News

ROCHESTER, Minn. — Mayo Clinic physicians will present findings at the American College of Gastroenterologists Annual Scientific Meeting, Oct. 25–30 in San Antonio. Findings to be presented are: Patients with microscopic colitis do not have reduced risk of developing colon polyps Newswise — Cross-sectional studies have suggested that patients with microscopic colitis have a lower risk than the general population of developing colon polyps after diagnosis, but a 10-year, multicenter cohort study finds that there's no change in risk. Microscopic colitis is a common cause of chronic diarrhea, and previous studies have found that these patients have a lower incidence of colon polyps. The cohort study, which reviewed 1,128 cases of patients who underwent colonoscopy at Mayo Clinic and Columbia University Irving Medical Center in New York City, found that there was no significant association between microscopic colitis and risk of polyps, says Darrell Pardi, M.D., a Mayo Clinic gastroenterologist and the study's senior author. "Our data suggest that patients with microscopic colitis are at the same risk of developing polyps during follow-up examinations as the general population and therefore their need for surveillance colonoscopy is also the same," says Dr. Pardi. Anti-tumor necrosis factor (TNF) therapy linked to preeclampsia in women with inflammatory bowel disease Women with inflammatory bowel disease have an increased risk of adverse pregnancy outcomes, and some studies have suggested an association between the disease and preeclampsia, a pregnancy complication that results in high blood pressure, and possible damage to the liver, kidneys or other organs. Mayo Clinic researchers looked into whether anti-tumor necrosis factor therapy, which commonly is used to treat inflammatory bowel disease, reduced the risk of patients developing preeclampsia. The results of the small study, which involved nine women with preeclampsia and 18 controls, were surprising. "When we examined the risk for preeclampsia in those on anti-TNF therapy, it was actually higher than in the nonexposed group," says Sunanda Kane, M.D., a Mayo Clinic gastroenterologist and senior author. "We theorize that exposure to anti-TNF agents is a marker of more severe disease, and the amount of inflammation in the body is what drives the increased risk for preeclampsia." Positive polymerase chain reaction (PCR) test results may not predict recurrence of common infection Clostridioides difficile infection is the most common health care-associated infection in the U.S., and it sometimes recurs after initial treatment. Several tests are available for diagnosis, including polymerase chain reaction. This test provides quick results, but can produce a positive result, even after appropriate treatment of the infection. Mayo Clinic researchers wanted to determine whether a positive polymerase chain reaction result during or after treatment predicted infection recurrence. The study involved 50 patients with C. diffinfection who submitted stool samples for polymerase chain reaction testing. The infection recurred within 56 days for 28% of patients, but the study found that patients with a positive polymerase chain reaction after treatment completion did not have a higher risk of recurrence. "We were surprised that positive PCR results during or after treatment did not seem to predict recurrence," says Sahil Khanna, M.B.B.S., a Mayo Clinic gastroenterologist and the study's corresponding author. Though more research is needed, Dr. Khanna says patients with C. diff infection should not routinely undergo repeat polymerase chain reaction testing to predict recurrence. Study proposes new method, protocol to study stomach function after bariatric surgery Bariatric surgery reduces the size of the stomach and is intended to help patients lose weight by limiting how much they can eat. Some patients don't achieve significant weight loss, however, while some regain weight later. It's difficult to measure and assess the patient's stomach after surgery, which limits doctors' ability to develop treatment strategies. Mayo Clinic researchers set out to develop a new way to study stomach function after bariatric surgery. They also sought to develop a new protocol to evaluate stomach accommodation — how much the stomach increased in size after eating — and stomach emptying at the same time. Their study outlines values for the new test protocol. "Utilizing this new test, we will be able to have a better idea of how the stomach functions after bariatric surgery," says Xiao Jing Wang, M.D., a Mayo Clinic gastroenterology fellow and the study's lead author. "This protocol may lead to additional treatments, such as medications that delay stomach emptying, to restore the sensation of fullness after meals." About Mayo ClinicMayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news and An Inside Look at Mayo Clinic for more information about Mayo.
Credit: Allison Carter, Georgia Tech Graduate Student Chia-Heng Chu adjusts a 3D-printed cell trap in the laboratory of Assistant Professor A. Fatih Sarioglu at Georgia Tech. The trap captures white blood cells to isolate tumor cells from a blood sample.   Newswise — Finding a handful of cancer cells hiding among billions of blood cells in a patient sample can be like finding a needle in a haystack. In a new approach enabled by 3D-printed cell traps, researchers are removing the hay to expose the cancer cells. Trapping the white blood cells – which are about the size of cancer cells – and filtering out smaller red blood cells leaves behind the tumor cells, which could then be used to diagnose the disease, potentially provide early warning of recurrence and enable research into the cancer metastasis process. The work, led by researchers at the Georgia Institute of Technology, could advance the goal of personalized cancer treatment by allowing rapid and low-cost separation of tumor cells circulating in the bloodstream. “Isolating circulating tumor cells from whole blood samples has been a challenge because we are looking for a handful of cancer cells mixed with billions of normal red and white blood cells,” said A. Fatih Sarioglu, an assistant professor in Georgia Tech’s School of Electrical and Computer Engineering (ECE). “With this device, we can process a clinically-relevant volume of blood by capturing nearly all of the white blood cells and then filtering out the red blood cells by size. That leaves us with undamaged tumor cells that can be sequenced to determine the specific cancer type and the unique characteristics of each patient’s tumor.” The research was reported September 20 in the journal Lab on a Chip, and was supported by a seed grant from the Integrated Cancer Research Center at Georgia Tech. Other attempts to capture circulating tumor cells have attempted to extract them from the blood using microfluidic technology that recognizes specific surface markers on the cancer cells. But because the cancer can change over time, the malignant cells can’t be recognized with certainty. And even if they can be captured, the tumor cells must be removed from circuitous channels in the device and separated from the antigen without causing damage. Sarioglu and collaborators, including ECE graduate student and first author Chia-Heng Chu, decided to take a different approach, building 3D-printed traps lined with antigens to capture the white blood cells in a sample. The 3D printed traps allowed the researchers to greatly expand the surface area for capturing the white blood cells as they pass by in blood samples. Zig-zagging fluid channels, some as much as half a meter long, increase the likelihood that every white blood cell would come into contact with a channel wall. “Usual microfluidic devices have just a single layer with channel heights of 50 to 100 microns,” Sarioglu said. “They are thick, but most of it just empty plastic. Using 3D printing liberates us from the single channel and allows us to create many channels in three dimensions that better utilize the space.” While the 3D printing allowed an increase in channel density, that came with a significant challenge. Earlier microfluidic devices could be designed with etched channels to carry the blood. But with 3D printing processes that are fabricated layer-by-layer, channels had to be filled with wax to allow more channels to be built atop them. The torturous channel structure, designed to maximize cell-wall interaction, made it virtually impossible to get the wax out after fabrication. The solution was to design cell traps that fit into standard centrifuges designed to spin samples for separation. The traps were heated in the centrifuge and then spun to allow the melted wax to escape. After removing the liquid wax, the channels received the antigen coating. After the white blood cells are removed, the smaller red blood cells pass through a simple commercial filter that traps the cancer cells and any remaining white blood cells. The tumor cells can then be removed from the filter, which is integrated into the 3D printed device. Minimal processing of blood samples is a goal for the project to make the process available to clinics and hospitals without requiring specialized technician skills. Less processing also reduces the risk of damage to the tumor cells and minimizes other cellular changes that could skew the evaluation. As part of the proof of principle testing, the researchers coated the white blood cells with biotin to accelerate testing. Future cell traps will use antigens designed to attract the cells to the channel walls without the biotin processing step. The researchers tested their approach by adding cancer cells to blood taken from healthy people. Because they knew how many cells were added, they could tell how many they should extract, and the experiment showed the trap could capture around 90 percent of the tumor cells. Later testing of blood samples from prostate cancer patients isolated tumor cells from a 10-milliliter whole blood sample. Testing included cells from prostate, breast and ovarian cancer, but Sarioglu believes that the device will capture circulating tumor cells from any type of cancer because the removal mechanism targets blood cells rather than cancer cells. Next steps will be to narrow the channels in the device, test white blood cell removal without the use of biotin, boost the percentage of white cell extraction and connect cell traps to increase trapping capacity. “We expect that this will really be an enabling tool for clinicians,” Sarioglu said. “In our lab, the mindset is always toward translating our research by making the device simple enough to be used in hospitals, clinics and other facilities that will help diagnose disease in patients.” Other co-authors of the paper include Ruxiu Liu, Tevhide Ozkaya-Ahmadov, Mert Boya, Brandi E. Swain, Jacob M. Owens, Enerelt Burentugs, and John F. McDonald, all from Georgia Tech, and Mehmet Asim Bilen from Emory University. CITATION: Chia-Heng Chu, et al, “Hybrid Negative Enrichment of Circulating Tumor Cells from Whole Blood in a 3D-Printed Monolithic Device.” (Lab on a Chip, 2019) http://dx.doi.org/10.1039/C9LC00575G
Newswise — Bethesda, Md. – The effects of a traumatic brain injury (TBI) are pretty clear – problems with memory, headaches, and emotions – but what’s unclear is the underlying pathological causes for those symptoms. According to new research led by researchers at the National Institutes of Neurological Disorders and Stroke (NINDS), those underlying pathological causes may actually involve more extensive blood vessel damage than previously known. These findings could help target better treatment of these common injuries. The study, “Traumatic microbleeds and vascular injury,” was published Oct. 13 in the journal Brain, and was a collaborative effort between the Uniformed Services University of the Health Sciences (USU), the National Institutes of Health (NIH), the University of Maryland, and the Cold Spring Harbor Laboratory. TBI sustained in sports or on the battlefield can have fatal or lasting effects, but until now it’s been unclear how these symptoms develop pathologically. Therefore, the researchers sought to better understand the pathological mechanisms that cause these symptoms by examining the brains of hundreds of patients very soon after injury using high-resolution imaging techniques. They looked, specifically, at traumatic microbleeds – where trauma left a physical imprint on the brain that appeared as dark lesions on MRI scans, according to Dr. Lawrence Latour, the study's lead author and a researcher at NINDS. Of the study’s 439 patients with acute TBI (less than 48 hours after injury), about 30 percent had evidence of traumatic microbleeds (blood vessel injury). The traumatic microbleeds were also identified in 27 percent of mild, 47 percent of moderate, and 58 percent of severe TBI patients. They also found that traumatic microbleeds were seen in more than 25 percent of patients with mild TBI, suggesting that traumatic microbleeds are not exclusive to patients with moderate or severe TBI.  Overall, blood vessel damage was much more widespread than expected in patients with TBI. “These findings are also significant because the presence of traumatic microbleeds was an independent predictor of outcome,” according to Dr. Regina Armstrong, director of Translational Research in USU’s Center for Neuroscience and Regenerative Medicine (CNRM) who also collaborated on the study. The researchers also found patients who had traumatic microbleeds were more than twice as likely to have a disability as a result of their TBI upon follow-up at 30 and 90 days post injury.  “This study is important to the general public, and especially the military, to help detect TBI and provide treatments to those at risk of prolonged symptoms,” Armstrong said. “Future studies are needed to explore therapies targeting the effects of traumatic microbleeds in acute TBI, including TBIs that result from high-impact blast exposures.” The study was supported by USU’s CNRM, the NINDS, and the Intramural Research Programs at the NIH Clinical Center. 
Photo credit: Katrina Wittcamp Elizabeth A. Myers, BSN, RN and Wendy K. Benson, MBA, OTR/L of 2x2 Health and authors of The Confident Patient.   On average, a typical doctor’s appointment lasts less than 15 minutes. Making the most of that opportunity is critical. The Confident Patient, a new book written by Chicago-based authors Wendy K. Benson, MBA, OTR/L and Elizabeth A. Myers, BSN, RN, coaches patients and their families through the complex healthcare system by providing real life stories, sample questions and advice from medical professionals. After years of experiences and interviews with medical teams across the country, Benson and Myers recognized a recurring theme: medical teams intuitively want to support their patients, but they don’t always feel they’re on the same page with their patients. Ranging from managing costly medications to finding trustworthy online resources to securing second opinions, The Confident Patient shares strategies and insights on ways to improve healthcare decision-making and outcomes. “As a nurse, I saw patients who were extremely overwhelmed with managing their healthcare experience – knowing which medical personnel said what, remembering which medications to take and when, keeping up-to-date with doctor appointments, understanding what is going on and next steps, as well as communicating with loved ones…it all adds up. This is compounded by health complications, insurance coverage, confusing medical terms – it’s no wonder anxiety builds,” explains Myers. “Our goal is to share our experiences with patients and their families, so they find comfort in knowing they are not alone, and they are empowered to take control of their own healthcare journey.” Research indicates that the connection patients build with their medical team directly correlates with the confidence they have in them, as well as the confidence they have in their own decision-making abilities. The Confident Patient go-to guide includes concrete tips and take-aways such as: How to become a confident patient A list of questions to bring with you to your next appointment Definitions of common medical terms and procedures Managing your healthcare information Guide to being a confident patient advocate for your loved one Considerations during follow-up appointments Planning for the ‘After’: Preparing for your return home/recovery period 10 Things your Medical Team Wants you to Know “A few years ago, as I was working with a client and I asked him about the goal of his upcoming surgery that he and his surgeon had discussed.  Unfortunately, the goals were either not discussed or the patient could not recall what the goals were,” recalls Benson. “So while the patient may have expected to return to his golf game within a matter of months, the surgeon could be primarily focused on pain relief with limited mobility. We realized at that point that there can be significant communication gaps between medical teams and their patients. And that’s where The Confident Patient steps in,” explains Benson. The Confident Patient is an international best-seller and is available on Amazon and Barnes and Noble in paperback, as an audio book and on Kindle, and on www.2x2Health.com. Co-authors Wendy K. Benson (Chief Operating Officer) and Elizabeth A. Myers (Chief Executive Officer) are the leaders of 2x2 Health: Private Health Concierge in Chicago. 2x2 Health is a team of experienced healthcare professionals who fill the gaps by providing coordination of services, clinical companionship and recovery care for individuals and their families. With more than 40 years of combined clinical and leadership experience, they are dedicated to helping others improve their health and their quality of life. Together, they have built a comprehensive team that helps with everything from navigating a complex health issue to attending doctor appointments to assisting with a hospital discharge and transitioning home. For more information about setting-up an interview or speaking event with Chicago-based authors Wendy K. Benson, MBA, OTR/L and Elizabeth A. Myers, BSN, RN, please contact: Katie Heraty at kheaty@cs-effect.com.  
Newswise — Halifax, NS (Sept. 30, 2019) – Most people can continue to eat red and processed meat as they do now. A panel of international scientists led by researchers at Dalhousie and McMaster universities systematically reviewed the evidence and have recommended that most adults should continue to eat their current levels of red and processed meat. The researchers performed four systematic reviews focused on randomized controlled trials and observational studies looking at the impact of red meat and processed meat consumption on cardiometabolic and cancer outcomes. In one review of 12 trials with 54,000 people, the researchers did not find statistically significant or an important association between meat consumption and the risk of heart disease, diabetes or cancer. In three systematic reviews of cohort studies following millions of people, a very small reduction in risk among those who had three fewer servings of red or processed meat a week, but the association was uncertain. The authors also did a fifth systematic review looking at people’s attitudes and health-related values around eating red and processed meats. They found people eat meat because they see it as healthy, they like the taste and they are reluctant to change their diet. Bradley Johnston, PhD, corresponding author on the reviews and guideline and an associate professor of community health and epidemiology at Dalhousie University, said the research team realizes its work is contrary to many current nutritional guidelines.  “This is not just another study on red and processed meat, but a series of high quality systematic reviews resulting in recommendations we think are far more transparent, robust and reliable,” he said. Johnston added: “We focused exclusively on health outcomes, and did not consider animal welfare or environmental concerns when making our recommendations.  “We are however sympathetic to animal welfare and environmental concerns with a number of the guideline panel members having eliminated or reduced their personal red and processed meat intake for these reasons.” The five systematic reviews, a recommendation and an editorial on the topic were published in the Annals of Internal Medicine today. The accompanying editorial by authors at the Indiana University School of Medicine said: “This is sure to be controversial, but is based on the most comprehensive review of the evidence to date. Because that review is inclusive, those who seek to dispute it will be hard pressed to find appropriate evidence with which to build an argument.”   Gordon Guyatt, chair of the guideline committee and a professor at McMaster, said the research group with a panel of 14 members from seven countries used a rigorous systematic review methodology, and GRADE methods which rate the certainty of evidence for each outcome, to move from evidence to dietary recommendations to develop their guidelines. “There is a worldwide interest in nutrition, and the issue of red meat in particular. People need to be able to make decisions about their own diet based on the best information available,” he said. Other researchers involved in the work included those from the Netherlands, Poland and Spain, and the guideline committee included lay people as well as the scientists. There were no primary external funding sources.
Newswise — Nearly one in three low-income people who enrolled in Michigan’s expanded Medicaid program discovered they had a chronic illness that had never been diagnosed before, according to a new study. And whether it was a newly found condition or one they’d known about before, half of Medicaid expansion enrollees with chronic conditions said their overall health improved after one year of coverage or more. Nearly as many said their mental health had improved. The study looked at common chronic diagnoses such as diabetes, high blood pressure, depression and asthma – the kinds of conditions that can worsen over time if not found and treated. Left untreated or under-treated for years, they can heighten risks for costly health crises such as heart attack, stroke, kidney failure, blindness and suicide. The study was conducted by a team from the University of Michigan Institute for Healthcare Policy and Innovation. They used surveys and interviews with people enrolled in the Healthy Michigan Plan, which extended health insurance coverage to adults living near or below the poverty line. Their findings are published in the Journal of General Internal Medicine. The findings suggest that low-income people enrolled in expanded Medicaid are now getting care that could prevent complications later in life. The interviews revealed that many knew they should be getting such care but couldn’t afford it. The findings also point to an important message for states that have recently expanded Medicaid or are considering it, says lead author Ann-Marie Rosland, M.D., M.S. “New Medicaid expansion programs will need to be prepared to provide a large amount of care for newly diagnosed or untreated chronic conditions,” says Rosland, a former U-M researcher now at the University of Pittsburgh. “But a focus on care for people with chronic conditions is particularly likely to lead to improvements in enrollees’ health.” Rosland worked with Susan D. Goold, M.D., MHSA, M.A., and other members of the IHPI team that is carrying out an official evaluation of the Healthy Michigan Plan. “Michigan’s Medicaid expansion emphasizes primary care and health risk assessment, and many enrollees were found to have a chronic condition that will benefit from ongoing management,” says Goold, a professor of internal medicine at U-M. “Soon after enrollment, those with chronic conditions reported substantial improvements in access to care and in health compared to before they got Healthy Michigan Plan coverage. Improvements in access and health could well lead to improved quality of life and ability to work and care for family.” More about the study The researchers tallied data from a representative sample of 4,090 people who had been covered by the Healthy Michigan Plan for at least a year, and compared them with a similar population of Michigan residents. They also conducted in-depth interviews with a diverse group of 67 people who had been enrolled in the program at least six months. In all, 68% of those surveyed had at least one chronic health condition, 58% had two or more, and 12% had four or more. Of those with a chronic condition of any kind, 42% said it had been identified after their enrollment. The researchers found that more than a third of those with diabetes or serious chronic lung disease said it had been diagnosed since they enrolled. So had one-third of those who said they had high blood pressure or heart disease, and nearly a third of those with depression, anxiety or bipolar disorder. Two-thirds of those who said their condition was newly diagnosed had been uninsured in the year before they enrolled. Those with chronic conditions were more likely to be white and have very low incomes, less than one-third the federal poverty level. In the year of the study, the poverty level was an annual income of $11,880 for an individual, and individuals making up to $16,394 qualified for Healthy Michigan Plan. Impacts on access and health Knowing about a diagnosis is only the first step in managing a chronic condition, the researchers note. Getting access to appointments with health providers, medicines and other treatments and support services is also important. Two-thirds of those with chronic conditions said their access to prescription drugs had improved. Ninety percent had seen a primary care physician within a year after enrolling. While studies of other states’ expansion programs haven’t found signs of improved health and access to care until two to four years after Medicaid expansion, the new study found signs that this was already happening over an even shorter time period in Michigan. In all, 52% of those with chronic conditions said their physical health had improved, and 43% said their mental health had improved. After the researchers adjusted for other health and demographic factors, those with chronic conditions were nearly twice as likely as other Healthy Michigan Plan participants to say that both types of health had improved. “For the enrollees with chronic conditions, we were particularly struck that people who reported they had better access to mental health care said their physical health improved more often,” says Rosland. “This was in addition to health improvements linked to things like better prescription and primary care access.” The interviews with enrollees also yielded interesting findings. Said one man, “I had diabetes for 7 years … I just ignored it because I couldn’t afford the medicine… I got my diabetes under control and I feel a lot better.”  And one woman told the researchers that after enrolling, “You’re not afraid to go to the doctor. So you take care of these situations before they get too bad.” In addition to Rosland and Goold, the paper’s authors are members of the IHPI Healthy Michigan Plan evaluation team: Edith C. Kieffer, Ph.D., M.P.H. of the U-M School of Social Work, who led the interview portion of the study; Renuka Tipirneni, M.D., M.Sc., Jeffrey T. Kullgren, M.D., M.S., M.P.H.,  Matthias Kirch, M.S., Emily K. Arntson, M.S., Sarah J. Clark, Ph.D., Sunghee Lee, Ph.D., Erica Solway, Ph.D., Erin Beathard, M.P.H., M.S.W., and IHPI director John Z. Ayanian, M.D., M.P.P. IHPI’s evaluation of the Healthy Michigan Plan, as required by the Centers for Medicare & Medicaid Services, is funded by a contract with the Michigan Department of Health and Human Services. To learn more, visit https://ihpi.umich.edu/signature-programs/healthy-michigan-plan-evaluation Reference: JGIM, DOI:10.1007/s11606-019-05323-w, https://link.springer.com/article/10.1007/s11606-019-05323-w
UNC School of Medicine researcher Rob Tarran, PhD, led a review of all published scientific literature on the effects of e-cigarette use on the respiratory system. The team of four authors strongly recommend tighter regulation of e-cigarette products. Newswise — CHAPEL HILL, NC – Four scientists from four leading universities in the United States conducted a comprehensive review of all e-cigarette/vaping peer-reviewed scientific papers that pertain to the lungs and published their findings today in the British Medical Journal. Corresponding author Rob Tarran, PhD, professor of cell biology and physiology and member of the UNC Marsico Lung Institute, said, “Studies show measurable adverse biologic effects on lung health and cells in humans, in animals, and in tissue samples studied in the lab. The effects of e-cigarettes have similarities to those seen in traditional cigarettes and important differences.” Doctors know that the development of chronic, life-threatening diseases related to cigarette smoking, such as lung cancer and emphysema, take decades to develop. Also, it took decades to scientifically prove that smoking cigarettes caused cancer. Vaping has been popular for about 10 years. Scientists have been studying the effects of e-cigarettes for about five years. What they’ve found suggests that vaping is not without effects. It is not “safe.” “The scientific community’s current knowledge is insufficient to determine whether the respiratory health effects of e-cigarettes are less than the now obvious health effects of combustible tobacco products,” said Tarran, who is also a member of the UNC Lineberger Comprehensive Cancer Center. The other authors of the BMJ paper are Jeffrey Gotts, MD, PhD, assistant professor of medicine at the University of California-San Francisco, Sven-Eric Jordt, PhD, associate professor of anesthesiology at Duke University with an adjunct appointment at Yale University, and Rob McConnell, MD, professor of preventative medicine at the Keck School of Medicine at the University of Southern California. Gotts is a pulmonologist/intensive care clinician, Jordt is a toxicologist, McConnell is an epidemiologist, and Tarran is a cell biologist and physiologist. The paper can be read in full. Below are a number of their key findings: A number of epidemiological studies showed increased respiratory symptoms in adolescent vapers, such as increased bronchitis-like symptoms, increased asthma, shortness of breath, etc. The researchers found a number of studies that showed effects of vaping on the whole lung, including possible lung damage (such as damage to the lung’s blood supply), and identified case reports from around the world indicating lipoid pneumonia that is similar to what is seen with the current epidemic in the United States. The researchers reported on a number of animal studies which typically found increased risk of lung damage and immunosuppression, such as increased susceptibility to bacterial or viral infections. “We also evaluated the effects of vaping on cells in the laboratory (in vitro studies),” Tarran said. “Most studies found that e-liquid exposure to pulmonary cells had effects including general cytotoxicity and impaired specialized functions, such as secretion and phagocytosis, which are important for proper lung function.” The researchers reviewed the possible health effects of e-liquid constituents including nicotine, propylene glycol/vegetable glycerin, and flavors. All have been shown to have adverse effects in animal and lab based studies at some concentrations. However, given the range of vaping behaviors in the real world, it is impossible to know the exact concentrations vapers are exposed to over any given timeframe. “Interestingly, when we looked at all the published papers on primary pulmonary cells – straight from the lungs of people to the lab – the only reports that did not see an effect of vaping on these cells were studies funded by the tobacco industry,” Tarran said.  The researchers also provided recommendations for clinicians and for future regulation of e-cigarettes. For heavy smokers, e-cigarettes should be prescribed cautiously as a smoking alternative, and should only be recommended as a cessation devise along with counseling and other therapies to help quit nicotine-product use permanently.  “We recommend that vape products be regulated more stringently along the lines of pharmaceutical products that go through a well-defined series of pre-clinical and human studies before they are released on the market,” Tarran said. The researchers also highlighted the challenges facing researchers in the field and provided recommendations for future research, such as the need to research the potential detrimental effects of vaping on adolescent lung development. The NIH and FDA funded this research.
Newswise — In early test tube and mouse studies, investigators at Johns Hopkins Medicine and the Johns Hopkins Kimmel Cancer Center have found that nonmuscle myosin IIC (MYH14), a protein activated in response to mechanical stress, helps promote metastatic behavior in pancreatic cancer cells, and that the compound 4-hydroxyacetophenone (4-HAP), known to stiffen myosin IIC-containing cells, can send it into overdrive, overwhelming the ability of cells to invade nearby tissue. The work, described online in July in the journal Cancer Research, found that 4-HAP reduced metastatic tumor formation in a mouse model of human pancreatic cancer by assessing the fraction of liver surface covered by tumor tissue. The researchers say their results suggest that targeting MYH14 and similar cytoskeletal proteins with 4-HAP is a potentially novel strategy for improving the survival of pancreatic cancer patients, and could eventually become part of a combination strategy with chemotherapy and/or immunotherapy agents. Much of the focus in developing new cancer drugs involves trying to inhibit a process or protein of interest, says senior study author Douglas N. Robinson, Ph.D., a professor of cell biology and oncology at Johns Hopkins. But some nonmuscle myosin II proteins have tumor-suppressive activities, so inhibiting them could increase rather than decrease the likelihood of metastasis. “There are two basic ways to stop the runaway train that is cancer metastasis. One is to throw up a roadblock in front of it, like an inhibitor. Or, we can get behind the train and push it faster and shove it off the tracks, and that’s kind of what we’re doing with 4-HAP,” he says. “We’re taking the system and shoving it to the right instead of the left, and thereby helping to halt the progression of disease-like behavior, such as invasion and metastasis.” The researchers first identified the proteins of interest by studying how cells change their shape in response to altering mechanical inputs, much like cancer cells will face as they navigate different mechanical environments as they metastasize, explains lead study author Alexandra Surcel, Ph.D., a research associate faculty member in Robinson’s lab. The investigators made some predictions about which proteins would be involved in the mechanobiome, a network of proteins that defines cells’ mechanical properties, senses and generates forces, and integrates mechanical with chemical cues. They studied seven proteins — nonmuscle myosin IIA, IIB and IIC; alpha-actinin 1 and 4; and filamin A and B — looking at a range of model systems, such as cell lines and human cancer patient tissue samples, to test the concept that overwhelming the response of some of these proteins could be harnessed as a tool to return invasive cells to a more stable, less active, noninvasive state. In a series of experiments, investigators found that these so-called mechanoresponsive proteins that accumulate in response to mechanical stress are upregulated or over-produced in human pancreatic cancer tissue samples and cell lines, and that these proteins directly impact cell mechanics. Highly mechanoresponsive proteins, including nonmuscle myosin IIA and IIC, α-actinin 4 and filamin B, increased in expression in human pancreatic cancer samples compared to levels found in healthy tissue.  In contrast, non-mechanoresponsive proteins — nonmuscle myosin IIB, α-actinin 1 and filamin A — had smaller changes in expression or disappeared with cancer progression. The team also found that myosin IIC, while low in overall abundance in pancreatic cancer cells, had a profound impact on cell architecture, movement, behavior and mechanics. Exposing cells to 4-HAP increased myosin IIC assembly, stiffening cells. The group then tested 4-HAP as a treatment in a mouse model of pancreatic cancer, finding that the compound led to a 50% reduction in metastases to the liver in mice transplanted with human pancreatic tissue. Modulating mechanoresponsive proteins like myosin IIC has several advantages over other cancer treatment strategies, says Robinson. First, scientists can fine-tune the activity of proteins that are upregulated in cancerous tissue, harnessing cells’ natural protein makeup to revert them to more normal types, while also protecting healthy cells that do not upregulate the targeted proteins. Second, this strategy draws upon the normal biochemistry of the protein to overwhelm the mechanics of the system. “There’s a misconception that proteins that make up the mechanobiome do not make good targets for pharmacological development for cancer patients,” adds Surcel. “That overlooks an entirely new targetable drug space, and our work on 4-HAP really demonstrates the viability of pursuing this class of proteins that have been relegated to the wayside.” According to the most recent figures from the National Cancer Institute, there are an estimated 73,554 people living with pancreatic cancer in the United States, according to the National Cancer Institute. Pancreatic cancer represents 3.2% of all new cancer cases in the U.S. Just 9.3% of patients survive five years or more after diagnosis. The laboratory is working on different versions of 4-HAP that could be tested on animals, Surcel says. Early evidence from Johns Hopkins and other labs indicates that 4-HAP also may be helpful in the treatment of colorectal and breast cancers. Study coauthors were Eric S. Schiffhauer, Dustin G. Thomas, Qingfeng Zhu, Kathleen T. DiNapoli, Hoku West-Foyle, Elizabeth M. Jaffee, Pablo A. Iglesias and Robert A. Anders of Johns Hopkins; and Maik Herbig, Oliver Otto, Angela Jacobi, Martin Kräter, Katarzyna Plak and Jochen Guck of Technical University of Dresden, Germany. The work was supported by the National Institutes of Health (grants GM66817 and GM109863), the Sol Goldman Foundation, a Johns Hopkins Discovery Award and the Alexander von Humboldt Foundation.
Newswise — Philadelphia, September 18, 2019 – Even though nonverbal or minimally verbal people who have autism spectrum disorder (ASD) make up between 25 and 30 percent of the total autistic population, almost no studies have been done focusing on this group and their particular needs.  To address this gap in knowledge of the true spectrum of autism, researchers at Children’s Hospital of Philadelphia (CHOP)’s Intellectual and Developmental Disabilities Research Center used state-of-the-art brain imaging techniques to determine how this specific group of children who have autism processes auditory stimuli, which could have important diagnostic and prognostic implications across the autism spectrum. The findings were published in the journal Molecular Autism. Previous brain imaging studies have found that children on the autism spectrum have prolonged or delayed auditory processing responses compared with their neurotypical peers. However, most imaging studies have focused on verbal children with autism. Children with limited or no speech have previously been excluded because they are more likely to have difficulty understanding the demands and requirements of the imaging process and are less likely to tolerate loud noises or other sensory experiences related to imaging techniques such as magnetic resonance imaging (MRI). In order to bridge this gap in understanding and to help answer questions about nonverbal or minimally verbal children with autism, CHOP scientists utilized a magnetoencephalography (MEG) technology, which allowed them to measure magnetic fields produced by electrical activity in the brain. This technology has previously been used to study brain signatures associated with autism.  With the support and input from parents and providers from the community, the study team developed the MEG Protocol for Low Language/Cognitive Ability (MEG-PLAN) specifically designed for this group of patients and for use with MEG technology. The interdisciplinary research team partners with families to implement MEG-PLAN.  “By using this plan, we’re able to provide families with materials that help familiarize them with the entire research visit process,” said Emily Kuschner, PhD, a licensed clinical psychologist and scientist at in the Lurie Family Foundations Magnetoencephalography (MEG) Center and the Center for Autism Research at CHOP. “For example, if a child has sensory sensitivities, they might be given scrubs to take home so they can get used to how they feel, or we might provide them with the adhesives used to attach the sensors to the face to desensitize a child to the experience.” “Since MEG is less invasive and does not expose the child to radiation, it can be less demanding than other imaging methods. We felt like we were in a better position to use this technology to study this population of children,” said Timothy Roberts, PhD, Vice-chair of Research for the Department of Radiology and the Oberkircher Family Endowed Chair in Pediatric Radiology, director of the Lurie Family Foundations MEG Imaging Center at CHOP and first author of the study.  A total of 105 patients were enrolled in the study (16 minimally verbal or nonverbal with autism, 55 verbal with autism, and 34 neurotypical patients to serve as a control). The researchers found that minimally verbal or nonverbal participants had delayed responses to simple auditory tones, and longer times to response were associated with poorer communication skills as measured by a standardized questionnaire completed by parents. Based on these findings, the authors said this study indicated that longer latency delays were associated with poorer language ability. Additionally, the findings suggest that measuring brain activity in the auditory cortex could serve as important objective markers for how these patients respond to sound.   “Given their association with language activity, we believe these measurements of response time have both prognostic and treatment ramifications,” Kuschner said. “It would be exciting if down the road we could use these MEG markers to understand the course of language development or personalize which treatment approach might be best for a particular child.” Roberts et al, “Delayed M50/M100 evoked response component latency in minimally verbal/nonverbal children who have autism spectrum disorder.” Mol Autism, online 15 August 2019. DOI: 10.1186/s13229-019-0283-3. About Children’s Hospital of Philadelphia: Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children’s Hospital has fostered many discoveries that have benefited children worldwide.  Its pediatric research program is among the largest in the country.  In addition, its unique family-centered care and public service programs have brought the 564-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu
By Andrea Madrigrano, MD, Breast Surgeon at Rush University Medical Center in Chicago and Associate Professor in the Department of Surgery at Rush Medical College; Kubtec Medical Imaging, The Mozart®   Receiving a breast cancer diagnosis is a confusing and traumatic experience for patients. Understanding what to expect prior to, during and after surgery, and knowing that a highly skilled surgeon will perform the operation can help reassure patients that they made the best possible choice for their cancer treatment.   The lumpectomy procedure (sometimes referred to as Breast Conserving Surgery, or BCS) is the treatment of choice for many patients, especially those with early-stage breast cancer. The surgeon seeks to remove the malignant tumor, while leaving behind as much healthy breast tissue as possible.  Studies show that this procedure is as effective as mastectomy (complete removal of the breast) at treating the disease, preserving much of the appearance and sensation of the breast.   Although lumpectomy surgery for breast cancer is a remarkably advanced and effective treatment, there are a number of topics patients should discuss with their doctors. For instance, a woman considering a lumpectomy may be unaware that in 20% of cases, a second surgery will be needed to remove lingering cancer cells.   The last thing a breast cancer patient wants to hear after the stress of having her first lumpectomy procedure is that the surgeon did not remove the full tumor and that she needs to have a second surgery, also known as re-excision. But how do you lower the risk of re-excision during lumpectomies? What do you need to know about your surgeon and the facility where the surgery takes place? And what happens after the surgery?   Below are eight questions patients should ask their surgeons prior to surgery.   How many breast cancer cases does the surgeon handle each year? How many mastectomies vs. lumpectomies does the surgeon perform and why? A second opinion can provide patients a more balanced and complete understanding of their options.   What is the surgeon’s re-excision rate? Nationwide figures show that one in five women undergoing lumpectomy will need a second procedure to remove lingering cancer cells. Many experts find this figure unacceptable. But re-excision rates can vary greatly from doctor to doctor and facility to facility. It’s also important to consider variables when talking about re-excision rates. Some surgeons will do more mastectomies and thus have lower re-excision rates. Others will remove a large volume of tissue.  There needs to be a balance of removing enough tissue to remove the cancer, while not removing too much tissue, which can leave the breast smaller and mis-shaped. The best surgeons will have both a low re-excision rate and low mastectomy rate and will remove the least amount of tissue possible. Some lumpectomies can be done with the help of a plastic surgeon to re-shape the other breast so that they match. Does the surgeon use intra-operative 3D specimen tomosynthesis imaging? 3D tomography has become the standard of care in mammography for screening. It is now also available to surgeons in the operating room, thus enabling a more precise surgery. Using 3D tomography during surgery has helped even very skilled surgeons increase their precision and reduce their re-excision rates even more. This is state-of-the art technology that enables the surgeon to the visualize the tumor right in the operating room, which no other technology or technique allows. In a recent study by researchers at UT Southwest Medical Center in Houston, surgeons reported that use of the 3D tomography technology during breast cancer surgery reduces re-excisions by more than 50 percent compared to the traditional 2D imaging methods commonly in use. This improvement translated into decreased returns to the operating room, decreased anxiety levels, and less costs to patients. It also saves on time in the operating room, because the surgeon does not have to wait while a specimen is taken to a separate radiology area for analysis. Evidence indicates that using 3D tomography during surgery can reduce a lumpectomy procedure by as much as 15 minutes, which for a patient means less time under anesthesia.   Does the surgeon use multi-disciplinary imaging review? Does the surgeon look at the images, not just the reports, with a radiologist in person? This in-person assessment is incredibly helpful for planning.   What is the post-operative pain plan? This is especially important in the current landscape, where doctors are faced with growing pressure to minimize opioid use but still provide patients with good pain control.   Is the facility a National Cancer Institutes-designated cancer center?   How well trained is the surgeon? Patients need to know more about their surgeons than whether they are board certified and where they performed their residency. Fellowship trained breast surgeons are recognized as experts in their ability to provide superior diagnosis and care related to breast cancer and disease.   Will the patient’s case be presented in a multidisciplinary breast cancer conference? Breast cancer is not a single disease, with only one approach to treatment. That’s why every woman has a different journey in her treatment.  Some women are cured with surgery alone, while other women require aggressive surgery, chemotherapy, radiation and targeted treatment to hopefully cure their disease.  Multidisciplinary Care involves input of medical oncologists, surgeons, radiation oncologists, pathologists and radiologists in determining the best treatment plan for a patient. This is important because some patients require medical treatment, or chemotherapy prior to surgery. In patients who have larger tumors, or tumors that have been found to have already spread to the lymph nodes, they benefit from treatment before surgery to help shrink the tumor and make surgery less involved.  More importantly, chemotherapy is used to reduce the chance that cancer can metastasize and some patients have better survival if the treatment is given prior to surgery.   Being fully informed arms breast cancer patients to make the best-possible choices for their treatment, and can have profound effects on recovery. Having the right information can assure patients they are being treated by the most highly qualified cancer care team, which includes using the most advanced surgical techniques and technologies available.