Although related by their European origins in neighboring countries and similar cultural lifestyles, the immune profiles and prevalences of asthma and allergic sensitization differ between Amish and Hutterite school children, according to the results of a study published in the New England Journal of Medicine.

The predominant differences between the Amish and Hutterite populations today are region of concentration (Indiana and South Dakota, respectively) and agrarian style (traditional and industrialized farming, respectively). First author Michelle M. Stein of the University of Chicago and her colleagues conducted a study of 30 Amish age- and sex-matched children (aged 7-14 years) living in Indiana and 30 Hutterite children living in South Dakota during the months of November and December, respectively. Immune profile–related variables examined included levels of common allergens and endotoxins detectable in airborne dust, percentages of total peripheral blood leukocytes, cell-surface markers on neutrophils and monocytes, cytokine levels from peripheral-blood leukocytes with or without innate or adaptive stimuli, and gene expression levels from peripheral-blood leukocytes. In additional experiments using a murine model of experimental allergic asthma, house dust from Amish and Hutterite homes was administered intranasally to mice for 4-5 weeks to gauge their immune responses (N Engl J Med. 2016;375:411-21).

©tupungato/Thinkstock.com

A genetic analysis revealed that the two populations shared a closer genetic relationship with each other than with populations from other countries in Europe. The study results also confirmed the known differences between the Amish and Hutterite prevalences of asthma (0% vs. 20%, respectively) and positivity for allergen-specific IgE (17% vs. 30% and 7% vs. 30% using cutoffs of greater than 0.7 and greater than 3.5 kUA/L, respectively). Also, median levels of endotoxins were found to be almost sevenfold greater in Amish homes (4,399 endotoxin units [EU] per square meter vs. 648 EU per square meter, P less than .001).

Compared with results generated using Hutterite peripheral-blood leukocytes, increased proportions of neutrophils, decreased proportions of eosinophils, and similar proportions of monocytes were observed in the Amish. In addition to proportional differences, the phenotypes of the neutrophils from the Amish children also differed by expressing lower levels of the chemokine receptor CXCR4 and the adhesion molecules CD11b and CD11c. The phenotypes of the monocytes differed as well, showing a suppressive phenotype in the Amish children. A specific network of differentially expressed innate immune genes in untreated peripheral-blood leukocytes was found to be associated with the observed differences in the relative amounts of neutrophils, eosinophils, and monocytes, as well as their phenotypes. The median levels of all 23 cytokines detected in peripheral-blood leukocytes following innate stimulation differed between the populations and showed lower levels among the Amish children (P less than .001). Adaptive stimulation, however, did not lead to differences in cytokine levels between the two groups. The results from the murine model indicated that exposure to the Amish conditions was associated with innate immune responses consistent with protective effects against asthma. Collectively, these results strongly suggest that the Amish environment affords protection against asthma via innate immune system signaling.

“A deeper understanding of the relevant stimuli and the innate immune pathways they engage may ultimately pave the way for the development of effective strategies for the prevention of asthma,” wrote Ms. Stein and her colleagues.

Funding for this project was provided by the National Institutes of Health, St. Vincent Foundation, and the American Academy of Allergy, Asthma, and Immunology Foundation. Several study authors disclosed grant support from the NIH; one received support from the European Research Council and the German Research Foundation; and several disclosed ties to industry sources.

Although related by their European origins in neighboring countries and similar cultural lifestyles, the immune profiles and prevalences of asthma and allergic sensitization differ between Amish and Hutterite school children, according to the results of a study published in the New England Journal of Medicine.

The predominant differences between the Amish and Hutterite populations today are region of concentration (Indiana and South Dakota, respectively) and agrarian style (traditional and industrialized farming, respectively). First author Michelle M. Stein of the University of Chicago and her colleagues conducted a study of 30 Amish age- and sex-matched children (aged 7-14 years) living in Indiana and 30 Hutterite children living in South Dakota during the months of November and December, respectively. Immune profile–related variables examined included levels of common allergens and endotoxins detectable in airborne dust, percentages of total peripheral blood leukocytes, cell-surface markers on neutrophils and monocytes, cytokine levels from peripheral-blood leukocytes with or without innate or adaptive stimuli, and gene expression levels from peripheral-blood leukocytes. In additional experiments using a murine model of experimental allergic asthma, house dust from Amish and Hutterite homes was administered intranasally to mice for 4-5 weeks to gauge their immune responses (N Engl J Med. 2016;375:411-21).

©tupungato/Thinkstock.com

A genetic analysis revealed that the two populations shared a closer genetic relationship with each other than with populations from other countries in Europe. The study results also confirmed the known differences between the Amish and Hutterite prevalences of asthma (0% vs. 20%, respectively) and positivity for allergen-specific IgE (17% vs. 30% and 7% vs. 30% using cutoffs of greater than 0.7 and greater than 3.5 kUA/L, respectively). Also, median levels of endotoxins were found to be almost sevenfold greater in Amish homes (4,399 endotoxin units [EU] per square meter vs. 648 EU per square meter, P less than .001).

Compared with results generated using Hutterite peripheral-blood leukocytes, increased proportions of neutrophils, decreased proportions of eosinophils, and similar proportions of monocytes were observed in the Amish. In addition to proportional differences, the phenotypes of the neutrophils from the Amish children also differed by expressing lower levels of the chemokine receptor CXCR4 and the adhesion molecules CD11b and CD11c. The phenotypes of the monocytes differed as well, showing a suppressive phenotype in the Amish children. A specific network of differentially expressed innate immune genes in untreated peripheral-blood leukocytes was found to be associated with the observed differences in the relative amounts of neutrophils, eosinophils, and monocytes, as well as their phenotypes. The median levels of all 23 cytokines detected in peripheral-blood leukocytes following innate stimulation differed between the populations and showed lower levels among the Amish children (P less than .001). Adaptive stimulation, however, did not lead to differences in cytokine levels between the two groups. The results from the murine model indicated that exposure to the Amish conditions was associated with innate immune responses consistent with protective effects against asthma. Collectively, these results strongly suggest that the Amish environment affords protection against asthma via innate immune system signaling.

“A deeper understanding of the relevant stimuli and the innate immune pathways they engage may ultimately pave the way for the development of effective strategies for the prevention of asthma,” wrote Ms. Stein and her colleagues.

Funding for this project was provided by the National Institutes of Health, St. Vincent Foundation, and the American Academy of Allergy, Asthma, and Immunology Foundation. Several study authors disclosed grant support from the NIH; one received support from the European Research Council and the German Research Foundation; and several disclosed ties to industry sources.

Although related by their European origins in neighboring countries and similar cultural lifestyles, the immune profiles and prevalences of asthma and allergic sensitization differ between Amish and Hutterite school children, according to the results of a study published in the New England Journal of Medicine.

The predominant differences between the Amish and Hutterite populations today are region of concentration (Indiana and South Dakota, respectively) and agrarian style (traditional and industrialized farming, respectively). First author Michelle M. Stein of the University of Chicago and her colleagues conducted a study of 30 Amish age- and sex-matched children (aged 7-14 years) living in Indiana and 30 Hutterite children living in South Dakota during the months of November and December, respectively. Immune profile–related variables examined included levels of common allergens and endotoxins detectable in airborne dust, percentages of total peripheral blood leukocytes, cell-surface markers on neutrophils and monocytes, cytokine levels from peripheral-blood leukocytes with or without innate or adaptive stimuli, and gene expression levels from peripheral-blood leukocytes. In additional experiments using a murine model of experimental allergic asthma, house dust from Amish and Hutterite homes was administered intranasally to mice for 4-5 weeks to gauge their immune responses (N Engl J Med. 2016;375:411-21).

©tupungato/Thinkstock.com

A genetic analysis revealed that the two populations shared a closer genetic relationship with each other than with populations from other countries in Europe. The study results also confirmed the known differences between the Amish and Hutterite prevalences of asthma (0% vs. 20%, respectively) and positivity for allergen-specific IgE (17% vs. 30% and 7% vs. 30% using cutoffs of greater than 0.7 and greater than 3.5 kUA/L, respectively). Also, median levels of endotoxins were found to be almost sevenfold greater in Amish homes (4,399 endotoxin units [EU] per square meter vs. 648 EU per square meter, P less than .001).

Compared with results generated using Hutterite peripheral-blood leukocytes, increased proportions of neutrophils, decreased proportions of eosinophils, and similar proportions of monocytes were observed in the Amish. In addition to proportional differences, the phenotypes of the neutrophils from the Amish children also differed by expressing lower levels of the chemokine receptor CXCR4 and the adhesion molecules CD11b and CD11c. The phenotypes of the monocytes differed as well, showing a suppressive phenotype in the Amish children. A specific network of differentially expressed innate immune genes in untreated peripheral-blood leukocytes was found to be associated with the observed differences in the relative amounts of neutrophils, eosinophils, and monocytes, as well as their phenotypes. The median levels of all 23 cytokines detected in peripheral-blood leukocytes following innate stimulation differed between the populations and showed lower levels among the Amish children (P less than .001). Adaptive stimulation, however, did not lead to differences in cytokine levels between the two groups. The results from the murine model indicated that exposure to the Amish conditions was associated with innate immune responses consistent with protective effects against asthma. Collectively, these results strongly suggest that the Amish environment affords protection against asthma via innate immune system signaling.

“A deeper understanding of the relevant stimuli and the innate immune pathways they engage may ultimately pave the way for the development of effective strategies for the prevention of asthma,” wrote Ms. Stein and her colleagues.

Funding for this project was provided by the National Institutes of Health, St. Vincent Foundation, and the American Academy of Allergy, Asthma, and Immunology Foundation. Several study authors disclosed grant support from the NIH; one received support from the European Research Council and the German Research Foundation; and several disclosed ties to industry sources.

Sickle cell trait doesn’t raise the risk of death but does raise the risk of exertional rhabdomyolysis among black soldiers, “a population that is known to engage consistently in regular and strenuous exercise while protected by exertional-injury precautions,” investigators reported. The study was published online Aug. 4 in the New England Journal of Medicine.

A number of high-profile deaths among athletes and military personnel involving exertional rhabdomyolysis have been attributed to sickle cell trait. The National Collegiate Athletic Association, the U.S. Air Force, and the U.S. Navy all require universal screening for sickle cell trait.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

“However, concerns have been raised by the American Society of Hematology and other professional organizations about the possibility of stigmatization and discrimination resulting from the mandated screening for sickle cell trait,” which predominantly affects people of African descent and some of Hispanic ancestry, but usually not whites, wrote D. Alan Nelson, PhD, of Stanford (Calif.) University, and his associates.

“These concerns warrant consideration, especially given the absence of published evidence that such screening is effective in preventing exertion-related events,” added the researchers.

The U.S. Army primarily screens for sickle cell trait among personnel deployed for combat and certain specialists whose work at high altitudes puts them at risk. To study a large enough population to generate accurate data about this rare blood abnormality, the investigators analyzed data for 47,944 black soldiers who had been tested for sickle cell trait and who served on active duty during a recent 3-year period.

The researchers assessed all inpatient and outpatient health care visits at military and civilian facilities. There were 391 exertional rhabdomyolysis events and 96 deaths from all causes during 1.61 million person-months of observation. A total of 7.4% of the study cohort carried sickle cell trait. These participants were similar to noncarriers in demographic characteristics and health predictors.

Soldiers with sickle cell trait did not have a greater risk of death than did those without sickle cell trait (hazard ratio, 0.99), and there also was no difference between carriers and noncarriers in either battle-related or non–battle-related mortality rates.

However, sickle cell trait was associated with a 54% greater risk of exertional rhabdomyolysis (HR, 1.54), Dr. Nelson and his associates noted (N Engl J Med. 2016 Aug 4. doi: 10.1056/NEJMoa1516257).

It is important to note that factors other than sickle cell trait raised the risk of exertional rhabdomyolysis to a similar or even greater degree, including obesity (HR, 1.39) and tobacco use (HR, 1.54). Recent use of antipsychotic medication tripled the risk for exertional rhabdomyolysis (HR, 3.02), and statin use nearly tripled it (HR, 2.89).

“These findings are compelling because case reports dominate the relevant literature and emphasize the presence of sickle cell trait as a risk factor for adverse outcomes, including exertional rhabdomyolysis and sudden death,” the researchers wrote. “A large longitudinal study involving a population fully tested for sickle cell trait that has formally investigated [these outcomes] while also examining other known major risk factors, such as medications, has been lacking.”

The study found that women were at much lower risk for exertional rhabdomyolysis than were men (HR, 0.51), and that risk increased with increasing age, so that soldiers aged 36 years and older had a 57% greater risk compared with those in the youngest age group.

The National Heart, Lung, and Blood Institute and the Uniformed Services University of the Health Sciences supported the study. Dr. Nelson and his associates reported having no relevant financial disclosures.

Sickle cell trait doesn’t raise the risk of death but does raise the risk of exertional rhabdomyolysis among black soldiers, “a population that is known to engage consistently in regular and strenuous exercise while protected by exertional-injury precautions,” investigators reported. The study was published online Aug. 4 in the New England Journal of Medicine.

A number of high-profile deaths among athletes and military personnel involving exertional rhabdomyolysis have been attributed to sickle cell trait. The National Collegiate Athletic Association, the U.S. Air Force, and the U.S. Navy all require universal screening for sickle cell trait.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

“However, concerns have been raised by the American Society of Hematology and other professional organizations about the possibility of stigmatization and discrimination resulting from the mandated screening for sickle cell trait,” which predominantly affects people of African descent and some of Hispanic ancestry, but usually not whites, wrote D. Alan Nelson, PhD, of Stanford (Calif.) University, and his associates.

“These concerns warrant consideration, especially given the absence of published evidence that such screening is effective in preventing exertion-related events,” added the researchers.

The U.S. Army primarily screens for sickle cell trait among personnel deployed for combat and certain specialists whose work at high altitudes puts them at risk. To study a large enough population to generate accurate data about this rare blood abnormality, the investigators analyzed data for 47,944 black soldiers who had been tested for sickle cell trait and who served on active duty during a recent 3-year period.

The researchers assessed all inpatient and outpatient health care visits at military and civilian facilities. There were 391 exertional rhabdomyolysis events and 96 deaths from all causes during 1.61 million person-months of observation. A total of 7.4% of the study cohort carried sickle cell trait. These participants were similar to noncarriers in demographic characteristics and health predictors.

Soldiers with sickle cell trait did not have a greater risk of death than did those without sickle cell trait (hazard ratio, 0.99), and there also was no difference between carriers and noncarriers in either battle-related or non–battle-related mortality rates.

However, sickle cell trait was associated with a 54% greater risk of exertional rhabdomyolysis (HR, 1.54), Dr. Nelson and his associates noted (N Engl J Med. 2016 Aug 4. doi: 10.1056/NEJMoa1516257).

It is important to note that factors other than sickle cell trait raised the risk of exertional rhabdomyolysis to a similar or even greater degree, including obesity (HR, 1.39) and tobacco use (HR, 1.54). Recent use of antipsychotic medication tripled the risk for exertional rhabdomyolysis (HR, 3.02), and statin use nearly tripled it (HR, 2.89).

“These findings are compelling because case reports dominate the relevant literature and emphasize the presence of sickle cell trait as a risk factor for adverse outcomes, including exertional rhabdomyolysis and sudden death,” the researchers wrote. “A large longitudinal study involving a population fully tested for sickle cell trait that has formally investigated [these outcomes] while also examining other known major risk factors, such as medications, has been lacking.”

The study found that women were at much lower risk for exertional rhabdomyolysis than were men (HR, 0.51), and that risk increased with increasing age, so that soldiers aged 36 years and older had a 57% greater risk compared with those in the youngest age group.

The National Heart, Lung, and Blood Institute and the Uniformed Services University of the Health Sciences supported the study. Dr. Nelson and his associates reported having no relevant financial disclosures.

Sickle cell trait doesn’t raise the risk of death but does raise the risk of exertional rhabdomyolysis among black soldiers, “a population that is known to engage consistently in regular and strenuous exercise while protected by exertional-injury precautions,” investigators reported. The study was published online Aug. 4 in the New England Journal of Medicine.

A number of high-profile deaths among athletes and military personnel involving exertional rhabdomyolysis have been attributed to sickle cell trait. The National Collegiate Athletic Association, the U.S. Air Force, and the U.S. Navy all require universal screening for sickle cell trait.

Courtesy Wikimedia Commons/Osaro Erhabor/Creative Commons License

“However, concerns have been raised by the American Society of Hematology and other professional organizations about the possibility of stigmatization and discrimination resulting from the mandated screening for sickle cell trait,” which predominantly affects people of African descent and some of Hispanic ancestry, but usually not whites, wrote D. Alan Nelson, PhD, of Stanford (Calif.) University, and his associates.

“These concerns warrant consideration, especially given the absence of published evidence that such screening is effective in preventing exertion-related events,” added the researchers.

The U.S. Army primarily screens for sickle cell trait among personnel deployed for combat and certain specialists whose work at high altitudes puts them at risk. To study a large enough population to generate accurate data about this rare blood abnormality, the investigators analyzed data for 47,944 black soldiers who had been tested for sickle cell trait and who served on active duty during a recent 3-year period.

The researchers assessed all inpatient and outpatient health care visits at military and civilian facilities. There were 391 exertional rhabdomyolysis events and 96 deaths from all causes during 1.61 million person-months of observation. A total of 7.4% of the study cohort carried sickle cell trait. These participants were similar to noncarriers in demographic characteristics and health predictors.

Soldiers with sickle cell trait did not have a greater risk of death than did those without sickle cell trait (hazard ratio, 0.99), and there also was no difference between carriers and noncarriers in either battle-related or non–battle-related mortality rates.

However, sickle cell trait was associated with a 54% greater risk of exertional rhabdomyolysis (HR, 1.54), Dr. Nelson and his associates noted (N Engl J Med. 2016 Aug 4. doi: 10.1056/NEJMoa1516257).

It is important to note that factors other than sickle cell trait raised the risk of exertional rhabdomyolysis to a similar or even greater degree, including obesity (HR, 1.39) and tobacco use (HR, 1.54). Recent use of antipsychotic medication tripled the risk for exertional rhabdomyolysis (HR, 3.02), and statin use nearly tripled it (HR, 2.89).

“These findings are compelling because case reports dominate the relevant literature and emphasize the presence of sickle cell trait as a risk factor for adverse outcomes, including exertional rhabdomyolysis and sudden death,” the researchers wrote. “A large longitudinal study involving a population fully tested for sickle cell trait that has formally investigated [these outcomes] while also examining other known major risk factors, such as medications, has been lacking.”

The study found that women were at much lower risk for exertional rhabdomyolysis than were men (HR, 0.51), and that risk increased with increasing age, so that soldiers aged 36 years and older had a 57% greater risk compared with those in the youngest age group.

The National Heart, Lung, and Blood Institute and the Uniformed Services University of the Health Sciences supported the study. Dr. Nelson and his associates reported having no relevant financial disclosures.

The MCR-1 gene is quickly emerging as a powerful roadblock in the fight against antibiotic-resistant bacteria, according to experts from the Centers for Disease Control and Prevention.

Alex J. Kallen, MD, of the CDC in Atlanta, said in an Aug. 2 webinar – cohosted by CDC and the Partnership for Quality Care – that the CDC is closely monitoring the emergence of antibiotic resistant bacteria in the United States. The prevailing message of Dr. Kallen and his CDC colleague Arjun Srinivasan, MD was that the importance of the MCR-1 gene should not be underestimated.

MacXever/Thinkstock

First discovered in a human patient last year, the presence of the MCR-1 gene makes bacteria resistant to colistin, an antibiotic used often as a last resort to “treat patients with multidrug-resistant infections,” according to the CDC. Because the MCR-1 gene exists on a plasmid, or a small piece of DNA, it is easily transferable among bacteria, making it a problem for health care providers treating a patient infected with bacteria that has the gene.

“As of this year, all state and some local health departments will be funded to respond to [antibiotic resistance] threats, including emerging threats like [MCR-1], within their jurisdiction,” Dr. Kallen said. This funding could be used to support technical assistance, contact investigations, and laboratory testing, among other things.

In order to help prevent the spread of MCR-1 and mitigate cases of novel antimicrobial resistance, health care providers and facilities should institute recommended intensive care precautions as soon as resistance is identified, along with alerting their local public health office. Isolates should be saved, and prospective and retrospective surveillance should be implemented to “identify isolates with similar phenotypes.” If an infected patient is being transferred to another facility, that facility should be notified ahead of time about the patient and what protocols to follow.

Because antibiotic-resistant organisms do not spread through the air like influenza, the risk that these organisms pose to health care workers is relatively low, Dr. Srinivasan explained. However, he stressed that a multifaceted, team-based approach to antibiotic stewardship and decontamination of health care facilities is absolutely necessary to achieve the best results for both patients and staff.

“We are now beginning to recognize that the contamination of surfaces and items in our health care environment is increasingly a problem in the transmission of these drug-resistant organisms,” Dr. Srinivasan explained. He said that, given the complexity of a typical health care environment, such as a hospital room or operating theater, it’s perhaps not so surprising that keeping everything clean is not the top priority.

In addition to making sure hospital rooms and other areas are properly cleaned, simple things like washing hands and keeping surfaces clean are just as important. Dr. Srinivasan pointed to a 2006 study by Philip C. Carling, MD, and his associates which showed that educational interventions can lead to substantial increases in hygiene and cleanliness, and that training of new staff is also important. Furthermore, giving staff enough time to properly clean rooms could significantly contribute to curtailing MCR-1 bacteria from spreading, he said.

“The other thing to keep in mind is that if we lose effective therapy, if we lose antibiotic therapy, the infections that are currently very treatable and are seldom deadly could again become very, very serious threats to life,” Dr. Srinivasan warned, specifically citing Escherichia coli, which is the leading cause of urinary tract infections. If community strains of E.coli become resistant to typical antibiotic treatment, these cases could become “difficult, if not impossible to treat.”

According to data shared by Dr. Srinivasan, in 2013 there were 2,049,422 illnesses in the United States attributed to antibiotic resistance and 23,000 fatalities.

AGA resource
The AGA Center for Gut Microbiome Research and Education was created to serve as a virtual “home” for AGA activities related to the gut microbiome. The center is focused on advancing gut microbiome research, educating AGA members and other stakeholders on the latest microbiome breakthroughs, and working with FDA and others to ensure that emerging microbiome-based treatments are safe and appropriately evaluated. Learn more here.

[email protected]

The MCR-1 gene is quickly emerging as a powerful roadblock in the fight against antibiotic-resistant bacteria, according to experts from the Centers for Disease Control and Prevention.

Alex J. Kallen, MD, of the CDC in Atlanta, said in an Aug. 2 webinar – cohosted by CDC and the Partnership for Quality Care – that the CDC is closely monitoring the emergence of antibiotic resistant bacteria in the United States. The prevailing message of Dr. Kallen and his CDC colleague Arjun Srinivasan, MD was that the importance of the MCR-1 gene should not be underestimated.

MacXever/Thinkstock

First discovered in a human patient last year, the presence of the MCR-1 gene makes bacteria resistant to colistin, an antibiotic used often as a last resort to “treat patients with multidrug-resistant infections,” according to the CDC. Because the MCR-1 gene exists on a plasmid, or a small piece of DNA, it is easily transferable among bacteria, making it a problem for health care providers treating a patient infected with bacteria that has the gene.

“As of this year, all state and some local health departments will be funded to respond to [antibiotic resistance] threats, including emerging threats like [MCR-1], within their jurisdiction,” Dr. Kallen said. This funding could be used to support technical assistance, contact investigations, and laboratory testing, among other things.

In order to help prevent the spread of MCR-1 and mitigate cases of novel antimicrobial resistance, health care providers and facilities should institute recommended intensive care precautions as soon as resistance is identified, along with alerting their local public health office. Isolates should be saved, and prospective and retrospective surveillance should be implemented to “identify isolates with similar phenotypes.” If an infected patient is being transferred to another facility, that facility should be notified ahead of time about the patient and what protocols to follow.

Because antibiotic-resistant organisms do not spread through the air like influenza, the risk that these organisms pose to health care workers is relatively low, Dr. Srinivasan explained. However, he stressed that a multifaceted, team-based approach to antibiotic stewardship and decontamination of health care facilities is absolutely necessary to achieve the best results for both patients and staff.

“We are now beginning to recognize that the contamination of surfaces and items in our health care environment is increasingly a problem in the transmission of these drug-resistant organisms,” Dr. Srinivasan explained. He said that, given the complexity of a typical health care environment, such as a hospital room or operating theater, it’s perhaps not so surprising that keeping everything clean is not the top priority.

In addition to making sure hospital rooms and other areas are properly cleaned, simple things like washing hands and keeping surfaces clean are just as important. Dr. Srinivasan pointed to a 2006 study by Philip C. Carling, MD, and his associates which showed that educational interventions can lead to substantial increases in hygiene and cleanliness, and that training of new staff is also important. Furthermore, giving staff enough time to properly clean rooms could significantly contribute to curtailing MCR-1 bacteria from spreading, he said.

“The other thing to keep in mind is that if we lose effective therapy, if we lose antibiotic therapy, the infections that are currently very treatable and are seldom deadly could again become very, very serious threats to life,” Dr. Srinivasan warned, specifically citing Escherichia coli, which is the leading cause of urinary tract infections. If community strains of E.coli become resistant to typical antibiotic treatment, these cases could become “difficult, if not impossible to treat.”

According to data shared by Dr. Srinivasan, in 2013 there were 2,049,422 illnesses in the United States attributed to antibiotic resistance and 23,000 fatalities.

AGA resource
The AGA Center for Gut Microbiome Research and Education was created to serve as a virtual “home” for AGA activities related to the gut microbiome. The center is focused on advancing gut microbiome research, educating AGA members and other stakeholders on the latest microbiome breakthroughs, and working with FDA and others to ensure that emerging microbiome-based treatments are safe and appropriately evaluated. Learn more here.

[email protected]

The MCR-1 gene is quickly emerging as a powerful roadblock in the fight against antibiotic-resistant bacteria, according to experts from the Centers for Disease Control and Prevention.

Alex J. Kallen, MD, of the CDC in Atlanta, said in an Aug. 2 webinar – cohosted by CDC and the Partnership for Quality Care – that the CDC is closely monitoring the emergence of antibiotic resistant bacteria in the United States. The prevailing message of Dr. Kallen and his CDC colleague Arjun Srinivasan, MD was that the importance of the MCR-1 gene should not be underestimated.

MacXever/Thinkstock

First discovered in a human patient last year, the presence of the MCR-1 gene makes bacteria resistant to colistin, an antibiotic used often as a last resort to “treat patients with multidrug-resistant infections,” according to the CDC. Because the MCR-1 gene exists on a plasmid, or a small piece of DNA, it is easily transferable among bacteria, making it a problem for health care providers treating a patient infected with bacteria that has the gene.

“As of this year, all state and some local health departments will be funded to respond to [antibiotic resistance] threats, including emerging threats like [MCR-1], within their jurisdiction,” Dr. Kallen said. This funding could be used to support technical assistance, contact investigations, and laboratory testing, among other things.

In order to help prevent the spread of MCR-1 and mitigate cases of novel antimicrobial resistance, health care providers and facilities should institute recommended intensive care precautions as soon as resistance is identified, along with alerting their local public health office. Isolates should be saved, and prospective and retrospective surveillance should be implemented to “identify isolates with similar phenotypes.” If an infected patient is being transferred to another facility, that facility should be notified ahead of time about the patient and what protocols to follow.

Because antibiotic-resistant organisms do not spread through the air like influenza, the risk that these organisms pose to health care workers is relatively low, Dr. Srinivasan explained. However, he stressed that a multifaceted, team-based approach to antibiotic stewardship and decontamination of health care facilities is absolutely necessary to achieve the best results for both patients and staff.

“We are now beginning to recognize that the contamination of surfaces and items in our health care environment is increasingly a problem in the transmission of these drug-resistant organisms,” Dr. Srinivasan explained. He said that, given the complexity of a typical health care environment, such as a hospital room or operating theater, it’s perhaps not so surprising that keeping everything clean is not the top priority.

In addition to making sure hospital rooms and other areas are properly cleaned, simple things like washing hands and keeping surfaces clean are just as important. Dr. Srinivasan pointed to a 2006 study by Philip C. Carling, MD, and his associates which showed that educational interventions can lead to substantial increases in hygiene and cleanliness, and that training of new staff is also important. Furthermore, giving staff enough time to properly clean rooms could significantly contribute to curtailing MCR-1 bacteria from spreading, he said.

“The other thing to keep in mind is that if we lose effective therapy, if we lose antibiotic therapy, the infections that are currently very treatable and are seldom deadly could again become very, very serious threats to life,” Dr. Srinivasan warned, specifically citing Escherichia coli, which is the leading cause of urinary tract infections. If community strains of E.coli become resistant to typical antibiotic treatment, these cases could become “difficult, if not impossible to treat.”

According to data shared by Dr. Srinivasan, in 2013 there were 2,049,422 illnesses in the United States attributed to antibiotic resistance and 23,000 fatalities.

AGA resource
The AGA Center for Gut Microbiome Research and Education was created to serve as a virtual “home” for AGA activities related to the gut microbiome. The center is focused on advancing gut microbiome research, educating AGA members and other stakeholders on the latest microbiome breakthroughs, and working with FDA and others to ensure that emerging microbiome-based treatments are safe and appropriately evaluated. Learn more here.

[email protected]

The MCR-1 gene is quickly emerging as a powerful roadblock in the fight against antibiotic-resistant bacteria, according to experts from the Centers for Disease Control and Prevention.

Alex J. Kallen, MD, of the CDC in Atlanta, said in an Aug. 2 webinar – cohosted by CDC and the Partnership for Quality Care – that the CDC is closely monitoring the emergence of antibiotic resistant bacteria in the United States. The prevailing message of Dr. Kallen and his CDC colleague Arjun Srinivasan, MD was that the importance of the MCR-1 gene should not be underestimated.

MacXever/Thinkstock

First discovered in a human patient last year, the presence of the MCR-1 gene makes bacteria resistant to colistin, an antibiotic used often as a last resort to “treat patients with multidrug-resistant infections,” according to the CDC. Because the MCR-1 gene exists on a plasmid, or a small piece of DNA, it is easily transferable among bacteria, making it a problem for health care providers treating a patient infected with bacteria that has the gene.

“As of this year, all state and some local health departments will be funded to respond to [antibiotic resistance] threats, including emerging threats like [MCR-1], within their jurisdiction,” Dr. Kallen said. This funding could be used to support technical assistance, contact investigations, and laboratory testing, among other things.

In order to help prevent the spread of MCR-1 and mitigate cases of novel antimicrobial resistance, health care providers and facilities should institute recommended intensive care precautions as soon as resistance is identified, along with alerting their local public health office. Isolates should be saved, and prospective and retrospective surveillance should be implemented to “identify isolates with similar phenotypes.” If an infected patient is being transferred to another facility, that facility should be notified ahead of time about the patient and what protocols to follow.

Because antibiotic-resistant organisms do not spread through the air like influenza, the risk that these organisms pose to health care workers is relatively low, Dr. Srinivasan explained. However, he stressed that a multifaceted, team-based approach to antibiotic stewardship and decontamination of health care facilities is absolutely necessary to achieve the best results for both patients and staff.

“We are now beginning to recognize that the contamination of surfaces and items in our health care environment is increasingly a problem in the transmission of these drug-resistant organisms,” Dr. Srinivasan explained. He said that, given the complexity of a typical health care environment, such as a hospital room or operating theater, it’s perhaps not so surprising that keeping everything clean is not the top priority.

In addition to making sure hospital rooms and other areas are properly cleaned, simple things like washing hands and keeping surfaces clean are just as important. Dr. Srinivasan pointed to a 2006 study by Philip C. Carling, MD, and his associates which showed that educational interventions can lead to substantial increases in hygiene and cleanliness, and that training of new staff is also important. Furthermore, giving staff enough time to properly clean rooms could significantly contribute to curtailing MCR-1 bacteria from spreading, he said.

“The other thing to keep in mind is that if we lose effective therapy, if we lose antibiotic therapy, the infections that are currently very treatable and are seldom deadly could again become very, very serious threats to life,” Dr. Srinivasan warned, specifically citing Escherichia coli, which is the leading cause of urinary tract infections. If community strains of E.coli become resistant to typical antibiotic treatment, these cases could become “difficult, if not impossible to treat.”

According to data shared by Dr. Srinivasan, in 2013 there were 2,049,422 illnesses in the United States attributed to antibiotic resistance and 23,000 fatalities.

[email protected]

The MCR-1 gene is quickly emerging as a powerful roadblock in the fight against antibiotic-resistant bacteria, according to experts from the Centers for Disease Control and Prevention.

Alex J. Kallen, MD, of the CDC in Atlanta, said in an Aug. 2 webinar – cohosted by CDC and the Partnership for Quality Care – that the CDC is closely monitoring the emergence of antibiotic resistant bacteria in the United States. The prevailing message of Dr. Kallen and his CDC colleague Arjun Srinivasan, MD was that the importance of the MCR-1 gene should not be underestimated.

MacXever/Thinkstock

First discovered in a human patient last year, the presence of the MCR-1 gene makes bacteria resistant to colistin, an antibiotic used often as a last resort to “treat patients with multidrug-resistant infections,” according to the CDC. Because the MCR-1 gene exists on a plasmid, or a small piece of DNA, it is easily transferable among bacteria, making it a problem for health care providers treating a patient infected with bacteria that has the gene.

“As of this year, all state and some local health departments will be funded to respond to [antibiotic resistance] threats, including emerging threats like [MCR-1], within their jurisdiction,” Dr. Kallen said. This funding could be used to support technical assistance, contact investigations, and laboratory testing, among other things.

In order to help prevent the spread of MCR-1 and mitigate cases of novel antimicrobial resistance, health care providers and facilities should institute recommended intensive care precautions as soon as resistance is identified, along with alerting their local public health office. Isolates should be saved, and prospective and retrospective surveillance should be implemented to “identify isolates with similar phenotypes.” If an infected patient is being transferred to another facility, that facility should be notified ahead of time about the patient and what protocols to follow.

Because antibiotic-resistant organisms do not spread through the air like influenza, the risk that these organisms pose to health care workers is relatively low, Dr. Srinivasan explained. However, he stressed that a multifaceted, team-based approach to antibiotic stewardship and decontamination of health care facilities is absolutely necessary to achieve the best results for both patients and staff.

“We are now beginning to recognize that the contamination of surfaces and items in our health care environment is increasingly a problem in the transmission of these drug-resistant organisms,” Dr. Srinivasan explained. He said that, given the complexity of a typical health care environment, such as a hospital room or operating theater, it’s perhaps not so surprising that keeping everything clean is not the top priority.

In addition to making sure hospital rooms and other areas are properly cleaned, simple things like washing hands and keeping surfaces clean are just as important. Dr. Srinivasan pointed to a 2006 study by Philip C. Carling, MD, and his associates which showed that educational interventions can lead to substantial increases in hygiene and cleanliness, and that training of new staff is also important. Furthermore, giving staff enough time to properly clean rooms could significantly contribute to curtailing MCR-1 bacteria from spreading, he said.

“The other thing to keep in mind is that if we lose effective therapy, if we lose antibiotic therapy, the infections that are currently very treatable and are seldom deadly could again become very, very serious threats to life,” Dr. Srinivasan warned, specifically citing Escherichia coli, which is the leading cause of urinary tract infections. If community strains of E.coli become resistant to typical antibiotic treatment, these cases could become “difficult, if not impossible to treat.”

According to data shared by Dr. Srinivasan, in 2013 there were 2,049,422 illnesses in the United States attributed to antibiotic resistance and 23,000 fatalities.

[email protected]

The MCR-1 gene is quickly emerging as a powerful roadblock in the fight against antibiotic-resistant bacteria, according to experts from the Centers for Disease Control and Prevention.

Alex J. Kallen, MD, of the CDC in Atlanta, said in an Aug. 2 webinar – cohosted by CDC and the Partnership for Quality Care – that the CDC is closely monitoring the emergence of antibiotic resistant bacteria in the United States. The prevailing message of Dr. Kallen and his CDC colleague Arjun Srinivasan, MD was that the importance of the MCR-1 gene should not be underestimated.

MacXever/Thinkstock

First discovered in a human patient last year, the presence of the MCR-1 gene makes bacteria resistant to colistin, an antibiotic used often as a last resort to “treat patients with multidrug-resistant infections,” according to the CDC. Because the MCR-1 gene exists on a plasmid, or a small piece of DNA, it is easily transferable among bacteria, making it a problem for health care providers treating a patient infected with bacteria that has the gene.

“As of this year, all state and some local health departments will be funded to respond to [antibiotic resistance] threats, including emerging threats like [MCR-1], within their jurisdiction,” Dr. Kallen said. This funding could be used to support technical assistance, contact investigations, and laboratory testing, among other things.

In order to help prevent the spread of MCR-1 and mitigate cases of novel antimicrobial resistance, health care providers and facilities should institute recommended intensive care precautions as soon as resistance is identified, along with alerting their local public health office. Isolates should be saved, and prospective and retrospective surveillance should be implemented to “identify isolates with similar phenotypes.” If an infected patient is being transferred to another facility, that facility should be notified ahead of time about the patient and what protocols to follow.

Because antibiotic-resistant organisms do not spread through the air like influenza, the risk that these organisms pose to health care workers is relatively low, Dr. Srinivasan explained. However, he stressed that a multifaceted, team-based approach to antibiotic stewardship and decontamination of health care facilities is absolutely necessary to achieve the best results for both patients and staff.

“We are now beginning to recognize that the contamination of surfaces and items in our health care environment is increasingly a problem in the transmission of these drug-resistant organisms,” Dr. Srinivasan explained. He said that, given the complexity of a typical health care environment, such as a hospital room or operating theater, it’s perhaps not so surprising that keeping everything clean is not the top priority.

In addition to making sure hospital rooms and other areas are properly cleaned, simple things like washing hands and keeping surfaces clean are just as important. Dr. Srinivasan pointed to a 2006 study by Philip C. Carling, MD, and his associates which showed that educational interventions can lead to substantial increases in hygiene and cleanliness, and that training of new staff is also important. Furthermore, giving staff enough time to properly clean rooms could significantly contribute to curtailing MCR-1 bacteria from spreading, he said.

“The other thing to keep in mind is that if we lose effective therapy, if we lose antibiotic therapy, the infections that are currently very treatable and are seldom deadly could again become very, very serious threats to life,” Dr. Srinivasan warned, specifically citing Escherichia coli, which is the leading cause of urinary tract infections. If community strains of E.coli become resistant to typical antibiotic treatment, these cases could become “difficult, if not impossible to treat.”

According to data shared by Dr. Srinivasan, in 2013 there were 2,049,422 illnesses in the United States attributed to antibiotic resistance and 23,000 fatalities.

[email protected]

A clinical trial to evaluate a candidate vaccine for Zika virus is underway, with preliminary results from the multisite phase I trial expected by the end of 2016.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, announced the trial and gave an update about other Zika virus vaccine development efforts during an Aug. 3 telephone briefing with reporters. The announcement came just days after the continental United States saw its first cases of local transmission of Zika virus in Florida.

Courtesy of the National Institute of Allergy and Infectious Diseases

The phase I clinical trial began on Aug. 2 and will evaluate the safety and immunogenicity of an investigational DNA vaccine for Zika virus. This vaccine is similar to one that early-stage trials have shown to be safe and immunogenic for West Nile virus, a flavivirus closely related to Zika. The Zika virus vaccine had promising preclinical results, Dr. Fauci said. “Preliminary immune responses that we’ve seen in a variety of animal models have been rather robust.”

The DNA vaccine uses a plasmid to deliver genes that code for specific Zika virus proteins. “When the plasmid expresses the envelope protein from the Zika virus, it does so in a way that mimics the virus,” provoking a host immune response that includes neutralizing antibodies and T cells, according to lead trial investigator Julie Ledgerwood, DO, chief of the clinical trials program at the NIAID’s Vaccine Research Center.

The phase I clinical trial will enroll 80 healthy volunteers, aged 18-35 years. All participants will receive the investigational Zika virus vaccine at their first visit, with vaccine delivery via a needle-free system that injects the vaccine directly into the deltoid muscle.

Forty participants will receive one additional dose of the vaccine, with half of those people receiving the additional dose at 8 weeks after the first vaccine, and the other half receiving the additional dose at 12 weeks after the first dose. The other 40 participants will receive two additional doses, with half receiving them at 4 and 8 weeks after the first vaccination, and the other half receiving the extra doses at 4 and 20 weeks. All participants will receive the same dose at each vaccination.

Participants will be asked to monitor their temperature daily for a week after each vaccine dose is received; they will also report any adverse events. The trial design provides for several follow-up visits to track safety and to measure immune response in 44 weeks of short-term follow-up. Additionally, two follow-up visits at 18 months and 2 years post vaccination will measure the durability of the immune response.

The clinical trial will be run at the National Institutes of Health Clinical Center in Bethesda, Md., at Emory University in Atlanta, and at the University of Maryland’s Center for Vaccine Development in Baltimore.

Initial safety and immune response data should be available by the end of 2016, Dr. Fauci said. If these data are promising, a phase II clinical trial will be launched in early 2017 in several Zika-endemic countries. The NIH has the in-house capability to manufacture the 2,500-5,000 doses of vaccine that the phase II trial is expected to require.

However, said Dr. Fauci, without congressional approval of additional funding for Zika virus vaccine efforts, the transition to a phase II clinical trial is far from certain. Interruption in funding would be “effectively impeding our smooth process on the vaccine development front,” he said. “When I say we are going to run out of money soon, I mean really soon.”

Dr. Fauci, in response to questions, said that he continues to be bullish on such platform-based approaches to vaccines. The DNA strategy, in particular, represents “a very convenient and easily scalable vaccine,” he said. “We are moving much more toward platform-based vaccines … because of their ease and convenience, and scaling up and rapidity.”

The scope of a vaccination program will depend on the endemicity of the virus in a given area, said Dr. Fauci. In an endemic area, “Ultimately, you want to get women of childbearing age, as well as their sexual partners,” he said. This means that target populations will be as young as possible, to make sure women and their partners are vaccinated by the time pregnancy becomes a possibility.

Other Zika virus vaccine development efforts underway at NIAID include a strategy that uses a live attenuated virus, an approach used for a dengue virus vaccine that is currently in a phase 3 clinical trial in Brazil, according to the agency’s website. Dengue and Zika are closely related viruses. Another investigational Zika virus vaccine uses genetic engineering to create a vaccine derived from vesicular stomatitis virus, which infects cattle. This strategy, also used in one approach to Ebola vaccination, is in the pre-clinical stage.

[email protected]

On Twitter @karioakes

A clinical trial to evaluate a candidate vaccine for Zika virus is underway, with preliminary results from the multisite phase I trial expected by the end of 2016.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, announced the trial and gave an update about other Zika virus vaccine development efforts during an Aug. 3 telephone briefing with reporters. The announcement came just days after the continental United States saw its first cases of local transmission of Zika virus in Florida.

Courtesy of the National Institute of Allergy and Infectious Diseases

The phase I clinical trial began on Aug. 2 and will evaluate the safety and immunogenicity of an investigational DNA vaccine for Zika virus. This vaccine is similar to one that early-stage trials have shown to be safe and immunogenic for West Nile virus, a flavivirus closely related to Zika. The Zika virus vaccine had promising preclinical results, Dr. Fauci said. “Preliminary immune responses that we’ve seen in a variety of animal models have been rather robust.”

The DNA vaccine uses a plasmid to deliver genes that code for specific Zika virus proteins. “When the plasmid expresses the envelope protein from the Zika virus, it does so in a way that mimics the virus,” provoking a host immune response that includes neutralizing antibodies and T cells, according to lead trial investigator Julie Ledgerwood, DO, chief of the clinical trials program at the NIAID’s Vaccine Research Center.

The phase I clinical trial will enroll 80 healthy volunteers, aged 18-35 years. All participants will receive the investigational Zika virus vaccine at their first visit, with vaccine delivery via a needle-free system that injects the vaccine directly into the deltoid muscle.

Forty participants will receive one additional dose of the vaccine, with half of those people receiving the additional dose at 8 weeks after the first vaccine, and the other half receiving the additional dose at 12 weeks after the first dose. The other 40 participants will receive two additional doses, with half receiving them at 4 and 8 weeks after the first vaccination, and the other half receiving the extra doses at 4 and 20 weeks. All participants will receive the same dose at each vaccination.

Participants will be asked to monitor their temperature daily for a week after each vaccine dose is received; they will also report any adverse events. The trial design provides for several follow-up visits to track safety and to measure immune response in 44 weeks of short-term follow-up. Additionally, two follow-up visits at 18 months and 2 years post vaccination will measure the durability of the immune response.

The clinical trial will be run at the National Institutes of Health Clinical Center in Bethesda, Md., at Emory University in Atlanta, and at the University of Maryland’s Center for Vaccine Development in Baltimore.

Initial safety and immune response data should be available by the end of 2016, Dr. Fauci said. If these data are promising, a phase II clinical trial will be launched in early 2017 in several Zika-endemic countries. The NIH has the in-house capability to manufacture the 2,500-5,000 doses of vaccine that the phase II trial is expected to require.

However, said Dr. Fauci, without congressional approval of additional funding for Zika virus vaccine efforts, the transition to a phase II clinical trial is far from certain. Interruption in funding would be “effectively impeding our smooth process on the vaccine development front,” he said. “When I say we are going to run out of money soon, I mean really soon.”

Dr. Fauci, in response to questions, said that he continues to be bullish on such platform-based approaches to vaccines. The DNA strategy, in particular, represents “a very convenient and easily scalable vaccine,” he said. “We are moving much more toward platform-based vaccines … because of their ease and convenience, and scaling up and rapidity.”

The scope of a vaccination program will depend on the endemicity of the virus in a given area, said Dr. Fauci. In an endemic area, “Ultimately, you want to get women of childbearing age, as well as their sexual partners,” he said. This means that target populations will be as young as possible, to make sure women and their partners are vaccinated by the time pregnancy becomes a possibility.

Other Zika virus vaccine development efforts underway at NIAID include a strategy that uses a live attenuated virus, an approach used for a dengue virus vaccine that is currently in a phase 3 clinical trial in Brazil, according to the agency’s website. Dengue and Zika are closely related viruses. Another investigational Zika virus vaccine uses genetic engineering to create a vaccine derived from vesicular stomatitis virus, which infects cattle. This strategy, also used in one approach to Ebola vaccination, is in the pre-clinical stage.

[email protected]

On Twitter @karioakes

A clinical trial to evaluate a candidate vaccine for Zika virus is underway, with preliminary results from the multisite phase I trial expected by the end of 2016.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health, announced the trial and gave an update about other Zika virus vaccine development efforts during an Aug. 3 telephone briefing with reporters. The announcement came just days after the continental United States saw its first cases of local transmission of Zika virus in Florida.

Courtesy of the National Institute of Allergy and Infectious Diseases

The phase I clinical trial began on Aug. 2 and will evaluate the safety and immunogenicity of an investigational DNA vaccine for Zika virus. This vaccine is similar to one that early-stage trials have shown to be safe and immunogenic for West Nile virus, a flavivirus closely related to Zika. The Zika virus vaccine had promising preclinical results, Dr. Fauci said. “Preliminary immune responses that we’ve seen in a variety of animal models have been rather robust.”

The DNA vaccine uses a plasmid to deliver genes that code for specific Zika virus proteins. “When the plasmid expresses the envelope protein from the Zika virus, it does so in a way that mimics the virus,” provoking a host immune response that includes neutralizing antibodies and T cells, according to lead trial investigator Julie Ledgerwood, DO, chief of the clinical trials program at the NIAID’s Vaccine Research Center.

The phase I clinical trial will enroll 80 healthy volunteers, aged 18-35 years. All participants will receive the investigational Zika virus vaccine at their first visit, with vaccine delivery via a needle-free system that injects the vaccine directly into the deltoid muscle.

Forty participants will receive one additional dose of the vaccine, with half of those people receiving the additional dose at 8 weeks after the first vaccine, and the other half receiving the additional dose at 12 weeks after the first dose. The other 40 participants will receive two additional doses, with half receiving them at 4 and 8 weeks after the first vaccination, and the other half receiving the extra doses at 4 and 20 weeks. All participants will receive the same dose at each vaccination.

Participants will be asked to monitor their temperature daily for a week after each vaccine dose is received; they will also report any adverse events. The trial design provides for several follow-up visits to track safety and to measure immune response in 44 weeks of short-term follow-up. Additionally, two follow-up visits at 18 months and 2 years post vaccination will measure the durability of the immune response.

The clinical trial will be run at the National Institutes of Health Clinical Center in Bethesda, Md., at Emory University in Atlanta, and at the University of Maryland’s Center for Vaccine Development in Baltimore.

Initial safety and immune response data should be available by the end of 2016, Dr. Fauci said. If these data are promising, a phase II clinical trial will be launched in early 2017 in several Zika-endemic countries. The NIH has the in-house capability to manufacture the 2,500-5,000 doses of vaccine that the phase II trial is expected to require.

However, said Dr. Fauci, without congressional approval of additional funding for Zika virus vaccine efforts, the transition to a phase II clinical trial is far from certain. Interruption in funding would be “effectively impeding our smooth process on the vaccine development front,” he said. “When I say we are going to run out of money soon, I mean really soon.”

Dr. Fauci, in response to questions, said that he continues to be bullish on such platform-based approaches to vaccines. The DNA strategy, in particular, represents “a very convenient and easily scalable vaccine,” he said. “We are moving much more toward platform-based vaccines … because of their ease and convenience, and scaling up and rapidity.”

The scope of a vaccination program will depend on the endemicity of the virus in a given area, said Dr. Fauci. In an endemic area, “Ultimately, you want to get women of childbearing age, as well as their sexual partners,” he said. This means that target populations will be as young as possible, to make sure women and their partners are vaccinated by the time pregnancy becomes a possibility.

Other Zika virus vaccine development efforts underway at NIAID include a strategy that uses a live attenuated virus, an approach used for a dengue virus vaccine that is currently in a phase 3 clinical trial in Brazil, according to the agency’s website. Dengue and Zika are closely related viruses. Another investigational Zika virus vaccine uses genetic engineering to create a vaccine derived from vesicular stomatitis virus, which infects cattle. This strategy, also used in one approach to Ebola vaccination, is in the pre-clinical stage.

[email protected]

On Twitter @karioakes

The long head of the biceps (LHB) tendon is a recognized source of shoulder pain. LHB tendon pathology is commonly associated with other shoulder conditions, such as superior labral tears, rotator cuff tears, or subacromial impingement, whereas isolated pathology, such as traumatic ruptures, tendinosis, or medial subluxation, is rare.¹ Treatment of LHB pathology ranges from conservative measures to surgical measures, including tenotomy or tenodesis.² LHB tenodesis offers the advantage of maintaining the length–tension relationship of the biceps muscle to prevent atrophy and avoid the Popeye deformity incurred from tenotomy alone. Tenodesis also prevents muscle cramping associated with contracted biceps muscle and better maintains elbow flexion and supination strength, which may be decreased with tenotomy.³ In addition, when a subpectoral biceps tenodesis technique is used, pain from LHB tendinopathy in the intertubercular groove may be reduced.⁴

Open subpectoral biceps tenodesis is a reproducible, efficient method for LHB tenodesis.^4,5 A variety of fixation devices has been used: bone tunnels,⁶ keyhole fixation,⁷ suture anchors,^6-9 and interference screws.^6-8,10,11 More recently, a bicortical button has been used for LHB tendon tenodesis.¹² Biomechanical studies have shown that load to failure is comparable for bicortical button fixation and interference screw fixation.^13,14 In other models of tendon repair, the bicortical button has strength and stability comparable to those of interference screw fixation and enables earlier rehabilitation.^15-17 However, there is concern that bicortical button fixation may result in axillary nerve (AN) or posterior circumflex humeral artery (PCHA) compromise because of the proximity of these neurovascular structures to the bicortical button.^13,18-21

We conducted a study to functionally and sonographically assess the outcomes of patients who underwent open subpectoral biceps tenodesis with a bicortical button. Functional outcomes were assessed with patient-reported outcomes and physician-reported outcomes. Sonographic studies were used to evaluate the integrity of the tenodesis and determine the proximity of the button to the AN and the PCHA along the posterior proximal humerus.

Methods

After obtaining Institutional Review Board approval for this study, we retrospectively identified 28 consecutive patients who had proximal biceps tenodesis performed by a single surgeon (Dr. K.E. Swanson) using a mini-open subpectoral biceps tenodesis technique with a bicortical button between March 2011 and January 2013. All 28 patients were asked to participate in the study. Twenty-four (86%) agreed to complete 2 surgical outcome surveys, and 18 (64%) completed a 3-part clinical examination at minimum 12-month follow-up.

One of the surveys was Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), a validated comprehensive disability survey that scores upper extremity functionality on a scale ranging from 0 (none) to 100 (extreme difficulty).^22,23 The other survey scored pain on a scale ranging from 0 (none) to 100 (worst pain).

The clinical examination was completed during a single visit by an orthopedic surgeon (Dr. Meadows or Dr. Diesselhorst) different from the primary surgeon (Dr. K.E. Swanson) and by a clinician-sonologist (Dr. Finnoff). The examination’s 3 parts were physical examination of arm, biceps supination strength test, and ultrasonographic evaluation.

Physical Examination of Arm. Physical examination included palpation of bicipital groove, range of motion (ROM) of shoulder and elbow, and clinical deformity of biceps. Patients were questioned regarding symptoms of AN damage, including sensory and motor findings. Bicipital groove tenderness was assessed with a visual analog scale rating pain 0 to 10. ROM was measured in degrees and was presented as a percentage of full elbow ROM (150°) and full shoulder ROM (180°).

Biceps Supination Strength Test. Biceps supination strength was tested with a baseline hydraulic wrist dynamometer with door handle attachment. Patients were seated with the elbow bent 90° and the forearm in a neutral position. In a series of 3 trials, the patient maintained grip of the dynamometer doorknob while supinating the forearm. The tenodesed (operated) arm and contralateral unaffected (nonoperated) arm were tested in random order and recorded in pounds.

Ultrasonographic Evaluation. Ultrasonography was used to evaluate the tenodesis site. In each case, the biceps tendon was assessed to determine the location of the bicortical button in relation to the AN/PCHA neurovascular bundle. Whereas nerves are difficult to visualize with ultrasonography, arteries are readily seen. Dr. Finnoff used a CX50 ultrasound machine (Philips Medical Systems) with either a 12-3 MHz linear array or a 5-1 MHz curvilinear array transducer to measure the shortest distance from the PCHA to the button.

Each patient was placed in a lateral decubitus or prone position, and the skin of the upper arm was exposed. Tendon integrity was deemed either intact (continuity between biceps tendon and cortical button) or disrupted (lack of continuity between tendon and cortical button). The transducer was then placed in an anatomical sagittal plane over the posterior aspect of the proximal humerus. Power Doppler and cephalad and caudad transducer glides were used to identify the location of the PCHA. The transducer was then glided laterally and anteriorly around the humerus, following the course of the PCHA, until the cortical button was located. The narrowest interval between the PCHA and the cortical button was measured using the ultrasound machine’s software. A still image of each measurement was saved.

Surgical Technique

Biceps tenodesis indications included high-demand heavy laborers, athletes, and patients who preferred the cosmetic results of tenodesis over tenotomy. Most patients had acute symptomatic tears of the superior labrum with instability of the biceps anchor complex. Others had fraying and tenosynovitis of the LHB tendon. Any associated pathology was addressed during the same surgical period.

The surgical technique used was similar to that described by Snir and colleagues.¹² Each patient was placed in the lateral decubitus position. Once pathology confirmed biceps tenodesis, the biceps tendon was tenotomized at the base of the superior labrum. A 3-cm incision was made along the axillary fold centered over the inferior border of the pectoralis major tendon. Blunt dissection was performed to define the inferior border of the pectoralis major tendon and to palpate the underlying biceps tendon as it exited the intertubercular groove. The LHB tendon was removed and prepared with No. 2 Fiberwire (Arthrex) in Krackow fashion starting 2 cm proximal to the musculotendinous junction. The excess tendon was excised.

A 3.2-mm guide wire was centered along the most distal aspect of the biceps groove and then drilled through the anterior cortex and just through the posterior cortex. A cannulated reamer, selected on the basis of the biceps tendon diameter (typically, 5-7 mm), was then drilled over the guide wire through the anterior cortex only. The Food and Drug Administration–approved cortical button (BicepsButton; Arthrex) was then loaded by passing the tendon suture ends through each side of the button in alternating fashion, thus allowing the button to slide along the sutures.

The button was loaded onto the BicepsButton deployment device and inserted through the drilled tunnel of the anterior cortex and just through the posterior cortex. The deployment device was then removed, and 1 suture end was pulled to allow the button to engage the posterior humeral cortex. Pulling on both sutures allowed the biceps tendon to slide through the anterior cortex hole of the humerus until the tendon reached the posterior humeral cortex. Tension was verified, and the sutures were tied over the tendon. The wound was then irrigated and closed.

Rehabilitation Program

Patients completed a standard rehabilitation protocol for biceps tenodesis²⁴ along with rehabilitation protocols for any additional procedures performed. In phase 1 (weeks 0-2), they focused on gradual restoration of passive ROM and remained in a sling. In phase 2 (weeks 2-6), they focused on gradual restoration of active ROM, and by week 3 were weaned out of the sling. In phase 3 (weeks 6-8), they continued ROM and strengthening exercises to normalize strength, endurance, and neuromuscular control. In phase 4 (weeks 8-12), they focused on advanced strengthening exercises and return to activities.

Statistical Analysis

Descriptive statistics included means, medians, and SDs. Comparisons between operated and nonoperated arms and between dominant and nondominant arms were performed by a statistician using paired t tests with P = .05. Confidence intervals were calculated for operated and nonoperated arms and for dominant and nondominant arms by using the differences between them.

Results

Functional Outcomes

Surgical outcome scores and pain scores were obtained from 24 patients (86%) at minimum 12-month follow-up. Mean (SD) DASH score was 15.15 (17.6; median, 9), and mean (median) pain score was 12.61 (7).

Eighteen patients (64%) completed the clinical examination: 16 men (88.9%) and 2 women (11.1%). Mean age was 48.3 years (age range, 33-59 years). Of these 18 patients, 9 (50%) had surgery on the dominant arm, and the other 9 had surgery on the nondominant arm. All patients were right-hand–dominant. In 3 patients, biceps tenodesis was performed with only minimal arthroscopic débridement (20%); in the other 15, biceps tenodesis was performed concomitantly with 1 or more additional arthroscopic procedures: acromioplasty (73%), rotator cuff repair (47%), distal clavicle resection (33%), subacromial bursectomy (13%), microfracture of glenoid (13%), and posterior labral repair (7%).

The clinical examination was performed a mean of 15.2 months (range, 12-26 months) after surgery. Physical examination findings are listed in Table 1.

Forearm supination strength, averaged from 3 trials on each arm, was significantly (P = .01) greater in the nonoperated arm than in the operated arm (Table 2, Figure 1). A 95% confidence interval for the mean (SD) difference in strength was 9.35 (7.76) pounds, meaning that on average, the nonoperated arm will be 1.59 to 17.11 pounds stronger than the operated arm. In addition, strength of the dominant arm was greater than that of the nondominant arm (P = .05) regardless of which arm underwent surgery (Table 2, Figure 1). However, the mean (SD) difference in strength was 6.94 (8.39) pounds, indicating the observed difference was not statistically significant.

Sonographic Evaluation

According to the sonographic evaluations, the tenodesis was intact in all 18 patients (Figure 2). Estimated mean (SD) distance from button to PCHA was 18.17 (9.0) mm (median, 16.1 mm; range, 9.4-48 mm) (Figure 2, Figure 3). No patient indicated any symptoms of AN damage.

Discussion

There are few studies of functional outcomes of biceps tenodesis. Pain is a common measure of patient satisfaction. Mazzocca and colleagues²⁵ reported a mean follow-up pain score of 1.1 (range, 0.5-1.9) out of 10 for a group of 41 patients who had subpectoral tenodesis with an interference screw. Millett and colleagues²⁶ reported a mean postoperative pain score of 2.5 out of 10 for patients who had subpectoral interference screw fixation. Our patients reported a mean pain score of 12.6 out of 100 after minimum 12-month follow-up. We also assessed for pain in the intertubercular groove during palpation. Although some studies have shown that groove pain was eliminated by subpectoral biceps tenodesis,⁵ 3 patients in our study had pain on groove palpation. The cause of this residual pain is unclear, but some studies have suggested a chronic degenerative pathologic process that occurs while the tendon is within the biceps groove.²⁷ Removing the tendon from the groove may not remove the underlying cause of pain.

Our patients’ mean DASH score was 15.15 (within the excellent range). Normative mean (SD) DASH score for the general population is 10.1 (14.68).²⁸

Functional strength of forearm supination, shoulder ROM, and elbow ROM are objective measures of patient performance after fixation. On Cybex testing, Phillips and colleagues²⁹ found no difference in forearm supination strength or elbow flexion (compared with contralateral arm) after biceps tenodesis or conservative treatment for proximal biceps ruptures. Shank and colleagues³⁰ compared elbow flexion and supination strength of the affected and unaffected arms after suture anchor subpectoral biceps tenodesis. There was no significant difference in Cybex results, but there was a 14% to 15% loss of average strength in the tenodesed versus nonsurgical arm. In the present study, we found a significant difference in forearm supination strength between the operated and nonoperated arms, but with only a 7% loss of average strength in the operated arms. The difference in strength ranged from 1.59 to 17.11 pounds, which may not be clinically significant, as supination strength ranged from 60 to 270 pounds.

Of the 18 patients in this study, 9 had surgery on the dominant arm, and the other 9 had surgery on the nondominant arm. Examining the effect of arm dominance on results revealed that patients with surgery on the nondominant arm tended to have substantially reduced supination strength in that arm vs the dominant arm. There was an 11% loss of average strength for nondominant vs dominant arms that had surgery. Examining nondominant arms only revealed a 13% loss of strength for operated vs nonoperated arms. There was no difference in forearm supination strengths between nonoperated arms (dominant vs nondominant) or between dominant arms (operated vs nonoperated). This suggests that, though hand dominance may not play a significant role in control patients’ forearm supination strength,³⁰ it may have a substantial effect on surgical patients’ ability to regain strength when the nondominant arm is the surgical arm.
One objective of this study was to measure the distance between the biceps cortical button on the posterior humeral cortex and the AN/PCHA neurovascular bundle. The AN bundles with the PCHA posterior to the humeral neck.^31-33 As the AN travels with the PCHA, and the PCHA has been reliably identified with Doppler ultrasonography,^34-36 the PCHA was used as a marker for the AN in this study. Our bicortical button technique places the button on the posterior aspect of the humerus, making AN and PCHA the nearest at-risk neurovascular structures. None of our patients had symptoms of AN damage. However, 2 patients indicated pain in the posterior aspect of the humerus during deltoid activation. Distance from the neurovascular structures to the button was 48 mm in one patient and 13.6 mm in the other. DASH scores were 43 and 27, respectively. Both patients’ 1-year pain score was 30. The first patient underwent arthroscopic acromioplasty, distal clavicle resection, and microfracture of the glenoid surface in addition to the subpectoral biceps tenodesis; the second underwent subacromial decompression and distal clavicle resection in addition to the subpectoral biceps tenodesis. Whether the associated pathology contributed to their persistent pain is unknown. However, given the distance from AN/PCHA to button, it is unlikely that their pain was a result of neurovascular compromise from the procedure.

Advantages of the cortical button include the ability to drill a smaller hole in the humerus for fixation, compared with the hole drilled for an interference screw. Despite the biomechanical strength of the screw, large (8 mm) cortical violations have been associated with increased fracture risk of the proximal humerus.^37,38 The tendon may experience less trauma than that caused by being twisted against an interference screw, the most common location of failure of which is the tendon–screw interface.³⁹ In addition, tendon healing may be improved through circumferential healing in the cortical button tunnel.

A concern of using a bicortical button for fixation is drilling through the posterior cortex, because of the proximity of the posterior neurovascular structures. In a case in which the posterior cord was injured, Rhee and colleagues⁴⁰ used a suture pullout technique whereby a Beath pin was passed out of the posterior humerus and soft tissues to then hold tension on the biceps tendon during the tenodesis. The radial nerve potentially could have been injured by pin overpenetration or by becoming wrapped up in the soft tissues as the pin was spinning through them. In our technique, the posterior humeral cortex is drilled cautiously to avoid overpenetration and possibly getting the posterior soft tissues wrapped up in the guide pin. No AN injuries have been reported with this technique. Mean distance from AN to posterior cortical button in this study was 18.17 mm. In 2 cadaver studies of bicortical drilling for subpectoral biceps tenodesis, the ANs were 25.1 mm and 36.7 mm from the posterior drill hole.^41,21

Limitations of this study included its design (case series) and limited number of follow-up patients. Of the 28 consecutive patients identified for the study, 10 did not undergo the clinical examination, as they either lived more than 3 hours away (8 patients) or could not be contacted (2 patients). Another study limitation was the inability to directly image ANs with ultrasound. Therefore, measurements of the distance from the PCHA to the button were used to estimate the distance from the AN/PCHA neurovascular bundle to the button.

In this study, functional outcomes were excellent, and there were no tenodesis failures or neurovascular complications. These preliminary findings indicate that subpectoral biceps tenodesis with a bicortical button is a viable treatment option for patients with the appropriate indications for this procedure.

The long head of the biceps (LHB) tendon is a recognized source of shoulder pain. LHB tendon pathology is commonly associated with other shoulder conditions, such as superior labral tears, rotator cuff tears, or subacromial impingement, whereas isolated pathology, such as traumatic ruptures, tendinosis, or medial subluxation, is rare.¹ Treatment of LHB pathology ranges from conservative measures to surgical measures, including tenotomy or tenodesis.² LHB tenodesis offers the advantage of maintaining the length–tension relationship of the biceps muscle to prevent atrophy and avoid the Popeye deformity incurred from tenotomy alone. Tenodesis also prevents muscle cramping associated with contracted biceps muscle and better maintains elbow flexion and supination strength, which may be decreased with tenotomy.³ In addition, when a subpectoral biceps tenodesis technique is used, pain from LHB tendinopathy in the intertubercular groove may be reduced.⁴

Open subpectoral biceps tenodesis is a reproducible, efficient method for LHB tenodesis.^4,5 A variety of fixation devices has been used: bone tunnels,⁶ keyhole fixation,⁷ suture anchors,^6-9 and interference screws.^6-8,10,11 More recently, a bicortical button has been used for LHB tendon tenodesis.¹² Biomechanical studies have shown that load to failure is comparable for bicortical button fixation and interference screw fixation.^13,14 In other models of tendon repair, the bicortical button has strength and stability comparable to those of interference screw fixation and enables earlier rehabilitation.^15-17 However, there is concern that bicortical button fixation may result in axillary nerve (AN) or posterior circumflex humeral artery (PCHA) compromise because of the proximity of these neurovascular structures to the bicortical button.^13,18-21

We conducted a study to functionally and sonographically assess the outcomes of patients who underwent open subpectoral biceps tenodesis with a bicortical button. Functional outcomes were assessed with patient-reported outcomes and physician-reported outcomes. Sonographic studies were used to evaluate the integrity of the tenodesis and determine the proximity of the button to the AN and the PCHA along the posterior proximal humerus.

Methods

After obtaining Institutional Review Board approval for this study, we retrospectively identified 28 consecutive patients who had proximal biceps tenodesis performed by a single surgeon (Dr. K.E. Swanson) using a mini-open subpectoral biceps tenodesis technique with a bicortical button between March 2011 and January 2013. All 28 patients were asked to participate in the study. Twenty-four (86%) agreed to complete 2 surgical outcome surveys, and 18 (64%) completed a 3-part clinical examination at minimum 12-month follow-up.

One of the surveys was Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), a validated comprehensive disability survey that scores upper extremity functionality on a scale ranging from 0 (none) to 100 (extreme difficulty).^22,23 The other survey scored pain on a scale ranging from 0 (none) to 100 (worst pain).

The clinical examination was completed during a single visit by an orthopedic surgeon (Dr. Meadows or Dr. Diesselhorst) different from the primary surgeon (Dr. K.E. Swanson) and by a clinician-sonologist (Dr. Finnoff). The examination’s 3 parts were physical examination of arm, biceps supination strength test, and ultrasonographic evaluation.

Physical Examination of Arm. Physical examination included palpation of bicipital groove, range of motion (ROM) of shoulder and elbow, and clinical deformity of biceps. Patients were questioned regarding symptoms of AN damage, including sensory and motor findings. Bicipital groove tenderness was assessed with a visual analog scale rating pain 0 to 10. ROM was measured in degrees and was presented as a percentage of full elbow ROM (150°) and full shoulder ROM (180°).

Biceps Supination Strength Test. Biceps supination strength was tested with a baseline hydraulic wrist dynamometer with door handle attachment. Patients were seated with the elbow bent 90° and the forearm in a neutral position. In a series of 3 trials, the patient maintained grip of the dynamometer doorknob while supinating the forearm. The tenodesed (operated) arm and contralateral unaffected (nonoperated) arm were tested in random order and recorded in pounds.

Ultrasonographic Evaluation. Ultrasonography was used to evaluate the tenodesis site. In each case, the biceps tendon was assessed to determine the location of the bicortical button in relation to the AN/PCHA neurovascular bundle. Whereas nerves are difficult to visualize with ultrasonography, arteries are readily seen. Dr. Finnoff used a CX50 ultrasound machine (Philips Medical Systems) with either a 12-3 MHz linear array or a 5-1 MHz curvilinear array transducer to measure the shortest distance from the PCHA to the button.

Each patient was placed in a lateral decubitus or prone position, and the skin of the upper arm was exposed. Tendon integrity was deemed either intact (continuity between biceps tendon and cortical button) or disrupted (lack of continuity between tendon and cortical button). The transducer was then placed in an anatomical sagittal plane over the posterior aspect of the proximal humerus. Power Doppler and cephalad and caudad transducer glides were used to identify the location of the PCHA. The transducer was then glided laterally and anteriorly around the humerus, following the course of the PCHA, until the cortical button was located. The narrowest interval between the PCHA and the cortical button was measured using the ultrasound machine’s software. A still image of each measurement was saved.

Surgical Technique

Biceps tenodesis indications included high-demand heavy laborers, athletes, and patients who preferred the cosmetic results of tenodesis over tenotomy. Most patients had acute symptomatic tears of the superior labrum with instability of the biceps anchor complex. Others had fraying and tenosynovitis of the LHB tendon. Any associated pathology was addressed during the same surgical period.

The surgical technique used was similar to that described by Snir and colleagues.¹² Each patient was placed in the lateral decubitus position. Once pathology confirmed biceps tenodesis, the biceps tendon was tenotomized at the base of the superior labrum. A 3-cm incision was made along the axillary fold centered over the inferior border of the pectoralis major tendon. Blunt dissection was performed to define the inferior border of the pectoralis major tendon and to palpate the underlying biceps tendon as it exited the intertubercular groove. The LHB tendon was removed and prepared with No. 2 Fiberwire (Arthrex) in Krackow fashion starting 2 cm proximal to the musculotendinous junction. The excess tendon was excised.

A 3.2-mm guide wire was centered along the most distal aspect of the biceps groove and then drilled through the anterior cortex and just through the posterior cortex. A cannulated reamer, selected on the basis of the biceps tendon diameter (typically, 5-7 mm), was then drilled over the guide wire through the anterior cortex only. The Food and Drug Administration–approved cortical button (BicepsButton; Arthrex) was then loaded by passing the tendon suture ends through each side of the button in alternating fashion, thus allowing the button to slide along the sutures.

The button was loaded onto the BicepsButton deployment device and inserted through the drilled tunnel of the anterior cortex and just through the posterior cortex. The deployment device was then removed, and 1 suture end was pulled to allow the button to engage the posterior humeral cortex. Pulling on both sutures allowed the biceps tendon to slide through the anterior cortex hole of the humerus until the tendon reached the posterior humeral cortex. Tension was verified, and the sutures were tied over the tendon. The wound was then irrigated and closed.

Rehabilitation Program

Patients completed a standard rehabilitation protocol for biceps tenodesis²⁴ along with rehabilitation protocols for any additional procedures performed. In phase 1 (weeks 0-2), they focused on gradual restoration of passive ROM and remained in a sling. In phase 2 (weeks 2-6), they focused on gradual restoration of active ROM, and by week 3 were weaned out of the sling. In phase 3 (weeks 6-8), they continued ROM and strengthening exercises to normalize strength, endurance, and neuromuscular control. In phase 4 (weeks 8-12), they focused on advanced strengthening exercises and return to activities.

Statistical Analysis

Descriptive statistics included means, medians, and SDs. Comparisons between operated and nonoperated arms and between dominant and nondominant arms were performed by a statistician using paired t tests with P = .05. Confidence intervals were calculated for operated and nonoperated arms and for dominant and nondominant arms by using the differences between them.

Results

Functional Outcomes

Surgical outcome scores and pain scores were obtained from 24 patients (86%) at minimum 12-month follow-up. Mean (SD) DASH score was 15.15 (17.6; median, 9), and mean (median) pain score was 12.61 (7).

Eighteen patients (64%) completed the clinical examination: 16 men (88.9%) and 2 women (11.1%). Mean age was 48.3 years (age range, 33-59 years). Of these 18 patients, 9 (50%) had surgery on the dominant arm, and the other 9 had surgery on the nondominant arm. All patients were right-hand–dominant. In 3 patients, biceps tenodesis was performed with only minimal arthroscopic débridement (20%); in the other 15, biceps tenodesis was performed concomitantly with 1 or more additional arthroscopic procedures: acromioplasty (73%), rotator cuff repair (47%), distal clavicle resection (33%), subacromial bursectomy (13%), microfracture of glenoid (13%), and posterior labral repair (7%).

The clinical examination was performed a mean of 15.2 months (range, 12-26 months) after surgery. Physical examination findings are listed in Table 1.

Forearm supination strength, averaged from 3 trials on each arm, was significantly (P = .01) greater in the nonoperated arm than in the operated arm (Table 2, Figure 1). A 95% confidence interval for the mean (SD) difference in strength was 9.35 (7.76) pounds, meaning that on average, the nonoperated arm will be 1.59 to 17.11 pounds stronger than the operated arm. In addition, strength of the dominant arm was greater than that of the nondominant arm (P = .05) regardless of which arm underwent surgery (Table 2, Figure 1). However, the mean (SD) difference in strength was 6.94 (8.39) pounds, indicating the observed difference was not statistically significant.

Sonographic Evaluation

According to the sonographic evaluations, the tenodesis was intact in all 18 patients (Figure 2). Estimated mean (SD) distance from button to PCHA was 18.17 (9.0) mm (median, 16.1 mm; range, 9.4-48 mm) (Figure 2, Figure 3). No patient indicated any symptoms of AN damage.

Discussion

There are few studies of functional outcomes of biceps tenodesis. Pain is a common measure of patient satisfaction. Mazzocca and colleagues²⁵ reported a mean follow-up pain score of 1.1 (range, 0.5-1.9) out of 10 for a group of 41 patients who had subpectoral tenodesis with an interference screw. Millett and colleagues²⁶ reported a mean postoperative pain score of 2.5 out of 10 for patients who had subpectoral interference screw fixation. Our patients reported a mean pain score of 12.6 out of 100 after minimum 12-month follow-up. We also assessed for pain in the intertubercular groove during palpation. Although some studies have shown that groove pain was eliminated by subpectoral biceps tenodesis,⁵ 3 patients in our study had pain on groove palpation. The cause of this residual pain is unclear, but some studies have suggested a chronic degenerative pathologic process that occurs while the tendon is within the biceps groove.²⁷ Removing the tendon from the groove may not remove the underlying cause of pain.

Our patients’ mean DASH score was 15.15 (within the excellent range). Normative mean (SD) DASH score for the general population is 10.1 (14.68).²⁸

Functional strength of forearm supination, shoulder ROM, and elbow ROM are objective measures of patient performance after fixation. On Cybex testing, Phillips and colleagues²⁹ found no difference in forearm supination strength or elbow flexion (compared with contralateral arm) after biceps tenodesis or conservative treatment for proximal biceps ruptures. Shank and colleagues³⁰ compared elbow flexion and supination strength of the affected and unaffected arms after suture anchor subpectoral biceps tenodesis. There was no significant difference in Cybex results, but there was a 14% to 15% loss of average strength in the tenodesed versus nonsurgical arm. In the present study, we found a significant difference in forearm supination strength between the operated and nonoperated arms, but with only a 7% loss of average strength in the operated arms. The difference in strength ranged from 1.59 to 17.11 pounds, which may not be clinically significant, as supination strength ranged from 60 to 270 pounds.

Of the 18 patients in this study, 9 had surgery on the dominant arm, and the other 9 had surgery on the nondominant arm. Examining the effect of arm dominance on results revealed that patients with surgery on the nondominant arm tended to have substantially reduced supination strength in that arm vs the dominant arm. There was an 11% loss of average strength for nondominant vs dominant arms that had surgery. Examining nondominant arms only revealed a 13% loss of strength for operated vs nonoperated arms. There was no difference in forearm supination strengths between nonoperated arms (dominant vs nondominant) or between dominant arms (operated vs nonoperated). This suggests that, though hand dominance may not play a significant role in control patients’ forearm supination strength,³⁰ it may have a substantial effect on surgical patients’ ability to regain strength when the nondominant arm is the surgical arm.
One objective of this study was to measure the distance between the biceps cortical button on the posterior humeral cortex and the AN/PCHA neurovascular bundle. The AN bundles with the PCHA posterior to the humeral neck.^31-33 As the AN travels with the PCHA, and the PCHA has been reliably identified with Doppler ultrasonography,^34-36 the PCHA was used as a marker for the AN in this study. Our bicortical button technique places the button on the posterior aspect of the humerus, making AN and PCHA the nearest at-risk neurovascular structures. None of our patients had symptoms of AN damage. However, 2 patients indicated pain in the posterior aspect of the humerus during deltoid activation. Distance from the neurovascular structures to the button was 48 mm in one patient and 13.6 mm in the other. DASH scores were 43 and 27, respectively. Both patients’ 1-year pain score was 30. The first patient underwent arthroscopic acromioplasty, distal clavicle resection, and microfracture of the glenoid surface in addition to the subpectoral biceps tenodesis; the second underwent subacromial decompression and distal clavicle resection in addition to the subpectoral biceps tenodesis. Whether the associated pathology contributed to their persistent pain is unknown. However, given the distance from AN/PCHA to button, it is unlikely that their pain was a result of neurovascular compromise from the procedure.

Advantages of the cortical button include the ability to drill a smaller hole in the humerus for fixation, compared with the hole drilled for an interference screw. Despite the biomechanical strength of the screw, large (8 mm) cortical violations have been associated with increased fracture risk of the proximal humerus.^37,38 The tendon may experience less trauma than that caused by being twisted against an interference screw, the most common location of failure of which is the tendon–screw interface.³⁹ In addition, tendon healing may be improved through circumferential healing in the cortical button tunnel.

A concern of using a bicortical button for fixation is drilling through the posterior cortex, because of the proximity of the posterior neurovascular structures. In a case in which the posterior cord was injured, Rhee and colleagues⁴⁰ used a suture pullout technique whereby a Beath pin was passed out of the posterior humerus and soft tissues to then hold tension on the biceps tendon during the tenodesis. The radial nerve potentially could have been injured by pin overpenetration or by becoming wrapped up in the soft tissues as the pin was spinning through them. In our technique, the posterior humeral cortex is drilled cautiously to avoid overpenetration and possibly getting the posterior soft tissues wrapped up in the guide pin. No AN injuries have been reported with this technique. Mean distance from AN to posterior cortical button in this study was 18.17 mm. In 2 cadaver studies of bicortical drilling for subpectoral biceps tenodesis, the ANs were 25.1 mm and 36.7 mm from the posterior drill hole.^41,21

Limitations of this study included its design (case series) and limited number of follow-up patients. Of the 28 consecutive patients identified for the study, 10 did not undergo the clinical examination, as they either lived more than 3 hours away (8 patients) or could not be contacted (2 patients). Another study limitation was the inability to directly image ANs with ultrasound. Therefore, measurements of the distance from the PCHA to the button were used to estimate the distance from the AN/PCHA neurovascular bundle to the button.

In this study, functional outcomes were excellent, and there were no tenodesis failures or neurovascular complications. These preliminary findings indicate that subpectoral biceps tenodesis with a bicortical button is a viable treatment option for patients with the appropriate indications for this procedure.

The long head of the biceps (LHB) tendon is a recognized source of shoulder pain. LHB tendon pathology is commonly associated with other shoulder conditions, such as superior labral tears, rotator cuff tears, or subacromial impingement, whereas isolated pathology, such as traumatic ruptures, tendinosis, or medial subluxation, is rare.¹ Treatment of LHB pathology ranges from conservative measures to surgical measures, including tenotomy or tenodesis.² LHB tenodesis offers the advantage of maintaining the length–tension relationship of the biceps muscle to prevent atrophy and avoid the Popeye deformity incurred from tenotomy alone. Tenodesis also prevents muscle cramping associated with contracted biceps muscle and better maintains elbow flexion and supination strength, which may be decreased with tenotomy.³ In addition, when a subpectoral biceps tenodesis technique is used, pain from LHB tendinopathy in the intertubercular groove may be reduced.⁴

Open subpectoral biceps tenodesis is a reproducible, efficient method for LHB tenodesis.^4,5 A variety of fixation devices has been used: bone tunnels,⁶ keyhole fixation,⁷ suture anchors,^6-9 and interference screws.^6-8,10,11 More recently, a bicortical button has been used for LHB tendon tenodesis.¹² Biomechanical studies have shown that load to failure is comparable for bicortical button fixation and interference screw fixation.^13,14 In other models of tendon repair, the bicortical button has strength and stability comparable to those of interference screw fixation and enables earlier rehabilitation.^15-17 However, there is concern that bicortical button fixation may result in axillary nerve (AN) or posterior circumflex humeral artery (PCHA) compromise because of the proximity of these neurovascular structures to the bicortical button.^13,18-21

We conducted a study to functionally and sonographically assess the outcomes of patients who underwent open subpectoral biceps tenodesis with a bicortical button. Functional outcomes were assessed with patient-reported outcomes and physician-reported outcomes. Sonographic studies were used to evaluate the integrity of the tenodesis and determine the proximity of the button to the AN and the PCHA along the posterior proximal humerus.

Methods

After obtaining Institutional Review Board approval for this study, we retrospectively identified 28 consecutive patients who had proximal biceps tenodesis performed by a single surgeon (Dr. K.E. Swanson) using a mini-open subpectoral biceps tenodesis technique with a bicortical button between March 2011 and January 2013. All 28 patients were asked to participate in the study. Twenty-four (86%) agreed to complete 2 surgical outcome surveys, and 18 (64%) completed a 3-part clinical examination at minimum 12-month follow-up.

One of the surveys was Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH), a validated comprehensive disability survey that scores upper extremity functionality on a scale ranging from 0 (none) to 100 (extreme difficulty).^22,23 The other survey scored pain on a scale ranging from 0 (none) to 100 (worst pain).

The clinical examination was completed during a single visit by an orthopedic surgeon (Dr. Meadows or Dr. Diesselhorst) different from the primary surgeon (Dr. K.E. Swanson) and by a clinician-sonologist (Dr. Finnoff). The examination’s 3 parts were physical examination of arm, biceps supination strength test, and ultrasonographic evaluation.

Physical Examination of Arm. Physical examination included palpation of bicipital groove, range of motion (ROM) of shoulder and elbow, and clinical deformity of biceps. Patients were questioned regarding symptoms of AN damage, including sensory and motor findings. Bicipital groove tenderness was assessed with a visual analog scale rating pain 0 to 10. ROM was measured in degrees and was presented as a percentage of full elbow ROM (150°) and full shoulder ROM (180°).

Biceps Supination Strength Test. Biceps supination strength was tested with a baseline hydraulic wrist dynamometer with door handle attachment. Patients were seated with the elbow bent 90° and the forearm in a neutral position. In a series of 3 trials, the patient maintained grip of the dynamometer doorknob while supinating the forearm. The tenodesed (operated) arm and contralateral unaffected (nonoperated) arm were tested in random order and recorded in pounds.

Ultrasonographic Evaluation. Ultrasonography was used to evaluate the tenodesis site. In each case, the biceps tendon was assessed to determine the location of the bicortical button in relation to the AN/PCHA neurovascular bundle. Whereas nerves are difficult to visualize with ultrasonography, arteries are readily seen. Dr. Finnoff used a CX50 ultrasound machine (Philips Medical Systems) with either a 12-3 MHz linear array or a 5-1 MHz curvilinear array transducer to measure the shortest distance from the PCHA to the button.

Each patient was placed in a lateral decubitus or prone position, and the skin of the upper arm was exposed. Tendon integrity was deemed either intact (continuity between biceps tendon and cortical button) or disrupted (lack of continuity between tendon and cortical button). The transducer was then placed in an anatomical sagittal plane over the posterior aspect of the proximal humerus. Power Doppler and cephalad and caudad transducer glides were used to identify the location of the PCHA. The transducer was then glided laterally and anteriorly around the humerus, following the course of the PCHA, until the cortical button was located. The narrowest interval between the PCHA and the cortical button was measured using the ultrasound machine’s software. A still image of each measurement was saved.

Surgical Technique

Biceps tenodesis indications included high-demand heavy laborers, athletes, and patients who preferred the cosmetic results of tenodesis over tenotomy. Most patients had acute symptomatic tears of the superior labrum with instability of the biceps anchor complex. Others had fraying and tenosynovitis of the LHB tendon. Any associated pathology was addressed during the same surgical period.

The surgical technique used was similar to that described by Snir and colleagues.¹² Each patient was placed in the lateral decubitus position. Once pathology confirmed biceps tenodesis, the biceps tendon was tenotomized at the base of the superior labrum. A 3-cm incision was made along the axillary fold centered over the inferior border of the pectoralis major tendon. Blunt dissection was performed to define the inferior border of the pectoralis major tendon and to palpate the underlying biceps tendon as it exited the intertubercular groove. The LHB tendon was removed and prepared with No. 2 Fiberwire (Arthrex) in Krackow fashion starting 2 cm proximal to the musculotendinous junction. The excess tendon was excised.

A 3.2-mm guide wire was centered along the most distal aspect of the biceps groove and then drilled through the anterior cortex and just through the posterior cortex. A cannulated reamer, selected on the basis of the biceps tendon diameter (typically, 5-7 mm), was then drilled over the guide wire through the anterior cortex only. The Food and Drug Administration–approved cortical button (BicepsButton; Arthrex) was then loaded by passing the tendon suture ends through each side of the button in alternating fashion, thus allowing the button to slide along the sutures.

The button was loaded onto the BicepsButton deployment device and inserted through the drilled tunnel of the anterior cortex and just through the posterior cortex. The deployment device was then removed, and 1 suture end was pulled to allow the button to engage the posterior humeral cortex. Pulling on both sutures allowed the biceps tendon to slide through the anterior cortex hole of the humerus until the tendon reached the posterior humeral cortex. Tension was verified, and the sutures were tied over the tendon. The wound was then irrigated and closed.

Rehabilitation Program

Patients completed a standard rehabilitation protocol for biceps tenodesis²⁴ along with rehabilitation protocols for any additional procedures performed. In phase 1 (weeks 0-2), they focused on gradual restoration of passive ROM and remained in a sling. In phase 2 (weeks 2-6), they focused on gradual restoration of active ROM, and by week 3 were weaned out of the sling. In phase 3 (weeks 6-8), they continued ROM and strengthening exercises to normalize strength, endurance, and neuromuscular control. In phase 4 (weeks 8-12), they focused on advanced strengthening exercises and return to activities.

Statistical Analysis

Descriptive statistics included means, medians, and SDs. Comparisons between operated and nonoperated arms and between dominant and nondominant arms were performed by a statistician using paired t tests with P = .05. Confidence intervals were calculated for operated and nonoperated arms and for dominant and nondominant arms by using the differences between them.

Results

Functional Outcomes

Surgical outcome scores and pain scores were obtained from 24 patients (86%) at minimum 12-month follow-up. Mean (SD) DASH score was 15.15 (17.6; median, 9), and mean (median) pain score was 12.61 (7).

Eighteen patients (64%) completed the clinical examination: 16 men (88.9%) and 2 women (11.1%). Mean age was 48.3 years (age range, 33-59 years). Of these 18 patients, 9 (50%) had surgery on the dominant arm, and the other 9 had surgery on the nondominant arm. All patients were right-hand–dominant. In 3 patients, biceps tenodesis was performed with only minimal arthroscopic débridement (20%); in the other 15, biceps tenodesis was performed concomitantly with 1 or more additional arthroscopic procedures: acromioplasty (73%), rotator cuff repair (47%), distal clavicle resection (33%), subacromial bursectomy (13%), microfracture of glenoid (13%), and posterior labral repair (7%).

The clinical examination was performed a mean of 15.2 months (range, 12-26 months) after surgery. Physical examination findings are listed in Table 1.

Forearm supination strength, averaged from 3 trials on each arm, was significantly (P = .01) greater in the nonoperated arm than in the operated arm (Table 2, Figure 1). A 95% confidence interval for the mean (SD) difference in strength was 9.35 (7.76) pounds, meaning that on average, the nonoperated arm will be 1.59 to 17.11 pounds stronger than the operated arm. In addition, strength of the dominant arm was greater than that of the nondominant arm (P = .05) regardless of which arm underwent surgery (Table 2, Figure 1). However, the mean (SD) difference in strength was 6.94 (8.39) pounds, indicating the observed difference was not statistically significant.

Sonographic Evaluation

According to the sonographic evaluations, the tenodesis was intact in all 18 patients (Figure 2). Estimated mean (SD) distance from button to PCHA was 18.17 (9.0) mm (median, 16.1 mm; range, 9.4-48 mm) (Figure 2, Figure 3). No patient indicated any symptoms of AN damage.

Discussion

There are few studies of functional outcomes of biceps tenodesis. Pain is a common measure of patient satisfaction. Mazzocca and colleagues²⁵ reported a mean follow-up pain score of 1.1 (range, 0.5-1.9) out of 10 for a group of 41 patients who had subpectoral tenodesis with an interference screw. Millett and colleagues²⁶ reported a mean postoperative pain score of 2.5 out of 10 for patients who had subpectoral interference screw fixation. Our patients reported a mean pain score of 12.6 out of 100 after minimum 12-month follow-up. We also assessed for pain in the intertubercular groove during palpation. Although some studies have shown that groove pain was eliminated by subpectoral biceps tenodesis,⁵ 3 patients in our study had pain on groove palpation. The cause of this residual pain is unclear, but some studies have suggested a chronic degenerative pathologic process that occurs while the tendon is within the biceps groove.²⁷ Removing the tendon from the groove may not remove the underlying cause of pain.

Our patients’ mean DASH score was 15.15 (within the excellent range). Normative mean (SD) DASH score for the general population is 10.1 (14.68).²⁸

Functional strength of forearm supination, shoulder ROM, and elbow ROM are objective measures of patient performance after fixation. On Cybex testing, Phillips and colleagues²⁹ found no difference in forearm supination strength or elbow flexion (compared with contralateral arm) after biceps tenodesis or conservative treatment for proximal biceps ruptures. Shank and colleagues³⁰ compared elbow flexion and supination strength of the affected and unaffected arms after suture anchor subpectoral biceps tenodesis. There was no significant difference in Cybex results, but there was a 14% to 15% loss of average strength in the tenodesed versus nonsurgical arm. In the present study, we found a significant difference in forearm supination strength between the operated and nonoperated arms, but with only a 7% loss of average strength in the operated arms. The difference in strength ranged from 1.59 to 17.11 pounds, which may not be clinically significant, as supination strength ranged from 60 to 270 pounds.

Of the 18 patients in this study, 9 had surgery on the dominant arm, and the other 9 had surgery on the nondominant arm. Examining the effect of arm dominance on results revealed that patients with surgery on the nondominant arm tended to have substantially reduced supination strength in that arm vs the dominant arm. There was an 11% loss of average strength for nondominant vs dominant arms that had surgery. Examining nondominant arms only revealed a 13% loss of strength for operated vs nonoperated arms. There was no difference in forearm supination strengths between nonoperated arms (dominant vs nondominant) or between dominant arms (operated vs nonoperated). This suggests that, though hand dominance may not play a significant role in control patients’ forearm supination strength,³⁰ it may have a substantial effect on surgical patients’ ability to regain strength when the nondominant arm is the surgical arm.
One objective of this study was to measure the distance between the biceps cortical button on the posterior humeral cortex and the AN/PCHA neurovascular bundle. The AN bundles with the PCHA posterior to the humeral neck.^31-33 As the AN travels with the PCHA, and the PCHA has been reliably identified with Doppler ultrasonography,^34-36 the PCHA was used as a marker for the AN in this study. Our bicortical button technique places the button on the posterior aspect of the humerus, making AN and PCHA the nearest at-risk neurovascular structures. None of our patients had symptoms of AN damage. However, 2 patients indicated pain in the posterior aspect of the humerus during deltoid activation. Distance from the neurovascular structures to the button was 48 mm in one patient and 13.6 mm in the other. DASH scores were 43 and 27, respectively. Both patients’ 1-year pain score was 30. The first patient underwent arthroscopic acromioplasty, distal clavicle resection, and microfracture of the glenoid surface in addition to the subpectoral biceps tenodesis; the second underwent subacromial decompression and distal clavicle resection in addition to the subpectoral biceps tenodesis. Whether the associated pathology contributed to their persistent pain is unknown. However, given the distance from AN/PCHA to button, it is unlikely that their pain was a result of neurovascular compromise from the procedure.

Advantages of the cortical button include the ability to drill a smaller hole in the humerus for fixation, compared with the hole drilled for an interference screw. Despite the biomechanical strength of the screw, large (8 mm) cortical violations have been associated with increased fracture risk of the proximal humerus.^37,38 The tendon may experience less trauma than that caused by being twisted against an interference screw, the most common location of failure of which is the tendon–screw interface.³⁹ In addition, tendon healing may be improved through circumferential healing in the cortical button tunnel.

A concern of using a bicortical button for fixation is drilling through the posterior cortex, because of the proximity of the posterior neurovascular structures. In a case in which the posterior cord was injured, Rhee and colleagues⁴⁰ used a suture pullout technique whereby a Beath pin was passed out of the posterior humerus and soft tissues to then hold tension on the biceps tendon during the tenodesis. The radial nerve potentially could have been injured by pin overpenetration or by becoming wrapped up in the soft tissues as the pin was spinning through them. In our technique, the posterior humeral cortex is drilled cautiously to avoid overpenetration and possibly getting the posterior soft tissues wrapped up in the guide pin. No AN injuries have been reported with this technique. Mean distance from AN to posterior cortical button in this study was 18.17 mm. In 2 cadaver studies of bicortical drilling for subpectoral biceps tenodesis, the ANs were 25.1 mm and 36.7 mm from the posterior drill hole.^41,21

Limitations of this study included its design (case series) and limited number of follow-up patients. Of the 28 consecutive patients identified for the study, 10 did not undergo the clinical examination, as they either lived more than 3 hours away (8 patients) or could not be contacted (2 patients). Another study limitation was the inability to directly image ANs with ultrasound. Therefore, measurements of the distance from the PCHA to the button were used to estimate the distance from the AN/PCHA neurovascular bundle to the button.

In this study, functional outcomes were excellent, and there were no tenodesis failures or neurovascular complications. These preliminary findings indicate that subpectoral biceps tenodesis with a bicortical button is a viable treatment option for patients with the appropriate indications for this procedure.

Over the years, operative treatment of biceps pathology has escalated, likely secondary to increased identification and successful clinical outcomes. Although its true function remains controversial, the biceps tendon has been well accepted as a primary pain generator in the anterior aspect of the shoulder.^1,2 Biceps pathology involves a spectrum of often overlapping findings—varying degrees of tearing, tendinitis, and instability. Pathology may be isolated or may present in association with other shoulder conditions, including impingement, bursitis, rotator cuff tears, SLAP (superior labral tear anterior to posterior) lesions, and acromioclavicular disorders.³

Operative treatment of disease of the long head of the biceps mandates an initial choice of tenotomy or tenodesis. Which approach is superior is controversial.^4-6 Although tenotomy and tenodesis have comparably favorable clinical results, tenodesis is often recommended, particularly for younger, active patients, mostly because cosmetic deformity is possible with tenotomy.

Tenodesis may be performed arthroscopically or through an open incision, and the biceps tendon may be placed anywhere from in the joint to under the tendon of the pectoralis major tendon. In many recent biomechanical studies, interference screws had higher load to failure and improved stiffness in comparison with other fixation methods.^7-19 Most of those studies focused on fixation in a subpectoral location. To our knowledge, only 2 studies of soft-tissue fixation have compared the percutaneous intra-articular transtendon (PITT) technique with other popular tenodesis techniques.^20,21 The PITT technique demonstrated a common failure point, with sutures pulling through the tendon substance. It was hypothesized that adding a locking loop to the PITT suture configuration would further improve fixation.

We conducted a study to compare the biomechanical characteristics of 2 techniques for all-arthroscopic proximal biceps tenodesis: bioabsorbable interference screw (Biceptor; Smith & Nephew) and a locking-loop PITT modification developed at our institution.

Methods

Sixteen nonembalmed fresh-frozen human cadaveric shoulders (8 pairs: 3 male, 5 female) were used in this study. Mean specimen age was 55 years (range, 51-59 years). The specimens showed no evidence of high-grade osteoarthritic changes, biceps tendon fraying or tearing, biceps pulley lesions, or full-thickness rotator cuff tears. They were thawed at room temperature for 24 hours before the procedure.

In each pair, 1 shoulder was randomized to be treated with 1 of 2 arthroscopic biceps tenodesis techniques—modified PITT or Biceptor interference screw—and the other shoulder was treated with the other technique. Surgery was performed in an open fashion, and every attempt was made to simulate the arthroscopic approach. In all shoulders, biomechanical testing was completed immediately after tenodesis.

Modified PITT Technique

In an outside-in fashion, an 18-gauge spinal needle was used to pierce the transverse humeral ligament, the lateral aspect of the rotator interval tissue, and the biceps tendon. A second needle was then passed in similar fashion, piercing the biceps tendon just adjacent to the first needle (Figure 1A). A 0-polydioxanone monofilament suture (0-PDS; Ethicon, Johnson & Johnson) was threaded through the first needle and used to shuttle a single No. 2 braided nonabsorbable polyethylene suture (MaxBraid; Biomet Sports Medicine) back through the biceps tendon.

At this point, the free end of the nonabsorbable suture, which comes out of the anterior cannula during an arthroscopic procedure, was passed back into the glenohumeral joint (using a suture grasper), looped over the top of the biceps tendon, and brought back out of the joint anteriorly, thereby creating a locking loop around the tendon (Figure 1B). A shuttle suture (0-PDS) passed through the second needle was used to bring that anterior limb of nonabsorbable suture back through the biceps tendon, completing the stitch configuration (Figure 1C).

This process was repeated with another nonabsorbable suture. After suture passing was completed, the biceps was detached from its insertion at the superior labrum. The 2 nonabsorbable sutures, which would later be retrieved from the subacromial space, were then tied in standard fashion, securing the biceps tendon to the transverse humeral ligament/rotator interval tissue (Figure 1D).

Biceptor Interference Screw Technique

The interference screw technique was performed in accordance with the manufacturer’s operative instructions.²² An 8 × 25-mm polyetheretherketone interference screw was used in all specimens, and the medium tendon fork was used to maintain tension on the biceps tendon during fixation (Figure 2A).

A 2.4-mm guide wire was inserted perpendicular to the humeral shaft, at the planned site of tenodesis, 10 mm distal to the entrance of the bicipital groove. An 8-mm cannulated reamer was passed over the wire, and a 30-mm tunnel was drilled (Figure 2B). The proximal part of the tendon was advanced into the center of the tunnel using the tendon fork (Figure 2C), and the tendon was held at the bottom of the tunnel with a 1.5-mm guide pin. The tendon fork was removed, and the cannulated interference screw was inserted over the guide pin between the 2 limbs of the biceps tendon (Figure 2D). The tendon was closely monitored to ensure it was not wrapped up when the screw was placed.

Biomechanical Testing

After each tenodesis, the humerus was amputated 5 inches distal to the fixation site. All extraneous soft tissue was dissected away, leaving the distal aspect of the biceps tendon as a free graft. Each proximal humerus–biceps tendon construct was then mounted on a materials testing machine. A custom-designed soft-tissue clamp was used to secure the distal aspect of the biceps tendon to the test actuator and load cell (Figure 3A). A custom-designed jig was used to stabilize the proximal humerus to the platform of the materials testing machine (Figure 3B). The specimens were mounted so that the line of pull throughout the testing protocol was applied parallel to the long axis of the humerus, thereby approximating the in vivo biceps force vector (Figure 3C). Digital cameras recorded each test for analysis of the mechanism of failure for each specimen. Marker dots were drawn on each tendon to assess tendon stretch before construct failure.

The tendons were preloaded to 10 N and then cycled at 0 to 50 N for 100 cycles at 1 Hz. After cyclic loading, axial load to failure was performed at a rate of 1.0 mm per second until a peak load was observed and subsequent loading led to tendon elongation with no further increase in load. Displacement and force applied during cyclic loading and load to failure were recorded. Stiffness was then calculated as the slope of the linear portion of the force-displacement curve using the least mean squares approach. Mechanism of failure was documented for each specimen.

Statistical Analysis

Analyzing our preliminary data with G*Power, we determined that a total sample size of 8 would be required (effect size [Cohen dz] was 1, α error probability was .05, power was .8). We hypothesized that the ultimate strength and stiffness of one group would be less than 1 SD above those of the other group. Paired t test with significance set at P < .05 was used to compare the techniques.

Results

Both repair constructs exhibited standard load-displacement curves, with a linear increase in load with displacement until the point of failure, at which time further displacement occurred with no discernible increase in load (Figure 4). Ultimate load to failure is determined as the highest point of the curve, and stiffness is calculated as the slope of the load-displacement curve.

Mean axial displacement parallel to the shaft of the humerus with cyclic loading was 7.1 mm with the modified PITT technique and 7.9 mm with the interference screw technique. There was no macroscopically visible high-grade tearing or slippage of the biceps tendon in any specimen with cyclic loading for either repair construct.

Mean (SD) ultimate load to failure was significantly (P = .003) higher with the modified PITT technique, 157 (41) N, than with the interference screw technique, 107 (29) N; actual effect size (Cohen dz) was 1.19, difference of means was 50 N, and pooled SD was 42 N. The interference screw technique yielded significantly (P = .010) more mean (SD) stiffness, 38.7 (14.7) N/mm, than the modified PITT technique, 15.8 (9.1) N/mm; actual effect size (Cohen dz) was 1.37, difference of means was 22.9 N/mm, and pooled SD was 16.7 N/mm.

In the interference screw technique, the mode of failure was consistent. Of the 8 specimens, 7 failed at the screw–tendon interface at the distal aspect of the tunnel; in the eighth specimen, the entire tendon pulled out from under the screw construct. In the modified PITT technique, there was more variability in failure: tendon slipped through suture (4 specimens), tendon/suture construct as unit pulled through transverse ligament/rotator interval tissue (3), and suture failure (1).

Discussion

This study was the first to directly compare a bony interference screw technique with a soft-tissue technique (modified PITT). Fixation strength is crucial. A load of 112 N is applied to the long head of the biceps tendon when a person holds 1 kg of weight in the hand with the elbow at 90° flexion.²² As mean (SD) ultimate load to failure was 157 (41) N with the modified PITT technique and 107 (29) N with the interference screw technique in this study, the interference screw can be recommended only with some hesitation.

The interference screw was stiffer with cyclic loading—an expected outcome, as it was secured to rigid bone—vs soft tissue, as in the modified PITT technique. Although the clinical implications for the modified PITT technique are unknown, more than likely, with the tendon being secured to soft tissue, there will be scarring over time.

In laboratory testing of biceps tenodesis constructs, interference screw fixation has had superior load-to-failure characteristics in comparisons with other fixation methods. Golish and colleagues¹³ found significantly higher load to failure with a biotenodesis screw than with a double-loaded suture anchor for subpectoral tenodesis. Testing similar implants, in a location more proximal in the bicipital groove, Richards and Burkhart¹⁴ likewise found superior fixation strength with an interference screw. Ozalay and colleagues¹⁶ found superior strength in an interference screw compared with suture anchor, keyhole, and bone tunnel in sheep. In a pig model, the highest ultimate load to failure was found in an interference screw—vs keyhole, bone tunnel, suture anchor, and ligament washer.¹⁹ Load to failure for the interference screw in these studies ranged from 170 N to over 400 N.^13,14,16,19

A few other investigators have studied the Biceptor interference screw. Slabaugh and colleagues¹⁵ found a mean (SD) load to failure of 173.9 (27.2) N for all specimens tested. Patzer and colleagues^9,17 found that the mean (SD) ultimate load to failure with the Biceptor proximal interference screw, 173.9 (27.2) N, was superior to that of a suture anchor.

The mean (SD) ultimate load to failure reported for the Biceptor interference screw in the present study, 107 (29) N, is lower than the values reported in the other studies—not only for the Biceptor screw but for interference screws in general. Nevertheless, we performed the technique as the manufacturer recommended.²² Our results were consistent across all specimens studied. Interestingly, in the study by Slabaugh and colleagues,¹⁵ 7 specimens failed at the tendon–screw interface during cyclic testing and were not included in the analysis of ultimate load to failure. As these specimens failed at a load between 5 N and 70 N, including their data would have significantly lowered the mean load to failure.

Concern over the Biceptor interference screw’s lower failure load relative to that of other interference screws has been raised before.^9,17 A major issue is possible overstuffing of the humeral tunnel, as the hole is reamed the same size as the screw. With the Biceptor, the proximal and distal portions of the tendon are placed in the tunnel in a U-shaped configuration with the screw between these limbs. The idea is that the 2 biceps tendon limbs might become abraded and consecutively weaken as the screw is inserted between the tendon limbs, more so than with a single loop. This idea was suggested by the typical longitudinal tendon splitting that occurs at the screw–tendon interface at the distal aspect of the tunnel.²³ In the present study, consistent failure (Figures 5A-5C) at the distal aspect of the screw–tendon junction supported the idea that the tendon is abraded during placement of the interference screw or during the friction-causing 90° turn the tendon takes into the bone on loading. There is no way to quantitatively examine tendon quality before interference screw placement, but on gross inspection all the tendons were of good quality. Slabaugh and colleagues¹⁵ also found consistent failure at the screw–tunnel interface.

The PITT technique has been described as a simple all-arthroscopic soft-tissue technique for biceps tenodesis.^23,24 Subsequently developed soft-tissue techniques have demonstrated clinical benefits.^25-27 Proposed advantages of these techniques are lower cost associated with decreased implant needs, no reliance on quality of bone for fixation, suturing while biceps tendon is still attached to anchor (anatomical tension is closely reproduced), and less interference with any subsequent use of magnetic resonance imaging for diagnostic purposes in the shoulder.

There have been only 2 biomechanical studies of the PITT technique. Lopez-Vidriero and colleagues²⁰ compared the biomechanical properties of the PITT and suture anchor techniques in a human cadaveric laboratory study and found that the PITT technique had mean (SD) ultimate load to failure of 142.7 (30.9) N and mean (SD) stiffness of 13.3 (3) N/mm. They observed consistent suture pullout through the tendon substance during failure, which suggests the most important factor for strength is the quality of the biceps tendon. Su and colleagues²¹ found biomechanically inferior results of the classic PITT technique as compared with the interference screw technique.

This article provides the first description of the modified PITT technique. Our mean (SD) load to failure of the modified PITT technique was 157 (41) N, slightly higher than that reported for the classic PITT technique, albeit under a different setup.²⁰ There was more variation in ultimate load to failure in our study than in previous studies, which could be secondary to tissue quality. As the modified PITT technique relies on surrounding tissue holding the biceps in place, this tissue would need to be of good quality and strength to obtain strong fixation. A possible concern is that placing stitches in the rotator interval could increase the risk of shoulder stiffness, but this has not been encountered clinically.

A more variable mechanism of failure was also found in the present study. Although half the specimens failed by suture pullout through the tendon, similar to what Lopez-Vidriero and colleagues²⁰ described, 3 of our 8 specimens failed with the entire biceps tendon–suture construct pulling through the transverse ligament tissue, and 1 specimen failed by suture breakage. Although these numbers are too small for making definitive statements, our modified PITT technique may add some security to the tendon–suture construct. Such added security may be of particular value in the setting of poor-quality, diseased tendon tissue, and the construct may be more limited by the strength of surrounding tissues. In addition, if failure occurs at the suture transverse humeral ligament–rotator interval interface, more surrounding rotator interval tissue can be incorporated into the tenodesis to decrease the likelihood of failure through this mechanism.

This study had several limitations. First, it was a time zero study in a cadaveric model with simulated biomechanical loading. As such, it provided information only on initial fixation strength and could not prove any superior clinical outcomes or account for any biological changes with healing that occurred over time. Second, the study may have been underpowered, though sample size was chosen in accordance with other cadaveric biomechanical studies. Third, all procedures were performed in an open manner, simulating the arthroscopic approach. Particularly in the setting of the modified PITT technique, this represented a best case scenario. Spinal needles and subsequent sutures were easily passed under direct visualization through the transverse humeral ligament, rotator interval, and biceps tendon. There is likely marked variability in this step during arthroscopy in which visualization is more limited, as in the setting of concomitant procedures, such as subacromial decompression or rotator cuff repair. In addition, all tendons tested were normal in appearance and gave no indication of chronic degenerative changes.

Another study limitation is that we did not quantify bone mineral density, which if poor would have affected interference screw strength. However, mean specimen age was 55 years, minimizing chances of poor bone quality. In addition, 7 of the 8 failures in the interference screw group occurred not with pullout but at the screw–tendon junction, suggesting poor bone quality was not a significant factor. As tendon diameter was not measured before the procedures were performed, there is the possibility it could have been better in the modified PITT group and worse in the interference screw group because of tunnel crowding, as noted.

Over the years, operative treatment of biceps pathology has escalated, likely secondary to increased identification and successful clinical outcomes. Although its true function remains controversial, the biceps tendon has been well accepted as a primary pain generator in the anterior aspect of the shoulder.^1,2 Biceps pathology involves a spectrum of often overlapping findings—varying degrees of tearing, tendinitis, and instability. Pathology may be isolated or may present in association with other shoulder conditions, including impingement, bursitis, rotator cuff tears, SLAP (superior labral tear anterior to posterior) lesions, and acromioclavicular disorders.³

Operative treatment of disease of the long head of the biceps mandates an initial choice of tenotomy or tenodesis. Which approach is superior is controversial.^4-6 Although tenotomy and tenodesis have comparably favorable clinical results, tenodesis is often recommended, particularly for younger, active patients, mostly because cosmetic deformity is possible with tenotomy.

Tenodesis may be performed arthroscopically or through an open incision, and the biceps tendon may be placed anywhere from in the joint to under the tendon of the pectoralis major tendon. In many recent biomechanical studies, interference screws had higher load to failure and improved stiffness in comparison with other fixation methods.^7-19 Most of those studies focused on fixation in a subpectoral location. To our knowledge, only 2 studies of soft-tissue fixation have compared the percutaneous intra-articular transtendon (PITT) technique with other popular tenodesis techniques.^20,21 The PITT technique demonstrated a common failure point, with sutures pulling through the tendon substance. It was hypothesized that adding a locking loop to the PITT suture configuration would further improve fixation.

We conducted a study to compare the biomechanical characteristics of 2 techniques for all-arthroscopic proximal biceps tenodesis: bioabsorbable interference screw (Biceptor; Smith & Nephew) and a locking-loop PITT modification developed at our institution.

Methods

Sixteen nonembalmed fresh-frozen human cadaveric shoulders (8 pairs: 3 male, 5 female) were used in this study. Mean specimen age was 55 years (range, 51-59 years). The specimens showed no evidence of high-grade osteoarthritic changes, biceps tendon fraying or tearing, biceps pulley lesions, or full-thickness rotator cuff tears. They were thawed at room temperature for 24 hours before the procedure.

In each pair, 1 shoulder was randomized to be treated with 1 of 2 arthroscopic biceps tenodesis techniques—modified PITT or Biceptor interference screw—and the other shoulder was treated with the other technique. Surgery was performed in an open fashion, and every attempt was made to simulate the arthroscopic approach. In all shoulders, biomechanical testing was completed immediately after tenodesis.

Modified PITT Technique

In an outside-in fashion, an 18-gauge spinal needle was used to pierce the transverse humeral ligament, the lateral aspect of the rotator interval tissue, and the biceps tendon. A second needle was then passed in similar fashion, piercing the biceps tendon just adjacent to the first needle (Figure 1A). A 0-polydioxanone monofilament suture (0-PDS; Ethicon, Johnson & Johnson) was threaded through the first needle and used to shuttle a single No. 2 braided nonabsorbable polyethylene suture (MaxBraid; Biomet Sports Medicine) back through the biceps tendon.

At this point, the free end of the nonabsorbable suture, which comes out of the anterior cannula during an arthroscopic procedure, was passed back into the glenohumeral joint (using a suture grasper), looped over the top of the biceps tendon, and brought back out of the joint anteriorly, thereby creating a locking loop around the tendon (Figure 1B). A shuttle suture (0-PDS) passed through the second needle was used to bring that anterior limb of nonabsorbable suture back through the biceps tendon, completing the stitch configuration (Figure 1C).

This process was repeated with another nonabsorbable suture. After suture passing was completed, the biceps was detached from its insertion at the superior labrum. The 2 nonabsorbable sutures, which would later be retrieved from the subacromial space, were then tied in standard fashion, securing the biceps tendon to the transverse humeral ligament/rotator interval tissue (Figure 1D).

Biceptor Interference Screw Technique

The interference screw technique was performed in accordance with the manufacturer’s operative instructions.²² An 8 × 25-mm polyetheretherketone interference screw was used in all specimens, and the medium tendon fork was used to maintain tension on the biceps tendon during fixation (Figure 2A).

A 2.4-mm guide wire was inserted perpendicular to the humeral shaft, at the planned site of tenodesis, 10 mm distal to the entrance of the bicipital groove. An 8-mm cannulated reamer was passed over the wire, and a 30-mm tunnel was drilled (Figure 2B). The proximal part of the tendon was advanced into the center of the tunnel using the tendon fork (Figure 2C), and the tendon was held at the bottom of the tunnel with a 1.5-mm guide pin. The tendon fork was removed, and the cannulated interference screw was inserted over the guide pin between the 2 limbs of the biceps tendon (Figure 2D). The tendon was closely monitored to ensure it was not wrapped up when the screw was placed.

Biomechanical Testing

After each tenodesis, the humerus was amputated 5 inches distal to the fixation site. All extraneous soft tissue was dissected away, leaving the distal aspect of the biceps tendon as a free graft. Each proximal humerus–biceps tendon construct was then mounted on a materials testing machine. A custom-designed soft-tissue clamp was used to secure the distal aspect of the biceps tendon to the test actuator and load cell (Figure 3A). A custom-designed jig was used to stabilize the proximal humerus to the platform of the materials testing machine (Figure 3B). The specimens were mounted so that the line of pull throughout the testing protocol was applied parallel to the long axis of the humerus, thereby approximating the in vivo biceps force vector (Figure 3C). Digital cameras recorded each test for analysis of the mechanism of failure for each specimen. Marker dots were drawn on each tendon to assess tendon stretch before construct failure.

The tendons were preloaded to 10 N and then cycled at 0 to 50 N for 100 cycles at 1 Hz. After cyclic loading, axial load to failure was performed at a rate of 1.0 mm per second until a peak load was observed and subsequent loading led to tendon elongation with no further increase in load. Displacement and force applied during cyclic loading and load to failure were recorded. Stiffness was then calculated as the slope of the linear portion of the force-displacement curve using the least mean squares approach. Mechanism of failure was documented for each specimen.

Statistical Analysis

Analyzing our preliminary data with G*Power, we determined that a total sample size of 8 would be required (effect size [Cohen dz] was 1, α error probability was .05, power was .8). We hypothesized that the ultimate strength and stiffness of one group would be less than 1 SD above those of the other group. Paired t test with significance set at P < .05 was used to compare the techniques.

Results

Both repair constructs exhibited standard load-displacement curves, with a linear increase in load with displacement until the point of failure, at which time further displacement occurred with no discernible increase in load (Figure 4). Ultimate load to failure is determined as the highest point of the curve, and stiffness is calculated as the slope of the load-displacement curve.

Mean axial displacement parallel to the shaft of the humerus with cyclic loading was 7.1 mm with the modified PITT technique and 7.9 mm with the interference screw technique. There was no macroscopically visible high-grade tearing or slippage of the biceps tendon in any specimen with cyclic loading for either repair construct.

Mean (SD) ultimate load to failure was significantly (P = .003) higher with the modified PITT technique, 157 (41) N, than with the interference screw technique, 107 (29) N; actual effect size (Cohen dz) was 1.19, difference of means was 50 N, and pooled SD was 42 N. The interference screw technique yielded significantly (P = .010) more mean (SD) stiffness, 38.7 (14.7) N/mm, than the modified PITT technique, 15.8 (9.1) N/mm; actual effect size (Cohen dz) was 1.37, difference of means was 22.9 N/mm, and pooled SD was 16.7 N/mm.

In the interference screw technique, the mode of failure was consistent. Of the 8 specimens, 7 failed at the screw–tendon interface at the distal aspect of the tunnel; in the eighth specimen, the entire tendon pulled out from under the screw construct. In the modified PITT technique, there was more variability in failure: tendon slipped through suture (4 specimens), tendon/suture construct as unit pulled through transverse ligament/rotator interval tissue (3), and suture failure (1).

Discussion

This study was the first to directly compare a bony interference screw technique with a soft-tissue technique (modified PITT). Fixation strength is crucial. A load of 112 N is applied to the long head of the biceps tendon when a person holds 1 kg of weight in the hand with the elbow at 90° flexion.²² As mean (SD) ultimate load to failure was 157 (41) N with the modified PITT technique and 107 (29) N with the interference screw technique in this study, the interference screw can be recommended only with some hesitation.

The interference screw was stiffer with cyclic loading—an expected outcome, as it was secured to rigid bone—vs soft tissue, as in the modified PITT technique. Although the clinical implications for the modified PITT technique are unknown, more than likely, with the tendon being secured to soft tissue, there will be scarring over time.

In laboratory testing of biceps tenodesis constructs, interference screw fixation has had superior load-to-failure characteristics in comparisons with other fixation methods. Golish and colleagues¹³ found significantly higher load to failure with a biotenodesis screw than with a double-loaded suture anchor for subpectoral tenodesis. Testing similar implants, in a location more proximal in the bicipital groove, Richards and Burkhart¹⁴ likewise found superior fixation strength with an interference screw. Ozalay and colleagues¹⁶ found superior strength in an interference screw compared with suture anchor, keyhole, and bone tunnel in sheep. In a pig model, the highest ultimate load to failure was found in an interference screw—vs keyhole, bone tunnel, suture anchor, and ligament washer.¹⁹ Load to failure for the interference screw in these studies ranged from 170 N to over 400 N.^13,14,16,19

A few other investigators have studied the Biceptor interference screw. Slabaugh and colleagues¹⁵ found a mean (SD) load to failure of 173.9 (27.2) N for all specimens tested. Patzer and colleagues^9,17 found that the mean (SD) ultimate load to failure with the Biceptor proximal interference screw, 173.9 (27.2) N, was superior to that of a suture anchor.

The mean (SD) ultimate load to failure reported for the Biceptor interference screw in the present study, 107 (29) N, is lower than the values reported in the other studies—not only for the Biceptor screw but for interference screws in general. Nevertheless, we performed the technique as the manufacturer recommended.²² Our results were consistent across all specimens studied. Interestingly, in the study by Slabaugh and colleagues,¹⁵ 7 specimens failed at the tendon–screw interface during cyclic testing and were not included in the analysis of ultimate load to failure. As these specimens failed at a load between 5 N and 70 N, including their data would have significantly lowered the mean load to failure.

Concern over the Biceptor interference screw’s lower failure load relative to that of other interference screws has been raised before.^9,17 A major issue is possible overstuffing of the humeral tunnel, as the hole is reamed the same size as the screw. With the Biceptor, the proximal and distal portions of the tendon are placed in the tunnel in a U-shaped configuration with the screw between these limbs. The idea is that the 2 biceps tendon limbs might become abraded and consecutively weaken as the screw is inserted between the tendon limbs, more so than with a single loop. This idea was suggested by the typical longitudinal tendon splitting that occurs at the screw–tendon interface at the distal aspect of the tunnel.²³ In the present study, consistent failure (Figures 5A-5C) at the distal aspect of the screw–tendon junction supported the idea that the tendon is abraded during placement of the interference screw or during the friction-causing 90° turn the tendon takes into the bone on loading. There is no way to quantitatively examine tendon quality before interference screw placement, but on gross inspection all the tendons were of good quality. Slabaugh and colleagues¹⁵ also found consistent failure at the screw–tunnel interface.

The PITT technique has been described as a simple all-arthroscopic soft-tissue technique for biceps tenodesis.^23,24 Subsequently developed soft-tissue techniques have demonstrated clinical benefits.^25-27 Proposed advantages of these techniques are lower cost associated with decreased implant needs, no reliance on quality of bone for fixation, suturing while biceps tendon is still attached to anchor (anatomical tension is closely reproduced), and less interference with any subsequent use of magnetic resonance imaging for diagnostic purposes in the shoulder.

There have been only 2 biomechanical studies of the PITT technique. Lopez-Vidriero and colleagues²⁰ compared the biomechanical properties of the PITT and suture anchor techniques in a human cadaveric laboratory study and found that the PITT technique had mean (SD) ultimate load to failure of 142.7 (30.9) N and mean (SD) stiffness of 13.3 (3) N/mm. They observed consistent suture pullout through the tendon substance during failure, which suggests the most important factor for strength is the quality of the biceps tendon. Su and colleagues²¹ found biomechanically inferior results of the classic PITT technique as compared with the interference screw technique.

This article provides the first description of the modified PITT technique. Our mean (SD) load to failure of the modified PITT technique was 157 (41) N, slightly higher than that reported for the classic PITT technique, albeit under a different setup.²⁰ There was more variation in ultimate load to failure in our study than in previous studies, which could be secondary to tissue quality. As the modified PITT technique relies on surrounding tissue holding the biceps in place, this tissue would need to be of good quality and strength to obtain strong fixation. A possible concern is that placing stitches in the rotator interval could increase the risk of shoulder stiffness, but this has not been encountered clinically.

A more variable mechanism of failure was also found in the present study. Although half the specimens failed by suture pullout through the tendon, similar to what Lopez-Vidriero and colleagues²⁰ described, 3 of our 8 specimens failed with the entire biceps tendon–suture construct pulling through the transverse ligament tissue, and 1 specimen failed by suture breakage. Although these numbers are too small for making definitive statements, our modified PITT technique may add some security to the tendon–suture construct. Such added security may be of particular value in the setting of poor-quality, diseased tendon tissue, and the construct may be more limited by the strength of surrounding tissues. In addition, if failure occurs at the suture transverse humeral ligament–rotator interval interface, more surrounding rotator interval tissue can be incorporated into the tenodesis to decrease the likelihood of failure through this mechanism.

This study had several limitations. First, it was a time zero study in a cadaveric model with simulated biomechanical loading. As such, it provided information only on initial fixation strength and could not prove any superior clinical outcomes or account for any biological changes with healing that occurred over time. Second, the study may have been underpowered, though sample size was chosen in accordance with other cadaveric biomechanical studies. Third, all procedures were performed in an open manner, simulating the arthroscopic approach. Particularly in the setting of the modified PITT technique, this represented a best case scenario. Spinal needles and subsequent sutures were easily passed under direct visualization through the transverse humeral ligament, rotator interval, and biceps tendon. There is likely marked variability in this step during arthroscopy in which visualization is more limited, as in the setting of concomitant procedures, such as subacromial decompression or rotator cuff repair. In addition, all tendons tested were normal in appearance and gave no indication of chronic degenerative changes.

Another study limitation is that we did not quantify bone mineral density, which if poor would have affected interference screw strength. However, mean specimen age was 55 years, minimizing chances of poor bone quality. In addition, 7 of the 8 failures in the interference screw group occurred not with pullout but at the screw–tendon junction, suggesting poor bone quality was not a significant factor. As tendon diameter was not measured before the procedures were performed, there is the possibility it could have been better in the modified PITT group and worse in the interference screw group because of tunnel crowding, as noted.

Over the years, operative treatment of biceps pathology has escalated, likely secondary to increased identification and successful clinical outcomes. Although its true function remains controversial, the biceps tendon has been well accepted as a primary pain generator in the anterior aspect of the shoulder.^1,2 Biceps pathology involves a spectrum of often overlapping findings—varying degrees of tearing, tendinitis, and instability. Pathology may be isolated or may present in association with other shoulder conditions, including impingement, bursitis, rotator cuff tears, SLAP (superior labral tear anterior to posterior) lesions, and acromioclavicular disorders.³

Operative treatment of disease of the long head of the biceps mandates an initial choice of tenotomy or tenodesis. Which approach is superior is controversial.^4-6 Although tenotomy and tenodesis have comparably favorable clinical results, tenodesis is often recommended, particularly for younger, active patients, mostly because cosmetic deformity is possible with tenotomy.

Tenodesis may be performed arthroscopically or through an open incision, and the biceps tendon may be placed anywhere from in the joint to under the tendon of the pectoralis major tendon. In many recent biomechanical studies, interference screws had higher load to failure and improved stiffness in comparison with other fixation methods.^7-19 Most of those studies focused on fixation in a subpectoral location. To our knowledge, only 2 studies of soft-tissue fixation have compared the percutaneous intra-articular transtendon (PITT) technique with other popular tenodesis techniques.^20,21 The PITT technique demonstrated a common failure point, with sutures pulling through the tendon substance. It was hypothesized that adding a locking loop to the PITT suture configuration would further improve fixation.

We conducted a study to compare the biomechanical characteristics of 2 techniques for all-arthroscopic proximal biceps tenodesis: bioabsorbable interference screw (Biceptor; Smith & Nephew) and a locking-loop PITT modification developed at our institution.

Methods

Sixteen nonembalmed fresh-frozen human cadaveric shoulders (8 pairs: 3 male, 5 female) were used in this study. Mean specimen age was 55 years (range, 51-59 years). The specimens showed no evidence of high-grade osteoarthritic changes, biceps tendon fraying or tearing, biceps pulley lesions, or full-thickness rotator cuff tears. They were thawed at room temperature for 24 hours before the procedure.

In each pair, 1 shoulder was randomized to be treated with 1 of 2 arthroscopic biceps tenodesis techniques—modified PITT or Biceptor interference screw—and the other shoulder was treated with the other technique. Surgery was performed in an open fashion, and every attempt was made to simulate the arthroscopic approach. In all shoulders, biomechanical testing was completed immediately after tenodesis.

Modified PITT Technique

In an outside-in fashion, an 18-gauge spinal needle was used to pierce the transverse humeral ligament, the lateral aspect of the rotator interval tissue, and the biceps tendon. A second needle was then passed in similar fashion, piercing the biceps tendon just adjacent to the first needle (Figure 1A). A 0-polydioxanone monofilament suture (0-PDS; Ethicon, Johnson & Johnson) was threaded through the first needle and used to shuttle a single No. 2 braided nonabsorbable polyethylene suture (MaxBraid; Biomet Sports Medicine) back through the biceps tendon.

At this point, the free end of the nonabsorbable suture, which comes out of the anterior cannula during an arthroscopic procedure, was passed back into the glenohumeral joint (using a suture grasper), looped over the top of the biceps tendon, and brought back out of the joint anteriorly, thereby creating a locking loop around the tendon (Figure 1B). A shuttle suture (0-PDS) passed through the second needle was used to bring that anterior limb of nonabsorbable suture back through the biceps tendon, completing the stitch configuration (Figure 1C).

This process was repeated with another nonabsorbable suture. After suture passing was completed, the biceps was detached from its insertion at the superior labrum. The 2 nonabsorbable sutures, which would later be retrieved from the subacromial space, were then tied in standard fashion, securing the biceps tendon to the transverse humeral ligament/rotator interval tissue (Figure 1D).

Biceptor Interference Screw Technique

The interference screw technique was performed in accordance with the manufacturer’s operative instructions.²² An 8 × 25-mm polyetheretherketone interference screw was used in all specimens, and the medium tendon fork was used to maintain tension on the biceps tendon during fixation (Figure 2A).

A 2.4-mm guide wire was inserted perpendicular to the humeral shaft, at the planned site of tenodesis, 10 mm distal to the entrance of the bicipital groove. An 8-mm cannulated reamer was passed over the wire, and a 30-mm tunnel was drilled (Figure 2B). The proximal part of the tendon was advanced into the center of the tunnel using the tendon fork (Figure 2C), and the tendon was held at the bottom of the tunnel with a 1.5-mm guide pin. The tendon fork was removed, and the cannulated interference screw was inserted over the guide pin between the 2 limbs of the biceps tendon (Figure 2D). The tendon was closely monitored to ensure it was not wrapped up when the screw was placed.

Biomechanical Testing

After each tenodesis, the humerus was amputated 5 inches distal to the fixation site. All extraneous soft tissue was dissected away, leaving the distal aspect of the biceps tendon as a free graft. Each proximal humerus–biceps tendon construct was then mounted on a materials testing machine. A custom-designed soft-tissue clamp was used to secure the distal aspect of the biceps tendon to the test actuator and load cell (Figure 3A). A custom-designed jig was used to stabilize the proximal humerus to the platform of the materials testing machine (Figure 3B). The specimens were mounted so that the line of pull throughout the testing protocol was applied parallel to the long axis of the humerus, thereby approximating the in vivo biceps force vector (Figure 3C). Digital cameras recorded each test for analysis of the mechanism of failure for each specimen. Marker dots were drawn on each tendon to assess tendon stretch before construct failure.

The tendons were preloaded to 10 N and then cycled at 0 to 50 N for 100 cycles at 1 Hz. After cyclic loading, axial load to failure was performed at a rate of 1.0 mm per second until a peak load was observed and subsequent loading led to tendon elongation with no further increase in load. Displacement and force applied during cyclic loading and load to failure were recorded. Stiffness was then calculated as the slope of the linear portion of the force-displacement curve using the least mean squares approach. Mechanism of failure was documented for each specimen.

Statistical Analysis

Analyzing our preliminary data with G*Power, we determined that a total sample size of 8 would be required (effect size [Cohen dz] was 1, α error probability was .05, power was .8). We hypothesized that the ultimate strength and stiffness of one group would be less than 1 SD above those of the other group. Paired t test with significance set at P < .05 was used to compare the techniques.

Results

Both repair constructs exhibited standard load-displacement curves, with a linear increase in load with displacement until the point of failure, at which time further displacement occurred with no discernible increase in load (Figure 4). Ultimate load to failure is determined as the highest point of the curve, and stiffness is calculated as the slope of the load-displacement curve.

Mean axial displacement parallel to the shaft of the humerus with cyclic loading was 7.1 mm with the modified PITT technique and 7.9 mm with the interference screw technique. There was no macroscopically visible high-grade tearing or slippage of the biceps tendon in any specimen with cyclic loading for either repair construct.

Mean (SD) ultimate load to failure was significantly (P = .003) higher with the modified PITT technique, 157 (41) N, than with the interference screw technique, 107 (29) N; actual effect size (Cohen dz) was 1.19, difference of means was 50 N, and pooled SD was 42 N. The interference screw technique yielded significantly (P = .010) more mean (SD) stiffness, 38.7 (14.7) N/mm, than the modified PITT technique, 15.8 (9.1) N/mm; actual effect size (Cohen dz) was 1.37, difference of means was 22.9 N/mm, and pooled SD was 16.7 N/mm.

In the interference screw technique, the mode of failure was consistent. Of the 8 specimens, 7 failed at the screw–tendon interface at the distal aspect of the tunnel; in the eighth specimen, the entire tendon pulled out from under the screw construct. In the modified PITT technique, there was more variability in failure: tendon slipped through suture (4 specimens), tendon/suture construct as unit pulled through transverse ligament/rotator interval tissue (3), and suture failure (1).

Discussion

This study was the first to directly compare a bony interference screw technique with a soft-tissue technique (modified PITT). Fixation strength is crucial. A load of 112 N is applied to the long head of the biceps tendon when a person holds 1 kg of weight in the hand with the elbow at 90° flexion.²² As mean (SD) ultimate load to failure was 157 (41) N with the modified PITT technique and 107 (29) N with the interference screw technique in this study, the interference screw can be recommended only with some hesitation.

The interference screw was stiffer with cyclic loading—an expected outcome, as it was secured to rigid bone—vs soft tissue, as in the modified PITT technique. Although the clinical implications for the modified PITT technique are unknown, more than likely, with the tendon being secured to soft tissue, there will be scarring over time.

In laboratory testing of biceps tenodesis constructs, interference screw fixation has had superior load-to-failure characteristics in comparisons with other fixation methods. Golish and colleagues¹³ found significantly higher load to failure with a biotenodesis screw than with a double-loaded suture anchor for subpectoral tenodesis. Testing similar implants, in a location more proximal in the bicipital groove, Richards and Burkhart¹⁴ likewise found superior fixation strength with an interference screw. Ozalay and colleagues¹⁶ found superior strength in an interference screw compared with suture anchor, keyhole, and bone tunnel in sheep. In a pig model, the highest ultimate load to failure was found in an interference screw—vs keyhole, bone tunnel, suture anchor, and ligament washer.¹⁹ Load to failure for the interference screw in these studies ranged from 170 N to over 400 N.^13,14,16,19

A few other investigators have studied the Biceptor interference screw. Slabaugh and colleagues¹⁵ found a mean (SD) load to failure of 173.9 (27.2) N for all specimens tested. Patzer and colleagues^9,17 found that the mean (SD) ultimate load to failure with the Biceptor proximal interference screw, 173.9 (27.2) N, was superior to that of a suture anchor.

The mean (SD) ultimate load to failure reported for the Biceptor interference screw in the present study, 107 (29) N, is lower than the values reported in the other studies—not only for the Biceptor screw but for interference screws in general. Nevertheless, we performed the technique as the manufacturer recommended.²² Our results were consistent across all specimens studied. Interestingly, in the study by Slabaugh and colleagues,¹⁵ 7 specimens failed at the tendon–screw interface during cyclic testing and were not included in the analysis of ultimate load to failure. As these specimens failed at a load between 5 N and 70 N, including their data would have significantly lowered the mean load to failure.

Concern over the Biceptor interference screw’s lower failure load relative to that of other interference screws has been raised before.^9,17 A major issue is possible overstuffing of the humeral tunnel, as the hole is reamed the same size as the screw. With the Biceptor, the proximal and distal portions of the tendon are placed in the tunnel in a U-shaped configuration with the screw between these limbs. The idea is that the 2 biceps tendon limbs might become abraded and consecutively weaken as the screw is inserted between the tendon limbs, more so than with a single loop. This idea was suggested by the typical longitudinal tendon splitting that occurs at the screw–tendon interface at the distal aspect of the tunnel.²³ In the present study, consistent failure (Figures 5A-5C) at the distal aspect of the screw–tendon junction supported the idea that the tendon is abraded during placement of the interference screw or during the friction-causing 90° turn the tendon takes into the bone on loading. There is no way to quantitatively examine tendon quality before interference screw placement, but on gross inspection all the tendons were of good quality. Slabaugh and colleagues¹⁵ also found consistent failure at the screw–tunnel interface.

The PITT technique has been described as a simple all-arthroscopic soft-tissue technique for biceps tenodesis.^23,24 Subsequently developed soft-tissue techniques have demonstrated clinical benefits.^25-27 Proposed advantages of these techniques are lower cost associated with decreased implant needs, no reliance on quality of bone for fixation, suturing while biceps tendon is still attached to anchor (anatomical tension is closely reproduced), and less interference with any subsequent use of magnetic resonance imaging for diagnostic purposes in the shoulder.

There have been only 2 biomechanical studies of the PITT technique. Lopez-Vidriero and colleagues²⁰ compared the biomechanical properties of the PITT and suture anchor techniques in a human cadaveric laboratory study and found that the PITT technique had mean (SD) ultimate load to failure of 142.7 (30.9) N and mean (SD) stiffness of 13.3 (3) N/mm. They observed consistent suture pullout through the tendon substance during failure, which suggests the most important factor for strength is the quality of the biceps tendon. Su and colleagues²¹ found biomechanically inferior results of the classic PITT technique as compared with the interference screw technique.

This article provides the first description of the modified PITT technique. Our mean (SD) load to failure of the modified PITT technique was 157 (41) N, slightly higher than that reported for the classic PITT technique, albeit under a different setup.²⁰ There was more variation in ultimate load to failure in our study than in previous studies, which could be secondary to tissue quality. As the modified PITT technique relies on surrounding tissue holding the biceps in place, this tissue would need to be of good quality and strength to obtain strong fixation. A possible concern is that placing stitches in the rotator interval could increase the risk of shoulder stiffness, but this has not been encountered clinically.

A more variable mechanism of failure was also found in the present study. Although half the specimens failed by suture pullout through the tendon, similar to what Lopez-Vidriero and colleagues²⁰ described, 3 of our 8 specimens failed with the entire biceps tendon–suture construct pulling through the transverse ligament tissue, and 1 specimen failed by suture breakage. Although these numbers are too small for making definitive statements, our modified PITT technique may add some security to the tendon–suture construct. Such added security may be of particular value in the setting of poor-quality, diseased tendon tissue, and the construct may be more limited by the strength of surrounding tissues. In addition, if failure occurs at the suture transverse humeral ligament–rotator interval interface, more surrounding rotator interval tissue can be incorporated into the tenodesis to decrease the likelihood of failure through this mechanism.

This study had several limitations. First, it was a time zero study in a cadaveric model with simulated biomechanical loading. As such, it provided information only on initial fixation strength and could not prove any superior clinical outcomes or account for any biological changes with healing that occurred over time. Second, the study may have been underpowered, though sample size was chosen in accordance with other cadaveric biomechanical studies. Third, all procedures were performed in an open manner, simulating the arthroscopic approach. Particularly in the setting of the modified PITT technique, this represented a best case scenario. Spinal needles and subsequent sutures were easily passed under direct visualization through the transverse humeral ligament, rotator interval, and biceps tendon. There is likely marked variability in this step during arthroscopy in which visualization is more limited, as in the setting of concomitant procedures, such as subacromial decompression or rotator cuff repair. In addition, all tendons tested were normal in appearance and gave no indication of chronic degenerative changes.

Another study limitation is that we did not quantify bone mineral density, which if poor would have affected interference screw strength. However, mean specimen age was 55 years, minimizing chances of poor bone quality. In addition, 7 of the 8 failures in the interference screw group occurred not with pullout but at the screw–tendon junction, suggesting poor bone quality was not a significant factor. As tendon diameter was not measured before the procedures were performed, there is the possibility it could have been better in the modified PITT group and worse in the interference screw group because of tunnel crowding, as noted.

The International Antiviral Society–USA has updated its recommendations for the use of antiretroviral drugs to treat or to prevent HIV infection in adults.

In light of new evidence emerging since its 2014 report on antiretroviral drugs (ARVs), the International Antiviral Society–USA convened a panel of HIV experts to review data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences that would change previous recommendations or ratings. The resulting recommendations were published online in the Journal of the American Medical Association. (JAMA. 2016;316[2]:191-210. doi:10.1001/jama.2016.8900)

The panel concluded that newer data support the “widely accepted” recommendation that antiretroviral therapy (ART) should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. They said optimal initial regimens for most patients should include two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). The panel concluded that other effective regimens may include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with two NRTIs.

©grandeduc/Thinkstock

Also of note are the panel’s recommendations for certain special populations. The panel said HIV-infected pregnant women should initiate ART for their own health and to reduce the likelihood of HIV transmission to the infant. HIV-infected patients with hepatitis B virus (HBV) coinfection should initiate a recommended ART regimen that contains tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF), lamivudine or emtricitabine, and a third component.

In addition, the panel said ART should be started within the first 2 weeks after diagnosis for most acute opportunistic infections, with the possible exception of acute cryptococcal meningitis, and ART should be started within the first 2 weeks of initiation of tuberculosis treatment for those with CD4 cell counts of 50/mcL or less and within the first 2-8 weeks for those with CD4 cell counts above 50/mcL.

For prevention of HIV infection, the panel concluded that preexposure prophylaxis (PrEP) should be considered for anyone from a population whose HIV incidence is at least 2% per year, or for HIV-seronegative partners of HIV-infected persons who do not have viral suppression. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. Also, postexposure prophylaxis should be started as soon as possible after exposure.

For the complete list of ARV recommendations, see the report in JAMA (doi:10.1001/jama.2016.8900).

[email protected]

On Twitter @richpizzi

The International Antiviral Society–USA has updated its recommendations for the use of antiretroviral drugs to treat or to prevent HIV infection in adults.

In light of new evidence emerging since its 2014 report on antiretroviral drugs (ARVs), the International Antiviral Society–USA convened a panel of HIV experts to review data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences that would change previous recommendations or ratings. The resulting recommendations were published online in the Journal of the American Medical Association. (JAMA. 2016;316[2]:191-210. doi:10.1001/jama.2016.8900)

The panel concluded that newer data support the “widely accepted” recommendation that antiretroviral therapy (ART) should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. They said optimal initial regimens for most patients should include two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). The panel concluded that other effective regimens may include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with two NRTIs.

©grandeduc/Thinkstock

Also of note are the panel’s recommendations for certain special populations. The panel said HIV-infected pregnant women should initiate ART for their own health and to reduce the likelihood of HIV transmission to the infant. HIV-infected patients with hepatitis B virus (HBV) coinfection should initiate a recommended ART regimen that contains tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF), lamivudine or emtricitabine, and a third component.

In addition, the panel said ART should be started within the first 2 weeks after diagnosis for most acute opportunistic infections, with the possible exception of acute cryptococcal meningitis, and ART should be started within the first 2 weeks of initiation of tuberculosis treatment for those with CD4 cell counts of 50/mcL or less and within the first 2-8 weeks for those with CD4 cell counts above 50/mcL.

For prevention of HIV infection, the panel concluded that preexposure prophylaxis (PrEP) should be considered for anyone from a population whose HIV incidence is at least 2% per year, or for HIV-seronegative partners of HIV-infected persons who do not have viral suppression. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. Also, postexposure prophylaxis should be started as soon as possible after exposure.

For the complete list of ARV recommendations, see the report in JAMA (doi:10.1001/jama.2016.8900).

[email protected]

On Twitter @richpizzi

The International Antiviral Society–USA has updated its recommendations for the use of antiretroviral drugs to treat or to prevent HIV infection in adults.

In light of new evidence emerging since its 2014 report on antiretroviral drugs (ARVs), the International Antiviral Society–USA convened a panel of HIV experts to review data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences that would change previous recommendations or ratings. The resulting recommendations were published online in the Journal of the American Medical Association. (JAMA. 2016;316[2]:191-210. doi:10.1001/jama.2016.8900)

The panel concluded that newer data support the “widely accepted” recommendation that antiretroviral therapy (ART) should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. They said optimal initial regimens for most patients should include two nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). The panel concluded that other effective regimens may include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with two NRTIs.

©grandeduc/Thinkstock

Also of note are the panel’s recommendations for certain special populations. The panel said HIV-infected pregnant women should initiate ART for their own health and to reduce the likelihood of HIV transmission to the infant. HIV-infected patients with hepatitis B virus (HBV) coinfection should initiate a recommended ART regimen that contains tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF), lamivudine or emtricitabine, and a third component.

In addition, the panel said ART should be started within the first 2 weeks after diagnosis for most acute opportunistic infections, with the possible exception of acute cryptococcal meningitis, and ART should be started within the first 2 weeks of initiation of tuberculosis treatment for those with CD4 cell counts of 50/mcL or less and within the first 2-8 weeks for those with CD4 cell counts above 50/mcL.

For prevention of HIV infection, the panel concluded that preexposure prophylaxis (PrEP) should be considered for anyone from a population whose HIV incidence is at least 2% per year, or for HIV-seronegative partners of HIV-infected persons who do not have viral suppression. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. Also, postexposure prophylaxis should be started as soon as possible after exposure.

For the complete list of ARV recommendations, see the report in JAMA (doi:10.1001/jama.2016.8900).

[email protected]

On Twitter @richpizzi

The spinal vacuum sign or vacuum phenomenon (VP) is the radiographic finding of an air-density linear radiolucency in the intervertebral disc or vertebral body. The result of a gaseous accumulation, it is often a diagnostic sign of disc degeneration as well as a rare sign of infection, Schmorl node formation, or osteonecrosis.^1,2 Although the VP was first described on plain radiographs, it is better seen on computed tomography (CT).³ Multiple studies have found a possible association between the VP and nonunion in diaphyseal fractures,⁴ ankylosing spondylitis,^5,6 and lumbar spinal fusion.⁷

To our knowledge, no one has studied whether the intervertebral VP resolves after posterolateral lumbar spinal fusion in adults with degenerative spinal pathology, and no one has investigated the association between the persistence of the intervertebral VP and pseudarthrosis after posterolateral spinal fusion.

We conducted a study to determine whether the VP resolves after posterolateral lumbar spinal fusion procedures and whether persistence of the VP after fusion surgery is indicative of pseudarthrosis.

Materials and Methods

After obtaining Institutional Review Board approval for this study, we retrospectively reviewed the medical records of patients who had degenerative spinal stenosis with instability and the intervertebral vacuum sign on preoperative digital lumbar spine CT scans and who underwent posterolateral lumbar spinal fusion with or without instrumentation. Study inclusion criteria were lumbar spine CT at minimum 6-month follow-up after spinal fusion and preoperative and postoperative lumbar spine radiographs. Exclusion criteria were any type of interbody fusion procedure (anterior, posterior, transforaminal, lateral) at a level with the VP, age under 21 years, follow-up of less than 6 months, and incomplete radiographic records. As this was a retrospective study, patient consent was not required.

CT was performed with a 16-, 64-, or 128-slice multidetector CT scanner with effective tube current set at 250 to 320 mA, voltage set at 120 to 140 kV, and pitch set at 0.75 to 0.9. After axial acquisition of 3×3-mm isometric voxels, sagittal and coronal multiplanar images were reconstructed with a slice thickness of 2 mm. Patient demographics, diagnoses, and surgical details were recorded. All digital lumbar spine CT scans and radiographs were initially screened on PACS (picture archiving and communication system) by the orthopedic spine surgery fellow at an academic medical institution; then they were reviewed on a radiology reading room monitor by 3 observers (senior radiologist, senior orthopedic spine surgeon, orthopedic spine surgery fellow). Axial images and sagittal and coronal reconstructed images of the preoperative and postoperative follow-up lumbar CT scans—together with the lateral and anteroposterior lumbar spine radiographs—were evaluated for the intervertebral VP. Mean (SD) follow-up (with CT to assess fusion) was 1.6 (0.86) years (range, 0.75-3.38 years). Fusion at each level was evaluated on the postoperative follow-up CT on axial images and sagittal and coronal reconstructed images; criteria for fusion were continuous bridging bone across posterolateral gutters and facets on one or both sides at each intervertebral level.⁸ Pseudarthrosis was recorded if there was no continuity of bridging bone across both posterolateral gutters and facets, a complete radiolucent line on both sides across a level, or lysis or loosening around screws. All recordings were made by consensus, or by majority decision in case of disagreement.

Presence of the VP at the lumbar levels not included in the fusion was also recorded on the preoperative and follow-up CT scan and radiographs.

Descriptive and inferential statistical tests were performed as applicable. Pearson χ² test and Fischer exact test were used to evaluate if there was a significant association between the groups where the VP disappeared and persisted and fusion and pseudarthrosis. Significance was set at P < .05. Statistical analysis was performed with Stata Version 10.0.

Results

Using the preoperative lumbar spine CT scans of 18 patients (10 men, 8 women), we identified 36 cases of intervertebral levels exhibiting the VP (median positive vacuum sign levels per patient, 2; minimum, 1; maximum, 5) at the levels included in the fusion (Table 1). Mean (SD) age at surgery was 67.6 (9.4) years (range, 46.5-79.6 years). Mean (SD) radiologic follow-up was 1.6 (0.86) years (range, 0.75-3.38 years). All patients underwent lumbar fusion with local autograft, allograft, and recombinant human bone morphogenetic protein 2. Spinal instrumentation was used in 16 of the 18 patients.

On preoperative CT, positive VP was diagnosed in the 36 cases as follows: L5–S1 (11 cases), L4–L5 (9 cases), L3–L4 (4 cases), L2–L3 (6 cases), L1–L2 (4 cases), and T12–L1 (2 cases). On follow-up CT, 15 cases showed persistence of the VP, and 21 cases showed disappearance of the VP (Table 1).

Evidence of spinal fusion was identified on follow-up CT in 32 (88.9%) of the 36 cases. In 3 of the 18 patients, nonunion was diagnosed. Of the 15 intervertebral cases in which the VP persisted, 13 (86.7%) showed evidence of fusion on CT, and 2 (13.3%) showed evidence of pseudarthrosis. Of the 21 intervertebral cases in which the VP disappeared, 19 (90.5%) showed evidence of fusion on CT, and 2 (9.5%) showed evidence of pseudarthrosis (Table 2). There was no significant difference in fusion rate or pseudarthrosis rate in the groups in which the VP persisted or disappeared (Fischer exact test, P = .99). There was no significant association between VP persistence or disappearance and sex, primary or revision surgery, or intervertebral level (Fischer exact test, P > .05). A case example is shown in the Figure.

At levels not included in spinal fusion, CT identified the VP at 6 lumbar intervertebral levels before surgery and 11 levels at follow-up. The VP did not disappear at any level not included in the fusion. At follow-up, no new VP was identified in a segment included in fusion. Results are summarized in Table 3.

Discussion

The association of radiologic intervertebral VP and disc degeneration, first recognized by Knutsson¹ in 1942, refers to the presence of gas, mainly containing nitrogen, in the crevices between or within vertebrae.² The VP is more often seen in patients older than 50 years, on plain radiographs in hyperextension.⁹ CT is more sensitive than radiography in detecting the VP; Lardé and colleagues³ found it in about 50% of 50 patients on CT scans but in only 12% of patients on radiographs. The VP is visible because of the nitrogen gas that accumulates when there is a negative pressure within the disc space. Nitrogen emerges from the blood and moves into the disc space; perhaps the disc space opens, causing the negative pressure.^1-3 On T1- or T2-weighted magnetic resonance imaging (MRI), the VP is visible as a signal void. MRI, however, is less accurate than CT.¹⁰ In a study of 10 patients who had low back pain and more than 1 level of intradiscal VP, and who underwent supine MRI examinations at 0, 1, and 2 hours, Wang and colleagues¹¹ found that, after prolonged supine positioning, the signal intensity of the vacuum was replaced by hyperintense fluid contents. D’Anastasi and colleagues,¹² in a study of 20 patients who had lumbar vacuum phenomenon on CT and underwent MRI examinations, found a significant correlation between presence of intradiscal fluid and amount of bone marrow edema on MRI and degenerative endplate abnormalities on CT. In the present study, we found that, after the spinal fusion vacuum phenomenon disappeared in 58.3% of the lumbar levels and persisted in 41.7% on follow-up CT at the levels included in posterolateral fusion, there were 5 new levels, adjacent to the lumbar fusion, where the VP was seen on the follow-up CT.

We studied whether evidence of a persistent vacuum sign on CT is indicative of pseudarthrosis. Other authors have reported an association between the VP and nonunion in fractures⁴ and ankylosing spondylitis.^5,6 In a study of 19 patients with diaphyseal fractures, Stallenberg and colleagues⁴ found that, in 7 of the 10 patients with nonunion, the VP was detected on CT at the nonunion site. Martel⁵ first reported on the intervertebral VP in a case of ankylosing spondylitis with spinal pseudarthrosis. Ten years later, in a study of 18 patients with advanced ankylosing spondylitis with spinal pseudarthrosis, Chan and colleagues⁶ identified the intervertebral VP on CT in 7 patients. Edwards and colleagues⁷ studied 15 patients with prior lumbar fusion with 17 positive intervertebral VP levels on CT and found that the vacuum disc sign was a strong predictor of lumbar nonunion as determined by surgical exploration. Mirovsky and colleagues¹³ identified the intravertebral vacuum cleft in 26 patients with an osteoporotic vertebral fracture treated with vertebroplasty and concluded that nonunion of the vertebral fracture could be identified by presence of the intravertebral vacuum cleft on radiography. In the present study, there was radiologic evidence of lumbar spinal fusion in 89% of disc levels with a preoperative positive intervertebral VP and pseudarthrosis in 11% of disc levels. The rate of fusion at levels with the VP was comparable to the rate at intervertebral levels without the phenomenon. These findings indicate that persistence of the VP after spinal fusion is not an indication that fusion has not been achieved. Preoperative VP also did not predispose to failure of fusion. That there is a persistent vacuum disc might imply that, even after successful fusion as seen on CT, some motion may be occurring at the disc level to cause a negative pressure phenomenon. Even in cases of facet fusion with bridging bone, there may still be motion at the disc level, as fusions can plastically deform (even with screws in), particularly in elderly osteopenic bone. We found no association between a persistent vacuum sign and pseudarthrosis. Our study findings are clinically useful even if the benefits are limited. These findings may help surgeons avoid misinterpreting this sign as an indication for additional surgery.

This study had some limitations. First, radiographs were used to determine presence or absence of fusion. Although CT is widely considered the gold standard for noninvasive assessment of fusion,¹⁴ even when both posterolateral gutters and facets have been found to be fused on CT, the probability of a solid fusion on exploration ranges from 69% to 96%.^8,15 Second, detection of the VP on radiographs and CT may be affected by patient position.¹¹ Third, this was a retrospective series with a small number of patients and limited follow-up with CT. Arthrodesis and the VP may take years to fully evolve. It is possible that fusion rates could be higher on longer follow-up, and resolution of the VP may occur with longer follow-up. Fourth, clinical outcomes were not evaluated, as there are other confounding factors, apart from successful fusion, that could affect clinical outcomes. A larger prospective controlled study would be helpful.

Conclusion

The radiologic intervertebral VP may persist after posterolateral lumbar spinal fusion. We did not find an association between the VP and pseudarthrosis. In addition, VP persistence on follow-up CT was not indicative of pseudarthrosis, and VP disappearance was not indicative of fusion. The vacuum sign should not be misinterpreted as an indication for additional surgery.

The spinal vacuum sign or vacuum phenomenon (VP) is the radiographic finding of an air-density linear radiolucency in the intervertebral disc or vertebral body. The result of a gaseous accumulation, it is often a diagnostic sign of disc degeneration as well as a rare sign of infection, Schmorl node formation, or osteonecrosis.^1,2 Although the VP was first described on plain radiographs, it is better seen on computed tomography (CT).³ Multiple studies have found a possible association between the VP and nonunion in diaphyseal fractures,⁴ ankylosing spondylitis,^5,6 and lumbar spinal fusion.⁷

To our knowledge, no one has studied whether the intervertebral VP resolves after posterolateral lumbar spinal fusion in adults with degenerative spinal pathology, and no one has investigated the association between the persistence of the intervertebral VP and pseudarthrosis after posterolateral spinal fusion.

We conducted a study to determine whether the VP resolves after posterolateral lumbar spinal fusion procedures and whether persistence of the VP after fusion surgery is indicative of pseudarthrosis.

Materials and Methods

After obtaining Institutional Review Board approval for this study, we retrospectively reviewed the medical records of patients who had degenerative spinal stenosis with instability and the intervertebral vacuum sign on preoperative digital lumbar spine CT scans and who underwent posterolateral lumbar spinal fusion with or without instrumentation. Study inclusion criteria were lumbar spine CT at minimum 6-month follow-up after spinal fusion and preoperative and postoperative lumbar spine radiographs. Exclusion criteria were any type of interbody fusion procedure (anterior, posterior, transforaminal, lateral) at a level with the VP, age under 21 years, follow-up of less than 6 months, and incomplete radiographic records. As this was a retrospective study, patient consent was not required.

CT was performed with a 16-, 64-, or 128-slice multidetector CT scanner with effective tube current set at 250 to 320 mA, voltage set at 120 to 140 kV, and pitch set at 0.75 to 0.9. After axial acquisition of 3×3-mm isometric voxels, sagittal and coronal multiplanar images were reconstructed with a slice thickness of 2 mm. Patient demographics, diagnoses, and surgical details were recorded. All digital lumbar spine CT scans and radiographs were initially screened on PACS (picture archiving and communication system) by the orthopedic spine surgery fellow at an academic medical institution; then they were reviewed on a radiology reading room monitor by 3 observers (senior radiologist, senior orthopedic spine surgeon, orthopedic spine surgery fellow). Axial images and sagittal and coronal reconstructed images of the preoperative and postoperative follow-up lumbar CT scans—together with the lateral and anteroposterior lumbar spine radiographs—were evaluated for the intervertebral VP. Mean (SD) follow-up (with CT to assess fusion) was 1.6 (0.86) years (range, 0.75-3.38 years). Fusion at each level was evaluated on the postoperative follow-up CT on axial images and sagittal and coronal reconstructed images; criteria for fusion were continuous bridging bone across posterolateral gutters and facets on one or both sides at each intervertebral level.⁸ Pseudarthrosis was recorded if there was no continuity of bridging bone across both posterolateral gutters and facets, a complete radiolucent line on both sides across a level, or lysis or loosening around screws. All recordings were made by consensus, or by majority decision in case of disagreement.

Presence of the VP at the lumbar levels not included in the fusion was also recorded on the preoperative and follow-up CT scan and radiographs.

Descriptive and inferential statistical tests were performed as applicable. Pearson χ² test and Fischer exact test were used to evaluate if there was a significant association between the groups where the VP disappeared and persisted and fusion and pseudarthrosis. Significance was set at P < .05. Statistical analysis was performed with Stata Version 10.0.

Results

Using the preoperative lumbar spine CT scans of 18 patients (10 men, 8 women), we identified 36 cases of intervertebral levels exhibiting the VP (median positive vacuum sign levels per patient, 2; minimum, 1; maximum, 5) at the levels included in the fusion (Table 1). Mean (SD) age at surgery was 67.6 (9.4) years (range, 46.5-79.6 years). Mean (SD) radiologic follow-up was 1.6 (0.86) years (range, 0.75-3.38 years). All patients underwent lumbar fusion with local autograft, allograft, and recombinant human bone morphogenetic protein 2. Spinal instrumentation was used in 16 of the 18 patients.

On preoperative CT, positive VP was diagnosed in the 36 cases as follows: L5–S1 (11 cases), L4–L5 (9 cases), L3–L4 (4 cases), L2–L3 (6 cases), L1–L2 (4 cases), and T12–L1 (2 cases). On follow-up CT, 15 cases showed persistence of the VP, and 21 cases showed disappearance of the VP (Table 1).

Evidence of spinal fusion was identified on follow-up CT in 32 (88.9%) of the 36 cases. In 3 of the 18 patients, nonunion was diagnosed. Of the 15 intervertebral cases in which the VP persisted, 13 (86.7%) showed evidence of fusion on CT, and 2 (13.3%) showed evidence of pseudarthrosis. Of the 21 intervertebral cases in which the VP disappeared, 19 (90.5%) showed evidence of fusion on CT, and 2 (9.5%) showed evidence of pseudarthrosis (Table 2). There was no significant difference in fusion rate or pseudarthrosis rate in the groups in which the VP persisted or disappeared (Fischer exact test, P = .99). There was no significant association between VP persistence or disappearance and sex, primary or revision surgery, or intervertebral level (Fischer exact test, P > .05). A case example is shown in the Figure.

At levels not included in spinal fusion, CT identified the VP at 6 lumbar intervertebral levels before surgery and 11 levels at follow-up. The VP did not disappear at any level not included in the fusion. At follow-up, no new VP was identified in a segment included in fusion. Results are summarized in Table 3.

Discussion

The association of radiologic intervertebral VP and disc degeneration, first recognized by Knutsson¹ in 1942, refers to the presence of gas, mainly containing nitrogen, in the crevices between or within vertebrae.² The VP is more often seen in patients older than 50 years, on plain radiographs in hyperextension.⁹ CT is more sensitive than radiography in detecting the VP; Lardé and colleagues³ found it in about 50% of 50 patients on CT scans but in only 12% of patients on radiographs. The VP is visible because of the nitrogen gas that accumulates when there is a negative pressure within the disc space. Nitrogen emerges from the blood and moves into the disc space; perhaps the disc space opens, causing the negative pressure.^1-3 On T1- or T2-weighted magnetic resonance imaging (MRI), the VP is visible as a signal void. MRI, however, is less accurate than CT.¹⁰ In a study of 10 patients who had low back pain and more than 1 level of intradiscal VP, and who underwent supine MRI examinations at 0, 1, and 2 hours, Wang and colleagues¹¹ found that, after prolonged supine positioning, the signal intensity of the vacuum was replaced by hyperintense fluid contents. D’Anastasi and colleagues,¹² in a study of 20 patients who had lumbar vacuum phenomenon on CT and underwent MRI examinations, found a significant correlation between presence of intradiscal fluid and amount of bone marrow edema on MRI and degenerative endplate abnormalities on CT. In the present study, we found that, after the spinal fusion vacuum phenomenon disappeared in 58.3% of the lumbar levels and persisted in 41.7% on follow-up CT at the levels included in posterolateral fusion, there were 5 new levels, adjacent to the lumbar fusion, where the VP was seen on the follow-up CT.

We studied whether evidence of a persistent vacuum sign on CT is indicative of pseudarthrosis. Other authors have reported an association between the VP and nonunion in fractures⁴ and ankylosing spondylitis.^5,6 In a study of 19 patients with diaphyseal fractures, Stallenberg and colleagues⁴ found that, in 7 of the 10 patients with nonunion, the VP was detected on CT at the nonunion site. Martel⁵ first reported on the intervertebral VP in a case of ankylosing spondylitis with spinal pseudarthrosis. Ten years later, in a study of 18 patients with advanced ankylosing spondylitis with spinal pseudarthrosis, Chan and colleagues⁶ identified the intervertebral VP on CT in 7 patients. Edwards and colleagues⁷ studied 15 patients with prior lumbar fusion with 17 positive intervertebral VP levels on CT and found that the vacuum disc sign was a strong predictor of lumbar nonunion as determined by surgical exploration. Mirovsky and colleagues¹³ identified the intravertebral vacuum cleft in 26 patients with an osteoporotic vertebral fracture treated with vertebroplasty and concluded that nonunion of the vertebral fracture could be identified by presence of the intravertebral vacuum cleft on radiography. In the present study, there was radiologic evidence of lumbar spinal fusion in 89% of disc levels with a preoperative positive intervertebral VP and pseudarthrosis in 11% of disc levels. The rate of fusion at levels with the VP was comparable to the rate at intervertebral levels without the phenomenon. These findings indicate that persistence of the VP after spinal fusion is not an indication that fusion has not been achieved. Preoperative VP also did not predispose to failure of fusion. That there is a persistent vacuum disc might imply that, even after successful fusion as seen on CT, some motion may be occurring at the disc level to cause a negative pressure phenomenon. Even in cases of facet fusion with bridging bone, there may still be motion at the disc level, as fusions can plastically deform (even with screws in), particularly in elderly osteopenic bone. We found no association between a persistent vacuum sign and pseudarthrosis. Our study findings are clinically useful even if the benefits are limited. These findings may help surgeons avoid misinterpreting this sign as an indication for additional surgery.

This study had some limitations. First, radiographs were used to determine presence or absence of fusion. Although CT is widely considered the gold standard for noninvasive assessment of fusion,¹⁴ even when both posterolateral gutters and facets have been found to be fused on CT, the probability of a solid fusion on exploration ranges from 69% to 96%.^8,15 Second, detection of the VP on radiographs and CT may be affected by patient position.¹¹ Third, this was a retrospective series with a small number of patients and limited follow-up with CT. Arthrodesis and the VP may take years to fully evolve. It is possible that fusion rates could be higher on longer follow-up, and resolution of the VP may occur with longer follow-up. Fourth, clinical outcomes were not evaluated, as there are other confounding factors, apart from successful fusion, that could affect clinical outcomes. A larger prospective controlled study would be helpful.

Conclusion

The radiologic intervertebral VP may persist after posterolateral lumbar spinal fusion. We did not find an association between the VP and pseudarthrosis. In addition, VP persistence on follow-up CT was not indicative of pseudarthrosis, and VP disappearance was not indicative of fusion. The vacuum sign should not be misinterpreted as an indication for additional surgery.

The spinal vacuum sign or vacuum phenomenon (VP) is the radiographic finding of an air-density linear radiolucency in the intervertebral disc or vertebral body. The result of a gaseous accumulation, it is often a diagnostic sign of disc degeneration as well as a rare sign of infection, Schmorl node formation, or osteonecrosis.^1,2 Although the VP was first described on plain radiographs, it is better seen on computed tomography (CT).³ Multiple studies have found a possible association between the VP and nonunion in diaphyseal fractures,⁴ ankylosing spondylitis,^5,6 and lumbar spinal fusion.⁷

To our knowledge, no one has studied whether the intervertebral VP resolves after posterolateral lumbar spinal fusion in adults with degenerative spinal pathology, and no one has investigated the association between the persistence of the intervertebral VP and pseudarthrosis after posterolateral spinal fusion.

We conducted a study to determine whether the VP resolves after posterolateral lumbar spinal fusion procedures and whether persistence of the VP after fusion surgery is indicative of pseudarthrosis.

Materials and Methods

After obtaining Institutional Review Board approval for this study, we retrospectively reviewed the medical records of patients who had degenerative spinal stenosis with instability and the intervertebral vacuum sign on preoperative digital lumbar spine CT scans and who underwent posterolateral lumbar spinal fusion with or without instrumentation. Study inclusion criteria were lumbar spine CT at minimum 6-month follow-up after spinal fusion and preoperative and postoperative lumbar spine radiographs. Exclusion criteria were any type of interbody fusion procedure (anterior, posterior, transforaminal, lateral) at a level with the VP, age under 21 years, follow-up of less than 6 months, and incomplete radiographic records. As this was a retrospective study, patient consent was not required.

CT was performed with a 16-, 64-, or 128-slice multidetector CT scanner with effective tube current set at 250 to 320 mA, voltage set at 120 to 140 kV, and pitch set at 0.75 to 0.9. After axial acquisition of 3×3-mm isometric voxels, sagittal and coronal multiplanar images were reconstructed with a slice thickness of 2 mm. Patient demographics, diagnoses, and surgical details were recorded. All digital lumbar spine CT scans and radiographs were initially screened on PACS (picture archiving and communication system) by the orthopedic spine surgery fellow at an academic medical institution; then they were reviewed on a radiology reading room monitor by 3 observers (senior radiologist, senior orthopedic spine surgeon, orthopedic spine surgery fellow). Axial images and sagittal and coronal reconstructed images of the preoperative and postoperative follow-up lumbar CT scans—together with the lateral and anteroposterior lumbar spine radiographs—were evaluated for the intervertebral VP. Mean (SD) follow-up (with CT to assess fusion) was 1.6 (0.86) years (range, 0.75-3.38 years). Fusion at each level was evaluated on the postoperative follow-up CT on axial images and sagittal and coronal reconstructed images; criteria for fusion were continuous bridging bone across posterolateral gutters and facets on one or both sides at each intervertebral level.⁸ Pseudarthrosis was recorded if there was no continuity of bridging bone across both posterolateral gutters and facets, a complete radiolucent line on both sides across a level, or lysis or loosening around screws. All recordings were made by consensus, or by majority decision in case of disagreement.

Presence of the VP at the lumbar levels not included in the fusion was also recorded on the preoperative and follow-up CT scan and radiographs.

Descriptive and inferential statistical tests were performed as applicable. Pearson χ² test and Fischer exact test were used to evaluate if there was a significant association between the groups where the VP disappeared and persisted and fusion and pseudarthrosis. Significance was set at P < .05. Statistical analysis was performed with Stata Version 10.0.

Results

Using the preoperative lumbar spine CT scans of 18 patients (10 men, 8 women), we identified 36 cases of intervertebral levels exhibiting the VP (median positive vacuum sign levels per patient, 2; minimum, 1; maximum, 5) at the levels included in the fusion (Table 1). Mean (SD) age at surgery was 67.6 (9.4) years (range, 46.5-79.6 years). Mean (SD) radiologic follow-up was 1.6 (0.86) years (range, 0.75-3.38 years). All patients underwent lumbar fusion with local autograft, allograft, and recombinant human bone morphogenetic protein 2. Spinal instrumentation was used in 16 of the 18 patients.

On preoperative CT, positive VP was diagnosed in the 36 cases as follows: L5–S1 (11 cases), L4–L5 (9 cases), L3–L4 (4 cases), L2–L3 (6 cases), L1–L2 (4 cases), and T12–L1 (2 cases). On follow-up CT, 15 cases showed persistence of the VP, and 21 cases showed disappearance of the VP (Table 1).

Evidence of spinal fusion was identified on follow-up CT in 32 (88.9%) of the 36 cases. In 3 of the 18 patients, nonunion was diagnosed. Of the 15 intervertebral cases in which the VP persisted, 13 (86.7%) showed evidence of fusion on CT, and 2 (13.3%) showed evidence of pseudarthrosis. Of the 21 intervertebral cases in which the VP disappeared, 19 (90.5%) showed evidence of fusion on CT, and 2 (9.5%) showed evidence of pseudarthrosis (Table 2). There was no significant difference in fusion rate or pseudarthrosis rate in the groups in which the VP persisted or disappeared (Fischer exact test, P = .99). There was no significant association between VP persistence or disappearance and sex, primary or revision surgery, or intervertebral level (Fischer exact test, P > .05). A case example is shown in the Figure.

At levels not included in spinal fusion, CT identified the VP at 6 lumbar intervertebral levels before surgery and 11 levels at follow-up. The VP did not disappear at any level not included in the fusion. At follow-up, no new VP was identified in a segment included in fusion. Results are summarized in Table 3.

Discussion

The association of radiologic intervertebral VP and disc degeneration, first recognized by Knutsson¹ in 1942, refers to the presence of gas, mainly containing nitrogen, in the crevices between or within vertebrae.² The VP is more often seen in patients older than 50 years, on plain radiographs in hyperextension.⁹ CT is more sensitive than radiography in detecting the VP; Lardé and colleagues³ found it in about 50% of 50 patients on CT scans but in only 12% of patients on radiographs. The VP is visible because of the nitrogen gas that accumulates when there is a negative pressure within the disc space. Nitrogen emerges from the blood and moves into the disc space; perhaps the disc space opens, causing the negative pressure.^1-3 On T1- or T2-weighted magnetic resonance imaging (MRI), the VP is visible as a signal void. MRI, however, is less accurate than CT.¹⁰ In a study of 10 patients who had low back pain and more than 1 level of intradiscal VP, and who underwent supine MRI examinations at 0, 1, and 2 hours, Wang and colleagues¹¹ found that, after prolonged supine positioning, the signal intensity of the vacuum was replaced by hyperintense fluid contents. D’Anastasi and colleagues,¹² in a study of 20 patients who had lumbar vacuum phenomenon on CT and underwent MRI examinations, found a significant correlation between presence of intradiscal fluid and amount of bone marrow edema on MRI and degenerative endplate abnormalities on CT. In the present study, we found that, after the spinal fusion vacuum phenomenon disappeared in 58.3% of the lumbar levels and persisted in 41.7% on follow-up CT at the levels included in posterolateral fusion, there were 5 new levels, adjacent to the lumbar fusion, where the VP was seen on the follow-up CT.

We studied whether evidence of a persistent vacuum sign on CT is indicative of pseudarthrosis. Other authors have reported an association between the VP and nonunion in fractures⁴ and ankylosing spondylitis.^5,6 In a study of 19 patients with diaphyseal fractures, Stallenberg and colleagues⁴ found that, in 7 of the 10 patients with nonunion, the VP was detected on CT at the nonunion site. Martel⁵ first reported on the intervertebral VP in a case of ankylosing spondylitis with spinal pseudarthrosis. Ten years later, in a study of 18 patients with advanced ankylosing spondylitis with spinal pseudarthrosis, Chan and colleagues⁶ identified the intervertebral VP on CT in 7 patients. Edwards and colleagues⁷ studied 15 patients with prior lumbar fusion with 17 positive intervertebral VP levels on CT and found that the vacuum disc sign was a strong predictor of lumbar nonunion as determined by surgical exploration. Mirovsky and colleagues¹³ identified the intravertebral vacuum cleft in 26 patients with an osteoporotic vertebral fracture treated with vertebroplasty and concluded that nonunion of the vertebral fracture could be identified by presence of the intravertebral vacuum cleft on radiography. In the present study, there was radiologic evidence of lumbar spinal fusion in 89% of disc levels with a preoperative positive intervertebral VP and pseudarthrosis in 11% of disc levels. The rate of fusion at levels with the VP was comparable to the rate at intervertebral levels without the phenomenon. These findings indicate that persistence of the VP after spinal fusion is not an indication that fusion has not been achieved. Preoperative VP also did not predispose to failure of fusion. That there is a persistent vacuum disc might imply that, even after successful fusion as seen on CT, some motion may be occurring at the disc level to cause a negative pressure phenomenon. Even in cases of facet fusion with bridging bone, there may still be motion at the disc level, as fusions can plastically deform (even with screws in), particularly in elderly osteopenic bone. We found no association between a persistent vacuum sign and pseudarthrosis. Our study findings are clinically useful even if the benefits are limited. These findings may help surgeons avoid misinterpreting this sign as an indication for additional surgery.

This study had some limitations. First, radiographs were used to determine presence or absence of fusion. Although CT is widely considered the gold standard for noninvasive assessment of fusion,¹⁴ even when both posterolateral gutters and facets have been found to be fused on CT, the probability of a solid fusion on exploration ranges from 69% to 96%.^8,15 Second, detection of the VP on radiographs and CT may be affected by patient position.¹¹ Third, this was a retrospective series with a small number of patients and limited follow-up with CT. Arthrodesis and the VP may take years to fully evolve. It is possible that fusion rates could be higher on longer follow-up, and resolution of the VP may occur with longer follow-up. Fourth, clinical outcomes were not evaluated, as there are other confounding factors, apart from successful fusion, that could affect clinical outcomes. A larger prospective controlled study would be helpful.

Conclusion

The radiologic intervertebral VP may persist after posterolateral lumbar spinal fusion. We did not find an association between the VP and pseudarthrosis. In addition, VP persistence on follow-up CT was not indicative of pseudarthrosis, and VP disappearance was not indicative of fusion. The vacuum sign should not be misinterpreted as an indication for additional surgery.

TORONTO – Patients with amnestic mild cognitive impairment made significantly more errors during a complex test of driving skills and showed altered brain activity while performing this test in a two-part study.

The findings are the first to show a correlation between physiologic brain activity and driving and suggest that patients with mild cognitive impairment (MCI) may already be experiencing potentially dangerous changes in their ability to operate a motor vehicle, Megan Hird said at the Alzheimer’s Association International Conference 2016.

Michele G. Sullivan/Frontline Medical News

“Driving is a highly complex behavior that requires the integration of cognitive, motor function, and perceptual abilities,” said Ms. Hird, a researcher at the University of Toronto. “Individuals with multidomain MCI can express memory, visuospatial, and executive function deficits” even before their less demanding activities of daily living are affected. Nevertheless, Ms. Hird said, “these deficits can affect someone’s ability to drive safely.”

The decision to hang up the car keys is always a tough one for patients with dementia, their families, and their physicians, and there are no guidelines in the United States or Canada to help in that decision. But Ms. Hird and her colleagues recently published a meta-analysis of driving studies in which patients with very mild Alzheimer’s were 10 times more likely to fail an on-road driving test than were cognitively healthy drivers (J Alz Dis. 2016;53[2]:713-29).

Nevertheless, both the American and Canadian Medical Associations state that a diagnosis of cognitive impairment is not sufficient to withdraw driving privileges, and no cognitive test is capable of determining driving ability.

Ms. Hird used a combination of a driving simulator and functional MRI to study driving skill and the neural correlates of that activity. There were two parts to the study. The first comprised 20 healthy controls and 24 amnestic MCI patients (11 with single-domain MCI and 13 with multidomain MCI). The driving tasks were routine right and left turns, plus left turns against traffic and left turns against traffic with auditory distraction.

Overall, those with MCI (both single- and multi-domain patients combined) committed significantly more risky driving errors than the control group (mean of 9 vs. 3). Risky errors were considered errors that could result in an imminent collision, crossing the center line into oncoming traffic, or crossing onto the sidewalk.

When the researchers examined the MCI groups separately, they determined that only those with multi-domain MCI performed significantly worse than did controls (mean of 14 vs. 2.7 errors). These errors were most often committed during the more complicated left turns. There were no significant between-group differences in routine right and left turns.

Differences in brain activation revealed

The second part comprised 32 patients: 16 with MCI and 16 age-matched, cognitively normal controls. These subjects undertook both the driving simulation and the functional MRI test.

On the uncomplicated right turns, there were no between-group differences in errors, Ms. Hird said. However, there were some differences in the way the subjects’ brains reacted to the task. “On the brain activation patterns, the healthy controls showed some negative activation in the temporal and occipital regions, areas that actually were activated in the patients. The patients also showed some increased signal in the posterior medial regions, compared with the healthy controls. Overall, however, the activation patterns looked quite similar between the two groups.”

The left turn into traffic task showed quite different results. “In the MCI group, there was more anterior activation. They also showed significantly higher activation than did the control group in the orbitofrontal, medial superior, and midfrontal cortex – all of which are involved in planning, higher-order attention, and cognitive control.”

Recognizing that there are demonstrable differences in brain activation that correlate with poor driving performance could spark the creation of an objective clinical measurement tool for determining driving status, Ms. Hird said.

“This is an important fundamental step in the development of a tool that is sensitive and specific for addressing the driving safety of these patients.”

During discussion after her presentation, she fielded a question from an Australian clinician, who said his country likewise has no objective measure of when driving is no longer safe for a dementia patient.

“We accept the fact that people do drive with some degree of cognitive impairment,” said the physician, who did not identify himself. “But there are regions where having a license is important for social engagement. And we know that social disengagement drives rapid progression of cognitive decline. I think there is a real tension here between the withdrawal of licensure and the preservation of social engagement.”

Ms. Hird agreed. “Obviously, many MCI patients do retain the ability to drive safely. But we need to achieve a balance between maintaining patient autonomy and the safety of the general public.”

Ms. Hird had no financial disclosures.

[email protected]

On Twitter @alz_gal

TORONTO – Patients with amnestic mild cognitive impairment made significantly more errors during a complex test of driving skills and showed altered brain activity while performing this test in a two-part study.

The findings are the first to show a correlation between physiologic brain activity and driving and suggest that patients with mild cognitive impairment (MCI) may already be experiencing potentially dangerous changes in their ability to operate a motor vehicle, Megan Hird said at the Alzheimer’s Association International Conference 2016.

Michele G. Sullivan/Frontline Medical News

“Driving is a highly complex behavior that requires the integration of cognitive, motor function, and perceptual abilities,” said Ms. Hird, a researcher at the University of Toronto. “Individuals with multidomain MCI can express memory, visuospatial, and executive function deficits” even before their less demanding activities of daily living are affected. Nevertheless, Ms. Hird said, “these deficits can affect someone’s ability to drive safely.”

The decision to hang up the car keys is always a tough one for patients with dementia, their families, and their physicians, and there are no guidelines in the United States or Canada to help in that decision. But Ms. Hird and her colleagues recently published a meta-analysis of driving studies in which patients with very mild Alzheimer’s were 10 times more likely to fail an on-road driving test than were cognitively healthy drivers (J Alz Dis. 2016;53[2]:713-29).

Nevertheless, both the American and Canadian Medical Associations state that a diagnosis of cognitive impairment is not sufficient to withdraw driving privileges, and no cognitive test is capable of determining driving ability.

Ms. Hird used a combination of a driving simulator and functional MRI to study driving skill and the neural correlates of that activity. There were two parts to the study. The first comprised 20 healthy controls and 24 amnestic MCI patients (11 with single-domain MCI and 13 with multidomain MCI). The driving tasks were routine right and left turns, plus left turns against traffic and left turns against traffic with auditory distraction.

Overall, those with MCI (both single- and multi-domain patients combined) committed significantly more risky driving errors than the control group (mean of 9 vs. 3). Risky errors were considered errors that could result in an imminent collision, crossing the center line into oncoming traffic, or crossing onto the sidewalk.

When the researchers examined the MCI groups separately, they determined that only those with multi-domain MCI performed significantly worse than did controls (mean of 14 vs. 2.7 errors). These errors were most often committed during the more complicated left turns. There were no significant between-group differences in routine right and left turns.

Differences in brain activation revealed

The second part comprised 32 patients: 16 with MCI and 16 age-matched, cognitively normal controls. These subjects undertook both the driving simulation and the functional MRI test.

On the uncomplicated right turns, there were no between-group differences in errors, Ms. Hird said. However, there were some differences in the way the subjects’ brains reacted to the task. “On the brain activation patterns, the healthy controls showed some negative activation in the temporal and occipital regions, areas that actually were activated in the patients. The patients also showed some increased signal in the posterior medial regions, compared with the healthy controls. Overall, however, the activation patterns looked quite similar between the two groups.”

The left turn into traffic task showed quite different results. “In the MCI group, there was more anterior activation. They also showed significantly higher activation than did the control group in the orbitofrontal, medial superior, and midfrontal cortex – all of which are involved in planning, higher-order attention, and cognitive control.”

Recognizing that there are demonstrable differences in brain activation that correlate with poor driving performance could spark the creation of an objective clinical measurement tool for determining driving status, Ms. Hird said.

“This is an important fundamental step in the development of a tool that is sensitive and specific for addressing the driving safety of these patients.”

During discussion after her presentation, she fielded a question from an Australian clinician, who said his country likewise has no objective measure of when driving is no longer safe for a dementia patient.

“We accept the fact that people do drive with some degree of cognitive impairment,” said the physician, who did not identify himself. “But there are regions where having a license is important for social engagement. And we know that social disengagement drives rapid progression of cognitive decline. I think there is a real tension here between the withdrawal of licensure and the preservation of social engagement.”

Ms. Hird agreed. “Obviously, many MCI patients do retain the ability to drive safely. But we need to achieve a balance between maintaining patient autonomy and the safety of the general public.”

Ms. Hird had no financial disclosures.

[email protected]

On Twitter @alz_gal

TORONTO – Patients with amnestic mild cognitive impairment made significantly more errors during a complex test of driving skills and showed altered brain activity while performing this test in a two-part study.

The findings are the first to show a correlation between physiologic brain activity and driving and suggest that patients with mild cognitive impairment (MCI) may already be experiencing potentially dangerous changes in their ability to operate a motor vehicle, Megan Hird said at the Alzheimer’s Association International Conference 2016.

Michele G. Sullivan/Frontline Medical News

“Driving is a highly complex behavior that requires the integration of cognitive, motor function, and perceptual abilities,” said Ms. Hird, a researcher at the University of Toronto. “Individuals with multidomain MCI can express memory, visuospatial, and executive function deficits” even before their less demanding activities of daily living are affected. Nevertheless, Ms. Hird said, “these deficits can affect someone’s ability to drive safely.”

The decision to hang up the car keys is always a tough one for patients with dementia, their families, and their physicians, and there are no guidelines in the United States or Canada to help in that decision. But Ms. Hird and her colleagues recently published a meta-analysis of driving studies in which patients with very mild Alzheimer’s were 10 times more likely to fail an on-road driving test than were cognitively healthy drivers (J Alz Dis. 2016;53[2]:713-29).

Nevertheless, both the American and Canadian Medical Associations state that a diagnosis of cognitive impairment is not sufficient to withdraw driving privileges, and no cognitive test is capable of determining driving ability.

Ms. Hird used a combination of a driving simulator and functional MRI to study driving skill and the neural correlates of that activity. There were two parts to the study. The first comprised 20 healthy controls and 24 amnestic MCI patients (11 with single-domain MCI and 13 with multidomain MCI). The driving tasks were routine right and left turns, plus left turns against traffic and left turns against traffic with auditory distraction.

Overall, those with MCI (both single- and multi-domain patients combined) committed significantly more risky driving errors than the control group (mean of 9 vs. 3). Risky errors were considered errors that could result in an imminent collision, crossing the center line into oncoming traffic, or crossing onto the sidewalk.

When the researchers examined the MCI groups separately, they determined that only those with multi-domain MCI performed significantly worse than did controls (mean of 14 vs. 2.7 errors). These errors were most often committed during the more complicated left turns. There were no significant between-group differences in routine right and left turns.

Differences in brain activation revealed

The second part comprised 32 patients: 16 with MCI and 16 age-matched, cognitively normal controls. These subjects undertook both the driving simulation and the functional MRI test.

On the uncomplicated right turns, there were no between-group differences in errors, Ms. Hird said. However, there were some differences in the way the subjects’ brains reacted to the task. “On the brain activation patterns, the healthy controls showed some negative activation in the temporal and occipital regions, areas that actually were activated in the patients. The patients also showed some increased signal in the posterior medial regions, compared with the healthy controls. Overall, however, the activation patterns looked quite similar between the two groups.”

The left turn into traffic task showed quite different results. “In the MCI group, there was more anterior activation. They also showed significantly higher activation than did the control group in the orbitofrontal, medial superior, and midfrontal cortex – all of which are involved in planning, higher-order attention, and cognitive control.”

Recognizing that there are demonstrable differences in brain activation that correlate with poor driving performance could spark the creation of an objective clinical measurement tool for determining driving status, Ms. Hird said.

“This is an important fundamental step in the development of a tool that is sensitive and specific for addressing the driving safety of these patients.”

During discussion after her presentation, she fielded a question from an Australian clinician, who said his country likewise has no objective measure of when driving is no longer safe for a dementia patient.

“We accept the fact that people do drive with some degree of cognitive impairment,” said the physician, who did not identify himself. “But there are regions where having a license is important for social engagement. And we know that social disengagement drives rapid progression of cognitive decline. I think there is a real tension here between the withdrawal of licensure and the preservation of social engagement.”

Ms. Hird agreed. “Obviously, many MCI patients do retain the ability to drive safely. But we need to achieve a balance between maintaining patient autonomy and the safety of the general public.”

Ms. Hird had no financial disclosures.

[email protected]

On Twitter @alz_gal