recipient of a grant from the American Physicians and Friends For Medicine in Israel. No conflicts of interest were declared.

SOURCE: Geller S et al. J Eur Acad Dermatol Venereol. 2018 Jan;32(1):53-6.

A salmon-colored background and prominent serpentine blood vessels are two characteristic features of primary cutaneous B-cell lymphoma (PCBCL) that can be identified dermoscopically and may aid diagnosis, researchers say.

In the January issue of the Journal of the European Academy of Dermatology and Venereology, researchers reported the results of a retrospective observational study using the dermoscopic images of 58 biopsy-confirmed primary cutaneous B-cell lymphoma lesions in 51 patients.

While all the lesions were nonpigmented, 46 (79.3%) of them showed salmon- or yellow- to orange- colored background areas. More than three-quarters of the lesions also featured prominent blood vessels (77.6%), the majority of which were serpentine in nature.

Just over half of the PCBCL lesions (55%) featured both a salmon-colored background and serpentine blood vessels, while only 8.6% of the lesions showed neither feature.

Of the 58 lesions, the authors selected 17 to be evaluated by two dermoscopy experts who were blinded to the diagnosis. In 70.6% of these cases they included cutaneous B-cell lymphoma in the differential diagnosis, while other diagnoses included spider bite (58.8%), basal cell carcinoma (52.9%), amelanotic melanoma (47.1%), and scar/keloid (47.1%). Overall, the two experts did not agree on almost 30% of the suggested differential diagnoses.

“The presentation of cutaneous lymphomas in general and of PCBCLs in particular can be nonspecific, and a biopsy is essential for a definitive diagnosis,” wrote Shamir Geller, MD, of the dermatology service at Memorial Sloan Kettering Cancer Center, New York, and his coauthors.

The 58 PCBCLs analyzed were among 172 biopsy-proven PCBCL lesions in the study, which were newly diagnosed and whose pathology reports included the clinical differential diagnosis in the pathology requisition slip, in patients referred to the cancer center between 1992 and 2016. In only 16.3% of these cases, the clinician suspected cutaneous lymphoma. Skin malignancies were suspected in 54.7% of cases, with the leading diagnosis being basal cell carcinoma in 17.4% of cases. Basal cell carcinoma was considered in nearly one-third of lesions, particularly those on the head and neck.

Nonneoplastic conditions suspected by clinicians included cyst in 21.5% of cases, granulomatous processes in 15.7%, and infectious disease in 4.7%.

The authors commented that a low index of suspicion for skin lymphoma was seen regardless of the subtype or site.

“While dermoscopy offers a bridge between the naked eye examination and the histopathological appearance, cutaneous lymphoma is diagnosed on a cellular level using histopathology, immunohistochemistry and molecular studies,” they wrote. “Therefore, dermoscopy may serve as an ancillary tool in PCBCL; however, it cannot be diagnostic.”

The study was supported in part by the National Institutes of Health/National Cancer Institute Cancer Center. Dr. Geller is a recipient of a grant from the American Physicians and Friends For Medicine in Israel. No conflicts of interest were declared.

SOURCE: Geller S et al. J Eur Acad Dermatol Venereol. 2018 Jan;32(1):53-6.

CHICAGO – The use of therapeutic-dose anticoagulation in hospitalized patients with calf vein thrombosis significantly reduces the risk of venous thromboembolic complications, compared with lower-dose prophylactic anticoagulation or surveillance alone, Heron E. Rodriguez, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

Moreover, placement of an inferior vena cava filter in patients with calf vein thrombosis when anticoagulation is contraindicated accomplishes nothing beneficial and had a 10% complication rate in a large retrospective single-center study, added Dr. Rodriguez of Northwestern University, Chicago.

Bruce Jancin/Frontline Medical News

[email protected]

CHICAGO – The use of therapeutic-dose anticoagulation in hospitalized patients with calf vein thrombosis significantly reduces the risk of venous thromboembolic complications, compared with lower-dose prophylactic anticoagulation or surveillance alone, Heron E. Rodriguez, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

Moreover, placement of an inferior vena cava filter in patients with calf vein thrombosis when anticoagulation is contraindicated accomplishes nothing beneficial and had a 10% complication rate in a large retrospective single-center study, added Dr. Rodriguez of Northwestern University, Chicago.

Bruce Jancin/Frontline Medical News

[email protected]

CHICAGO – The use of therapeutic-dose anticoagulation in hospitalized patients with calf vein thrombosis significantly reduces the risk of venous thromboembolic complications, compared with lower-dose prophylactic anticoagulation or surveillance alone, Heron E. Rodriguez, MD, said at a symposium on vascular surgery sponsored by Northwestern University.

Moreover, placement of an inferior vena cava filter in patients with calf vein thrombosis when anticoagulation is contraindicated accomplishes nothing beneficial and had a 10% complication rate in a large retrospective single-center study, added Dr. Rodriguez of Northwestern University, Chicago.

Bruce Jancin/Frontline Medical News

[email protected]

Toxic epidermal necrolysis (TEN) is a rare, life-threatening adverse drug reaction with an estimated incidence of 0.4 to 1.9 cases per million persons per year worldwide and an estimated mortality rate of 25% to 35%.^1,2 This dermatologic emergency is characterized by extensive detachment of the epidermis and erosions of the mucous membranes secondary to massive keratinocyte cell death via apoptosis, evolving quickly into full-thickness epidermal necrosis.

Primary treatment of TEN includes (1) prompt discontinuation of the suspected medication; (2) rapid transfer to an intensive care unit, burn center, or other specialty unit; and (3) supportive care, including wound care, fluid and electrolyte maintenance, and treatment of infections. Aside from the primary treatment, controversy remains over the most effective adjunctive therapy for TEN, as none has proven consistent superiority over well-conducted primary treatment alone. Therefore, established therapeutic guidelines do not exist.^1-3

The use of adjunctive systemic therapy in TEN (eg, corticosteroids, intravenous immunoglobulin [IVIG], cyclosporine, plasmapheresis, granulocyte-colony stimulating factor) is based primarily on theories of pathogenesis, which unfortunately remain unclear. Activated CD8⁺ T cells are thought to increase the expression and production of granulysin, granzyme B, and perforins, leading to keratinocyte apoptosis. Fas ligand and tumor necrosis factor α (TNF-α) also are implicated as secondary mediators of cell death via the inducible nitric oxide synthase pathway.^1,4-6

Since TNF-α was found to be elevated in serum and blister fluid in patients with TEN,^7,8 medications aimed at decreasing the TNF-α concentration, such as pentoxifylline (PTX) and thalidomide, have been attempted for treatment.^9,10 Biologic inhibitors of TNF-α, such as infliximab and etanercept, are novel therapeutic options in the treatment of TEN, as numerous reports document their successful use in the treatment of this disease.^11-24 The purpose of this study is to systematically review the current literature on the use of TNF-α antagonists in the treatment of TEN.

METHODS

A PubMed search of all available articles indexed for MEDLINE using the terms toxic epidermal necrolysis and TNF-alpha and pentoxifylline or thalidomide or infliximab or etanercept or adalimumab was conducted.

RESULTS

Sixteen articles published between 1994 and 2014 were retrieved from PubMed and reviewed.^9-24 Fourteen articles were case reports and case series involving the use of TNF-α inhibitors as either monotherapy, second-line agents, or in combination with other medications in the treatment of TEN, providing a total of 28 patients.^9,11-23 Two articles were prospective trials, one evaluating the efficacy of thalidomide¹⁰ and the other infliximab²⁴ in treating TEN. All studies implemented primary treatment (ie, prompt discontinuation of the suspected medication and aggressive supportive care) in addition to TNF-α inhibition.

Pentoxifylline

The first case report describing the use of an anti–TNF-α inhibitor for TEN was with PTX in 1994.⁹ Pentoxifylline, a vasoactive drug with immunomodulatory properties including the downregulation of TNF-α synthesis, was used to treat a 26-year-old woman with TEN on phenylhydantoin 15 days following resection of a grade II astrocytoma. The patient initially received intravenous N-acetylcysteine (NAC) (9 g once daily) and S-adenosyl-L-methionine (100 mg once daily) for antioxidant effects. On the second day of treatment, intravenous PTX (900 mg once daily) was added for TNF-α inhibition. Following PTX administration, the investigators reported quick stabilization of the eruption and achievement of reepithelialization after 7 days of therapy. Upon cessation of PTX therapy, a recurrence of generalized erythema occurred, suggesting a relapse of TEN; therefore, PTX was reinitiated for an additional 3 days, and the patient’s skin remained clear.⁹

Thalidomide

The earliest prospective trial we reviewed using anti–TNF-α therapy in TEN occurred in 1998 with thalidomide, a moderate inhibitor of TNF-α.¹⁰ In this randomized controlled trial, 22 TEN patients received either a 5-day course of thalidomide (400 mg once daily) or placebo. There was increased mortality in the thalidomide group (10/12 [83.3%]) versus the placebo group (3/10 [30.0%]). Additionally, the plasma TNF-α concentrations in the thalidomide group were higher than the control group. This study was stopped prematurely due to the excess mortality in the thalidomide group.¹⁰

Biologic TNF-α Antagonists

Following the PTX case report and the thalidomide trial, there was increased interest in using newer-generation TNF-α inhibitors, such as the monoclonal antibody infliximab or the fusion protein etanercept, in the treatment of TEN. To date, there are 10 known published case reports,^{11,12,15-21,23} 3 case series,^13,14,22 and 1 trial²⁴ describing the use of these agents; however, treatment protocols vary. Categories of treatment protocols include the use of TNF-α inhibitors as monotherapy, following failure of other systemic agents, and in combination with other systemic therapies.

TNF-α Inhibitors as Monotherapy
Review of the literature yielded 2 case reports using infliximab monotherapy^11,12 and 2 case series using infliximab or etanercept monotherapy^13,14 with a total of 14 patients (Table 1). Fischer et al¹¹ was the first of these reports to describe a patient successfully treated with supportive care and a single dose of infliximab 5 mg/kg. The dose was given 4 days after the onset of symptoms, and the rapid progression of the disease was stopped, with complete recovery in less than 4 weeks.¹¹ Hunger et al¹² also described the successful treatment of a patient using a similar protocol: a single dose of infliximab 5 mg/kg given 3 days after symptom onset. Epidermal detachment was abated within 24 hours and the patient had almost complete reepithelialization within 5 days.¹² In a case series published by Zárate-Correa et al,¹³ 2 patients with near 100% body surface area involvement were successfully treated with a single dose of infliximab 300 mg. Although both of these patients experienced fairly rapid recoveries, one patient’s course was complicated by methicillin-resistant Staphylococcus aureus bacteremia.¹³ Paradisi et al¹⁴ described 10 consecutive patients treated with a single dose of etanercept 50 mg given within 6 hours of hospital admission and within 72 hours of symptom onset. The SCORTEN (SCORe of Toxic Epidermal Necrolysis) scale—a severity-of-illness assessment for TEN based on body surface area involvement, comorbidities, and metabolic abnormalities—was used to predict mortality in these patients. The investigators reported an expected mortality of 46.9%; however, the observed mortality was 0%, and there were no reported infections.¹⁴

TNF-α Inhibitors Following Failure of Other Systemic Agents in TEN
Seven case reports and 1 case series using anti–TNF-α therapy following failure of other systemic agents were reviewed for a total of 9 patients (3 pediatric/adolescent patients, 6 adult patients)(Table 2).^13,15-21 Seven patients were treated with infliximab,^{13,15,17,19-21} and the remaining 2 patients were treated with etanercept.^16,18 All patients were treated initially with corticosteroids and/or IVIG. In each case, anti–TNF-α therapy was introduced when prior treatment failed to halt the progression of TEN. Most reports claimed a rapid and beneficial response to anti–TNF-α therapy. Eight of 9 (88.9%) patients recovered.^13,15,17-21 Famularo et al¹⁶ described 1 patient who was treated with 2 doses of etanercept following prednisolone but died on the tenth day of hospitalization secondary to disseminated intravascular coagulation and multiorgan failure; however, the patient reportedly had near-complete reepithelialization of the skin on the sixth day of the hospital course.¹⁶ Of the 8 surviving patients, 3 (37.5%) experienced hospital courses complicated by nosocomial gram-negative bacteremia, including Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae.^13,15 Interestingly, a patient described by Worsnop et al²⁰ developed erosive lichen planus of the mouth and vulva 31 days after infliximab infusion.

Combination of TNF-α Inhibitor With Other Systemic Agents in TEN
One case series²² and 1 case report²³ using infliximab in combination with other systemic therapies were reviewed with a total of 4 patients (Table 3). Both reports utilized the same treatment protocol, which consisted of a single bolus of intravenous methylprednisolone 500 mg followed by a single dose of infliximab 5 mg/kg and then IVIG 2 g/kg over 5 days. Three of 4 (75%) patients recovered.^22,23 Gaitanis et al²² reported a patient who died on the ninth day of hospitalization secondary to multiorgan dysfunction caused by a catheter-related bacteremia. Similar to the patient described by Famularo et al,¹⁶ this patient also was noted to have remarkably improved skin prior to death. Two of the other 3 patients that survived had their hospital course complicated by infection, requiring antibiotics.²² In the Gaitanis et al²² series, the average predicted mortality according to a SCORTEN assessment was 50.8%; however, mortality was observed in 33.3% (1/3) of patients in the case series.

N-Acetylcysteine and Infliximab
The combination of NAC and infliximab was studied in a randomized controlled trial using TNF-α inhibition in TEN.²⁴ In this study, 10 patients were admitted to a burn unit and treated with either 3 doses of intravenous NAC (150 mg/kg per dose) plus 1 dose of infliximab 5 mg/kg or NAC alone. Unlike some of the previously described articles, Paquet et al²⁴ utilized an illness auxiliary score (IAS), which predicts both disease duration and mortality. An IAS was taken at admission and again 48 hours after completion of NAC and/or infliximab administration. The mean clinical IAS score was reported to have remained unchanged at treatment completion in the NAC group and slightly worsened in the NAC-infliximab group. One patient died in the NAC group and 2 patients died in the NAC-infliximab group, each due to infection. These fatalities corresponded to a mean mortality of 20% in the NAC-treated group and 40% for the NAC-infliximab group. To compare, the predicted mortalities based on the IAS were 20.4% and 21.4%, respectively.²⁴

COMMENT

Tumor necrosis factor α inhibition in the treatment of TEN was first utilized in the 1990s with PTX and thalidomide.^9,10 In 1994, PTX in addition to antioxidant therapy was found to successfully treat a 26-year-old woman with TEN attributed to anticonvulsant therapy.⁹ Other reports of PTX in the treatment of TEN were not found; however, there is a case series describing the successful treatment of 2 pediatric patients with Stevens-Johnson syndrome (SJS) and SJS-TEN overlap with PTX.²⁵ Thalidomide, however, proved detrimental to patients with TEN as evidenced by an increased mortality in the 1998 trial.¹⁰ Paradoxically, the treatment group was found to have increased rather than decreased TNF-α concentrations, which was hypothesized to be the cause of increased mortality. This finding furthered the theory that TNF-α is an important mediator in TEN pathogenesis and a potential novel target in disease management.¹⁰

Since the PTX case report and the thalidomide trial, many physicians have reported the beneficial effects of biologic TNF-α inhibitors in the course of TEN; however, most of the literature is composed of case reports and case series describing a small number of patients. Therefore, the beneficial effects of anti–TNF-α therapy in TEN cannot be conclusively derived. Furthermore, cases using TNF-α inhibitors in combination with or after other systemic agents complicate the effects of TNF-α inhibitors themselves. Most of these case reports and case series describe the beneficial effects of TNF-α inhibitors in TEN; however, it is important to remember that cases in which these agents were ineffective are less likely to be published. The strongest evidence for TNF-α inhibitor use in the treatment TEN comes from the Paradisi et al¹⁴ case series, which showed a decrease in expected mortality with etanercept monotherapy in a relatively large cohort of patients. However, when evaluated prospectively by Paquet et al,²⁴ there was no benefit seen by adding infliximab to NAC therapy and possibly an increased mortality in the group treated with both agents.

In the cases reviewed, a total of 32 patients were treated with infliximab or etanercept, and of these patients there were 4 deaths (12.5%).^16,22,24 Three deaths were attributed to infection and 1 was attributed to disseminated intravascular coagulation. Furthermore, infection complicated the hospital course of 9 (28.1%) patients.^13,15,22,24 The bacteria cultured from these patients included methicillin-resistant S aureus, P aeruginosa, E coli, Enterobacter aerogenes, and K pneumoniae. Patients who received TNF-α antagonists in combination with or after other systemic immunosuppressants appeared to have a higher incidence of infections. All patients treated with TNF-α antagonists in TEN should undergo careful evaluation and monitoring for infections due to the immunosuppressant effect of these drugs.

In our review, a total of 3 pediatric/adolescent patients received a TNF-α inhibitor for the treatment of TEN.^13,17,21 Two patients received infliximab as a second-line medication after failure of IVIG to arrest progression of disease^13,17 and one patient received infliximab as a second-line medication after dexamethasone.²¹ Each of these patients recovered without any reported infections or long-term complications.

Although excluded from this review, both infliximab and etanercept have been reported to show benefit in acute generalized exanthematous pustulosis/TEN overlap.^26,27 Interestingly, in postmarketing surveillance, rare reports have implicated both infliximab and etanercept in causing both SJS and TEN.²⁸ Also, there have been case reports of adalimumab causing SJS, but no cases of it causing TEN were identified.^29,30

CONCLUSION

Rapid discontinuation of the culprit drug and aggressive supportive care remain the primary treatment of TEN. Tumor necrosis factor α inhibitors as monotherapy or as second-line agents show promise in the treatment of this complex disease state in both the adult and pediatric populations. The risks of these potent immunosuppressants must be weighed, and if administered, patients must be closely monitored for infections. Additional studies are needed to further characterize the role of TNF-α inhibition in the treatment of TEN.

Toxic epidermal necrolysis (TEN) is a rare, life-threatening adverse drug reaction with an estimated incidence of 0.4 to 1.9 cases per million persons per year worldwide and an estimated mortality rate of 25% to 35%.^1,2 This dermatologic emergency is characterized by extensive detachment of the epidermis and erosions of the mucous membranes secondary to massive keratinocyte cell death via apoptosis, evolving quickly into full-thickness epidermal necrosis.

Primary treatment of TEN includes (1) prompt discontinuation of the suspected medication; (2) rapid transfer to an intensive care unit, burn center, or other specialty unit; and (3) supportive care, including wound care, fluid and electrolyte maintenance, and treatment of infections. Aside from the primary treatment, controversy remains over the most effective adjunctive therapy for TEN, as none has proven consistent superiority over well-conducted primary treatment alone. Therefore, established therapeutic guidelines do not exist.^1-3

The use of adjunctive systemic therapy in TEN (eg, corticosteroids, intravenous immunoglobulin [IVIG], cyclosporine, plasmapheresis, granulocyte-colony stimulating factor) is based primarily on theories of pathogenesis, which unfortunately remain unclear. Activated CD8⁺ T cells are thought to increase the expression and production of granulysin, granzyme B, and perforins, leading to keratinocyte apoptosis. Fas ligand and tumor necrosis factor α (TNF-α) also are implicated as secondary mediators of cell death via the inducible nitric oxide synthase pathway.^1,4-6

Since TNF-α was found to be elevated in serum and blister fluid in patients with TEN,^7,8 medications aimed at decreasing the TNF-α concentration, such as pentoxifylline (PTX) and thalidomide, have been attempted for treatment.^9,10 Biologic inhibitors of TNF-α, such as infliximab and etanercept, are novel therapeutic options in the treatment of TEN, as numerous reports document their successful use in the treatment of this disease.^11-24 The purpose of this study is to systematically review the current literature on the use of TNF-α antagonists in the treatment of TEN.

METHODS

A PubMed search of all available articles indexed for MEDLINE using the terms toxic epidermal necrolysis and TNF-alpha and pentoxifylline or thalidomide or infliximab or etanercept or adalimumab was conducted.

RESULTS

Sixteen articles published between 1994 and 2014 were retrieved from PubMed and reviewed.^9-24 Fourteen articles were case reports and case series involving the use of TNF-α inhibitors as either monotherapy, second-line agents, or in combination with other medications in the treatment of TEN, providing a total of 28 patients.^9,11-23 Two articles were prospective trials, one evaluating the efficacy of thalidomide¹⁰ and the other infliximab²⁴ in treating TEN. All studies implemented primary treatment (ie, prompt discontinuation of the suspected medication and aggressive supportive care) in addition to TNF-α inhibition.

Pentoxifylline

The first case report describing the use of an anti–TNF-α inhibitor for TEN was with PTX in 1994.⁹ Pentoxifylline, a vasoactive drug with immunomodulatory properties including the downregulation of TNF-α synthesis, was used to treat a 26-year-old woman with TEN on phenylhydantoin 15 days following resection of a grade II astrocytoma. The patient initially received intravenous N-acetylcysteine (NAC) (9 g once daily) and S-adenosyl-L-methionine (100 mg once daily) for antioxidant effects. On the second day of treatment, intravenous PTX (900 mg once daily) was added for TNF-α inhibition. Following PTX administration, the investigators reported quick stabilization of the eruption and achievement of reepithelialization after 7 days of therapy. Upon cessation of PTX therapy, a recurrence of generalized erythema occurred, suggesting a relapse of TEN; therefore, PTX was reinitiated for an additional 3 days, and the patient’s skin remained clear.⁹

Thalidomide

The earliest prospective trial we reviewed using anti–TNF-α therapy in TEN occurred in 1998 with thalidomide, a moderate inhibitor of TNF-α.¹⁰ In this randomized controlled trial, 22 TEN patients received either a 5-day course of thalidomide (400 mg once daily) or placebo. There was increased mortality in the thalidomide group (10/12 [83.3%]) versus the placebo group (3/10 [30.0%]). Additionally, the plasma TNF-α concentrations in the thalidomide group were higher than the control group. This study was stopped prematurely due to the excess mortality in the thalidomide group.¹⁰

Biologic TNF-α Antagonists

Following the PTX case report and the thalidomide trial, there was increased interest in using newer-generation TNF-α inhibitors, such as the monoclonal antibody infliximab or the fusion protein etanercept, in the treatment of TEN. To date, there are 10 known published case reports,^{11,12,15-21,23} 3 case series,^13,14,22 and 1 trial²⁴ describing the use of these agents; however, treatment protocols vary. Categories of treatment protocols include the use of TNF-α inhibitors as monotherapy, following failure of other systemic agents, and in combination with other systemic therapies.

TNF-α Inhibitors as Monotherapy
Review of the literature yielded 2 case reports using infliximab monotherapy^11,12 and 2 case series using infliximab or etanercept monotherapy^13,14 with a total of 14 patients (Table 1). Fischer et al¹¹ was the first of these reports to describe a patient successfully treated with supportive care and a single dose of infliximab 5 mg/kg. The dose was given 4 days after the onset of symptoms, and the rapid progression of the disease was stopped, with complete recovery in less than 4 weeks.¹¹ Hunger et al¹² also described the successful treatment of a patient using a similar protocol: a single dose of infliximab 5 mg/kg given 3 days after symptom onset. Epidermal detachment was abated within 24 hours and the patient had almost complete reepithelialization within 5 days.¹² In a case series published by Zárate-Correa et al,¹³ 2 patients with near 100% body surface area involvement were successfully treated with a single dose of infliximab 300 mg. Although both of these patients experienced fairly rapid recoveries, one patient’s course was complicated by methicillin-resistant Staphylococcus aureus bacteremia.¹³ Paradisi et al¹⁴ described 10 consecutive patients treated with a single dose of etanercept 50 mg given within 6 hours of hospital admission and within 72 hours of symptom onset. The SCORTEN (SCORe of Toxic Epidermal Necrolysis) scale—a severity-of-illness assessment for TEN based on body surface area involvement, comorbidities, and metabolic abnormalities—was used to predict mortality in these patients. The investigators reported an expected mortality of 46.9%; however, the observed mortality was 0%, and there were no reported infections.¹⁴

TNF-α Inhibitors Following Failure of Other Systemic Agents in TEN
Seven case reports and 1 case series using anti–TNF-α therapy following failure of other systemic agents were reviewed for a total of 9 patients (3 pediatric/adolescent patients, 6 adult patients)(Table 2).^13,15-21 Seven patients were treated with infliximab,^{13,15,17,19-21} and the remaining 2 patients were treated with etanercept.^16,18 All patients were treated initially with corticosteroids and/or IVIG. In each case, anti–TNF-α therapy was introduced when prior treatment failed to halt the progression of TEN. Most reports claimed a rapid and beneficial response to anti–TNF-α therapy. Eight of 9 (88.9%) patients recovered.^13,15,17-21 Famularo et al¹⁶ described 1 patient who was treated with 2 doses of etanercept following prednisolone but died on the tenth day of hospitalization secondary to disseminated intravascular coagulation and multiorgan failure; however, the patient reportedly had near-complete reepithelialization of the skin on the sixth day of the hospital course.¹⁶ Of the 8 surviving patients, 3 (37.5%) experienced hospital courses complicated by nosocomial gram-negative bacteremia, including Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae.^13,15 Interestingly, a patient described by Worsnop et al²⁰ developed erosive lichen planus of the mouth and vulva 31 days after infliximab infusion.

Combination of TNF-α Inhibitor With Other Systemic Agents in TEN
One case series²² and 1 case report²³ using infliximab in combination with other systemic therapies were reviewed with a total of 4 patients (Table 3). Both reports utilized the same treatment protocol, which consisted of a single bolus of intravenous methylprednisolone 500 mg followed by a single dose of infliximab 5 mg/kg and then IVIG 2 g/kg over 5 days. Three of 4 (75%) patients recovered.^22,23 Gaitanis et al²² reported a patient who died on the ninth day of hospitalization secondary to multiorgan dysfunction caused by a catheter-related bacteremia. Similar to the patient described by Famularo et al,¹⁶ this patient also was noted to have remarkably improved skin prior to death. Two of the other 3 patients that survived had their hospital course complicated by infection, requiring antibiotics.²² In the Gaitanis et al²² series, the average predicted mortality according to a SCORTEN assessment was 50.8%; however, mortality was observed in 33.3% (1/3) of patients in the case series.

N-Acetylcysteine and Infliximab
The combination of NAC and infliximab was studied in a randomized controlled trial using TNF-α inhibition in TEN.²⁴ In this study, 10 patients were admitted to a burn unit and treated with either 3 doses of intravenous NAC (150 mg/kg per dose) plus 1 dose of infliximab 5 mg/kg or NAC alone. Unlike some of the previously described articles, Paquet et al²⁴ utilized an illness auxiliary score (IAS), which predicts both disease duration and mortality. An IAS was taken at admission and again 48 hours after completion of NAC and/or infliximab administration. The mean clinical IAS score was reported to have remained unchanged at treatment completion in the NAC group and slightly worsened in the NAC-infliximab group. One patient died in the NAC group and 2 patients died in the NAC-infliximab group, each due to infection. These fatalities corresponded to a mean mortality of 20% in the NAC-treated group and 40% for the NAC-infliximab group. To compare, the predicted mortalities based on the IAS were 20.4% and 21.4%, respectively.²⁴

COMMENT

Tumor necrosis factor α inhibition in the treatment of TEN was first utilized in the 1990s with PTX and thalidomide.^9,10 In 1994, PTX in addition to antioxidant therapy was found to successfully treat a 26-year-old woman with TEN attributed to anticonvulsant therapy.⁹ Other reports of PTX in the treatment of TEN were not found; however, there is a case series describing the successful treatment of 2 pediatric patients with Stevens-Johnson syndrome (SJS) and SJS-TEN overlap with PTX.²⁵ Thalidomide, however, proved detrimental to patients with TEN as evidenced by an increased mortality in the 1998 trial.¹⁰ Paradoxically, the treatment group was found to have increased rather than decreased TNF-α concentrations, which was hypothesized to be the cause of increased mortality. This finding furthered the theory that TNF-α is an important mediator in TEN pathogenesis and a potential novel target in disease management.¹⁰

Since the PTX case report and the thalidomide trial, many physicians have reported the beneficial effects of biologic TNF-α inhibitors in the course of TEN; however, most of the literature is composed of case reports and case series describing a small number of patients. Therefore, the beneficial effects of anti–TNF-α therapy in TEN cannot be conclusively derived. Furthermore, cases using TNF-α inhibitors in combination with or after other systemic agents complicate the effects of TNF-α inhibitors themselves. Most of these case reports and case series describe the beneficial effects of TNF-α inhibitors in TEN; however, it is important to remember that cases in which these agents were ineffective are less likely to be published. The strongest evidence for TNF-α inhibitor use in the treatment TEN comes from the Paradisi et al¹⁴ case series, which showed a decrease in expected mortality with etanercept monotherapy in a relatively large cohort of patients. However, when evaluated prospectively by Paquet et al,²⁴ there was no benefit seen by adding infliximab to NAC therapy and possibly an increased mortality in the group treated with both agents.

In the cases reviewed, a total of 32 patients were treated with infliximab or etanercept, and of these patients there were 4 deaths (12.5%).^16,22,24 Three deaths were attributed to infection and 1 was attributed to disseminated intravascular coagulation. Furthermore, infection complicated the hospital course of 9 (28.1%) patients.^13,15,22,24 The bacteria cultured from these patients included methicillin-resistant S aureus, P aeruginosa, E coli, Enterobacter aerogenes, and K pneumoniae. Patients who received TNF-α antagonists in combination with or after other systemic immunosuppressants appeared to have a higher incidence of infections. All patients treated with TNF-α antagonists in TEN should undergo careful evaluation and monitoring for infections due to the immunosuppressant effect of these drugs.

In our review, a total of 3 pediatric/adolescent patients received a TNF-α inhibitor for the treatment of TEN.^13,17,21 Two patients received infliximab as a second-line medication after failure of IVIG to arrest progression of disease^13,17 and one patient received infliximab as a second-line medication after dexamethasone.²¹ Each of these patients recovered without any reported infections or long-term complications.

Although excluded from this review, both infliximab and etanercept have been reported to show benefit in acute generalized exanthematous pustulosis/TEN overlap.^26,27 Interestingly, in postmarketing surveillance, rare reports have implicated both infliximab and etanercept in causing both SJS and TEN.²⁸ Also, there have been case reports of adalimumab causing SJS, but no cases of it causing TEN were identified.^29,30

CONCLUSION

Rapid discontinuation of the culprit drug and aggressive supportive care remain the primary treatment of TEN. Tumor necrosis factor α inhibitors as monotherapy or as second-line agents show promise in the treatment of this complex disease state in both the adult and pediatric populations. The risks of these potent immunosuppressants must be weighed, and if administered, patients must be closely monitored for infections. Additional studies are needed to further characterize the role of TNF-α inhibition in the treatment of TEN.

Toxic epidermal necrolysis (TEN) is a rare, life-threatening adverse drug reaction with an estimated incidence of 0.4 to 1.9 cases per million persons per year worldwide and an estimated mortality rate of 25% to 35%.^1,2 This dermatologic emergency is characterized by extensive detachment of the epidermis and erosions of the mucous membranes secondary to massive keratinocyte cell death via apoptosis, evolving quickly into full-thickness epidermal necrosis.

Primary treatment of TEN includes (1) prompt discontinuation of the suspected medication; (2) rapid transfer to an intensive care unit, burn center, or other specialty unit; and (3) supportive care, including wound care, fluid and electrolyte maintenance, and treatment of infections. Aside from the primary treatment, controversy remains over the most effective adjunctive therapy for TEN, as none has proven consistent superiority over well-conducted primary treatment alone. Therefore, established therapeutic guidelines do not exist.^1-3

The use of adjunctive systemic therapy in TEN (eg, corticosteroids, intravenous immunoglobulin [IVIG], cyclosporine, plasmapheresis, granulocyte-colony stimulating factor) is based primarily on theories of pathogenesis, which unfortunately remain unclear. Activated CD8⁺ T cells are thought to increase the expression and production of granulysin, granzyme B, and perforins, leading to keratinocyte apoptosis. Fas ligand and tumor necrosis factor α (TNF-α) also are implicated as secondary mediators of cell death via the inducible nitric oxide synthase pathway.^1,4-6

Since TNF-α was found to be elevated in serum and blister fluid in patients with TEN,^7,8 medications aimed at decreasing the TNF-α concentration, such as pentoxifylline (PTX) and thalidomide, have been attempted for treatment.^9,10 Biologic inhibitors of TNF-α, such as infliximab and etanercept, are novel therapeutic options in the treatment of TEN, as numerous reports document their successful use in the treatment of this disease.^11-24 The purpose of this study is to systematically review the current literature on the use of TNF-α antagonists in the treatment of TEN.

METHODS

A PubMed search of all available articles indexed for MEDLINE using the terms toxic epidermal necrolysis and TNF-alpha and pentoxifylline or thalidomide or infliximab or etanercept or adalimumab was conducted.

RESULTS

Sixteen articles published between 1994 and 2014 were retrieved from PubMed and reviewed.^9-24 Fourteen articles were case reports and case series involving the use of TNF-α inhibitors as either monotherapy, second-line agents, or in combination with other medications in the treatment of TEN, providing a total of 28 patients.^9,11-23 Two articles were prospective trials, one evaluating the efficacy of thalidomide¹⁰ and the other infliximab²⁴ in treating TEN. All studies implemented primary treatment (ie, prompt discontinuation of the suspected medication and aggressive supportive care) in addition to TNF-α inhibition.

Pentoxifylline

The first case report describing the use of an anti–TNF-α inhibitor for TEN was with PTX in 1994.⁹ Pentoxifylline, a vasoactive drug with immunomodulatory properties including the downregulation of TNF-α synthesis, was used to treat a 26-year-old woman with TEN on phenylhydantoin 15 days following resection of a grade II astrocytoma. The patient initially received intravenous N-acetylcysteine (NAC) (9 g once daily) and S-adenosyl-L-methionine (100 mg once daily) for antioxidant effects. On the second day of treatment, intravenous PTX (900 mg once daily) was added for TNF-α inhibition. Following PTX administration, the investigators reported quick stabilization of the eruption and achievement of reepithelialization after 7 days of therapy. Upon cessation of PTX therapy, a recurrence of generalized erythema occurred, suggesting a relapse of TEN; therefore, PTX was reinitiated for an additional 3 days, and the patient’s skin remained clear.⁹

Thalidomide

The earliest prospective trial we reviewed using anti–TNF-α therapy in TEN occurred in 1998 with thalidomide, a moderate inhibitor of TNF-α.¹⁰ In this randomized controlled trial, 22 TEN patients received either a 5-day course of thalidomide (400 mg once daily) or placebo. There was increased mortality in the thalidomide group (10/12 [83.3%]) versus the placebo group (3/10 [30.0%]). Additionally, the plasma TNF-α concentrations in the thalidomide group were higher than the control group. This study was stopped prematurely due to the excess mortality in the thalidomide group.¹⁰

Biologic TNF-α Antagonists

Following the PTX case report and the thalidomide trial, there was increased interest in using newer-generation TNF-α inhibitors, such as the monoclonal antibody infliximab or the fusion protein etanercept, in the treatment of TEN. To date, there are 10 known published case reports,^{11,12,15-21,23} 3 case series,^13,14,22 and 1 trial²⁴ describing the use of these agents; however, treatment protocols vary. Categories of treatment protocols include the use of TNF-α inhibitors as monotherapy, following failure of other systemic agents, and in combination with other systemic therapies.

TNF-α Inhibitors as Monotherapy
Review of the literature yielded 2 case reports using infliximab monotherapy^11,12 and 2 case series using infliximab or etanercept monotherapy^13,14 with a total of 14 patients (Table 1). Fischer et al¹¹ was the first of these reports to describe a patient successfully treated with supportive care and a single dose of infliximab 5 mg/kg. The dose was given 4 days after the onset of symptoms, and the rapid progression of the disease was stopped, with complete recovery in less than 4 weeks.¹¹ Hunger et al¹² also described the successful treatment of a patient using a similar protocol: a single dose of infliximab 5 mg/kg given 3 days after symptom onset. Epidermal detachment was abated within 24 hours and the patient had almost complete reepithelialization within 5 days.¹² In a case series published by Zárate-Correa et al,¹³ 2 patients with near 100% body surface area involvement were successfully treated with a single dose of infliximab 300 mg. Although both of these patients experienced fairly rapid recoveries, one patient’s course was complicated by methicillin-resistant Staphylococcus aureus bacteremia.¹³ Paradisi et al¹⁴ described 10 consecutive patients treated with a single dose of etanercept 50 mg given within 6 hours of hospital admission and within 72 hours of symptom onset. The SCORTEN (SCORe of Toxic Epidermal Necrolysis) scale—a severity-of-illness assessment for TEN based on body surface area involvement, comorbidities, and metabolic abnormalities—was used to predict mortality in these patients. The investigators reported an expected mortality of 46.9%; however, the observed mortality was 0%, and there were no reported infections.¹⁴

TNF-α Inhibitors Following Failure of Other Systemic Agents in TEN
Seven case reports and 1 case series using anti–TNF-α therapy following failure of other systemic agents were reviewed for a total of 9 patients (3 pediatric/adolescent patients, 6 adult patients)(Table 2).^13,15-21 Seven patients were treated with infliximab,^{13,15,17,19-21} and the remaining 2 patients were treated with etanercept.^16,18 All patients were treated initially with corticosteroids and/or IVIG. In each case, anti–TNF-α therapy was introduced when prior treatment failed to halt the progression of TEN. Most reports claimed a rapid and beneficial response to anti–TNF-α therapy. Eight of 9 (88.9%) patients recovered.^13,15,17-21 Famularo et al¹⁶ described 1 patient who was treated with 2 doses of etanercept following prednisolone but died on the tenth day of hospitalization secondary to disseminated intravascular coagulation and multiorgan failure; however, the patient reportedly had near-complete reepithelialization of the skin on the sixth day of the hospital course.¹⁶ Of the 8 surviving patients, 3 (37.5%) experienced hospital courses complicated by nosocomial gram-negative bacteremia, including Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae.^13,15 Interestingly, a patient described by Worsnop et al²⁰ developed erosive lichen planus of the mouth and vulva 31 days after infliximab infusion.

Combination of TNF-α Inhibitor With Other Systemic Agents in TEN
One case series²² and 1 case report²³ using infliximab in combination with other systemic therapies were reviewed with a total of 4 patients (Table 3). Both reports utilized the same treatment protocol, which consisted of a single bolus of intravenous methylprednisolone 500 mg followed by a single dose of infliximab 5 mg/kg and then IVIG 2 g/kg over 5 days. Three of 4 (75%) patients recovered.^22,23 Gaitanis et al²² reported a patient who died on the ninth day of hospitalization secondary to multiorgan dysfunction caused by a catheter-related bacteremia. Similar to the patient described by Famularo et al,¹⁶ this patient also was noted to have remarkably improved skin prior to death. Two of the other 3 patients that survived had their hospital course complicated by infection, requiring antibiotics.²² In the Gaitanis et al²² series, the average predicted mortality according to a SCORTEN assessment was 50.8%; however, mortality was observed in 33.3% (1/3) of patients in the case series.

N-Acetylcysteine and Infliximab
The combination of NAC and infliximab was studied in a randomized controlled trial using TNF-α inhibition in TEN.²⁴ In this study, 10 patients were admitted to a burn unit and treated with either 3 doses of intravenous NAC (150 mg/kg per dose) plus 1 dose of infliximab 5 mg/kg or NAC alone. Unlike some of the previously described articles, Paquet et al²⁴ utilized an illness auxiliary score (IAS), which predicts both disease duration and mortality. An IAS was taken at admission and again 48 hours after completion of NAC and/or infliximab administration. The mean clinical IAS score was reported to have remained unchanged at treatment completion in the NAC group and slightly worsened in the NAC-infliximab group. One patient died in the NAC group and 2 patients died in the NAC-infliximab group, each due to infection. These fatalities corresponded to a mean mortality of 20% in the NAC-treated group and 40% for the NAC-infliximab group. To compare, the predicted mortalities based on the IAS were 20.4% and 21.4%, respectively.²⁴

COMMENT

Tumor necrosis factor α inhibition in the treatment of TEN was first utilized in the 1990s with PTX and thalidomide.^9,10 In 1994, PTX in addition to antioxidant therapy was found to successfully treat a 26-year-old woman with TEN attributed to anticonvulsant therapy.⁹ Other reports of PTX in the treatment of TEN were not found; however, there is a case series describing the successful treatment of 2 pediatric patients with Stevens-Johnson syndrome (SJS) and SJS-TEN overlap with PTX.²⁵ Thalidomide, however, proved detrimental to patients with TEN as evidenced by an increased mortality in the 1998 trial.¹⁰ Paradoxically, the treatment group was found to have increased rather than decreased TNF-α concentrations, which was hypothesized to be the cause of increased mortality. This finding furthered the theory that TNF-α is an important mediator in TEN pathogenesis and a potential novel target in disease management.¹⁰

Since the PTX case report and the thalidomide trial, many physicians have reported the beneficial effects of biologic TNF-α inhibitors in the course of TEN; however, most of the literature is composed of case reports and case series describing a small number of patients. Therefore, the beneficial effects of anti–TNF-α therapy in TEN cannot be conclusively derived. Furthermore, cases using TNF-α inhibitors in combination with or after other systemic agents complicate the effects of TNF-α inhibitors themselves. Most of these case reports and case series describe the beneficial effects of TNF-α inhibitors in TEN; however, it is important to remember that cases in which these agents were ineffective are less likely to be published. The strongest evidence for TNF-α inhibitor use in the treatment TEN comes from the Paradisi et al¹⁴ case series, which showed a decrease in expected mortality with etanercept monotherapy in a relatively large cohort of patients. However, when evaluated prospectively by Paquet et al,²⁴ there was no benefit seen by adding infliximab to NAC therapy and possibly an increased mortality in the group treated with both agents.

In the cases reviewed, a total of 32 patients were treated with infliximab or etanercept, and of these patients there were 4 deaths (12.5%).^16,22,24 Three deaths were attributed to infection and 1 was attributed to disseminated intravascular coagulation. Furthermore, infection complicated the hospital course of 9 (28.1%) patients.^13,15,22,24 The bacteria cultured from these patients included methicillin-resistant S aureus, P aeruginosa, E coli, Enterobacter aerogenes, and K pneumoniae. Patients who received TNF-α antagonists in combination with or after other systemic immunosuppressants appeared to have a higher incidence of infections. All patients treated with TNF-α antagonists in TEN should undergo careful evaluation and monitoring for infections due to the immunosuppressant effect of these drugs.

In our review, a total of 3 pediatric/adolescent patients received a TNF-α inhibitor for the treatment of TEN.^13,17,21 Two patients received infliximab as a second-line medication after failure of IVIG to arrest progression of disease^13,17 and one patient received infliximab as a second-line medication after dexamethasone.²¹ Each of these patients recovered without any reported infections or long-term complications.

Although excluded from this review, both infliximab and etanercept have been reported to show benefit in acute generalized exanthematous pustulosis/TEN overlap.^26,27 Interestingly, in postmarketing surveillance, rare reports have implicated both infliximab and etanercept in causing both SJS and TEN.²⁸ Also, there have been case reports of adalimumab causing SJS, but no cases of it causing TEN were identified.^29,30

CONCLUSION

Rapid discontinuation of the culprit drug and aggressive supportive care remain the primary treatment of TEN. Tumor necrosis factor α inhibitors as monotherapy or as second-line agents show promise in the treatment of this complex disease state in both the adult and pediatric populations. The risks of these potent immunosuppressants must be weighed, and if administered, patients must be closely monitored for infections. Additional studies are needed to further characterize the role of TNF-α inhibition in the treatment of TEN.

ABSTRACT

In a previous study, compared with throwing athletes with superior labral anterior posterior (SLAP) tears, those with concomitant SLAP tears and rotator cuff tears (RCTs) had significantly poorer outcome scores and return to play. Posterior shoulder instability also occurs in throwing athletes, but no studies currently exist regarding outcomes of these patients with concomitant RCTs.

The authors hypothesized that throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent rotator cuff pathology would have poorer outcome scores and return to play.

Fifty-six consecutive throwing athletes with unidirectional posterior shoulder instability underwent arthroscopic capsulolabral repair. Preoperative and postoperative patient-centered outcomes of pain, stability, function, range of motion, strength, and American Shoulder and Elbow Surgeons Shoulder (ASES) scores, as well as return to play, were evaluated. Patients with and without rotator cuff pathology were compared.

Forty-three percent (24/56) of throwing athletes had rotator cuff pathology in addition to posterior capsulolabral pathology. All RCTs were débrided. At a mean of 3 years, there were no differences in preoperative and postoperative patient-centered outcomes between those with and without RCTs. Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport (P = .414) and 67% (16/24) returned to the same level (P = .430).

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike the previous study evaluating throwers outcomes after surgical treatment for concomitant SLAP tears and RCTs, the authors found no difference in patient-reported outcome measures or return to play for throwing athletes with concomitant posterior shoulder instability and RCTs. In throwing athletes with concomitant posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

Continue to: Posterior shoulder instability...

Posterior shoulder instability is an important and increasingly recognized pathology among throwers. Like the superior labrum, the posterior capsulolabral complex is also susceptible to injury during the throwing motion; the posterior labrum being most at risk during the late cocking and follow-through phases. Recent studies have found that arthroscopic capsulolabral reconstruction in posterior shoulder instability is successful in allowing athletes to return to their preinjury sports activities, with 2 studies detailing outcomes in throwing athletes.^1-4 However, superior labral anterior posterior (SLAP) tears are common in throwing athletes and have been treated with varying and limited success. Further, in a study of outcomes of arthroscopic repair of SLAP lesions, Neri and colleagues⁵ found that, compared with throwing athletes with SLAP tears, throwing athletes with concomitant SLAP tears and partial-thickness rotator cuff tears (RCTs) had significantly poorer outcomes and return-to-play rates after surgical repair.

The purpose of this study was to determine outcome scores and return to play of throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent RCTs and to compare them with outcome scores as well as return to play of throwing athletes with isolated posterior shoulder instability. It was hypothesized that throwing athletes with a combination of posterior shoulder instability and RCT would have poorer outcomes and poorer return to play after surgery.⁵

METHODS

PATIENT SELECTION

After Institutional Review Board approval, informed consent was obtained, and consecutive throwing athletes who underwent arthroscopic posterior capsulolabral reconstruction for posterior shoulder instability were followed in the perioperative period. Inclusion criteria were throwing athletes participating in competitive sports at the high school, collegiate, or professional level, minimum 1-year follow-up, presence of unidirectional posterior instability, and absence of symptoms of instability in any direction other than posterior. Patients with inferior instability, SLAP pathology on examination and on magnetic resonance imaging, multidirectional instability, or habitual or psychogenic voluntary shoulder subluxations were excluded. Patients with diagnoses of both posterior shoulder instability and impingement treated with subacromial decompression and distal clavicle resection were also excluded.

After this cohort was identified, patient records were reviewed for pertinent operative data, such as procedure, complications, and evidence of RCT by operative report and arthroscopic photographs. A partial RCT was defined as a tear of 10% to 50%; those with rotator cuff fraying were determined not to be significant.

PATIENT EVALUATION

Surgeries were performed between January 1998 and December 2009 by the senior author (JPB). All patients were followed with clinical examinations, radiographs, and subjective grading scales. Recorded patient demographic data included age, sex, sport, position, competition level, and follow-up duration.

Continue to: All patients had...

All patients had symptomatic posterior shoulder instability, including posterior shoulder pain, clicking, a sensation of subluxation, or instability/apprehension with motion. Each athlete’s shoulder was palpated for tenderness and tested for impingement. Specific posterior glenohumeral instability tests, including the Kim test,⁶ the circumduction test, the jerk test,⁷ the posterior load-and-shift test,⁸ and the posterior stress test,⁹ were performed on all patients. Patients with multidirectional instability on the sulcus test, as well as provocative tests indicating SLAP pathology, such as the Crank test and the active compression test, were not included. Standard radiography and magnetic resonance arthrography (MRA) were performed to further narrow inclusion and exclusion criteria.

Both before surgery and at latest follow-up, patient outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) score (range, 0-100) which combines a subjective functional scale measuring activities of daily living (0-3 for each of 10 tasks, with a total of 0-30) and a subjective pain scale (0-10, with 10 being worst pain). Values >80 were described as excellent, and failures were defined as scores <60 after surgery.¹⁰ A subjective stability scale (0-10, with 0 indicating completely stable and 10 completely unstable), strength scale (0-3, with 0 indicating none, 1 markedly decreased, 2 slightly decreased, and 3 normal), and ROM scale (0-3, with 0 indicating poor, 1 limited, 2 satisfactory, and 3 full) were evaluated both before surgery and at the latest follow-up. A stability score >5 after surgery was defined as a failure.^1,2,11 Patients were also asked if, based on their current state, they would undergo surgery again. Intraoperative findings and specific surgical procedures performed were correlated with the aforementioned subjective and objective outcome scores.

OPERATIVE TREATMENT

Throwing athletes who met inclusion criteria and failed nonoperative management underwent surgery by the senior author (JPB). Each patient was examined under anesthesia and, with the patient in the lateral decubitus position, a diagnostic arthroscopy was performed to identify posterior capsulolabral complex pathology, including a patulous capsule, capsular tears, labral fraying, and labral tears. A careful examination for rotator cuff pathology was also performed. Based on preoperative clinical examination, MRA, examination under anesthesia, pathologic findings at diagnostic arthroscopic surgery, and surgeon experience, capsulolabral plication was performed with or without suture anchors.^2,5 After capsulolabral repair, the capsule was evaluated for residual laxity, and additional plication sutures were placed, as indicated, with care to avoid overconstraint in these throwing athletes.¹ Posterior glenohumeral stability restoration was judged by removing traction and performing posterior load-and-shift and posterior stress tests. Any RCT with <50% thickness was débrided. Postoperative care and rehabilitation were carried out as previously described and were not altered by the presence or absence of a RCT.³

STATISTICAL ANALYSIS

Preoperative and latest follow-up ASES scores, stability scores, functional scores, and pain-level findings were compared using paired-samples Comparisons between groups, including throwing athletes with and without rotator cuff pathology, were done using the Student t test. Outcome comparisons between multiple groups, which included intraoperative findings and surgical fixation methods, were analyzed with c² modeling for nonparametric data. Statistical significance was set at P < .05. A power analysis found that this study was able to detect a meaningful difference of 10 ASES points.

RESULTS

PATIENT DEMOGRAPHIC CHARACTERISTICS

Of the 56 throwing athletes who met the inclusion criteria, 24 were found to have rotator cuff pathology in addition to posterior capsulolabral pathology, while 32 were found to have capsulolabral pathology alone. Demographic data are listed in Table 1. Mean age was 20.1 years for patients with rotator cuff pathology and 17.8 years for patients without RCTs. All 24 athletes with rotator cuff pathology were treated with arthroscopic débridement. Mean follow-up was 38.6 months (range, 16.5-63.6 months) for patients with RCTs and 39.1 months (range, 12-98.8 months) for patients without RCTs. No significant difference was found in age, sports level, or follow-up between groups.

Table 1. Demographic Data for Athletes With Posterior Instability With and Without Rotator Cuff Tears (N = 56 Shoulders)^a

^aThe majority of athletes were males in high school and their mean follow-up was 3 years.

Continue to: Outcomes

Table 2 lists the preoperative and postoperative scores for shoulder performance in throwing athletes with posterior shoulder instability, with and without RCTs.

Table 2. Preoperative and Postoperative Scores for Shoulder Performance in Throwing Athletes With Posterior Shoulder Instability With and Without Rotator Cuff Tears^a

^aThere was no difference in ASES, stability, pain, or functional scores between athletes with posterior instability alone compared with patients with concomitant rotator cuff tears.

Abbreviation: ASES, American Shoulder and Elbow Surgeons.

ASES Scores. Mean preoperative ASES scores for patients with RCTs improved significantly (t = –13.8, P < .001), as did those for patients without rotator cuff pathology (t = –8.9, P < .001). No significant differences in ASES score were found between patients with and without rotator cuff pathology before or after surgery (t = 1.9, P = .07; t = .58, P = .06). In addition, 70.8% (17/24) of throwing athletes with rotator cuff pathology had an excellent postoperative outcome (ASES score >80), and 29.2% (7/24) had a satisfactory outcome (ASES score, 60-80). Thus, 100% of those with concomitant posterior shoulder instability and RCTs had a good or excellent outcome after surgical intervention. In those without rotator cuff pathology, 78.1% (25/32) had an excellent outcome, 12.5% (4/32) had a satisfactory outcome, and 9.4% (3/32) had a poor outcome. Thus, 91% of those without rotator cuff pathology had a good or excellent outcome after surgery.

Stability. Preoperative stability scores improved significantly after surgery in both groups (t = 7.2, P < .001; t = 10.5, P < .001). There were no statistical differences between preoperative or postoperative stability scores in those with or without rotator cuff pathology (t = 1.7, P = .095; t = .03, P = .975). Of throwing athletes with RCTs, 54.2% (13/24) had an excellent outcome, 33.3% (8/24) a good outcome, and 12.5% (3/24) a satisfactory outcome. Thus, 87.5% (21/24) of those with RCTs had a good or excellent outcome in terms of stability. In those without rotator cuff pathology, 46.9% (15/32) had excellent stability, 46.9% (15/32) had good stability, and 3.1% (1/32) had satisfactory stability after surgery. Thus, 93.8% (30/32) of throwing athletes without rotator cuff pathology had good or excellent stability after surgery.

Pain. Mean preoperative pain scores for those with and without rotator cuff pathology improved significantly (t = 13.4, P < .001; t = 7.1, P < .001). There was no statistical difference in preoperative or postoperative pain scores between those with and without rotator cuff pathology (t = 1.99, P = .051; t = .49, P = .627).

Function. Mean preoperative function scores for both groups improved significantly (t = 7.7, P < .001; t = 8.0, P < .001). There was no difference in improvement in functional scores between the two groups before or after surgery (t = .36, P = .721; t = .5, P = .622).

Continue to: ROM

ROM. Of those with rotator cuff pathology, 54% (13/24) had normal ROM, 42% (10/24) had satisfactory ROM, and 4% (1/24) had limited ROM. In throwing athletes without rotator cuff pathology, 34% (11/32) had normal ROM, 53.1% (17/32) had satisfactory ROM, and 9% (3/32) had limited ROM after surgery. There was no significant difference in ROM between the groups (c² = 2.7, P = .260).

Strength. Of those with RCTs, 67% (16/24) reported normal strength, 29% (7/24) slightly decreased strength, and 4% (1/24) markedly decreased strength. Of those throwing athletes without rotator cuff pathology, 50% (16/32) had normal strength, 41% (13/32) had slightly decreased strength, and 9% (3/32) had markedly decreased strength. No statistical difference was noted between the two groups (c² = 1.7, P = .429).

Return to Sport. Of those with RCTs, 92% (22/24) returned to sport while 84% (27/32) of throwing athletes without RCTs returned to sport. There was no difference between the two groups (c² = .667, P = .414). Sixty-seven percent (16/24) of those with RCTs and 56% (18/32) of those without RCTs returned to the same level of sport. No statistical difference was found in return to play between throwing athletes with and without rotator cuff pathology (c² = .624, P = .430).

Failures. According to ASES scores, no throwers with RCTs failed, while 9.4% (3/32) with posterior instability alone failed. Regarding stability, 8.3% (2/24) of athletes with RCTs failed, while 6.3% (2/32) with posterior instability alone failed. 

SURGICAL FINDINGS AND PROCEDURES

Of the 24 throwing athletes with rotator cuff pathology, 92% (22/24) had labral tears, while 78% (25/32) of those without RCTs had labral tears. The majority of RCTs were in the posterior supraspinatus and anterior infraspinatus regions. This was not significantly different between groups (c² = 1.86, P = .172). All labral pathology was posterior-inferior, and all RCTs were <50% thickness, and therefore were débrided. Fifty-four percent (13/24) of those with RCTs had a patulous capsule and 63% (20/32) of throwing athletes without rotator cuff pathology had a patulous capsule. There was no significant difference between groups (c² = .393, P = .530). Of those with RCTs, 92% (22/24) had surgical fixation with anchors, while 78% (25/32) of those without rotator cuff pathology underwent repair with anchor fixation. There was no statistically significant difference in anchor use between groups (c² = 1.86, P = .172).

Continue to: Discussion

Throwing athletes with and without RCTs had similar rates of recovery and return to play after arthroscopic capsular labral repair, with rotator cuff débridement if a tear was present. The mean follow-up was 3.2 years. Further, there was no difference in return to play (92% vs 84%), ASES score, stability, pain, function, ROM, or strength between the 2 groups before or after surgery. In this cohort of 56 patients, 24 throwing athletes (43%) were found to have RCTs.

Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport, and 67% (16/24) returned to the same level. Eight percent of throwing athletes with RCTs were unable to return to sport after surgery. These return-to-play rates are an improvement over most previously reported rates in throwing athletes and in posterior shoulder instability in general.^1-4,11 When these athletes are compared with their counterparts with combined SLAP tears and RCTs, return-to-play rates are notably higher. There may be discrepancies in interpreting return-to-play between the two studies, but in the current study, 67% of those with concomitant RCTs achieved return to preinjury level of play. This is 10% higher than the rate reported in athletes with SLAP tears alone (57%) and even higher than in those with concomitant SLAP and RCTs. It is also essential to note that a number of this cohort’s athletes who did not return to play did so for factors (eg, graduation) unrelated to the shoulder. However, the study by Neri and colleagues⁵ included professional athletes who likely all attempted to return to play and, if unable to perform at the same level, likely were unable to continue their professional career.⁵

All patients with RCTs had a good or excellent outcome (ASES score), and 70.8% had an excellent outcome. Similarly, 97% of those without rotator cuff pathology had a good or excellent outcome, and 81.3% had an excellent outcome. There was no significant difference between the two groups. These results parallel those of Neri and colleagues’⁵ study of SLAP tears with RCTs, where 96% (22/23) of throwing athletes had a good or excellent outcome. Despite these high outcome scores in patients with SLAP tears, only 57% were able to return to elite pitching.⁵ In the current study, pain was slightly higher for those with rotator cuff pathology before surgery—a finding consistent with pain frequently being found in patients with isolated partial-thickness RCTs. Their postoperative pain scores were actually lower on average than those of patients without RCTs, which suggests simple débridement of undersurface tears adequately addressed the pathology. The authors theorize that the main pain generator in this population may be posterior instability, and that the rotator cuff has less of an influence. In the SLAP population, the main pain generator likely is the RCT.

Failures by ASES score or strength were fairly rare in this cohort. Many patients opted to have revision surgery because of continued instability, pain, decreased function, or reinjury. One potential cause of failure in this cohort is inadequate capsular shift. However, capsular plication in throwing athletes is difficult to address, as overtensioning the repair can lead to the inability to adequately perform overhead activites.^3,4 This cannot be overemphasized, particularly with pitchers.

Partial-thickness RCTs, particularly those on the articular side, are common in throwing athletes because of high tensile and compressive loads.¹² Despite the known risk of RCTs with posterior shoulder instability in throwing athletes, the authors are unaware of reports of the incidence or treatment of this pathology. RCTs in this posterior instability group likely represent a pathology other than internal impingement. The high proportion of throwing athletes with RCTs in this study (43%) indicates a need for close evaluation of rotator cuff pathology in young throwing athletes. Ide et al found that 75% of patients with SLAP tears had partial articular-sided RCTs.¹³ In the current study, all RCTs were small partial tears, and arthroscopic débridement was performed. It is unknown whether repair of these RCTs would impact return to play. However, rotator cuff repair in this population has been shown to have poor outcomes. Tear thickness typically is used to determine treatment, with débridement performed if <50% tendon thickness is affected. More recently, many have advocated having greater tendon involvement in throwers before repair, because of poor outcomes. Although studies are limited, tear size does seem to correlate with outcomes.¹⁴

Continue to: Study Limitations

Limitations of this study include its small number of professional throwing athletes, with the majority being high school athletes. Further, although ASES scores are consistently used in posterior shoulder instability studies, these scores are influenced highly by pain scores, and some argue that other scoring systems may provide more useful information. However, none of the more modern scoring systems have been studied extensively in posterior glenohumeral instability. Further, because the authors used the present scoring systems previously,^1-4 they were continued to be used for comparison and consistency. Outcomes such as ROM and strength may carry more weight if measured and documented by clinical examination. Further testing, such as clinical evaluation of the jerk test or the posterior load-and-shift test, and their comparison before and after surgery may provide more objective data.

CONCLUSION

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike a previous study of throwing athletes’ outcomes after surgery for concomitant SLAP tears and RCTs,⁵ this study of throwing athletes with concomitant posterior shoulder instability and RCTs found no difference in patient-reported outcome measures or return to play. In throwing athletes with posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

ABSTRACT

In a previous study, compared with throwing athletes with superior labral anterior posterior (SLAP) tears, those with concomitant SLAP tears and rotator cuff tears (RCTs) had significantly poorer outcome scores and return to play. Posterior shoulder instability also occurs in throwing athletes, but no studies currently exist regarding outcomes of these patients with concomitant RCTs.

The authors hypothesized that throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent rotator cuff pathology would have poorer outcome scores and return to play.

Fifty-six consecutive throwing athletes with unidirectional posterior shoulder instability underwent arthroscopic capsulolabral repair. Preoperative and postoperative patient-centered outcomes of pain, stability, function, range of motion, strength, and American Shoulder and Elbow Surgeons Shoulder (ASES) scores, as well as return to play, were evaluated. Patients with and without rotator cuff pathology were compared.

Forty-three percent (24/56) of throwing athletes had rotator cuff pathology in addition to posterior capsulolabral pathology. All RCTs were débrided. At a mean of 3 years, there were no differences in preoperative and postoperative patient-centered outcomes between those with and without RCTs. Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport (P = .414) and 67% (16/24) returned to the same level (P = .430).

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike the previous study evaluating throwers outcomes after surgical treatment for concomitant SLAP tears and RCTs, the authors found no difference in patient-reported outcome measures or return to play for throwing athletes with concomitant posterior shoulder instability and RCTs. In throwing athletes with concomitant posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

Continue to: Posterior shoulder instability...

Posterior shoulder instability is an important and increasingly recognized pathology among throwers. Like the superior labrum, the posterior capsulolabral complex is also susceptible to injury during the throwing motion; the posterior labrum being most at risk during the late cocking and follow-through phases. Recent studies have found that arthroscopic capsulolabral reconstruction in posterior shoulder instability is successful in allowing athletes to return to their preinjury sports activities, with 2 studies detailing outcomes in throwing athletes.^1-4 However, superior labral anterior posterior (SLAP) tears are common in throwing athletes and have been treated with varying and limited success. Further, in a study of outcomes of arthroscopic repair of SLAP lesions, Neri and colleagues⁵ found that, compared with throwing athletes with SLAP tears, throwing athletes with concomitant SLAP tears and partial-thickness rotator cuff tears (RCTs) had significantly poorer outcomes and return-to-play rates after surgical repair.

The purpose of this study was to determine outcome scores and return to play of throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent RCTs and to compare them with outcome scores as well as return to play of throwing athletes with isolated posterior shoulder instability. It was hypothesized that throwing athletes with a combination of posterior shoulder instability and RCT would have poorer outcomes and poorer return to play after surgery.⁵

METHODS

PATIENT SELECTION

After Institutional Review Board approval, informed consent was obtained, and consecutive throwing athletes who underwent arthroscopic posterior capsulolabral reconstruction for posterior shoulder instability were followed in the perioperative period. Inclusion criteria were throwing athletes participating in competitive sports at the high school, collegiate, or professional level, minimum 1-year follow-up, presence of unidirectional posterior instability, and absence of symptoms of instability in any direction other than posterior. Patients with inferior instability, SLAP pathology on examination and on magnetic resonance imaging, multidirectional instability, or habitual or psychogenic voluntary shoulder subluxations were excluded. Patients with diagnoses of both posterior shoulder instability and impingement treated with subacromial decompression and distal clavicle resection were also excluded.

After this cohort was identified, patient records were reviewed for pertinent operative data, such as procedure, complications, and evidence of RCT by operative report and arthroscopic photographs. A partial RCT was defined as a tear of 10% to 50%; those with rotator cuff fraying were determined not to be significant.

PATIENT EVALUATION

Surgeries were performed between January 1998 and December 2009 by the senior author (JPB). All patients were followed with clinical examinations, radiographs, and subjective grading scales. Recorded patient demographic data included age, sex, sport, position, competition level, and follow-up duration.

Continue to: All patients had...

All patients had symptomatic posterior shoulder instability, including posterior shoulder pain, clicking, a sensation of subluxation, or instability/apprehension with motion. Each athlete’s shoulder was palpated for tenderness and tested for impingement. Specific posterior glenohumeral instability tests, including the Kim test,⁶ the circumduction test, the jerk test,⁷ the posterior load-and-shift test,⁸ and the posterior stress test,⁹ were performed on all patients. Patients with multidirectional instability on the sulcus test, as well as provocative tests indicating SLAP pathology, such as the Crank test and the active compression test, were not included. Standard radiography and magnetic resonance arthrography (MRA) were performed to further narrow inclusion and exclusion criteria.

Both before surgery and at latest follow-up, patient outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) score (range, 0-100) which combines a subjective functional scale measuring activities of daily living (0-3 for each of 10 tasks, with a total of 0-30) and a subjective pain scale (0-10, with 10 being worst pain). Values >80 were described as excellent, and failures were defined as scores <60 after surgery.¹⁰ A subjective stability scale (0-10, with 0 indicating completely stable and 10 completely unstable), strength scale (0-3, with 0 indicating none, 1 markedly decreased, 2 slightly decreased, and 3 normal), and ROM scale (0-3, with 0 indicating poor, 1 limited, 2 satisfactory, and 3 full) were evaluated both before surgery and at the latest follow-up. A stability score >5 after surgery was defined as a failure.^1,2,11 Patients were also asked if, based on their current state, they would undergo surgery again. Intraoperative findings and specific surgical procedures performed were correlated with the aforementioned subjective and objective outcome scores.

OPERATIVE TREATMENT

Throwing athletes who met inclusion criteria and failed nonoperative management underwent surgery by the senior author (JPB). Each patient was examined under anesthesia and, with the patient in the lateral decubitus position, a diagnostic arthroscopy was performed to identify posterior capsulolabral complex pathology, including a patulous capsule, capsular tears, labral fraying, and labral tears. A careful examination for rotator cuff pathology was also performed. Based on preoperative clinical examination, MRA, examination under anesthesia, pathologic findings at diagnostic arthroscopic surgery, and surgeon experience, capsulolabral plication was performed with or without suture anchors.^2,5 After capsulolabral repair, the capsule was evaluated for residual laxity, and additional plication sutures were placed, as indicated, with care to avoid overconstraint in these throwing athletes.¹ Posterior glenohumeral stability restoration was judged by removing traction and performing posterior load-and-shift and posterior stress tests. Any RCT with <50% thickness was débrided. Postoperative care and rehabilitation were carried out as previously described and were not altered by the presence or absence of a RCT.³

STATISTICAL ANALYSIS

Preoperative and latest follow-up ASES scores, stability scores, functional scores, and pain-level findings were compared using paired-samples Comparisons between groups, including throwing athletes with and without rotator cuff pathology, were done using the Student t test. Outcome comparisons between multiple groups, which included intraoperative findings and surgical fixation methods, were analyzed with c² modeling for nonparametric data. Statistical significance was set at P < .05. A power analysis found that this study was able to detect a meaningful difference of 10 ASES points.

RESULTS

PATIENT DEMOGRAPHIC CHARACTERISTICS

Of the 56 throwing athletes who met the inclusion criteria, 24 were found to have rotator cuff pathology in addition to posterior capsulolabral pathology, while 32 were found to have capsulolabral pathology alone. Demographic data are listed in Table 1. Mean age was 20.1 years for patients with rotator cuff pathology and 17.8 years for patients without RCTs. All 24 athletes with rotator cuff pathology were treated with arthroscopic débridement. Mean follow-up was 38.6 months (range, 16.5-63.6 months) for patients with RCTs and 39.1 months (range, 12-98.8 months) for patients without RCTs. No significant difference was found in age, sports level, or follow-up between groups.

Table 1. Demographic Data for Athletes With Posterior Instability With and Without Rotator Cuff Tears (N = 56 Shoulders)^a

^aThe majority of athletes were males in high school and their mean follow-up was 3 years.

Continue to: Outcomes

Table 2 lists the preoperative and postoperative scores for shoulder performance in throwing athletes with posterior shoulder instability, with and without RCTs.

Table 2. Preoperative and Postoperative Scores for Shoulder Performance in Throwing Athletes With Posterior Shoulder Instability With and Without Rotator Cuff Tears^a

^aThere was no difference in ASES, stability, pain, or functional scores between athletes with posterior instability alone compared with patients with concomitant rotator cuff tears.

Abbreviation: ASES, American Shoulder and Elbow Surgeons.

ASES Scores. Mean preoperative ASES scores for patients with RCTs improved significantly (t = –13.8, P < .001), as did those for patients without rotator cuff pathology (t = –8.9, P < .001). No significant differences in ASES score were found between patients with and without rotator cuff pathology before or after surgery (t = 1.9, P = .07; t = .58, P = .06). In addition, 70.8% (17/24) of throwing athletes with rotator cuff pathology had an excellent postoperative outcome (ASES score >80), and 29.2% (7/24) had a satisfactory outcome (ASES score, 60-80). Thus, 100% of those with concomitant posterior shoulder instability and RCTs had a good or excellent outcome after surgical intervention. In those without rotator cuff pathology, 78.1% (25/32) had an excellent outcome, 12.5% (4/32) had a satisfactory outcome, and 9.4% (3/32) had a poor outcome. Thus, 91% of those without rotator cuff pathology had a good or excellent outcome after surgery.

Stability. Preoperative stability scores improved significantly after surgery in both groups (t = 7.2, P < .001; t = 10.5, P < .001). There were no statistical differences between preoperative or postoperative stability scores in those with or without rotator cuff pathology (t = 1.7, P = .095; t = .03, P = .975). Of throwing athletes with RCTs, 54.2% (13/24) had an excellent outcome, 33.3% (8/24) a good outcome, and 12.5% (3/24) a satisfactory outcome. Thus, 87.5% (21/24) of those with RCTs had a good or excellent outcome in terms of stability. In those without rotator cuff pathology, 46.9% (15/32) had excellent stability, 46.9% (15/32) had good stability, and 3.1% (1/32) had satisfactory stability after surgery. Thus, 93.8% (30/32) of throwing athletes without rotator cuff pathology had good or excellent stability after surgery.

Pain. Mean preoperative pain scores for those with and without rotator cuff pathology improved significantly (t = 13.4, P < .001; t = 7.1, P < .001). There was no statistical difference in preoperative or postoperative pain scores between those with and without rotator cuff pathology (t = 1.99, P = .051; t = .49, P = .627).

Function. Mean preoperative function scores for both groups improved significantly (t = 7.7, P < .001; t = 8.0, P < .001). There was no difference in improvement in functional scores between the two groups before or after surgery (t = .36, P = .721; t = .5, P = .622).

Continue to: ROM

ROM. Of those with rotator cuff pathology, 54% (13/24) had normal ROM, 42% (10/24) had satisfactory ROM, and 4% (1/24) had limited ROM. In throwing athletes without rotator cuff pathology, 34% (11/32) had normal ROM, 53.1% (17/32) had satisfactory ROM, and 9% (3/32) had limited ROM after surgery. There was no significant difference in ROM between the groups (c² = 2.7, P = .260).

Strength. Of those with RCTs, 67% (16/24) reported normal strength, 29% (7/24) slightly decreased strength, and 4% (1/24) markedly decreased strength. Of those throwing athletes without rotator cuff pathology, 50% (16/32) had normal strength, 41% (13/32) had slightly decreased strength, and 9% (3/32) had markedly decreased strength. No statistical difference was noted between the two groups (c² = 1.7, P = .429).

Return to Sport. Of those with RCTs, 92% (22/24) returned to sport while 84% (27/32) of throwing athletes without RCTs returned to sport. There was no difference between the two groups (c² = .667, P = .414). Sixty-seven percent (16/24) of those with RCTs and 56% (18/32) of those without RCTs returned to the same level of sport. No statistical difference was found in return to play between throwing athletes with and without rotator cuff pathology (c² = .624, P = .430).

Failures. According to ASES scores, no throwers with RCTs failed, while 9.4% (3/32) with posterior instability alone failed. Regarding stability, 8.3% (2/24) of athletes with RCTs failed, while 6.3% (2/32) with posterior instability alone failed. 

SURGICAL FINDINGS AND PROCEDURES

Of the 24 throwing athletes with rotator cuff pathology, 92% (22/24) had labral tears, while 78% (25/32) of those without RCTs had labral tears. The majority of RCTs were in the posterior supraspinatus and anterior infraspinatus regions. This was not significantly different between groups (c² = 1.86, P = .172). All labral pathology was posterior-inferior, and all RCTs were <50% thickness, and therefore were débrided. Fifty-four percent (13/24) of those with RCTs had a patulous capsule and 63% (20/32) of throwing athletes without rotator cuff pathology had a patulous capsule. There was no significant difference between groups (c² = .393, P = .530). Of those with RCTs, 92% (22/24) had surgical fixation with anchors, while 78% (25/32) of those without rotator cuff pathology underwent repair with anchor fixation. There was no statistically significant difference in anchor use between groups (c² = 1.86, P = .172).

Continue to: Discussion

Throwing athletes with and without RCTs had similar rates of recovery and return to play after arthroscopic capsular labral repair, with rotator cuff débridement if a tear was present. The mean follow-up was 3.2 years. Further, there was no difference in return to play (92% vs 84%), ASES score, stability, pain, function, ROM, or strength between the 2 groups before or after surgery. In this cohort of 56 patients, 24 throwing athletes (43%) were found to have RCTs.

Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport, and 67% (16/24) returned to the same level. Eight percent of throwing athletes with RCTs were unable to return to sport after surgery. These return-to-play rates are an improvement over most previously reported rates in throwing athletes and in posterior shoulder instability in general.^1-4,11 When these athletes are compared with their counterparts with combined SLAP tears and RCTs, return-to-play rates are notably higher. There may be discrepancies in interpreting return-to-play between the two studies, but in the current study, 67% of those with concomitant RCTs achieved return to preinjury level of play. This is 10% higher than the rate reported in athletes with SLAP tears alone (57%) and even higher than in those with concomitant SLAP and RCTs. It is also essential to note that a number of this cohort’s athletes who did not return to play did so for factors (eg, graduation) unrelated to the shoulder. However, the study by Neri and colleagues⁵ included professional athletes who likely all attempted to return to play and, if unable to perform at the same level, likely were unable to continue their professional career.⁵

All patients with RCTs had a good or excellent outcome (ASES score), and 70.8% had an excellent outcome. Similarly, 97% of those without rotator cuff pathology had a good or excellent outcome, and 81.3% had an excellent outcome. There was no significant difference between the two groups. These results parallel those of Neri and colleagues’⁵ study of SLAP tears with RCTs, where 96% (22/23) of throwing athletes had a good or excellent outcome. Despite these high outcome scores in patients with SLAP tears, only 57% were able to return to elite pitching.⁵ In the current study, pain was slightly higher for those with rotator cuff pathology before surgery—a finding consistent with pain frequently being found in patients with isolated partial-thickness RCTs. Their postoperative pain scores were actually lower on average than those of patients without RCTs, which suggests simple débridement of undersurface tears adequately addressed the pathology. The authors theorize that the main pain generator in this population may be posterior instability, and that the rotator cuff has less of an influence. In the SLAP population, the main pain generator likely is the RCT.

Failures by ASES score or strength were fairly rare in this cohort. Many patients opted to have revision surgery because of continued instability, pain, decreased function, or reinjury. One potential cause of failure in this cohort is inadequate capsular shift. However, capsular plication in throwing athletes is difficult to address, as overtensioning the repair can lead to the inability to adequately perform overhead activites.^3,4 This cannot be overemphasized, particularly with pitchers.

Partial-thickness RCTs, particularly those on the articular side, are common in throwing athletes because of high tensile and compressive loads.¹² Despite the known risk of RCTs with posterior shoulder instability in throwing athletes, the authors are unaware of reports of the incidence or treatment of this pathology. RCTs in this posterior instability group likely represent a pathology other than internal impingement. The high proportion of throwing athletes with RCTs in this study (43%) indicates a need for close evaluation of rotator cuff pathology in young throwing athletes. Ide et al found that 75% of patients with SLAP tears had partial articular-sided RCTs.¹³ In the current study, all RCTs were small partial tears, and arthroscopic débridement was performed. It is unknown whether repair of these RCTs would impact return to play. However, rotator cuff repair in this population has been shown to have poor outcomes. Tear thickness typically is used to determine treatment, with débridement performed if <50% tendon thickness is affected. More recently, many have advocated having greater tendon involvement in throwers before repair, because of poor outcomes. Although studies are limited, tear size does seem to correlate with outcomes.¹⁴

Continue to: Study Limitations

Limitations of this study include its small number of professional throwing athletes, with the majority being high school athletes. Further, although ASES scores are consistently used in posterior shoulder instability studies, these scores are influenced highly by pain scores, and some argue that other scoring systems may provide more useful information. However, none of the more modern scoring systems have been studied extensively in posterior glenohumeral instability. Further, because the authors used the present scoring systems previously,^1-4 they were continued to be used for comparison and consistency. Outcomes such as ROM and strength may carry more weight if measured and documented by clinical examination. Further testing, such as clinical evaluation of the jerk test or the posterior load-and-shift test, and their comparison before and after surgery may provide more objective data.

CONCLUSION

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike a previous study of throwing athletes’ outcomes after surgery for concomitant SLAP tears and RCTs,⁵ this study of throwing athletes with concomitant posterior shoulder instability and RCTs found no difference in patient-reported outcome measures or return to play. In throwing athletes with posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

ABSTRACT

In a previous study, compared with throwing athletes with superior labral anterior posterior (SLAP) tears, those with concomitant SLAP tears and rotator cuff tears (RCTs) had significantly poorer outcome scores and return to play. Posterior shoulder instability also occurs in throwing athletes, but no studies currently exist regarding outcomes of these patients with concomitant RCTs.

The authors hypothesized that throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent rotator cuff pathology would have poorer outcome scores and return to play.

Fifty-six consecutive throwing athletes with unidirectional posterior shoulder instability underwent arthroscopic capsulolabral repair. Preoperative and postoperative patient-centered outcomes of pain, stability, function, range of motion, strength, and American Shoulder and Elbow Surgeons Shoulder (ASES) scores, as well as return to play, were evaluated. Patients with and without rotator cuff pathology were compared.

Forty-three percent (24/56) of throwing athletes had rotator cuff pathology in addition to posterior capsulolabral pathology. All RCTs were débrided. At a mean of 3 years, there were no differences in preoperative and postoperative patient-centered outcomes between those with and without RCTs. Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport (P = .414) and 67% (16/24) returned to the same level (P = .430).

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike the previous study evaluating throwers outcomes after surgical treatment for concomitant SLAP tears and RCTs, the authors found no difference in patient-reported outcome measures or return to play for throwing athletes with concomitant posterior shoulder instability and RCTs. In throwing athletes with concomitant posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

Continue to: Posterior shoulder instability...

Posterior shoulder instability is an important and increasingly recognized pathology among throwers. Like the superior labrum, the posterior capsulolabral complex is also susceptible to injury during the throwing motion; the posterior labrum being most at risk during the late cocking and follow-through phases. Recent studies have found that arthroscopic capsulolabral reconstruction in posterior shoulder instability is successful in allowing athletes to return to their preinjury sports activities, with 2 studies detailing outcomes in throwing athletes.^1-4 However, superior labral anterior posterior (SLAP) tears are common in throwing athletes and have been treated with varying and limited success. Further, in a study of outcomes of arthroscopic repair of SLAP lesions, Neri and colleagues⁵ found that, compared with throwing athletes with SLAP tears, throwing athletes with concomitant SLAP tears and partial-thickness rotator cuff tears (RCTs) had significantly poorer outcomes and return-to-play rates after surgical repair.

The purpose of this study was to determine outcome scores and return to play of throwing athletes treated with arthroscopic capsulolabral repair for posterior shoulder instability with coexistent RCTs and to compare them with outcome scores as well as return to play of throwing athletes with isolated posterior shoulder instability. It was hypothesized that throwing athletes with a combination of posterior shoulder instability and RCT would have poorer outcomes and poorer return to play after surgery.⁵

METHODS

PATIENT SELECTION

After Institutional Review Board approval, informed consent was obtained, and consecutive throwing athletes who underwent arthroscopic posterior capsulolabral reconstruction for posterior shoulder instability were followed in the perioperative period. Inclusion criteria were throwing athletes participating in competitive sports at the high school, collegiate, or professional level, minimum 1-year follow-up, presence of unidirectional posterior instability, and absence of symptoms of instability in any direction other than posterior. Patients with inferior instability, SLAP pathology on examination and on magnetic resonance imaging, multidirectional instability, or habitual or psychogenic voluntary shoulder subluxations were excluded. Patients with diagnoses of both posterior shoulder instability and impingement treated with subacromial decompression and distal clavicle resection were also excluded.

After this cohort was identified, patient records were reviewed for pertinent operative data, such as procedure, complications, and evidence of RCT by operative report and arthroscopic photographs. A partial RCT was defined as a tear of 10% to 50%; those with rotator cuff fraying were determined not to be significant.

PATIENT EVALUATION

Surgeries were performed between January 1998 and December 2009 by the senior author (JPB). All patients were followed with clinical examinations, radiographs, and subjective grading scales. Recorded patient demographic data included age, sex, sport, position, competition level, and follow-up duration.

Continue to: All patients had...

All patients had symptomatic posterior shoulder instability, including posterior shoulder pain, clicking, a sensation of subluxation, or instability/apprehension with motion. Each athlete’s shoulder was palpated for tenderness and tested for impingement. Specific posterior glenohumeral instability tests, including the Kim test,⁶ the circumduction test, the jerk test,⁷ the posterior load-and-shift test,⁸ and the posterior stress test,⁹ were performed on all patients. Patients with multidirectional instability on the sulcus test, as well as provocative tests indicating SLAP pathology, such as the Crank test and the active compression test, were not included. Standard radiography and magnetic resonance arthrography (MRA) were performed to further narrow inclusion and exclusion criteria.

Both before surgery and at latest follow-up, patient outcomes were evaluated using the American Shoulder and Elbow Surgeons (ASES) score (range, 0-100) which combines a subjective functional scale measuring activities of daily living (0-3 for each of 10 tasks, with a total of 0-30) and a subjective pain scale (0-10, with 10 being worst pain). Values >80 were described as excellent, and failures were defined as scores <60 after surgery.¹⁰ A subjective stability scale (0-10, with 0 indicating completely stable and 10 completely unstable), strength scale (0-3, with 0 indicating none, 1 markedly decreased, 2 slightly decreased, and 3 normal), and ROM scale (0-3, with 0 indicating poor, 1 limited, 2 satisfactory, and 3 full) were evaluated both before surgery and at the latest follow-up. A stability score >5 after surgery was defined as a failure.^1,2,11 Patients were also asked if, based on their current state, they would undergo surgery again. Intraoperative findings and specific surgical procedures performed were correlated with the aforementioned subjective and objective outcome scores.

OPERATIVE TREATMENT

Throwing athletes who met inclusion criteria and failed nonoperative management underwent surgery by the senior author (JPB). Each patient was examined under anesthesia and, with the patient in the lateral decubitus position, a diagnostic arthroscopy was performed to identify posterior capsulolabral complex pathology, including a patulous capsule, capsular tears, labral fraying, and labral tears. A careful examination for rotator cuff pathology was also performed. Based on preoperative clinical examination, MRA, examination under anesthesia, pathologic findings at diagnostic arthroscopic surgery, and surgeon experience, capsulolabral plication was performed with or without suture anchors.^2,5 After capsulolabral repair, the capsule was evaluated for residual laxity, and additional plication sutures were placed, as indicated, with care to avoid overconstraint in these throwing athletes.¹ Posterior glenohumeral stability restoration was judged by removing traction and performing posterior load-and-shift and posterior stress tests. Any RCT with <50% thickness was débrided. Postoperative care and rehabilitation were carried out as previously described and were not altered by the presence or absence of a RCT.³

STATISTICAL ANALYSIS

Preoperative and latest follow-up ASES scores, stability scores, functional scores, and pain-level findings were compared using paired-samples Comparisons between groups, including throwing athletes with and without rotator cuff pathology, were done using the Student t test. Outcome comparisons between multiple groups, which included intraoperative findings and surgical fixation methods, were analyzed with c² modeling for nonparametric data. Statistical significance was set at P < .05. A power analysis found that this study was able to detect a meaningful difference of 10 ASES points.

RESULTS

PATIENT DEMOGRAPHIC CHARACTERISTICS

Of the 56 throwing athletes who met the inclusion criteria, 24 were found to have rotator cuff pathology in addition to posterior capsulolabral pathology, while 32 were found to have capsulolabral pathology alone. Demographic data are listed in Table 1. Mean age was 20.1 years for patients with rotator cuff pathology and 17.8 years for patients without RCTs. All 24 athletes with rotator cuff pathology were treated with arthroscopic débridement. Mean follow-up was 38.6 months (range, 16.5-63.6 months) for patients with RCTs and 39.1 months (range, 12-98.8 months) for patients without RCTs. No significant difference was found in age, sports level, or follow-up between groups.

Table 1. Demographic Data for Athletes With Posterior Instability With and Without Rotator Cuff Tears (N = 56 Shoulders)^a

^aThe majority of athletes were males in high school and their mean follow-up was 3 years.

Continue to: Outcomes

Table 2 lists the preoperative and postoperative scores for shoulder performance in throwing athletes with posterior shoulder instability, with and without RCTs.

Table 2. Preoperative and Postoperative Scores for Shoulder Performance in Throwing Athletes With Posterior Shoulder Instability With and Without Rotator Cuff Tears^a

^aThere was no difference in ASES, stability, pain, or functional scores between athletes with posterior instability alone compared with patients with concomitant rotator cuff tears.

Abbreviation: ASES, American Shoulder and Elbow Surgeons.

ASES Scores. Mean preoperative ASES scores for patients with RCTs improved significantly (t = –13.8, P < .001), as did those for patients without rotator cuff pathology (t = –8.9, P < .001). No significant differences in ASES score were found between patients with and without rotator cuff pathology before or after surgery (t = 1.9, P = .07; t = .58, P = .06). In addition, 70.8% (17/24) of throwing athletes with rotator cuff pathology had an excellent postoperative outcome (ASES score >80), and 29.2% (7/24) had a satisfactory outcome (ASES score, 60-80). Thus, 100% of those with concomitant posterior shoulder instability and RCTs had a good or excellent outcome after surgical intervention. In those without rotator cuff pathology, 78.1% (25/32) had an excellent outcome, 12.5% (4/32) had a satisfactory outcome, and 9.4% (3/32) had a poor outcome. Thus, 91% of those without rotator cuff pathology had a good or excellent outcome after surgery.

Stability. Preoperative stability scores improved significantly after surgery in both groups (t = 7.2, P < .001; t = 10.5, P < .001). There were no statistical differences between preoperative or postoperative stability scores in those with or without rotator cuff pathology (t = 1.7, P = .095; t = .03, P = .975). Of throwing athletes with RCTs, 54.2% (13/24) had an excellent outcome, 33.3% (8/24) a good outcome, and 12.5% (3/24) a satisfactory outcome. Thus, 87.5% (21/24) of those with RCTs had a good or excellent outcome in terms of stability. In those without rotator cuff pathology, 46.9% (15/32) had excellent stability, 46.9% (15/32) had good stability, and 3.1% (1/32) had satisfactory stability after surgery. Thus, 93.8% (30/32) of throwing athletes without rotator cuff pathology had good or excellent stability after surgery.

Pain. Mean preoperative pain scores for those with and without rotator cuff pathology improved significantly (t = 13.4, P < .001; t = 7.1, P < .001). There was no statistical difference in preoperative or postoperative pain scores between those with and without rotator cuff pathology (t = 1.99, P = .051; t = .49, P = .627).

Function. Mean preoperative function scores for both groups improved significantly (t = 7.7, P < .001; t = 8.0, P < .001). There was no difference in improvement in functional scores between the two groups before or after surgery (t = .36, P = .721; t = .5, P = .622).

Continue to: ROM

ROM. Of those with rotator cuff pathology, 54% (13/24) had normal ROM, 42% (10/24) had satisfactory ROM, and 4% (1/24) had limited ROM. In throwing athletes without rotator cuff pathology, 34% (11/32) had normal ROM, 53.1% (17/32) had satisfactory ROM, and 9% (3/32) had limited ROM after surgery. There was no significant difference in ROM between the groups (c² = 2.7, P = .260).

Strength. Of those with RCTs, 67% (16/24) reported normal strength, 29% (7/24) slightly decreased strength, and 4% (1/24) markedly decreased strength. Of those throwing athletes without rotator cuff pathology, 50% (16/32) had normal strength, 41% (13/32) had slightly decreased strength, and 9% (3/32) had markedly decreased strength. No statistical difference was noted between the two groups (c² = 1.7, P = .429).

Return to Sport. Of those with RCTs, 92% (22/24) returned to sport while 84% (27/32) of throwing athletes without RCTs returned to sport. There was no difference between the two groups (c² = .667, P = .414). Sixty-seven percent (16/24) of those with RCTs and 56% (18/32) of those without RCTs returned to the same level of sport. No statistical difference was found in return to play between throwing athletes with and without rotator cuff pathology (c² = .624, P = .430).

Failures. According to ASES scores, no throwers with RCTs failed, while 9.4% (3/32) with posterior instability alone failed. Regarding stability, 8.3% (2/24) of athletes with RCTs failed, while 6.3% (2/32) with posterior instability alone failed. 

SURGICAL FINDINGS AND PROCEDURES

Of the 24 throwing athletes with rotator cuff pathology, 92% (22/24) had labral tears, while 78% (25/32) of those without RCTs had labral tears. The majority of RCTs were in the posterior supraspinatus and anterior infraspinatus regions. This was not significantly different between groups (c² = 1.86, P = .172). All labral pathology was posterior-inferior, and all RCTs were <50% thickness, and therefore were débrided. Fifty-four percent (13/24) of those with RCTs had a patulous capsule and 63% (20/32) of throwing athletes without rotator cuff pathology had a patulous capsule. There was no significant difference between groups (c² = .393, P = .530). Of those with RCTs, 92% (22/24) had surgical fixation with anchors, while 78% (25/32) of those without rotator cuff pathology underwent repair with anchor fixation. There was no statistically significant difference in anchor use between groups (c² = 1.86, P = .172).

Continue to: Discussion

Throwing athletes with and without RCTs had similar rates of recovery and return to play after arthroscopic capsular labral repair, with rotator cuff débridement if a tear was present. The mean follow-up was 3.2 years. Further, there was no difference in return to play (92% vs 84%), ASES score, stability, pain, function, ROM, or strength between the 2 groups before or after surgery. In this cohort of 56 patients, 24 throwing athletes (43%) were found to have RCTs.

Return-to-play rates showed no between-group differences; 92% (22/24) of athletes with concomitant RCTs returned to sport, and 67% (16/24) returned to the same level. Eight percent of throwing athletes with RCTs were unable to return to sport after surgery. These return-to-play rates are an improvement over most previously reported rates in throwing athletes and in posterior shoulder instability in general.^1-4,11 When these athletes are compared with their counterparts with combined SLAP tears and RCTs, return-to-play rates are notably higher. There may be discrepancies in interpreting return-to-play between the two studies, but in the current study, 67% of those with concomitant RCTs achieved return to preinjury level of play. This is 10% higher than the rate reported in athletes with SLAP tears alone (57%) and even higher than in those with concomitant SLAP and RCTs. It is also essential to note that a number of this cohort’s athletes who did not return to play did so for factors (eg, graduation) unrelated to the shoulder. However, the study by Neri and colleagues⁵ included professional athletes who likely all attempted to return to play and, if unable to perform at the same level, likely were unable to continue their professional career.⁵

All patients with RCTs had a good or excellent outcome (ASES score), and 70.8% had an excellent outcome. Similarly, 97% of those without rotator cuff pathology had a good or excellent outcome, and 81.3% had an excellent outcome. There was no significant difference between the two groups. These results parallel those of Neri and colleagues’⁵ study of SLAP tears with RCTs, where 96% (22/23) of throwing athletes had a good or excellent outcome. Despite these high outcome scores in patients with SLAP tears, only 57% were able to return to elite pitching.⁵ In the current study, pain was slightly higher for those with rotator cuff pathology before surgery—a finding consistent with pain frequently being found in patients with isolated partial-thickness RCTs. Their postoperative pain scores were actually lower on average than those of patients without RCTs, which suggests simple débridement of undersurface tears adequately addressed the pathology. The authors theorize that the main pain generator in this population may be posterior instability, and that the rotator cuff has less of an influence. In the SLAP population, the main pain generator likely is the RCT.

Failures by ASES score or strength were fairly rare in this cohort. Many patients opted to have revision surgery because of continued instability, pain, decreased function, or reinjury. One potential cause of failure in this cohort is inadequate capsular shift. However, capsular plication in throwing athletes is difficult to address, as overtensioning the repair can lead to the inability to adequately perform overhead activites.^3,4 This cannot be overemphasized, particularly with pitchers.

Partial-thickness RCTs, particularly those on the articular side, are common in throwing athletes because of high tensile and compressive loads.¹² Despite the known risk of RCTs with posterior shoulder instability in throwing athletes, the authors are unaware of reports of the incidence or treatment of this pathology. RCTs in this posterior instability group likely represent a pathology other than internal impingement. The high proportion of throwing athletes with RCTs in this study (43%) indicates a need for close evaluation of rotator cuff pathology in young throwing athletes. Ide et al found that 75% of patients with SLAP tears had partial articular-sided RCTs.¹³ In the current study, all RCTs were small partial tears, and arthroscopic débridement was performed. It is unknown whether repair of these RCTs would impact return to play. However, rotator cuff repair in this population has been shown to have poor outcomes. Tear thickness typically is used to determine treatment, with débridement performed if <50% tendon thickness is affected. More recently, many have advocated having greater tendon involvement in throwers before repair, because of poor outcomes. Although studies are limited, tear size does seem to correlate with outcomes.¹⁴

Continue to: Study Limitations

Limitations of this study include its small number of professional throwing athletes, with the majority being high school athletes. Further, although ASES scores are consistently used in posterior shoulder instability studies, these scores are influenced highly by pain scores, and some argue that other scoring systems may provide more useful information. However, none of the more modern scoring systems have been studied extensively in posterior glenohumeral instability. Further, because the authors used the present scoring systems previously,^1-4 they were continued to be used for comparison and consistency. Outcomes such as ROM and strength may carry more weight if measured and documented by clinical examination. Further testing, such as clinical evaluation of the jerk test or the posterior load-and-shift test, and their comparison before and after surgery may provide more objective data.

CONCLUSION

Arthroscopic capsulolabral reconstruction is successful in throwing athletes with RCTs treated with arthroscopic débridement. Unlike a previous study of throwing athletes’ outcomes after surgery for concomitant SLAP tears and RCTs,⁵ this study of throwing athletes with concomitant posterior shoulder instability and RCTs found no difference in patient-reported outcome measures or return to play. In throwing athletes with posterior instability and RCTs, arthroscopic posterior capsulolabral repair with rotator cuff débridement is successful.

LOS ANGELES – The number of ischemic stroke patients with a clinical core mismatch showing salvageable tissue who need to be treated with thrombectomy to obtain a significant benefit on functional outcomes is just 2 when the time frame from last known well extends out to 24 hours, according a subanalysis of results from the DAWN trial.

The Jan. 4, 2018, publication of the DAWN trial revealed that patients with ischemic strokes can benefit from thrombectomy long after the time window generally thought to afford benefits had closed (N Engl J Med. 2018;378:11-21). The procedure yielded significant benefits in functional outcomes at 90 days in patients with a clinical core mismatch showing salvageable tissue.

Mitchel L. Zoler/Frontline Medical News

[email protected]

SOURCE: Saver J et al., ISC 2018 abstract LB3

LOS ANGELES – The number of ischemic stroke patients with a clinical core mismatch showing salvageable tissue who need to be treated with thrombectomy to obtain a significant benefit on functional outcomes is just 2 when the time frame from last known well extends out to 24 hours, according a subanalysis of results from the DAWN trial.

The Jan. 4, 2018, publication of the DAWN trial revealed that patients with ischemic strokes can benefit from thrombectomy long after the time window generally thought to afford benefits had closed (N Engl J Med. 2018;378:11-21). The procedure yielded significant benefits in functional outcomes at 90 days in patients with a clinical core mismatch showing salvageable tissue.

Mitchel L. Zoler/Frontline Medical News

[email protected]

SOURCE: Saver J et al., ISC 2018 abstract LB3

LOS ANGELES – The number of ischemic stroke patients with a clinical core mismatch showing salvageable tissue who need to be treated with thrombectomy to obtain a significant benefit on functional outcomes is just 2 when the time frame from last known well extends out to 24 hours, according a subanalysis of results from the DAWN trial.

The Jan. 4, 2018, publication of the DAWN trial revealed that patients with ischemic strokes can benefit from thrombectomy long after the time window generally thought to afford benefits had closed (N Engl J Med. 2018;378:11-21). The procedure yielded significant benefits in functional outcomes at 90 days in patients with a clinical core mismatch showing salvageable tissue.

Mitchel L. Zoler/Frontline Medical News

[email protected]

SOURCE: Saver J et al., ISC 2018 abstract LB3

ORLANDO – When patients with atrial fibrillation have a history of cardioembolic events despite optimal anticoagulant therapy, treatment with left atrial appendage occlusion can substantially improve protection against future events, according to a multicenter review of 22 patients.

During the 2 years prior to undergoing left atrial appendage (LAA) occlusion, the 22 atrial fibrillation (AF) patients studied had a total of 44 cardioembolic events despite receiving “optimal” treatment with an oral anticoagulant, including nine patients with one event, six patients with two events, five patients with three events, and two patients with four events each, Xavier Freixa, MD, said at the annual International AF Symposium. In contrast, during a median follow-up of 1.8 years after their procedure additional events occurred in just two patients – one with a stroke, the other with a transient ischemic attack, while the remaining 20 patients remained free of any additional events.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

SOURCE: Freixa X et al. AF Symposium 2018 Abstract 1821.

ORLANDO – When patients with atrial fibrillation have a history of cardioembolic events despite optimal anticoagulant therapy, treatment with left atrial appendage occlusion can substantially improve protection against future events, according to a multicenter review of 22 patients.

During the 2 years prior to undergoing left atrial appendage (LAA) occlusion, the 22 atrial fibrillation (AF) patients studied had a total of 44 cardioembolic events despite receiving “optimal” treatment with an oral anticoagulant, including nine patients with one event, six patients with two events, five patients with three events, and two patients with four events each, Xavier Freixa, MD, said at the annual International AF Symposium. In contrast, during a median follow-up of 1.8 years after their procedure additional events occurred in just two patients – one with a stroke, the other with a transient ischemic attack, while the remaining 20 patients remained free of any additional events.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

SOURCE: Freixa X et al. AF Symposium 2018 Abstract 1821.

ORLANDO – When patients with atrial fibrillation have a history of cardioembolic events despite optimal anticoagulant therapy, treatment with left atrial appendage occlusion can substantially improve protection against future events, according to a multicenter review of 22 patients.

During the 2 years prior to undergoing left atrial appendage (LAA) occlusion, the 22 atrial fibrillation (AF) patients studied had a total of 44 cardioembolic events despite receiving “optimal” treatment with an oral anticoagulant, including nine patients with one event, six patients with two events, five patients with three events, and two patients with four events each, Xavier Freixa, MD, said at the annual International AF Symposium. In contrast, during a median follow-up of 1.8 years after their procedure additional events occurred in just two patients – one with a stroke, the other with a transient ischemic attack, while the remaining 20 patients remained free of any additional events.

Mitchel L. Zoler/Frontline Medical News

[email protected]

On Twitter @mitchelzoler

SOURCE: Freixa X et al. AF Symposium 2018 Abstract 1821.