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ChristianaCare is out to revolutionize health care. One of the country’s most dynamic health care systems, ChristianaCare is partnering with two leaders in medical and therapy services to provide comprehensive, integrated virtual health services 24/7 to colleges, universities and other institutions of higher education. Together with PursueCare and SimpleTherapy, ChristianaCare created a bundled health care product that combines general medical services from ChristianaCare’s Center for Virtual Health, mental health and addiction treatment programs from PursueCare and hyper-personalized musculoskeletal care from SimpleTherapy. ‘The future of health care is virtual’ “At ChristianaCare, we know that the future of health care is virtual,” said Sharon Anderson, MS, RN, FACHE, ChristianaCare’s chief virtual health officer and president of ChristianaCare’s Center for Virtual Health. “When college students are able to access medical, behavioral health and musculoskeletal services through their phone or laptop, from their dorm room or a private space on campus, they’ll be more likely to get help when they need it. This is about delivering care to students on their terms, so that they can be healthy and supported with high-quality care throughout their college experience.” Personalized virtual health solutions will be available to students at participating higher education institutions through a customized portal accessible from any computer or mobile device. Students will be able to access assessments, resources and virtual treatment via modules or telemedicine sessions with licensed providers. The offering provides students with unlimited, on-demand care from a multidisciplinary team solving for a multitude of conditions. “For college and university student health services and administrators, this partnership offers a powerful new way to provide comprehensive, affordable health solutions that benefit students,” Anderson said. “In a highly competitive recruiting environment, these solutions are easy to implement and can add tremendous value. We are excited to partner with colleges and universities to strengthen their student health programs by creating a comprehensive virtual care solution to meet their student’s health care needs.” Through a single digital portal, participating students can access internal and family medicine providers from ChristianaCare’s Center for Virtual Health. PursueCare’s Joint Commission-accredited mental health, psychiatric and medication-assisted treatment providers, and SimpleTherapy’s licensed physical therapists specializing in musculoskeletal care, acute or chronic pain management, and strength and mobility training can all be accessed through the portal. Students will also have the option of using PursueCareRx for their pharmacy needs. PursueCareRx is a competitively priced full-service pharmacy that accepts most major insurance and delivers directly to customers. “Young adults face an escalating mental health and substance use crisis,” said Nick Mercadante, founder, and CEO of PursueCare. “Colleges and universities are frequently unable to comprehensively serve the increased need, and research suggests substance use, mental health and suicide carry a significant social stigma. Our goal is to work collaboratively with campus health resources to bring a low-barrier solution students can access privately, any time, on their terms. Additionally, partnering with a world-class health system like ChristianaCare means we can help support whole-person care needs.” “Chronic musculoskeletal disorders have never been more prevalent and traditional care pathways are often ineffective and costly,” said Arpit Khemka, co-founder and CEO of SimpleTherapy. "SimpleTherapy removes barriers for students allowing them to take control of their musculoskeletal health, reducing their need for high-cost, high-risk services, such as surgery and opioids, to manage pain. This results in higher compliance rates and more successful outcomes." Customized and co-branded product The product is designed for colleges, universities and all other higher education institutions. For a flat fee, a school will be able to offer care that is customized and co-branded with school-specific content to be an extension of existing campus health services. It provides curated resources for rapid pre-assessment, on-demand chat and discreet, personalized access to care for students on or off-campus. The innovative patient portal aims to improve and strengthen how schools offer health care solutions to their student population while reducing any potential interruptions of academic and athletic pursuits by making it possible for students to conveniently access care from anywhere. In addition, the offering eliminates social stigma and other access obstacles for students who are at-risk or potentially at-risk, making it more likely that students will avail themselves of treatment options and remain in school. These services are currently licensed to operate in Delaware, New Jersey, Pennsylvania and Maryland. Applications for licenses are underway in other states. ChristianaCare has long been a trailblazer in virtual health. Among its achievements, during the COVID-19 pandemic, ChristianaCare developed a COVID-19 virtual monitoring program that helped 37 companies in 14 states safely reopen with daily symptom monitoring, testing and connections to care for more than 10,000 employees. It’s Center for Virtual Health makes receiving care radically convenient, offering a full continuum of virtual care delivery programs. These programs include virtual primary care, specialty care programs and a Hospital Care at Home Program bringing hospital level of care to a patient’s home. The Center for Virtual Health cares for thousands of patients using state-of-the-art virtual care capabilities supporting patients in receiving care anytime, anyplace, including in the comfort of their own homes. For more information about the program, visit StudentCareSolutions.com.
ChristianaCare Launches Gender Wellness Program for Transgender and Gender Diverse Individuals
Pride Month announcement highlights need for quality health care for LGBTQ+ community ChristianaCare has opened a Gender Wellness Program to provide psychotherapy and support services for individuals age 13 and older who are exploring their gender identity or experiencing gender dysphoria—a sense of incongruence and distress that a person may have because of a mismatch between their gender identity and their sex affirmed at birth. Downloadable: PHOTOS VIDEO The program also provides treatment for any behavioral health condition the individual may be struggling with, such as anxiety and depression. People who identify as transgender have higher rates of suicide attempts than individuals who do not identify as transgender, according to the National Institutes of Health. “ChristianaCare aims to provide the safest, highest quality health care and the best experience possible for our entire community, guided by our values of love and excellence,” said Mustafa A. Mufti, M.D., interim chair of the ChristianaCare Department of Psychiatry. “Caring for our entire community means providing sensitive, compassionate, and state-of-the-art behavioral health and medical care to transgender and gender-diverse individuals. Our Gender Wellness Program will help improve health equity and outcomes for individuals and families who need these services. We know that transgender and gender-diverse individuals face health disparities, and our program will help address that.” The program follows the guidelines of the World Professional Association for Transgender Health (WPATH). WPATH promotes the highest standards of health care for the health of transsexual, transgender and gender-nonconforming people based on the best available science and expert professional consensus. “Our Gender Wellness Program is ready to support anyone age 13 or older who is exploring their gender identity, experiencing gender dysphoria or who needs education and support around social and medical transition,” said Brett E. Herb, DSW, LCSW, program manager of the Gender Wellness Program. Dr. Herb has been in clinical practice for more than 25 years as a psychotherapist and a clinical and administrative manager for numerous behavioral health programs, and has been working with the transgender and gender-diverse populations for the past 17 years. “We provide referrals to compassionate, gender-affirming health care experts,” Dr. Herb said. “Often, families find themselves having to educate their primary care providers, schools, neighbors and family members about how to appropriately care for gender-diverse individuals. Our program provides individuals and families with access to specially trained gender therapists they can trust who can get them the answers they need to help navigate the complexities they may encounter.” The Gender Wellness Program provides referrals to trans-competent primary care providers who prescribe gender-affirming hormone treatment, along with specialists for gynecological and obstetrics care. The program offers individual, couples, family and group therapy sessions. It also provides existing patients with assistance with personal documentation changes and letters of surgical support. “This program has provided me with tremendous support throughout my transition,” said Julie Brown of Wilmington, Delaware. “My therapist empathizes with what I am experiencing in my life, and has guided me through my evolution. The group therapy sessions help me understand that I am not alone. “We form a community, share information and support each other in a safe environment. My child is also a patient of the Gender Wellness Program. Their support has helped him deal with my changes and understand his gender dysphoria.” “Brett Herb and the Gender Wellness Program have helped me grow the confidence I needed,” said Kristopher Snedeker of Newark, Delaware. “Working with the professionals at the program has provided resources to help further my gender transition to become who I truly am.” Gender therapists at the Gender Wellness Program are: Brett E. Herb, DSW, LCSW, Program Manager. Amanda Pope Evans, MSW, LCSW. Katherine Goemaat-Suarez, MSW, LCSW. ChristianaCare is a national leader in LGBTQ+ health care. For the past 11 consecutive years, Christiana and Wilmington hospitals have been recognized by the Healthcare Equality Index as an LGBTQ+ Healthcare Equality Leader. Individuals who would like to learn more can contact the Gender Wellness Program at genderwellnessprogram@christianacare.org or call 302-623-6773. For more on ChristianaCare’s LGBTQ+ health initiatives, visit LGBTQ Health Initiatives.
Covering the music beat? Then tune in and get in touch with our resident hip-hop expert
Augusta University Professor Adam Diehl is an expert in hip-hop culture, lyrical analysis, rap as a form of literature and specifically, the works of Kendrick Lamar. Diehl gives an update on what's new in hip-hop and of course, answers questions about Lamar and his highly anticipated new album. How has the hip-hop music scene changed over the last 5 years? The hip-hop music scene has changed faster than any other genre the last five years. Whereas country still uses radio play and music videos to gauge success (along with album sales and streaming numbers) and rock uses touring to supplement and offset recording costs, pop and hip-hop have a great advantage in that they can raise people to stardom almost overnight. In fact, several of the biggest pop stars like Billie Eilish and Post Malone made their rapid ascents through the same channel many of the top hip-hop stars did: Soundcloud. Because this platform allowed new artists the chance to put their music alongside heavyweights, it democratized the listening process. What sent Soundcloud soaring? To put it succinctly, Soundcloud was the great reset of the hip-hop world. But when COVID hit and musicians couldn't tour for upwards of two years, the hip-hop community soared past country and rock (which they were already outselling pre-pandemic) because they didn't base their profit model on touring. Even pop stars were at a disadvantage, because the TV appearances and interviews they used to promote their new releases were few and far between for at least a year, and virtual events just couldn't replicate award show appearances and performances. Hip-hop, meanwhile, continued to be "Black America's CNN" and reported on the protests and outrage following the high-profile deaths of George Floyd and Breonna Taylor. The resurgence of Black Lives Matter brought mainstream media and cultural attention to the Black community, and as such the importance of hip-hop grew, just as it did in the wake of the Rodney King verdict and the deaths of Trayvon Martin, Michael Brown and Eric Garner. How has the economy of music changed? Most people under 20 don't own any CDs. What money these kids don't spend on music can now go to a modern cultural institution: the music festival. Increasingly, cities are hosting these previously camping-required concerts, which has been a particular advantage for hip-hop artists, who don't need roadies or sometimes even other people on stage. All they need is a setlist with six to 10 catchy songs, an entrancing light show, a DJ/engineer and a strong stage presence, and they can captivate the audience as easily as some of the all-time greats of any genre. Going forward, the music industry is going to be about return on investment. Instead of developing artists over a five-year period and then letting them blossom for two to three decades, they are looking for someone to explode in popularity instantly, stay in the spotlight and public consciousness consistently for three to five years, and then maybe stick around. TikTok is, in many ways, analogous to this career arc: the videos are short, the makers are -- to some extent -- largely forgettable, and the popularity relies heavily on a "hook." It's no surprise that hip-hop has been the most adopted genre by TikTokers: the genre has been more effective than any other in terms of codifying "catch phrases." And that's what TikTok is going for: something to hook viewers into watching more. Did the Super Bowl appearance by hip-hop artists take the genre to a whole new level as far as mainstream music? If the Super Bowl halftime show in 2022 did anything, it showed that rap and hip-hop are now as household friendly as rock, country and pop. Perhaps because so many best-selling rock acts had already played the halftime show, and perhaps because the pop acts of recent years had failed to maintain the public's attention, the 2022 halftime show featured one of hip-hop's founding fathers: Dr. Dre. His menagerie of artists' careers stretched over 30 years, and the time constraints of the show made hip-hop the ideal soundtrack. In a 13-minute set, six performers all got their moment in the California sun, and the mega-mix model so often used in clubs was perfect to segue from artist to artist. What 30 to 35 years ago was "Parental Advisory" is now the music that parents listen to. The target demo of the Super Bowl would've thought someone like Simon & Garfunkel or The Eagles much more risky picks than Dr. Dre & Co., even if their music was more family-friendly. Many casual music fans thought Kendrick Lamar was the head-scratcher because of his shorter tenure in the spotlight, but the younger generations watching were much more interested in what Kendrick did than "old heads" like Snoop Dogg and Mary J. Blige. Was this new album by Kendrick Lamar overdue? The new Kendrick Lamar album comes right on time: it is the definitive COVID album. If he had released in spring/summer 2020 when he originally intended (i.e. if the early March 2020 pgLang rollout was foreshadowing his record release), this would be a substantially different work of art. Instead, the project voices what so many people have endured in the pandemic: domestic turmoil. The tracks cover a vast array of topics -- from vaccinations to transgenderism to cancel culture -- but the unifying theme is therapy. As much emphasis as physical health got over the past two years, the pandemic was arguably just as bad if not worse for people's mental health. Accordingly, this album goes into dark valleys in Kendrick's and his family's trials and traumas: child abuse, sex addiction, separation/divorce, deaths, etc. In the two years that society has been persevering through the pandemic, countless marriages and millions of lives have been shaken to their cores. Listening to this double-album adds another tremor to our already-jostled souls. Tracks like "We Cry Together" capture the rapid-fire romantic arguments that can quickly escalate from disappointment to suicidal ideation, and "United in Grief" recreates the sense of a panic attack with its intensifying lyric delivery and drumbeats. Anxiety and depression are the recurring moods of this album, and the track list ranges in sonic textures -- from Lamar's tried-and-true vintage gangsta rap beats to the utterly unpredictable piano flourishes that come straight from a spoken word poetry reading -- to reflect the all-too-familiar combination of monotony and chaos that the world has undergone for the last two years. It is unforgettable -- just like COVID-19 -- but also, perhaps, something we'd rather not relive. Why do some consider Lamar the most influential rapper of our generation? Kendrick Lamar only has two real rivals for most influential rapper of the generation: Kanye West and Drake. Although Kanye is 10 years older, his career overlaps to a large degree with Kendrick's. Kanye's influence certainly comes more in the production of songs than in lyrical delivery, but his subject matter has been very contagious. Kendrick's mentioning of a Birkin bag in "N95" would never have happened if not for Kanye's lyrical (and career) forays into high fashion. Drake, on the other hand, is probably the rapper most influenced by Kanye...who went on to influence the most artists. Without Drake, many rappers wouldn't have had the blueprint for being singers as well as MCs. What Kendrick brings to the conversation is, in a way, more elusive; however, he without a doubt has raised the bar for lyrical delivery and flow, such that rappers have a better chance at success if they are comically basic than if they are merely competent. It's as if Kendrick took Eminem's velocity and used it to speak on bigger picture issues. Kendrick has also proven to be a fashion-forward rapper, collaborating with Reebok, Nike and Converse over the last few years. His influence might be most prominent in the "realness" of his lyrics: without Kendrick's "everyday life music," the emergence and popularization of "Soundcloud rap" might have been significantly limited. Instead, he uses Kodak Black -- one of the most successful of all Soundcloud-era rappers -- on Mr. Morale & the Big Steppers. If Kendrick isn't the most influential rapper of his generation, it's because his ambition and execution have placed him with the all-time greats, and oftentimes that puts artists at odds with their contemporaries. In 100 years, people won't remember some big acts because popularity wears off, but they will still celebrate Kendrick because his work is excellent. Looking to know more? Hit up Adam Diehl today -- simply click on his icon now to arrange an interview.
Does medical marijuana work? Florida consortium seeks answers
By Emma Richards A consortium of nine universities in Florida, led by faculty at the University of Florida, is in the early stages of investigating the effectiveness of marijuana as a medical treatment. Almut Winterstein, a professor at the University of Florida who also serves as the director of the Consortium for Medical Marijuana Outcomes Research, says there is promising data on pain therapy and epilepsy but much still to learn about cannabis as a medical treatment. The Consortium for Medical Marijuana Outcomes Research is assessing the drug’s risks and benefits for different medical conditions and its safety and side effects when used alone or in conjunction with other prescription medications. “What I can tell you is that right now there is promising and fairly solid data that supports the use of medical marijuana as an adjuvant for pain therapy,” said Almut Winterstein, a professor in the College of Pharmacy at UF who also serves as the director of the consortium. “And there’s also evidence that supports the use for certain types of epilepsy.” As for other conditions, the impacts of medical marijuana are still unknown. The Florida State Legislature created the consortium in 2019, four years after enacting legislation that permits use of marijuana for certain clinical conditions. Currently, 37 states have a medical marijuana program, though the programs vary as far as how and to whom cannabis can be prescribed. But, Winterstein said, little is known about marijuana’s clinical safety and effectiveness. “I think that the Legislature was really forward looking in creating something that supplements the research that is currently not sufficient,” she said in an episode of the From Florida Podcast. The consortium will also gauge who is using and able to access medical marijuana and determine the benefits and drawbacks of different dosages. To do so, the group is working on three primary branches of research. The first area is a competitive grants program that funds researchers across all participating universities. The second branch is M3, or Medical Marijuana and Me, a new study that will track patients from their first use of medical marijuana for a year to assess their experiences. “That will give us ideas about what type of dosage, form and product do patients eventually end up on,” Winterstein said. “That is a very empirical approach because we have no head-to-head comparison of what works better or worse, but we can capture patients’ experiences, what they think works, what doesn't, what kind of side effects they might experience and so on.” Finally, what Winterstein calls the consortium’s “biggest baby and most important baby” is the Medical Marijuana Outcomes Research Repository, known as MEMORY. The repository will allow researchers to use de-identified dispensing data from the Department of Health to monitor health outcomes of the large population of 700,000 registered medical marijuana patients. These data will give researchers insight on cannabis safety and effects, whether positive or negative, linking to healthcare utilization, such as hospitalization or emergency department visits. The consortium is hosting the second annual Cannabis Clinical Outcomes Research Conference May, 19-20 in Orlando, where researchers will discuss the latest research on medical marijuana. “We are really trying to get people interested in this topic,” Winterstein said. “And in particular making sure that they have access to objective information that really allows them to make the right decision with respect to the use of medical marijuana.” To hear more about the consortium’s medical marijuana research, listen to the episode on From Florida at this link. Listen to other episodes in the From Florida podcast here. Read a recent article quoting Professor Winterstein here:
Findings point to potential new therapeutic targets for this highly aggressive, drug-resistant breast cancer subtype In breakthrough research at ChristianaCare’s Helen F. Graham Cancer Center & Research Institute, scientists have discovered that a protein secreted by tumor cells can switch off the body’s natural defenses against triple negative breast cancer (TNBC). The study, led by Jennifer Sims-Mourtada, Ph.D., lead research scientist at the Cawley Center for Translational Cancer Research (CTCR), at the Graham Cancer Center, is reported in The Journal of Translational Medicine, available online. “What we found is that TNBC tumor cells can effectively shut down the body’s defense systems against the tumor by secreting a type of protein called IL-10,” Dr. Sims-Mourtada said. “The presence of this immune system protein forces the antibodies that would normally be created to attack the tumor to become non-reactive and not do what they are supposed to do.” The study was initiated in partnership with The Wistar Institute of Philadelphia, Pennsylvania, in collaboration with the late Raj “Shyam” Somasundaram, Ph.D., a cell biologist at the Melanoma Research Center. “Dr. Sims-Mourtada and her team have brought us tantalizingly close to understanding what drives the aggressive nature of triple negative breast cancer, a treatment-starved disease that disproportionately affects Delaware women,” said Nicholas J. Petrelli, M.D., Bank of America endowed medical director of the Helen F. Graham Cancer Center & Research Institute. “Their work underscores our belief that scientific collaborations such as this one between our Cawley CTCR clinicians and Wistar scientists can smooth the way for new findings to become effective therapies, especially for hard-to-treat and aggressive forms of cancer like TNBC.” Understanding the mechanism behind TNBC Delaware ranks highest in the nation for incidence of triple negative breast cancer. TNBC is an aggressive form that affects Black women at twice the rate of white women with poorer outcomes. Patients have higher rates of early recurrence than other breast cancer subtypes, particularly in the first five years after diagnosis. Currently there is no targeted therapy for TNBC. “One of our missions within the Cawley CTCR is to understand the mechanisms behind TNBC and find a treatment for it,” Dr. Sims-Mourtada said. “Our study sheds new light on what is prompting the body’s immune response to the cancer cells and offers clues to potential new therapeutic targets.” Normally it is the job of the B cells to regulate the immune response against foreign invaders like cancer. Among other jobs, they control inflammation at the site of an attack by releasing proteins including IL-10 to signal the defender cells to stand down. “Previously it was thought that the immune cells were the ones to express IL-10 to regulate themselves,” Dr. Sims-Mourtada said. “But our study shows that the tumor cells also release this protein, which means they are driving how the immune system behaves.” Within the tumor microenvironment, IgG4 is one of four antibody subclasses expressed and secreted by B cells. Whereas another type of antibody would urge the immune system to press on with the attack, activation of IgG4 signals the job is done. TNBC and activation of IgG4 “Our findings support that TNBC may create a tumor environment that supports activation of IgG4, and messaging from IL10 is triggering the switch,” Dr. Sims-Mourtada said. As previously reported with other cancers, such as melanoma, this study confirms that the presence of IgG4-positive B cells within the tumor associates with advanced disease increased recurrence and poor overall breast cancer survival. It is also possible that IL-10 expression by tumor cells may also be a cause of poor outcomes in TNBC, and this may be independent of IgG4+ B cells. “At this point, we don’t know what causes tumor cells to start secreting IL-10, but we know that B cell-tumor cell interactions are involved,” Dr. Sims-Mourtada said. “We still have to look at what is really going on in the B cell population to determine which subtypes of B cells are affected by this tumor crosstalk and why some forms of TNBC express IL-10 (the ones with poor outcomes) and others do not. “We think that the presence or absence of other immune cells in the microenvironment may affect how B cells interact with tumor cells to drive IL-10 expression,” she said. Resources for the study, including blood and tissue samples from consenting patients, were obtained through the Graham Cancer Center’s Tissue Procurement program. Interestingly, in a small subset of samples, the researchers found that IL-10 expression was significantly higher in Black patients than non-Hispanic white patients. These findings need to be confirmed in a larger more diverse population with different TNBC subtypes. Understanding tumor-infiltrating B cells “Our growing understanding of the contribution of IgG4+ cells to the immune microenvironment of TNBC and what drives IL-10 expression may reveal ways in which tumor-infiltrating B cells can contribute to tumor growth and provide new targets to increase the immune response to TNBC,” Dr. Sims-Mourtada said. As partners for more than a decade, Graham Cancer Center research clinicians and Wistar scientists collaborate across disciplines to translate cancer research into more effective therapies for patients everywhere. In addition to providing high-quality, viable tissue samples for Wistar research studies, Graham Cancer Center clinicians actively participate in concept development, sharing their unique understanding of the everyday patient experience.
Vitamin D2 and D3: what’s the difference and which should you take?
Both vitamins D2 and D3 are essentially inactive until they go through two processes in the body. First, the liver changes their chemical structure to form a molecule known as calcidiol. This is the form in which vitamin D is stored in the body. Calcidiol is then further altered in the kidneys to form calcitriol, the active form of the hormone. It is calcitriol that is responsible for the biological actions of vitamin D, including helping bones to form, metabolising calcium and supporting how our immune system works. Technically, vitamin D isn’t a vitamin at all, but a pro-hormone. This means the body converts it into an active hormone. All hormones have receptors (on bone cells, muscle cells, white blood cells) that they bind to and activate, like a key unlocking a lock. Vitamin D2 has the same affinity for the vitamin D receptor as vitamin D3, meaning neither form is better at binding to its receptor. Different effects on the immune system A recent study found that vitamin D2 and D3 supplementation had different effects on genes important for immune function. These findings are significant, as most previous research has failed to find much difference in the effect of supplementation with either vitamin D2 or D3. Most of the research published to date has suggested that the main difference between vitamin D2 and D3 supplementation is the effect on circulating vitamin D levels in the bloodstream. Studies have repeatedly shown that vitamin D3 is superior at raising levels of vitamin D in the body. These findings were supported by a recent review of the evidence which found that vitamin D3 supplementation increased vitamin D levels in the body better than vitamin D2. But not all studies agree. Very few studies support vitamin D2 supplementation being superior to vitamin D3. One trial showed that vitamin D2 was better at treating immune issues in patients who were on steroid therapy. However, other than increasing vitamin D levels in the body, there is not much evidence that vitamin D3 supplements are better than vitamin D2 supplements. One study found that vitamin D3 improved calcium levels more than vitamin D2. But we need more research to provide definitive answers. So which should I take? Vitamin D deficiency is now more prevalent than ever, with around a billion people worldwide being vitamin D deficient. It is important that people at risk of vitamin D deficiency – older adults, people living in less sunny climates and people with darker skin – take vitamin D supplements. Health professionals recommend that most people take 10 micrograms of vitamin D a day, especially in winter. It would appear that vitamin D3 supplements are the superior option for maintaining vitamin D levels, but short exposure of the skin to the sun, even on a cloudy day, will also help you keep healthy vitamin D levels.
In new study in journal Gene Therapy, researchers at ChristianaCare’s Gene Editing Institute describe how the advance is validating the safety and efficacy of their novel approach for using CRISPR to improve lung cancer treatments A new study from scientists at ChristianaCare’s Gene Editing Institute is advancing the safety and efficacy of using CRISPR gene editing in patient treatments by demonstrating how to identify and evaluate the broad-based biological impact of gene editing on targeted tissues, where the edits are designed to fully disable or “knock out” a specific sequence of genetic code. The work, published today in the Nature journal Gene Therapy, supports the Institute’s efforts to improve lung cancer treatments by using CRISPR to disable or alter a master regulator gene to prevent it from producing a protein that blunts the impact of chemotherapy. “We found that when you use CRISPR, the edits sometimes end up altering rather than completely disabling the target gene, so we developed a process to gain a more complete understanding of what that means for patients,” said Eric Kmiec, Ph.D., executive director and chief scientific officer of ChristianaCare’s Gene Editing Institute and the principal author of the study. Dr. Kmiec said that for his team’s lung cancer work, “We discovered that even when our CRISPR-based genetic manipulation did not completely disable the targeted gene, it altered it in ways that appear to make lung cancer tumors more sensitive to chemotherapy. Validating lung cancer research using CRISPR “We were fortunate that our strategy for using CRISPR to improve lung cancer treatments has been validated once again,” he added. “But our commitment to conducting an unbiased assessment of our approach highlights the importance of examining all potential outcomes of an attempt to use CRISPR to knock out a specific gene. Specifically, anyone developing CRISPR therapies needs to be on the lookout for edits that don’t fully knock out a section of DNA code—and evaluate the potential impacts for patients. They could be positive, as they were in our case, negative or neutral, but they need to be known.” Much of the excitement around medical applications of CRISPR involves using the tool to disable harmful genes by editing or “knocking out” a specific sequence of DNA code. But there is increasing evidence that in the wake of a CRISPR edit, cells may remain that contain merely an altered form of the targeted code that allows the gene to continue to produce biologically active proteins. Scientists at the Gene Editing Institute are investigating the potential of using CRISPR to disable a gene called NRF2 to alter production of the protein that protects squamous cell carcinoma lung cancer tumors from the effects of chemotherapy or radiation. They already have shown, in studies with tumor cells and in animals, that they can selectively target the NRF2 gene without affecting normal cells, where the gene confers health benefits. In the present study they wanted to go further. They wanted to fully understand the implications of a CRISPR gene edit that allowed the NRF2 gene to retain enough DNA code to continue making a version of the protein, albeit in an altered or truncated form. The team is laying the groundwork for a clinical trial that would use CRISPR to improve the efficacy of conventional chemotherapy and radiation treatments. Dr. Kmiec said that before proceeding, he wanted his team to develop a clear process for identifying and evaluating all outcomes of CRISPR edits. Identifying and understanding the diversity of genetic outcomes produced by CRISPR-directed gene editing has been a centerpiece of the foundational research programs established by the Gene Editing Institute. Using CRISPR in a safe way “We carry out experiments in an unbiased fashion, not hoping for a particular outcome, but with patient safety and efficacy serving as the true north for our scientific endeavors,” Dr. Kmiec said. “No matter what we uncover or elucidate, the insights will help both ChristianaCare and the entire field use CRISPR in a safer and more efficacious manner.” The researchers found multiple cells where the targeted strand of DNA code in the NRF2 gene was not completely knocked out. Rather, following the CRISPR edit, cells emerged that had retained enough of the original code to continue producing a different form of the protein. Tests revealed that cancer tumor cells generating these altered proteins may be more vulnerable to chemotherapy drugs. "For the work we are doing with NRF2, the truncated proteins generated by the CRISPR edit appear to be beneficial for making tumors more sensitive to treatment,” said lead author Kelly Banas, Ph.D. “But the key point is these proteins were clearly biologically active. And that means we needed to determine their potential impact on the safety and efficacy of using CRISPR to treat lung cancer patients.” Dr. Banas noted that the study points to the limits of considering a CRISPR edit to be successful simply by testing for the absence of a targeted protein in its original form. She said by that standard, their edit was successful. The edited NRF2 genes were no longer producing the same protein. But she said if that’s all the ChristianaCare team had looked for, they would have missed the altered proteins coming from the NRF2 gene—and overlooked an important outcome that, in this case, strengthens the original hypothesis and experimental approach: that using CRISPR to target the NRF2 gene holds promise for improving outcomes for lung cancer patients. Importance of due diligence “The process we describe in this study is a template that should be followed in any effort to develop CRISPR as a medical treatment,” Dr. Kmiec said. “We’re part of a health care organization where patient safety is the top priority. We also are working at the vanguard of an exciting area of cutting-edge medicine, where a failure to conduct due diligence could cause tragic outcomes that would set back this field for decades. With this study, we have validated a process that can help this field move forward rapidly but safely.” CRISPR stands for “clustered regularly interspaced short palindromic repeats.” It is a defense mechanism found in bacteria that can recognize and slice up the DNA of invading viruses. Scientists have learned how to modify this mechanism so it can be directed to “edit” specific sequences of DNA code. About ChristianaCare’s Gene Editing Institute The Gene Editing Institute, a worldwide leader in CRISPR gene editing technology and the only institute of its kind based within a community health care system, takes a patient-first approach in all its research to improve the lives of people with life-threatening disease. Since 2015, researchers at the Gene Editing Institute have been involved in several ground-breaking firsts in the field, including the development of the first CRISPR gene editing tool to allow DNA repairs outside the human cell which will rapidly speed therapies to patients and the ExACT ™pathway of single-stranded DNA repair, which increased the on-target efficacy of CRISPR and paved the way for new CRISPR breakthroughs in precise DNA edits. Its researchers created CRISPR in a Box™, the leading educational toolkit to teach gene editing, DECODR™, recognized as the most user-friendly and precise analytical tool to understand the diversity of genetic outcomes of gene editing and are currently developing a patient trial for lung cancer using CRISPR.
ChristianaCare and The Wistar Institute advance partnership with new cancer research strategies
ChristianaCare’s Helen F. Graham Cancer Center & Research Institute is advancing its historic partnership with the Ellen and Ronald Caplan Cancer Center of The Wistar Institute in Philadelphia with three new research projects under way. The new research projects consist of a population health study targeting triple negative breast cancer. Other projects focus on a new therapeutic target for epithelial ovarian cancer, the most lethal gynecologic cancer in the developed world, and the development of “mini organs” derived from stem cells. Targeting triple negative breast cancer Delaware has one of the highest incidence rates of triple-negative breast cancer in the United States. This highly aggressive cancer has few treatment options, because the cells test negative for three known treatment targets – estrogen, progesterone and HER2 protein receptors. Working with patient data from the Graham Cancer Center, researchers are investigating potential contributing factors such as diet, alcohol use and genetic variants among women, and the effects of these on cancer metabolism. The team will also examine spatial relationships between cancer “hot spots”—geographic areas with a higher-than-expected prevalence—and modifiable risk factors. Key resources for the study are blood and tissue samples from the Graham Cancer Center’s Tissue Procurement Center and its statewide High-Risk Family Cancer Registry. The research team will be led by Director of Population Health Research at ChristianaCare Scott Siegel, Ph.D., and Lead Research Scientist Jennifer Sims Mourtada, Ph.D., at the Graham Cancer Center’s Cawley Center for Translational Cancer Research (CTCR). They will join Zachary Schug, Ph.D., at Wistar’s Molecular and Cellular Oncogenesis Program. Researching novel therapy for ovarian cancer The latest study supported by the Graham Cancer Center’s Tissue Procurement Program targets KAT6A expression as a novel therapy for ovarian cancer caused by a specific genetic mutation, called PP2R1A. Epithelial ovarian cancer is the most common form of ovarian cancer and the leading cause of gynecologic cancer deaths in the United States. Chemoresistance to currently available platinum-based drugs like cisplatin represents a major treatment challenge, as more than 50 percent of affected women ultimately relapse and die from this disease. Wistar’s Rugang Zhang, Ph.D., leader of the Immunology, Microenvironment and Metastases Program, is focused on developing novel therapeutics for subtypes of ovarian cancer that currently have no effective therapies and on improving the current standard of care. Dr. Zhang’s previous work suggests that KAT6A signaling plays a critical role in ovarian cancer progression. Targeting this signaling pathway could be an effective strategy for treating ovarian cancer. Working with Dr. Zhang on this project are Graham Cancer Center gynecologic oncologists Mark Cadungog, M.D., director of Robotic Surgery, and Sudeshna Chatterjee-Paer, M.D., and Cawley CTCR’s Stephanie Jean, M.D., director of Gynecologic Oncology Research. Also collaborating with the team is Wistar’s Alessandro Gardini, Ph.D., assistant professor in the Gene Expression & Regulation Program. ‘Mini organs’ offer hope for therapeutics Dr. Sims-Mourtada at the Cawley CTCR will lead a new program to culture organ-specific tissue from stem cells that could change the way diseases are studied and treated. These so called “mini organs” or “organoids” are three-dimensional tissue cultures grown in the lab that replicate the complexity and functions of a specific tissue or organ found in the body. Organoids offer scientists a better model for how drugs and other therapeutics might interact with a patient’s particular type of tumor, opening new avenues for precision medicine. “The ability to grow each patient’s tumor in a three-dimensional organoid along with our capability to create patient-derived xenograft or animal models as part of our PDX core, will allow us to fully capture the effects of genetic as well as gene altering behavioral and environmental influences that are lacking in current research models,” said Dr. Sims-Mourtada. “Our collaboration with Wistar to build these programs raises our clinical platform to the next level for studying new cancer biomarkers and treatments.” Advancing a Pioneering Partnership The Graham Cancer Center made history when it signed a first-of-its-kind agreement in 2011 with The Wistar Institute, pairing a National Cancer Institute, NCI-designated basic research institution with a community cancer center that is also an NCI Community Oncology Research Program (NCORP). “Our partnership with Wistar has attracted national recognition as a model of collaboration that leverages cutting-edge research to benefit cancer prevention and therapy statewide,” says Nicholas J. Petrelli, M.D., Bank of America endowed medical director of ChristianaCare’s Helen F. Graham Cancer Center and Research Institute. “With Wistar, our productive collaborations over the last decade continue to drive discovery research toward clinical trials to benefit patients here at the Graham Cancer Center and in communities everywhere.” “The Graham Center has been an ideal partner in our mission,” said Dario C. Altieri, M.D., Wistar president and CEO and director of the Ellen and Ronald Caplan Cancer Center. “Our scientists at Wistar have access to clinically-annotated primary patient specimens of the highest quality. As the majority of patients at the Graham Cancer Center are treatment naïve, this collaboration affords an opportunity to conduct unique, high impact mechanistic and correlative studies that will ultimately advance important scientific discoveries that hopefully will lead to better cancer therapies.”
Bowel or fecal incontinence, according to the Mayo Clinic, “is the inability to control bowel movements, causing stool (feces) to leak unexpectedly from the rectum. Also called bowel incontinence, fecal incontinence ranges from an occasional leakage of stool while passing gas to a complete loss of bowel control. Common causes of fecal incontinence include diarrhea, constipation, and muscle or nerve damage. The muscle or nerve damage may be associated with aging or with giving birth.” Dr. Satish Rao is a seasoned gastroenterologist and an expert in digestive health, particularly the brain-gut connection. Rao, a professor of medicine at the Medical College of Georgia at Augusta University, recently offered a Q&A on the topic of fecal incontinence with the journal Gastroenterology & Hepatology. What is the prevalence of fecal incontinence in the adult population? Surveys have indicated a prevalence of approximately 9% to 10% in the United States. A recent study reported a 14% prevalence, although this study was Internet-based and, thus, may not have included many elderly patients, as they may not be as computer-savvy as younger patients. It is safe to say that one in seven Americans currently suffers from fecal incontinence. Prevalence appears to be equal in men and women, although women outnumber men almost three to one when it comes to gastroenterology clinic visits and health care-seeking. Men may be too embarrassed to bring the issue of fecal incontinence to the attention of a physician, but when asked about it, they will admit and discuss it. Also, extracting information from a patient about fecal incontinence depends on how the question is asked. Asking patients whether they have daily leakage vs whether they ever have had leakage or have had leakage in the past month will elicit different responses that a clinician may interpret differently. It is important to remember that leakage is not a physiologic event that a healthy adult should have at any time, even once a month or once a year. Not having the capacity to control bowel evacuation or having leakage unaware of its occurrence signals an abnormality. What are notable risk factors for fecal incontinence? In women, pregnancy can be a risk factor, particularly if giving birth involves pelvic tissue damage, such as injury inflicted by forceps use or the unfortunate occurrence of a significant tear. Neurologic or back injuries are other common risk factors. Also, chronic diarrhea can progress to fecal incontinence owing to severe irritation of the rectum or irritants in stool. Further, any condition that changes the ability of rectal capacity can result in fecal incontinence. These circumstances can include surgery or radiation to the rectal area. Hear from a patient and learn more about Rao's research using magnetic stimulation to treat fecal incontinence. What treatment modalities are currently available? Simple, conservative treatment consists of educating patients about fecal incontinence and instructing them to avoid precipitating events. For example, although many people love to have a meal followed by a cup of coffee and a walk, such a sequence of activities is ill-advised for an incontinent patient: the meal provokes a gastric-colonic response, coffee is a powerful colonic stimulant, and exercise also stimulates motility. This triad creates the perfect storm for a stool leakage or accident while the patient is out on the after-dinner walk. Antidiarrheal therapies can be very effective but only in approximately 15% to 20% of patients. Another treatment is biofeedback, which can correct muscle weakness using behavioral techniques. Biofeedback provides resolution in approximately 50% to 70% of patients. The traditional model of office-based biofeedback requires that the patient make 6 or even up to 10 visits to a specialty clinic. This may mean that some patients must drive very long distances to an appropriate care facility that is staffed with trained personnel or physical therapists. This scenario presents a significant challenge for many patients, which is increasingly being recognized by health care professionals and researchers. Good devices for home-based biofeedback have been scarce; however, such a device was recently approved by the US Food and Drug Administration. The research center at Augusta University has tested it in a clinical trial setting and found it to be quite effective as a home biofeedback treatment. Dextranomer is another treatment modality. It involves injection of small beads of dextran polymers into the anorectal region. The beads form a protective cuff or a buffer to stop stool leakage. Another treatment modality is sacral nerve stimulation using the Medtronic InterStim system. The patient is outfitted with a pacemaker-like device with wires that continuously stimulate the sacral nerves that control stool events. In the case of a torn muscle, suturing the torn ends to reduce the size of the anorectal opening is usually useful for women postpartum, although the effect may not be sustained in the long term. What emerging treatments and research should clinicians be aware of? One emerging treatment developed at Augusta University’s Clinical Research Center is called translumbosacral neuromodulation therapy (TNT). TNT is similar to TAMS and involves the fecal delivery of magnetic energy through an insulated coil to the lumbosacral nerves that regulate anorectal function. The pulses generated are of the same strength as those of magnetic resonance imaging. The team at Augusta University’s research center has shown that TNT mechanistically improves nerve function and substantively improves stool leakage. A sham-controlled study and long-term study are currently underway at Augusta University and Harvard University’s Massachusetts General Hospital. These studies are being sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases. A multicenter study sponsored by the National Institutes of Health that the team at Augusta University also is involved with is the FIT (Fecal Incontinence Treatment) trial. This randomized study compares biofeedback with dextranomer injection. Also, as mentioned, tools are becoming available for home biofeedback that should allow many more affected patients to receive treatment because they can do so in the comfort of their own home. The research center at Augusta University is working on a novel home biofeedback protocol for the treatment of constipation and fecal incontinence. Thus, novel noninvasive tools are emerging for fecal incontinence. The repertoire of current and emerging tools holds the promise of improved outcomes for patients with fecal incontinence. Rao is also the founder of the Augusta University Digestive Health Center. He is available to speak to media regarding any aspect of digestive health -- simply click on his icon now to arrange an interview today.
Antimicrobial resistance now causes more deaths than HIV/AIDS and malaria worldwide – new study
Antimicrobial resistance is spreading rapidly worldwide, and has even been likened to the next pandemic – one that many people may not even be aware is happening. A recent paper, published in Lancet, has revealed that antimicrobial resistant infections caused 1.27 millions deaths and were associated with 4.95 million deaths in 2019. This is greater than the number of people who died from HIV/AIDS and malaria that year combined. Antimicobial resistance happens when infection-causing microbes (such as bacteria, viruses or fungi) evolve to become resistant to the drug designed to kill them. This means than an antibiotic will no longer work to treat that infection anymore. The new findings makes it clear that antimicrobial resistance is progressing faster than the previous worst-case scenario estimates – which is of concern for everyone. The simple fact is that we’re running out of antibiotics that work. This could mean everyday bacterial infections become life-threatening again. While antimicrobial resistance has been a problem since penicillin was discovered in 1928, our continued exposure to antibiotics has enabled bacteria and other pathogens to evolve powerful resistance. In some cases, these microbes are resistant even to multiple different drugs. This latest study now shows the current scale of this problem globally – and the harm it’s causing. Global problem The study involved 204 countries around the world, looking at data from 471 million individual patient records. By looking at deaths due to and associated with antimicrobial resistance, the team was then able to estimate the impact antimicrobial resistance had in each country. Antimicrobial resistance was directly responsible for an estimated 1.27 million deaths worldwide and was associated with an estimated 4.95 millions deaths. In comparison, HIV/AIDS and malaria were estimated to have caused 860,000 and 640,000 deaths respectively the same year. The researchers also found that low- and middle-income countries were worst hit by antimicrobial resistance – although higher income countries also face alarmingly high levels. They also found that of the 23 different types of bacteria studied, drug resistance in only six types of bacteria contributed to 3.57 million deaths. The report also shows that 70% of deaths that resulted from antimicrobial resistance were caused by resistance to antibiotics often considered the first line of defence against severe infections. These included beta-lactams and fluoroquinolones, which are commonly prescribed for many infections, such as urinary tract, upper- and lower-respiratory and bone and joint infections. This study highlights a very clear message that global antimicrobial resistance could make everyday bacterial infections untreatable. By some estimates, antimicrobial resistance could cause 10 million deaths per year by 2050. This would overtake cancer as a leading cause of death worldwide. Next pandemic Bacteria can develop antimicrobial resistance in a number of ways. First, bacteria develop antimicrobial resistance naturally. It’s part of the normal push and pull observed throughout the natural world. As we get stronger, bacteria will get stronger too. It’s part of our co-evolution with bacteria – they’re just quicker at evolving than we are, partly because they replicate faster and get more genetic mutations than we do. But the way we use antibiotics can also cause resistance. For example, one common cause is if people fail to complete a course of antibiotics. Although people may feel better a few days after starting antibiotics, not all bacteria are made equal. Some may be slower to be affected by the antibiotic than others. This means that if you stop taking the antibiotic early, the bacteria that were initially able to avoid the effect of the antibiotics will be able to multiply, thus passing their resistance on. Likewise, taking antibiotics unnecessarily can help bacteria to evolve resistance to antibiotics faster. This is why it’s important not to take antibiotics unless they’re prescribed, and to only use them for the infection they’re prescribed for. Resistance can also be spread from person to person. For example, if someone who has antibiotic-resistant bacteria in their nose sneezes or coughs, it may be spread to people nearby. Research also shows that antimicrobial resistance can be spread through the environment, such as in unclean drinking water. The causes driving this global antimicrobial resistance crisis are complex. Everything from how we take antibiotics to environmental pollution with antimicrobial chemicals, use of antibiotics in agriculture and even preservatives in our shampoo and toothpaste are all contributing to resistance. This is why a global, unified effort will be needed to make a difference. Urgent change is needed in many industries to slow the spread of antimicrobial resistance. Of the greatest importance is using the antibiotics we have smarter. Combination therapy could hold the answer to slowing down antimicrobial resistance. This involves using several drugs in combination, rather than one drug on its own – making it more difficult for bacteria to evolve resistance, while still successfully treating an infection. The next pandemic is already here – so further investment in research that looks at how we can stop this problem will be key.
