StemCell Therapy

Michigan Gov. Gretchen Whitmer appointed a number of faculty members and alumni of the Wayne State University School of Medicine to several state boards overseeing medicine and medical licensing.

Appointments to the Michigan Board of Medicine, which works with the Department of Licensing and Regulatory Affairs to oversee the practice of medical doctors ascertaining minimal entry-level competency of medical doctors and requiring continuing medical education during licensure include:

Bryan Little, M.D., Class of 1998, is the specialist in chief of Orthopedic Surgery at the Detroit Medical Center. The governor also appointed Dr. Little to the Michigan Task Force on Physicians Assistants. That entity works with the Department of Licensing and Regulatory affairs to oversee the practice of physicians assistants. The terms of both appointments expire Dec. 31, 2023.

Angela Trepanier, M.S., CGC, professor of Molecular Medicine and Genetics and director of the Genetic Counseling Masters Program at the School of Medicine. She will represent genetic counselors during her term, which expires Dec. 31, 2023.

Donald Tynes, M.D., Class of 1995, clinical assistant professor for the School of Medicine and chief medical officer of the Benton Harbor Health Center, will serve a term through Dec. 31, 2023.

Hsin Wang, M.D., Class of 1999, was appointed to the Michigan Board of Licensed Midwifery, which works with the Department of Licensing and Regulatory Affairs to establish and implement the licensure program for the practice of midwifery in the state. Dr. Wang is an obstetrician-gynecologist with the Detroit Medical Center and the director of the Pelvic Health Program for DMC Huron Valley-Sinai Hospital. Her term runs through Dec. 31, 2023.

Melissa Mafiah, M.D., Class of 2014, was appointed to the Michigan Board of Occupational Therapists for a term that expires Dec. 31, 2023. Dr. Mafiah is a physical medicine and rehabilitation physician at W.H. Beaumont Hospital. The board works with the Department of Licensing and Regulatory Affairs to promulgate rules for licensing occupational therapists and ascertaining minimal entry level competency of occupational therapists and occupational therapy assistants.

Michael Dunn, M.D., chief of Medicine at the Henry Ford West Bloomfield Hospital and the senior staff physician for the hospitals Pulmonary and Critical Care Medicine Division, is an assistant clinical professor of Medicine for the School of Medicine. He was appointed to the Michigan Board of Respiratory Care, which oversees the licensure requirements and standards for respiratory therapists. His appointment runs through Dec. 31, 2023.

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Faculty and alumni appointed to state medical boards - The South End

Lately, Ive been very interested in learning more about teaching and learning. Ive been involved in coaching public speaking and debate for nearly a decade, and taught ESL classes off and on, and have recently come to realize that I am an educator. I had a professor in college who told us that if we were going to read one book on a subject, we might as well read tenwed learn a lot more and if we just kept going, before we knew it all ten would be finished. Well, often I dont do that, but recently Ive been raiding the Education section at several branches of the local library systemlearning about teaching reading, differentiated learning for gifted students, controversies over giving homework, and much more.

One gem I came across was Mary Cay Riccis Mindsets in the Classroom. And it clicked with my work at Discovery.

In learning about what Ricci and others call the growth mindset, I was reminded that the way to teach critical thinking in science is to have students engage with the content like scientists.

Growth mindset is an idea popularized by Stanford psychology professor Carol Dweck. She contrasts the idea of a growth mindset that we can become smarter as we work hard and our brains make new connections to the notion of a fixed mindset that we have whatever talents we were born with, or that our growth is limited. Here is a helpful video from Dweck on growth mindset, speaking for Khan Academy.

Mary Cay Riccis book takes Dwecks concept and gives teachers concrete nuts and bolts for how to teach growth mindset in the classroom.

I found her section on critical thinking striking. She notes:

Another important factor to consider about critical thinking is that it is not a simple skill (Willingham, 2008). According to Willingham (2008), critical thinking is a process that must be infused with content; it is not something that you can just check off a list once it is mastered. Why? Well, one reason is that the content being focused on and the complexity of thinking critically becomes more sophisticated over time it is always evolving. The practice component applied to the content knowledge is essential to develop learners who can apply critical thinking when they need to. Hand in hand with practice is persistence and effort, probably the two most important attributes of having a growth mindset!

If you embrace Willinghams argument that critical thinking is not a bunch of isolated skills, then you too (like me) may become annoyed by the amount of resources on the market that advertise ways to build critical thinking skills. Due in part to the way critical thinking is framed in these resources, the concept of accepting critical thinking as a process embedded in content rather than a set of skills can require a major shift in thinking.

As an aside, note her use of the word evolution to signify things becoming more complex over time! Thats not how evolutionists use the term. But never mind that. Ricci sees critical thinking as an essential component of the growth mindset it is key to practicing new learning.

When applied to the subject of science, critical thinking as defined here becomes synonymous with scientific inquiry. Critical thinking is a process that must be infused with content.the content being focused on and the complexity of thinking critically becomes more sophisticated over time And it is true that one cannot teach critical thinking skills in isolation. There must be a content area to analyze, and the critical thinking skills for one content area are not the same as critical thinking skills for another content area. In science, critical thinking is scientific inquiry observing, coming up with hypotheses, experimenting, recording data, drawing conclusions, etc.

One of the worlds foremost science publications, the journal Nature, has noted: [S]tudents gain a much deeper understanding of science when they actively grapple with questions than when they passively listen to answers.

Also in Nature, Jay Labov, senior education advisor from the U.S. National Academy of Sciences, commented that he sees active engagement as learning content not as something you memorize and regurgitate, but as raw material for making connections, drawing inferences, creating new information learning how to learn.

Teaching evolution well means educating in relevant aspects of scientific inquiry critical thinking too. This means, in short, exposing students to current scientific inquiries in the field the relevant, recent research.

This is from Denis Noble, Professor Emeritus and co-Director of Cardiovascular Physiology at Oxford University, and Fellow of the Royal Society, writing in the journal Experimental Physiology. He describes scientists as they learn and change their views in response to evidence.

The Modern Synthesis (NeoDarwinism) is a mid20th century genecentric view of evolution, based on random mutations accumulating to produce gradual change through natural selection. Any role of physiological function in influencing genetic inheritance was excluded. The organism became a mere carrier of the real objects of selection, its genes. We now know that genetic change is far from random and often not gradual. Molecular genetics and genome sequencing have deconstructed this unnecessarily restrictive view of evolution in a way that reintroduces physiological function and interactions with the environment as factors influencing the speed and nature of inherited change. Acquired characteristics can be inherited, and in a few but growing number of cases that inheritance has now been shown to be robust for many generations. The 21st century can look forward to a new synthesis that will reintegrate physiology with evolutionary biology. [Emphasis added.]

As I said earlier, the way to teach critical thinking in science is to have students engage with the content like scientists. What could be better than exposing them to current scientific debates and asking them to examine the evidence for themselves?

What would this kind of activity foster? I can easily see it planting questions in students minds that may blossom into full-fledged scientific inquiries. The leap is not great between enjoying science in high school and trying out science classes as a freshman or sophomore in college, and onward to graduating with a STEM degree and beginning a graduate program or ones first job in industry. For fostering future scientists, physicians, and engineers, inspiration and a growth mindset are the key.

Photo credit:Chetan MenariaonUnsplash.

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Science Education and the Growth Mindset - Discovery Institute

When Katy Mathes and six of her family members learned they had a mutation on a BRCA gene that significantly raised their risk of breast cancer they underwent major surgery. But years later, the genetic testing company lowered the family's odds of getting the disease, Amy Dockser Marcus reports for the Wall Street Journal.

In August 2015, Mathes decided to get a BRCA test. Mathes' mother had been diagnosed with breast cancer at 49, and four of her aunts had tested positive for the BRCA gene, and "moved quickly to get surgery," Dockser Marcus reports.

Mathes and her sister, Tricia Leigh, also had positive tests. The test results showed that Mathes had up to an 84% risk of developing breast cancer by age 70 and up to a 27% risk of developing ovarian cancer by age 70. Among the general population, the odds of developing breast or ovarian cancer are 7.3% and 0.7%, respectively, Dockser Marcus reports.

But the two women grappled over the decision of whether to get surgery: Mathes wanted another child and her sister was breastfeeding her second child.

After consulting with additional doctors, Mathes eventually decided to have her ovaries and fallopian tubes removed, the same procedure her aunts, sister, and mother underwent. In addition, Mathes and her sister had double mastectomies.

"I treated my test results like the Bible," Mathes said. "There was no questioning the report."

But years after the initial test, Myriad Genetics, the molecular diagnostics company that did Mathes' test as well as her relatives', changed its classification of the BRCA variant Mathes has from "pathogenic" to "unknown significance," a move that Myriad said is very unusual.

By this point, Mathes and six of her family members had undergone surgery based on their test results. When the sisters learned the news, Mathes said, "My brain just shut off."

Susan Manley, SVP of medical services at Myriad and a board-certified genetic counselor, said, "We know these are very difficult situations. We make these reclassifications very carefully. The science is evolving." She added that changing a classification from harmful to uncertain "is a rare event, but I understand that rare is of no consolation to the patient when it happens to them."

BRCA tests are among the most common genetic tests in existence, Dockser Marcus writes, and genetic testing guidelines have expanded who should receive BRCA tests. Major genetic testing companies such as 23andMe, Ancestry, and MyHeritage now offer the tests for BRCA1 and BRCA2 genes.

However, not every lab agrees on the specific classification of a BRCA gene variant, Dockser Marcus reports. That's in part because there are "tens of thousands of BRCA variants" and not all of them necessarily carry the same level of risk for a patient, Dockser Marcus reports.

Fergus Couch, a professor at the Mayo Clinic, said some variants "have intermediate or moderate levels of risk, not full-blown risk." For a number of those variants, labs "are making a judgment call but that is not always clear to the public," Couch said.

Stephen Chanock, a geneticist at the National Cancer Institute, said, "[G]enetics is murky." He added, "It's not so simple as 'Doctor, do I have to worry or don't I have to worry?'"

According to Melissa Cline, a researcher at the University of California Santa Cruz Genomics Institute, and project manager of the BRCA Exchange, the analysis on the BRCA variant in the Mathes' family put a lot of weight on a 2011 paper that found the variant likely alters the BRCA2 protein, which can help suppress tumors.

Seth Marcus, a genetic counselor at Advocate Health Care who counseled Mathes' mother and one of her aunts, said he checked a public database to see how other labs classify the variant once he heard of Myriad's change. He said six labs still classify the variant as "likely pathogenic."

"In the end, you give the patient the data and the knowledge you know," he said.

Dockser Marcus reports that Myriad currently has 38 people in its database with the BRCA variant Mathes and her relatives have, 12 of whom come from Mathes' family. Mathes said that if she had known about the sample size, she and her husband may have asked more questions about whether surgery was appropriate.

Now, based on Mathes' family history and Myriad's classification change, Mathes' genetic counselor estimated her lifetime risk of developing breast cancer is 21%, Dockser Marcus writes.

"That is not high enough to make me remove organs," Mathes said. "I would have had another kid. I would have waited to do surgery" (Dockser Marcus, Wall Street Journal, 12/20/19).

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'I would have had another kid': How an imperfect gene test led to major surgeryand big regrets - The Daily Briefing

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A massive genome-wide analysis of approximately 200,000 military veterans has identified six genetic variants linked to anxiety.

Some of the variants associated with anxiety had previously been implicated as risk factors for bipolar disorder, post-traumatic stress disorder, and schizophrenia.

The new study further contributes the first convincing molecular explanation for why anxiety and depression often coexist.

There has been no explanation for the comorbidity of anxiety and depression and other mental health disorders, but here we have found specific, shared genetic risks.

This is the richest set of results for the genetic basis of anxiety to date, says co-lead author Joel Gelernter, a professor of psychiatry, of genetics, and of neuroscience at Yale University.

There has been no explanation for the comorbidity of anxiety and depression and other mental health disorders, but here we have found specific, shared genetic risks.

Finding the genetic underpinnings of mental health disorders is the primary goal of the Million Veteran Program, a compilation of health and genetic data on US military veterans run by the US Veterans Administration. The research team analyzed the programs data and zeroed in on six variants linked to anxiety. Researchers found five in European Americans and one only in African Americans.

While there have been many studies on the genetic basis of depression, far fewer have looked for variants linked to anxiety, disorders of which afflict as many as 1 in 10 Americans, says senior author Murray Stein, San Diego VA staff psychiatrist and professor of psychiatry and of family medicine and public health at the University of California, San Diego.

Researchers found some variants linked to genes that help govern gene activity or, intriguingly, to a gene involved in the functioning of receptors for the sex hormone estrogen. While this finding might help explain why women are more than twice as likely as men to suffer from anxiety disorders, researchers stressed that they identified the variant affecting estrogen receptors in a veteran cohort made up mostly of men, and that further investigation is necessary.

Another of the newly discovered anxiety gene variants, MAD1L1, whose function researchers dont fully understand, was also highly notable. Variants of this gene have already been linked to bipolar disorder, post-traumatic stress disorder, and schizophrenia.

One of the goals of this research is to find important risk genes that are associated with risk for many psychiatric and behavioral traits for which we dont have a good explanation, says co-lead author Daniel Levey, a postdoctoral associate.

This is a rich vein we have just begun to tap, says Gelernter.

The research appears in the American Journal of Psychiatry.

Additional researchers from the Veteran Affairs Connecticut Healthcare System; VA San Diego Healthcare System; and the University of California, San Diego contributed to the work.

Source: Yale University

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Genes explain why anxiety and depression go hand-in-hand - Futurity: Research News

Behnam Kamalidehghan,1,* Mohsen Habibi,2,* Sara S Afjeh,1 Maryam Shoai,3 Saeideh Alidoost,4 Rouzbeh Almasi Ghale,4 Nahal Eshghifar,5 Farkhondeh Pouresmaeili1,6

1Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Central Laboratory, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; 4Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran; 5Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran and Mens Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 6Mens Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

*These authors contributed equally to this work

Correspondence: Farkhondeh PouresmaeiliMens Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranTel/Fax +98 21-23872572Email pouresfar@gmail.com

Background: MicroRNAs (miRNA) play a key role in the regulation of gene expression through the translational suppression and control of post-transcriptional modifications.Aim: Previous studies demonstrated that miRNAs conduct the pathways involved in human reproduction including maintenance of primordial germ cells (PGCs), spermatogenesis, oocyte maturation, folliculogenesis and corpus luteum function. The association of miRNA expression with infertility, polycystic ovary syndrome (PCOS), premature ovarian failure (POF), and repeated implantation failure (RIF) was previously revealed. Furthermore, there are evidences of the importance of miRNAs in embryonic development and implantation. Piwi-interacting RNAs (piRNAs) and miRNAs play an important role in the post-transcriptional regulatory processes of germ cells. Indeed, the investigation of small RNAs including miRNAs and piRNAs increase our understanding of the mechanisms involved in fertility. In this review, the current knowledge of microRNAs in embryogenesis and fertility is discussed.Conclusion: Further research is necessary to provide new insights into the application of small RNAs in the diagnosis and therapeutic approaches to infertility.

Keywords: miRNA, female fertility, male fertility, piwi-interacting RNAs, piRNAs

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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The Importance of Small Non-Coding RNAs in Human Reproduction: A Revie | TACG - Dove Medical Press

Mass coral-bleaching events, which occur when high ocean temperatures cause coral to expel the algae that dwell inside them, are a relatively recent phenomenon. The first widespread bleaching event occurred in 1983, the year before Penn marine biologist Katie Barott was born.

The next one happened about 15 years later. And the intervals between them continue to shrink. In 2014, one bleaching event in Hawaii was so extreme that it carried over to affect corals into a second summer.

Theyre increasing in frequency, getting closer and closer, says Barott, an assistant professor in the School of Arts and Sciences Department of Biology. And the ocean temperature is getting warmer and warmer, so the severity is increasing, too.

Yet as dramatic as the phenomenon soundsand appearscoral bleaching does not always equate with coral death. Algae can return to corals once ocean temperatures cool, and scientists have observed formerly white corals regain their color in subsequent seasons.

In a multifaceted research project funded by a grant from the National Science Foundation (NSF), Barott and members of her lab are studying the mechanisms by which corals withstand the effects of climate change, which include not only the warmer temperatures that trigger bleaching but also acidification of ocean waters, a slower-moving creep with subtle yet significant consequences.

Barotts work, based in Kaneohe Bay on Oahu, Hawaii, focuses on two of the bays dominant coral species: rice coral (Montipora capitata) and finger coral (Porites compressa). Barott began working there during a postdoctoral fellowship at the Hawaii Institute of Marine Biology, conducting studies on which the new work is based.

Corals are invertebrate animals that live in large colonies, together forming intricate skeletons of varied shapes. To obtain food, they rely heavily on a symbiotic relationship with algae, which establish themselves within the corals tissue and produce food and energy for the coral through photosynthesis. A change in temperature or pH can upset this partnership, triggering the algaes expulsion.

That leaves the coral essentially starving, Barott says.

Since her postdoctoral days, Barott has been working with colleagues in Hawaii to monitor coral patches. After the 2014-15 bleaching event, researchers were surprised and heartened to find certain patches of corals didnt succumb to the bleaching, even those located directly adjacent to stark white corals. And many of those that did bleach bounced back within a month or so of the onset of cooling autumn temperatures.

At the time Barott was writing her NSF grant application, she planned to compare the differences between bleached and unbleached corals. Yet just as the grant kicked off in July, another bleaching event was unfolding in Hawaii.

That gave us this unexpected opportunity to go back to those same colonies to see if the ones that bleached last time were the same ones that bleached again this past fall, she says. And more or less we saw the same patterns: The ones that bleached last time bleached again this time and vice versa. That gives us compelling evidence that theres something specific about these resilient individuals that is make them resist bleaching, even in very warm temperatures.

While high temperatures triggers bleaching, acidity plays a key role in coral vitality as well. Lower seawater pH impedes corals ability to build their calcium carbonite skeletons, resulting in weaker, more fragile structures.

In earlier work, Barott had discovered that corals possess a pH sensor that can respond to changes in their environment. And, indeed, sea water acidity can vary widely in the course of a day, a season, or a year, swinging as much as 0.75 pH units in a day. Perhaps, Barott hypothesizes, coral have molecular tools that they use to withstand these daily fluctuations that they could also employ to contend with the gradual ocean acidification that is occurring as the concentration of CO2 in sea water rises.

Maybe there are some reefs that are going to be more resistant to ocean acidification because theyre used to seeing these really large daily swings and are sort of primed to deal with that challenge, she says.

Shes also curious about how bleaching impacts corals ability to tolerate pH changes more generally. Using molecular tools, she and her students are investigating the epigenetic changes that affect how genes are read and translated into functional proteins in the organisms. Such changes could occur much more rapidly than coral, a long-lived species, could evolve to deal with a changing environment.

In a variety of projects, the scientists are examining differences between species of coral, between species of the algal symbionts, and between populations located in different places in the Kaneohe lagoon.

Early results suggest differences between the rice and finger coral in their strategies for managing bleaching.

One really resists the bleaching, but if it does succumb then it fares a lot worse than the one that bleaches more readily, says Barott. That one seems to be more susceptible to losing its symbionts, but if it does it recovers fast and has lower overall mortality.

Barotts group is collaborating with others in Hawaii to see if hardier corals could be propagated to rebuild damaged reef communities.

Were at the proof-of-principle stage, she says, where were trying to figure out if some of these differences are heritable.

While some of that work is being completed in Hawaii, carefully tended tanks in the basement of the Leidy Laboratories of Biology allow Barott and her students to complete experiments in Philadelphia on corals. Using both corals shipped from the field and sea anemones, a useful stand-in for corals due to their ease of care and rapid reproduction, the lab has been tracking the impacts of temperature and pH stress on energy systems, genetics, and even the microbiome of corals, the bacteria with which the corals and algae cohabitate.

The surface of coral is analogous to the lining of your lungs or intestines, Barott says. Its covered in cilia, its got a mucus layer over the top of it, and there are tons and tons of bacteria that live in that mucus layer. We think those bacteria are playing a role in the health of the coral, but we dont know if its playing a role in their temperature sensitivity, so thats something well be looking at.

With this whole organism approach, Barotts aims to inject some optimism and scientific rigor into what is a largely dire outlook for corals worldwide. Encouragingly, she notes, this years bleaching event in Hawaii was much less severe than predicted, and corals that had bleached in 2014 were less strongly affected by this years event.

These reefs are facing a lot of impacts, not just from climate but also from local development, sedimentation, nutrient pollution, she says. Our hope is to predict how corals will respond to these challenges and maybe one day use our findings to assist them in rebuilding resilient reefs.

Katie Barott is an assistant professor in the University of Pennsylvania School of Arts and Sciences Department of Biology.

Much of the work described above is funded by the National Science Foundation (Grant 1923743).

Link:
Coral reef resilience - Penn: Office of University Communications

The new year new decade is afoot. What are you hoping to do better moving forward?

Usually its a self-help extravaganza. Hit the gym and shed a few pounds? Or maybe fix certain behavioral traits, with a philanthropic tie-in. Swear jars anyone?

Unfortunately, as January gym goers know, the most well-intentioned resolutions often fall by the wayside tempered by the crushing weight of existence!

No doubt, honoring resolutions is a challenge. But theres one resolute contingent of farmers that not only aspire, but deliver yearly. These are royalty, a select group of hyperyielders that squeeze every last bit of productivity out of their crops.

Appropriately named with a predictable focus on a certain ubiquitous crop the National Corn Yield Contest is organized by the National Corn Growers Association.

The reigning king is David Hula of Charles City, Virginia. In a carnival-like atmosphere often dubbed the corn wars, the Hula dynasty is unmatched.

His irrigated yield of 616 bushels per acre (bu/acre) this isnt a typo in an industry that averages 175 bushels per acre (from a diminutive 25 bu/acre in 1910) is jaw-dropping. Even more astonishing is the venue: a farm outside the Corn Belt, lacking the rich prairie soils ordinarily well-suited to the challenge.

But whats the point of this yield obsession? Is it all just chest pounding posturing by farmers seeking alpha status among their peers?

Bragging rights plays a part. But it runs beyond pride.

As expected, competition spurs and diffuses innovation. Consider the space race (OK, maybe not so friendly) between the U.S. and the former USSR, the first in flight race, or the pursuit of the land speed record. One-upmanship fuels advancement.

On occasion, it also shatters records long held as unbreakable. Consider Olympian Bob Beamons leap of the century in 1968 a feat that rewrote the record books. After breaking the previous long jump record by nearly 22 inches initially beyond the limits of the measuring equipment on hand he broke down after realizing the enormity of his accomplishment.

Similarly, Hulas 2019 entry decimated the previous corn yield record of 542 bu/acre, and set a new aspirational benchmark for productivity.

Its also instructive on another level. Despite a cavalcade of improvements, from hybrid seeds, to high density spacing, to uniform germination, to nutrition, to ag protectants, to biotech applications, were still not fully utilizing the genetic potential embedded in the humble corn seed.

But surely, were reaching a point of diminishing returns. That yield curve is going to flatten. Yet theres no evidence were even remotely close to a plateau. Indeed, Hula thinks we can attain yields of 800 to 850 bu/acre out of the bag. Its just a matter of providing the proper regimen to maximize genetic potential. A blessed union of nature and nurture.

So agronomy how the plant is tended to in the field plays a critical role in squeezing out more yield. But is nature increasingly going to be the dominant factor? As we strive toward topping out yields, its increasingly mission critical need to decipher an old enigma genetics.

That complexity has historically discouraged researchers from searching for the silver bullet a gene solely responsible for yield. Large investment, minimal success. So weve stuck with simpler applications, like transgenic (GMO) herbicide tolerance (Roundup Ready) and/or Bt proteins (built in insecticides). These arent necessarily yield-boosting on the surface. In the absence of pests and weeds, they can actually cause a yield depression. But we dont grow corn in a pest-free vacuum. In the real-world, these GMO applications do at least maintain potential yield when plants are under pressure.

Despite past challenges,a team of researchers recently identified a single gene responsible for up to 10 percent boosts in corn yield, largely independent of growing conditions. All they needed to do was tack on a new promoter, a central switch box of sorts that acts like on/off switch and volume control. Turn on that boombox 24/7, max out the volume, and plant physiology kicks in. The leaves grow larger and photosynthesize, translating to better field performance. Its like enabling a cheat code for growth.

Though the promoter and gene are already found in corn, the method used to join them together falls under the traditional definition of a GMO so expect unjustified regulatory hurdles at every turn.

Most assuredly, the next frontier in research (that will invigorate the hyperyielders of the future) is at the molecular level, paired with field optimization. Unprecedented gains are in the cards, if the neo-luddities dont evangelize a bygone past and stifle the gears of progress.

While the 10th Commandment says thou shalt not covet, everyone should be shamelessly envious. With more mouths to feed, we need to address the existential threat of food security, population growth, and environmental stewardship. David Hula and company model an algorithm that we should all emulate; the proof is in the harvest.

Tim Durhams family operates Deer Run Farm a truck (vegetable) farm on Long Island, New York. As a columnist and agvocate, he counters heated rhetoric with sensible facts. Tim has a degree in plant medicine and is an Associate Professor at Ferrum College in Virginia.

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Durham: Hyperyields on the horizon -- the competition and innovation of it all - AGDAILY

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Reasons to buy this Report: Achieve an up-to-date understanding of the area, with a comprehensive reference of key products within the gene therapy landscape, compared across technology-specific relevant characteristics such as editing mechanism and delivery vector. Conduct competitive analysis using indication-specific, side-by-side comparisons of the latest data for key gene therapy products in the strategically relevant areas of eye, blood, and liver. Conduct strategic analysis using an overview of gene therapy specific considerations for evaluating and developing gene therapy products the CRISPR patent space, emerging regulatory trends, innovation leaders and the interests of pharma in gene therapy.

Table of Contents in this Report:1.1 List of Tables 71.2 List of Figures 82 Introduction 102.1 Gene Therapy Definitions 102.2 Report Coverage the Emerging Gene Therapy Pipeline 112.3 History of Gene Therapy 122.4 Limitations of Gene Transfer 132.5 The Development of Targeted Gene Editing 132.6 Overview of Gene Editing Platforms 132.6.1 Zinc Fingers (1996) 132.6.2 Transcription Activator-Like Effectors (2011) 142.6.3 The CRISPR/Cas System (2013) 152.6.4 Effectors for Targeting Domains 192.6.5 Comparison of Gene Editing Systems 192.6.6 Summary of Gene Editing Systems 192.7 Overview of In Vivo Gene Therapy 212.7.1 Editing is Dependent on Cell Type, Stage, and Repair Pathway 212.7.2 Delivery 212.7.3 Emerging Safety Concerns with Editing Platforms 242.7.4 Editing Products are Reliant on the Target Cells Cycle Stage and DNA Repair Machinery 272.7.5 Advantages of Gene Editing over Gene Transfer 282.7.6 Integration into Safe Harbor Sites 282.7.7 The Increasing Complexity of Gene Therapy 302.7.8 Summary of In Vivo Gene Therapy 313 Gene Therapy Near Term Product Pipeline 333.1 Leber Congenital Amaurosis 333.1.1 Unmet Need 333.1.2 Molecular Genetics 333.1.3 Luxturna (Voretigene neparvovec) 333.1.4 Editas Medicine: EDIT-101 353.1.5 Trial Design 363.1.6 EDIT-101 and Off-Target Effects 373.1.7 The Potential Advantage of EDIT-101 is the Longevity of its Therapeutic Effect 373.1.8 Summary LCA 383.2 Choroideremia 383.3 Hurler Syndrome (MPS I) 393.3.1 Key Clinical Studies 403.3.2 Regenex: RGX-111 403.3.3 Sangamo Therapeutics: SB-318 403.4 Hunter Syndrome (MPS II) 413.4.1 Unmet Need 413.4.2 Sangamo Therapeutics: SB-913 413.4.3 Immusoft Corporation: Cell Therapy 433.5 Sanfilippo Syndrome (MPS III) 433.5.1 Lysogene: LYS-SAF302 433.6 Summary MPS Disorders 443.7 Hemophilia 443.7.1 Hemophilia A 463.7.2 Summary Hemophilia A 503.7.3 Hemophilia B 513.7.4 Summary Hemophilia B 533.8 Hemoglobinopathies 543.8.1 Beta Thalassemia: Unmet Need 543.8.2 Beta Thalassemia: Molecular Genetics 553.8.3 Sickle Cell Disease: Unmet Need 563.8.4 Sickle Cell Disease: Molecular Genetics 563.9 Cellular Therapies for Hemoglobinopathies 573.9.1 Blue Bird Bio: BB-305 (LentiGlobin) 573.9.2 Sangamo: ST-400 603.9.3 CRISPR Therapeutics: CTX-001 613.9.4 Summary: Cellular Therapies for Hemoglobinopathies 623.10 Duchenne Muscular Dystrophy 633.10.1 Unmet Need 633.10.2 Molecular Genetics 633.10.3 ExonDys 51 Sarepta Therapeutics 643.10.4 Solid BioSciences: SGT-001 663.10.5 Exonics Therapeutics: CRISPR Approach 673.10.6 Summary Duchenne Muscular Dystrophy 684 Competitive Landscape 694.1 Regulatory Considerations for Developing Gene Therapy Products 694.1.1 Product Characteristics 694.1.2 Clinical Study Design for Gene Therapy Products 694.1.3 Disease specific guidance 704.1.4 Reimbursement and Payment 714.1.5 Summary Regulatory Considerations 724.2 Intellectual Property CRISPR/Cas 724.2.1 Licensing, Exploitation, and MPEG Pool 744.3 Company Analysis: Gene Editing Companies 754.3.1 Sangamo Therapeutics 754.3.2 CRISPR Therapeutics 794.3.3 Casebia Therapeutics 814.3.4 Editas Medicine 824.3.5 Intellia Therapeutics 844.3.6 Homology Medicines 864.4 Company Analysis: Pharma 874.4.1 Amgen 874.4.2 Gilead Sciences 874.4.3 Novartis 874.4.4 Sanofi 884.4.5 GlaxoSmithKline 884.4.6 Pfizer 885 Appendix 895.1 References 895.2 Report Methodology 98

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2020 Emerging Gene Therapies Market- Trends within the Technological, Clinical, Regulatory and Competitive Landscape to 2022 - Instanews247

NEW YORK, Jan. 07, 2020 (GLOBE NEWSWIRE) -- BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, announced today that Chaim Lebovits, President and Chief Executive Officer, will provide a corporate overview at the 2020 Biotech Showcase, being held on January 13-15, 2020 at the Hilton San Francisco Union Square in San Francisco, California.

Mr. Lebovits will also present at the 3rd Annual Neuroscience Innovation Forum, taking place on January 12, 2020, at the Marines Memorial Club in San Francisco. Additionally, Ralph Kern M.D., MHSc, BrainStorms Chief Operating Officer and Chief Medical Officer, will participate on aRare & Orphan Diseases Panel.

Meetings

BrainStorms senior management will also be hosting institutional investor and partnering meetings at the 2020 Biotech Showcase conference (https://goo.gl/SGFm62). Please use the Investor contact information provided below to schedule a meeting.

About NurOwn

NurOwn (autologous MSC-NTF cells) represent a promising investigational approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors. Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. NurOwn is currently being evaluated in a Phase 3 ALS randomized placebo-controlled trial and in a Phase 2 open-label multicenter trial in Progressive MS.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (U.S. FDA) and the European Medicines Agency (EMA) in ALS. BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six sites in the U.S., supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. For more information, visit BrainStorm's website at http://www.brainstorm-cell.com.

Safe-Harbor Statement

Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could causeBrainStorm Cell Therapeutics Inc.'sactual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorms need to raise additional capital, BrainStorms ability to continue as a going concern, regulatory approval of BrainStorms NurOwn treatment candidate, the success of BrainStorms product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorms NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorms ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorms ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available athttp://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

CONTACTS

Corporate:Uri YablonkaChief Business OfficerBrainStorm Cell Therapeutics Inc.Phone: 646-666-3188uri@brainstorm-cell.com

Media:Sean LeousWestwicke/ICR PRPhone: +1.646.677.1839sean.leous@icrinc.com

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BrainStorm Cell Therapeutics to Present at the 2020 Biotech Showcase and 3rd Annual Neuroscience Innovation Forum at JPM Week - GlobeNewswire

The start of a new year is the perfect time to prioritize self-care and set health and wellness goals, so make 2020 your happiest yet with a new, enhanced version of you. Use this guide to find the doctors, therapists and practitioners that can help you look and feel your best.

When diet and exercise just wont provide the results youre looking for, visit Skiin Anti-Aging Lounge. They offer the only procedure that builds muscle. EMSCULPT has been proven safe and effective by the most reputable scientific methods. The procedure induces strong muscle contractions with Hifem (high-intensity electromagnetic) technology not achievable through voluntary contractions. This builds muscle and creates a sculpted, toned physique. Other services like CoolSculpting and Exilis also help clients reshape their bodies through nonsurgical, noninvasive methods. Skiin is the first and only CoolSculpting advanced education center in the nation. Another first: Exilis is the first and only device to combine radio frequency and ultrasound to tighten skin through heating and cooling.

Your face is the first place to show signs of aging, but there is a way to take back those years. Dr. John Yousif has received several awards for his research in facial aging. He has been practicing plastic and cosmetic surgery for over 30 years and has even pioneered new techniques like the Gortex Midface Lift and the Hyoid Suspension Neck Lift. At both Sier Medi-Spa and Ascension in Mequon, he offers surgical and nonsurgical procedures to reverse the signs of aging. All of the types of facelifts offered are long-lasting and natural looking, leaving clients feeling like a younger version of themselves.

RELATED The Homebody's Guide to Winter in Milwaukee

Aqua, under the direction of Dr. Christopher Hussussian, is a full-service salon, spa and med spa offering a wide range of services in a luxurious setting on Pewaukee Lake. Whether you are hoping to change the way you look or feel or both Aqua has a solution to enhance your skin and hair for both body and face. New services for the new year include hair restoration for both men and women using PRP (platelet-rich plasma) with biotin and a new weight-loss program using the HCG hormone. They also offer advanced laser hair removal, Clear Lift skin tightening, ThermiVa and CoolSculpting, a popular nonsurgical fat cell reduction with lasting results. A consultation can help you decide what services would work best to achieve a healthier, happier version of yourself.

Serving the Lake Country area, Dr. Tom Stamas is helping people put their best face forward, one smile at a time. He specializes in smile design, a full dental restoration and reconstruction for those suffering from tooth damage or loss, or for those looking to fix crooked, worn or yellowed teeth. During your personalized consultation, Stamas and his team will help you select which treatments will bring your smile to life. Dental treatments like bridges, dental implants, crowns and state-of-the-art diagnostic tools are all available to restore the health, function and appearance of your smile. Youll feel good about the natural-looking results, and your self-esteem will get a boost too.

What if you could use undesired fat from your belly to get rid of the bags under your eyes? Sounds too good to be true, right? Anew Skin and Wellness has a procedure that is done right in the office with long lasting results. The nano-fat transfer removes a small amount of fat with micro liposuction. That fat is harvested for re-injection to the appropriate areas of the face, neck, earlobes, hands and thighs. It can also be used to plump thin lips, smooth cellulite and scars and restore skin elasticity. The nano-fat transfer is safe, effective, economical and helps clients look their best. The in-office procedure provides long-lasting results because the bodys stem cells can turn the aging skin into new, rejuvenated skin. Its the natural way to tighten and smooth skin, allowing you to turn back the clock without a surgical face- or neck-lift.

RELATED Your Guide to the New and Improved Wauwatosa Village

Dr. Arvind Ahuja has provided neurosurgical and endovascular care in southeastern Wisconsin for more than 20 years for brain, spine, artery and peripheral nerve conditions. Whether patients come to Neurosurgery and Endovascular Associates for neck and/or arm pain, back and/or leg pain or headache, the first step is always diagnostic testing to determine the cause of the pain, rather than just treating the symptoms. Often through treatments like medication, steroid injections, physical therapies and if need be surgery, patients achieve improved functioning and long-term relief. Ahujas specialized training in the nervous system is incredibly effective in treating spinal conditions, and his treatments give patients the opportunity to live a happier and morefunctional life.

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How These Practitioners Can Help with New Year, New You Goals - Milwaukee Magazine

Cynata Therapeutics (CYP) has received a research and development tax incentive refund of $1,891,795 for the 2018-2019 financial year.

This tax incentive refund increases the company's cash position which stood at $9.2 million at the end of the September quarter.

It also enables further resources to be invested towards Cynata's phase 2 clinical trial programs for the critical limb ischemia (CLI) (reduced blood flow) and osteoarthritis products.

This will be alongside the anticipated phase 2 trial for CYP-001 in graft-versus-host disease which will be conducted by Fujifilm.

CLI is an advanced stage of peripheral artery disease which is the narrowing of the arteries in the limbs, typically in the lower legs.

It results from severely impaired blood flow which can cause pain, tissue damage, and gangrene.

Around 25 per cent of CLI patients who are unable to undergo surgery to remove the affected area, often an amputation, will die within a year of diagnosis.

Cynata' Cymerus mesenchymal stem cells (MSCs) have been successfully tested in a mouse model of CLI.

Muscles on the ischaemic leg were injected with Cymerus MSCs or a control.

Over a four-week follow-up period, the return of blood flow was measured and in animals treated with Cymerus MSCs blood flow in the injured limb was significantly higher at every point compared to the control.

MSCs are an adult stem cell found in a wide range of human tissues including bone marrow, fat tissue and placenta.

They are multi-potent which means they can produce more than one type of cell, for example they can differentiate into cartilage cells, bone cells and fat cells.

MSCs have been shown to ease regeneration and effects on the immune system without relying on engraftment (when the transplanted cells start to grow and make healthy cells).

The research and development tax incentive is an important Australian Government program that encourages companies to engage in research and development benefiting Australia by providing a tax offset for eligible activities.

Cynata's share price is up a steady 4.82 per cent with shares trading for $1.20 apiece at 3:29 pm AEDT.

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Cynata Therapeutics (ASX:CYP) receives R&D tax incentive refund of more than $1.8M - The Market Herald

At the Francis Crick Institute in central London, Andrew Rowan is labelling test tubes filled with chunks of human brain. The pieces are brown and spongy-looking, as if they would be springy to the touch; the rest of the brain sits to his right, in a large, smoking polystyrene box of dry ice. On a shelf above him is a row of food blenders. There is a curious smell in the laboratory not entirely unpleasant, but the kind one chooses not to ask about.

Rowan is excited. This particular brain is fresh from an autopsy conducted the previous week, and the donor a man in his 60s was found to have unforeseen tumours in his lower abdomen. We were prompted that the case would be mainly brain disease, so we were surprised at the extent of it elsewhere, Rowan says. Hopefully it will give us some clues.

As a senior research scientist at the institutes Cancer Evolution and Genome Instability Laboratory, Rowan has handled his fair share of human tissue to the extent that he can tell by eye which of his dissected samples are cancerous and which are not. (Theyre often different in colour, morphology, appearance.) When he has finished organising these 100 samples of brain some are set in liquid paraffin so they can be studied at room temperature, others kept frozen for longer-term study he will select the best quality ones for genetic sequencing. As for the rest of the patients organs, thats where the blenders come in.

We're making a slurry soup of matter, he says. We will then conduct something called deep sequencing we try and make sure we are picking up the total number of [genetic] mutations from that sample. All tumour tissue that is left over is collected for this, as we want to make sure nothing gets wasted. Tools used for liquidising the tissue before it is sequenced can only be used once owing to the risk of contamination, so Rowan gets his homogenisers (standard food blenders) for cheap from Argos.

It sounds macabre, but its important research. Rowan is one of a team of experts working on a new study into the way tumours spread. The Posthumous Evaluation of Advanced Cancer Environment (PEACE) study is an ongoing project, funded by Cancer Research UK, that follows a simple premise: terminally ill cancer patients agree to donate their body to science after they die, allowing researchers to perform autopsies to collect their blood and tissue for testing.

Until recently, scientists working in labs such as this one have relied upon cancer tissue taken from surgically removed biopsies a small section of disease taken from one site while the patient is alive. But the scope for experimentation with these samples is limited, and reveals very little about the wider ecosystem of the disease inside a patients body. Thanks to the volunteers signed up to PEACE, the team is now able to access entire, fresh organs from multiple sites in a patients body. It is the only study like it in the world, and the researchers believe the discoveries made from it could be revolutionary both in furthering scientific understanding of cancer, and in the continuing quest to find a cure.

Dr Andrew Rowan in the Francis Crick freezer farm, where tissue is stored at -80C

Sebastian Nevols

Some of the first recorded human autopsies are thought to have taken place in Egypt around 300 BCE, and throughout history medics, artists, philosophers and legal authorities have all taken inspiration or evidence from human and animal dissections. But while post-mortems remain relatively common, and are a legal requirement in many countries when a death is unexpected or suspicious, there has been a steep decline in hospital autopsies for research purposes over the past few decades. This is in part due to a misconception that, given the advances of modern technology, such apparently medieval practices are no longer useful. It is also a subject that makes many people squeamish including, PEACE co-ordinators suggest, doctors and clinicians.

When we were medical students, we used to go to the mortuary frequently to understand why patients died of that particular disease, says Charles Swanton, one of the Cricks leading cancer geneticists. Now, I think there is a sort of view that we dont need to know that it's not terribly important and its not going to tell us very much.

As group leader of the Cancer Evolution and Genome Instability Lab, Swanton first broached the idea for PEACE during a conversation with his colleague, Mariam Jamal-Hanjani, in 2014. I remember he walked into the lab late one night when I was still working and said You should set up a patient autopsy, Jamal-Hanjani recalls. Id only just joined his lab and I thought Thats a bit controversial. But hed planted the seed, and we just kept it going from there.

It took several more conversations for the pair to convince their colleagues, but by November 2016 they had managed to gather the resources and ethical approval required for the study. For decades, science and medicine had been waiting to be invigorated with new technologies, Swanton says. Probably part of the reason why nobody's been terribly interested in studying death is because, until recently, we've lacked the means to probe it.

One in two people will develop cancer in their lifetime, according to figures from Cancer Research UK. And while research has advanced in leaps and bounds in terms of finding drugs and improving our understanding of the disease, doctors still dont know the answer to one of the biggest questions: why do patients die? There is some degree of complacency, says Jamal-Hanjani. If a patient's got lung cancer or any type of cancer and then they die clinicians will presume that they have died of their cancer. But thats really a failure on our part.

In patients with cancer, there are some obvious reasons, Swanton says. Organ failure comes into it, [or] if you've got a brain metastasis patients can develop blood clots. But there are many other, much more subtle causes of death we know next to nothing about.

One interesting finding to come out of the PEACE study already is that the degree of cancer cells found within patients at death can vary by several million, demonstrating how some peoples bodies can live much longer than others when faced with tumour spread. A lung cancer patient, for example, may have a tumour containing between 100 and 300 million tumour cells at the point of diagnosis. By the time they die, that figure may have reached one trillion.

But what we are finding is that some patients really don't have much of the disease in their body at all, and so we really don't know how they die, says Swanton. There may be complex metabolic syndromes going on, it could be immune failure we just don't know. And we hope that PEACE can start to illuminate some of these questions.

A sample of metastatic bone tissue

Sebastian Nevols

With so much money being pumped into cancer research (Cancer Research UK alone had an income exceeding 670 million in 2018-19), one common question researchers face is why we havent found a cure. While cancer drugs often work for months, and sometimes years, drug resistance is the norm rather than the exception, Swanton says. Although there are thousands of treatments in development, the prospect of a one-stop drug that could help all cancer patients is a particular challenge, he says, because of the way cancer cells evolve.

In many living organisms, evolution happens in a linear pattern. For instance, a mutation will form in a cell that becomes replicated several times until all the cells contain the same mutation. If that were the case with tumour cells, one could imagine it would be possible to wipe out the entire tumour with a single drug because every cell in every tumour would essentially be the same. But we now know that these tumours aren't developing in a linear fashion at all they are evolving in a branch manner, Swanton says. While some cells contain mutations number one and two, others will have one, four and five; and others could have mutations one, six and seven the evolution of the cells becomes increasingly unpredictable and complex. This, he says, is a major reason why the drugs we use in the clinical setting fail.

The PEACE project is trying a new approach, by looking at the wider human biology, beyond a specific tumour site hence the need for access to the full human system. In our diagnostic practice we tend to get a biopsy from one metastatic site [an area to which a tumour has spread] it's very rare that we ever get more, says Swanton. But if you could sample a lung and a brain and an adrenal gland and the liver you could start to understand how the tumour cells start to react within the local environment. Because you cannot understand evolution unless you understand the species in this case cancer but also the environment in which it's evolving.

Through PEACE, Swanton and his team hope to develop their understanding of how and why tumours spread through the body, and attempt to find genetic patterns that might help explain cancer progression. A major purpose of the study is to collect enough material from autopsies to create a longstanding database of samples, which can hopefully be used in cancer research for decades to come.

The study is already producing results. In one paper, published in the journal Nature last year, the team looked at a patient with lung cancer. Analysing samples from different sites in the body to which the cancer had spread, they were able to identify genetic abnormalities. They then retrospectively analysed blood samples collected prior to the patients death, and detected the same genetic abnormalities. This showed us that blood could be used as a predictor of genetic changes that may be involved in cancer progression and metastasis, Jamal-Hanjani explains.

Another study, published in Cell, looked at two patients with kidney cancer one who died six months after diagnosis and another who died 17 years after diagnosis. Again, researchers analysed samples from different sites in the body. They identified distinct evolutionary patterns in each patients cancer progression, indicating that the genetic pattern in which a cancer evolves and spreads may offer clues to an individuals clinical outcome.

This means scientists may one day be able to predict a patients experience with a particular type of cancer based on their genes. It could help doctors accurately prescribe drugs they know are more likely to benefit the patient, and stop wasting time on those that wont eventually tailoring each persons treatment plan to their genetic make-up. We know that the environment in which a cancer grows plays a crucial role in its behaviour and progression or regression, Jamal-Hanjani says. Its by knowing how this genetic landscape changes in time, and how it leads to increasing disease burden, that we can understand better why drugs dont work and why patients eventually die from their disease.

Oncologist Mariam Jamal-Hajani, co-leader of the PEACE project

Sebastian Nevols

The PEACE researchers work usually starts with a phone call. Sometimes this comes with forewarning: the patient is unwell, it wont be long now. Other times, the death is more sudden: at home in the middle of the night, or in another hospital, and the team must make arrangements for autopsy as soon as possible.

As co-leader of the project, it is Jamal-Hanjanis task to make this happen. If I learn of a patients death, the next 24 hours are mayhem, she says. My team is communicating throughout the night. We'll be sending emails even at midnight saying: Where are we going to collect tissue from tomorrow? What did the last scan show? Have we got a slot with the mortuary? Have we found an undertaker?

For the autopsy to go ahead, the researchers must first secure copies of the patients consent form and death certificate. Jamal-Hanjani must also make sure there is no-one contesting the cause of death if there is, it will complicate matters, although a coronary post-mortem can take place alongside the autopsy. She aims to strike a balance between practical concerns booking a slot in the mortuary, bringing together the required staff and a sense of duty to the patients and their family. We try not to delay the process because families want it to happen fast, she says. The study is not suitable for some people from Jewish or Muslim backgrounds, since their religion may require a rapid burial. But sometimes we've been able to accommodate for that.

Once permission has been secured, a team of clinicians, research assistants and mortuary technicians meets to gather the equipment needed: liquid nitrogen to freeze fresh tissue samples at -80C, chemicals to preserve tissue into blocks, a dissection kit and medical packaging. The process itself can be brutally physical. Chests are cracked open to access lungs. Organs are removed in blocks, often the lungs and heart combined. A pathologist removes a kidney, slices it. The next person in line dissects it a little more. Another person puts it in the liquid nitrogen tank, and someone else labels it. The system is an exacting and precise conveyor belt, from the point of death to the moment the samples are brought back to the lab, with every piece barcoded and tracked.

Well-preserved tissue can last for many years often for as long as a study has ethical approval and so the researchers hope to build up a bank of good-quality samples to use in future work as well.

In the mortuary, the noise from the 24-hour flurry of emails, phone calls and planning comes to an abrupt stop. The mood is sombre, respectful. Theres no laughter, there's no discussion, says Jamal-Hajani. We just know that this is what our patient wanted, and we all get on with our business. The researchers are looking for evidence of tumour spread, so major tumour sites will be collected, but, unlike any kind of surgery when the patient is alive, the team will also collect some healthy tissue from surrounding regions for the purposes of comparison.

Everything else is replaced as it was inside the body, and the patient is sewn back up. Attention to detail and duty of care take priority; even in cases where the donors skull must be opened for access to the brain, pathologists will make their incision at the back of the patients neck, so that once the procedure is over no scarring can be seen.

People have asked me, What kind of scars will I have, what colour stitching will you use? says Jamal-Hanjani. She tells them that the stitching is subcutaneous under the skin and uses flesh-coloured thread. If its not a cremation, families sometimes haven't had time to view the body, and they'll do it after an autopsy, so we'll try to minimise any incisions, she explains. But beyond this, she takes such care because she believes the team is so privileged. Some patients say, When I'm dead, I'm dead I don't care what you do with my body. But for me, that respect and dignity that we try to maintain when patients are alive that's got to follow through even after death.

Human tissue, fixed for pathology analysis

Sebastian Nevols

The first person Jamal-Hanjani recruited to the PEACE study was 19 years old. A Cambridge University undergraduate studying politics, philosophy and economics, she was at the top of her class and had a bright future. But cancer is not one to discriminate, and, despite her youth, intelligence and ambitions, she died within 18 months.

That first conversation really stayed with me, Jamal-Hanjani remembers. She was so bright, so interested in what we were doing. She asked real specific questions. She wanted to know what would happen to her eyes. Would her body be scarred, would there be bruising? She cared about the research, but also what her family would be left with.

Approaching a patient about signing up to the study can be difficult. In the case of this young woman, I told her that donating herself to medical science could help us to learn why some patients develop drug resistance and why, in her case, we didnt have any treatment options that would work for her, Jamal-Hanjani says. I made it clear that she wouldnt benefit from any of this herself.

In the end, the team never did get to fulfil the students wish and go through with her autopsy. At that time, the project leader was heavily pregnant, and the study was in its early stages and had few resources. But the patient had also got married shortly before her death, and the sense was that her husband was not comfortable with the agreement. It was bittersweet, Jamal-Hanjani says. I really do feel strongly that we must try to keep the patients living wish. I couldnt do that for her, but I feel comfortable that I respected the wishes of her family whom she loved.

More than this, Jamal-Hanjani says the student gave her the push she needed in those early stages of the project. She taught me that there are patients out there who want to selflessly give like this because they want to help research, because they know thats how other patients might benefit in the future, she says. Before then, I had patients come to me and ask if there was anything they could do for instance, donate their organs after death. With her, it was the first time I could say: Heres a study you could be involved in. I have something for you. We may not have collected samples from her, but at that point in my life she really motivated me to make it happen for others.

A box of slides containing slices of preserved human tissue

Sebastian Nevols

Usually, a patient is approached to join the study by Jamal-Hanjani or a fellow clinician, but sometimes individuals get in touch themselves after hearing about it through their doctor or online. To date, the project has recruited around 190 patients across the UK and completed more than 100 autopsies. Initially starting as a collaboration between the Francis Crick Institute and the nearby University College Hospital, the programme has expanded to include ten sites across Britain, including Glasgow, Sheffield, Southampton and Birmingham. The study is potentially open to anyone with tumours that have spread, but Jamal-Hanjani is cautious about who she recruits, and has turned people down if there is a chance their tissue would not be useful for the study.

On the flipside, there have been cases where patients are included who have not had the chance to personally consent while alive. The study was set up with doctors and scientists, but also really heavy and ongoing input from patient advocacy groups, she explains. The feedback we had was that patients still want to be part of this study but maybe they're physically not well enough to come and give consent. At a certain point, a patient may have given power of attorney to a close relative so a family might give consent on the patient's behalf. Jamal-Hanjani admits it is difficult to that sort of patient down.

Every funded research project has targets. On paper, PEACEs aim is to perform 500 research autopsies in five years. In reality, it is not on track. It's rather ambitious because, logistically, this study has been a nightmare, says Jamal-Hanjani. These patients can die anywhere. At home, in a hospice, in another hospital. They can be hours away from where we perform the autopsies. We don't always know when a patient has died, simply that interaction with the family's relatives after death can be incredibly difficult for us and for them.

Theres also the issue of funding. PEACE was originally promised 5 million from Cancer Research UK spread over five years, but this was unexpectedly dropped to 4 million. According to Jamal-Hanjani, the amount is only enough to cover the basic infrastructure for the setup of the study any analysis of samples relies on additional funding. The current round of financial backing ends in October 2021, and the team is desperately hoping to keep going for another five years beyond that. It's a horrible thought that weve got fixed funding for a certain number of autopsies, says Swanton. It's a terribly cold measure.

More than that, of course, the future of PEACE will depend on the continued willingness of volunteers to participate. Patients have been our greatest advocate here, not doctors or lawyers, says Swanton. It's been patients who have really wanted this to happen. And theyve been incredible with their generosity in enabling us to do this. We really owe everything to them.

Thomas Filson, a cancer patient who has signed up to the PEACE trial, with his dog, Petal

Sebastian Nevols

The discoveries coming out of PEACE are too late to help Thomas Filson, but the decision to donate his body to the study was a no-brainer nonetheless. Why? Well youve just seen two reasons why, he says, indicating the two small boys scampering around him. Its a warm day, and the 70-year-old is sitting in an armchair at the home he shares with his wife, Lynn, in Ashford, Surrey. The boys two of his four grandchildren are making a convincing case for ice-cream. Thomas is stoic, a straight-talking former carpenter with a star dangling unexpectedly from his left earlobe (his daughters belly button ring, he explains just because she didnt think Id dare). On his wrists are piles of multicoloured woven bracelets and charity bands. He very much embraces life but doesnt take it too seriously certainly not since his diagnosis six years ago.

Thomas was just half a year from retirement when he was diagnosed with lung cancer. Then, as if to demonstrate how unfair life can be, Lynn's breast cancer was identified. She has since made a full recovery, but spent the first few months of Thomass diagnosis sick from her own chemotherapy.

From a lifetime of smoking and working with wood, Thomas says his lungs have had a fairly stressful time with dust and muck and everything. They told me at 50 I had to stop smoking because I'd kill myself. Then of course, years later, life comes and surprises you.

Like several PEACE recruits, Thomas was already signed up to a different cancer research trial run through the Crick called TRACERx, which studies the biopsies of tumours surgically removed from living patients. Being part of active research appeals to him, so he was an ideal candidate for researchers to bring up the subject of autopsy. I've been a carpenter all my life dirt's dirt, isnt it? he says. I've got a fairly rounded view of life and death. I'm a Christian, don't get me wrong, but I think of myself as just another ant, running over this planet destroying it. So I said Yes, let's go for it because there is no cure for this type of cancer, what have I got to lose? Let's give something back.

Behind Thomass upbeat demeanour is a man whose body is increasingly weak. He can no longer walk very far, and his skin has suffered since his last round of immunotherapy drugs. But every morning, he takes out his deaf Staffordshire bull terrier out to the waterfront near his house. The two of them will sit, sometimes for a couple of hours, and give space to their thoughts. I don't get emotional because I think I'm going to die, but sometimes I get a bit frustrated because I can't do what I want to do, he says. I very rarely get depressed, because I think my life has been good. But it's easy to die; its harder for your family or your partner.

For Lynn, the road ahead will no doubt be difficult. But she agrees Thomas is making the right choice. Tom and I we're at the stage now where if I woke up tomorrow and he was gone, I couldn't grieve, because I've done my grieving, she says. People will probably look at me and think What a hard woman. But they haven't lived with him with the knowledge that he's going to die. And I think hes absolutely doing the right thing.

To spend time with both patients such as Thomas and the researchers behind the PEACE study, is to see the strong, mutual respect. Ultimately, it is this human level of understanding and the shared experiences of how cancer affects a family that drives the study.

Im not daft enough to think my body will be the breakthrough, says Thomas. It will take many more volunteers before that happens. But both he and Lynn take courage from the hope that his death may ultimately help people. Lynn says she thinks taking part in the research has helped Thomas, too.

I don't get down, Thomas nods. Not really. I think what keeps me so buoyant is the fact that I have given myself to research and to PEACE, and to know that it's not all in vain. I'm not dying in vain.

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Dead bodies are revealing the secrets of how cancer kills - Wired.co.uk

Justin Kaus has officiated thousands of basketball games in the last couple of decades, but on Friday night, in the locker room a few minutes before taking the court at Fitzgerald Gym, his resting heart rate was a rapid 118 beats per minute.

Its been a long time since Ive been that nervous and had that much adrenaline for a (junior-varsity) game, Kaus said, gathering with friends later Friday night to celebrate the way basketball officials often do on the weekend. It was awesome.

Kaus returned to the basketball court Friday for the first time since early February, having battled a form of leukemia that halted his professional and athletic career and nearly took his life.

It was great, he said, flexing some stiff muscles and joints. The interaction with coaches, talking with fans, interacting with the players ... you forget how much fun and rewarding that it.

It was more than 14 months since Kaus, 44, went to the clinic, feeling run down and with little energy or strength. He was diagnosed with a sinus infection, but two weeks passed, with stronger antibiotics, and he wasnt feeling any better.

He scheduled a visit to another doctor, who put him through a more extensive examination. He had blood drawn, and, as he was driving home, his doctor called and told him to get to the emergency room.

His hemoglobin level was dangerously low, and Kaus was taken by ambulance to the hospital in Rochester.

I went from thinking I had a sinus infection to having blood cancer in about 6 hours, Kaus said.

Thus began the yearlong process of trying to survive a diagnosis of primary myelofibrosis, a treatable form of leukemia. He continued his normal routine of work and officiating basketball games for a couple of months, trying not to get too worn down.

By February, after finding a couple of perfect donors for a bone-marrow transplant, the treatment became more rigorous and dangerous.

There was a round of chemotherapy in mid-February, followed by a stem cell transplant on Feb. 28. He was told to expect at least 100 days in the hospital, but that time more than doubled when he had to have his spleen removed in March. He developed an infection that required the removal of most of his colon, forcing a lifesaving surgery on May 25.

The doctor told me that if I didnt have my colon removed, it would likely burst, Kaus said. At that point, there would have been nothing more they could do for me.

There were a few weeks during the summer that he cant remember. At one point, he shut off his cell phone after staring at it one day, not sure what he was supposed to do with it. His friends stayed in touch through an online diary, written by his girlfriend, Delight Simpson.

In May, hundreds of Kaus friends gathered for a fundraiser, collecting thousands of dollars to help him with his monthly bills and extra expenses and exchanging hope for Kaus.

I cant thank people enough, he said, getting momentarily choked up with emotion. The support Ive received from my family, my work family, my basketball family has been unbelievable.

Kaus said that since that surgery, his recovery has been rapid and remarkable. Its about what he had originally been told had he not had any complications. Hes had more than 100 blood transfusions, and ironically, he now goes in a couple of times each month to have some blood removed.

After what Ive been through, its hard to watch them just throw that blood away, he said.

He weighed 153 pounds when the treatments began but slipped to 98 pounds. Hes worked hard to get his weight back to near normal, and hes done of lot of rehab work to regain strength. He was unable to lift 2 pounds at his most dire times. He still sees a doctor a couple of times each month, but those visits have become less frequent.

Until recently, he had to rely on Simpson, his daughter, Taylor, and his mom, Sally, to get around, but now hes driving again.

When he started rehab, he couldnt lift 10 pounds on the single-leg press, but hes now up to 125. Hes always been active, participating in sports, and his conditioning has slowly returned.

It felt so good to see him there, said Ben Kaus, Justins cousin and officiating partner on Friday. There was such a shock factor (a year ago) when we found out about his condition, and it took a while to sink in. For a while, we didnt know if Justin was going to be around much longer.

But at one of the visits, when it didnt look very good, he told us that he was going to make it. His positive attitude is what made the difference. Justin has always been like a big brother to me, and its great to have him back.

On Feb. 28, which will be one year from the stem-cell transplant, Kaus will have a checkup to see if the cancer is gone or he needs more treatment. Hell also know shortly after that if he needs to continue with colostomy and ileostomy bags or he can have surgery to reattach his colon to the digestive tract.

Until then, hes going to continue to increase his work hours and officiate basketball as much as his body can tolerate. He wanted to get that first assignment out of the way to see how he felt, then he can plan the next couple of months. Being on the court is as much of a mental triumph as a physical milestone.

In August, I had pretty much written off this season, he said. In early December, it was my 40th physical therapy session in Mankato, my physical therapist suggested that I talk with some coach and go to a scrimmage to simulate basketball movements.

Its the coolest thing to be back on the court, he said. Ive gotten so many messages and words of encouragement and support from the start to this point. This was another step in getting back to normal, and its something Ive worked hard for.

Its never been about me, but the camaraderie being around other officials and telling stories and talking about the games has been very therapeutic. We dont have to (officiate basketball games). We do it because we still enjoy the games and we want to give something back. I hope the coaches, the players, the fans appreciate what we do, but in the end, all that matters is were spending time in the gym, around a game that we love.

Follow Chad Courrier on Twitter @ChadCourrier.

Read more from the original source:
For Kaus, getting back on court is next step in recovery - Mankato Free Press

Updated January 06, 2020 08:30:20

Since being diagnosed with Hodgkin's lymphoma 18 months ago, Aliona Grytsenko has spent much of her time in and out of hospital.

When the 22-year-old architecture student developed an infection after having a stem cell transplant, she had to be woken every hour to have her vital signs checked.

"It made it really hard to sleep and rest in the midst of having fevers and going through the treatment and side effects themselves. It's really difficult to manage that when you're so sleep-deprived," Ms Grytsenko said.

Registered nurse and researcher Elise Button has worked in cancer and palliative care for 10 years and said waking people up was one of the worst parts of the job.

"We routinely wake people up every four hours if they're more unwell we wake them up every hour or 15 minutes to do vital sign monitoring to make sure they're safe," Dr Button said.

"The sicker they are, the more we wake them up."

But new technology being trialled at the 20-bed Kilcoy Hospital, north-west of Brisbane, may put an end to what has been one of nurses' core responsibilities taking and recording vital signs.

Patients are being fitted with wearable body sensors that will automatically record their temperature, heart rate, oxygen levels and blood pressure.

Dr Button said it was a potential game-changer in nursing care.

"It gives us more time to focus on all the other roles that a nurse does that are important particularly communicating with people, sitting down and talking to them, while we know they're being safely monitored," Dr Button said.

"This allows people who are unwell to get sleep and rest, with peace of mind that they're being safely monitored."

The Metro North Hospital and Health Service's Adam Scott is overseeing the trial and says the feedback so far has been positive.

"Patients have commented they no longer have to be woken through the night. They can sleep through the process," Professor Scott said.

The wireless monitoring technology has been in development for a decade, but it is the first time in the world it has been put to the test by an entire hospital.

It could also help save hospital bottom lines.

"We have a growing level and burden of chronic disease, we have higher life expectancies and higher community expectations on how healthcare is provided," Professor Scott said.

"We know we have to move towards a value-based healthcare approach to better provide services and care for our patients."

The Australian distributor for the wireless monitoring device, Wearable Health Tech, estimates there are more than 100 million patient observations performed each year in Australia.

Company spokesman Ben Magid said the system not only gave time back to staff to spend on patient care, but improved patient safety through continuous monitoring.

"If patients do start to go downhill, staff are alerted so they can intervene sooner and prevent adverse events and complications from developing," Mr Magid said.

If the trial goes well, the technology could be used more widely, allowing patients to recover at home, while still being monitored by hospital staff.

Ms Grytsenko said it would have given her peace of mind.

"In the first few weeks after the stem cell transplant you don't know how you're going, you don't know, is that bad enough that I should call someone and ask or is it OK?'' Ms Grytsenko said.

Professor Scott said he believed it could also revolutionise rural medicine.

"We could have a command centre located in a metropolitan city where the specialist staff are sitting supervising and looking after and viewing patients that are located in a rural facility," Professor Scott said.

The trial will run until June.

Topics:healthcare-facilities,health-policy,health,government-and-politics,public-sector,medical-research,medical-procedures,doctors-and-medical-professionals,brisbane-4000,qld,maroochydore-4558,kilcoy-4515,australia

First posted January 06, 2020 06:56:17

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Wearable monitoring technology helps nurses avoid waking sleep-deprived patients - ABC News

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the Phase 3 KEYNOTE-604 trial investigating KEYTRUDA, Mercks anti-PD-1 therapy, in combination with chemotherapy met one of its dual primary endpoints of progression-free survival (PFS) in the first-line treatment of patients with extensive stage small cell lung cancer (ES-SCLC). In the study, treatment with KEYTRUDA in combination with chemotherapy (etoposide plus cisplatin or carboplatin) resulted in a statistically significant improvement in PFS compared to chemotherapy alone (HR=0.75 [95% CI, 0.61-0.91]), which was observed at a prior interim analysis. At the final analysis of the study, there was also an improvement in overall survival (OS) for patients treated with KEYTRUDA in combination with chemotherapy compared to chemotherapy alone; however, these OS results did not meet statistical significance per the pre-specified statistical plan (HR=0.80 [95% CI, 0.64-0.98]). The safety profile of KEYTRUDA in this trial was consistent with that observed in previously reported studies. Results will be presented at an upcoming medical meeting and discussed with regulatory authorities.

Results of KEYNOTE-604 demonstrated the potential of KEYTRUDA, in combination with chemotherapy, to improve outcomes for patients newly diagnosed with extensive stage small cell lung cancer, a highly aggressive malignancy, said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. We sincerely thank the patients and investigators for their participation in this study and are committed to helping patients who face difficult-to-treat types of lung cancer.

In addition to KEYTRUDAs five current indications in lung cancer, Merck is continuing to study KEYTRUDA across multiple settings and stages of lung cancer through a broad clinical program, which is comprised of more than 10,000 patients enrolled or expected to be enrolled across 20 Merck-sponsored clinical studies.

About KEYNOTE-604

KEYNOTE-604 is a randomized, double-blind, placebo-controlled Phase 3 trial (ClinicalTrials.gov, NCT03066778) investigating KEYTRUDA in combination with chemotherapy compared to chemotherapy alone in patients with newly diagnosed ES-SCLC. The dual primary endpoints were OS and PFS. Secondary endpoints included objective response rate (ORR), duration of response (DOR), safety and quality of life (QoL). The study enrolled 453 patients who were randomized to receive either:

About Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon and breast cancers combined. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all cases. Small cell lung cancer (SCLC) accounts for about 10 to 15% of all lung cancers. The five-year survival rate for patients diagnosed in the U.S. with any stage of SCLC is estimated to be 6%.

About KEYTRUDA (pembrolizumab) Injection, 100mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,000 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patients likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency), thyroid function (prior to and periodically during treatment), and hyperglycemia. For hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or 4 hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those 1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those 2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those 2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with esophageal cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

Adverse reactions occurring in patients with hepatocellular carcinoma (HCC) were generally similar to those in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 34) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 34) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 34) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

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Merck's KEYTRUDA (pembrolizumab) in Combination with Chemotherapy Significantly Improved Progression-Free Survival Compared to Chemotherapy Alone as...

Nobody likes being sick. Skipping work can be fun sometimes, but when you're miserable, it's hard to enjoy it. And if you're an entrepreneur or freelancer who isn't salaried, you simply can't afford it.

You need to do everything you can to stay healthy, especially during flu season. And while ingesting vitamin C is a good bet, there's another hack you should take advantage of immediately, due to its sheer multitude of advantages.

If you live in a heated house or apartment, the air in your home is dry. Really dry. This is a problem for a variety of reasons, the most salient being that a2013 study showed that in a low-humidity environment, 70-77 percent of flu viruses can transmit themselves through coughs. When humidity levels were boosted to 43 percent or higher, the transmission number fell to just 14 percent.

In the words of study researcher John Noti of the CDC's National Institute for Occupational Safety and Health, at high humidity levels "the [flu] virus just falls apart."

In short,if you want to protect yourself and your family from cold and flu season this year, you need a humidifier. Where? In your bedroom, where you spend crucial resting hours.

Here are a few other advantages to using a humidifier:

1. It softens your skin

Dry air saps the moisture from your skin, which you already know leads to noticeably dry skin and flaking. But did you know that this dryness also accelerates the aging process?A humidifier gives your skin that precious moisture back, which keeps you looking your best.

2. It promotes quicker healing

Say do end up succumbing to a cold or flu--using a humidifier helps you get better faster. Why? Because when you keep your nasal passages and throat moist, it reduces coughing and sneezing, which helps you recover quicker.

3. It gives your sinuses a break

Winter air dries out your sinuses--you're already familiar with that annoying, tight feeling you get in your nose when it's cold out. But dry sinuses are more than just uncomfortable--they leave you more vulnerable to bacteria and viruses. A humidifier keeps your sinuses healthy and happy, which keeps you the same.

4. It lowers your heating bill

Ever feel like when it's more humid out, it's hotter? It's true--moist air feels warmer. When you add moisture to the air in your home, it'll feel warmer, so you'll be able to lower the thermostat and save money on your heating bill.

5. It reduces electric shocks

If you feel likestatic electricity is worse in the winter, you're right. The dry air increases your chances of that painful snap when you touch a doorknob after moving over carpet. Add moisture back into the air and you'll be shockedby how much better this issue gets.

6. It protects your wood furniture

Dry air is bad for wood furniture, moldings and doors--it can cause the wood to split and crack. A humidifier helps preserve the integrity of the wood, maintaining your valuable pieces.

7. Better sleep

If you or your partner snores, a humidifier can help, since snoring often worsens when the person has a dry throat or sinuses. Plus, moist air in your bedroom will make the room warmer and more comfortable overall, which promotes restful sleep.

Ready to take the plunge? There are a few things to keep in mind. First, you'll need to regularly clean your humidifier (about once a week). If you don't, the humidifier itself can turn into a source of bacteria and mold.

Second, it's best to use distilled or de-mineralized water in your humidifier. Depending on where you live, your tap is likely to have minerals in it that will generate buildup in your machine (which then promotes the growth of bacteria).

It's easy tomake distilled water from tap water at home, for free. Useit in your humidifier and you'll have to clean it less often.

Third, if your humidifier has a filter, be sure to change it regularly. Same idea--you don't want bacteria to grow in there.

Finally, don't go overboard and turnyour bedroom into thetropics--too much humidity is just as bad as too little. Pick up a hygrometer to measure the humidity level in your room (they cost less than $8). According to the study, the ideal humidity level is 40-50 percent.

Then breathe deeply and be proud. You're taking good care of yourself.

The opinions expressed here by Inc.com columnists are their own, not those of Inc.com.

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Want Glowing Skin and a Healthy Immune System This Winter? Institute This 1 House Hack Immediately - Inc.

An unpleasant tingling in the hands and feet, numbness, furry and burning sensations these symptoms may indicate a neuropathy, a disease of the nervous system. If the pain persists for several months, it is referred to as chronic pain. By then, it is very difficult to treat, and the available drugs often have serious side effects. Researchers at the Translational Medicine and Pharmacology TMP branch of the Fraunhofer Institute for Molecular Biology and Applied Ecology IME have found a way to prevent the development of neuropathic pain early on.

Around five million people in Germany suffer from neuropathic pain, which is the result of damage to the peripheral or central nervous system. Its causes are numerous and diverse. Neuropathic pain can occur after an operation, such as bypass surgery, or an accident, for instance when the spinal cord has been injured. Phantom pain, which many patients experience following an amputation, is also a neuropathic, mechanically induced pain.

A change in skin sensitivity is typical for neuropathic pain. Stimuli such as cold, heat or touches are felt more intensely or hardly at all. The situation becomes problematic when the pain takes on a life of its own and becomes chronic, as this has a major adverse effect on the patients quality of life.

The development of neuropathic, trauma-induced pain that often occurs following an operation or accident should be prevented at as early a stage as possible, because once neuropathic pain has developed, treatment has only a limited effect and the relevant drugs have strong side effects.

When immune cells become the enemy

This is where the researchers at the Frankfurt-based Fraunhofer IME began their approach. They are researching alternative therapies for the early treatment of neuropathic pain. They conducted tests in which they were able to show that various lipids that act as signaling molecules and are produced when an injury occurs control the inflammatory responses in the damaged nerves. The nerves sound the alarm and release lipids to signal to the immune system that an injury has occurred and the cause must be eliminated, says Prof. Klaus Scholich, group manager for biomedical analytics and imaging at Fraunhofer IME.

In the case of neuropathic pain, the immune cells that were lured to the site of the injury soon become the enemy, interacting with the nerves in a way that results in permanent inflammation in the affected areas. The neuropathic pain can no longer subside and becomes chronic. We can significantly reduce the pain by blocking signaling pathways that attract immune cells. One way to do this is by using painkillers such as ibuprofen and diclofenac. Administered at an early stage, these drugs can stop the production of prostaglandin E2, a lipid that plays a key role in trauma-induced pain because it both sensitizes the nerves and activates the immune system.

Prostaglandin E2 also binds the EP3 receptor. Neurons that express this receptor produce the signaling molecule CCL2, which in turn contributes significantly to pain development because it constantly lures new immune cells to the injured nerves and, as the IME researchers discovered in their studies, is itself involved in amplifying pain perception. We were able to shed light on the subsequent mechanisms that promote the genesis of neuropathic pain by means of inflammatory responses, explains Scholich.

The EP3 receptor recognizes the prostaglandin E2. By switching off the EP3, thus inhibiting CCL2 release, pain genesis can now be significantly reduced. The CCL2 could be intercepted with specific therapeutic antibodies, which are used for chronic pain when conventional drugs such as ibuprofen no longer work. The disadvantage of this approach is that antibodies have to be injected. Since most patients find this unpleasant, Scholich and his colleagues are researching alternative agents that can be administered orally.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Targeting the Immune System Could Prevent Neuropathic Pain - Technology Networks

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A number of years back, there was a great deal of excitement about using viruses to target cancer. A number of viruses explode the cells that they've infected in order to spread to new ones. Engineering those viruses so that they could only grow in cancer cells would seem to provide a way of selectively killing these cells. And some preliminary tests were promising, showing massive tumors nearly disappearing.

But the results were inconsistent, and there were complications. The immune system would respond to the virus, limiting our ability to use it more than once. And some of the tumor killing seemed to be the result of the immune system, rather than the virus.

Now, some researchers have focused on the immune response, inducing it at the site of the tumor. And they do so by a remarkably simple method: injecting the tumor with the flu vaccine. As a bonus, the mice it was tested on were successfully immunized, too.

This is one of those ideas that seems nuts but had so many earlier results pointing toward it working that it was really just a matter of time before someone tried it. To understand it, you have to overcome the idea that the immune system is always diffuse, composed of cells that wander the blood stream. Instead, immune cells organize at the sites of infections (or tumors), where they communicate with each other to both organize an attack and limit that attack so that healthy tissue isn't also targeted.

From this perspective, the immune system's inability to eliminate tumor cells isn't only the product of their similarities to healthy cells. It's also the product of the signaling networks that help restrain the immune system to prevent it from attacking normal cells. A number of recently developed drugs help release this self-imposed limit, winning their developers Nobel Prizes in the process. These drugs convert a "cold" immune response, dominated by signaling that shuts things down, into a "hot" one that is able to attack a tumor.

But not everyone has a response to these drugs, raising the question of whether there are other ways to activate the immune system at the site of a tumor. One potential option is simply the things that normally rev up the immune system: infectious agents. The immune response to cancer-targeting viruses mentioned above would provide an indication that this does occur. Others have targeted a variety of pathogens to the sites of tumors and found that this increases the immune response to the tumor as well.

To check whether something similar might be happening in humans, the researchers identified over 30,000 people being treated for lung cancer and found those who also received an influenza diagnosis. You might expect that the combination of the flu and cancer would be very difficult for those patients, but instead, they had lower mortality than the patients who didn't get the flu.

For more detailed tests, the researchers moved to mice, using melanoma cells that can form tumors when transplanted into the lungs of the mice. These model systems often respond to treatments that don't end up working in humans, so the results have to be treated with appropriate caution. Still, they can be a valuable way of understanding the biology of the immune response here.

The use of melanoma cells is informative, as these cells cannot be infected by the influenza virus. So this system also provides a test of whether the tumor cells themselves have to be infected in order to increase the immune response to them. Apparently they do not. Having an active influenza virus infection reduced the ability of the melanoma cells to establish themselves in the lung. The effect isn't limited to the location of the infection, though, as tumors in the lung that wasn't infected were also inhibited. The effects were similar when breast cancer cells were placed into the lung, as well.

All of this is consistent with the immune stimulation provided by a pathogen. The stimulation causes a general activation of the immune system that releases it from limits on its activity that prevent it from attacking tumor cells. But does it require an actual infection? To find out, the researchers used a flu virus that had been inactivated by heat treatment. Normally, heat treating a virus is used to create a control for an effect that needs an active virus. But here, it turned out to be another experiment, as the heat-treated virus was also able to work just as effectively as the live virus.

This isn't entirely surprising, given that inactive viruses are often used as vaccines and thus clearly can stimulate the immune system. But that, in turn, suggested another experiment: would vaccines actually work? To find out, the researchers obtained this year's flu vaccine and injected it into the sites of tumors. Not only was tumor growth slowed, but the mice ended up immune to the flu virus.

Oddly, this wasn't true for every flu vaccine. Some vaccines contain chemicals that enhance the immune system's memory, promoting the formation of a long-term response to pathogens (called adjuvants). When a vaccine containing one of these chemicals was used, the immune system wasn't stimulated to limit the tumors' growth.

This suggests that it's less a matter of stimulating the immune system and more an issue of triggering it to attack immediately. But this is one of the things that will need to be sorted out with further study. The location of the stimulation will also need to be sorted out, too. Here, stimulation in one lung increases activity in both. But injection into muscles didn't work at all, and earlier work by some of the same team had indicated a heavy infection outside the lungs enhanced tumor growth by diverting immune cells elsewhere.

But the story does fit in well with the general consensus that the immune system can be a powerful tool against cancer, provided it can be mobilized properly. And, in at least some cases, a flu vaccine just might do the trick.

PNAS, 2019. DOI: 10.1073/pnas.1904022116 (About DOIs).

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Injecting the flu vaccine into a tumor gets the immune system to attack it - Ars Technica

Serious infections increase the risk of life-threatening conditions such as deep vein thrombosis (DVT), a blood clot that can form in deep veins, and pulmonary embolisms (PE), a condition where an artery in the lung becomes blocked by a blood clot. These conditions affect 1 in 1000 adults and lead to approximately 200,000-300,000 deaths per year.

In an effort to better understand blood clots, Andrea Obi, M.D., a vascular surgeon and investigator at Michigan Medicines Frankel Cardiovascular Center, is exploring the condition further through new research in her lab.

Her team is establishing a link between infection, thrombosis and changes in the bone marrow programming of immune cells and working on understanding the interplay between the immune system and thrombosis to help identify new, non-blood thinning techniques for preventing and treating DVT in the future.

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Obi, also the winner of the 2019 Wylie award from Vascular Cures, takes a deeper dive into her work here with questions from the Michigan Health Lab:

Whats the focus of your research?

My research focuses on the intersection between innate immunity and the coagulation system, specifically evaluating the role immune cells play in forming and breaking down blood clots in the venous system.

What sparked your interest in this?

My current work, like many surgeons, was the result of observing human suffering. During the 2009-2010 H1N1 influenza outbreak, I spent much time in the surgical intensive care unit caring for young individuals, some in their 20s and 30s, with severe pulmonary disease requiring advanced life support. We noticed that a large number of these patients developed severe venous clotting, leading to a very high mortality. Blood thinners helped us decrease the risk of death but led to a host of other bleeding complications for these ill patients.

When I had a chance to review data from large population studies, it became evident that DVT was associated with all types of infections to varying degrees, and the risk persisted over the course of the persons next year of life, even if he or she made a rapid recovery.

What discoveries has your team already made?

So far weve discovered that even with a remote infection, such as a pneumonia, the endothelium (inner lining of the blood vessel) in a remote location changes the proteins expressed on the cell surface and talks to circulating leukocytes differently.

How will patients benefit from this research?

My hope is that by using both animal models and human tissue we can identify some of the changes that occur in innate immune cell memory that predisposes individuals to form a DVT after suffering from an infection.

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In recent years, the pharmacology for a wide range of diseases such as rheumatoid arthritis, psoriasis, and melanoma have been transformed by the ability to target the immune system. Despite the fact that its never been tried in DVT, doesnt mean that it is impossible, rather that we just dont understand enough about the crosstalk between the immune system and coagulation (blood clotting) system to identify a protein or molecule that we can manipulate to change the course of human disease.

I hope that in the course of my work and in my lifetime we can make a discovery that decreases the need for dangerous blood thinning medication and improves the lives of individuals who are at high risk or whom have suffered from a DVT.

Read more from Dr. Obi about her research goals and progress in this blog post from the Michigan Medicine Department of Surgery.

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Investigating the Immune System's Connection to Blood Clots | University of Michigan - Michigan Medicine

The importance of a healthy immune system cant be overstatedespecially during the cold winter months. Common colds and the full-on flu are at their worst throughout the winter, so youll want to do whatever you can to boost your immune system and stay as healthy as possible. Follow this guide onhow to keep your immune system strong during winterto avoid untimely sickness.

Stress can do all kinds of terrible and negative things to your body. If your stress levels are through the roof, take a moment to find a release for relaxation. Without stress to weigh your body down, it can focus on building your immune system and keeping you at tip-top shape to face the harsh winter.

Drinking enough water is crucial to supporting your immune health; a healthy body requires eight cups of water a day. Unfortunately, many people dont like the way water tastes and consider it an unfulfilling drink. As a result, they dont drink itor they dont drink enough of it. One way to combat these issues is to jazz up plain water with some additional goodness. Heat up water and add lemonsfora delicious and nutritious wayto increase your H2O intake.

Vitamin C and zinc are common ingredients in many over-the-counter medicines because they help prevent and fight sicknesses. You dont have to rely on medicine, though. Many common foods contain vitamin C, zinc, or both: potatoes, broccoli, chicken, and tomatoes are some of the most popular items. Simply increasing your daily intake of these essentials can slowly and surely build extra immune system health and strength.

As you sleep, your body slows down and recharges. Consequently, your immune system can heal from the many battles it fought over the course of your day. While there are some exceptions to this rule, most of us need at least eight hours of sleep at nightthis give our bodies enough time to fully recover. Enough sleep is equally as important during the spring and summer seasons, too, as it gives your body time to fend off any germs it encountered during the day.

Exercise helps your body maintain health and can even contribute to building a stronger immune system. If youd like to go to the gym, thats great! However, even though exercise helps boost your immune systemand the gym is a wonderful place to exercisegyms are home to many different types of germs. Here are a few ways you can avoid germs before, during, and after your work out.

The winter is chilly, and keeping your body warm will help your immune system avoid fights and become stronger. Wear a hat when outdoors, as most of your bodys heat actually escapes through the top of the head. You should also wear a coat, proper footwear, gloves, and a scarf.

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How to Keep Your Immune System Strong During Winter - The Free Press of the University of Southern Maine