Men do not know as much about skin cancer prevention and detection techniques as women, according to a recent survey conducted by the American Academy of Dermatology (AAD). This lack of knowledge may delay or prevent early diagnosis and treatment of melanoma and other nonmelanoma skin cancers in this patient population.

The survey results showed that only 56% of men versus 76% of women know there is no such thing as a healthy tan, and only 54% of men versus 70% of women know that getting a base tan is not a healthy way to protect skin from the sun. Furthermore, only 56% of men surveyed were aware that skin cancer could occur on areas of the skin not typically exposed to the sun compared to 65% of women.

“While our survey results indicate that men don’t know as much about skin cancer prevention and detection as women, men over 50 have a higher risk of developing melanoma, so it’s especially important for them to be vigilant about protecting and monitoring their skin,” said AAD President Abel Torres, MD, JD.

More resources on the diagnosis and treatment of melanoma.

May is skin cancer awareness month and the AAD is encouraging patients to make sure their skin is “Looking Good in 2016” by using sun protection and regularly examining skin for signs of skin cancer. The campaign features a public service announcement encouraging men to check their skin for signs of skin cancer and find a partner to help. The AAD also released a new infographic with tips on performing a skin cancer self-examination that dermatologists can share with patients to promote early detection of skin cancer.

More resources on nonmelanoma skin cancers. 

Dermatologist intervention in catching skin cancers when they are easier to treat also is key. At the 74th Annual Meeting of the American Academy of Dermatology in Washington, DC, Dr. Orit Markowitz discussed noninvasive imaging tools that can help dermatologists diagnose skin cancers earlier. She noted that even when a lesion looks very small, tools such as dermoscopy can reveal features that indicate it already has depth and therefore may progress to a more serious malignancy. Early detection is particularly crucial in cases of rare aggressive tumors such as amelanotic melanoma. “If something is very pink clinically and then suddenly has pigmentation dermoscopically, you really have to be considering biopsying that lesion because you may be looking at an early amelanotic melanoma,” Dr. Markowitz explained. By the time the lesion develops more obvious clinical features suggesting malignancy, the tumor progression may be far more advanced.

Men do not know as much about skin cancer prevention and detection techniques as women, according to a recent survey conducted by the American Academy of Dermatology (AAD). This lack of knowledge may delay or prevent early diagnosis and treatment of melanoma and other nonmelanoma skin cancers in this patient population.

The survey results showed that only 56% of men versus 76% of women know there is no such thing as a healthy tan, and only 54% of men versus 70% of women know that getting a base tan is not a healthy way to protect skin from the sun. Furthermore, only 56% of men surveyed were aware that skin cancer could occur on areas of the skin not typically exposed to the sun compared to 65% of women.

“While our survey results indicate that men don’t know as much about skin cancer prevention and detection as women, men over 50 have a higher risk of developing melanoma, so it’s especially important for them to be vigilant about protecting and monitoring their skin,” said AAD President Abel Torres, MD, JD.

More resources on the diagnosis and treatment of melanoma.

May is skin cancer awareness month and the AAD is encouraging patients to make sure their skin is “Looking Good in 2016” by using sun protection and regularly examining skin for signs of skin cancer. The campaign features a public service announcement encouraging men to check their skin for signs of skin cancer and find a partner to help. The AAD also released a new infographic with tips on performing a skin cancer self-examination that dermatologists can share with patients to promote early detection of skin cancer.

More resources on nonmelanoma skin cancers. 

Dermatologist intervention in catching skin cancers when they are easier to treat also is key. At the 74th Annual Meeting of the American Academy of Dermatology in Washington, DC, Dr. Orit Markowitz discussed noninvasive imaging tools that can help dermatologists diagnose skin cancers earlier. She noted that even when a lesion looks very small, tools such as dermoscopy can reveal features that indicate it already has depth and therefore may progress to a more serious malignancy. Early detection is particularly crucial in cases of rare aggressive tumors such as amelanotic melanoma. “If something is very pink clinically and then suddenly has pigmentation dermoscopically, you really have to be considering biopsying that lesion because you may be looking at an early amelanotic melanoma,” Dr. Markowitz explained. By the time the lesion develops more obvious clinical features suggesting malignancy, the tumor progression may be far more advanced.

Men do not know as much about skin cancer prevention and detection techniques as women, according to a recent survey conducted by the American Academy of Dermatology (AAD). This lack of knowledge may delay or prevent early diagnosis and treatment of melanoma and other nonmelanoma skin cancers in this patient population.

The survey results showed that only 56% of men versus 76% of women know there is no such thing as a healthy tan, and only 54% of men versus 70% of women know that getting a base tan is not a healthy way to protect skin from the sun. Furthermore, only 56% of men surveyed were aware that skin cancer could occur on areas of the skin not typically exposed to the sun compared to 65% of women.

“While our survey results indicate that men don’t know as much about skin cancer prevention and detection as women, men over 50 have a higher risk of developing melanoma, so it’s especially important for them to be vigilant about protecting and monitoring their skin,” said AAD President Abel Torres, MD, JD.

More resources on the diagnosis and treatment of melanoma.

May is skin cancer awareness month and the AAD is encouraging patients to make sure their skin is “Looking Good in 2016” by using sun protection and regularly examining skin for signs of skin cancer. The campaign features a public service announcement encouraging men to check their skin for signs of skin cancer and find a partner to help. The AAD also released a new infographic with tips on performing a skin cancer self-examination that dermatologists can share with patients to promote early detection of skin cancer.

More resources on nonmelanoma skin cancers. 

Dermatologist intervention in catching skin cancers when they are easier to treat also is key. At the 74th Annual Meeting of the American Academy of Dermatology in Washington, DC, Dr. Orit Markowitz discussed noninvasive imaging tools that can help dermatologists diagnose skin cancers earlier. She noted that even when a lesion looks very small, tools such as dermoscopy can reveal features that indicate it already has depth and therefore may progress to a more serious malignancy. Early detection is particularly crucial in cases of rare aggressive tumors such as amelanotic melanoma. “If something is very pink clinically and then suddenly has pigmentation dermoscopically, you really have to be considering biopsying that lesion because you may be looking at an early amelanotic melanoma,” Dr. Markowitz explained. By the time the lesion develops more obvious clinical features suggesting malignancy, the tumor progression may be far more advanced.

Question: An injured patient alleges that her eye doctor was negligent in failing to adhere to national treatment guidelines and in not using modern medical equipment. The encounter took place in a rural setting, with the nearest hospital 100 miles away.

In her malpractice lawsuit, which of the following choices is incorrect?

A. One of the doctor’s defenses may be the locality rule.

B. The plaintiff’s strongest argument is that community standards should parallel national standards for a specialist doctor such as an ophthalmologist.

C. Her expert witness must be a practicing ophthalmologist from the area.

D. The expert must be familiar with the local standards but does not have to practice there.

E. It all depends on what the state statute says, because the locality rule is not uniform settled law.

Answer: C. In traditional medical tort law, courts would rely on the standard of the particular locale where the tortious act took place, the so-called locality rule. This was based on the belief that different standards of care were applicable in different areas of the country, e.g., urban vs. rural. The rule can be traced to Small v. Howard,¹ an 1880 Massachusetts opinion, which was subsequently overruled in 1968.

Factors favoring the trend away from a local standard toward a national standard include conformity in medical school and residency curricula, and prescribed board certification requirements. Internet access and telemedicine have further propagated this uniformity. Finally, two additional facets of modern medicine – continuing medical education and published clinical practice guidelines – are at odds with a rule geared toward local standards.

One argument against the locality rule is that undue reliance on an outdated mode of practice will perpetuate substandard care. In an older New York malpractice case where a newborn became blind, the pediatrician cited local custom to defend the prolonged use of oxygen to treat preterm infants, despite evidence that this practice might have serious consequences. However, the court of appeals held that the pediatrician’s superior knowledge of the increased risk of hyperoxygenation should have enabled him to use his best judgment instead of relying on the indefensible local custom.

Under a strict version of the locality rule, otherwise qualified expert witnesses may be excluded if they are not practitioners in the locale in question. Still, some courts may allow out-of-state experts to offer their opinions. This has been especially helpful to plaintiffs who are far less likely to be able to secure willing local experts, given the reluctance of many physicians to testify against a fellow doctor in their community.

Take Tennessee as an example. It once excluded the expert testimony of an orthopedic surgeon from Johnson City because the expert witness testified about the national standard and did not have actual knowledge of the standard of care in Nashville, the community where the alleged malpractice occurred.

The Tennessee Court of Appeals later ruled that expert witnesses had to have “personal” or “firsthand knowledge” of the community standard of care, and that interviewing other physicians in the area did not suffice. It subsequently clarified that an expert witness need not actually practice in the same or similar locale, and that professional contact with physicians from comparable communities, such as through referrals, would be acceptable.

Two well-known cases touching on the locality rule bear summarizing: In Swink v. Weintraub,² Mrs. Swink bled into her pericardium during repair of a defective pacemaker electric lead. She died as a result, and her family pursued a wrongful death action, alleging negligence including delayed pericardiocentesis and surgical intervention.

The jury returned a verdict for the plaintiff, awarding damages in the amount of $1,047,732.20. On appeal, the defendants argued that North Carolina’s locality rule extended to all aspects of a negligence action, and that the trial court erred in admitting expert opinions without regard to whether those opinions reflected the “same or similar community” standard of care.

But the court of appeals disagreed, emphasizing that compliance with the “same or similar community” standard does not necessarily exonerate a defendant from an allegation of medical negligence. The court said liability can be established if the defendant did not exercise his “best judgment” in the treatment of the patient or if the defendant failed to use “reasonable care and diligence” in his efforts to render medical assistance.

In McClure v. Inova Medical Group, a Virginia jury found that a family practice resident had failed to meet the Virginia community standard of care when he did not order the prostate-specific antigen (PSA) test in a 53-year-old patient who was subsequently diagnosed with prostate cancer. The doctor had discussed the risks and benefits of PSA testing, but the patient declined taking the test. Jurors sided with the plaintiff’s argument that according to the local or statewide standard, Virginia doctors simply ordered the test as a matter of routine for men older than 50 years without necessarily discussing risks and benefits. The court awarded $1 million to the patient.³

Although the majority of jurisdictions have abandoned the locality rule, several continue to adhere to either a strict or modified version.⁴ Examples are Arizona, Idaho, New York, Tennessee, Virginia, and Washington. A modified rule exists in Louisiana, which holds general practitioners to a community standard and specialists to a national standard.

Finally, many authors have recommended a narrowly constructed rule based not on geographic boundaries, but on the availability of local resources. Courts would then look at the totality of circumstances, but remember that there is always the duty to refer or transfer to an available specialist/facility – and that the failure to do so may form the basis of liability.

As one physician put it: Location should not come into play with respect to the knowledge or skill of the treating physician; and even if a physician may not have the facilities to perform an emergency cesarean section, he or she should still know when it’s called for.

References

1. Small v. Howard, 128 Mass 131 (1880).

2. Swink v. Weintraub, 672 S.E.2d 53 (N.C. Court of Appeals 2009).

3. JAMA. 2004 Jan 7;291(1):15-6.

4. JAMA. 2007 Jun 20;297(23):2633-7.

Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at siang@hawaii.edu.

Question: An injured patient alleges that her eye doctor was negligent in failing to adhere to national treatment guidelines and in not using modern medical equipment. The encounter took place in a rural setting, with the nearest hospital 100 miles away.

In her malpractice lawsuit, which of the following choices is incorrect?

A. One of the doctor’s defenses may be the locality rule.

B. The plaintiff’s strongest argument is that community standards should parallel national standards for a specialist doctor such as an ophthalmologist.

C. Her expert witness must be a practicing ophthalmologist from the area.

D. The expert must be familiar with the local standards but does not have to practice there.

E. It all depends on what the state statute says, because the locality rule is not uniform settled law.

Answer: C. In traditional medical tort law, courts would rely on the standard of the particular locale where the tortious act took place, the so-called locality rule. This was based on the belief that different standards of care were applicable in different areas of the country, e.g., urban vs. rural. The rule can be traced to Small v. Howard,¹ an 1880 Massachusetts opinion, which was subsequently overruled in 1968.

Factors favoring the trend away from a local standard toward a national standard include conformity in medical school and residency curricula, and prescribed board certification requirements. Internet access and telemedicine have further propagated this uniformity. Finally, two additional facets of modern medicine – continuing medical education and published clinical practice guidelines – are at odds with a rule geared toward local standards.

One argument against the locality rule is that undue reliance on an outdated mode of practice will perpetuate substandard care. In an older New York malpractice case where a newborn became blind, the pediatrician cited local custom to defend the prolonged use of oxygen to treat preterm infants, despite evidence that this practice might have serious consequences. However, the court of appeals held that the pediatrician’s superior knowledge of the increased risk of hyperoxygenation should have enabled him to use his best judgment instead of relying on the indefensible local custom.

Under a strict version of the locality rule, otherwise qualified expert witnesses may be excluded if they are not practitioners in the locale in question. Still, some courts may allow out-of-state experts to offer their opinions. This has been especially helpful to plaintiffs who are far less likely to be able to secure willing local experts, given the reluctance of many physicians to testify against a fellow doctor in their community.

Take Tennessee as an example. It once excluded the expert testimony of an orthopedic surgeon from Johnson City because the expert witness testified about the national standard and did not have actual knowledge of the standard of care in Nashville, the community where the alleged malpractice occurred.

The Tennessee Court of Appeals later ruled that expert witnesses had to have “personal” or “firsthand knowledge” of the community standard of care, and that interviewing other physicians in the area did not suffice. It subsequently clarified that an expert witness need not actually practice in the same or similar locale, and that professional contact with physicians from comparable communities, such as through referrals, would be acceptable.

Two well-known cases touching on the locality rule bear summarizing: In Swink v. Weintraub,² Mrs. Swink bled into her pericardium during repair of a defective pacemaker electric lead. She died as a result, and her family pursued a wrongful death action, alleging negligence including delayed pericardiocentesis and surgical intervention.

The jury returned a verdict for the plaintiff, awarding damages in the amount of $1,047,732.20. On appeal, the defendants argued that North Carolina’s locality rule extended to all aspects of a negligence action, and that the trial court erred in admitting expert opinions without regard to whether those opinions reflected the “same or similar community” standard of care.

But the court of appeals disagreed, emphasizing that compliance with the “same or similar community” standard does not necessarily exonerate a defendant from an allegation of medical negligence. The court said liability can be established if the defendant did not exercise his “best judgment” in the treatment of the patient or if the defendant failed to use “reasonable care and diligence” in his efforts to render medical assistance.

In McClure v. Inova Medical Group, a Virginia jury found that a family practice resident had failed to meet the Virginia community standard of care when he did not order the prostate-specific antigen (PSA) test in a 53-year-old patient who was subsequently diagnosed with prostate cancer. The doctor had discussed the risks and benefits of PSA testing, but the patient declined taking the test. Jurors sided with the plaintiff’s argument that according to the local or statewide standard, Virginia doctors simply ordered the test as a matter of routine for men older than 50 years without necessarily discussing risks and benefits. The court awarded $1 million to the patient.³

Although the majority of jurisdictions have abandoned the locality rule, several continue to adhere to either a strict or modified version.⁴ Examples are Arizona, Idaho, New York, Tennessee, Virginia, and Washington. A modified rule exists in Louisiana, which holds general practitioners to a community standard and specialists to a national standard.

Finally, many authors have recommended a narrowly constructed rule based not on geographic boundaries, but on the availability of local resources. Courts would then look at the totality of circumstances, but remember that there is always the duty to refer or transfer to an available specialist/facility – and that the failure to do so may form the basis of liability.

As one physician put it: Location should not come into play with respect to the knowledge or skill of the treating physician; and even if a physician may not have the facilities to perform an emergency cesarean section, he or she should still know when it’s called for.

References

1. Small v. Howard, 128 Mass 131 (1880).

2. Swink v. Weintraub, 672 S.E.2d 53 (N.C. Court of Appeals 2009).

3. JAMA. 2004 Jan 7;291(1):15-6.

4. JAMA. 2007 Jun 20;297(23):2633-7.

Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at siang@hawaii.edu.

Question: An injured patient alleges that her eye doctor was negligent in failing to adhere to national treatment guidelines and in not using modern medical equipment. The encounter took place in a rural setting, with the nearest hospital 100 miles away.

In her malpractice lawsuit, which of the following choices is incorrect?

A. One of the doctor’s defenses may be the locality rule.

B. The plaintiff’s strongest argument is that community standards should parallel national standards for a specialist doctor such as an ophthalmologist.

C. Her expert witness must be a practicing ophthalmologist from the area.

D. The expert must be familiar with the local standards but does not have to practice there.

E. It all depends on what the state statute says, because the locality rule is not uniform settled law.

Answer: C. In traditional medical tort law, courts would rely on the standard of the particular locale where the tortious act took place, the so-called locality rule. This was based on the belief that different standards of care were applicable in different areas of the country, e.g., urban vs. rural. The rule can be traced to Small v. Howard,¹ an 1880 Massachusetts opinion, which was subsequently overruled in 1968.

Factors favoring the trend away from a local standard toward a national standard include conformity in medical school and residency curricula, and prescribed board certification requirements. Internet access and telemedicine have further propagated this uniformity. Finally, two additional facets of modern medicine – continuing medical education and published clinical practice guidelines – are at odds with a rule geared toward local standards.

One argument against the locality rule is that undue reliance on an outdated mode of practice will perpetuate substandard care. In an older New York malpractice case where a newborn became blind, the pediatrician cited local custom to defend the prolonged use of oxygen to treat preterm infants, despite evidence that this practice might have serious consequences. However, the court of appeals held that the pediatrician’s superior knowledge of the increased risk of hyperoxygenation should have enabled him to use his best judgment instead of relying on the indefensible local custom.

Under a strict version of the locality rule, otherwise qualified expert witnesses may be excluded if they are not practitioners in the locale in question. Still, some courts may allow out-of-state experts to offer their opinions. This has been especially helpful to plaintiffs who are far less likely to be able to secure willing local experts, given the reluctance of many physicians to testify against a fellow doctor in their community.

Take Tennessee as an example. It once excluded the expert testimony of an orthopedic surgeon from Johnson City because the expert witness testified about the national standard and did not have actual knowledge of the standard of care in Nashville, the community where the alleged malpractice occurred.

The Tennessee Court of Appeals later ruled that expert witnesses had to have “personal” or “firsthand knowledge” of the community standard of care, and that interviewing other physicians in the area did not suffice. It subsequently clarified that an expert witness need not actually practice in the same or similar locale, and that professional contact with physicians from comparable communities, such as through referrals, would be acceptable.

Two well-known cases touching on the locality rule bear summarizing: In Swink v. Weintraub,² Mrs. Swink bled into her pericardium during repair of a defective pacemaker electric lead. She died as a result, and her family pursued a wrongful death action, alleging negligence including delayed pericardiocentesis and surgical intervention.

The jury returned a verdict for the plaintiff, awarding damages in the amount of $1,047,732.20. On appeal, the defendants argued that North Carolina’s locality rule extended to all aspects of a negligence action, and that the trial court erred in admitting expert opinions without regard to whether those opinions reflected the “same or similar community” standard of care.

But the court of appeals disagreed, emphasizing that compliance with the “same or similar community” standard does not necessarily exonerate a defendant from an allegation of medical negligence. The court said liability can be established if the defendant did not exercise his “best judgment” in the treatment of the patient or if the defendant failed to use “reasonable care and diligence” in his efforts to render medical assistance.

In McClure v. Inova Medical Group, a Virginia jury found that a family practice resident had failed to meet the Virginia community standard of care when he did not order the prostate-specific antigen (PSA) test in a 53-year-old patient who was subsequently diagnosed with prostate cancer. The doctor had discussed the risks and benefits of PSA testing, but the patient declined taking the test. Jurors sided with the plaintiff’s argument that according to the local or statewide standard, Virginia doctors simply ordered the test as a matter of routine for men older than 50 years without necessarily discussing risks and benefits. The court awarded $1 million to the patient.³

Although the majority of jurisdictions have abandoned the locality rule, several continue to adhere to either a strict or modified version.⁴ Examples are Arizona, Idaho, New York, Tennessee, Virginia, and Washington. A modified rule exists in Louisiana, which holds general practitioners to a community standard and specialists to a national standard.

Finally, many authors have recommended a narrowly constructed rule based not on geographic boundaries, but on the availability of local resources. Courts would then look at the totality of circumstances, but remember that there is always the duty to refer or transfer to an available specialist/facility – and that the failure to do so may form the basis of liability.

As one physician put it: Location should not come into play with respect to the knowledge or skill of the treating physician; and even if a physician may not have the facilities to perform an emergency cesarean section, he or she should still know when it’s called for.

References

1. Small v. Howard, 128 Mass 131 (1880).

2. Swink v. Weintraub, 672 S.E.2d 53 (N.C. Court of Appeals 2009).

3. JAMA. 2004 Jan 7;291(1):15-6.

4. JAMA. 2007 Jun 20;297(23):2633-7.

Dr. Tan is professor emeritus of medicine and former adjunct professor of law at the University of Hawaii, and currently directs the St. Francis International Center for Healthcare Ethics in Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. Some of the articles in this series are adapted from the author’s 2006 book, “Medical Malpractice: Understanding the Law, Managing the Risk,” and his 2012 Halsbury treatise, “Medical Negligence and Professional Misconduct.” For additional information, readers may contact the author at siang@hawaii.edu.

The use of lung ultrasound, both alone and in combination with clinical and microbiologic data, can improve the early diagnosis of ventilator-associated pneumonia (VAP), according to the results of a study published in Chest.

The early diagnosis of VAP is challenging, and leaves intensivists with two options. The first is waiting for positive results from patients’ specimens, which delays treatment and increases mortality risk. The other is to administer antibiotics to all patients suspected of having VAP, which may be inappropriate and can lead to the development of multiresistant bacteria. “A pressing need therefore exists for reliable diagnostic tools to diagnose VAP early so that antibiotics can be promptly initiated, avoiding two extreme approaches,” wrote Dr. Silvia Mongodi of the Fondazione IRCCS Policlinico San Matteo in Pavia, Italy, and her colleagues.

Based on the results of previous research, the investigators hypothesized that lung ultrasound (LUS) could be used to diagnose VAP early and help to avoid treatment delays or mistakes. To test this hypothesis, the diagnostic performance of LUS alone and in combination with clinical and microbiologic data was evaluated prospectively in 99 patients with suspected VAP in ICUs at Saint Joseph Hospital (Paris), Fondazione IRCCS Policlinico San Matteo, and Centre Hospitalier de l’Université de Montréal (Chest. 2016 Apr;149[4]:969-80. doi: 10.1016/j.chest.2015.12.012).

The study results showed that subpleural consolidations and dynamic linear/arborescent air bronchograms were the principal LUS signs of VAP, and that the presence of both in the same individual made the diagnosis highly specific (88%), with a high positive predictive value (86%) and a positive likelihood ratio of 2.9. Furthermore, the addition of data from either of two different endotracheal aspirate assessment techniques (EAgram [direct Gram stain examination] or EAquant [direct Gram stain culture]) to the data from the principal LUS signs showed 97% specificity with each technique and positive likelihood ratios of 6.6 and 7.1, respectively, Dr. Mongodi and her associates reported.

Dr. Mongodi and her colleagues said that their results were encouraging but would need to be validated in larger clinical trials.

No funding was received for this study. The authors reported no conflicts of interest.

The use of lung ultrasound, both alone and in combination with clinical and microbiologic data, can improve the early diagnosis of ventilator-associated pneumonia (VAP), according to the results of a study published in Chest.

The early diagnosis of VAP is challenging, and leaves intensivists with two options. The first is waiting for positive results from patients’ specimens, which delays treatment and increases mortality risk. The other is to administer antibiotics to all patients suspected of having VAP, which may be inappropriate and can lead to the development of multiresistant bacteria. “A pressing need therefore exists for reliable diagnostic tools to diagnose VAP early so that antibiotics can be promptly initiated, avoiding two extreme approaches,” wrote Dr. Silvia Mongodi of the Fondazione IRCCS Policlinico San Matteo in Pavia, Italy, and her colleagues.

Based on the results of previous research, the investigators hypothesized that lung ultrasound (LUS) could be used to diagnose VAP early and help to avoid treatment delays or mistakes. To test this hypothesis, the diagnostic performance of LUS alone and in combination with clinical and microbiologic data was evaluated prospectively in 99 patients with suspected VAP in ICUs at Saint Joseph Hospital (Paris), Fondazione IRCCS Policlinico San Matteo, and Centre Hospitalier de l’Université de Montréal (Chest. 2016 Apr;149[4]:969-80. doi: 10.1016/j.chest.2015.12.012).

The study results showed that subpleural consolidations and dynamic linear/arborescent air bronchograms were the principal LUS signs of VAP, and that the presence of both in the same individual made the diagnosis highly specific (88%), with a high positive predictive value (86%) and a positive likelihood ratio of 2.9. Furthermore, the addition of data from either of two different endotracheal aspirate assessment techniques (EAgram [direct Gram stain examination] or EAquant [direct Gram stain culture]) to the data from the principal LUS signs showed 97% specificity with each technique and positive likelihood ratios of 6.6 and 7.1, respectively, Dr. Mongodi and her associates reported.

Dr. Mongodi and her colleagues said that their results were encouraging but would need to be validated in larger clinical trials.

No funding was received for this study. The authors reported no conflicts of interest.

The use of lung ultrasound, both alone and in combination with clinical and microbiologic data, can improve the early diagnosis of ventilator-associated pneumonia (VAP), according to the results of a study published in Chest.

The early diagnosis of VAP is challenging, and leaves intensivists with two options. The first is waiting for positive results from patients’ specimens, which delays treatment and increases mortality risk. The other is to administer antibiotics to all patients suspected of having VAP, which may be inappropriate and can lead to the development of multiresistant bacteria. “A pressing need therefore exists for reliable diagnostic tools to diagnose VAP early so that antibiotics can be promptly initiated, avoiding two extreme approaches,” wrote Dr. Silvia Mongodi of the Fondazione IRCCS Policlinico San Matteo in Pavia, Italy, and her colleagues.

Based on the results of previous research, the investigators hypothesized that lung ultrasound (LUS) could be used to diagnose VAP early and help to avoid treatment delays or mistakes. To test this hypothesis, the diagnostic performance of LUS alone and in combination with clinical and microbiologic data was evaluated prospectively in 99 patients with suspected VAP in ICUs at Saint Joseph Hospital (Paris), Fondazione IRCCS Policlinico San Matteo, and Centre Hospitalier de l’Université de Montréal (Chest. 2016 Apr;149[4]:969-80. doi: 10.1016/j.chest.2015.12.012).

The study results showed that subpleural consolidations and dynamic linear/arborescent air bronchograms were the principal LUS signs of VAP, and that the presence of both in the same individual made the diagnosis highly specific (88%), with a high positive predictive value (86%) and a positive likelihood ratio of 2.9. Furthermore, the addition of data from either of two different endotracheal aspirate assessment techniques (EAgram [direct Gram stain examination] or EAquant [direct Gram stain culture]) to the data from the principal LUS signs showed 97% specificity with each technique and positive likelihood ratios of 6.6 and 7.1, respectively, Dr. Mongodi and her associates reported.

Dr. Mongodi and her colleagues said that their results were encouraging but would need to be validated in larger clinical trials.

No funding was received for this study. The authors reported no conflicts of interest.

WASHINGTON – It will be up to the lower courts to decide how to work out religious exemptions under the Affordable Care Act’s contraception mandate, following the Supreme Court’s decision to remand Zubik v. Burwell back to the U.S. Court of Appeals for the 3rd, 5th, 10th, and District of Columbia Circuits.

In an unusual move, on May 16 the Supreme Court vacated the lower court rulings related to Zubik v. Burwell and has remanded the case back to the four appeals courts that had originally ruled on the issue.

At issue in the case is the implementation of the Affordable Care Act’s contraception mandate and specifically how nonprofit religious employers can opt out of directly paying for their employees’ contraception. The federal government had created a workaround that required employers to submit a form stating that they have religious objections, but the plaintiffs asserted that the process itself was a violation of their religious freedom.

In March, the high court asked all parties in the case to submit additional briefs outlining how contraception could be provided without requiring notice on the part of the employers. After reviewing the briefs, the Supreme Court justices concluded that “such an option is feasible.”

“Given the gravity of the dispute and the substantial clarification and refinement in the positions of the parties, the parties on remand should be afforded an opportunity to arrive at an approach going forward that accommodates petitioners’ religious exercise while at the same time ensuring that women covered by petitioners’ health plans ‘receive full and equal health coverage, including contraceptive coverage,’ ” the justices wrote in the decision. “We anticipate that the Courts of Appeals will allow the parties sufficient time to resolve any outstanding issues between them.”

The Supreme Court made no decision about the merits of Zubik v. Burwell.

Dr. Sara Imershein, a clinical professor at George Washington University and an ob.gyn. at Planned Parenthood in Washington, said the decision was a disappointment because it requires the courts to sort out a workaround to the contraception mandate when the government has already put one in place. Dr. Imershein, who is a reproductive rights advocate, commented on the news in a video interview while attending the annual meeting of the American College of Obstetricians and Gynecologists.

Dr. Mark S. DeFrancesco, ACOG president, expressed the college’s disappointment in the Supreme Court’s decision.

“ACOG strongly believes that contraception is an essential part of women’s preventive care, and that any accommodation to employers’ beliefs must not impose barriers to women’s ability to access contraception,” Dr. DeFrancesco said in a statement. “We encourage the lower courts to adopt a solution that ensures that coverage is provided seamlessly ‘through petitioner’s insurance companies.’”

mschneider@frontlinemedcom.com

On Twitter @maryellenny

WASHINGTON – It will be up to the lower courts to decide how to work out religious exemptions under the Affordable Care Act’s contraception mandate, following the Supreme Court’s decision to remand Zubik v. Burwell back to the U.S. Court of Appeals for the 3rd, 5th, 10th, and District of Columbia Circuits.

In an unusual move, on May 16 the Supreme Court vacated the lower court rulings related to Zubik v. Burwell and has remanded the case back to the four appeals courts that had originally ruled on the issue.

At issue in the case is the implementation of the Affordable Care Act’s contraception mandate and specifically how nonprofit religious employers can opt out of directly paying for their employees’ contraception. The federal government had created a workaround that required employers to submit a form stating that they have religious objections, but the plaintiffs asserted that the process itself was a violation of their religious freedom.

In March, the high court asked all parties in the case to submit additional briefs outlining how contraception could be provided without requiring notice on the part of the employers. After reviewing the briefs, the Supreme Court justices concluded that “such an option is feasible.”

“Given the gravity of the dispute and the substantial clarification and refinement in the positions of the parties, the parties on remand should be afforded an opportunity to arrive at an approach going forward that accommodates petitioners’ religious exercise while at the same time ensuring that women covered by petitioners’ health plans ‘receive full and equal health coverage, including contraceptive coverage,’ ” the justices wrote in the decision. “We anticipate that the Courts of Appeals will allow the parties sufficient time to resolve any outstanding issues between them.”

The Supreme Court made no decision about the merits of Zubik v. Burwell.

Dr. Sara Imershein, a clinical professor at George Washington University and an ob.gyn. at Planned Parenthood in Washington, said the decision was a disappointment because it requires the courts to sort out a workaround to the contraception mandate when the government has already put one in place. Dr. Imershein, who is a reproductive rights advocate, commented on the news in a video interview while attending the annual meeting of the American College of Obstetricians and Gynecologists.

Dr. Mark S. DeFrancesco, ACOG president, expressed the college’s disappointment in the Supreme Court’s decision.

“ACOG strongly believes that contraception is an essential part of women’s preventive care, and that any accommodation to employers’ beliefs must not impose barriers to women’s ability to access contraception,” Dr. DeFrancesco said in a statement. “We encourage the lower courts to adopt a solution that ensures that coverage is provided seamlessly ‘through petitioner’s insurance companies.’”

mschneider@frontlinemedcom.com

On Twitter @maryellenny

WASHINGTON – It will be up to the lower courts to decide how to work out religious exemptions under the Affordable Care Act’s contraception mandate, following the Supreme Court’s decision to remand Zubik v. Burwell back to the U.S. Court of Appeals for the 3rd, 5th, 10th, and District of Columbia Circuits.

In an unusual move, on May 16 the Supreme Court vacated the lower court rulings related to Zubik v. Burwell and has remanded the case back to the four appeals courts that had originally ruled on the issue.

At issue in the case is the implementation of the Affordable Care Act’s contraception mandate and specifically how nonprofit religious employers can opt out of directly paying for their employees’ contraception. The federal government had created a workaround that required employers to submit a form stating that they have religious objections, but the plaintiffs asserted that the process itself was a violation of their religious freedom.

In March, the high court asked all parties in the case to submit additional briefs outlining how contraception could be provided without requiring notice on the part of the employers. After reviewing the briefs, the Supreme Court justices concluded that “such an option is feasible.”

“Given the gravity of the dispute and the substantial clarification and refinement in the positions of the parties, the parties on remand should be afforded an opportunity to arrive at an approach going forward that accommodates petitioners’ religious exercise while at the same time ensuring that women covered by petitioners’ health plans ‘receive full and equal health coverage, including contraceptive coverage,’ ” the justices wrote in the decision. “We anticipate that the Courts of Appeals will allow the parties sufficient time to resolve any outstanding issues between them.”

The Supreme Court made no decision about the merits of Zubik v. Burwell.

Dr. Sara Imershein, a clinical professor at George Washington University and an ob.gyn. at Planned Parenthood in Washington, said the decision was a disappointment because it requires the courts to sort out a workaround to the contraception mandate when the government has already put one in place. Dr. Imershein, who is a reproductive rights advocate, commented on the news in a video interview while attending the annual meeting of the American College of Obstetricians and Gynecologists.

Dr. Mark S. DeFrancesco, ACOG president, expressed the college’s disappointment in the Supreme Court’s decision.

“ACOG strongly believes that contraception is an essential part of women’s preventive care, and that any accommodation to employers’ beliefs must not impose barriers to women’s ability to access contraception,” Dr. DeFrancesco said in a statement. “We encourage the lower courts to adopt a solution that ensures that coverage is provided seamlessly ‘through petitioner’s insurance companies.’”

mschneider@frontlinemedcom.com

On Twitter @maryellenny

Human Tregs

Image by Kathryn T. Iacono

A new approach to cancer immunotherapy may avoid some of the shortcomings associated with other methods, according to researchers.

The group found that eliminating a key protein in regulatory T cells (Tregs) makes them so unstable that they become effector T cells (Teff) and begin to attack the cancer.

And this conversion from Treg to Teff occurs only in the inflammatory conditions that prevail within many tumors.

As a result, Tregs embedded in normal tissue throughout the body continue to have a restraining effect on their local Teffs, protecting healthy organs and tissues from attack.

The researchers said this raises the prospect of therapies that concentrate the immune system’s firepower on tumors without producing residual damage and harmful side effects.

“Many current approaches to immunotherapy involve depleting or blocking Tregs in order to shift the balance toward Teff cells,” said Harvey Cantor, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“This, however, runs the risk of triggering an autoimmune response in which the Teff cells attack normal as well as malignant tissue. The key to our approach is that it singles out the Tregs inside a tumor for conversion, leaving Tregs elsewhere in the body unchanged.”

Dr Cantor and his colleagues described the approach in PNAS.

The study builds on research published last year in Science. That study showed that Tregs maintain their immune-suppressive properties under inflammatory conditions as long as they have high enough levels of a protein called Helios. Depriving Tregs of sufficient Helios caused them to lose that stability and turn into Teff cells.

The new study explored whether this convertibility could be harnessed for therapeutic purposes in cancers.

The first set of experiments involved mice engineered to lack Helios in their Tregs. When the animals were injected with melanoma or colon cancer cells, they developed tumors far more slowly than animals with normal Tregs.

“Inspection of the animals’ tumor tissue showed an unstable set of T regulatory cells, many of which had converted into Teffs,” said Hye-Jung Kim, PhD, also of the Dana-Farber Cancer Institute.

The researchers then explored whether stanching Helios production in tumor-dwelling Tregs could have the same effect. They tested several antibodies that bind to key receptors on Tregs and cause a downturn in Helios production.

The team chose an antibody that worked well, DTA-1, and tested it in mice with Treg-laden tumors. When they analyzed the tumor tissue, it was clear that DTA-1 had triggered conversion of Tregs to Teffs.

“This represents a next stage in cancer immunotherapy,” Dr Cantor said. “We now have a very specific, targeted way of inducing a T-effector-cell attack on cancer while lowering the risk of adverse effects on healthy tissue. The next step will be to organize a clinical trial using this approach in patients.”

Human Tregs

Image by Kathryn T. Iacono

A new approach to cancer immunotherapy may avoid some of the shortcomings associated with other methods, according to researchers.

The group found that eliminating a key protein in regulatory T cells (Tregs) makes them so unstable that they become effector T cells (Teff) and begin to attack the cancer.

And this conversion from Treg to Teff occurs only in the inflammatory conditions that prevail within many tumors.

As a result, Tregs embedded in normal tissue throughout the body continue to have a restraining effect on their local Teffs, protecting healthy organs and tissues from attack.

The researchers said this raises the prospect of therapies that concentrate the immune system’s firepower on tumors without producing residual damage and harmful side effects.

“Many current approaches to immunotherapy involve depleting or blocking Tregs in order to shift the balance toward Teff cells,” said Harvey Cantor, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“This, however, runs the risk of triggering an autoimmune response in which the Teff cells attack normal as well as malignant tissue. The key to our approach is that it singles out the Tregs inside a tumor for conversion, leaving Tregs elsewhere in the body unchanged.”

Dr Cantor and his colleagues described the approach in PNAS.

The study builds on research published last year in Science. That study showed that Tregs maintain their immune-suppressive properties under inflammatory conditions as long as they have high enough levels of a protein called Helios. Depriving Tregs of sufficient Helios caused them to lose that stability and turn into Teff cells.

The new study explored whether this convertibility could be harnessed for therapeutic purposes in cancers.

The first set of experiments involved mice engineered to lack Helios in their Tregs. When the animals were injected with melanoma or colon cancer cells, they developed tumors far more slowly than animals with normal Tregs.

“Inspection of the animals’ tumor tissue showed an unstable set of T regulatory cells, many of which had converted into Teffs,” said Hye-Jung Kim, PhD, also of the Dana-Farber Cancer Institute.

The researchers then explored whether stanching Helios production in tumor-dwelling Tregs could have the same effect. They tested several antibodies that bind to key receptors on Tregs and cause a downturn in Helios production.

The team chose an antibody that worked well, DTA-1, and tested it in mice with Treg-laden tumors. When they analyzed the tumor tissue, it was clear that DTA-1 had triggered conversion of Tregs to Teffs.

“This represents a next stage in cancer immunotherapy,” Dr Cantor said. “We now have a very specific, targeted way of inducing a T-effector-cell attack on cancer while lowering the risk of adverse effects on healthy tissue. The next step will be to organize a clinical trial using this approach in patients.”

Human Tregs

Image by Kathryn T. Iacono

A new approach to cancer immunotherapy may avoid some of the shortcomings associated with other methods, according to researchers.

The group found that eliminating a key protein in regulatory T cells (Tregs) makes them so unstable that they become effector T cells (Teff) and begin to attack the cancer.

And this conversion from Treg to Teff occurs only in the inflammatory conditions that prevail within many tumors.

As a result, Tregs embedded in normal tissue throughout the body continue to have a restraining effect on their local Teffs, protecting healthy organs and tissues from attack.

The researchers said this raises the prospect of therapies that concentrate the immune system’s firepower on tumors without producing residual damage and harmful side effects.

“Many current approaches to immunotherapy involve depleting or blocking Tregs in order to shift the balance toward Teff cells,” said Harvey Cantor, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts.

“This, however, runs the risk of triggering an autoimmune response in which the Teff cells attack normal as well as malignant tissue. The key to our approach is that it singles out the Tregs inside a tumor for conversion, leaving Tregs elsewhere in the body unchanged.”

Dr Cantor and his colleagues described the approach in PNAS.

The study builds on research published last year in Science. That study showed that Tregs maintain their immune-suppressive properties under inflammatory conditions as long as they have high enough levels of a protein called Helios. Depriving Tregs of sufficient Helios caused them to lose that stability and turn into Teff cells.

The new study explored whether this convertibility could be harnessed for therapeutic purposes in cancers.

The first set of experiments involved mice engineered to lack Helios in their Tregs. When the animals were injected with melanoma or colon cancer cells, they developed tumors far more slowly than animals with normal Tregs.

“Inspection of the animals’ tumor tissue showed an unstable set of T regulatory cells, many of which had converted into Teffs,” said Hye-Jung Kim, PhD, also of the Dana-Farber Cancer Institute.

The researchers then explored whether stanching Helios production in tumor-dwelling Tregs could have the same effect. They tested several antibodies that bind to key receptors on Tregs and cause a downturn in Helios production.

The team chose an antibody that worked well, DTA-1, and tested it in mice with Treg-laden tumors. When they analyzed the tumor tissue, it was clear that DTA-1 had triggered conversion of Tregs to Teffs.

“This represents a next stage in cancer immunotherapy,” Dr Cantor said. “We now have a very specific, targeted way of inducing a T-effector-cell attack on cancer while lowering the risk of adverse effects on healthy tissue. The next step will be to organize a clinical trial using this approach in patients.”

Marathon runners

Photo by K. Johansson

Being physically active during leisure time may lower a person’s risk of certain cancers, according to a new study.

A high level of physical activity was associated with a 20% lower risk of myeloid leukemia, a 17% lower risk of myeloma, a 9% lower risk of non-Hodgkin lymphoma, and a 7% lower risk of cancer in general.

On the other hand, a high level of physical activity was also associated with a higher risk of malignant melanoma and prostate cancer.

Steven C. Moore, PhD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues reported these findings in JAMA Internal Medicine.

The researchers pooled data from 12 US and European study cohorts with self-reported physical activity (1987-2004). And they analyzed associations between physical activity and 26 types of cancer.

The study included 1.4 million participants, and 186,932 cancers were identified during a median of 11 years of follow-up.

Compared with the lowest level of leisure-time physical activity (10th percentile), the highest level of activity (90th percentile) had strong inverse associations (a 20% or greater reduction in risk) for 7 cancer types:

• Myeloid leukemia (hazard ratio [HR]=0.80 [95% CI, 0.70-0.92])
• Esophageal adenocarcinoma (HR=0.58 [95% CI, 0.37-0.89])
• Liver cancer (HR=0.73 [95% CI, 0.55-0.98])
• Lung cancer (HR=0.74 [95% CI, 0.71-0.77])
• Kidney cancer (HR=0.77 [95% CI, 0.70-0.85])
• Gastric cardia (HR=0.78 [95% CI, 0.64-0.95])
• Endometrial cancer (HR=0.79 [95% CI, 0.68-0.92]).

There were moderate inverse associations (a 10% to 20% reduction in risk) between the highest level of activity and 6 cancers:

• Myeloma (HR=0.83 [95% CI, 0.72-0.95])
• Colon cancer (HR=0.84 [95% CI, 0.77-0.91])
• Head and neck cancer (HR=0.85 [95% CI, 0.78-0.93])
• Rectal cancer (HR=0.87 [95% CI, 0.80-0.95])
• Bladder cancer (HR=0.87 [95% CI, 0.82-0.92])
• Breast cancer (HR=0.90 [95% CI, 0.87-0.93]).

And there were suggestive inverse associations between the highest level of activity and 3 cancers:

• Non-Hodgkin lymphoma (HR=0.91 [95% CI, 0.83-1.00])
• Gallbladder cancer (HR=0.72 [95% CI, 0.51-1.01])
• Small intestine cancer (HR=0.78 [95% CI, 0.60-1.00]).

However, the highest level of activity was also associated with an increased risk of prostate cancer (HR=1.05 [95% CI, 1.03-1.08]) and malignant melanoma (HR=1.27 [95% CI, 1.16-1.40]).

The researchers said the main limitation of this study is that they cannot fully exclude the possibility that diet, smoking, and other factors may have affected these results. Also, the study used self-reported physical activity, which can mean errors in recall.

Still, the team said these findings support promoting physical activity as a key component of population-wide cancer prevention and control efforts.

Marathon runners

Photo by K. Johansson

Being physically active during leisure time may lower a person’s risk of certain cancers, according to a new study.

A high level of physical activity was associated with a 20% lower risk of myeloid leukemia, a 17% lower risk of myeloma, a 9% lower risk of non-Hodgkin lymphoma, and a 7% lower risk of cancer in general.

On the other hand, a high level of physical activity was also associated with a higher risk of malignant melanoma and prostate cancer.

Steven C. Moore, PhD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues reported these findings in JAMA Internal Medicine.

The researchers pooled data from 12 US and European study cohorts with self-reported physical activity (1987-2004). And they analyzed associations between physical activity and 26 types of cancer.

The study included 1.4 million participants, and 186,932 cancers were identified during a median of 11 years of follow-up.

Compared with the lowest level of leisure-time physical activity (10th percentile), the highest level of activity (90th percentile) had strong inverse associations (a 20% or greater reduction in risk) for 7 cancer types:

• Myeloid leukemia (hazard ratio [HR]=0.80 [95% CI, 0.70-0.92])
• Esophageal adenocarcinoma (HR=0.58 [95% CI, 0.37-0.89])
• Liver cancer (HR=0.73 [95% CI, 0.55-0.98])
• Lung cancer (HR=0.74 [95% CI, 0.71-0.77])
• Kidney cancer (HR=0.77 [95% CI, 0.70-0.85])
• Gastric cardia (HR=0.78 [95% CI, 0.64-0.95])
• Endometrial cancer (HR=0.79 [95% CI, 0.68-0.92]).

There were moderate inverse associations (a 10% to 20% reduction in risk) between the highest level of activity and 6 cancers:

• Myeloma (HR=0.83 [95% CI, 0.72-0.95])
• Colon cancer (HR=0.84 [95% CI, 0.77-0.91])
• Head and neck cancer (HR=0.85 [95% CI, 0.78-0.93])
• Rectal cancer (HR=0.87 [95% CI, 0.80-0.95])
• Bladder cancer (HR=0.87 [95% CI, 0.82-0.92])
• Breast cancer (HR=0.90 [95% CI, 0.87-0.93]).

And there were suggestive inverse associations between the highest level of activity and 3 cancers:

• Non-Hodgkin lymphoma (HR=0.91 [95% CI, 0.83-1.00])
• Gallbladder cancer (HR=0.72 [95% CI, 0.51-1.01])
• Small intestine cancer (HR=0.78 [95% CI, 0.60-1.00]).

However, the highest level of activity was also associated with an increased risk of prostate cancer (HR=1.05 [95% CI, 1.03-1.08]) and malignant melanoma (HR=1.27 [95% CI, 1.16-1.40]).

The researchers said the main limitation of this study is that they cannot fully exclude the possibility that diet, smoking, and other factors may have affected these results. Also, the study used self-reported physical activity, which can mean errors in recall.

Still, the team said these findings support promoting physical activity as a key component of population-wide cancer prevention and control efforts.

Marathon runners

Photo by K. Johansson

Being physically active during leisure time may lower a person’s risk of certain cancers, according to a new study.

A high level of physical activity was associated with a 20% lower risk of myeloid leukemia, a 17% lower risk of myeloma, a 9% lower risk of non-Hodgkin lymphoma, and a 7% lower risk of cancer in general.

On the other hand, a high level of physical activity was also associated with a higher risk of malignant melanoma and prostate cancer.

Steven C. Moore, PhD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues reported these findings in JAMA Internal Medicine.

The researchers pooled data from 12 US and European study cohorts with self-reported physical activity (1987-2004). And they analyzed associations between physical activity and 26 types of cancer.

The study included 1.4 million participants, and 186,932 cancers were identified during a median of 11 years of follow-up.

Compared with the lowest level of leisure-time physical activity (10th percentile), the highest level of activity (90th percentile) had strong inverse associations (a 20% or greater reduction in risk) for 7 cancer types:

• Myeloid leukemia (hazard ratio [HR]=0.80 [95% CI, 0.70-0.92])
• Esophageal adenocarcinoma (HR=0.58 [95% CI, 0.37-0.89])
• Liver cancer (HR=0.73 [95% CI, 0.55-0.98])
• Lung cancer (HR=0.74 [95% CI, 0.71-0.77])
• Kidney cancer (HR=0.77 [95% CI, 0.70-0.85])
• Gastric cardia (HR=0.78 [95% CI, 0.64-0.95])
• Endometrial cancer (HR=0.79 [95% CI, 0.68-0.92]).

There were moderate inverse associations (a 10% to 20% reduction in risk) between the highest level of activity and 6 cancers:

• Myeloma (HR=0.83 [95% CI, 0.72-0.95])
• Colon cancer (HR=0.84 [95% CI, 0.77-0.91])
• Head and neck cancer (HR=0.85 [95% CI, 0.78-0.93])
• Rectal cancer (HR=0.87 [95% CI, 0.80-0.95])
• Bladder cancer (HR=0.87 [95% CI, 0.82-0.92])
• Breast cancer (HR=0.90 [95% CI, 0.87-0.93]).

And there were suggestive inverse associations between the highest level of activity and 3 cancers:

• Non-Hodgkin lymphoma (HR=0.91 [95% CI, 0.83-1.00])
• Gallbladder cancer (HR=0.72 [95% CI, 0.51-1.01])
• Small intestine cancer (HR=0.78 [95% CI, 0.60-1.00]).

However, the highest level of activity was also associated with an increased risk of prostate cancer (HR=1.05 [95% CI, 1.03-1.08]) and malignant melanoma (HR=1.27 [95% CI, 1.16-1.40]).

The researchers said the main limitation of this study is that they cannot fully exclude the possibility that diet, smoking, and other factors may have affected these results. Also, the study used self-reported physical activity, which can mean errors in recall.

Still, the team said these findings support promoting physical activity as a key component of population-wide cancer prevention and control efforts.

Patient taking dabigatran

to prevent thrombosis after

knee replacement surgery

© Boehringer Ingelheim

Health Canada has granted conditional approval for idarucizumab (Praxbind), a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa) in cases of emergency surgery/urgent procedures or in situations of life-threatening or uncontrolled bleeding.

The conditional approval of idarucizumab reflects the promising nature of the available clinical evidence.

For the drug to gain full approval, Boehringer Ingelheim—the company that markets both idarucizumab and dabigatran—must provide Health Canada with data confirming that idarucizumab provides a clinical benefit.

To date, study results have demonstrated that 5g of idarucizumab provides immediate, complete, and sustained reversal of the anticoagulant effects of dabigatran in most patients.

In the ongoing phase 3 RE-VERSE AD trial, researchers are evaluating idarucizumab in emergency settings.

Interim results from this trial showed that idarucizumab normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

Researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

Patient taking dabigatran

to prevent thrombosis after

knee replacement surgery

© Boehringer Ingelheim

Health Canada has granted conditional approval for idarucizumab (Praxbind), a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa) in cases of emergency surgery/urgent procedures or in situations of life-threatening or uncontrolled bleeding.

The conditional approval of idarucizumab reflects the promising nature of the available clinical evidence.

For the drug to gain full approval, Boehringer Ingelheim—the company that markets both idarucizumab and dabigatran—must provide Health Canada with data confirming that idarucizumab provides a clinical benefit.

To date, study results have demonstrated that 5g of idarucizumab provides immediate, complete, and sustained reversal of the anticoagulant effects of dabigatran in most patients.

In the ongoing phase 3 RE-VERSE AD trial, researchers are evaluating idarucizumab in emergency settings.

Interim results from this trial showed that idarucizumab normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

Researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

Patient taking dabigatran

to prevent thrombosis after

knee replacement surgery

© Boehringer Ingelheim

Health Canada has granted conditional approval for idarucizumab (Praxbind), a humanized antibody fragment designed to reverse the anticoagulant effects of dabigatran etexilate (Pradaxa) in cases of emergency surgery/urgent procedures or in situations of life-threatening or uncontrolled bleeding.

The conditional approval of idarucizumab reflects the promising nature of the available clinical evidence.

For the drug to gain full approval, Boehringer Ingelheim—the company that markets both idarucizumab and dabigatran—must provide Health Canada with data confirming that idarucizumab provides a clinical benefit.

To date, study results have demonstrated that 5g of idarucizumab provides immediate, complete, and sustained reversal of the anticoagulant effects of dabigatran in most patients.

In the ongoing phase 3 RE-VERSE AD trial, researchers are evaluating idarucizumab in emergency settings.

Interim results from this trial showed that idarucizumab normalized diluted thrombin time and ecarin clotting time in a majority of dabigatran-treated patients with uncontrolled or life-threatening bleeding complications and most patients who required emergency surgery or an invasive procedure.

Researchers said there were no safety concerns related to idarucizumab. However, 23% of patients in this trial experienced serious adverse events, 20% of patients died, and several patients had thrombotic or bleeding events.

NK cell destroying cancer cell

Image by Joshua Stokes

New findings published in PNAS may help scientists improve the efficacy of natural killer (NK) cell therapy for patients with leukemia.

The preclinical research revealed a tolerance mechanism that restrains the activity of NK cells, as well as a potential way to overcome this problem.

Investigators found that a transcription factor, Kruppel-like factor 2 (KFL2), is critical for NK cell expansion and survival.

Specifically, KLF2 limits immature NK cell proliferation and instructs mature NK cells to home to niches rich in interleukin 15 (IL-15), which is necessary for their continued survival.

“This is the same process likely used by cancer cells to avoid destruction by NK cells,” said study author Eric Sebzda, PhD, of Vanderbilt University Medical Center in Nashville, Tennessee.

In particular, tumors may avoid immune clearance by promoting KLF2 destruction within the NK cell population, thereby starving these cells of IL-15.

Dr Sebzda and his colleagues noted that increased expression of IL-15 can improve immune responses against tumors. Unfortunately, it’s not easy to introduce the cytokine only within a tumor microenvironment, and high systemic levels of IL-15 can be toxic.

Recruiting cells that transpresent IL-15 to the tumor microenvironment may overcome this barrier and therefore improve NK cell-mediated cancer therapy, the investigators said. However, the methodology hasn’t been worked out yet.

“Our paper should encourage this line of inquiry,” Dr Sebzda concluded.

NK cell destroying cancer cell

Image by Joshua Stokes

New findings published in PNAS may help scientists improve the efficacy of natural killer (NK) cell therapy for patients with leukemia.

The preclinical research revealed a tolerance mechanism that restrains the activity of NK cells, as well as a potential way to overcome this problem.

Investigators found that a transcription factor, Kruppel-like factor 2 (KFL2), is critical for NK cell expansion and survival.

Specifically, KLF2 limits immature NK cell proliferation and instructs mature NK cells to home to niches rich in interleukin 15 (IL-15), which is necessary for their continued survival.

“This is the same process likely used by cancer cells to avoid destruction by NK cells,” said study author Eric Sebzda, PhD, of Vanderbilt University Medical Center in Nashville, Tennessee.

In particular, tumors may avoid immune clearance by promoting KLF2 destruction within the NK cell population, thereby starving these cells of IL-15.

Dr Sebzda and his colleagues noted that increased expression of IL-15 can improve immune responses against tumors. Unfortunately, it’s not easy to introduce the cytokine only within a tumor microenvironment, and high systemic levels of IL-15 can be toxic.

Recruiting cells that transpresent IL-15 to the tumor microenvironment may overcome this barrier and therefore improve NK cell-mediated cancer therapy, the investigators said. However, the methodology hasn’t been worked out yet.

“Our paper should encourage this line of inquiry,” Dr Sebzda concluded.

NK cell destroying cancer cell

Image by Joshua Stokes

New findings published in PNAS may help scientists improve the efficacy of natural killer (NK) cell therapy for patients with leukemia.

The preclinical research revealed a tolerance mechanism that restrains the activity of NK cells, as well as a potential way to overcome this problem.

Investigators found that a transcription factor, Kruppel-like factor 2 (KFL2), is critical for NK cell expansion and survival.

Specifically, KLF2 limits immature NK cell proliferation and instructs mature NK cells to home to niches rich in interleukin 15 (IL-15), which is necessary for their continued survival.

“This is the same process likely used by cancer cells to avoid destruction by NK cells,” said study author Eric Sebzda, PhD, of Vanderbilt University Medical Center in Nashville, Tennessee.

In particular, tumors may avoid immune clearance by promoting KLF2 destruction within the NK cell population, thereby starving these cells of IL-15.

Dr Sebzda and his colleagues noted that increased expression of IL-15 can improve immune responses against tumors. Unfortunately, it’s not easy to introduce the cytokine only within a tumor microenvironment, and high systemic levels of IL-15 can be toxic.

Recruiting cells that transpresent IL-15 to the tumor microenvironment may overcome this barrier and therefore improve NK cell-mediated cancer therapy, the investigators said. However, the methodology hasn’t been worked out yet.

“Our paper should encourage this line of inquiry,” Dr Sebzda concluded.