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Just One Concussion Could Raise Parkinson’s Risk

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By Serena Gordon


HealthDay Reporter


WEDNESDAY, April 18, 2018 (HealthDay News) — If you’ve ever had a mild concussion, your risk of developing Parkinson’s disease goes up by 56 percent, a new study of more than 300,000 U.S. veterans suggests.

“Upwards of 40 percent of adults have had a traumatic brain injury [concussion], so these findings are definitely concerning,” said study author Dr. Raquel Gardner. She is an assistant professor of neurology at the University of California, San Francisco, and the San Francisco VA Medical Center.

But Gardner stressed that the findings don’t mean everyone who has ever had a concussion is doomed to develop the degenerative neurological disorder that affects coordination of movement.

“Even in this study, the vast majority of veterans with traumatic brain injury (TBI) did not develop Parkinson’s,” she said.

Dr. Rachel Dolhun, vice president of medical communications for the Michael J. Fox Foundation for Parkinson’s Research, pointed out the lifetime risk of Parkinson’s is probably about 1 to 2 percent, so a greater than 50 percent increase in that risk isn’t as alarming as it sounds.

“Having a TBI doesn’t definitively equate with getting Parkinson’s disease. The risk is still pretty small,” Dolhun said.

But these findings do lend credence to the idea that some professional athletes have developed Parkinson’s disease as a result of their athletic careers. The most famous is probably boxer Muhammad Ali.

Gardner explained that “we’ll never know definitively, but it’s absolutely a possibility. Many have suspected that his head injuries contributed to his Parkinson’s disease, but it’s impossible to say for sure.”

Previous research has linked TBI and Parkinson’s disease, but the new study’s design and large size makes it “among the most definitive,” according to Gardner.

Both Gardner and Dolhun said there are a number of plausible theories as to how a brain injury — even a slight one — might lead to Parkinson’s.

Gardner said it’s possible that traumatic brain injuries could cause abnormal proteins to accumulate in the brain. It’s also possible that a brain injury might make the brain less resilient to aging, she suggested.


Continued

Dolhun said another possibility is that a head injury might cause damage to dopamine-producing cells (which are cells that don’t function properly in Parkinson’s disease).

The new study identified more than 325,000 veterans from three U.S. Veterans Health Administration databases. Half of this group had experienced a traumatic brain injury at some point in their lives. The TBIs were mild, moderate or severe. The other half of participants had never had a TBI. Some of their injuries were due to combat, but some were from falls or motor vehicle accidents.

Study volunteers were aged 31 to 65, and were followed for up to 12 years.

None of the vets had a diagnosis of Parkinson’s when the study began. During the study, almost 1,500 were diagnosed with Parkinson’s disease. Of those, 949 had previously had a traumatic brain injury.

The overall risk of developing Parkinson’s in this group was slightly more than a half of 1 percent for those with a traumatic brain injury. For those without brain injuries, the risk of Parkinson’s was just under one-third of 1 percent, the study found.

When the researchers compared those who had brain injuries to those who didn’t, and controlled the data for other risk factors — such as age, sex, race, education and other health conditions — the overall risk of Parkinson’s disease was 71 percent higher for people who had any type of TBI.

The risk for those with a mild TBI (concussion) was 56 percent higher, and for those with moderate to severe TBIs, the risk was 83 percent greater, the findings showed.

Gardner said the study highlights the need to prevent head injuries. She also said that people should reassess their lifestyle and try to live as healthy as possible.

“A healthy lifestyle gives the brain an extra chance at being resilient,” she noted.

Dolhun said that it’s not clear exactly what causes Parkinson’s or what can prevent it. But she agreed that the best advice right now is “to try to prevent TBIs and to practice good, solid healthy living with regular exercise and a healthy diet.”


Continued

The study was published online April 18 in the journal Neurology




WebMD News from HealthDay


Sources

SOURCES: Raquel Gardner, M.D., assistant professor,  neurology, University of California, San Francisco, and San Francisco VA Medical Center; Rachel Dolhun, M.D., vice president, medical communications, the Michael J. Fox Foundation for Parkinson’s Research; April 18, 2018,Neurology




Copyright © 2013-2018 HealthDay. All rights reserved.


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Could a Tattoo Someday Spot Your Cancer?

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By Alan Mozes


HealthDay Reporter


THURSDAY, April 19, 2018 (HealthDay News) — Tattoos serve many purposes, perhaps expressing artistry, loyalty or love. Now, scientists working with mice say they’ve engineered a medical “tattoo” that can screen for early signs of major disease.

The biomedical tattoo is made up of cells embedded with sensors that measure levels of blood calcium.

It’s initially invisible when implanted under the skin. But the sensors become apparent if blood calcium levels rise. This indicates a condition called hypercalcemia, which is a marker for several cancers and other major diseases.

“Forty percent of all cancers — including colon cancer, lung cancer, breast cancer and prostate cancer — disrupt calcium balance (homeostasis),” said study lead author Martin Fussenegger.

“The biomedical tattoo is designed to catch mild hypercalcemia,” which produces no symptoms, he said.

Appearance of the tattoo may signal that some of those cancers may start to develop, said Fussenegger, of ETH Zurich’s department of biosystems science and engineering in Basel, Switzerland.

When elevated blood calcium persists, the implant releases melanin, producing a telltale dark patch on the skin, he said. (Melanin is a dark pigment responsible for tanning.)

But whether this is just a fun gimmick or a reliable diagnostic tool remains to be seen.

Dr. Janice Dutcher is a medical oncologist with the Cancer Research Foundation in New York City.

She described the innovation as a “neat gimmick.”

“I guess in the context of looking for new and inventive ways to screen for disease, it’s a reasonable idea,” she said. “It’s always nice to try and conceive of a new, simple and accurate way to screen for disease.”

But Dutcher cautioned that screening for high calcium levels is not always an effective way to detect cancer early. Some cancers — kidney cancer, for example — only prompt high calcium after the disease has progressed, she said.

Dr. Norman Edelman, senior medical advisor for the American Lung Association, seconded that point.

In his experience, “the bulk” of tumor-related hypercalcemia occurs at a late stage, when cancer has spread. “It is also a late finding in kidney failure,” he added.


Continued

“So this is really fun science. But I would not spend a lot to license the patent,” Edelman said.

To test their design, the researchers implanted the engineered cells under the skin of mice with either cancerous tumors that cause hypercalcemia or tumors that do not alter calcium blood levels.

The tattoos only surfaced on the skin of mice with elevated blood calcium levels, according to the report.

In theory, said Fussenegger, a tattoo diagnosis would happen at such an early stage of disease “that over 95 percent of the above-mentioned cancer types will be cured.”

He and his colleagues were “impressed by the precision and sensitivity of the tattoo,” he said. A skin patch arose only when high calcium levels persisted, he explained, adding this would reduce the likelihood of false diagnoses.

Still, “animal experiments do not always translate to people,” Fussenegger acknowledged. Human trials are set to begin within five years, he said.

The goal is a human tattoo “universal system” that could detect multiple health issues at once. If all goes according to plan, Fussenegger predicted it could be available within 10 to 15 years.

Besides cancer, Fussenegger said the approach could be linked to other slow-developing diseases. These might include neurodegenerative disorders like Parkinson’s and Alzheimer’s, he said.

The findings were published April 18 in the journal Science Translational Medicine.




WebMD News from HealthDay


Sources

SOURCES: Martin Fussenegger, Ph.D.,  professor of biotechnology and bioengineering, department of biosystems science and engineering, ETH Zurich, Basel, Switzerland, and faculty of science, University of Basel; Norman Edelman, M.D., senior medical advisor, American Lung Association, and professor of medicine, program in public health, Stony Brook University, New York; Janice Dutcher, M.D., medical oncologist, Cancer Research Foundation,  New York City; April 18, 2018,Science Translational Medicine




Copyright © 2013-2018 HealthDay. All rights reserved.


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Large spleen helps explain deep-diving skills of Southeast Asian 'sea nomads'

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April 19, 2018 / 4:37 PM / Updated 38 minutes ago

Large spleen helps explain deep-diving skills of Southeast Asian 'sea nomads'

(Reuters Health) – An age-old nomadic community of Southeast Asian boat-dwellers who get their food from the sea appear to have evolved enlarged spleens that may help explain their extreme diving prowess, a new study suggests.

The spleen stores oxygen-rich red blood cells that it can release into the bloodstream, enabling divers to hold their breath for longer periods of time under water. While competitive divers can train to boost their lung capacity or increase their red blood cell count, the current study offers fresh evidence of the potential for humans to adapt genetically to a lack of oxygen and support a lifestyle centered on diving for food.

“We have examples of how humans have adapted genetically to new diets and to extreme environments, such as high-altitude living in Tibet or life near the Arctic circle in Greenland,” said senior study author Rasmus Nielsen, a professor of integrative biology at the University of California, Berkeley.

“Now we also have a new fascinating example of how humans have adapted genetically to a nomadic lifestyle on the ocean,” Nielsen said by email.

For the study, researchers focused on the Bajau people, who are spread among the islands of Indonesia, Malaysia and the Philippines. Often called sea nomads, they have traditionally lived on boats and harvested nearly everything they eat from the sea.

To spear fish and octopus and gather crustaceans and sea cucumbers, the Bajau often dive to depths greater than 70 meters, or 230 feet, using only a wooden mask. They’ve been subsisting like this for hundreds if not thousands of years, researchers note in Cell.

The study team used ultrasound scans to measure spleen sizes for 59 Bajau people and 34 individuals from the Saluan population, nearby seaside villagers who do not dive.

Overall, the Bajau people had spleens about 50 percent larger than the Saluan, the study found. That may translate into about a 10 percent increase in oxygen supply, Nielsen said.

Among the Bajau people, there wasn’t a meaningful difference in spleen size between divers and non-divers.

Researchers also collected spit samples from participants and identified several gene variants that were seen at much higher frequency in the genomes of the Bajau people than the Saluans.

Variations in one gene in particular, PDE10A, may cause changes in thyroid hormone levels that in turn lead to an enlarged spleen, researchers speculate.

A second genetic adaptation associated with the Bajau involves the constriction of blood vessels in the extremities to preserve oxygen for vital organs. Known as the diving reflex, this response is one competitive divers can encourage with intense training.

Beyond its small size, another limitation of the study is that it wasn’t a controlled experiment designed to prove whether or how generations of divers might evolve to adapt an underwater lifestyle.

More research is needed to answer these questions, said Erika Schagatay, head of the environmental physiology group at Mid Sweden University in Ostersund.

Still, the results offer fresh evidence of a genetic explanation for the development of a diving reflex in humans, Schagatay, who wasn’t involved in the study, said by email.

Beyond that, the results may also rekindle a debate in the scientific community about whether human evolution has unfolded entirely on land.

“An explanation for the presence of genes with diving promoting effects could be the controversial theory that humans have a waterside chapter in their evolutionary history,” Schagatay said. “The genetic diving adaptations present in many human groups but more frequent in the Bajau seem to be another finding supporting this idea.”

SOURCE: bit.ly/1NdTbTa Cell, online April 19, 2016.




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WHO recommends more tests for Sanofi's dengue vaccine

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April 19, 2018 / 2:42 PM / Updated 25 minutes ago

WHO recommends more tests for Sanofi's dengue vaccine

PARIS/CHICAGO (Reuters) – The World Health Organization (WHO) said on Thursday Sanofi’s vaccine against dengue should only be used after testing on individuals to assess whether they have ever been exposed to the infection.

FILE PHOTO: Boxes of anti-dengue vaccine Dengvaxia are placed inside a freezer for storage at the Manila Health Department in Sta Cruz, metro Manila, Philippines December 5, 2017. REUTERS/Romeo Ranoco

After a two-day meeting in Geneva, Switzerland, experts at the U.N. agency recommended extra safety measures for the medicine.

“We have now clear information that the vaccine needs to be dealt with in a much safer way by using it exclusively in people already infected with dengue before,” Alejandro Cravioto, Chair of the WHO’s Strategic Advisory Group of Experts (SAGE) on Immunization, told reporters.

“It requires for the people to be tested through a system that is not currently available but that we feel will be developed in the next years,” he said.

A spokeswoman for Sanofi had no immediate comment.

The French drugmaker warned in November that the vaccine, first approved in late 2015 and sold under the brand Dengvaxia, could increase the risk of severe dengue in some cases in people who had not been previously exposed to the disease.

Mosquito-borne dengue is the world’s fastest-growing infectious disease, afflicting hundreds of millions of people worldwide. It causes half a million life-threatening infections and kills about 20,000 people, mostly children, annually.

HEALTH SCARE

Dengvaxia, the world’s sole licensed vaccine against dengue, is at the center of a health scare in the Philippines where the government suspended its use last year amid safety fears.

The company has repeatedly said it knows of no deaths resulting from the medicine.

Joachim Hombach, executive secretary of WHO’s SAGE group, said: “For us, the primary consideration is to assure our recommendation makes public health sense in terms of ensuring the use of vaccine will maximize public health benefit and minimize risk.”

“It is very important we signal ways in which this vaccine could be used,” he said, adding that it was up to the company to decide how to deal with this.

Hombach defended the WHO’s initial recommendation that the vaccine could be used in children aged 9 and older in places where 70 percent of the population had previously been exposed to the virus, and were likely to benefit from the vaccine.

He said the WHO pointed out a gap in data on the use of the vaccine in people who had never been exposed to the virus, and asked Sanofi to study the impact of the vaccine on children who had never been exposed to the virus.

COMMITTED

Executives at Sanofi have denied any wrongdoing and insist on the benefits the medicine brings as a whole.

In a interview with Reuters last month, David Loew, head of Sanofi Pasteur, the group’s vaccines division, said Sanofi remained committed to Dengvaxia.

He added Sanofi was holding discussions with external partners and universities to come up with a test which would be applicable before vaccination. Such a test, however, would take at least two years to bring to the market, he said.

Dengvaxia has been approved and registered in 19 countries and is currently under review by the European Medicines Agency.

Japan’s Takeda Pharmaceutical, the United States National Institute of Health and Brazil’s Butantan Institute are developing rival products.

Initially touted as potential $1-billion-a-year-plus product, Dengvaxia net sales stood at 3 million euros ($3.71 million) in 2017 as Sanofi was forced to buy back unused doses. The company took a charge of 87 million euros in the fourth quarter.

($1 = 0.8090 euros)

Editing by Jane Merriman




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Drug May Reverse Anti-PD-1 Resistance in Melanoma (CME/CE)

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Medpage Today

Drug May Reverse Anti-PD-1 Resistance in Melanoma

Responses in 22% of resistant patients with TLR9 agonist

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  • by Senior Associate Editor, MedPage Today

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Melanoma that developed resistance to anti-PD-1 therapy started responding again after injection of a toll-like receptor 9 (TLR9) agonist directly into the tumor.
  • Note that examination of untreated melanoma lesions revealed shrinkage in some cases, suggesting an “abscopal” effect, or local treatment that induces a systemic effect.

CHICAGO — Melanoma that developed resistance to anti-PD-1 therapy started responding again after injection of a toll-like receptor 9 (TLR9) agonist directly into the tumor, a preliminary clinical trial showed.

Overall, 18 of 85 patients regained responsiveness to the PD-1 inhibitor pembrolizumab (Keytruda) after injection with CMP-001. The total response rate included three patients who continued treatment after progression.

Examination of untreated melanoma lesions revealed shrinkage in some cases, suggesting an “abscopal” effect, or local treatment that induces a systemic effect, Mohammed Milhem, MD, of the University of Iowa in Iowa City, reported at the American Association for Cancer Research (AACR) annual meeting.

“The combination of CMP-001 and pembrolizumab appears well tolerated and can produce deep and durable systemic clinical responses,” Milhem said during an AACR press briefing. “Results from immunohistochemistry, RNA sequencing, and chemokine analysis are consistent with activation of plasmacytoid dendritic cells by CMP-001 through TLR9 signaling. Enrollment into the expansion phase of this study continues, and clinical investigation in other tumor types is under way.”

The phase Ib study involved patients with advanced melanoma that did not respond or developed resistance to anti-PD-1 immunotherapy, which is standard of care for the disease. About half of patients who initially respond to anti-PD-1 therapy subsequently develop resistance to treatment, leaving them with limited options for continued treatment.

Multiple strategies to prevent resistance or restore melanoma’s responsiveness to immunotherapy are under investigation.

“Toll-like receptors are found in the innate immune system,” said press briefing moderator Suzanne Topalian, MD, of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore. “In this case, one of the toll-like receptors, TLR9, is being leveraged therapeutically to provide a strong stimulus for immune responses.”

Previous studies showed that tumors with increased expression of interferon are more responsive to anti-PD-1 immunotherapy. The TLR9 signaling pathway has the greatest potential for induction of interferon gene expression, Milhem said of the rationale for developing a TLR9 agonist to restore anti-PD-1 activity in melanoma.

CMP-001 consists of a synthetic immunostimulatory DNA molecule (CpG-A) encased in a nonreplicating virus-like particle that protects the DNA from degradation. The drug stimulates TLR9 activity, which leads to activation of tumor-associated plasmacytoid dendritic cells and induction of an interferon-rich microenvironment and antitumor T-cell activation.

The phase Ib trial consisted of a dose-finding component, followed by an expansion study with the chosen dose and administration schedule. Patients continued to receive pembrolizumab along with CMP-001. Milhem reported results from the dose-finding and expansion phases, the latter of which is ongoing.

The combination of CMP-001 and pembrolizumab led to an overall response rate of 22%, consisting of two complete responses, 13 partial responses, and three additional responses that occurred after initial disease progression. Milhem said 13 of the 18 responding patients continued to receive treatment, and the median duration of response had yet to be reached.

Most responses persisted beyond 6 months and several for more than a year, he added. Responses continued in some patients after treatment ended.

A limitation of CMP-001 is the requirement for an accessible lesion, such as one on the skin surface, a palpable lesion under the skin, or a lymph node. However, investigators detected shrinkage of untreated melanoma lesions in several patients, providing evidence that the treatment has abscopal activity, essentially stimulating a systemic immune response that affects lesions other than those that are directly injected, said Milhem.

Enrollment in the expansion of the phase continues, he added, and clinical investigation of CMP-001 has expanded into other types of tumors.

Given that many patients do not respond to immunotherapy and others develop resistance to the treatment, investigations such as the one described by Milhem have substantial implications for the field of immuno-oncology, said Topalian.

“This trial looks at a very important group of patients — those who do not respond to anti-PD-1 treatment or who have stable disease but don’t make it over the threshold to a complete or partial response,” she said. “The question is how can we further activate the immune system to get those patients over that threshold to response?”

In response to a question, Milhem acknowledged that CMP-001 might also have a “priming” effect in patients who discontinued anti-PD-1 treatment because of loss of response. Rechallenging with anti-PD-1 therapy might be feasible in such patients.

The study was supported by Checkmate Pharmaceuticals.

Milhem disclosed no relevant relationships with industry.

  • Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
2018-04-19T10:30:00-0400
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At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.

Medpage Today

Drug May Reverse Anti-PD-1 Resistance in Melanoma

Responses in 22% of resistant patients with TLR9 agonist

MedpageToday

  • register today

    Earn Free CME Credits by reading the latest medical news in your specialty.

    sign up

  • by Senior Associate Editor, MedPage Today

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Melanoma that developed resistance to anti-PD-1 therapy started responding again after injection of a toll-like receptor 9 (TLR9) agonist directly into the tumor.
  • Note that examination of untreated melanoma lesions revealed shrinkage in some cases, suggesting an "abscopal" effect, or local treatment that induces a systemic effect.

CHICAGO -- Melanoma that developed resistance to anti-PD-1 therapy started responding again after injection of a toll-like receptor 9 (TLR9) agonist directly into the tumor, a preliminary clinical trial showed.

Overall, 18 of 85 patients regained responsiveness to the PD-1 inhibitor pembrolizumab (Keytruda) after injection with CMP-001. The total response rate included three patients who continued treatment after progression.

Examination of untreated melanoma lesions revealed shrinkage in some cases, suggesting an "abscopal" effect, or local treatment that induces a systemic effect, Mohammed Milhem, MD, of the University of Iowa in Iowa City, reported at the American Association for Cancer Research (AACR) annual meeting.

"The combination of CMP-001 and pembrolizumab appears well tolerated and can produce deep and durable systemic clinical responses," Milhem said during an AACR press briefing. "Results from immunohistochemistry, RNA sequencing, and chemokine analysis are consistent with activation of plasmacytoid dendritic cells by CMP-001 through TLR9 signaling. Enrollment into the expansion phase of this study continues, and clinical investigation in other tumor types is under way."

The phase Ib study involved patients with advanced melanoma that did not respond or developed resistance to anti-PD-1 immunotherapy, which is standard of care for the disease. About half of patients who initially respond to anti-PD-1 therapy subsequently develop resistance to treatment, leaving them with limited options for continued treatment.

Multiple strategies to prevent resistance or restore melanoma's responsiveness to immunotherapy are under investigation.

"Toll-like receptors are found in the innate immune system," said press briefing moderator Suzanne Topalian, MD, of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore. "In this case, one of the toll-like receptors, TLR9, is being leveraged therapeutically to provide a strong stimulus for immune responses."

Previous studies showed that tumors with increased expression of interferon are more responsive to anti-PD-1 immunotherapy. The TLR9 signaling pathway has the greatest potential for induction of interferon gene expression, Milhem said of the rationale for developing a TLR9 agonist to restore anti-PD-1 activity in melanoma.

CMP-001 consists of a synthetic immunostimulatory DNA molecule (CpG-A) encased in a nonreplicating virus-like particle that protects the DNA from degradation. The drug stimulates TLR9 activity, which leads to activation of tumor-associated plasmacytoid dendritic cells and induction of an interferon-rich microenvironment and antitumor T-cell activation.

The phase Ib trial consisted of a dose-finding component, followed by an expansion study with the chosen dose and administration schedule. Patients continued to receive pembrolizumab along with CMP-001. Milhem reported results from the dose-finding and expansion phases, the latter of which is ongoing.

The combination of CMP-001 and pembrolizumab led to an overall response rate of 22%, consisting of two complete responses, 13 partial responses, and three additional responses that occurred after initial disease progression. Milhem said 13 of the 18 responding patients continued to receive treatment, and the median duration of response had yet to be reached.

Most responses persisted beyond 6 months and several for more than a year, he added. Responses continued in some patients after treatment ended.

A limitation of CMP-001 is the requirement for an accessible lesion, such as one on the skin surface, a palpable lesion under the skin, or a lymph node. However, investigators detected shrinkage of untreated melanoma lesions in several patients, providing evidence that the treatment has abscopal activity, essentially stimulating a systemic immune response that affects lesions other than those that are directly injected, said Milhem.

Enrollment in the expansion of the phase continues, he added, and clinical investigation of CMP-001 has expanded into other types of tumors.

Given that many patients do not respond to immunotherapy and others develop resistance to the treatment, investigations such as the one described by Milhem have substantial implications for the field of immuno-oncology, said Topalian.

"This trial looks at a very important group of patients -- those who do not respond to anti-PD-1 treatment or who have stable disease but don't make it over the threshold to a complete or partial response," she said. "The question is how can we further activate the immune system to get those patients over that threshold to response?"

In response to a question, Milhem acknowledged that CMP-001 might also have a "priming" effect in patients who discontinued anti-PD-1 treatment because of loss of response. Rechallenging with anti-PD-1 therapy might be feasible in such patients.

The study was supported by Checkmate Pharmaceuticals.

Milhem disclosed no relevant relationships with industry.

  • Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
2018-04-19T10:30:00-0400
Take Posttest Comments

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EHR State of Mind: Epic Rap Smackdown

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Medpage Today

EHR State of Mind: Epic Rap Smackdown

ZdoggMD’s got 99 problems, and the EHR is one

MedpageToday

  • by

Click-boxes? Endless typing? Less face time with patients? EHRs are a point of contention for a lot of physicians and nurses.

ZdoggMD — or should we say Jay-ZdoggMD — feels your pain and lets his beef be known by putting those EHRs on blast in this savage smackdown track.

This video originally appeared on ZDoggMD.

2018-04-19T11:00:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.

Medpage Today

EHR State of Mind: Epic Rap Smackdown

ZdoggMD's got 99 problems, and the EHR is one

MedpageToday

  • by

Click-boxes? Endless typing? Less face time with patients? EHRs are a point of contention for a lot of physicians and nurses.

ZdoggMD -- or should we say Jay-ZdoggMD -- feels your pain and lets his beef be known by putting those EHRs on blast in this savage smackdown track.

This video originally appeared on ZDoggMD.

2018-04-19T11:00:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.



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Gut Bacteria Tx Holds Promise for Alcoholic Liver Disease (CME/CE)

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Medpage Today

Gut Bacteria Tx Holds Promise for Alcoholic Liver Disease

Akkermansia muciniphila supplementation may become a new therapeutic option

MedpageToday

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  • by Contributing Writer

Action Points

  • Manipulating the microbiota with supplemental Akkermansia muciniphila may offer hope for the global and hard-to-treat problem of alcoholic liver disease (ALD).
  • The study suggests that recovery of ethanol-induced Akkermansia muciniphila depletion by oral supplementation could represent a novel treatment option for patients with ALD.

Manipulating the microbiota with supplemental Akkermansia muciniphila may offer hope for the global and hard-to-treat problem of alcoholic liver disease (ALD), a preliminary U.S.-European study in humans and mice suggested.

One modulator of ALD is the integrity of the intestinal barrier, and this integrity is supported by A. muciniphila, a Gram-negative intestinal commensal bacterium that enhances mucus production. In healthy people, this organism constitutes as much as 4% of fecal microbiota, according to Herbert Tilg, MD, of the Medical University in Innsbruck, Austria, and colleagues.

“We propose that depletion of A. muciniphila reflects an early event in the pathophysiology of ALD, probably by regulating gut barrier function. Recovery of ethanol-induced A. muciniphila depletion by oral supplementation could represent a novel treatment option for patients with ALD,” they wrote in Gut.

ALD is the most common cause of liver-related deaths worldwide and is responsible for 5.9% of all global deaths. It encompasses simple steatosis, fibrosis, and cirrhosis, all of which can deteriorate toward acute alcoholic steatohepatitis (ASH) with its high mortality rates.

“Despite our increasing understanding of ALD pathogenesis, treatment strategies remain scarce,” Tilg’s group stated.

The degree of liver injury varies among individuals with ALD, and researchers increasingly believe that the microbiota plays a role in this variation. They are hopeful that appropriate probiotic supplementation may reduce hepatic injury.

The intestinal microbiota has evolved as a major player in various hepatic disorders, with several studies suggesting that it is important for the development of ALD.

A. muciniphila has already shown promising probiotic effects in diabetes and obesity.

Tilg’s group studied stored stool samples from 36 adult ALD patients from a single hospital in France. Patients were characterized as alcoholic if they had a daily alcohol consumption of 50 g ethanol over the past year and a liver biopsy showing the presence of acidophilic bodies, ballooning of hepatocytes, Mallory bodies, neutrophil infiltration, steatosis, and fibrosis.

In this cohort, 21 patients (mean age 50.9) had ASH, and 15 patients (mean age 55.1) had severe ASH. They were compared with a control group of 16 healthy non-obese individuals (mean age 41.1).

The investigators found that ASH patients had a decreased abundance of fecal A. muciniphila versus controls, and abundance levels indirectly correlated with hepatic disease severity in patients. According to Tilg, other commensals such as Lactobacillus rhamnosus and the probiotic VSL#3 may also be prophylactic and therapeutic in ASH.

Alcohol intake has been associated with negative gut microbial alterations, a dysbiosis that appears to be a driving force in the development of ALD. Patients with ALD have exhibited lower median levels of Bacteroidetes and increased levels of Proteobacteria, for example, and in a subset of alcoholics, these alterations correlated with high levels of serum endotoxins, which are co-factors in tissue injury.

In parallel experimental studies, the current investigators fed ethanol to wild-type mice, which resulted in a significant decline in A. muciniphila abundance, while oral supplementation with the bacterium reversed ethanol-induced disruption of the intestinal barrier integrity.

Given prophylactically against ethanol, the bacterium resulted in less hepatic injury, steatosis, and neutrophil infiltration. It also protected against ethanol-induced gut leakiness and enhanced mucus thickness and tight-junction expression. In already established ALD, A. muciniphila used therapeutically also improved hepatic injury and neutrophil infiltration. “At least in these preclinical models, supplementation worked in the therapeutic context,” Tilg told MedPage Today.

Last year, other researchers also reported that the intestinal microbiota status influenced susceptibility to ALD in ethanol-fed mice.

Currently Tilg’s group is testing the effect of A. muciniphila in a phase I clinical study of obesity patients and is planning to further explore its impact on ASH and ALD.

The study’s limitations include its preliminary, retrospective, and nonclinical nature and its small sample size.

The study was supported by the Christian Doppler Research Society.

Tilg disclosed support from the Competence Centers for Excellent Technologies of the Austrian Research Promotion agency.

  • Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
1969-12-31T19:00:00-0500

last updated

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Gut Bacteria Tx Holds Promise for Alcoholic Liver Disease

Akkermansia muciniphila supplementation may become a new therapeutic option

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  • by Contributing Writer

Action Points

  • Manipulating the microbiota with supplemental Akkermansia muciniphila may offer hope for the global and hard-to-treat problem of alcoholic liver disease (ALD).
  • The study suggests that recovery of ethanol-induced Akkermansia muciniphila depletion by oral supplementation could represent a novel treatment option for patients with ALD.

Manipulating the microbiota with supplemental Akkermansia muciniphila may offer hope for the global and hard-to-treat problem of alcoholic liver disease (ALD), a preliminary U.S.-European study in humans and mice suggested.

One modulator of ALD is the integrity of the intestinal barrier, and this integrity is supported by A. muciniphila, a Gram-negative intestinal commensal bacterium that enhances mucus production. In healthy people, this organism constitutes as much as 4% of fecal microbiota, according to Herbert Tilg, MD, of the Medical University in Innsbruck, Austria, and colleagues.

"We propose that depletion of A. muciniphila reflects an early event in the pathophysiology of ALD, probably by regulating gut barrier function. Recovery of ethanol-induced A. muciniphila depletion by oral supplementation could represent a novel treatment option for patients with ALD," they wrote in Gut.

ALD is the most common cause of liver-related deaths worldwide and is responsible for 5.9% of all global deaths. It encompasses simple steatosis, fibrosis, and cirrhosis, all of which can deteriorate toward acute alcoholic steatohepatitis (ASH) with its high mortality rates.

"Despite our increasing understanding of ALD pathogenesis, treatment strategies remain scarce," Tilg's group stated.

The degree of liver injury varies among individuals with ALD, and researchers increasingly believe that the microbiota plays a role in this variation. They are hopeful that appropriate probiotic supplementation may reduce hepatic injury.

The intestinal microbiota has evolved as a major player in various hepatic disorders, with several studies suggesting that it is important for the development of ALD.

A. muciniphila has already shown promising probiotic effects in diabetes and obesity.

Tilg's group studied stored stool samples from 36 adult ALD patients from a single hospital in France. Patients were characterized as alcoholic if they had a daily alcohol consumption of 50 g ethanol over the past year and a liver biopsy showing the presence of acidophilic bodies, ballooning of hepatocytes, Mallory bodies, neutrophil infiltration, steatosis, and fibrosis.

In this cohort, 21 patients (mean age 50.9) had ASH, and 15 patients (mean age 55.1) had severe ASH. They were compared with a control group of 16 healthy non-obese individuals (mean age 41.1).

The investigators found that ASH patients had a decreased abundance of fecal A. muciniphila versus controls, and abundance levels indirectly correlated with hepatic disease severity in patients. According to Tilg, other commensals such as Lactobacillus rhamnosus and the probiotic VSL#3 may also be prophylactic and therapeutic in ASH.

Alcohol intake has been associated with negative gut microbial alterations, a dysbiosis that appears to be a driving force in the development of ALD. Patients with ALD have exhibited lower median levels of Bacteroidetes and increased levels of Proteobacteria, for example, and in a subset of alcoholics, these alterations correlated with high levels of serum endotoxins, which are co-factors in tissue injury.

In parallel experimental studies, the current investigators fed ethanol to wild-type mice, which resulted in a significant decline in A. muciniphila abundance, while oral supplementation with the bacterium reversed ethanol-induced disruption of the intestinal barrier integrity.

Given prophylactically against ethanol, the bacterium resulted in less hepatic injury, steatosis, and neutrophil infiltration. It also protected against ethanol-induced gut leakiness and enhanced mucus thickness and tight-junction expression. In already established ALD, A. muciniphila used therapeutically also improved hepatic injury and neutrophil infiltration. "At least in these preclinical models, supplementation worked in the therapeutic context," Tilg told MedPage Today.

Last year, other researchers also reported that the intestinal microbiota status influenced susceptibility to ALD in ethanol-fed mice.

Currently Tilg's group is testing the effect of A. muciniphila in a phase I clinical study of obesity patients and is planning to further explore its impact on ASH and ALD.

The study's limitations include its preliminary, retrospective, and nonclinical nature and its small sample size.

The study was supported by the Christian Doppler Research Society.

Tilg disclosed support from the Competence Centers for Excellent Technologies of the Austrian Research Promotion agency.

  • Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
1969-12-31T19:00:00-0500

last updated

Take Posttest Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.



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OncoBreak: Clinical Trial Barriers; Healthy Cancer Patients; Marriage and Melanoma

0


Medpage Today

OncoBreak: Clinical Trial Barriers; Healthy Cancer Patients; Marriage and Melanoma

News, features, and commentary about cancer-related issues

MedpageToday

  • by Senior Associate Editor, MedPage Today

An oncologist examines clinicians’ self-imposed barriers to enrolling patients in clinical trials. (ASCO Connection)

Yet another strategy offers the promise of delivering cancer drugs more precisely to reduce toxicity. (University of Cardiff)

Adolescents and young adults with leukemia have better outcomes when treated at specialized pediatric cancer centers. (American Society of Hematology)

The cells that make up unstable coronary plaque look and behave a lot like cancer cells. (University of Lund; page translation required)

The FDA approved osimertinib (Tagrisso) as first-line treatment for EGFR-mutated metastatic non-small cell lung cancer. (AstraZeneca)

Physically inactive cancer patients had an increased risk of dying of their disease. (Roswell Park Comprehensive Cancer Center)

Patients with colon cancer were less likely to die of the disease if they adhered to recommended healthy behaviors. (American Cancer Society, JAMA Oncology)

Two thirds of cancer survivors have significant treatment-related neuropathy, but managing symptoms remains an inexact science. (University of Michigan School of Nursing)

A study of people with newly diagnosed melanoma showed that those who were married were more likely to have early-stage disease. (JAMA Dermatology)

While hospitalized for spinal surgery, Abby Lee Miller, of the “Dance Moms” cable TV program, learned that she has Burkitt lymphoma. (Lifetime, Page Six)

2018-04-19T11:45:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.

Medpage Today

OncoBreak: Clinical Trial Barriers; Healthy Cancer Patients; Marriage and Melanoma

News, features, and commentary about cancer-related issues

MedpageToday

  • by Senior Associate Editor, MedPage Today

An oncologist examines clinicians' self-imposed barriers to enrolling patients in clinical trials. (ASCO Connection)

Yet another strategy offers the promise of delivering cancer drugs more precisely to reduce toxicity. (University of Cardiff)

Adolescents and young adults with leukemia have better outcomes when treated at specialized pediatric cancer centers. (American Society of Hematology)

The cells that make up unstable coronary plaque look and behave a lot like cancer cells. (University of Lund; page translation required)

The FDA approved osimertinib (Tagrisso) as first-line treatment for EGFR-mutated metastatic non-small cell lung cancer. (AstraZeneca)

Physically inactive cancer patients had an increased risk of dying of their disease. (Roswell Park Comprehensive Cancer Center)

Patients with colon cancer were less likely to die of the disease if they adhered to recommended healthy behaviors. (American Cancer Society, JAMA Oncology)

Two thirds of cancer survivors have significant treatment-related neuropathy, but managing symptoms remains an inexact science. (University of Michigan School of Nursing)

A study of people with newly diagnosed melanoma showed that those who were married were more likely to have early-stage disease. (JAMA Dermatology)

While hospitalized for spinal surgery, Abby Lee Miller, of the "Dance Moms" cable TV program, learned that she has Burkitt lymphoma. (Lifetime, Page Six)

2018-04-19T11:45:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.



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Three Lessons from 'Astounding' Barbershop HTN Intervention

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Medpage Today

Three Lessons from ‘Astounding’ Barbershop HTN Intervention

Leslie Cho, MD, trims up the trial’s real-world implications in this video

MedpageToday

Leslie Cho, MD

  • by Senior Associate Editor, MedPage Today

The 27.0-mm Hg systolic blood pressure reduction achieved by a specialty pharmacist intervention for black men at barbershops — reported at the American College of Cardiology meeting and New England Journal of Medicine last month — was on par with the early promise of renal denervation.

But does the “astounding” benefit stand a better chance in real-world use? Leslie Cho, MD, head of preventive cardiology at the Cleveland Clinic, discusses the implications in this exclusive MedPage Today video.

A transcript of her comments follows:

The Barbershop Study was a very interesting study. It’s a cluster, randomized control study of blood pressure control in African American men using barbershop as the intervention place and pharmacists with physician supervision as the focal person for adjusting blood pressure medicine.

The intervention arm where patients were seen every 2 weeks at the barbershop and had their medication adjusted had an astounding 27-mm Hg decrease in their systolic blood pressure. This is if those of you who know anything about hypertension trials knows that that is an amazing result in terms of blood pressure reduction. The study brings up three very interesting questions and that is: Number 1, all of us have done trials, we’ve done trials in a hospital and physician’s office — this takes it to where patients are, in their community, and addressing them at that point of contact.

The second very interesting question is in very difficult-to-manage hypertension patients, like African American men who have greater than 80% risk of having cardiovascular disease compared to their Caucasian counterpart, really doing a targeted, culturally sensitive, focused intervention and seeing the result that’s so spectacular as you saw in the Barbershop Study.

Then the third is the economic impact of doing something like this in an everyday clinical setting.

Let’s just talk about the interesting trial design and that is taking the trial outside of hospitals and physician’s office and going to your local community. I think we’ll be seeing more and more of these kind of trials. In the era of social media, in an era of smartphones, I think you will see more and more of these kind of patient-directed, culturally-sensitive trials coming down the line. For that, this trial is spectacular in terms of bringing that first of that kind of trial to light.

In terms of the patient population and really catering our treatment to patient preference and their cultural needs, I think that’s also great. Now the issue about how to target individual patients so it really is a personalized medicine. We always talk about personalized medicine and think about genes. But honestly, the personalized medicine aspect is meeting patients where they’re at and finding what works for them. I think trials like this really bring that to fruition, and I think it’s really important that we target patients and treat them appropriately to whatever that they need. I think for that this trial is also excellent.

The thing about this trial that I think will be a little problematic is how to do something like this in a clinical setting, because it requires so much money. Economically, I think it’s a little bit unfeasible to have a pharmacist in barbershops, seeing patients every 2 weeks, adjusting, very aggressive medication adjustment, going from calcium channel blockers plus ACE inhibitors and escalating to Aldactone [spironolactone] and then escalating to a fourth drug. I think that economic-wise we really, as a society, need to think about how else we can do something similar to this, but would make more economic sense.

But I think, overall, it’s a really great study, taking us to a new paradigm in terms of patient contact, patient intervention, and thinking about economic implication.

2018-04-19T12:00:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.

Medpage Today

Three Lessons from 'Astounding' Barbershop HTN Intervention

Leslie Cho, MD, trims up the trial's real-world implications in this video

MedpageToday

Leslie Cho, MD

  • by Senior Associate Editor, MedPage Today

The 27.0-mm Hg systolic blood pressure reduction achieved by a specialty pharmacist intervention for black men at barbershops -- reported at the American College of Cardiology meeting and New England Journal of Medicine last month -- was on par with the early promise of renal denervation.

But does the "astounding" benefit stand a better chance in real-world use? Leslie Cho, MD, head of preventive cardiology at the Cleveland Clinic, discusses the implications in this exclusive MedPage Today video.

A transcript of her comments follows:

The Barbershop Study was a very interesting study. It's a cluster, randomized control study of blood pressure control in African American men using barbershop as the intervention place and pharmacists with physician supervision as the focal person for adjusting blood pressure medicine.

The intervention arm where patients were seen every 2 weeks at the barbershop and had their medication adjusted had an astounding 27-mm Hg decrease in their systolic blood pressure. This is if those of you who know anything about hypertension trials knows that that is an amazing result in terms of blood pressure reduction. The study brings up three very interesting questions and that is: Number 1, all of us have done trials, we've done trials in a hospital and physician's office -- this takes it to where patients are, in their community, and addressing them at that point of contact.

The second very interesting question is in very difficult-to-manage hypertension patients, like African American men who have greater than 80% risk of having cardiovascular disease compared to their Caucasian counterpart, really doing a targeted, culturally sensitive, focused intervention and seeing the result that's so spectacular as you saw in the Barbershop Study.

Then the third is the economic impact of doing something like this in an everyday clinical setting.

Let's just talk about the interesting trial design and that is taking the trial outside of hospitals and physician's office and going to your local community. I think we'll be seeing more and more of these kind of trials. In the era of social media, in an era of smartphones, I think you will see more and more of these kind of patient-directed, culturally-sensitive trials coming down the line. For that, this trial is spectacular in terms of bringing that first of that kind of trial to light.

In terms of the patient population and really catering our treatment to patient preference and their cultural needs, I think that's also great. Now the issue about how to target individual patients so it really is a personalized medicine. We always talk about personalized medicine and think about genes. But honestly, the personalized medicine aspect is meeting patients where they're at and finding what works for them. I think trials like this really bring that to fruition, and I think it's really important that we target patients and treat them appropriately to whatever that they need. I think for that this trial is also excellent.

The thing about this trial that I think will be a little problematic is how to do something like this in a clinical setting, because it requires so much money. Economically, I think it's a little bit unfeasible to have a pharmacist in barbershops, seeing patients every 2 weeks, adjusting, very aggressive medication adjustment, going from calcium channel blockers plus ACE inhibitors and escalating to Aldactone [spironolactone] and then escalating to a fourth drug. I think that economic-wise we really, as a society, need to think about how else we can do something similar to this, but would make more economic sense.

But I think, overall, it's a really great study, taking us to a new paradigm in terms of patient contact, patient intervention, and thinking about economic implication.

2018-04-19T12:00:00-0400
Comments

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.



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