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FDA warning: General anesthetics may damage young brains
The Food and Drug Administration has issued a warning that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children’s brains.
“Recent human studies suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning.” The studies suggesting a problem with longer or repeat exposures “had limitations, and it is unclear whether any negative effects seen in children’s learning or behavior were due to the drugs or to other factors, such as the underlying medical condition that led to the need for the surgery or procedure.” Further research is needed, the agency said.
FDA is adding its warning to the labels of 11 general anesthetics and sedatives, including desflurane, halothane, ketamine, lorazepam injection, methohexital, pentobarbital, and propofol. The drugs block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity. No specific medications have been shown to be safer than any other, the agency said.
FDA will continue to monitor the situation, and update its warning as additional information comes in. “We urge health care professionals, patients, parents, and caregivers to report side effects involving anesthetic and sedation drugs or other medicines to the FDA MedWatch program,” the FDA said.
The Food and Drug Administration has issued a warning that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children’s brains.
“Recent human studies suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning.” The studies suggesting a problem with longer or repeat exposures “had limitations, and it is unclear whether any negative effects seen in children’s learning or behavior were due to the drugs or to other factors, such as the underlying medical condition that led to the need for the surgery or procedure.” Further research is needed, the agency said.
FDA is adding its warning to the labels of 11 general anesthetics and sedatives, including desflurane, halothane, ketamine, lorazepam injection, methohexital, pentobarbital, and propofol. The drugs block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity. No specific medications have been shown to be safer than any other, the agency said.
FDA will continue to monitor the situation, and update its warning as additional information comes in. “We urge health care professionals, patients, parents, and caregivers to report side effects involving anesthetic and sedation drugs or other medicines to the FDA MedWatch program,” the FDA said.
The Food and Drug Administration has issued a warning that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children’s brains.
“Recent human studies suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning.” The studies suggesting a problem with longer or repeat exposures “had limitations, and it is unclear whether any negative effects seen in children’s learning or behavior were due to the drugs or to other factors, such as the underlying medical condition that led to the need for the surgery or procedure.” Further research is needed, the agency said.
FDA is adding its warning to the labels of 11 general anesthetics and sedatives, including desflurane, halothane, ketamine, lorazepam injection, methohexital, pentobarbital, and propofol. The drugs block N-methyl-D-aspartate (NMDA) receptors and/or potentiate gamma-aminobutyric acid (GABA) activity. No specific medications have been shown to be safer than any other, the agency said.
FDA will continue to monitor the situation, and update its warning as additional information comes in. “We urge health care professionals, patients, parents, and caregivers to report side effects involving anesthetic and sedation drugs or other medicines to the FDA MedWatch program,” the FDA said.
Widespread lack of awareness of pancreatic insufficiency
Individuals experiencing chronic GI symptoms waited a mean of 3.7 years to see a health care professional, according to a recent survey.
Thus, for persons with chronic GI issues, inadequate communication may be a factor contributing to underdiagnosis. Fully 60% of patients surveyed cited embarrassment as the reason it was difficult to disclose GI symptoms to a doctor. Nearly half (47%) said they simply wanted to wait to see if their problems would go away. And 66% of patients interviewed had never heard of exocrine pancreatic insufficiency (EPI), while an additional 21% had heard of EPI but were not familiar with it.
Financial support for the survey came from AbbVie, which manufactures a Food and Drug Administration–approved pharmaceutical used to treat EPI.
EPI occurs when the production of pancreatic enzymes is insufficient and the digestion of food incomplete. Untreated EPI can lead to distressing symptoms and malnutrition, Phil Hart, MD, of the Ohio State University, Columbus, said in an interview.
Diagnosis can be challenging, but a high index of suspicion for EPI is appropriate for patients with unexplained weight loss and those with a personal or family history of pancreatic disease. An additional red flag is “a greasy, oily film in the toilet water, a sign indicating the malabsorption of nutrients, Dr. Hart pointed out.
Other symptoms may also be relevant to the diagnosis. “EPI is certainly not the most common reason for symptoms like diarrhea, flatulence, weight loss, etc. That being said, it is much more common than is appreciated,” Christopher E. Forsmark, MD, AGAF, of the University of Florida, Gainesville, said in an interview.
EPI should frequently be considered in the differential diagnosis of such conditions as functional bowel disease, irritable bowel disease, and lactose intolerance.
“We do not have accurate methods for diagnosis. Many patients with EPI, even those with underlying pancreatic disease who are at highest risk, are not diagnosed and therefore not treated,” said Dr. Forsmark.
The gold standard for diagnosis is a 72-hour stool collection and fecal fat analysis, which is both labor intensive, expensive, and rarely done. Other tests more-commonly done are fecal elastase and serum trypsin level or a mixed triglyceride breath test.
Dr. Hart and Dr. Forsmark were involved as AGA medical advisers in the development and drafting of the EPI Uncovered survey.
Of providers surveyed who had treated patient with EPI during the past 3 months, 70% of gastroenterologists reported that they had initiated discussion of EPI symptoms, prevention, diagnosis, or treatment; 24% of the time, it was the patient who had initiated that discussion. In contrast, primary care physicians reported that only 35% of the time had they initiated the discussion, while 43% of the time it was the patient who had done so. In 6% of the cases, gastroenterologists were unsure who had initiated the discussion or did not recall who had done so, while the corresponding figure for primary care physicians was 22%.
“Patients will usually respond honestly to direct questions but may not spontaneously volunteer to report their symptoms. This means that their physician must ask these questions, and not assume that the patient would let them know if GI symptoms were present,” Dr. Forsmark said.
Some patients might be gently and sensitively pushed to reveal information, Dr. Hart said. For example, he may ask patients if their symptoms are interfering with their work or their social interactions. Further, in his experience family members may prove to be better sources of relevant information than patients themselves.
The physicians surveyed revealed that approximately one-quarter of their patients (25% of primary care patients and 24% of patients of gastroenterologists) who are eventually diagnosed with EPI had previously been diagnosed with a different condition.
“There is a widespread lack of knowledge on the part of patients and even doctors about the pancreas and about EPI. There is also a widespread lack of knowledge on appropriate treatment of EPI. Patients often are not treated at all, or are treated with an inadequate dosage of pancreatic enzyme replacement therapy,” Dr. Forsmark said.
Further, while 63% of gastroenterologists said they considered the pancreas when diagnosing gastrointestinal symptoms, only 48% of primary care physicians reported considering the pancreas in these situations.
“In our culture, discussing GI symptoms is particularly embarrassing,” said Dr. Forsmark. “This is not uniform across these symptoms. For instance, patients will often report heartburn or GERD [gastroesophageal reflux disease] or difficulty swallowing but are more embarrassed to report bloating or flatulence or changes in bowel habits, or even abdominal pain.”
“In addition, as we have all had these types of symptoms during our lives and they often spontaneously improve, our tendency is to ignore them for prolonged periods,” Dr. Forsmark said.
“A recent patient of mine presented with some loose stools and severe weight loss. This patient reported that symptoms – in retrospect – had been present for more than 6 months. And noted that although he had lost more than 40 pounds, he had been ‘trying to lose weight.’ ” This patient seemed to ignore the fact that “all previous attempts at dieting had been ineffective, and his diet had not really changed. Only when a family member insisted did he agree to an evaluation, Dr. Forsmark said.
Of gastroenterologists surveyed, only 2% had not personally diagnosed at least one patient with EPI. In contrast, 57% of primary care physicians surveyed had never diagnosed a patient with EPI. Gastroenterologists should have all or most of the responsibility in educating patients about gastrointestinal symptoms, according to 78% of the primary care physicians and 92% of the gastroenterologists surveyed. And gastroenterologists should have all or most of the responsibility in treating EPI, said 84% of the primary care physicians and 93% of the gastroenterologists.
While 96% of gastroenterologists reported being either very or somewhat familiar with pancreatic enzyme replacement therapies, among primary care physicians surveyed only 52% expressed a similar level of familiarity with these drugs.
According to the National Institute for Diabetes and Digestive and Kidney Diseases 60-70 million Americans are affected by all digestive diseases. The exact prevalence of exocrine pancreatic insufficiency in not well defined, it is a symptom of a pancreatic disorder such as chronic pancreatitis.
Individuals experiencing chronic GI symptoms waited a mean of 3.7 years to see a health care professional, according to a recent survey.
Thus, for persons with chronic GI issues, inadequate communication may be a factor contributing to underdiagnosis. Fully 60% of patients surveyed cited embarrassment as the reason it was difficult to disclose GI symptoms to a doctor. Nearly half (47%) said they simply wanted to wait to see if their problems would go away. And 66% of patients interviewed had never heard of exocrine pancreatic insufficiency (EPI), while an additional 21% had heard of EPI but were not familiar with it.
Financial support for the survey came from AbbVie, which manufactures a Food and Drug Administration–approved pharmaceutical used to treat EPI.
EPI occurs when the production of pancreatic enzymes is insufficient and the digestion of food incomplete. Untreated EPI can lead to distressing symptoms and malnutrition, Phil Hart, MD, of the Ohio State University, Columbus, said in an interview.
Diagnosis can be challenging, but a high index of suspicion for EPI is appropriate for patients with unexplained weight loss and those with a personal or family history of pancreatic disease. An additional red flag is “a greasy, oily film in the toilet water, a sign indicating the malabsorption of nutrients, Dr. Hart pointed out.
Other symptoms may also be relevant to the diagnosis. “EPI is certainly not the most common reason for symptoms like diarrhea, flatulence, weight loss, etc. That being said, it is much more common than is appreciated,” Christopher E. Forsmark, MD, AGAF, of the University of Florida, Gainesville, said in an interview.
EPI should frequently be considered in the differential diagnosis of such conditions as functional bowel disease, irritable bowel disease, and lactose intolerance.
“We do not have accurate methods for diagnosis. Many patients with EPI, even those with underlying pancreatic disease who are at highest risk, are not diagnosed and therefore not treated,” said Dr. Forsmark.
The gold standard for diagnosis is a 72-hour stool collection and fecal fat analysis, which is both labor intensive, expensive, and rarely done. Other tests more-commonly done are fecal elastase and serum trypsin level or a mixed triglyceride breath test.
Dr. Hart and Dr. Forsmark were involved as AGA medical advisers in the development and drafting of the EPI Uncovered survey.
Of providers surveyed who had treated patient with EPI during the past 3 months, 70% of gastroenterologists reported that they had initiated discussion of EPI symptoms, prevention, diagnosis, or treatment; 24% of the time, it was the patient who had initiated that discussion. In contrast, primary care physicians reported that only 35% of the time had they initiated the discussion, while 43% of the time it was the patient who had done so. In 6% of the cases, gastroenterologists were unsure who had initiated the discussion or did not recall who had done so, while the corresponding figure for primary care physicians was 22%.
“Patients will usually respond honestly to direct questions but may not spontaneously volunteer to report their symptoms. This means that their physician must ask these questions, and not assume that the patient would let them know if GI symptoms were present,” Dr. Forsmark said.
Some patients might be gently and sensitively pushed to reveal information, Dr. Hart said. For example, he may ask patients if their symptoms are interfering with their work or their social interactions. Further, in his experience family members may prove to be better sources of relevant information than patients themselves.
The physicians surveyed revealed that approximately one-quarter of their patients (25% of primary care patients and 24% of patients of gastroenterologists) who are eventually diagnosed with EPI had previously been diagnosed with a different condition.
“There is a widespread lack of knowledge on the part of patients and even doctors about the pancreas and about EPI. There is also a widespread lack of knowledge on appropriate treatment of EPI. Patients often are not treated at all, or are treated with an inadequate dosage of pancreatic enzyme replacement therapy,” Dr. Forsmark said.
Further, while 63% of gastroenterologists said they considered the pancreas when diagnosing gastrointestinal symptoms, only 48% of primary care physicians reported considering the pancreas in these situations.
“In our culture, discussing GI symptoms is particularly embarrassing,” said Dr. Forsmark. “This is not uniform across these symptoms. For instance, patients will often report heartburn or GERD [gastroesophageal reflux disease] or difficulty swallowing but are more embarrassed to report bloating or flatulence or changes in bowel habits, or even abdominal pain.”
“In addition, as we have all had these types of symptoms during our lives and they often spontaneously improve, our tendency is to ignore them for prolonged periods,” Dr. Forsmark said.
“A recent patient of mine presented with some loose stools and severe weight loss. This patient reported that symptoms – in retrospect – had been present for more than 6 months. And noted that although he had lost more than 40 pounds, he had been ‘trying to lose weight.’ ” This patient seemed to ignore the fact that “all previous attempts at dieting had been ineffective, and his diet had not really changed. Only when a family member insisted did he agree to an evaluation, Dr. Forsmark said.
Of gastroenterologists surveyed, only 2% had not personally diagnosed at least one patient with EPI. In contrast, 57% of primary care physicians surveyed had never diagnosed a patient with EPI. Gastroenterologists should have all or most of the responsibility in educating patients about gastrointestinal symptoms, according to 78% of the primary care physicians and 92% of the gastroenterologists surveyed. And gastroenterologists should have all or most of the responsibility in treating EPI, said 84% of the primary care physicians and 93% of the gastroenterologists.
While 96% of gastroenterologists reported being either very or somewhat familiar with pancreatic enzyme replacement therapies, among primary care physicians surveyed only 52% expressed a similar level of familiarity with these drugs.
According to the National Institute for Diabetes and Digestive and Kidney Diseases 60-70 million Americans are affected by all digestive diseases. The exact prevalence of exocrine pancreatic insufficiency in not well defined, it is a symptom of a pancreatic disorder such as chronic pancreatitis.
Individuals experiencing chronic GI symptoms waited a mean of 3.7 years to see a health care professional, according to a recent survey.
Thus, for persons with chronic GI issues, inadequate communication may be a factor contributing to underdiagnosis. Fully 60% of patients surveyed cited embarrassment as the reason it was difficult to disclose GI symptoms to a doctor. Nearly half (47%) said they simply wanted to wait to see if their problems would go away. And 66% of patients interviewed had never heard of exocrine pancreatic insufficiency (EPI), while an additional 21% had heard of EPI but were not familiar with it.
Financial support for the survey came from AbbVie, which manufactures a Food and Drug Administration–approved pharmaceutical used to treat EPI.
EPI occurs when the production of pancreatic enzymes is insufficient and the digestion of food incomplete. Untreated EPI can lead to distressing symptoms and malnutrition, Phil Hart, MD, of the Ohio State University, Columbus, said in an interview.
Diagnosis can be challenging, but a high index of suspicion for EPI is appropriate for patients with unexplained weight loss and those with a personal or family history of pancreatic disease. An additional red flag is “a greasy, oily film in the toilet water, a sign indicating the malabsorption of nutrients, Dr. Hart pointed out.
Other symptoms may also be relevant to the diagnosis. “EPI is certainly not the most common reason for symptoms like diarrhea, flatulence, weight loss, etc. That being said, it is much more common than is appreciated,” Christopher E. Forsmark, MD, AGAF, of the University of Florida, Gainesville, said in an interview.
EPI should frequently be considered in the differential diagnosis of such conditions as functional bowel disease, irritable bowel disease, and lactose intolerance.
“We do not have accurate methods for diagnosis. Many patients with EPI, even those with underlying pancreatic disease who are at highest risk, are not diagnosed and therefore not treated,” said Dr. Forsmark.
The gold standard for diagnosis is a 72-hour stool collection and fecal fat analysis, which is both labor intensive, expensive, and rarely done. Other tests more-commonly done are fecal elastase and serum trypsin level or a mixed triglyceride breath test.
Dr. Hart and Dr. Forsmark were involved as AGA medical advisers in the development and drafting of the EPI Uncovered survey.
Of providers surveyed who had treated patient with EPI during the past 3 months, 70% of gastroenterologists reported that they had initiated discussion of EPI symptoms, prevention, diagnosis, or treatment; 24% of the time, it was the patient who had initiated that discussion. In contrast, primary care physicians reported that only 35% of the time had they initiated the discussion, while 43% of the time it was the patient who had done so. In 6% of the cases, gastroenterologists were unsure who had initiated the discussion or did not recall who had done so, while the corresponding figure for primary care physicians was 22%.
“Patients will usually respond honestly to direct questions but may not spontaneously volunteer to report their symptoms. This means that their physician must ask these questions, and not assume that the patient would let them know if GI symptoms were present,” Dr. Forsmark said.
Some patients might be gently and sensitively pushed to reveal information, Dr. Hart said. For example, he may ask patients if their symptoms are interfering with their work or their social interactions. Further, in his experience family members may prove to be better sources of relevant information than patients themselves.
The physicians surveyed revealed that approximately one-quarter of their patients (25% of primary care patients and 24% of patients of gastroenterologists) who are eventually diagnosed with EPI had previously been diagnosed with a different condition.
“There is a widespread lack of knowledge on the part of patients and even doctors about the pancreas and about EPI. There is also a widespread lack of knowledge on appropriate treatment of EPI. Patients often are not treated at all, or are treated with an inadequate dosage of pancreatic enzyme replacement therapy,” Dr. Forsmark said.
Further, while 63% of gastroenterologists said they considered the pancreas when diagnosing gastrointestinal symptoms, only 48% of primary care physicians reported considering the pancreas in these situations.
“In our culture, discussing GI symptoms is particularly embarrassing,” said Dr. Forsmark. “This is not uniform across these symptoms. For instance, patients will often report heartburn or GERD [gastroesophageal reflux disease] or difficulty swallowing but are more embarrassed to report bloating or flatulence or changes in bowel habits, or even abdominal pain.”
“In addition, as we have all had these types of symptoms during our lives and they often spontaneously improve, our tendency is to ignore them for prolonged periods,” Dr. Forsmark said.
“A recent patient of mine presented with some loose stools and severe weight loss. This patient reported that symptoms – in retrospect – had been present for more than 6 months. And noted that although he had lost more than 40 pounds, he had been ‘trying to lose weight.’ ” This patient seemed to ignore the fact that “all previous attempts at dieting had been ineffective, and his diet had not really changed. Only when a family member insisted did he agree to an evaluation, Dr. Forsmark said.
Of gastroenterologists surveyed, only 2% had not personally diagnosed at least one patient with EPI. In contrast, 57% of primary care physicians surveyed had never diagnosed a patient with EPI. Gastroenterologists should have all or most of the responsibility in educating patients about gastrointestinal symptoms, according to 78% of the primary care physicians and 92% of the gastroenterologists surveyed. And gastroenterologists should have all or most of the responsibility in treating EPI, said 84% of the primary care physicians and 93% of the gastroenterologists.
While 96% of gastroenterologists reported being either very or somewhat familiar with pancreatic enzyme replacement therapies, among primary care physicians surveyed only 52% expressed a similar level of familiarity with these drugs.
According to the National Institute for Diabetes and Digestive and Kidney Diseases 60-70 million Americans are affected by all digestive diseases. The exact prevalence of exocrine pancreatic insufficiency in not well defined, it is a symptom of a pancreatic disorder such as chronic pancreatitis.
Key clinical point: Embarrassment hinders diagnosis of lower GI conditions, including exocrine pancreatic insufficiency.
Major finding: Individuals experiencing chronic GI symptoms waited a mean of 3.7 years to see a health care professional.
Data source: An online survey of 1,001 patients, 250 gastroenterologists, and 250 primary care providers.
Disclosures: Financial support for the survey came from AbbVie, which manufactures an FDA-approved pharmaceutical used to treat EPI.
Antibiotic resistance remains a challenge for hospitals
The Centers for Disease Control and Prevention just released a surveillance report describing national estimates of antimicrobial resistance among health care–associated infections (HAIs) in hospitals. The report compiles HAI data submitted to the CDC’s National Healthcare Safety Network (NHSN) from almost all short-term acute care hospitals, inpatient rehabilitation facilities, and long-term acute care hospitals in the country.
These data highlight the broad reach and urgent nature of the drug resistance problem challenging clinicians today; resistance is occurring across different types of infections and patient populations, and dangerous resistance profiles such as carbapenem-resistant Enterobacteriaceae, or CRE, are not going away.
The report highlights the percentage of HAI organisms that were resistant to select antibiotics for 21 different bug-drug combinations from 2011 to 2014. Most noticeable across this time period was an increase in the percentage of Escherichia coli that tested resistant to extended-spectrum cephalosporins, fluoroquinolones, and were identified as multidrug resistant (Infect Control Hosp Epidemiol. 2016 Aug 30. doi: 10.1017/ice.2016.174).
In 2011, 41.1% of E. coli central line–associated bloodstream infections (CLABSIs) were resistant to fluoroquinolones; this percentage increased to 49.3% by 2014. And, among catheter-associated UTIs (CAUTIs), 8% of E. coli were identified as multidrug resistant in 2014, an increase from 5.5% in 2011.
Hospitals continue to report CRE infections, which are often untreatable and represent a serious public health threat. Across the major HAI types analyzed in this report, CRE were found in CLABSIs (7.1% of Enterobacteriaceae were resistant to carbapenems), CAUTIs (4.0% resistant), and surgical site infections (1.8% resistant). After taking a closer look at individual species of bacteria, we found that almost 11% of CLABSIs caused by Klebsiella species were resistant to carbapenems, which was the highest resistance among all Enterobacteriaceae species. Furthermore, Enterobacter species showed increasing resistance to carbapenems, as the percentage resistant in CLABSIs increased from 3.0% in 2011 to 6.6% in 2014.
These data underscore the urgent nature of CRE prevention efforts, and fighting back against these deadly bacteria will require collaborative efforts from the entire health care community including health care facility leaders, health care providers, and state and local health departments.
Antibiotic-resistant infections are an important patient safety issue and continue to pose a threat to modern medicine. There are small improvements in some phenotypes such as multidrug-resistant Acinetobacter, in which the percentage resistant in CLABSIs decreased from 60.9% in 2011 to 43.7% in 2014. Multidrug-resistant Klebsiella appears to be declining as well, from 20.9% resistant to 17.2%. Despite some improvements, the data in this report support the conclusion that much more work is needed to combat antibiotic resistance. The CDC has identified three critical efforts to slow the spread of resistant HAIs:
• Prevent infections related to devices and surgeries.
• Prevent the spread of bacteria between patients and between facilities.
• Improve antibiotic use in health care settings.
In addition to drug resistance, this report looked at the frequency of pathogens causing HAIs. The No. 1 and No. 3 most common pathogens among all HAIs were E.coli and Klebsiella, both of which are gram-negative bacteria with the propensity to develop antibiotic resistance.
The data also help identify important differences in the causes of HAIs across each of the infection types. For example, CLABSIs were more commonly due to gram positive organisms and Candida (a fungus), while surgical site infections (SSIs) were most frequently caused by Staph aureus. NHSN tracks SSIs following 39 different types of procedures, and while Staph aureus was the most common pathogen reported overall, the pathogen distributions did vary by surgery site. For example, almost 30% of SSIs following transplant procedures were caused by a species of Enterococcus.
Obviously, there’s far more data in the report than we can discuss here. Fortunately, the CDC’s new Antibiotic Resistance Patient Safety Atlas gives everyone an opportunity to explore these resistance patterns further; color-coded maps and charts included within the Atlas can help you identify common resistance phenotypes in your state and region. While these data give us a national snapshot of resistance profiles, we know there is wide variation among individual health care settings. It is important for providers to become familiar with the common pathogens and resistance profiles in their hospitals and recognize that common infecting organisms vary across different types of infections.
This report underscores the important challenges posed by resistant organisms in hospitals. Combating antibiotic resistance is a top public health priority in the United States and around the world, and having data to direct action is a key part of tackling the problem.
The CDC will continue to use and expand its efforts to monitor antibiotic resistance through surveillance systems such as NHSN, and will remain committed to providing data to support the health care community in efforts to reduce the spread of resistance and improve antibiotic use.
Lindsey Weiner, MPH, is an epidemiologist and associate service fellow in the Surveillance Branch, Division of Healthcare Quality Promotion, at the Centers for Disease Control and Prevention.
The Centers for Disease Control and Prevention just released a surveillance report describing national estimates of antimicrobial resistance among health care–associated infections (HAIs) in hospitals. The report compiles HAI data submitted to the CDC’s National Healthcare Safety Network (NHSN) from almost all short-term acute care hospitals, inpatient rehabilitation facilities, and long-term acute care hospitals in the country.
These data highlight the broad reach and urgent nature of the drug resistance problem challenging clinicians today; resistance is occurring across different types of infections and patient populations, and dangerous resistance profiles such as carbapenem-resistant Enterobacteriaceae, or CRE, are not going away.
The report highlights the percentage of HAI organisms that were resistant to select antibiotics for 21 different bug-drug combinations from 2011 to 2014. Most noticeable across this time period was an increase in the percentage of Escherichia coli that tested resistant to extended-spectrum cephalosporins, fluoroquinolones, and were identified as multidrug resistant (Infect Control Hosp Epidemiol. 2016 Aug 30. doi: 10.1017/ice.2016.174).
In 2011, 41.1% of E. coli central line–associated bloodstream infections (CLABSIs) were resistant to fluoroquinolones; this percentage increased to 49.3% by 2014. And, among catheter-associated UTIs (CAUTIs), 8% of E. coli were identified as multidrug resistant in 2014, an increase from 5.5% in 2011.
Hospitals continue to report CRE infections, which are often untreatable and represent a serious public health threat. Across the major HAI types analyzed in this report, CRE were found in CLABSIs (7.1% of Enterobacteriaceae were resistant to carbapenems), CAUTIs (4.0% resistant), and surgical site infections (1.8% resistant). After taking a closer look at individual species of bacteria, we found that almost 11% of CLABSIs caused by Klebsiella species were resistant to carbapenems, which was the highest resistance among all Enterobacteriaceae species. Furthermore, Enterobacter species showed increasing resistance to carbapenems, as the percentage resistant in CLABSIs increased from 3.0% in 2011 to 6.6% in 2014.
These data underscore the urgent nature of CRE prevention efforts, and fighting back against these deadly bacteria will require collaborative efforts from the entire health care community including health care facility leaders, health care providers, and state and local health departments.
Antibiotic-resistant infections are an important patient safety issue and continue to pose a threat to modern medicine. There are small improvements in some phenotypes such as multidrug-resistant Acinetobacter, in which the percentage resistant in CLABSIs decreased from 60.9% in 2011 to 43.7% in 2014. Multidrug-resistant Klebsiella appears to be declining as well, from 20.9% resistant to 17.2%. Despite some improvements, the data in this report support the conclusion that much more work is needed to combat antibiotic resistance. The CDC has identified three critical efforts to slow the spread of resistant HAIs:
• Prevent infections related to devices and surgeries.
• Prevent the spread of bacteria between patients and between facilities.
• Improve antibiotic use in health care settings.
In addition to drug resistance, this report looked at the frequency of pathogens causing HAIs. The No. 1 and No. 3 most common pathogens among all HAIs were E.coli and Klebsiella, both of which are gram-negative bacteria with the propensity to develop antibiotic resistance.
The data also help identify important differences in the causes of HAIs across each of the infection types. For example, CLABSIs were more commonly due to gram positive organisms and Candida (a fungus), while surgical site infections (SSIs) were most frequently caused by Staph aureus. NHSN tracks SSIs following 39 different types of procedures, and while Staph aureus was the most common pathogen reported overall, the pathogen distributions did vary by surgery site. For example, almost 30% of SSIs following transplant procedures were caused by a species of Enterococcus.
Obviously, there’s far more data in the report than we can discuss here. Fortunately, the CDC’s new Antibiotic Resistance Patient Safety Atlas gives everyone an opportunity to explore these resistance patterns further; color-coded maps and charts included within the Atlas can help you identify common resistance phenotypes in your state and region. While these data give us a national snapshot of resistance profiles, we know there is wide variation among individual health care settings. It is important for providers to become familiar with the common pathogens and resistance profiles in their hospitals and recognize that common infecting organisms vary across different types of infections.
This report underscores the important challenges posed by resistant organisms in hospitals. Combating antibiotic resistance is a top public health priority in the United States and around the world, and having data to direct action is a key part of tackling the problem.
The CDC will continue to use and expand its efforts to monitor antibiotic resistance through surveillance systems such as NHSN, and will remain committed to providing data to support the health care community in efforts to reduce the spread of resistance and improve antibiotic use.
Lindsey Weiner, MPH, is an epidemiologist and associate service fellow in the Surveillance Branch, Division of Healthcare Quality Promotion, at the Centers for Disease Control and Prevention.
The Centers for Disease Control and Prevention just released a surveillance report describing national estimates of antimicrobial resistance among health care–associated infections (HAIs) in hospitals. The report compiles HAI data submitted to the CDC’s National Healthcare Safety Network (NHSN) from almost all short-term acute care hospitals, inpatient rehabilitation facilities, and long-term acute care hospitals in the country.
These data highlight the broad reach and urgent nature of the drug resistance problem challenging clinicians today; resistance is occurring across different types of infections and patient populations, and dangerous resistance profiles such as carbapenem-resistant Enterobacteriaceae, or CRE, are not going away.
The report highlights the percentage of HAI organisms that were resistant to select antibiotics for 21 different bug-drug combinations from 2011 to 2014. Most noticeable across this time period was an increase in the percentage of Escherichia coli that tested resistant to extended-spectrum cephalosporins, fluoroquinolones, and were identified as multidrug resistant (Infect Control Hosp Epidemiol. 2016 Aug 30. doi: 10.1017/ice.2016.174).
In 2011, 41.1% of E. coli central line–associated bloodstream infections (CLABSIs) were resistant to fluoroquinolones; this percentage increased to 49.3% by 2014. And, among catheter-associated UTIs (CAUTIs), 8% of E. coli were identified as multidrug resistant in 2014, an increase from 5.5% in 2011.
Hospitals continue to report CRE infections, which are often untreatable and represent a serious public health threat. Across the major HAI types analyzed in this report, CRE were found in CLABSIs (7.1% of Enterobacteriaceae were resistant to carbapenems), CAUTIs (4.0% resistant), and surgical site infections (1.8% resistant). After taking a closer look at individual species of bacteria, we found that almost 11% of CLABSIs caused by Klebsiella species were resistant to carbapenems, which was the highest resistance among all Enterobacteriaceae species. Furthermore, Enterobacter species showed increasing resistance to carbapenems, as the percentage resistant in CLABSIs increased from 3.0% in 2011 to 6.6% in 2014.
These data underscore the urgent nature of CRE prevention efforts, and fighting back against these deadly bacteria will require collaborative efforts from the entire health care community including health care facility leaders, health care providers, and state and local health departments.
Antibiotic-resistant infections are an important patient safety issue and continue to pose a threat to modern medicine. There are small improvements in some phenotypes such as multidrug-resistant Acinetobacter, in which the percentage resistant in CLABSIs decreased from 60.9% in 2011 to 43.7% in 2014. Multidrug-resistant Klebsiella appears to be declining as well, from 20.9% resistant to 17.2%. Despite some improvements, the data in this report support the conclusion that much more work is needed to combat antibiotic resistance. The CDC has identified three critical efforts to slow the spread of resistant HAIs:
• Prevent infections related to devices and surgeries.
• Prevent the spread of bacteria between patients and between facilities.
• Improve antibiotic use in health care settings.
In addition to drug resistance, this report looked at the frequency of pathogens causing HAIs. The No. 1 and No. 3 most common pathogens among all HAIs were E.coli and Klebsiella, both of which are gram-negative bacteria with the propensity to develop antibiotic resistance.
The data also help identify important differences in the causes of HAIs across each of the infection types. For example, CLABSIs were more commonly due to gram positive organisms and Candida (a fungus), while surgical site infections (SSIs) were most frequently caused by Staph aureus. NHSN tracks SSIs following 39 different types of procedures, and while Staph aureus was the most common pathogen reported overall, the pathogen distributions did vary by surgery site. For example, almost 30% of SSIs following transplant procedures were caused by a species of Enterococcus.
Obviously, there’s far more data in the report than we can discuss here. Fortunately, the CDC’s new Antibiotic Resistance Patient Safety Atlas gives everyone an opportunity to explore these resistance patterns further; color-coded maps and charts included within the Atlas can help you identify common resistance phenotypes in your state and region. While these data give us a national snapshot of resistance profiles, we know there is wide variation among individual health care settings. It is important for providers to become familiar with the common pathogens and resistance profiles in their hospitals and recognize that common infecting organisms vary across different types of infections.
This report underscores the important challenges posed by resistant organisms in hospitals. Combating antibiotic resistance is a top public health priority in the United States and around the world, and having data to direct action is a key part of tackling the problem.
The CDC will continue to use and expand its efforts to monitor antibiotic resistance through surveillance systems such as NHSN, and will remain committed to providing data to support the health care community in efforts to reduce the spread of resistance and improve antibiotic use.
Lindsey Weiner, MPH, is an epidemiologist and associate service fellow in the Surveillance Branch, Division of Healthcare Quality Promotion, at the Centers for Disease Control and Prevention.
Ulnar Collateral Ligament Reconstruction: Current Philosophy in 2016
The ulnar collateral ligament (UCL) is the primary restraint to valgus stress between 20° and 125° of motion.1-5 Overhead athletes, most commonly baseball pitchers, are at risk of developing UCL insufficiency, and dysfunction presents as pain with loss of velocity and control. Some injuries may present acutely while throwing, but many patients, when questioned, report a preceding period of either pain or loss of velocity and control.
Authors have documented a significant rise in elbow injuries in young athletes, especially pitchers.6 Extended seasons, higher pitch counts, year-round pitching, pitching while fatigued, and pitching for multiple teams are risk factors for elbow injuries.7 Pitchers in the southern United States are more likely to undergo UCL reconstruction than those from the northern states.8 Pitchers who also play catcher are at a higher risk due to more total throws than those who pitch and play other positions or pitch only. Throwers with higher velocity are more likely to pitch in showcases, pitch for multiple teams, and pitch with pain and fatigue, and these are all risk factors.6 Also, in one study of youth baseball injuries, individuals in the injured group were found to be taller and heavier than those in the uninjured group.6 Pitch counts, rest from pitching during the off-season, adequate rest, and ensuring pain-free pitching can lessen the risk of injury.6 As expected with the rise in throwing injuries, the rise in medial elbow procedures has risen.9
While throwing, stress across the medial elbow has been measured to be nearly 300 N. A maximum varus force during pitching was measured to be 64 N-m at 95° ± 14°.10 Morrey and An4 determined that the UCL generated 54% of the varus force at 90° of flexion. During active pitching, this value is likely reduced due to simultaneous muscle contraction, but if one assumes the UCL bears 54% of the maximal load, the UCL must be able to withstand 34 N-m. The UCL can withstand a maximum valgus torque between 22.7 and 34 N-m11-13; therefore, during pitching, the UCL is at or above its failure load. After thousands of cycles over many years, one can imagine how the UCL might be injured.
Multiple techniques have been proposed in the surgical treatment of UCL injuries. Jobe14 pioneered UCL reconstruction in 1974 in Tommy John, a Major League Baseball pitcher. John returned to pitch successfully, and both the UCL and the reconstruction are commonly called by his name. Jobe14 reported his technique in 1986, and it has remained, with a few modifications, the primary method for reconstruction of the UCL (Figure 1). 
Evaluation
A standard evaluation with physical examination and imaging is completed in all throwers with elbow pain. In our prior study,16 we found that 100% of patients experienced pain during athletic activity and that 96% of throwers complained of pain during late cocking and acceleration phases of the throwing motion. Nearly half reported an acute onset of pain, while 53% were unable to identify a single inciting event. Seventy-five percent of the acute injuries were during competition. Delayed diagnosis was very common, with an average time to diagnosis after onset of symptoms of 6.4 months. Neurologic symptoms were seen in 23% of athletes, most of which were ulnar nerve paresthesias during throwing.16
Physical examination includes inspection for swelling, hand intrinsic atrophy, neurovascular examination, range of motion, shoulder examination, and elbow stress examination. Range of motion at presentation averaged 5° to 135° with 85° of supination and pronation.16 All patients need neurologic evaluation for ulnar nerve dysfunction. Tinel test of the cubital tunnel was positive in 21%.16 Significant ulnar nerve dysfunction, including hand weakness, is much less common but must be well examined and documented. The shoulder must also be evaluated for loss of rotation, which can lead to increased stress on the elbow. An evaluation of mechanics may point out flaws in technique, which may be contributing to elbow stress. The UCL stress examination includes static stress at 30° of flexion, the milking test at 90°, and the moving valgus stress test. The presence of pain directly over the UCL or laxity compared to the uninvolved side is suggestive of UCL injury.
Radiographic evaluation is completed in all patients with concern for UCL injury. Standard x-rays of the elbow, including anteroposterior, medial, and lateral obliques, axial olecranon, and lateral views, are obtained to evaluate bony abnormalities. Fifty-seven percent of our series showed some abnormality, most commonly olecranon osteophyte formation or ectopic calcification within the UCL substance. Stress radiography rarely changed the treatment course and is somewhat difficult to interpret because of the reports documenting normal increased medial elbow opening in the dominant arm of throwing athletes.21 Magnetic resonance imaging (MRI) is obtained very commonly in this patient population, and intra-articular contrast is crucial. Partial, undersurface tears are common, and a contrasted study better demonstrates undersurface tears or avulsions. The T-sign as described by Timmerman and colleagues22 using computed tomography (CT) arthrography shows partial undersurface detachment, which can be difficult to see without intra-articular contrast.22 This finding is very well visualized on MRI arthrogram as well (Figure 3). 
Nonoperative Management
Nonoperative treatment is recommended for 3 months prior to performing reconstruction. Patients are given complete rest from throwing, but rehabilitation is initiated immediately. Rehabilitation exercises and nonsteroidal anti-inflammatory medications are prescribed, and activities that place valgus stress across the elbow are avoided. After resolution of symptoms, an interval throwing program is initiated, and the athlete is gradually returned to sport. Unfortunately, due to season-specific schedules and time-sensitive demands in high-level throwers, operative treatment is often chosen without an extended period of conservative treatment.
Platelet-rich plasma (PRP) therapy has recently been shown to improve healing rates and promote healing in partial UCL tears,23 and as orthobiologics are advanced, they will likely play a larger role in the treatment of UCL injuries.
Surgical Technique
At our institution, UCL reconstruction is performed with the modified Jobe technique as described by Azar and colleagues.17 Arthroscopy prior to reconstruction was routinely performed at our institution until we recognized that arthroscopy rarely changed the preoperative plan.16 Currently, the presence of anterior pathology such as loose bodies or osteochondral defect is our only indication for arthroscopy before reconstruction.
Ipsilateral palmaris autograft is our current graft of choice. This must be examined preoperatively because 16% of patients have unilateral absence and 9% have bilateral absence.24 In revision cases or in patients with insufficient or absent palmaris, contralateral palmaris followed by contralateral gracilis tendon is used. The contralateral gracilis is chosen because of ease of setup and position of the surgeon during the harvest. Gracilis tendon is also used in cases with bony involvement of the ligament based on the results from Dugas and colleagues.25 Toe extensors, plantaris, and patellar tendon grafts have also been used. One recent study showed that neither graft choice nor diameter affected resistance to valgus stress, and that all reconstruction types restored strength at 60° to 120° of flexion.26
Ulnar nerve transposition is performed in all cases regardless of the presence of preoperative nerve symptoms. A complete decompression is completed proximally to the Arcade of Struthers and distally to the deep portion of the flexor carpi ulnaris. A single fascial sling of medial intermuscular septum originating from the epicondylar attachment is used to stabilize the nerve without compression. At wound closure, the deep fascia on the posterior skin flap is also sewn into the cubital tunnel to prevent the nerve from subluxating back into the groove. A single suture is placed distally closing the muscle fascia to prevent propagation of the fascial incision, which can lead to herniation. Transposition is necessary because of the ulnar nerve exposure required in the modified Jobe technique to allow elevation of the deep flexor muscle mass for ligament exposure.
The reconstruction is completed as described by Jobe14 but with a few modifications as described by Azar and colleagues17 and slight adaptations implemented since that time. The flexor-pronator mass is retracted laterally instead of detachment or splitting as described by Thompson and colleagues.27 A subcutaneous rather than a submuscular ulnar nerve transposition is used.
The patient is positioned supine using an arm board. If gracilis tendon is chosen, the contralateral leg is prepped and draped simultaneously. A tourniquet is inflated after exsanguination. A medial approach is performed, and the medial antebrachial nerve is located and protected. The ulnar nerve is then located in the cubital tunnel and mobilized. The neurolysis extends to the deep portion of the flexor carpi ulnaris distally and proximally to the Arcade of Struthers, and the nerve is retracted with a vessel loop. The flexor muscle mass is not elevated from the medial epicondyle; rather, it is retracted anteriorly by small Hohmann retractors. The dissection is carried down to the UCL and found at its attachments to the medial epicondyle and sublime tubercle. If no tear is seen on the superficial surface of the ligament, a longitudinal incision is made through the ligament. Undersurface tears, partial tears, and avulsions can then be identified (Figure 4). 
The autologous graft of choice is then harvested. Our technique for palmaris harvest is performed with three 1-cm transverse incisions. The palmaris is palpated and marked with the first incision made near the distal wrist crease, and the second incision is made 3 to 4 cm proximal to the first. The tendon is found in both distal incisions and cut distally with the wrist flexed to maximize tendon length. The tendon is then pulled through the second incision and tensioned to identify the most proximal location the tendon can be palpated. A third incision is made directly over this point and carried down to cut the tendon. This usually provides a graft length of 15 to 20 cm; 13 cm is the minimum graft length to ensure good graft fixation. Muscle is removed from the tendon and each end is secured with a No. 1 nonabsorbable suture in a locking fashion.
If posterior osteophytes are present, they are removed through a posterior, vertical arthrotomy. Over-resection of the olecranon must be avoided, as this can further destabilize the elbow and place increased stress on the reconstruction. Posterior loose bodies can also be removed through this arthrotomy. The arthrotomy is then closed with absorbable suture.
Tunnel placement is critical to success. A 3.2-mm drill bit is used with palmaris grafts and a 4-mm drill bit is used with gracilis grafts. Two convergent tunnels are drilled in the medial epicondyle in a Y fashion and 2 convergent tunnels are drilled at the sublime tubercle in a U or V fashion. After drilling the first tunnel on each side, a hemostat is placed in the tunnel as an aiming point to ensure a complete tunnel is made. The junction is smoothed with a curette, leaving a 5-mm bone bridge between the articular surface and the tunnels. A bent Hewson suture passer is used to pass one end of the graft through the ulna. The 2 limbs of the tendon graft are then passed through the humeral tunnels, creating a figure-of-eight. A varus stress is applied with the elbow at roughly 30° and the 2 limbs are tied together with a No. 1 nonabsorbable suture. If enough graft remains, one or both limbs are passed back through the tunnels and secured again with No. 1 nonabsorbable suture. The 2 limbs are then tied side-to-side, incorporating the native ligament to further secure and tighten the reconstruction.
The ulnar nerve is then secured using a strip of medial intermuscular septum left intact to its insertion at the medial epicondyle. This is attached to the flexor-pronator muscle fascia with a 3-0 nonabsorbable suture. Enough length should be harvested from the septum to ensure there is no compression on the nerve. The deep posterior fascial tissue is then sewn to the periosteum of the medial epicondyle to further prevent subluxation of the nerve back into the groove. The skin is then closed in layered fashion over a superficial drain. The patient is placed in a well-padded posterior splint for 1 week, then the rehabilitation protocol is initiated as discussed below.
Postoperative Rehabilitation
A standardized postoperative 4-phase rehabilitation program for ulnar collateral reconstruction is followed as described by Wilk and colleagues.28-30 The first phase begins immediately after surgery and continues for 4 weeks. During surgery, the patient’s elbow is placed in a compression dressing with a posterior splint to immobilize the elbow in 90° of flexion with wrist motion for 1 week to allow initial healing. Full range of motion of the elbow joint is restored by the end of the fifth to sixth week after surgery.
During phase II (weeks 4-10), a progressive isotonic strengthening program is initiated. Exercises are focused on scapular, rotator cuff, deltoid, and arm musculature. Shoulder range of motion and stretching exercises are performed during this phase and the Thrower’s Ten exercise program is initiated. Any adaptations or strength deficits are addressed during this phase.
During the advanced strengthening phase (phase III), from weeks 10 to 16, a sport-specific exercise/rehabilitation program is initiated. During this phase, stretching and flexibility exercises are performed to enhance strength, power, and endurance. During this phase the patient is placed on the advanced Thrower’s Ten program. Isotonic strengthening exercises are progressed, and at week 12, the athlete is allowed to begin an isotonic lifting program, including bench press, seated rowing, latissimus dorsi pull downs, triceps push downs, and biceps curls. In addition, the athlete performs specific exercises to emphasize sport-specific movements. At week 12, overhead athletes begin a 2-hand plyometric throwing program, and at 14 weeks, a 1
Discussion
Results after ulnar collateral reconstruction have been good. In our series of 743 patients, 83% returned to the same or higher level at an average of 11.6 months.16 There was a 4% major complication rate and 16% minor complication rate. Major complications included medial epicondyle fracture (0.5%), significant ulnar nerve dysfunction (1 patient), rupture of graft (1%), and graft site infection. Sixteen percent of patients had ulnar nerve dysfunction, and 82% of these resolved within 6 weeks. All but 1 patient’s paresthesias resolved within 1 year.16 The 10-year follow-up of this group of patients included 256 patients and was reported by Osbahr and colleagues31 in 2014. Retirement from baseball was due to reasons other than the elbow in 86%, and 98% were still able to throw on at least a recreational level. The overall longevity was 3.6 years, with 2.9 years at pre-injury level or higher. Statistically, pitchers performed at a higher level after reconstruction.31
A recent review by Erickson and colleagues9 showed an overall 82% excellent and 8% good result when evaluating different techniques, including the American Sports Medicine Institute (ASMI) modification of Jobe’s technique, docking technique, and Jobe’s technique. With an overall complication rate of 10% (75% of which was transient ulnar neuritis), the procedure was deemed overall a safe surgical option. Collegiate athletes had the highest return to sport (95%) compared with high school athletes (89%) and professional athletes (86%). The docking technique had the highest rate of return to play (97%) compared with ASMI technique (93%) and Jobe technique (66%).9 Results after repair have not been as good as reconstruction, as reported in 2 studies.16,32 Savoie and colleagues,15 however, reported 93% good/excellent results after primary UCL repair alone.
Another recent review of outcomes showed an overall return to same or higher level was best with docking or modified docking techniques (90.4% and 91.3%, respectively).19 Overall return with modified Jobe technique was 77%.19 O’Brien and colleagues20 performed a review of 33 patients with either modified Jobe or docking technique that showed 81% return to same or higher level with modified Jobe vs 92% with docking technique. The Kerlan-Jobe Orthopaedic Clinic scores were higher in the modified Jobe group (79 vs 74) and the docking technique group returned to play nearly 1 month sooner (12.4 months vs 11.8 months).20 However, comparing different techniques in a heterogenous patient population over 40 years is difficult. Many of the modified Jobe technique cases were performed in the early evolution of the rehabilitation and return-to-play programs. We believe that the current modified Jobe technique has results equal to any other variation.
Despite good results with reconstructions, the recovery is lengthy and most pitchers cannot fully return to competition level for 12 to 18 months. Extensive research has been performed in exploring alternatives to the traditional reconstruction. Advancements in orthobiologics and development of new surgical options seem to provide an alternative to reconstruction, and may allow faster return to competition with less morbidity.
PRP has been at the forefront of orthopedic research for the last 2 decades, mostly focused in tendon and bone healing. Due to the release of many inflammatory mediators, PRP is theorized to initiate a healing response with growth factors that can direct healing towards normal tissue.33 Two main types of PRP are reported based on the presence or absence of leukocytes. PRP has been studied in many applications, but only one clinical study on the UCL has been published to date. Podesta and colleagues23 injected PRP into the elbow of 34 baseball players with MRI-confirmed partial UCL tear. The athletes then underwent a rehabilitation program, which limited stress across the UCL. Type 1A PRP was used (leukocyte-rich, unactivated, 5x or greater platelet concentration33). Athletes were allowed to return to sport based on symptoms and examination findings. Eighty-eight percent returned to same level of play without complaints at average 70 week follow-up, and average return to play ranged from 10 to 15 weeks.23 No specific data were given on the 16 pitchers in the group, but with such a high rate of return, PRP needs to be further evaluated in the treatment of UCL injuries.
Another recent study from Dugas and colleagues18 presented primary UCL repair using a tape augment (InternalBrace, Arthrex). Nine matched cadaver elbows underwent UCL sectioning and then either modified Jobe reconstruction or primary repair of the UCL with placement of the InternalBrace. The biomechanical data showed the repair with internal brace to have slightly less gap, more stiffness, and higher failure strength, although these findings were not statistically significant.18 This bone-preserving technique with less exposure and healing of the native ligament may be another step towards good results with a quicker return to throwing.
Conclusion
UCL injuries can be disabling in throwers. Reconstruction has afforded throwers a high rate of return to preinjury function or better, and several techniques have been presented that produce acceptable results. Overall complication rates range from 10% to 15%, and the majority of complications are transient ulnar neuropraxias. Orthobiologics and repair with augmentation have more recently offered additional options that may improve success of nonoperative treatment or allow less-invasive surgical treatment. Increased involvement in youth sports and early specialization is driving injury rates in young athletes. The orthopedic community must continue to look for better ways to prevent these injuries and investigate better methods to return athletes to high-level competition.
Am J Orthop. 2016;45(7):E534-E540. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
1. Fuss FK. The ulnar collateral ligament of the human elbow joint. Anatomy, function and biomechanics. J Anat. 1991;175:203-212.
2. Hotchkiss RN, Weiland AJ. Valgus stability of the elbow. J Orthop Res. 1987;5(3):372-377.
3. Morrey BF. Applied anatomy and biomechanics of the elbow joint. Instr Course Lect. 1986;35:59-68.
4. Morrey BF, An KN. Articular and ligamentous contributions to the stability of the elbow joint. Am J Sports Med. 1983;11(5):315-319.
5. Morrey BF, An KN. Functional anatomy of the ligaments of the elbow. Clin Orthop. 1985;(201):84-90.
6. Olsen SJ 2nd, Fleisig GS, Dun S, Loftice J, Andrews JR. Risk factors for shoulder and elbow injuries in adolescent baseball pitchers. Am J Sports Med. 2006;34(6):905-912.
7. Fleisig GS, Andrews JR. Prevention of elbow injuries in youth baseball pitchers. Sports Health. 2012;4(5):419-424.
8. Zaremski JL, Horodyski M, Donlan RM, Brisbane ST, Farmer KW. Does geographic location matter on the prevalence of ulnar collateral ligament reconstruction in collegiate baseball pitchers? Orthop J Sports Med. 2015;3(11):2325967115616582.
9. Erickson BJ, Nwachukwu BU, Rosas S, et al. Trends in medial ulnar collateral ligament reconstruction in the United States: A retrospective review of a large private-payer database from 2007 to 2011. Am J Sports Med. 2015;43(7):1770-1774.
10. Fleisig GS, Andrews JR, Dillman CJ. Kinetics of baseball pitching with implications about injury mechanism. Am J Sports Med. 1995;23(2):233-239.
11. Dillman CJ, Smutz P, Werner S. Valgus extension overload in baseball pitching. Med Sci Sports Exerc. 1991;23(suppl 4):S135.
12. Hechtman KS, Tjin-A-Tsoi EW, Zvijac JE, Uribe JW, Latta LL. Biomechanics of a less invasive procedure for reconstruction of the ulnar collateral ligament of the elbow. Am J Sports Med. 1998;26(5):620-624.
13. Ahmad CS, Lee TQ, ElAttrache NS. Biomechanical evaluation of a new ulnar collateral ligament reconstruction technique with interference screw fixation. Am J Sports Med. 2003;31(3):332-337.
14. Jobe FW, Stark HE, Lombardo SJ. Reconstruction of the ulnar collateral ligament in athletes. J Bone Joint Surg Am. 1986;68(8):1158-1163.
15. Savoie FH 3rd, Trenhaile SW, Roberts J, Field LD, Ramsey JR. Primary repair of ulnar collateral ligament injuries of the elbow in young athletes: a case series of injuries to the proximal and distal ends of the ligament. Am J Sports Med. 2008;36(6):1066-1072.
16. Cain EL, Andrews JR, Dugas JR, et al. Outcome of ulnar collateral ligament reconstruction of the elbow in 1281 athletes results in 743 athletes with minimum 2-year follow-up. Am J Sports Med. 2010;38(12):2426-2434.
17. Azar FM, Andrews JR, Wilk KE, Groh D. Operative treatment of ulnar collateral ligament injuries of the elbow in athletes. Am J Sports Med. 2000;28(1):16-23.
18. Dugas JR, Walters BL, Beason DP, Fleisig GS, Chronister JE. Biomechanical comparison of ulnar collateral ligament repair with internal bracing versus modified Jobe reconstruction. Am J Sports Med. 2016;44(3):735-741.
19. Watson JN, McQueen P, Hutchinson MR. A systematic review of ulnar collateral ligament reconstruction techniques. Am J Sports Med. 2014;42(10):2510-2516.
20. O’Brien DF, O’Hagan T, Stewart R, et al. Outcomes for ulnar collateral ligament reconstruction: A retrospective review using the KJOC assessment score with two-year follow-up in an overhead throwing population. J Shoulder Elbow Surg. 2015;24(6):934-940.
21. Ellenbecker TS, Mattalino AJ, Elam EA, Caplinger RA. Medial elbow joint laxity in professional baseball pitchers a bilateral comparison using stress radiography. Am J Sports Med. 1998;26(3):420-424.
22. Timmerman LA, Schwartz ML, Andrews JR. Preoperative evaluation of the ulnar collateral ligament by magnetic resonance imaging and computed tomography arthrography evaluation in 25 baseball players with surgical confirmation. Am J Sports Med. 1994;22(1):26-32.
23. Podesta L, Crow SA, Volkmer D, Bert T, Yocum LA. Treatment of partial ulnar collateral ligament tears in the elbow with platelet-rich plasma. Am J Sports Med. 2013;41(7):1689-1694.
24. Thompson NW, Mockford BJ, Cran GW. Absence of the palmaris longus muscle: a population study. Ulster Med J. 2001;70(1):22-24.
25. Dugas JR, Bilotta J, Watts CD, et al. Ulnar collateral ligament reconstruction with gracilis tendon in athletes with intraligamentous bony excision technique and results. Am J Sports Med. 2012;40(7):1578-1582.
26. Dargel J, Küpper F, Wegmann K, Oppermann J, Eysel P, Müller LP. Graft diameter does not influence primary stability of ulnar collateral ligament reconstruction of the elbow. J Orthop Sci. 2015;20(2):307-313.
27. Thompson WH, Jobe FW, Yocum LA, Pink MM. Ulnar collateral ligament reconstruction in athletes: muscle-splitting approach without transposition of the ulnar nerve. J Shoulder Elbow Surg. 2001;10(2):152-157.
28. Wilk KE, Arrigo CA, Andrews JR. Rehabilitation of the elbow in the throwing athlete. J Orthop Sports Phys Ther. 1993;17(6):305-317.
29. Wilk KE, Arrigo CA, Andrews JR, et al. Rehabilitation following elbow surgery in the throwing athlete. Oper Tech Sports Med. 1996;4:114-132.
30. Wilk KE, Arrigo CA, Andrews JR, et al. Preventative and Rehabilitation Exercises for the Shoulder and Elbow. 4th ed. Birmingham, AL: American Sports Medicine Institute; 1996.
31. Osbahr DC, Cain EL, Raines BT, Fortenbaugh D, Dugas JR, Andrews JR. Long-term outcomes after ulnar collateral ligament reconstruction in competitive baseball players minimum 10-year follow-up. Am J Sports Med. 2014;42(6):1333-1342.
32. Conway JE, Jobe FW, Glousman RE, Pink M. Medial instability of the elbow in throwing athletes. Treatment by repair or reconstruction of the ulnar collateral ligament. J Bone Joint Surg Am. 1992;74(1):67-83.
33. Mishra A, Harmon K, Woodall J, Vieira A. Sports medicine applications of platelet rich plasma. Curr Pharm Biotechnol. 2012;13(7):1185-1195.
The ulnar collateral ligament (UCL) is the primary restraint to valgus stress between 20° and 125° of motion.1-5 Overhead athletes, most commonly baseball pitchers, are at risk of developing UCL insufficiency, and dysfunction presents as pain with loss of velocity and control. Some injuries may present acutely while throwing, but many patients, when questioned, report a preceding period of either pain or loss of velocity and control.
Authors have documented a significant rise in elbow injuries in young athletes, especially pitchers.6 Extended seasons, higher pitch counts, year-round pitching, pitching while fatigued, and pitching for multiple teams are risk factors for elbow injuries.7 Pitchers in the southern United States are more likely to undergo UCL reconstruction than those from the northern states.8 Pitchers who also play catcher are at a higher risk due to more total throws than those who pitch and play other positions or pitch only. Throwers with higher velocity are more likely to pitch in showcases, pitch for multiple teams, and pitch with pain and fatigue, and these are all risk factors.6 Also, in one study of youth baseball injuries, individuals in the injured group were found to be taller and heavier than those in the uninjured group.6 Pitch counts, rest from pitching during the off-season, adequate rest, and ensuring pain-free pitching can lessen the risk of injury.6 As expected with the rise in throwing injuries, the rise in medial elbow procedures has risen.9
While throwing, stress across the medial elbow has been measured to be nearly 300 N. A maximum varus force during pitching was measured to be 64 N-m at 95° ± 14°.10 Morrey and An4 determined that the UCL generated 54% of the varus force at 90° of flexion. During active pitching, this value is likely reduced due to simultaneous muscle contraction, but if one assumes the UCL bears 54% of the maximal load, the UCL must be able to withstand 34 N-m. The UCL can withstand a maximum valgus torque between 22.7 and 34 N-m11-13; therefore, during pitching, the UCL is at or above its failure load. After thousands of cycles over many years, one can imagine how the UCL might be injured.
Multiple techniques have been proposed in the surgical treatment of UCL injuries. Jobe14 pioneered UCL reconstruction in 1974 in Tommy John, a Major League Baseball pitcher. John returned to pitch successfully, and both the UCL and the reconstruction are commonly called by his name. Jobe14 reported his technique in 1986, and it has remained, with a few modifications, the primary method for reconstruction of the UCL (Figure 1).
Evaluation
A standard evaluation with physical examination and imaging is completed in all throwers with elbow pain. In our prior study,16 we found that 100% of patients experienced pain during athletic activity and that 96% of throwers complained of pain during late cocking and acceleration phases of the throwing motion. Nearly half reported an acute onset of pain, while 53% were unable to identify a single inciting event. Seventy-five percent of the acute injuries were during competition. Delayed diagnosis was very common, with an average time to diagnosis after onset of symptoms of 6.4 months. Neurologic symptoms were seen in 23% of athletes, most of which were ulnar nerve paresthesias during throwing.16
Physical examination includes inspection for swelling, hand intrinsic atrophy, neurovascular examination, range of motion, shoulder examination, and elbow stress examination. Range of motion at presentation averaged 5° to 135° with 85° of supination and pronation.16 All patients need neurologic evaluation for ulnar nerve dysfunction. Tinel test of the cubital tunnel was positive in 21%.16 Significant ulnar nerve dysfunction, including hand weakness, is much less common but must be well examined and documented. The shoulder must also be evaluated for loss of rotation, which can lead to increased stress on the elbow. An evaluation of mechanics may point out flaws in technique, which may be contributing to elbow stress. The UCL stress examination includes static stress at 30° of flexion, the milking test at 90°, and the moving valgus stress test. The presence of pain directly over the UCL or laxity compared to the uninvolved side is suggestive of UCL injury.
Radiographic evaluation is completed in all patients with concern for UCL injury. Standard x-rays of the elbow, including anteroposterior, medial, and lateral obliques, axial olecranon, and lateral views, are obtained to evaluate bony abnormalities. Fifty-seven percent of our series showed some abnormality, most commonly olecranon osteophyte formation or ectopic calcification within the UCL substance. Stress radiography rarely changed the treatment course and is somewhat difficult to interpret because of the reports documenting normal increased medial elbow opening in the dominant arm of throwing athletes.21 Magnetic resonance imaging (MRI) is obtained very commonly in this patient population, and intra-articular contrast is crucial. Partial, undersurface tears are common, and a contrasted study better demonstrates undersurface tears or avulsions. The T-sign as described by Timmerman and colleagues22 using computed tomography (CT) arthrography shows partial undersurface detachment, which can be difficult to see without intra-articular contrast.22 This finding is very well visualized on MRI arthrogram as well (Figure 3).
Nonoperative Management
Nonoperative treatment is recommended for 3 months prior to performing reconstruction. Patients are given complete rest from throwing, but rehabilitation is initiated immediately. Rehabilitation exercises and nonsteroidal anti-inflammatory medications are prescribed, and activities that place valgus stress across the elbow are avoided. After resolution of symptoms, an interval throwing program is initiated, and the athlete is gradually returned to sport. Unfortunately, due to season-specific schedules and time-sensitive demands in high-level throwers, operative treatment is often chosen without an extended period of conservative treatment.
Platelet-rich plasma (PRP) therapy has recently been shown to improve healing rates and promote healing in partial UCL tears,23 and as orthobiologics are advanced, they will likely play a larger role in the treatment of UCL injuries.
Surgical Technique
At our institution, UCL reconstruction is performed with the modified Jobe technique as described by Azar and colleagues.17 Arthroscopy prior to reconstruction was routinely performed at our institution until we recognized that arthroscopy rarely changed the preoperative plan.16 Currently, the presence of anterior pathology such as loose bodies or osteochondral defect is our only indication for arthroscopy before reconstruction.
Ipsilateral palmaris autograft is our current graft of choice. This must be examined preoperatively because 16% of patients have unilateral absence and 9% have bilateral absence.24 In revision cases or in patients with insufficient or absent palmaris, contralateral palmaris followed by contralateral gracilis tendon is used. The contralateral gracilis is chosen because of ease of setup and position of the surgeon during the harvest. Gracilis tendon is also used in cases with bony involvement of the ligament based on the results from Dugas and colleagues.25 Toe extensors, plantaris, and patellar tendon grafts have also been used. One recent study showed that neither graft choice nor diameter affected resistance to valgus stress, and that all reconstruction types restored strength at 60° to 120° of flexion.26
Ulnar nerve transposition is performed in all cases regardless of the presence of preoperative nerve symptoms. A complete decompression is completed proximally to the Arcade of Struthers and distally to the deep portion of the flexor carpi ulnaris. A single fascial sling of medial intermuscular septum originating from the epicondylar attachment is used to stabilize the nerve without compression. At wound closure, the deep fascia on the posterior skin flap is also sewn into the cubital tunnel to prevent the nerve from subluxating back into the groove. A single suture is placed distally closing the muscle fascia to prevent propagation of the fascial incision, which can lead to herniation. Transposition is necessary because of the ulnar nerve exposure required in the modified Jobe technique to allow elevation of the deep flexor muscle mass for ligament exposure.
The reconstruction is completed as described by Jobe14 but with a few modifications as described by Azar and colleagues17 and slight adaptations implemented since that time. The flexor-pronator mass is retracted laterally instead of detachment or splitting as described by Thompson and colleagues.27 A subcutaneous rather than a submuscular ulnar nerve transposition is used.
The patient is positioned supine using an arm board. If gracilis tendon is chosen, the contralateral leg is prepped and draped simultaneously. A tourniquet is inflated after exsanguination. A medial approach is performed, and the medial antebrachial nerve is located and protected. The ulnar nerve is then located in the cubital tunnel and mobilized. The neurolysis extends to the deep portion of the flexor carpi ulnaris distally and proximally to the Arcade of Struthers, and the nerve is retracted with a vessel loop. The flexor muscle mass is not elevated from the medial epicondyle; rather, it is retracted anteriorly by small Hohmann retractors. The dissection is carried down to the UCL and found at its attachments to the medial epicondyle and sublime tubercle. If no tear is seen on the superficial surface of the ligament, a longitudinal incision is made through the ligament. Undersurface tears, partial tears, and avulsions can then be identified (Figure 4).
The autologous graft of choice is then harvested. Our technique for palmaris harvest is performed with three 1-cm transverse incisions. The palmaris is palpated and marked with the first incision made near the distal wrist crease, and the second incision is made 3 to 4 cm proximal to the first. The tendon is found in both distal incisions and cut distally with the wrist flexed to maximize tendon length. The tendon is then pulled through the second incision and tensioned to identify the most proximal location the tendon can be palpated. A third incision is made directly over this point and carried down to cut the tendon. This usually provides a graft length of 15 to 20 cm; 13 cm is the minimum graft length to ensure good graft fixation. Muscle is removed from the tendon and each end is secured with a No. 1 nonabsorbable suture in a locking fashion.
If posterior osteophytes are present, they are removed through a posterior, vertical arthrotomy. Over-resection of the olecranon must be avoided, as this can further destabilize the elbow and place increased stress on the reconstruction. Posterior loose bodies can also be removed through this arthrotomy. The arthrotomy is then closed with absorbable suture.
Tunnel placement is critical to success. A 3.2-mm drill bit is used with palmaris grafts and a 4-mm drill bit is used with gracilis grafts. Two convergent tunnels are drilled in the medial epicondyle in a Y fashion and 2 convergent tunnels are drilled at the sublime tubercle in a U or V fashion. After drilling the first tunnel on each side, a hemostat is placed in the tunnel as an aiming point to ensure a complete tunnel is made. The junction is smoothed with a curette, leaving a 5-mm bone bridge between the articular surface and the tunnels. A bent Hewson suture passer is used to pass one end of the graft through the ulna. The 2 limbs of the tendon graft are then passed through the humeral tunnels, creating a figure-of-eight. A varus stress is applied with the elbow at roughly 30° and the 2 limbs are tied together with a No. 1 nonabsorbable suture. If enough graft remains, one or both limbs are passed back through the tunnels and secured again with No. 1 nonabsorbable suture. The 2 limbs are then tied side-to-side, incorporating the native ligament to further secure and tighten the reconstruction.
The ulnar nerve is then secured using a strip of medial intermuscular septum left intact to its insertion at the medial epicondyle. This is attached to the flexor-pronator muscle fascia with a 3-0 nonabsorbable suture. Enough length should be harvested from the septum to ensure there is no compression on the nerve. The deep posterior fascial tissue is then sewn to the periosteum of the medial epicondyle to further prevent subluxation of the nerve back into the groove. The skin is then closed in layered fashion over a superficial drain. The patient is placed in a well-padded posterior splint for 1 week, then the rehabilitation protocol is initiated as discussed below.
Postoperative Rehabilitation
A standardized postoperative 4-phase rehabilitation program for ulnar collateral reconstruction is followed as described by Wilk and colleagues.28-30 The first phase begins immediately after surgery and continues for 4 weeks. During surgery, the patient’s elbow is placed in a compression dressing with a posterior splint to immobilize the elbow in 90° of flexion with wrist motion for 1 week to allow initial healing. Full range of motion of the elbow joint is restored by the end of the fifth to sixth week after surgery.
During phase II (weeks 4-10), a progressive isotonic strengthening program is initiated. Exercises are focused on scapular, rotator cuff, deltoid, and arm musculature. Shoulder range of motion and stretching exercises are performed during this phase and the Thrower’s Ten exercise program is initiated. Any adaptations or strength deficits are addressed during this phase.
During the advanced strengthening phase (phase III), from weeks 10 to 16, a sport-specific exercise/rehabilitation program is initiated. During this phase, stretching and flexibility exercises are performed to enhance strength, power, and endurance. During this phase the patient is placed on the advanced Thrower’s Ten program. Isotonic strengthening exercises are progressed, and at week 12, the athlete is allowed to begin an isotonic lifting program, including bench press, seated rowing, latissimus dorsi pull downs, triceps push downs, and biceps curls. In addition, the athlete performs specific exercises to emphasize sport-specific movements. At week 12, overhead athletes begin a 2-hand plyometric throwing program, and at 14 weeks, a 1
Discussion
Results after ulnar collateral reconstruction have been good. In our series of 743 patients, 83% returned to the same or higher level at an average of 11.6 months.16 There was a 4% major complication rate and 16% minor complication rate. Major complications included medial epicondyle fracture (0.5%), significant ulnar nerve dysfunction (1 patient), rupture of graft (1%), and graft site infection. Sixteen percent of patients had ulnar nerve dysfunction, and 82% of these resolved within 6 weeks. All but 1 patient’s paresthesias resolved within 1 year.16 The 10-year follow-up of this group of patients included 256 patients and was reported by Osbahr and colleagues31 in 2014. Retirement from baseball was due to reasons other than the elbow in 86%, and 98% were still able to throw on at least a recreational level. The overall longevity was 3.6 years, with 2.9 years at pre-injury level or higher. Statistically, pitchers performed at a higher level after reconstruction.31
A recent review by Erickson and colleagues9 showed an overall 82% excellent and 8% good result when evaluating different techniques, including the American Sports Medicine Institute (ASMI) modification of Jobe’s technique, docking technique, and Jobe’s technique. With an overall complication rate of 10% (75% of which was transient ulnar neuritis), the procedure was deemed overall a safe surgical option. Collegiate athletes had the highest return to sport (95%) compared with high school athletes (89%) and professional athletes (86%). The docking technique had the highest rate of return to play (97%) compared with ASMI technique (93%) and Jobe technique (66%).9 Results after repair have not been as good as reconstruction, as reported in 2 studies.16,32 Savoie and colleagues,15 however, reported 93% good/excellent results after primary UCL repair alone.
Another recent review of outcomes showed an overall return to same or higher level was best with docking or modified docking techniques (90.4% and 91.3%, respectively).19 Overall return with modified Jobe technique was 77%.19 O’Brien and colleagues20 performed a review of 33 patients with either modified Jobe or docking technique that showed 81% return to same or higher level with modified Jobe vs 92% with docking technique. The Kerlan-Jobe Orthopaedic Clinic scores were higher in the modified Jobe group (79 vs 74) and the docking technique group returned to play nearly 1 month sooner (12.4 months vs 11.8 months).20 However, comparing different techniques in a heterogenous patient population over 40 years is difficult. Many of the modified Jobe technique cases were performed in the early evolution of the rehabilitation and return-to-play programs. We believe that the current modified Jobe technique has results equal to any other variation.
Despite good results with reconstructions, the recovery is lengthy and most pitchers cannot fully return to competition level for 12 to 18 months. Extensive research has been performed in exploring alternatives to the traditional reconstruction. Advancements in orthobiologics and development of new surgical options seem to provide an alternative to reconstruction, and may allow faster return to competition with less morbidity.
PRP has been at the forefront of orthopedic research for the last 2 decades, mostly focused in tendon and bone healing. Due to the release of many inflammatory mediators, PRP is theorized to initiate a healing response with growth factors that can direct healing towards normal tissue.33 Two main types of PRP are reported based on the presence or absence of leukocytes. PRP has been studied in many applications, but only one clinical study on the UCL has been published to date. Podesta and colleagues23 injected PRP into the elbow of 34 baseball players with MRI-confirmed partial UCL tear. The athletes then underwent a rehabilitation program, which limited stress across the UCL. Type 1A PRP was used (leukocyte-rich, unactivated, 5x or greater platelet concentration33). Athletes were allowed to return to sport based on symptoms and examination findings. Eighty-eight percent returned to same level of play without complaints at average 70 week follow-up, and average return to play ranged from 10 to 15 weeks.23 No specific data were given on the 16 pitchers in the group, but with such a high rate of return, PRP needs to be further evaluated in the treatment of UCL injuries.
Another recent study from Dugas and colleagues18 presented primary UCL repair using a tape augment (InternalBrace, Arthrex). Nine matched cadaver elbows underwent UCL sectioning and then either modified Jobe reconstruction or primary repair of the UCL with placement of the InternalBrace. The biomechanical data showed the repair with internal brace to have slightly less gap, more stiffness, and higher failure strength, although these findings were not statistically significant.18 This bone-preserving technique with less exposure and healing of the native ligament may be another step towards good results with a quicker return to throwing.
Conclusion
UCL injuries can be disabling in throwers. Reconstruction has afforded throwers a high rate of return to preinjury function or better, and several techniques have been presented that produce acceptable results. Overall complication rates range from 10% to 15%, and the majority of complications are transient ulnar neuropraxias. Orthobiologics and repair with augmentation have more recently offered additional options that may improve success of nonoperative treatment or allow less-invasive surgical treatment. Increased involvement in youth sports and early specialization is driving injury rates in young athletes. The orthopedic community must continue to look for better ways to prevent these injuries and investigate better methods to return athletes to high-level competition.
Am J Orthop. 2016;45(7):E534-E540. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
The ulnar collateral ligament (UCL) is the primary restraint to valgus stress between 20° and 125° of motion.1-5 Overhead athletes, most commonly baseball pitchers, are at risk of developing UCL insufficiency, and dysfunction presents as pain with loss of velocity and control. Some injuries may present acutely while throwing, but many patients, when questioned, report a preceding period of either pain or loss of velocity and control.
Authors have documented a significant rise in elbow injuries in young athletes, especially pitchers.6 Extended seasons, higher pitch counts, year-round pitching, pitching while fatigued, and pitching for multiple teams are risk factors for elbow injuries.7 Pitchers in the southern United States are more likely to undergo UCL reconstruction than those from the northern states.8 Pitchers who also play catcher are at a higher risk due to more total throws than those who pitch and play other positions or pitch only. Throwers with higher velocity are more likely to pitch in showcases, pitch for multiple teams, and pitch with pain and fatigue, and these are all risk factors.6 Also, in one study of youth baseball injuries, individuals in the injured group were found to be taller and heavier than those in the uninjured group.6 Pitch counts, rest from pitching during the off-season, adequate rest, and ensuring pain-free pitching can lessen the risk of injury.6 As expected with the rise in throwing injuries, the rise in medial elbow procedures has risen.9
While throwing, stress across the medial elbow has been measured to be nearly 300 N. A maximum varus force during pitching was measured to be 64 N-m at 95° ± 14°.10 Morrey and An4 determined that the UCL generated 54% of the varus force at 90° of flexion. During active pitching, this value is likely reduced due to simultaneous muscle contraction, but if one assumes the UCL bears 54% of the maximal load, the UCL must be able to withstand 34 N-m. The UCL can withstand a maximum valgus torque between 22.7 and 34 N-m11-13; therefore, during pitching, the UCL is at or above its failure load. After thousands of cycles over many years, one can imagine how the UCL might be injured.
Multiple techniques have been proposed in the surgical treatment of UCL injuries. Jobe14 pioneered UCL reconstruction in 1974 in Tommy John, a Major League Baseball pitcher. John returned to pitch successfully, and both the UCL and the reconstruction are commonly called by his name. Jobe14 reported his technique in 1986, and it has remained, with a few modifications, the primary method for reconstruction of the UCL (Figure 1).
Evaluation
A standard evaluation with physical examination and imaging is completed in all throwers with elbow pain. In our prior study,16 we found that 100% of patients experienced pain during athletic activity and that 96% of throwers complained of pain during late cocking and acceleration phases of the throwing motion. Nearly half reported an acute onset of pain, while 53% were unable to identify a single inciting event. Seventy-five percent of the acute injuries were during competition. Delayed diagnosis was very common, with an average time to diagnosis after onset of symptoms of 6.4 months. Neurologic symptoms were seen in 23% of athletes, most of which were ulnar nerve paresthesias during throwing.16
Physical examination includes inspection for swelling, hand intrinsic atrophy, neurovascular examination, range of motion, shoulder examination, and elbow stress examination. Range of motion at presentation averaged 5° to 135° with 85° of supination and pronation.16 All patients need neurologic evaluation for ulnar nerve dysfunction. Tinel test of the cubital tunnel was positive in 21%.16 Significant ulnar nerve dysfunction, including hand weakness, is much less common but must be well examined and documented. The shoulder must also be evaluated for loss of rotation, which can lead to increased stress on the elbow. An evaluation of mechanics may point out flaws in technique, which may be contributing to elbow stress. The UCL stress examination includes static stress at 30° of flexion, the milking test at 90°, and the moving valgus stress test. The presence of pain directly over the UCL or laxity compared to the uninvolved side is suggestive of UCL injury.
Radiographic evaluation is completed in all patients with concern for UCL injury. Standard x-rays of the elbow, including anteroposterior, medial, and lateral obliques, axial olecranon, and lateral views, are obtained to evaluate bony abnormalities. Fifty-seven percent of our series showed some abnormality, most commonly olecranon osteophyte formation or ectopic calcification within the UCL substance. Stress radiography rarely changed the treatment course and is somewhat difficult to interpret because of the reports documenting normal increased medial elbow opening in the dominant arm of throwing athletes.21 Magnetic resonance imaging (MRI) is obtained very commonly in this patient population, and intra-articular contrast is crucial. Partial, undersurface tears are common, and a contrasted study better demonstrates undersurface tears or avulsions. The T-sign as described by Timmerman and colleagues22 using computed tomography (CT) arthrography shows partial undersurface detachment, which can be difficult to see without intra-articular contrast.22 This finding is very well visualized on MRI arthrogram as well (Figure 3).
Nonoperative Management
Nonoperative treatment is recommended for 3 months prior to performing reconstruction. Patients are given complete rest from throwing, but rehabilitation is initiated immediately. Rehabilitation exercises and nonsteroidal anti-inflammatory medications are prescribed, and activities that place valgus stress across the elbow are avoided. After resolution of symptoms, an interval throwing program is initiated, and the athlete is gradually returned to sport. Unfortunately, due to season-specific schedules and time-sensitive demands in high-level throwers, operative treatment is often chosen without an extended period of conservative treatment.
Platelet-rich plasma (PRP) therapy has recently been shown to improve healing rates and promote healing in partial UCL tears,23 and as orthobiologics are advanced, they will likely play a larger role in the treatment of UCL injuries.
Surgical Technique
At our institution, UCL reconstruction is performed with the modified Jobe technique as described by Azar and colleagues.17 Arthroscopy prior to reconstruction was routinely performed at our institution until we recognized that arthroscopy rarely changed the preoperative plan.16 Currently, the presence of anterior pathology such as loose bodies or osteochondral defect is our only indication for arthroscopy before reconstruction.
Ipsilateral palmaris autograft is our current graft of choice. This must be examined preoperatively because 16% of patients have unilateral absence and 9% have bilateral absence.24 In revision cases or in patients with insufficient or absent palmaris, contralateral palmaris followed by contralateral gracilis tendon is used. The contralateral gracilis is chosen because of ease of setup and position of the surgeon during the harvest. Gracilis tendon is also used in cases with bony involvement of the ligament based on the results from Dugas and colleagues.25 Toe extensors, plantaris, and patellar tendon grafts have also been used. One recent study showed that neither graft choice nor diameter affected resistance to valgus stress, and that all reconstruction types restored strength at 60° to 120° of flexion.26
Ulnar nerve transposition is performed in all cases regardless of the presence of preoperative nerve symptoms. A complete decompression is completed proximally to the Arcade of Struthers and distally to the deep portion of the flexor carpi ulnaris. A single fascial sling of medial intermuscular septum originating from the epicondylar attachment is used to stabilize the nerve without compression. At wound closure, the deep fascia on the posterior skin flap is also sewn into the cubital tunnel to prevent the nerve from subluxating back into the groove. A single suture is placed distally closing the muscle fascia to prevent propagation of the fascial incision, which can lead to herniation. Transposition is necessary because of the ulnar nerve exposure required in the modified Jobe technique to allow elevation of the deep flexor muscle mass for ligament exposure.
The reconstruction is completed as described by Jobe14 but with a few modifications as described by Azar and colleagues17 and slight adaptations implemented since that time. The flexor-pronator mass is retracted laterally instead of detachment or splitting as described by Thompson and colleagues.27 A subcutaneous rather than a submuscular ulnar nerve transposition is used.
The patient is positioned supine using an arm board. If gracilis tendon is chosen, the contralateral leg is prepped and draped simultaneously. A tourniquet is inflated after exsanguination. A medial approach is performed, and the medial antebrachial nerve is located and protected. The ulnar nerve is then located in the cubital tunnel and mobilized. The neurolysis extends to the deep portion of the flexor carpi ulnaris distally and proximally to the Arcade of Struthers, and the nerve is retracted with a vessel loop. The flexor muscle mass is not elevated from the medial epicondyle; rather, it is retracted anteriorly by small Hohmann retractors. The dissection is carried down to the UCL and found at its attachments to the medial epicondyle and sublime tubercle. If no tear is seen on the superficial surface of the ligament, a longitudinal incision is made through the ligament. Undersurface tears, partial tears, and avulsions can then be identified (Figure 4).
The autologous graft of choice is then harvested. Our technique for palmaris harvest is performed with three 1-cm transverse incisions. The palmaris is palpated and marked with the first incision made near the distal wrist crease, and the second incision is made 3 to 4 cm proximal to the first. The tendon is found in both distal incisions and cut distally with the wrist flexed to maximize tendon length. The tendon is then pulled through the second incision and tensioned to identify the most proximal location the tendon can be palpated. A third incision is made directly over this point and carried down to cut the tendon. This usually provides a graft length of 15 to 20 cm; 13 cm is the minimum graft length to ensure good graft fixation. Muscle is removed from the tendon and each end is secured with a No. 1 nonabsorbable suture in a locking fashion.
If posterior osteophytes are present, they are removed through a posterior, vertical arthrotomy. Over-resection of the olecranon must be avoided, as this can further destabilize the elbow and place increased stress on the reconstruction. Posterior loose bodies can also be removed through this arthrotomy. The arthrotomy is then closed with absorbable suture.
Tunnel placement is critical to success. A 3.2-mm drill bit is used with palmaris grafts and a 4-mm drill bit is used with gracilis grafts. Two convergent tunnels are drilled in the medial epicondyle in a Y fashion and 2 convergent tunnels are drilled at the sublime tubercle in a U or V fashion. After drilling the first tunnel on each side, a hemostat is placed in the tunnel as an aiming point to ensure a complete tunnel is made. The junction is smoothed with a curette, leaving a 5-mm bone bridge between the articular surface and the tunnels. A bent Hewson suture passer is used to pass one end of the graft through the ulna. The 2 limbs of the tendon graft are then passed through the humeral tunnels, creating a figure-of-eight. A varus stress is applied with the elbow at roughly 30° and the 2 limbs are tied together with a No. 1 nonabsorbable suture. If enough graft remains, one or both limbs are passed back through the tunnels and secured again with No. 1 nonabsorbable suture. The 2 limbs are then tied side-to-side, incorporating the native ligament to further secure and tighten the reconstruction.
The ulnar nerve is then secured using a strip of medial intermuscular septum left intact to its insertion at the medial epicondyle. This is attached to the flexor-pronator muscle fascia with a 3-0 nonabsorbable suture. Enough length should be harvested from the septum to ensure there is no compression on the nerve. The deep posterior fascial tissue is then sewn to the periosteum of the medial epicondyle to further prevent subluxation of the nerve back into the groove. The skin is then closed in layered fashion over a superficial drain. The patient is placed in a well-padded posterior splint for 1 week, then the rehabilitation protocol is initiated as discussed below.
Postoperative Rehabilitation
A standardized postoperative 4-phase rehabilitation program for ulnar collateral reconstruction is followed as described by Wilk and colleagues.28-30 The first phase begins immediately after surgery and continues for 4 weeks. During surgery, the patient’s elbow is placed in a compression dressing with a posterior splint to immobilize the elbow in 90° of flexion with wrist motion for 1 week to allow initial healing. Full range of motion of the elbow joint is restored by the end of the fifth to sixth week after surgery.
During phase II (weeks 4-10), a progressive isotonic strengthening program is initiated. Exercises are focused on scapular, rotator cuff, deltoid, and arm musculature. Shoulder range of motion and stretching exercises are performed during this phase and the Thrower’s Ten exercise program is initiated. Any adaptations or strength deficits are addressed during this phase.
During the advanced strengthening phase (phase III), from weeks 10 to 16, a sport-specific exercise/rehabilitation program is initiated. During this phase, stretching and flexibility exercises are performed to enhance strength, power, and endurance. During this phase the patient is placed on the advanced Thrower’s Ten program. Isotonic strengthening exercises are progressed, and at week 12, the athlete is allowed to begin an isotonic lifting program, including bench press, seated rowing, latissimus dorsi pull downs, triceps push downs, and biceps curls. In addition, the athlete performs specific exercises to emphasize sport-specific movements. At week 12, overhead athletes begin a 2-hand plyometric throwing program, and at 14 weeks, a 1
Discussion
Results after ulnar collateral reconstruction have been good. In our series of 743 patients, 83% returned to the same or higher level at an average of 11.6 months.16 There was a 4% major complication rate and 16% minor complication rate. Major complications included medial epicondyle fracture (0.5%), significant ulnar nerve dysfunction (1 patient), rupture of graft (1%), and graft site infection. Sixteen percent of patients had ulnar nerve dysfunction, and 82% of these resolved within 6 weeks. All but 1 patient’s paresthesias resolved within 1 year.16 The 10-year follow-up of this group of patients included 256 patients and was reported by Osbahr and colleagues31 in 2014. Retirement from baseball was due to reasons other than the elbow in 86%, and 98% were still able to throw on at least a recreational level. The overall longevity was 3.6 years, with 2.9 years at pre-injury level or higher. Statistically, pitchers performed at a higher level after reconstruction.31
A recent review by Erickson and colleagues9 showed an overall 82% excellent and 8% good result when evaluating different techniques, including the American Sports Medicine Institute (ASMI) modification of Jobe’s technique, docking technique, and Jobe’s technique. With an overall complication rate of 10% (75% of which was transient ulnar neuritis), the procedure was deemed overall a safe surgical option. Collegiate athletes had the highest return to sport (95%) compared with high school athletes (89%) and professional athletes (86%). The docking technique had the highest rate of return to play (97%) compared with ASMI technique (93%) and Jobe technique (66%).9 Results after repair have not been as good as reconstruction, as reported in 2 studies.16,32 Savoie and colleagues,15 however, reported 93% good/excellent results after primary UCL repair alone.
Another recent review of outcomes showed an overall return to same or higher level was best with docking or modified docking techniques (90.4% and 91.3%, respectively).19 Overall return with modified Jobe technique was 77%.19 O’Brien and colleagues20 performed a review of 33 patients with either modified Jobe or docking technique that showed 81% return to same or higher level with modified Jobe vs 92% with docking technique. The Kerlan-Jobe Orthopaedic Clinic scores were higher in the modified Jobe group (79 vs 74) and the docking technique group returned to play nearly 1 month sooner (12.4 months vs 11.8 months).20 However, comparing different techniques in a heterogenous patient population over 40 years is difficult. Many of the modified Jobe technique cases were performed in the early evolution of the rehabilitation and return-to-play programs. We believe that the current modified Jobe technique has results equal to any other variation.
Despite good results with reconstructions, the recovery is lengthy and most pitchers cannot fully return to competition level for 12 to 18 months. Extensive research has been performed in exploring alternatives to the traditional reconstruction. Advancements in orthobiologics and development of new surgical options seem to provide an alternative to reconstruction, and may allow faster return to competition with less morbidity.
PRP has been at the forefront of orthopedic research for the last 2 decades, mostly focused in tendon and bone healing. Due to the release of many inflammatory mediators, PRP is theorized to initiate a healing response with growth factors that can direct healing towards normal tissue.33 Two main types of PRP are reported based on the presence or absence of leukocytes. PRP has been studied in many applications, but only one clinical study on the UCL has been published to date. Podesta and colleagues23 injected PRP into the elbow of 34 baseball players with MRI-confirmed partial UCL tear. The athletes then underwent a rehabilitation program, which limited stress across the UCL. Type 1A PRP was used (leukocyte-rich, unactivated, 5x or greater platelet concentration33). Athletes were allowed to return to sport based on symptoms and examination findings. Eighty-eight percent returned to same level of play without complaints at average 70 week follow-up, and average return to play ranged from 10 to 15 weeks.23 No specific data were given on the 16 pitchers in the group, but with such a high rate of return, PRP needs to be further evaluated in the treatment of UCL injuries.
Another recent study from Dugas and colleagues18 presented primary UCL repair using a tape augment (InternalBrace, Arthrex). Nine matched cadaver elbows underwent UCL sectioning and then either modified Jobe reconstruction or primary repair of the UCL with placement of the InternalBrace. The biomechanical data showed the repair with internal brace to have slightly less gap, more stiffness, and higher failure strength, although these findings were not statistically significant.18 This bone-preserving technique with less exposure and healing of the native ligament may be another step towards good results with a quicker return to throwing.
Conclusion
UCL injuries can be disabling in throwers. Reconstruction has afforded throwers a high rate of return to preinjury function or better, and several techniques have been presented that produce acceptable results. Overall complication rates range from 10% to 15%, and the majority of complications are transient ulnar neuropraxias. Orthobiologics and repair with augmentation have more recently offered additional options that may improve success of nonoperative treatment or allow less-invasive surgical treatment. Increased involvement in youth sports and early specialization is driving injury rates in young athletes. The orthopedic community must continue to look for better ways to prevent these injuries and investigate better methods to return athletes to high-level competition.
Am J Orthop. 2016;45(7):E534-E540. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.
1. Fuss FK. The ulnar collateral ligament of the human elbow joint. Anatomy, function and biomechanics. J Anat. 1991;175:203-212.
2. Hotchkiss RN, Weiland AJ. Valgus stability of the elbow. J Orthop Res. 1987;5(3):372-377.
3. Morrey BF. Applied anatomy and biomechanics of the elbow joint. Instr Course Lect. 1986;35:59-68.
4. Morrey BF, An KN. Articular and ligamentous contributions to the stability of the elbow joint. Am J Sports Med. 1983;11(5):315-319.
5. Morrey BF, An KN. Functional anatomy of the ligaments of the elbow. Clin Orthop. 1985;(201):84-90.
6. Olsen SJ 2nd, Fleisig GS, Dun S, Loftice J, Andrews JR. Risk factors for shoulder and elbow injuries in adolescent baseball pitchers. Am J Sports Med. 2006;34(6):905-912.
7. Fleisig GS, Andrews JR. Prevention of elbow injuries in youth baseball pitchers. Sports Health. 2012;4(5):419-424.
8. Zaremski JL, Horodyski M, Donlan RM, Brisbane ST, Farmer KW. Does geographic location matter on the prevalence of ulnar collateral ligament reconstruction in collegiate baseball pitchers? Orthop J Sports Med. 2015;3(11):2325967115616582.
9. Erickson BJ, Nwachukwu BU, Rosas S, et al. Trends in medial ulnar collateral ligament reconstruction in the United States: A retrospective review of a large private-payer database from 2007 to 2011. Am J Sports Med. 2015;43(7):1770-1774.
10. Fleisig GS, Andrews JR, Dillman CJ. Kinetics of baseball pitching with implications about injury mechanism. Am J Sports Med. 1995;23(2):233-239.
11. Dillman CJ, Smutz P, Werner S. Valgus extension overload in baseball pitching. Med Sci Sports Exerc. 1991;23(suppl 4):S135.
12. Hechtman KS, Tjin-A-Tsoi EW, Zvijac JE, Uribe JW, Latta LL. Biomechanics of a less invasive procedure for reconstruction of the ulnar collateral ligament of the elbow. Am J Sports Med. 1998;26(5):620-624.
13. Ahmad CS, Lee TQ, ElAttrache NS. Biomechanical evaluation of a new ulnar collateral ligament reconstruction technique with interference screw fixation. Am J Sports Med. 2003;31(3):332-337.
14. Jobe FW, Stark HE, Lombardo SJ. Reconstruction of the ulnar collateral ligament in athletes. J Bone Joint Surg Am. 1986;68(8):1158-1163.
15. Savoie FH 3rd, Trenhaile SW, Roberts J, Field LD, Ramsey JR. Primary repair of ulnar collateral ligament injuries of the elbow in young athletes: a case series of injuries to the proximal and distal ends of the ligament. Am J Sports Med. 2008;36(6):1066-1072.
16. Cain EL, Andrews JR, Dugas JR, et al. Outcome of ulnar collateral ligament reconstruction of the elbow in 1281 athletes results in 743 athletes with minimum 2-year follow-up. Am J Sports Med. 2010;38(12):2426-2434.
17. Azar FM, Andrews JR, Wilk KE, Groh D. Operative treatment of ulnar collateral ligament injuries of the elbow in athletes. Am J Sports Med. 2000;28(1):16-23.
18. Dugas JR, Walters BL, Beason DP, Fleisig GS, Chronister JE. Biomechanical comparison of ulnar collateral ligament repair with internal bracing versus modified Jobe reconstruction. Am J Sports Med. 2016;44(3):735-741.
19. Watson JN, McQueen P, Hutchinson MR. A systematic review of ulnar collateral ligament reconstruction techniques. Am J Sports Med. 2014;42(10):2510-2516.
20. O’Brien DF, O’Hagan T, Stewart R, et al. Outcomes for ulnar collateral ligament reconstruction: A retrospective review using the KJOC assessment score with two-year follow-up in an overhead throwing population. J Shoulder Elbow Surg. 2015;24(6):934-940.
21. Ellenbecker TS, Mattalino AJ, Elam EA, Caplinger RA. Medial elbow joint laxity in professional baseball pitchers a bilateral comparison using stress radiography. Am J Sports Med. 1998;26(3):420-424.
22. Timmerman LA, Schwartz ML, Andrews JR. Preoperative evaluation of the ulnar collateral ligament by magnetic resonance imaging and computed tomography arthrography evaluation in 25 baseball players with surgical confirmation. Am J Sports Med. 1994;22(1):26-32.
23. Podesta L, Crow SA, Volkmer D, Bert T, Yocum LA. Treatment of partial ulnar collateral ligament tears in the elbow with platelet-rich plasma. Am J Sports Med. 2013;41(7):1689-1694.
24. Thompson NW, Mockford BJ, Cran GW. Absence of the palmaris longus muscle: a population study. Ulster Med J. 2001;70(1):22-24.
25. Dugas JR, Bilotta J, Watts CD, et al. Ulnar collateral ligament reconstruction with gracilis tendon in athletes with intraligamentous bony excision technique and results. Am J Sports Med. 2012;40(7):1578-1582.
26. Dargel J, Küpper F, Wegmann K, Oppermann J, Eysel P, Müller LP. Graft diameter does not influence primary stability of ulnar collateral ligament reconstruction of the elbow. J Orthop Sci. 2015;20(2):307-313.
27. Thompson WH, Jobe FW, Yocum LA, Pink MM. Ulnar collateral ligament reconstruction in athletes: muscle-splitting approach without transposition of the ulnar nerve. J Shoulder Elbow Surg. 2001;10(2):152-157.
28. Wilk KE, Arrigo CA, Andrews JR. Rehabilitation of the elbow in the throwing athlete. J Orthop Sports Phys Ther. 1993;17(6):305-317.
29. Wilk KE, Arrigo CA, Andrews JR, et al. Rehabilitation following elbow surgery in the throwing athlete. Oper Tech Sports Med. 1996;4:114-132.
30. Wilk KE, Arrigo CA, Andrews JR, et al. Preventative and Rehabilitation Exercises for the Shoulder and Elbow. 4th ed. Birmingham, AL: American Sports Medicine Institute; 1996.
31. Osbahr DC, Cain EL, Raines BT, Fortenbaugh D, Dugas JR, Andrews JR. Long-term outcomes after ulnar collateral ligament reconstruction in competitive baseball players minimum 10-year follow-up. Am J Sports Med. 2014;42(6):1333-1342.
32. Conway JE, Jobe FW, Glousman RE, Pink M. Medial instability of the elbow in throwing athletes. Treatment by repair or reconstruction of the ulnar collateral ligament. J Bone Joint Surg Am. 1992;74(1):67-83.
33. Mishra A, Harmon K, Woodall J, Vieira A. Sports medicine applications of platelet rich plasma. Curr Pharm Biotechnol. 2012;13(7):1185-1195.
1. Fuss FK. The ulnar collateral ligament of the human elbow joint. Anatomy, function and biomechanics. J Anat. 1991;175:203-212.
2. Hotchkiss RN, Weiland AJ. Valgus stability of the elbow. J Orthop Res. 1987;5(3):372-377.
3. Morrey BF. Applied anatomy and biomechanics of the elbow joint. Instr Course Lect. 1986;35:59-68.
4. Morrey BF, An KN. Articular and ligamentous contributions to the stability of the elbow joint. Am J Sports Med. 1983;11(5):315-319.
5. Morrey BF, An KN. Functional anatomy of the ligaments of the elbow. Clin Orthop. 1985;(201):84-90.
6. Olsen SJ 2nd, Fleisig GS, Dun S, Loftice J, Andrews JR. Risk factors for shoulder and elbow injuries in adolescent baseball pitchers. Am J Sports Med. 2006;34(6):905-912.
7. Fleisig GS, Andrews JR. Prevention of elbow injuries in youth baseball pitchers. Sports Health. 2012;4(5):419-424.
8. Zaremski JL, Horodyski M, Donlan RM, Brisbane ST, Farmer KW. Does geographic location matter on the prevalence of ulnar collateral ligament reconstruction in collegiate baseball pitchers? Orthop J Sports Med. 2015;3(11):2325967115616582.
9. Erickson BJ, Nwachukwu BU, Rosas S, et al. Trends in medial ulnar collateral ligament reconstruction in the United States: A retrospective review of a large private-payer database from 2007 to 2011. Am J Sports Med. 2015;43(7):1770-1774.
10. Fleisig GS, Andrews JR, Dillman CJ. Kinetics of baseball pitching with implications about injury mechanism. Am J Sports Med. 1995;23(2):233-239.
11. Dillman CJ, Smutz P, Werner S. Valgus extension overload in baseball pitching. Med Sci Sports Exerc. 1991;23(suppl 4):S135.
12. Hechtman KS, Tjin-A-Tsoi EW, Zvijac JE, Uribe JW, Latta LL. Biomechanics of a less invasive procedure for reconstruction of the ulnar collateral ligament of the elbow. Am J Sports Med. 1998;26(5):620-624.
13. Ahmad CS, Lee TQ, ElAttrache NS. Biomechanical evaluation of a new ulnar collateral ligament reconstruction technique with interference screw fixation. Am J Sports Med. 2003;31(3):332-337.
14. Jobe FW, Stark HE, Lombardo SJ. Reconstruction of the ulnar collateral ligament in athletes. J Bone Joint Surg Am. 1986;68(8):1158-1163.
15. Savoie FH 3rd, Trenhaile SW, Roberts J, Field LD, Ramsey JR. Primary repair of ulnar collateral ligament injuries of the elbow in young athletes: a case series of injuries to the proximal and distal ends of the ligament. Am J Sports Med. 2008;36(6):1066-1072.
16. Cain EL, Andrews JR, Dugas JR, et al. Outcome of ulnar collateral ligament reconstruction of the elbow in 1281 athletes results in 743 athletes with minimum 2-year follow-up. Am J Sports Med. 2010;38(12):2426-2434.
17. Azar FM, Andrews JR, Wilk KE, Groh D. Operative treatment of ulnar collateral ligament injuries of the elbow in athletes. Am J Sports Med. 2000;28(1):16-23.
18. Dugas JR, Walters BL, Beason DP, Fleisig GS, Chronister JE. Biomechanical comparison of ulnar collateral ligament repair with internal bracing versus modified Jobe reconstruction. Am J Sports Med. 2016;44(3):735-741.
19. Watson JN, McQueen P, Hutchinson MR. A systematic review of ulnar collateral ligament reconstruction techniques. Am J Sports Med. 2014;42(10):2510-2516.
20. O’Brien DF, O’Hagan T, Stewart R, et al. Outcomes for ulnar collateral ligament reconstruction: A retrospective review using the KJOC assessment score with two-year follow-up in an overhead throwing population. J Shoulder Elbow Surg. 2015;24(6):934-940.
21. Ellenbecker TS, Mattalino AJ, Elam EA, Caplinger RA. Medial elbow joint laxity in professional baseball pitchers a bilateral comparison using stress radiography. Am J Sports Med. 1998;26(3):420-424.
22. Timmerman LA, Schwartz ML, Andrews JR. Preoperative evaluation of the ulnar collateral ligament by magnetic resonance imaging and computed tomography arthrography evaluation in 25 baseball players with surgical confirmation. Am J Sports Med. 1994;22(1):26-32.
23. Podesta L, Crow SA, Volkmer D, Bert T, Yocum LA. Treatment of partial ulnar collateral ligament tears in the elbow with platelet-rich plasma. Am J Sports Med. 2013;41(7):1689-1694.
24. Thompson NW, Mockford BJ, Cran GW. Absence of the palmaris longus muscle: a population study. Ulster Med J. 2001;70(1):22-24.
25. Dugas JR, Bilotta J, Watts CD, et al. Ulnar collateral ligament reconstruction with gracilis tendon in athletes with intraligamentous bony excision technique and results. Am J Sports Med. 2012;40(7):1578-1582.
26. Dargel J, Küpper F, Wegmann K, Oppermann J, Eysel P, Müller LP. Graft diameter does not influence primary stability of ulnar collateral ligament reconstruction of the elbow. J Orthop Sci. 2015;20(2):307-313.
27. Thompson WH, Jobe FW, Yocum LA, Pink MM. Ulnar collateral ligament reconstruction in athletes: muscle-splitting approach without transposition of the ulnar nerve. J Shoulder Elbow Surg. 2001;10(2):152-157.
28. Wilk KE, Arrigo CA, Andrews JR. Rehabilitation of the elbow in the throwing athlete. J Orthop Sports Phys Ther. 1993;17(6):305-317.
29. Wilk KE, Arrigo CA, Andrews JR, et al. Rehabilitation following elbow surgery in the throwing athlete. Oper Tech Sports Med. 1996;4:114-132.
30. Wilk KE, Arrigo CA, Andrews JR, et al. Preventative and Rehabilitation Exercises for the Shoulder and Elbow. 4th ed. Birmingham, AL: American Sports Medicine Institute; 1996.
31. Osbahr DC, Cain EL, Raines BT, Fortenbaugh D, Dugas JR, Andrews JR. Long-term outcomes after ulnar collateral ligament reconstruction in competitive baseball players minimum 10-year follow-up. Am J Sports Med. 2014;42(6):1333-1342.
32. Conway JE, Jobe FW, Glousman RE, Pink M. Medial instability of the elbow in throwing athletes. Treatment by repair or reconstruction of the ulnar collateral ligament. J Bone Joint Surg Am. 1992;74(1):67-83.
33. Mishra A, Harmon K, Woodall J, Vieira A. Sports medicine applications of platelet rich plasma. Curr Pharm Biotechnol. 2012;13(7):1185-1195.
New book tackles complex issues involved in treating depression
“Still Down: What to Do When Antidepressants Fail” by Dean F. MacKinnon, MD, is a compact little book that recently was released by Johns Hopkins University Press. The title, “Still Down,” says it all. At 152 pages, the book is short, but not because it isn’t jammed full of information, but because – like the title – the writing is succinct and straight to the point; there’s no flowery detail, and Dr. MacKinnon doesn’t parse words. He tells the reader up front what his mission is, how the book is organized, and who his audience is. He’s an organized writer who captures the reader while getting his point across.
The book is divided into three distinct parts. In chapter 1, Ann suffers from “textbook depression.” Dr. MacKinnon uses this as an opportunity to educate the reader on the signs and symptoms of major depression, and the fact that treatment takes several weeks, during which side effects may occur before the resolution of symptoms. He talks about depression as a recurring medical illness, lists the available antidepressants by their class, and mentions that depression can be a result of other medical illnesses such as thyroid disease. In chapter 2, college student Bob remains depressed until he takes the medications as prescribed at a steady dose on a daily basis. This involves some coaxing, education, and even outreach by the school nurse, all while being cognizant of things that can go wrong in a young person on antidepressants.
Part 2 of “Still Down” takes on the sticky issue of misdiagnosis. Darius sees Dr. Dennis for treatment of depression during a distressing period of his life when treatment with another doctor had already failed. After careful assessment, Dr. Dennis concludes that while antidepressants weren’t unreasonable to try, Darius is actually suffering from demoralization from losing his business, a miserable divorce, and a child custody battle. Dr. Dennis suggests therapy instead of medications at this point. This was where I found that, I, as a clinician, swayed from Dr. MacKinnon’s treatment approach: He emphasizes an inability to function and to feel pleasure as necessary elements of major depression, and Darius could do both to some extent. But still, his sleep was poor from shift work. He’d gained 30 pounds; he had little energy for activities besides work; and he was in a rut, unhappy, and having trouble entertaining his children when they visited and feeling too lazy to make changes. I thought Darius was depressed and demoralized, and while I agreed with the author that he needed psychotherapy, I also would have continued with medication trials. Dr. MacKinnon certainly doesn’t dismiss the idea of medication, and I found it helpful to revisit demoralization as a state responsible for many psychiatric symptoms.
Moving on in the section on misdiagnoses, the author talks about Evelyn, who turns out to have bipolar versus unipolar depression, and Frances, who carries an incorrect diagnosis of bipolar disorder, and has been overmedicated into a state of delirium. They both do well with time, thoughtful assessment, and treatment. Clinical pearls are threaded through these chapters.
“Depression-plus” is the title of the final section. Gary has major depression superimposed on his dysthymia, or persistent depressive disorder, and Dr. MacKinnon notes that people with constitutionally gloomy moods may have persistent sadness even after successful treatment of major depression. Here, there is a need for accommodation to a given personality state, and therapy can be helpful. Hannah, a patient of Dr. Hernandez, has what the author calls “depressed functioning.” This part I found most interesting, because I see this often in practice – a patient with a long history of being unmotivated and underfunctioning does not get fully (or any) better with antidepressants. Here, the functioning must improve before mood and self-esteem lift, and this is not an easy task. Finally, Irma has treatment-resistant depression, and with her doctor, considers a variety of augmentation medications as well as more novel strategies.
Simply stated, this book is a gem. It’s a very understandable guide to a very complex and frustrating issue, one that needs more time-consuming and thoughtful evaluation, and more intensive resources than a simple episode of depression usually entails.
Finally, I have to admit that I enjoyed Dr. MacKinnon’s quiet jabs at electronic medical records.
Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has known Dr. MacKinnon for many years.
“Still Down: What to Do When Antidepressants Fail” by Dean F. MacKinnon, MD, is a compact little book that recently was released by Johns Hopkins University Press. The title, “Still Down,” says it all. At 152 pages, the book is short, but not because it isn’t jammed full of information, but because – like the title – the writing is succinct and straight to the point; there’s no flowery detail, and Dr. MacKinnon doesn’t parse words. He tells the reader up front what his mission is, how the book is organized, and who his audience is. He’s an organized writer who captures the reader while getting his point across.
The book is divided into three distinct parts. In chapter 1, Ann suffers from “textbook depression.” Dr. MacKinnon uses this as an opportunity to educate the reader on the signs and symptoms of major depression, and the fact that treatment takes several weeks, during which side effects may occur before the resolution of symptoms. He talks about depression as a recurring medical illness, lists the available antidepressants by their class, and mentions that depression can be a result of other medical illnesses such as thyroid disease. In chapter 2, college student Bob remains depressed until he takes the medications as prescribed at a steady dose on a daily basis. This involves some coaxing, education, and even outreach by the school nurse, all while being cognizant of things that can go wrong in a young person on antidepressants.
Part 2 of “Still Down” takes on the sticky issue of misdiagnosis. Darius sees Dr. Dennis for treatment of depression during a distressing period of his life when treatment with another doctor had already failed. After careful assessment, Dr. Dennis concludes that while antidepressants weren’t unreasonable to try, Darius is actually suffering from demoralization from losing his business, a miserable divorce, and a child custody battle. Dr. Dennis suggests therapy instead of medications at this point. This was where I found that, I, as a clinician, swayed from Dr. MacKinnon’s treatment approach: He emphasizes an inability to function and to feel pleasure as necessary elements of major depression, and Darius could do both to some extent. But still, his sleep was poor from shift work. He’d gained 30 pounds; he had little energy for activities besides work; and he was in a rut, unhappy, and having trouble entertaining his children when they visited and feeling too lazy to make changes. I thought Darius was depressed and demoralized, and while I agreed with the author that he needed psychotherapy, I also would have continued with medication trials. Dr. MacKinnon certainly doesn’t dismiss the idea of medication, and I found it helpful to revisit demoralization as a state responsible for many psychiatric symptoms.
Moving on in the section on misdiagnoses, the author talks about Evelyn, who turns out to have bipolar versus unipolar depression, and Frances, who carries an incorrect diagnosis of bipolar disorder, and has been overmedicated into a state of delirium. They both do well with time, thoughtful assessment, and treatment. Clinical pearls are threaded through these chapters.
“Depression-plus” is the title of the final section. Gary has major depression superimposed on his dysthymia, or persistent depressive disorder, and Dr. MacKinnon notes that people with constitutionally gloomy moods may have persistent sadness even after successful treatment of major depression. Here, there is a need for accommodation to a given personality state, and therapy can be helpful. Hannah, a patient of Dr. Hernandez, has what the author calls “depressed functioning.” This part I found most interesting, because I see this often in practice – a patient with a long history of being unmotivated and underfunctioning does not get fully (or any) better with antidepressants. Here, the functioning must improve before mood and self-esteem lift, and this is not an easy task. Finally, Irma has treatment-resistant depression, and with her doctor, considers a variety of augmentation medications as well as more novel strategies.
Simply stated, this book is a gem. It’s a very understandable guide to a very complex and frustrating issue, one that needs more time-consuming and thoughtful evaluation, and more intensive resources than a simple episode of depression usually entails.
Finally, I have to admit that I enjoyed Dr. MacKinnon’s quiet jabs at electronic medical records.
Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has known Dr. MacKinnon for many years.
“Still Down: What to Do When Antidepressants Fail” by Dean F. MacKinnon, MD, is a compact little book that recently was released by Johns Hopkins University Press. The title, “Still Down,” says it all. At 152 pages, the book is short, but not because it isn’t jammed full of information, but because – like the title – the writing is succinct and straight to the point; there’s no flowery detail, and Dr. MacKinnon doesn’t parse words. He tells the reader up front what his mission is, how the book is organized, and who his audience is. He’s an organized writer who captures the reader while getting his point across.
The book is divided into three distinct parts. In chapter 1, Ann suffers from “textbook depression.” Dr. MacKinnon uses this as an opportunity to educate the reader on the signs and symptoms of major depression, and the fact that treatment takes several weeks, during which side effects may occur before the resolution of symptoms. He talks about depression as a recurring medical illness, lists the available antidepressants by their class, and mentions that depression can be a result of other medical illnesses such as thyroid disease. In chapter 2, college student Bob remains depressed until he takes the medications as prescribed at a steady dose on a daily basis. This involves some coaxing, education, and even outreach by the school nurse, all while being cognizant of things that can go wrong in a young person on antidepressants.
Part 2 of “Still Down” takes on the sticky issue of misdiagnosis. Darius sees Dr. Dennis for treatment of depression during a distressing period of his life when treatment with another doctor had already failed. After careful assessment, Dr. Dennis concludes that while antidepressants weren’t unreasonable to try, Darius is actually suffering from demoralization from losing his business, a miserable divorce, and a child custody battle. Dr. Dennis suggests therapy instead of medications at this point. This was where I found that, I, as a clinician, swayed from Dr. MacKinnon’s treatment approach: He emphasizes an inability to function and to feel pleasure as necessary elements of major depression, and Darius could do both to some extent. But still, his sleep was poor from shift work. He’d gained 30 pounds; he had little energy for activities besides work; and he was in a rut, unhappy, and having trouble entertaining his children when they visited and feeling too lazy to make changes. I thought Darius was depressed and demoralized, and while I agreed with the author that he needed psychotherapy, I also would have continued with medication trials. Dr. MacKinnon certainly doesn’t dismiss the idea of medication, and I found it helpful to revisit demoralization as a state responsible for many psychiatric symptoms.
Moving on in the section on misdiagnoses, the author talks about Evelyn, who turns out to have bipolar versus unipolar depression, and Frances, who carries an incorrect diagnosis of bipolar disorder, and has been overmedicated into a state of delirium. They both do well with time, thoughtful assessment, and treatment. Clinical pearls are threaded through these chapters.
“Depression-plus” is the title of the final section. Gary has major depression superimposed on his dysthymia, or persistent depressive disorder, and Dr. MacKinnon notes that people with constitutionally gloomy moods may have persistent sadness even after successful treatment of major depression. Here, there is a need for accommodation to a given personality state, and therapy can be helpful. Hannah, a patient of Dr. Hernandez, has what the author calls “depressed functioning.” This part I found most interesting, because I see this often in practice – a patient with a long history of being unmotivated and underfunctioning does not get fully (or any) better with antidepressants. Here, the functioning must improve before mood and self-esteem lift, and this is not an easy task. Finally, Irma has treatment-resistant depression, and with her doctor, considers a variety of augmentation medications as well as more novel strategies.
Simply stated, this book is a gem. It’s a very understandable guide to a very complex and frustrating issue, one that needs more time-consuming and thoughtful evaluation, and more intensive resources than a simple episode of depression usually entails.
Finally, I have to admit that I enjoyed Dr. MacKinnon’s quiet jabs at electronic medical records.
Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has known Dr. MacKinnon for many years.
Replicative Zika RNA found in brain and placental tissue
U.S.-based researchers have isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placenta and fetal tissues from women suspected of being infected with Zika virus during pregnancy.
In a paper published online in Emerging Infectious Diseases, Julu Bhatnagar, PhD, of the Infectious Diseases Pathology Branch at the Center for Emerging and Zoonotic Infectious Diseases in Atlanta, and her coauthors reported a case series in 52 patients – 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy – using Zika virus reverse transcription PCR and in situ hybridization assay to detect the virus.
“Nevertheless, localization of replicating Zika virus RNA directly in the tissues of patients with congenital and pregnancy-associated infections is critical for identifying cellular targets of Zika virus infection and virus persistence in various tissues and for further investigating the mechanism of Zika virus intrauterine transmission,” Dr. Bhatnagar said.
Using RT-PCR, the researchers were able to isolate Zika virus RNA from 32 (62%) of the case-patients – all 8 infants with microcephaly who died, and 24 women.
There were no major clinical differences between the women who tested positive for Zika virus with RT-PCR and those who tested negative; the most common symptoms in both groups were rash, fever, arthralgia, headache and conjunctivitis.
Among women who had an adverse pregnancy or birth outcome, 24 (75%) tested positive for Zika virus via RT-PCR, compared to 8 (36%) women with live-born healthy infants (P = .0082).
Symptom onset during the first trimester was associated with a significantly higher risk of adverse pregnancy and birth outcomes. Of the 24 women with positive RT-PCR results and adverse pregnancy outcomes, 23 had symptom onset during the first trimester, while all 8 patients with positive RT-PCR results but healthy infants had symptom onset in the third trimester (P less than .0001).
There were eight cases of infants with microcephaly who died within a few minutes to 2 months after birth, and five women who delivered live infants with microcephaly who survived.
All but one of these tested positive for Zika virus by RT-PCR, either in brain tissue or placental/fetal tissue, and all the women experienced symptom onset during the first trimester. Zika virus was not detected in other tissues from the infants.
Researchers also found that the levels of Zika virus RNA in the brain tissues of the infants who had microcephaly and died were around 1,200-fold higher than the levels observed in second or third trimester or full-term placentas.
Using in situ hybridization assays, researchers found Zika virus RNA in half of the tissues of the 32 case-patients who tested positive with RT-PCR.
“Zika virus replicative RNA, detected by using sense probe, was observed in the neural cells, neurons, and degenerating glial cells within the cerebral cortex of the brain,” the authors wrote.
Zika virus genomic and replicative RNA also was found in the placental chorionic villi – predominantly in the Hofbauer cells – in 9 (75%) of the 12 women with positive RT-PCR results who had experienced an adverse pregnancy outcome during the first or second trimester. The authors said this indicated the possibility that the Hofbauer cells may play a role in disseminating or transferring the virus to the fetal brain.
“This article highlights the value of tissue analysis to expand opportunities to diagnose Zika virus congenital and pregnancy-associated infections and to enhance the understanding of mechanism of Zika virus intrauterine transmission and pathogenesis,” the authors wrote. “In addition, the tissue-based RT-PCRs extend the time frame for Zika virus detection and particularly help to establish a diagnosis retrospectively, enabling pregnant women and their health care providers to identify the cause of severe microcephaly or fetal loss.”
No conflicts of interest were declared.
[email protected]
On Twitter @idpractitioner
U.S.-based researchers have isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placenta and fetal tissues from women suspected of being infected with Zika virus during pregnancy.
In a paper published online in Emerging Infectious Diseases, Julu Bhatnagar, PhD, of the Infectious Diseases Pathology Branch at the Center for Emerging and Zoonotic Infectious Diseases in Atlanta, and her coauthors reported a case series in 52 patients – 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy – using Zika virus reverse transcription PCR and in situ hybridization assay to detect the virus.
“Nevertheless, localization of replicating Zika virus RNA directly in the tissues of patients with congenital and pregnancy-associated infections is critical for identifying cellular targets of Zika virus infection and virus persistence in various tissues and for further investigating the mechanism of Zika virus intrauterine transmission,” Dr. Bhatnagar said.
Using RT-PCR, the researchers were able to isolate Zika virus RNA from 32 (62%) of the case-patients – all 8 infants with microcephaly who died, and 24 women.
There were no major clinical differences between the women who tested positive for Zika virus with RT-PCR and those who tested negative; the most common symptoms in both groups were rash, fever, arthralgia, headache and conjunctivitis.
Among women who had an adverse pregnancy or birth outcome, 24 (75%) tested positive for Zika virus via RT-PCR, compared to 8 (36%) women with live-born healthy infants (P = .0082).
Symptom onset during the first trimester was associated with a significantly higher risk of adverse pregnancy and birth outcomes. Of the 24 women with positive RT-PCR results and adverse pregnancy outcomes, 23 had symptom onset during the first trimester, while all 8 patients with positive RT-PCR results but healthy infants had symptom onset in the third trimester (P less than .0001).
There were eight cases of infants with microcephaly who died within a few minutes to 2 months after birth, and five women who delivered live infants with microcephaly who survived.
All but one of these tested positive for Zika virus by RT-PCR, either in brain tissue or placental/fetal tissue, and all the women experienced symptom onset during the first trimester. Zika virus was not detected in other tissues from the infants.
Researchers also found that the levels of Zika virus RNA in the brain tissues of the infants who had microcephaly and died were around 1,200-fold higher than the levels observed in second or third trimester or full-term placentas.
Using in situ hybridization assays, researchers found Zika virus RNA in half of the tissues of the 32 case-patients who tested positive with RT-PCR.
“Zika virus replicative RNA, detected by using sense probe, was observed in the neural cells, neurons, and degenerating glial cells within the cerebral cortex of the brain,” the authors wrote.
Zika virus genomic and replicative RNA also was found in the placental chorionic villi – predominantly in the Hofbauer cells – in 9 (75%) of the 12 women with positive RT-PCR results who had experienced an adverse pregnancy outcome during the first or second trimester. The authors said this indicated the possibility that the Hofbauer cells may play a role in disseminating or transferring the virus to the fetal brain.
“This article highlights the value of tissue analysis to expand opportunities to diagnose Zika virus congenital and pregnancy-associated infections and to enhance the understanding of mechanism of Zika virus intrauterine transmission and pathogenesis,” the authors wrote. “In addition, the tissue-based RT-PCRs extend the time frame for Zika virus detection and particularly help to establish a diagnosis retrospectively, enabling pregnant women and their health care providers to identify the cause of severe microcephaly or fetal loss.”
No conflicts of interest were declared.
[email protected]
On Twitter @idpractitioner
U.S.-based researchers have isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placenta and fetal tissues from women suspected of being infected with Zika virus during pregnancy.
In a paper published online in Emerging Infectious Diseases, Julu Bhatnagar, PhD, of the Infectious Diseases Pathology Branch at the Center for Emerging and Zoonotic Infectious Diseases in Atlanta, and her coauthors reported a case series in 52 patients – 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy – using Zika virus reverse transcription PCR and in situ hybridization assay to detect the virus.
“Nevertheless, localization of replicating Zika virus RNA directly in the tissues of patients with congenital and pregnancy-associated infections is critical for identifying cellular targets of Zika virus infection and virus persistence in various tissues and for further investigating the mechanism of Zika virus intrauterine transmission,” Dr. Bhatnagar said.
Using RT-PCR, the researchers were able to isolate Zika virus RNA from 32 (62%) of the case-patients – all 8 infants with microcephaly who died, and 24 women.
There were no major clinical differences between the women who tested positive for Zika virus with RT-PCR and those who tested negative; the most common symptoms in both groups were rash, fever, arthralgia, headache and conjunctivitis.
Among women who had an adverse pregnancy or birth outcome, 24 (75%) tested positive for Zika virus via RT-PCR, compared to 8 (36%) women with live-born healthy infants (P = .0082).
Symptom onset during the first trimester was associated with a significantly higher risk of adverse pregnancy and birth outcomes. Of the 24 women with positive RT-PCR results and adverse pregnancy outcomes, 23 had symptom onset during the first trimester, while all 8 patients with positive RT-PCR results but healthy infants had symptom onset in the third trimester (P less than .0001).
There were eight cases of infants with microcephaly who died within a few minutes to 2 months after birth, and five women who delivered live infants with microcephaly who survived.
All but one of these tested positive for Zika virus by RT-PCR, either in brain tissue or placental/fetal tissue, and all the women experienced symptom onset during the first trimester. Zika virus was not detected in other tissues from the infants.
Researchers also found that the levels of Zika virus RNA in the brain tissues of the infants who had microcephaly and died were around 1,200-fold higher than the levels observed in second or third trimester or full-term placentas.
Using in situ hybridization assays, researchers found Zika virus RNA in half of the tissues of the 32 case-patients who tested positive with RT-PCR.
“Zika virus replicative RNA, detected by using sense probe, was observed in the neural cells, neurons, and degenerating glial cells within the cerebral cortex of the brain,” the authors wrote.
Zika virus genomic and replicative RNA also was found in the placental chorionic villi – predominantly in the Hofbauer cells – in 9 (75%) of the 12 women with positive RT-PCR results who had experienced an adverse pregnancy outcome during the first or second trimester. The authors said this indicated the possibility that the Hofbauer cells may play a role in disseminating or transferring the virus to the fetal brain.
“This article highlights the value of tissue analysis to expand opportunities to diagnose Zika virus congenital and pregnancy-associated infections and to enhance the understanding of mechanism of Zika virus intrauterine transmission and pathogenesis,” the authors wrote. “In addition, the tissue-based RT-PCRs extend the time frame for Zika virus detection and particularly help to establish a diagnosis retrospectively, enabling pregnant women and their health care providers to identify the cause of severe microcephaly or fetal loss.”
No conflicts of interest were declared.
[email protected]
On Twitter @idpractitioner
FROM EMERGING INFECTIOUS DISEASES
Key clinical point: Researchers isolated replicative Zika virus RNA from the brain tissue of infants with microcephaly, and the placental tissues of women suspected of being infected with Zika virus during pregnancy.
Major finding: Among women who had an adverse pregnancy or birth outcome, 75% tested positive for Zika virus via RT-PCR, compared to 36% of women with live-born healthy infants.
Data source: Case series of 8 infants with microcephaly who died and 44 women thought to have been infected with Zika virus during pregnancy.
Disclosures: No conflicts of interest were declared.
Pulley Suture for Wound Closure
Cardiovascular disease: Innovations in devices and techniques
Supplement Editor:
Maan A. Fares, MD
Contents
Cardiovascular disease: Innovations in devices and techniques
Maan A. Fares
Transcatheter mitral valve replacement: A frontier in cardiac intervention
Amar Krishnaswamy, Stephanie Mick, Jose Navia, A. Marc Gillinov, E. Murrat Tuzcu, and Samir R. Kapadia
Bioresorbable stents: The future of Interventional cardiology?
Stephen G. Ellis and Haris Riaz
Leadless cardiac pacing: What primary care providers and non-EP cardiologists should know
Erich L. Kiehl and Daniel J. Cantillon
PCSK9 inhibition: A promise fulfilled?
Khendi White, Chaitra Mohan, and Michael Rocco
Fibromuscular dysplasia: Advances in understanding and management
Ellen K. Brinza and Heather L. Gornik
Supplement Editor:
Maan A. Fares, MD
Contents
Cardiovascular disease: Innovations in devices and techniques
Maan A. Fares
Transcatheter mitral valve replacement: A frontier in cardiac intervention
Amar Krishnaswamy, Stephanie Mick, Jose Navia, A. Marc Gillinov, E. Murrat Tuzcu, and Samir R. Kapadia
Bioresorbable stents: The future of Interventional cardiology?
Stephen G. Ellis and Haris Riaz
Leadless cardiac pacing: What primary care providers and non-EP cardiologists should know
Erich L. Kiehl and Daniel J. Cantillon
PCSK9 inhibition: A promise fulfilled?
Khendi White, Chaitra Mohan, and Michael Rocco
Fibromuscular dysplasia: Advances in understanding and management
Ellen K. Brinza and Heather L. Gornik
Supplement Editor:
Maan A. Fares, MD
Contents
Cardiovascular disease: Innovations in devices and techniques
Maan A. Fares
Transcatheter mitral valve replacement: A frontier in cardiac intervention
Amar Krishnaswamy, Stephanie Mick, Jose Navia, A. Marc Gillinov, E. Murrat Tuzcu, and Samir R. Kapadia
Bioresorbable stents: The future of Interventional cardiology?
Stephen G. Ellis and Haris Riaz
Leadless cardiac pacing: What primary care providers and non-EP cardiologists should know
Erich L. Kiehl and Daniel J. Cantillon
PCSK9 inhibition: A promise fulfilled?
Khendi White, Chaitra Mohan, and Michael Rocco
Fibromuscular dysplasia: Advances in understanding and management
Ellen K. Brinza and Heather L. Gornik
Why ustekinumab dosing differs in Crohn’s disease
ORLANDO – Preclinical studies and years of clinical experience using the monoclonal antibody ustekinumab (Stelara, Janssen Biotech) in psoriasis and psoriatic arthritis offer important clues to any gastroenterologist perplexed by the official Food and Drug Administration indication, dosing frequency, and intensity for Crohn’s disease. Phase II and phase III findings also reveal where the monoclonal antibody may offer particular advantages, compared with other agents.
“Ustekinumab landed in your lap in September. You’re probably all trying to figure out how to get the ID formulation paid for with insurance,” William J. Sanborn, MD, professor and chief of the division of gastroenterology at the University of California, San Diego, said at the Advances in Inflammatory Bowel Diseases meeting. “But this is now the reality that you have this in your Crohn’s practice.”
The FDA approved ustekinumab to treat adults with moderately to severely active Crohn’s disease who 1) failed or were intolerant to immune modulators or corticosteroids but did not fail tumor necrosis factor (TNF) blockers or 2) failed or were intolerant to one or more TNF blockers. Dr. Sanborn and colleagues observed a significant induction of clinical response in a subgroup of patients who previously failed a TNF blocker in an early efficacy study (Gastroenterology. 2008;135:1130-41). “This is where the idea of initially focusing on TNF failures came from,” he added at the meeting sponsored by the Crohn’s & Colitis Foundation of America.
Induction dosing in Crohn’s disease is intravenous versus subcutaneous in psoriasis and psoriatic arthritis, in part because of the same study. “It looked like relatively better bioavailability and relatively better effect with intravenous dosing,” Dr. Sanborn said. “In Crohn’s disease, it’s a completely different animal.”
Official induction dosing is approximately 6 mg/kg in three fixed doses according to patient weight in Crohn’s disease. The 6-mg/kg dose yielded the most consistent response, compared with 1-mg/kg or 3-mg/kg doses in a subsequent phase IIb study (N Engl J Med. 2012;367:1519-28).
The most consistent induction results at weeks 6 and 8 were observed with 6 mg/kg ustekinumab versus 1 mg/kg or 3 mg/kg.
Dr. Sanborn and coinvestigators also saw “numeric differences in drug versus placebo for remission at 6 and 8 weeks “but it was not that clear from the phase II trial what the remission efficacy was, so that needed more exploration to really understand.”
Another distinction for ustekinumab in Crohn’s disease is the approved maintenance dosing of 90 mg subcutaneously every 8 weeks versus a 12-week interval recommended for psoriasis. “Why so much more in Crohn’s disease, and is that necessary?” Dr. Sanborn asked.
Based on changes in C-reactive protein levels and a “rapid drop” in Crohn’s Disease Activity Index scores by 4 weeks, “clearly efficacy was there for induction,” he said. Ustekinumab has a “quick onset – analogous to the TNF blockers.”
“These were quite encouraging data, and paved the way to move on to phase III [studies],” Dr. Sanborn said. The preclinical studies up to this point focused on patients with Crohn’s disease who previously failed TNF blockers. However, “in clinical practice, we would be interested to know if it would work in anti-TNF naive or nonfailures as well.”
So two subsequent studies assessed safety and efficacy in a TNF blocker–failure population (UNITI-1 trial. Inflamm. Bowel Dis. 2016 Mar;22 Suppl 1:S1) and a non-TNF failure population of patients who did fail previous conventional therapy such as steroids or immunomodulators (UNITI-2 trial).
Clinical response and remission steadily rose following induction up to a significant difference versus placebo at 8 weeks in the non–TNF failure population. “Remember, in the phase IIa study, the remission rates were not as clear-cut, so this really nails down this as a good drug in both patient populations,” Dr. Sanborn said.
To evaluate long-term maintenance, investigators rerandomized all participants in the UNITI-1 and UNITI-2 studies. They saw a 15% gain in clinical remission out to week 44, compared with placebo. Dr. Sanborn noted that ustekinumab has a relatively long half-life, so the difference in patients switched to placebo may not have been as striking. “In practice it’s important to know the on-time and off-time of this agent, and I think the clinical trials make that clear.”
The trials also show that 12-week dosing works, Dr. Sanborn said. “You see about 20% gain for every 8-week dosing. You get extra 5% or 10% extra on all outcome measures at 8 weeks, compared to 12 weeks dosing, with no difference in safety signals.” He added, “So more intensive dosing of 90 mg every 8 weeks is what ended up getting approved in the United States.”
Safety profile
So what does all the preclinical evidence suggest about safety of ustekinumab? The UNITI trials combined included more than 1,000 patients, and there were no deaths, Dr. Sanborn said. “Usually with TNF blockers in 1,000 patients you would see a few deaths.”
Patient withdrawals from the preclinical studies were also relatively low, Dr. Sanborn reported. “With ustekinumab monotherapy, drug withdrawal is only 3% or 4%, so it seems to be different from TNF blockers in that sense [too].”
In addition, the rates of adverse events were similar between placebo (83.5%) and ustekinumab’s combined every 8 week and every 12 week dosing groups through 44 weeks (81.0%), Dr. Sanborn said. The rates of serious adverse events were likewise similar, 15.0% and 11.0%, respectively. Reported malignancy included two cases of basal cell skin cancers, one in the placebo group and one in the every-8-week dosing group, he added.
“So all those black box warnings you’re used to worrying about with TNF blockers – serious infections, about opportunistic infections, malignancy – there is no black box warning with this agent around that.”
Dr. Sanborn noted that the FDA labeling reports infections. “We know Crohn’s disease patients are [also] getting azathioprine, steroids, methotrexate, so you will see some infections, but there wasn’t a consistent opportunistic infection signal.”
One case of reversible posterior leukoencephalopathy syndrome is included on the labeling. Dr. Sanborn also put this in perspective: “With all the experience in psoriasis and psoriatic arthritis, and the clinical trials [in IBD], there is just one case. So the relationship is not very clear.”
“The safety signals with ustekinumab are really very good. It seems to be an extremely safe agent – we really don’t see much in terms of infections,” Brian Feagan, MD, an internist and gastroenterologist at the University of Western Ontario in London, said in a separate presentation at the conference. “We don’t have a lot of long-term experience with ustekinumab in Crohn’s disease, but we have a lot of experience in psoriasis, and it’s a safe drug.”
“Ustekinumab may be our first really valid monotherapy, with less immunogenicity,” Dr. Feagan said.
ORLANDO – Preclinical studies and years of clinical experience using the monoclonal antibody ustekinumab (Stelara, Janssen Biotech) in psoriasis and psoriatic arthritis offer important clues to any gastroenterologist perplexed by the official Food and Drug Administration indication, dosing frequency, and intensity for Crohn’s disease. Phase II and phase III findings also reveal where the monoclonal antibody may offer particular advantages, compared with other agents.
“Ustekinumab landed in your lap in September. You’re probably all trying to figure out how to get the ID formulation paid for with insurance,” William J. Sanborn, MD, professor and chief of the division of gastroenterology at the University of California, San Diego, said at the Advances in Inflammatory Bowel Diseases meeting. “But this is now the reality that you have this in your Crohn’s practice.”
The FDA approved ustekinumab to treat adults with moderately to severely active Crohn’s disease who 1) failed or were intolerant to immune modulators or corticosteroids but did not fail tumor necrosis factor (TNF) blockers or 2) failed or were intolerant to one or more TNF blockers. Dr. Sanborn and colleagues observed a significant induction of clinical response in a subgroup of patients who previously failed a TNF blocker in an early efficacy study (Gastroenterology. 2008;135:1130-41). “This is where the idea of initially focusing on TNF failures came from,” he added at the meeting sponsored by the Crohn’s & Colitis Foundation of America.
Induction dosing in Crohn’s disease is intravenous versus subcutaneous in psoriasis and psoriatic arthritis, in part because of the same study. “It looked like relatively better bioavailability and relatively better effect with intravenous dosing,” Dr. Sanborn said. “In Crohn’s disease, it’s a completely different animal.”
Official induction dosing is approximately 6 mg/kg in three fixed doses according to patient weight in Crohn’s disease. The 6-mg/kg dose yielded the most consistent response, compared with 1-mg/kg or 3-mg/kg doses in a subsequent phase IIb study (N Engl J Med. 2012;367:1519-28).
The most consistent induction results at weeks 6 and 8 were observed with 6 mg/kg ustekinumab versus 1 mg/kg or 3 mg/kg.
Dr. Sanborn and coinvestigators also saw “numeric differences in drug versus placebo for remission at 6 and 8 weeks “but it was not that clear from the phase II trial what the remission efficacy was, so that needed more exploration to really understand.”
Another distinction for ustekinumab in Crohn’s disease is the approved maintenance dosing of 90 mg subcutaneously every 8 weeks versus a 12-week interval recommended for psoriasis. “Why so much more in Crohn’s disease, and is that necessary?” Dr. Sanborn asked.
Based on changes in C-reactive protein levels and a “rapid drop” in Crohn’s Disease Activity Index scores by 4 weeks, “clearly efficacy was there for induction,” he said. Ustekinumab has a “quick onset – analogous to the TNF blockers.”
“These were quite encouraging data, and paved the way to move on to phase III [studies],” Dr. Sanborn said. The preclinical studies up to this point focused on patients with Crohn’s disease who previously failed TNF blockers. However, “in clinical practice, we would be interested to know if it would work in anti-TNF naive or nonfailures as well.”
So two subsequent studies assessed safety and efficacy in a TNF blocker–failure population (UNITI-1 trial. Inflamm. Bowel Dis. 2016 Mar;22 Suppl 1:S1) and a non-TNF failure population of patients who did fail previous conventional therapy such as steroids or immunomodulators (UNITI-2 trial).
Clinical response and remission steadily rose following induction up to a significant difference versus placebo at 8 weeks in the non–TNF failure population. “Remember, in the phase IIa study, the remission rates were not as clear-cut, so this really nails down this as a good drug in both patient populations,” Dr. Sanborn said.
To evaluate long-term maintenance, investigators rerandomized all participants in the UNITI-1 and UNITI-2 studies. They saw a 15% gain in clinical remission out to week 44, compared with placebo. Dr. Sanborn noted that ustekinumab has a relatively long half-life, so the difference in patients switched to placebo may not have been as striking. “In practice it’s important to know the on-time and off-time of this agent, and I think the clinical trials make that clear.”
The trials also show that 12-week dosing works, Dr. Sanborn said. “You see about 20% gain for every 8-week dosing. You get extra 5% or 10% extra on all outcome measures at 8 weeks, compared to 12 weeks dosing, with no difference in safety signals.” He added, “So more intensive dosing of 90 mg every 8 weeks is what ended up getting approved in the United States.”
Safety profile
So what does all the preclinical evidence suggest about safety of ustekinumab? The UNITI trials combined included more than 1,000 patients, and there were no deaths, Dr. Sanborn said. “Usually with TNF blockers in 1,000 patients you would see a few deaths.”
Patient withdrawals from the preclinical studies were also relatively low, Dr. Sanborn reported. “With ustekinumab monotherapy, drug withdrawal is only 3% or 4%, so it seems to be different from TNF blockers in that sense [too].”
In addition, the rates of adverse events were similar between placebo (83.5%) and ustekinumab’s combined every 8 week and every 12 week dosing groups through 44 weeks (81.0%), Dr. Sanborn said. The rates of serious adverse events were likewise similar, 15.0% and 11.0%, respectively. Reported malignancy included two cases of basal cell skin cancers, one in the placebo group and one in the every-8-week dosing group, he added.
“So all those black box warnings you’re used to worrying about with TNF blockers – serious infections, about opportunistic infections, malignancy – there is no black box warning with this agent around that.”
Dr. Sanborn noted that the FDA labeling reports infections. “We know Crohn’s disease patients are [also] getting azathioprine, steroids, methotrexate, so you will see some infections, but there wasn’t a consistent opportunistic infection signal.”
One case of reversible posterior leukoencephalopathy syndrome is included on the labeling. Dr. Sanborn also put this in perspective: “With all the experience in psoriasis and psoriatic arthritis, and the clinical trials [in IBD], there is just one case. So the relationship is not very clear.”
“The safety signals with ustekinumab are really very good. It seems to be an extremely safe agent – we really don’t see much in terms of infections,” Brian Feagan, MD, an internist and gastroenterologist at the University of Western Ontario in London, said in a separate presentation at the conference. “We don’t have a lot of long-term experience with ustekinumab in Crohn’s disease, but we have a lot of experience in psoriasis, and it’s a safe drug.”
“Ustekinumab may be our first really valid monotherapy, with less immunogenicity,” Dr. Feagan said.
ORLANDO – Preclinical studies and years of clinical experience using the monoclonal antibody ustekinumab (Stelara, Janssen Biotech) in psoriasis and psoriatic arthritis offer important clues to any gastroenterologist perplexed by the official Food and Drug Administration indication, dosing frequency, and intensity for Crohn’s disease. Phase II and phase III findings also reveal where the monoclonal antibody may offer particular advantages, compared with other agents.
“Ustekinumab landed in your lap in September. You’re probably all trying to figure out how to get the ID formulation paid for with insurance,” William J. Sanborn, MD, professor and chief of the division of gastroenterology at the University of California, San Diego, said at the Advances in Inflammatory Bowel Diseases meeting. “But this is now the reality that you have this in your Crohn’s practice.”
The FDA approved ustekinumab to treat adults with moderately to severely active Crohn’s disease who 1) failed or were intolerant to immune modulators or corticosteroids but did not fail tumor necrosis factor (TNF) blockers or 2) failed or were intolerant to one or more TNF blockers. Dr. Sanborn and colleagues observed a significant induction of clinical response in a subgroup of patients who previously failed a TNF blocker in an early efficacy study (Gastroenterology. 2008;135:1130-41). “This is where the idea of initially focusing on TNF failures came from,” he added at the meeting sponsored by the Crohn’s & Colitis Foundation of America.
Induction dosing in Crohn’s disease is intravenous versus subcutaneous in psoriasis and psoriatic arthritis, in part because of the same study. “It looked like relatively better bioavailability and relatively better effect with intravenous dosing,” Dr. Sanborn said. “In Crohn’s disease, it’s a completely different animal.”
Official induction dosing is approximately 6 mg/kg in three fixed doses according to patient weight in Crohn’s disease. The 6-mg/kg dose yielded the most consistent response, compared with 1-mg/kg or 3-mg/kg doses in a subsequent phase IIb study (N Engl J Med. 2012;367:1519-28).
The most consistent induction results at weeks 6 and 8 were observed with 6 mg/kg ustekinumab versus 1 mg/kg or 3 mg/kg.
Dr. Sanborn and coinvestigators also saw “numeric differences in drug versus placebo for remission at 6 and 8 weeks “but it was not that clear from the phase II trial what the remission efficacy was, so that needed more exploration to really understand.”
Another distinction for ustekinumab in Crohn’s disease is the approved maintenance dosing of 90 mg subcutaneously every 8 weeks versus a 12-week interval recommended for psoriasis. “Why so much more in Crohn’s disease, and is that necessary?” Dr. Sanborn asked.
Based on changes in C-reactive protein levels and a “rapid drop” in Crohn’s Disease Activity Index scores by 4 weeks, “clearly efficacy was there for induction,” he said. Ustekinumab has a “quick onset – analogous to the TNF blockers.”
“These were quite encouraging data, and paved the way to move on to phase III [studies],” Dr. Sanborn said. The preclinical studies up to this point focused on patients with Crohn’s disease who previously failed TNF blockers. However, “in clinical practice, we would be interested to know if it would work in anti-TNF naive or nonfailures as well.”
So two subsequent studies assessed safety and efficacy in a TNF blocker–failure population (UNITI-1 trial. Inflamm. Bowel Dis. 2016 Mar;22 Suppl 1:S1) and a non-TNF failure population of patients who did fail previous conventional therapy such as steroids or immunomodulators (UNITI-2 trial).
Clinical response and remission steadily rose following induction up to a significant difference versus placebo at 8 weeks in the non–TNF failure population. “Remember, in the phase IIa study, the remission rates were not as clear-cut, so this really nails down this as a good drug in both patient populations,” Dr. Sanborn said.
To evaluate long-term maintenance, investigators rerandomized all participants in the UNITI-1 and UNITI-2 studies. They saw a 15% gain in clinical remission out to week 44, compared with placebo. Dr. Sanborn noted that ustekinumab has a relatively long half-life, so the difference in patients switched to placebo may not have been as striking. “In practice it’s important to know the on-time and off-time of this agent, and I think the clinical trials make that clear.”
The trials also show that 12-week dosing works, Dr. Sanborn said. “You see about 20% gain for every 8-week dosing. You get extra 5% or 10% extra on all outcome measures at 8 weeks, compared to 12 weeks dosing, with no difference in safety signals.” He added, “So more intensive dosing of 90 mg every 8 weeks is what ended up getting approved in the United States.”
Safety profile
So what does all the preclinical evidence suggest about safety of ustekinumab? The UNITI trials combined included more than 1,000 patients, and there were no deaths, Dr. Sanborn said. “Usually with TNF blockers in 1,000 patients you would see a few deaths.”
Patient withdrawals from the preclinical studies were also relatively low, Dr. Sanborn reported. “With ustekinumab monotherapy, drug withdrawal is only 3% or 4%, so it seems to be different from TNF blockers in that sense [too].”
In addition, the rates of adverse events were similar between placebo (83.5%) and ustekinumab’s combined every 8 week and every 12 week dosing groups through 44 weeks (81.0%), Dr. Sanborn said. The rates of serious adverse events were likewise similar, 15.0% and 11.0%, respectively. Reported malignancy included two cases of basal cell skin cancers, one in the placebo group and one in the every-8-week dosing group, he added.
“So all those black box warnings you’re used to worrying about with TNF blockers – serious infections, about opportunistic infections, malignancy – there is no black box warning with this agent around that.”
Dr. Sanborn noted that the FDA labeling reports infections. “We know Crohn’s disease patients are [also] getting azathioprine, steroids, methotrexate, so you will see some infections, but there wasn’t a consistent opportunistic infection signal.”
One case of reversible posterior leukoencephalopathy syndrome is included on the labeling. Dr. Sanborn also put this in perspective: “With all the experience in psoriasis and psoriatic arthritis, and the clinical trials [in IBD], there is just one case. So the relationship is not very clear.”
“The safety signals with ustekinumab are really very good. It seems to be an extremely safe agent – we really don’t see much in terms of infections,” Brian Feagan, MD, an internist and gastroenterologist at the University of Western Ontario in London, said in a separate presentation at the conference. “We don’t have a lot of long-term experience with ustekinumab in Crohn’s disease, but we have a lot of experience in psoriasis, and it’s a safe drug.”
“Ustekinumab may be our first really valid monotherapy, with less immunogenicity,” Dr. Feagan said.
EXPERT ANALYSIS FROM AIBD 2016
Clinical Guidelines: Hospital-acquired and ventilator-associated pneumonia
Hospital-acquired pneumonia (HAP) is pneumonia that presents at least 48 hours after admission to the hospital. In contrast, ventilator-associated pneumonia (VAP), is pneumonia that clinically presents 48 hours after endotracheal intubation. Together, these are some of the most common hospital-acquired infections in the United States and pose a considerable burden on hospitals nationwide.
The Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) recently updated their management guidelines for HAP and VAP with a goal of striking a balance between providing appropriate early antibiotic coverage and avoiding unnecessary treatment that can lead to adverse effects such as Clostridium difficile infections and development of antibiotic resistance.1 This update eliminated the concept of Healthcare Associated Pneumonia (HCAP), often used for patients in skilled care facilities, because newer evidence has shown that patients who had met these criteria did not have a higher incidence of multidrug resistant pathogens; rather, they have microbial etiologies and sensitivities that are similar to adults with community acquired pneumonia (CAP).
Hospital-acquired pneumonia
Reasons to cover for MRSA in HAP:
Risk factors:
• IV antibiotic treatment within 90 days
• Treatment in a unit where the prevalence of MRSA is greater than 20% or unknown
• Prior detection of MRSA by culture or nonculture screening (weaker risk factor)
High risk of mortality: • Septic shock
• Need for ventilator support
MRSA should be covered with use of either vancomycin or linezolid in these cases.
In addition, patients with HAP should be covered for Pseudomonas aeruginosa and other gram-negative bacilli. For patients with risk factors for pseudomonas or other gram-negative infection or a high risk for mortality, then two antipseudomonal antibiotics from different classes are recommended, such as piperacillin-tazobactam/tobramycin or cefepime/amikacin.
Use two antipseudomonal antibiotics in HAP if the patient has these risk factors:
Pseudomonas risk factors:
• IV antibiotic treatment within 90 days
• Structural lung disease increasing the risk of gram-negative infection (bronchiectasis, cystic fibrosis)
• High-quality gram stain from respiratory specimen showing predominant and numerous gram-negative bacilli
High risk of mortality:
• Septic shock
• Need for ventilator support
Ventilator-associated pneumonia
General management of VAP is similar to HAP in that empiric treatment should be tailored to the local distribution and susceptibilities of pathogens based on each hospital’s antibiogram. All regimens should cover for S. aureus, P. aeruginosa, and other gram-negative bacilli based on the risk of mortality associated with the need for ventilator support. MSSA should be covered for VAP unless the patient has methicillin-resistant risk factors (see below).
MRSA should be covered for VAP if:
• Patient has had IV antibiotic use within past 90 days
• Hospital unit has greater than 10%-20% of S. aureus isolates are MRSA or MRSA prevalence unknown
Only one antipseudomonal agent should be used unless there are one of the following characteristics present, as described below.
Use two antipseudomonal agents in VAP if:
• Prior IV antibiotic use within 90 days
• Septic shock at time of VAP
• Acute respiratory distress syndrome preceding VAP
• 5 or more days of hospitalization prior to the occurrence of VAP
• Acute renal replacement therapy prior to VAP onset
• Greater than 10% of gram-negative isolates are resistant to an agent being considered for monotherapy
• Local antibiotic susceptibility rates unknown
In both HAP and VAP, antibiotics should be de-escalated to those with a narrower spectrum after initial empiric therapy, ideally within 72 hours and based on sputum or blood culture results. The guidelines support obtaining noninvasive sputum cultures in patients with VAP (endotracheal aspirates) and HAP (spontaneous expectoration, induced sputum, or nasotracheal suctioning in a patient who is unable to cooperate to produce a sputum sample). Patients who are improving clinically may be switched to appropriate oral therapy based on the susceptibility of an identified organism. Another key change is that of the standard duration of therapy. Previously, patients were treated for up to 2-3 weeks with antibiotics. The new IDSA/ATS guidelines recommend that patients should be treated with 7 days of antibiotics rather than a longer course.
The bottom line
Empiric therapy for HAP and VAP should be tailored to each hospital’s local pathogen distribution and antimicrobial susceptibilities, as detailed in an antibiogram. In HAP and VAP, empiric antibiotics should cover for S. aureus, but it only needs to target MRSA if risk factors are present, prevalence is greater than 20% or unknown, and – if HAP – a high risk of mortality. P. aeruginosa and other gram-negative bacilli should also be covered in empiric regimens. Dual antipseudomonal antibiotics is only recommended to be used in HAP if there are specific pseudomonal risk factors or a high risk of mortality. They should be used in VAP if there are multidrug-resistant risk factors present or there is a high/unknown prevalence of resistant organisms. All antibiotic regimens should be deescalated rather than maintained, and both HAP and VAP patients ought to be treated for 7 days.
References
1. Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63(5):557-82.
2. Beardsley JR, Williamson JC, Johnson JW, Ohl CA, Karchmer TB, Bowton DL. Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia. Chest. 2006 Sep;130(3):787-93.
Dr. Botti is a second-year resident in the family medicine residency program department of family and community medicine at Jefferson Medical College, Philadelphia. Dr. Mills is assistant residency program director and assistant professor in the department of family and community medicine and department of physiology at Jefferson Medical College, Philadelphia. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia.
Hospital-acquired pneumonia (HAP) is pneumonia that presents at least 48 hours after admission to the hospital. In contrast, ventilator-associated pneumonia (VAP), is pneumonia that clinically presents 48 hours after endotracheal intubation. Together, these are some of the most common hospital-acquired infections in the United States and pose a considerable burden on hospitals nationwide.
The Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) recently updated their management guidelines for HAP and VAP with a goal of striking a balance between providing appropriate early antibiotic coverage and avoiding unnecessary treatment that can lead to adverse effects such as Clostridium difficile infections and development of antibiotic resistance.1 This update eliminated the concept of Healthcare Associated Pneumonia (HCAP), often used for patients in skilled care facilities, because newer evidence has shown that patients who had met these criteria did not have a higher incidence of multidrug resistant pathogens; rather, they have microbial etiologies and sensitivities that are similar to adults with community acquired pneumonia (CAP).
Hospital-acquired pneumonia
Reasons to cover for MRSA in HAP:
Risk factors:
• IV antibiotic treatment within 90 days
• Treatment in a unit where the prevalence of MRSA is greater than 20% or unknown
• Prior detection of MRSA by culture or nonculture screening (weaker risk factor)
High risk of mortality: • Septic shock
• Need for ventilator support
MRSA should be covered with use of either vancomycin or linezolid in these cases.
In addition, patients with HAP should be covered for Pseudomonas aeruginosa and other gram-negative bacilli. For patients with risk factors for pseudomonas or other gram-negative infection or a high risk for mortality, then two antipseudomonal antibiotics from different classes are recommended, such as piperacillin-tazobactam/tobramycin or cefepime/amikacin.
Use two antipseudomonal antibiotics in HAP if the patient has these risk factors:
Pseudomonas risk factors:
• IV antibiotic treatment within 90 days
• Structural lung disease increasing the risk of gram-negative infection (bronchiectasis, cystic fibrosis)
• High-quality gram stain from respiratory specimen showing predominant and numerous gram-negative bacilli
High risk of mortality:
• Septic shock
• Need for ventilator support
Ventilator-associated pneumonia
General management of VAP is similar to HAP in that empiric treatment should be tailored to the local distribution and susceptibilities of pathogens based on each hospital’s antibiogram. All regimens should cover for S. aureus, P. aeruginosa, and other gram-negative bacilli based on the risk of mortality associated with the need for ventilator support. MSSA should be covered for VAP unless the patient has methicillin-resistant risk factors (see below).
MRSA should be covered for VAP if:
• Patient has had IV antibiotic use within past 90 days
• Hospital unit has greater than 10%-20% of S. aureus isolates are MRSA or MRSA prevalence unknown
Only one antipseudomonal agent should be used unless there are one of the following characteristics present, as described below.
Use two antipseudomonal agents in VAP if:
• Prior IV antibiotic use within 90 days
• Septic shock at time of VAP
• Acute respiratory distress syndrome preceding VAP
• 5 or more days of hospitalization prior to the occurrence of VAP
• Acute renal replacement therapy prior to VAP onset
• Greater than 10% of gram-negative isolates are resistant to an agent being considered for monotherapy
• Local antibiotic susceptibility rates unknown
In both HAP and VAP, antibiotics should be de-escalated to those with a narrower spectrum after initial empiric therapy, ideally within 72 hours and based on sputum or blood culture results. The guidelines support obtaining noninvasive sputum cultures in patients with VAP (endotracheal aspirates) and HAP (spontaneous expectoration, induced sputum, or nasotracheal suctioning in a patient who is unable to cooperate to produce a sputum sample). Patients who are improving clinically may be switched to appropriate oral therapy based on the susceptibility of an identified organism. Another key change is that of the standard duration of therapy. Previously, patients were treated for up to 2-3 weeks with antibiotics. The new IDSA/ATS guidelines recommend that patients should be treated with 7 days of antibiotics rather than a longer course.
The bottom line
Empiric therapy for HAP and VAP should be tailored to each hospital’s local pathogen distribution and antimicrobial susceptibilities, as detailed in an antibiogram. In HAP and VAP, empiric antibiotics should cover for S. aureus, but it only needs to target MRSA if risk factors are present, prevalence is greater than 20% or unknown, and – if HAP – a high risk of mortality. P. aeruginosa and other gram-negative bacilli should also be covered in empiric regimens. Dual antipseudomonal antibiotics is only recommended to be used in HAP if there are specific pseudomonal risk factors or a high risk of mortality. They should be used in VAP if there are multidrug-resistant risk factors present or there is a high/unknown prevalence of resistant organisms. All antibiotic regimens should be deescalated rather than maintained, and both HAP and VAP patients ought to be treated for 7 days.
References
1. Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63(5):557-82.
2. Beardsley JR, Williamson JC, Johnson JW, Ohl CA, Karchmer TB, Bowton DL. Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia. Chest. 2006 Sep;130(3):787-93.
Dr. Botti is a second-year resident in the family medicine residency program department of family and community medicine at Jefferson Medical College, Philadelphia. Dr. Mills is assistant residency program director and assistant professor in the department of family and community medicine and department of physiology at Jefferson Medical College, Philadelphia. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia.
Hospital-acquired pneumonia (HAP) is pneumonia that presents at least 48 hours after admission to the hospital. In contrast, ventilator-associated pneumonia (VAP), is pneumonia that clinically presents 48 hours after endotracheal intubation. Together, these are some of the most common hospital-acquired infections in the United States and pose a considerable burden on hospitals nationwide.
The Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) recently updated their management guidelines for HAP and VAP with a goal of striking a balance between providing appropriate early antibiotic coverage and avoiding unnecessary treatment that can lead to adverse effects such as Clostridium difficile infections and development of antibiotic resistance.1 This update eliminated the concept of Healthcare Associated Pneumonia (HCAP), often used for patients in skilled care facilities, because newer evidence has shown that patients who had met these criteria did not have a higher incidence of multidrug resistant pathogens; rather, they have microbial etiologies and sensitivities that are similar to adults with community acquired pneumonia (CAP).
Hospital-acquired pneumonia
Reasons to cover for MRSA in HAP:
Risk factors:
• IV antibiotic treatment within 90 days
• Treatment in a unit where the prevalence of MRSA is greater than 20% or unknown
• Prior detection of MRSA by culture or nonculture screening (weaker risk factor)
High risk of mortality: • Septic shock
• Need for ventilator support
MRSA should be covered with use of either vancomycin or linezolid in these cases.
In addition, patients with HAP should be covered for Pseudomonas aeruginosa and other gram-negative bacilli. For patients with risk factors for pseudomonas or other gram-negative infection or a high risk for mortality, then two antipseudomonal antibiotics from different classes are recommended, such as piperacillin-tazobactam/tobramycin or cefepime/amikacin.
Use two antipseudomonal antibiotics in HAP if the patient has these risk factors:
Pseudomonas risk factors:
• IV antibiotic treatment within 90 days
• Structural lung disease increasing the risk of gram-negative infection (bronchiectasis, cystic fibrosis)
• High-quality gram stain from respiratory specimen showing predominant and numerous gram-negative bacilli
High risk of mortality:
• Septic shock
• Need for ventilator support
Ventilator-associated pneumonia
General management of VAP is similar to HAP in that empiric treatment should be tailored to the local distribution and susceptibilities of pathogens based on each hospital’s antibiogram. All regimens should cover for S. aureus, P. aeruginosa, and other gram-negative bacilli based on the risk of mortality associated with the need for ventilator support. MSSA should be covered for VAP unless the patient has methicillin-resistant risk factors (see below).
MRSA should be covered for VAP if:
• Patient has had IV antibiotic use within past 90 days
• Hospital unit has greater than 10%-20% of S. aureus isolates are MRSA or MRSA prevalence unknown
Only one antipseudomonal agent should be used unless there are one of the following characteristics present, as described below.
Use two antipseudomonal agents in VAP if:
• Prior IV antibiotic use within 90 days
• Septic shock at time of VAP
• Acute respiratory distress syndrome preceding VAP
• 5 or more days of hospitalization prior to the occurrence of VAP
• Acute renal replacement therapy prior to VAP onset
• Greater than 10% of gram-negative isolates are resistant to an agent being considered for monotherapy
• Local antibiotic susceptibility rates unknown
In both HAP and VAP, antibiotics should be de-escalated to those with a narrower spectrum after initial empiric therapy, ideally within 72 hours and based on sputum or blood culture results. The guidelines support obtaining noninvasive sputum cultures in patients with VAP (endotracheal aspirates) and HAP (spontaneous expectoration, induced sputum, or nasotracheal suctioning in a patient who is unable to cooperate to produce a sputum sample). Patients who are improving clinically may be switched to appropriate oral therapy based on the susceptibility of an identified organism. Another key change is that of the standard duration of therapy. Previously, patients were treated for up to 2-3 weeks with antibiotics. The new IDSA/ATS guidelines recommend that patients should be treated with 7 days of antibiotics rather than a longer course.
The bottom line
Empiric therapy for HAP and VAP should be tailored to each hospital’s local pathogen distribution and antimicrobial susceptibilities, as detailed in an antibiogram. In HAP and VAP, empiric antibiotics should cover for S. aureus, but it only needs to target MRSA if risk factors are present, prevalence is greater than 20% or unknown, and – if HAP – a high risk of mortality. P. aeruginosa and other gram-negative bacilli should also be covered in empiric regimens. Dual antipseudomonal antibiotics is only recommended to be used in HAP if there are specific pseudomonal risk factors or a high risk of mortality. They should be used in VAP if there are multidrug-resistant risk factors present or there is a high/unknown prevalence of resistant organisms. All antibiotic regimens should be deescalated rather than maintained, and both HAP and VAP patients ought to be treated for 7 days.
References
1. Kalil AC, Metersky ML, Klompas M, et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63(5):557-82.
2. Beardsley JR, Williamson JC, Johnson JW, Ohl CA, Karchmer TB, Bowton DL. Using local microbiologic data to develop institution-specific guidelines for the treatment of hospital-acquired pneumonia. Chest. 2006 Sep;130(3):787-93.
Dr. Botti is a second-year resident in the family medicine residency program department of family and community medicine at Jefferson Medical College, Philadelphia. Dr. Mills is assistant residency program director and assistant professor in the department of family and community medicine and department of physiology at Jefferson Medical College, Philadelphia. Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia.