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.
Newswise — CHICAGO – Millennials lead the escalating interest in marijuana and cannabinoid compounds for managing pain – with older generations not far behind – and yet most are unaware of potential risks. Three-quarters (75%) of Americans who expressed interest in using marijuana or cannabinoids to address pain are under the impression they are safer or have fewer side effects than opioids or other medications, according to a nationwide survey commissioned by the American Society of Anesthesiologists (ASA) in conjunction with September’s Pain Awareness Month. More than two-thirds of those surveyed said they have used or would consider using marijuana or cannabinoid compounds – including cannabidiol (CBD) and tetrahydrocannabinol (THC) – to manage pain. Nearly three-quarters of millennials fall in that category, with 37% noting they have used them for pain. Two-thirds of Gen Xers and baby boomers expressed interest, with 25% of Gen Xers and 18% of baby boomers saying they have used them for pain. “As experts in managing pain, physician anesthesiologists are concerned about the lack of research regarding the safety and effectiveness of marijuana and cannabinoids,” said ASA President Linda J. Mason, M.D., FASA. “The good news is that until the research is completed and we fully understand the risks and potential benefits, physician anesthesiologists today can develop a personalized plan for patients’ pain drawing from effective alternatives such as non-opioid medications and other therapies, including injections, nerve blocks, physical therapy, radio waves and spinal cord stimulation.” ASA members express concern that patients in pain are unaware marijuana and cannabinoids may not be safer than other medications, that they can have side effects – ranging from excessive sleepiness to liver damage – and more importantly that these products are not regulated or monitored for quality. Misunderstandings about Marijuana and Cannabinoid Safety and Oversight Results of the nationwide survey of adults 18 or older confirm physician anesthesiologists’ concerns. When respondents who said they have used or would consider using marijuana or cannabinoids were asked why, the majority (62%) said they believe them to be safer than opioids and (57%) believe they have fewer side effects than other medications. Marijuana and cannabinoids currently are in uncharted territory with no way for people to know exactly what they are purchasing. Even though it is widely available, CBD is not regulated. The U.S. Food and Drug Administration (FDA) has approved only one prescription version of CBD for patients with one of two rare forms of epilepsy. (No form of marijuana is approved by the FDA and the federal government considers it a controlled substance and illegal). Thirty-three states and Washington, D.C. have legalized marijuana in some form (for recreational or medical use) but all set their own regulations, which vary widely. Further, studies have shown that no matter what the label says, the actual ingredients may differ, and may contain dangerous synthetic compounds, pesticides and other impurities. Nearly three out of five (58%) think they have fewer side effects than other medications; Nearly half (48%) think they know what they are getting with marijuana or cannabinoids; and 40% believe CBD sold at grocery stores, truck stops, health food stores or medical marijuana dispensaries is approved by the FDA. The younger the generation, the more likely they were to believe that is the case. The ASA recently endorsed two bills that seek to expand research on CBD and marijuana: H.R. 601, the Medical Cannabis Research Act of 2019 and S. 2032, the Cannabidiol and Marihuana Research Expansion Act. Alternative pain management options People in pain looking for alternatives to opioids should know there are other options besides marijuana or cannabinoids. For example, only 13% of respondents said they have used or would consider using marijuana or cannabinoids because no other type of pain management works for them. Physician anesthesiologists and other pain management specialists can work with people in pain to develop a safe, effective pain management plan that doesn’t include opioids, marijuana or cannabinoids. For more information about pain management alternatives visit https://www.asahq.org/whensecondscount/pain-management/non-opioid-treatment/. To learn more about the critical role physician anesthesiologists play in medical care including surgery, visit www.asahq.org/WhenSecondsCount. The five-question CARAVAN® Survey was conducted online by Engine, Aug. 5-7, 2019 among 1,005 adults, comprising 503 men and 502 women, 18 years or older. THE AMERICAN SOCIETY OF ANESTHESIOLOGISTS Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific society with more than 53,000 members organized to raise and maintain the standards of the medical practice of anesthesiology. ASA is committed to ensuring physician anesthesiologists evaluate and supervise the medical care of patients before, during and after surgery to provide the highest quality and safest care every patient deserves. For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at asahq.org. To learn more about the role physician anesthesiologists play in ensuring patient safety, visit asahq.org/WhenSecondsCount. Like ASA on Facebook; follow ASALifeline on Twitter.
Newswise — As a disposable version of the instrument used in one of the most common medical procedures in the United States inches closer to widespread availability, a team of Johns Hopkins data researchers is studying the economic and safety implications associated with the devices used to perform colonoscopies. Gastroenterology researcher Susan Hutfless led a first-of-its-kind study published online last week in the BMJ journal Gut, reporting that while disposable devices might lead to lower rates of post-colonoscopy infection, institutions that perform the procedure thousands of times per year might better benefit from improved disinfection methods of reusable scopes. Today, colonoscopies are performed with reusable scopes, which are flexible, fiber-optic devices that are inserted into the anus and guided through the colon. The scopes allow endoscopists to examine patients for cancerous or precancerous conditions, as well as diagnose chronic disease. The nature of the devices and the microorganisms they encounter during use mandates rigorous cleaning. In 2016, the Food and Drug Administration approved a disposable colonoscope designed to be used only once. With the new devices on the horizon, Hutfless and her colleagues aimed to determine which centers, if any, might benefit from using them. Only a small fraction of the more than 15 million Americans who had colonoscopies last year contracted infections from the procedure. But, as Hutfless noted in a 2018 publication, the rates of infection at facilities that perform a relatively small number of the procedures are far higher than previously believed. In that paper, Hutfless reported that rates of post-colonoscopy infection at facilities known as ambulatory surgery centers (ASCs) are more akin to 1 in 1,000, rather than the 1 in 1 million figure previously accepted in the field. Given that the one-time-use scopes have yet to be introduced, Hutfless focused on the cleaning, capital and operating costs associated with the reusable versions currently available. Purchase, maintenance and cleaning costs per procedure range from $189 at centers that perform at least 3,000 colonoscopies per year to $501 at centers performing 1,000 or fewer. When the cost of treating post-procedural infections is included, the numbers rise even higher, ranging from an additional $20 per procedure in high-volume, low-infection centers to almost $47 for centers with greater infection rates. The average cost of a hospitalization to treat a post-colonoscopy infection is more than $12,000. Colonoscopies are recommended for people age 50 and above for routine cancer screenings. The procedures are performed under mild sedation in hospitals or ASCs. Hutfless’ research has shown direct correlations between the number of procedures performed at a particular center and the rates of infection. “High-volume centers tend to have lower infection risks,” says Hutfless, adding that she and her colleagues attribute the lower risk to more experience and a faster turnover of colonoscopes. “It may not be cost-effective for high-volume centers to switch to disposable.” The researcher says that certain low-volume centers could benefit from disposable scopes. “They may decrease device-related infection transmission and may prove cost-effective for some facilities, particularly those with low volume and patients with a high infection risk.” She also points to the environmental impact that millions of throw-away plastic scopes would have. “That’s something that very much needs to be considered,” she says. Coauthors of the Gut article were Anthony Kalloo of the Johns Hopkins University School of Medicine and Sara Larsen, a student at the Aalborg University School of Medicine and Health. Kalloo is a founding member and equity holder of Apollo Endosurgery. Larsen received travel support from Ambu A/S and has received speaker fees and research support from Cantel. Hutfless declares no competing interests.
Newswise — PITTSBURGH, Aug. 26, 2019 – New, more effective antibiotics are being prescribed in only about a quarter of infections by carbapenem-resistant Enterobacteriaceae (CRE), a family of the world’s most intractable drug-resistant bacteria, according to an analysis by infectious disease and pharmaceutical scientists at the University of Pittsburgh School of Medicine and published today by the journal Open Forum Infectious Diseases. This sluggish uptake of such high-priority antibiotics prompted the researchers to call for an examination of clinical and pharmaceutical stewardship practices across U.S. hospitals, as well as behavioral and economic factors, to see if the trend can be reversed before lackluster sales lead the pharmaceutical industry to stop developing much-needed antibiotics. “The infectious diseases community spent the past decade saying, ‘We need new antibiotics, this is a top priority,’ and now we’re at risk of sounding like the boy who cried wolf,” said lead author Cornelius J. Clancy, M.D., associate professor of medicine and director of the mycology program and XDR Pathogen Laboratory in Pitt’s Division of Infectious Diseases. “We have a responsibility to learn why it takes so long for antibiotics to be adopted into practice and figure out what we need to do to ensure the best antibiotics quickly reach the patients who desperately need them.” The U.S. Centers for Disease Control and Prevention has classified CRE as urgent threat pathogens and calls them the “nightmare bacteria.” The World Health Organization and Infectious Disease Society of America have designated CRE as highest priority pathogens for development of new antibiotics. At the time of those declarations, polymyxins were the first-line antibiotics against CRE, even though they failed to work in about half the cases and carried a significant risk of damaging the kidneys. Since 2015, five antibiotics against CRE have gained U.S. Food and Drug Administration (FDA) approval: ceftazidime-avibactam, meropenem-vaborbactam, plazomicin, eravacycline and imipenem-relebactam. Studies, including those conducted at UPMC, have shown that the first three of these antibiotics are significantly more effective at fighting CRE and less toxic than polymyxins (eravacycline and imipenem-relebactam are still too new for conclusive data). Clancy and his colleagues surveyed hospital-based pharmacists in the U.S. to gauge their knowledge of the new antibiotics and their willingness to use them. The drugs were classified as the “first-line” choice against CRE blood infections by 90% of the pharmacists, pneumonia by 87%, intra-abdominal infections by 83% and urinary tract infections by 56%. “Clearly hospital-based pharmacists are aware of these antibiotics and believe they are the best choice for the vast majority of CRE infections,” said Clancy. But when the team estimated the number of CRE infections nationwide and used national prescription data to calculate the proportions of old vs. new antibiotics used to treat those infections, they found that from February 2018 through January 2019, the new antibiotics were used only about 23% of the time. Their use likely started to exceed that of polymyxins only in December 2018, nearly four years after the first of the new antibiotics was approved by the FDA. Even after accounting for CRE infections in which new antibiotics might not be first-choice agents, the team found that use was only about 35% of what was expected based on positioning by hospital-based pharmacists. Allergan and The Medicines Company, developers of two of the new antibiotics, have sought to exit the antimicrobial field since introducing their drugs because of insufficient returns on investment. Achaogen declared bankruptcy months after attaining FDA approval for a third new antibiotic. The researchers suggest several reasons for the slow uptake of the new antibiotics, starting with cost. A 14-day course of the new antibiotics costs between $13,230 and $15,070, compared to $305 to $784 for the old drugs. “Cost is a limitation, but I’m not convinced it is the sole cause of our findings,” said Clancy. “Clinicians may not be prescribing the new drugs due to concerns about accelerating antibiotic-resistance or because initial studies on their effectiveness were relatively small. We need to get at the root causes of the disconnect between what the doctors prescribe and what the pharmacists we surveyed believe they should be prescribing, and then find a solution.” Additional authors on this study are M. Hong Nguyen, M.D., and Brian A. Potoski, Pharm.D., of Pitt; and Deanna Buehrle, Pharm.D., of the VA Pittsburgh Healthcare System. There was no funding for this study. Clancy and Nguyen report unrelated research funded by various pharmaceutical and medical device companies, detailed in the study manuscript.
Newswise — Researchers from Queen’s University Belfast have developed a test that may be able to detect ovarian cancer up to two years earlier than current approaches. The researchers discovered that the presence of four proteins together, known as a biomarker panel, indicates the likelihood of Epithelial Ovarian Cancer (EOC), a type of ovarian cancer. Using these biomarkers the researchers then developed a screening test that initial studies suggest may be able to detect ovarian cancer up to two years before current detection tests. The research was carried out in partnership with the University of New South Wales Australia, University of Milan, University of Manchester and University College London. The study, published in British Journal of Cancer as part of Nature Group publication, involved the analysis of blood samples from 80 individuals across a seven-year period. Dr Bobby Graham from the School of Biological Sciences at Queen’s University Belfast and lead author of the study explains: “Firstly, we discovered that the presence of the biomarker panel will enable us to detect EOC. We then developed a screening test to detect this biomarker panel, making this a relatively simple diagnostic test. “The algorithm designed will screen the blood sample and flag any abnormal levels of the proteins associated with the cancer. The screening test identifies ovarian cancer up to two years before the current tests allow.” Most ovarian cancers are epithelial ovarian cancers, which is a cancer that forms in the tissue covering the ovary. In females in the UK, ovarian cancer is the sixth most common cancer. In 2016, 4227 deaths were reported as a result of EOC. If diagnosed at stage one of EOC, there is a 90% chance of five-year survival compared to 22% if diagnosed at a stage three or four. Dr Graham added: “The results of this study are encouraging, however, we now want to focus on testing it in a wider sample set so that we can use the data to advocate for an ovarian cancer screening programme.” Dr Rachel Shaw, Research Information Manager at Cancer Research UK, said: “Around half of ovarian cancer cases are picked up at a late stage, when treatment is less likely to be successful. So developing simple tests like these that could help detect the disease sooner is essential. "At Cancer Research UK, we’re working hard to find new ways to detect cancer early and improve the tests already available. It’s really exciting to see these encouraging results for this type of ovarian cancer.” Athena, CEO of the Eve Appeal says, “We are extremely proud to have part funded the PROMISE programme, which brought together experts for a 7 year project to try and diagnose ovarian cancer at an earlier stage. “Sadly, so many women are diagnosed late, to devastating effect. We are hopeful the outcomes of this project will have a positive affect on women in the future.” The project was jointly funded by the Eve Appeal charity and Cancer Research UK.
Credit: Michigan Medicine A new study from the University of Michigan finds people who have mild cognitive impairment (MCI), which lies on the continuum of cognitive decline between normal cognition and dementia, are less likely to receive proven heart attack treatment in the hospital. Newswise — A new study finds people who have mild cognitive impairment (MCI), which lies on the continuum of cognitive decline between normal cognition and dementia, are less likely to receive proven heart attack treatment in the hospital. Researchers found no evidence that those with MCI would derive less benefit from evidence-based treatment that’s offered to their cognitively normal peers who have heart attacks, says lead author Deborah Levine, M.D., MPH. “Patients should get the treatments they would want if they were properly informed,” says Levine, an associate professor of internal medicine and neurology at Michigan Medicine, the academic medical center of the University of Michigan. Some people with thinking, memory and language problems have MCI. Unlike dementia, which severely interferes with daily functioning and worsens over time, MCI does not severely interfere with daily functioning and might not worsen over time. Although people with MCI have an increased risk of developing dementia, it’s not an inevitable next step, Levine says. “While some may progress to dementia, many will persist in having MCI, and a few will actually improve and revert to normal cognition,” says Levine, also a member of the University of Michigan Institute for Healthcare Policy and Innovation. “Many older adults with MCI live years with good quality of life, and so face common health risks of aging like heart attack and stroke. “Clinicians, patients and families might be overestimating the risk of dementia after a mild cognitive impairment diagnosis even without realizing it. These older adults with MCI should still receive evidence-based treatments when indicated.” The research, published in the Journal of General Internal Medicine, found pre-existing MCI was associated with significantly lower use of guideline-concordant care after a heart attack, whether catheter-based or open surgery. The study measured 609 adults ages 65 and older who were hospitalized for a heart attack between 2000 and 2011. Levine notes both cardiac catheterization (35% less likely in patients with pre-existing MCI) and coronary revascularization (45% less likely in patients with pre-existing MCI) have been shown to be highly effective at reducing deaths and improving physical functioning after heart attack in multiple large clinical trials. ‘A timely issue’ Physicians must weigh the competing risks of all health problems that increase with age, Levine says, including heart disease and cognitive decline. Many families are dealing with both concerns at once in their older loved ones. “This is a timely issue because as the population ages, the number of seniors 85 years old and older has become the fastest-growing segment of the U.S. population,” Levine says. “Seniors 85 and older are most likely to have MCI, and their incidence of heart attack has surged.” However, cardiovascular disease, including heart attack and stroke, is still the leading cause of death and serious morbidity in older adults, whether they have MCI or normal cognitive functioning. Up to 1 in 5 adults ages 65 and older has MCI, although many may be undiagnosed, Levine says. Since the Affordable Care Act mandated coverage of cognitive impairment assessments for Medicare beneficiaries, MCI diagnoses are expected to increase, she adds. The need to question decision-making Although much recent medical literature addresses overtreatment, Levine says this research shows undertreatment with high-value therapies can also be a problem. Her team’s ongoing research finds physicians might not be recommending invasive treatments as often after an older patient with some memory and thinking problems has a heart attack. She encourages clinicians to reflect on the influence of MCI in their decision-making. “It’s important for providers to consider whether they are recommending against treating a patient just because they have MCI,” Levine says. “Physicians can think about offering treatments to all patients when clinically indicated.” Invasive treatments may not be indicated in those with advanced dementia or a limited life expectancy, she says, but MCI does not fall in that category. This potential disconnect in provider recommendations provides an opportunity for patients and families to empower themselves by having conversations about the care they’d want if they become ill, she says. People with MCI can still participate in these types of discussions, and families don’t need to wait until an event happens to start the conversation. “In these discussions, patients and families often think about catastrophic illnesses where life support measures may be used, but heart attacks and stroke are much more common, and they’re treatable,” Levine says. “Because dementia is so feared among older adults and their families, it’s understandable and appropriate that it may weigh heavily on the decisions for all types of care, including heart attack care,” adds co-author Kenneth Langa, M.D., Ph.D., a professor of internal medicine at Michigan Medicine and a member of the Institute for Healthcare Policy and Innovation. “Our study emphasizes the importance of differentiating between MCI and dementia and of educating patients, families and clinicians on the relative risks of further cognitive decline versus common cardiovascular conditions for people with MCI.” An ongoing effort Levine and colleagues used data from the Health and Retirement Study, a nationally representative longitudinal study of older Americans that’s based at U-M. Heart attack, or acute myocardial infarction, was an appealing lens to research whether patients with MCI receive guideline-based treatment, Levine says. Heart attacks are acute, emergent medical problems that are common in seniors and have robust evidence of effective treatment, she adds. Levine’s team is also studying the effect of pre-existing MCI on treatment for acute ischemic stroke, and the reasons physician recommendations and patient preferences for effective treatment after stroke or heart attack might be different if the patient already has MCI. “Studies like this are an important first step in raising awareness on MCI so that providers, like cardiologists, can make sure they offer the best therapies available during heart attacks,” says senior author Brahmajee Nallamothu, M.D., MPH, an interventional cardiologist and professor of internal medicine at Michigan Medicine. Story from Michigan Health Lab
Newswise — ATLANTA – Today, the American College of Rheumatology (ACR), in partnership with the Spondylitis Association of America (SAA) and the Spondyloarthritis Research and Treatment Network (SPARTAN), released the 2019 Update of the Recommendations for the Treatment of Ankylosing Spondylitis (AS) and Nonradiographic Axial Spondyloarthritis (nr-axSpA). The guideline includes 86 recommendations that provide updated and new guidance for the management of patients with AS and nr-axSpA in the areas of pharmacologic and non-pharmacologic treatment options; AS-related comorbidities; and disease activity assessment, imaging, and screening. “SAA is proud to be a co-sponsor of these updated guidelines. SAA is committed to expanding treatment options and ensuring that both spondyloarthritis patients and the medical practitioners that are entrusted with their care have the best resources to aid in their decision-making,” said Cassie Shafer, chief executive officer of the SAA. Axial SpA, which is comprised of AS and nr-axSpA, is the main form of chronic inflammatory arthritis affecting the axial skeleton. This condition is characterized by back and hip pain, peripheral joint pain, and fatigue, all of which can vary in severity. According to the SAA, as much as 1 percent of the adult United States population may have axial SpA. This means that as many as 2.7 million adults may be affected by the disease. The ACR’s previous guideline, published in 2015, provided recommendations for pharmacological treatments, management of selected comorbidities, disease monitoring, and preventive care. The 2019 update builds on these recommendations by adding information on new medications, managing biologic and biosimilars usage in patients, and best practices for utilizing imaging (MRI and radiographs). “Based on the literature, we felt it was important to address topics such as sequencing biologics for patients with active AS despite NSAID usage, whether to taper or discontinue biologics in the setting of remission, and clearer guidelines on when to obtain images – particularly in instances when results would likely lead to a change in treatment,” said Michael Ward, MD, MPH, researcher at the National Institute of Arthritis and Musculoskeletal and Skin Diseases and principal investigator of the guideline. “We hope this new information will help get patients on an effective treatment faster and ultimately improve patients’ health status and quality of life.” To update the guideline, a team of experts conducted a systematic literature review for 20 clinical questions on pharmacological treatment addressed in the 2015 guidelines along with 26 new questions on pharmacological treatment, treat-to-target strategy, and the use of imaging. The results of this review were then discussed by a separate voting panel and crafted into recommendations that were labeled conditional or strong based on the evidence available. A few of the recommendations from the guideline include: A strong recommendation to treat adults with active AS despite treatment with NSAIDs with a TNFi (no preferred choice) over no treatment with a TNFi. A conditional recommendation to treat with a TNFi over treatment with secukinumab, ixekizumab or tofacitinib, and a conditional recommendation to treat with seukinumab or ixekizumab over tofacitinib. A strong recommendation to continue treatment with the originator biologic over mandated switching to its biosimilar for adults with stable AS. A conditional recommendation against obtaining repeat spine radiographs at a scheduled interval as a standard approach for adults with active or stable nr-axSpA on any treatment. “These guidelines update those from four years ago by consolidating the expert thought around the use of the newest therapeutic agents and modifying a number of recommendations from the 2015 guideline to reflect recent evidence. They provide patients and the medical community with clear recommendations for spondyloarthritis management using a rigorous approach, and SPARTAN is proud to endorse them,” said Dr. Liron Caplan, chair of SPARTAN. ACR guidelines are currently developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, which creates rigorous standards for judging the quality of the literature available and assigns strengths to the recommendations. Due to limited data in some areas, the quality of evidence was most often low, very low or occasionally moderate. This led to nearly all recommendations being conditional, with only a few strong recommendations in cases in which there was sufficient evidence. The updated and expanded recommendations, supporting PICO questions and evidence report are available on the ACR website.
New research shows link between high chili intake and dementia. Newswise — Think twice before adding that extra kick of chili sauce or chopped jalapeno to your meal. New research involving the University of South Australia shows a spicy diet could be linked to dementia. A 15-year study of 4582 Chinese adults aged over 55 found evidence of faster cognitive decline in those who consistently ate more than 50 grams of chili a day. Memory decline was even more significant if the chili lovers were slim. The study, led by Dr Zumin Shi from Qatar University, showed that those who consumed in excess of 50 grams of chili a day had almost double the risk of memory decline and poor cognition. “Chili consumption was found to be beneficial for body weight and blood pressure in our previous studies. However, in this study, we found adverse effects on cognition among older adults,” Dr Zumin says. UniSA epidemiologist Dr Ming Li, one of five researchers involved in the study, says chili intake included both fresh and dried chili peppers but not sweet capsicum or black pepper. “Chili is one of the most commonly used spices in the world and particularly popular in Asia compared to European countries,” Dr Li says. “In certain regions of China, such as Sichuan and Hunan, almost one in three adults consume spicy food every day.” Capsaicin is the active component in chili which reportedly speeds up metabolism, fat loss and inhibits vascular disorders but this is the first longitudinal study to investigate the association between chili intake and cognitive function. Those who ate a lot of chili had a lower income and body mass index (BMI) and were more physically active compared to non-consumers. Researchers say people of normal body weight may be more sensitive to chili intake than overweight people, hence the impact on memory and weight. Education levels may also play a role in cognitive decline and this link requires further research.