Newswise — Within the next decade, the novel coronavirus responsible for COVID-19 could become little more than a nuisance, causing no more than common cold-like coughs and sniffles. That possible future is predicted by mathematical models that incorporate lessons learned from the current pandemic on how our body’s immunity changes over time. Scientists at the University of Utah carried out the research, now published in the journal Viruses. “This shows a possible future that has not yet been fully addressed,” says Fred Adler, PhD, professor of mathematics and biological sciences at the U. “Over the next decade, the severity of COVID-19 may decrease as populations collectively develop immunity.” The findings suggest that changes in the disease could be driven by adaptations of our immune response rather than by changes in the virus itself. Adler was senior author on the publication with Alexander Beams, first author and graduate student in the Department of Mathematics and the Division of Epidemiology at University of Utah Health, and undergraduate co-author Rebecca Bateman. Although SARS-CoV-2 (the sometimes-deadly coronavirus causing COVID-19) is the best-known member of that virus family, other seasonal coronaviruses circulate in the human population—and they are much more benign. Some evidence indicates that one of these cold-causing relatives might have once been severe, giving rise to the “Russian flu” pandemic in the late 19th century. The parallels led the U of U scientists to wonder whether the severity of SARS-CoV-2 could similarly lessen over time. To test the idea, they built mathematical models incorporating evidence on the body’s immune response to SARS-CoV-2 based on the following data from the current pandemic. There is likely a dose response between virus exposure and disease severity. A person exposed to a small dose of virus will be more likely to get a mild case of COVID-19 and shed small amounts of virus. By contrast, adults exposed to a large dose of virus are more likely to have severe disease and shed more virus. Masking and social distancing decrease the viral dose. Children are unlikely to develop severe disease. Adults who have had COVID-19 or have been vaccinated are protected against severe disease. Running several versions of these scenarios showed that the three mechanisms in combination set up a situation where an increasing proportion of the population will become predisposed for mild disease over the long term. The scientists felt the transformation was significant enough that it needed a new term. In this scenario, SARS-CoV-2 would become “Just Another Seasonal Coronavirus,” or JASC for short. “In the beginning of the pandemic, no one had seen the virus before,” Adler explains. “Our immune system was not prepared.” The models show that as more adults become partially immune, whether through prior infection or vaccination, severe infections all but disappear over the next decade. Eventually, the only people who will be exposed to the virus for the first time will be children—and they’re naturally less prone to severe disease. “The novel approach here is to recognize the competition taking place between mild and severe COVID-19 infections and ask which type will get to persist in the long run,” Beams says. “We’ve shown that mild infections will win, as long as they train our immune systems to fight against severe infections.” The models do not account for every potential influence on disease trajectory. For example, if new virus variants overcome partial immunity, COVID-19 could take a turn for the worse. In addition, the predictions rely on the key assumptions of the model holding up. “Our next step is comparing our model predictions with the most current disease data to assess which way the pandemic is going as it is happening,” Adler says. “Do things look like they’re heading in a bad or good direction? Is the proportion of mild cases increasing? Knowing that might affect decisions we make as a society.”
Newswise — Before undergoing surgery, patients often go through a number of tests: blood work, sometimes a chest X-ray, perhaps tests to measure heart and lung function. In fact, about half of patients who had one of three common surgical procedures done in Michigan between 2015 and the midway point of 2019 received at least one routine test beforehand. That’s according to new research in JAMA Internal Medicine from a collaboration between the University of Michigan-based Michigan Program on Value Enhancement (MPrOVE) and the Michigan Value Collaborative, a statewide initiative that focuses on improving medical and surgical quality. Yet plenty of evidence suggests that preoperative testing is often unnecessary for low-risk surgeries. At best, it’s costly and doesn’t usually improve outcomes for patients. At worst, it can lead to more invasive testing and delay surgery, which can create complications that could have been avoided if the tests weren’t done. “There aren’t that many areas in medicine where the data is pretty definitive that something is low-value,” says Lesly Dossett, M.D., the division chief of surgical oncology at Michigan Medicine and the co-director of MPrOVE, “but preoperative testing before low-risk surgeries is certainly one of them.” How testing started — and why it continues In the latter half of the 19th century, modern surgery was still in its infancy. Anesthesia was new, and even minor surgeries were not routine. So researchers used tests to assess their patients’ physical health and measure their risk of complications during operations. “There was probably a time when some of the testing did reduce adverse events,” Dossett says. “But now there’s been so many advances in surgery — complication rates are so low that a lot of these tests are not necessarily helpful anymore.” Others agree with her. Professional organizations ranging from the American College of Surgeons and the Society of General Internal Medicine to the American Society of Anesthesiologists have identified routine preoperative testing as a low-value type of care that should be reduced whenever possible. In 2012, the American Board of Internal Medicine Foundation even launched an initiative called the Choosing Wisely campaign that promotes conversations between health care providers and patients about unnecessary medical tests and procedures. But, almost a decade later, preoperative tests continue to be ordered. Of about 40,000 patients in the U-M study who had surgery to either remove the gall bladder, repair a groin hernia, or remove cancerous breast tissue, close to a third underwent two or more tests beforehand, and about 13% had three or more. The most common tests were a complete blood count, an electrocardiogram and a basic metabolic panel, all of which aren’t inherently necessary before these surgeries. “It’s one thing to say that this is well recognized in the literature,” says Hari Nathan, M.D., Ph.D., who happens to be the division chief of hepato-pancreato-biliary surgery at Michigan Medicine as well as the director of the MVC, “but it’s a different thing to put it in the hands of the clinicians who are at the bedside in an easy-to-read, easy-to-understand and convenient-to-carry-around format.” Patients who had a complete medical history and physical done during a visit that was separately billed were more likely to have had preoperative testing as were those who were older or had more than one medical condition. “I could see those two latter factors being in the background, hypothetically giving some pressure to do more testing,” says Nicholas Berlin, M.D., M.P.H., a plastic surgery resident at Michigan Medicine and the first author of the study. “That’s not to suggest there’s an age threshold or a comorbidity that requires preoperative testing every single time. There’s not.” A small number of people who fall into these categories may actually benefit from having these tests done, although it’s difficult to know exactly how many based on this data, the researchers say. Yet, when they adjusted their model to account for that issue, they still found overuse of testing. The data also revealed wide variations in testing, not only between the 63 hospitals studied but also within health systems for the same procedures, pointing to the need for more research to drill down further into the origins of the problem. “We have more work to do on our end to figure out what’s driving these differences within and between hospitals,” says Berlin, who’s also a National Clinician Scholar at the University of Michigan Institute for Healthcare Policy and Innovation. “This is signaling to other projects in the future between MPrOVE and statewide quality collaboratives that use more of an on-the-ground approach.” Value added statewide This study represents one of the first partnerships between the Michigan Value Collaborative and MPrOVE, a joint venture of IHPI and Michigan Medicine that tries to optimize patient care, improve quality and demonstrate the value of care at Michigan Medicine through research and analytics. In the past, MPrOVE has worked to reduce preoperative visits and tests such as EKGs before cataract surgery at Michigan Medicine, but its leaders wanted to expand the scope of their research to include other procedures and more hospitals. The MVC was an ideal partner to do so: Funded by Blue Cross Blue Shield of Michigan, the initiative allows more than 90 hospitals and 40 physician organizations in Michigan to compare their data and identify best practices as well as opportunities for improvement. “It’s something that’s squarely in MVC’s strike zone and fits very well with MPrOVE’s mission,” Nathan says, “It just made sense for us to work together on this.” Limiting preoperative testing is one of two signature projects for the MVC, and Nathan has already started meeting with area health systems to tackle the issue. “Some hospitals routinely send patients through a preoperative clinic, which represents a way to move the needle here in a very targeted way, just by influencing what gets ordered in the setting of that clinic,” he says. “At other hospitals, there is no such clinic, and the individual surgeons and/or anesthesiologists are ordering tests, so that might require a different approach in order to get more adherence to guidelines.” “But I love seeing variation because when we see variation, that means there’s an opportunity to learn from one another,” he adds. One of the challenges in reducing preoperative testing is that it generates revenue for hospitals, which means there’s not a financial incentive to do less of it, Dossett says. But Nathan says that, based on his interactions with local health systems, he believes there’s an appetite for change in this area. “At the end of the day, we all recognize that as a society, we need to find ways to curb health care costs,” he says. “That’s in everybody’s interest. Even if, on your balance sheet, you think it makes sense to do more tests just to make money, as health care providers and as a nation, it does not make sense. It is unsustainable. When we talk to our members, everybody gets that.”
Newswise — LEXINGTON, Ky. (May 5, 2021) - Collaborative research between the University of Kentucky (UK) and University of Southern California (USC) suggests that a noninvasive neuroimaging technique may index early-stage blood-brain barrier (BBB) dysfunction associated with small vessel disease (SVD). Cerebral SVD is the most common cause of vascular cognitive impairment, with a significant proportion of cases going on to develop dementia. BBB dysfunction represents a promising early marker of SVD because the BBB regulates a number of important metabolic functions, including clearance of toxic brain substances. Advanced BBB dysfunction can be detected with neuroimaging measures such as positron emission tomography (PET) scanning and dynamic contrast-enhanced (DCE) MRI. However, these methods require exposure to radiation or contrast agents and may only detect moderate to advanced stages of BBB tissue disruption. The UK-USC study used a novel, noninvasive MRI method called diffusion-prepared arterial spin labeling (DP-ASL), which was developed by Xingfeng Shao, Ph.D. and Danny Wang, Ph.D. at USC. The DP-ASL method indexes subtle BBB dysfunctions associated with altered water exchange rate across the BBB. In the UK-USC study, healthy older adults (67-86 years old) without cognitive impairment were scanned with the DP-ASL sequence at the UK’s Magnetic Resonance Imaging and Spectroscopy Center. In addition, study participants volunteered for lumbar cerebrospinal fluid (CSF) draw as part of their enrollment in the study at UK’s Sanders-Brown Center on Aging (SBCoA). The study focused on CSF levels of amyloid-beta (Aβ), which are abnormally low when this protein is not adequately cleared from the brain into the CSF. Results indicated that low CSF levels of Aβ were associated with a low BBB water exchange rate assessed with the DP-ASL method. “Our results suggest that DP-ASL may provide a noninvasive index of BBB clearance dysfunction prior to any detectable cognitive impairment,” said Brian Gold, Ph.D., professor in the UK department of Neuroscience and SBCoA. Gold is the lead author of the article, which appears in a recent issue of Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Wang, a professor of Neurology and Radiology at USC, the study’s senior author, said, “Our data indicate the important role of BBB water exchange in the clearance of amyloid-beta, and the potential for using DP-ASL to noninvasively assess BBB water exchange in clinical trials of SVD.” In addition to Gold, several others from UK contributed to the research including Dr. Gregory Jicha, professor in the department of Neurology and SBCoA, Donna Wilcock, Ph.D., professor in the department of Physiology and SBCoA, Tiffany Sudduth and Elayna Seago. Results from the UK-USC study also support growing evidence that BBB dysfunction may represent a link between SVD and clinical diagnosis of Alzheimer’s disease (AD). Excess accumulation of Aβ is a hallmark feature of individuals who receive a clinical diagnosis of AD. However, Aβ pathology is also seen in many cases of SVD. Results from the UK-USC study are consistent with theories suggesting that insufficient clearance of Aβ through the BBB may impair BBB function which, in turn, may further accelerate the accumulation of Aβ in the brain. Gold noted that “an important topic for future research is why some individuals with BBB dysfunction and impaired Aβ clearance may develop cognitive declines associated with AD while others develop more vascular-like cognitive declines.” Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health under Award Number R01AG055449, National Institute of General Medical Sciences of the National Institutes of Health under Award Number S10OD023573, National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Numbers UH3-NS100614 and R01NS114382, National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number R01EB028297.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
ewswise — Rockville, Md. – Data being presented at the 2021 virtual meeting of the Association for Research in Vision and Ophthalmology (ARVO) highlights the significant impact of inherited retinal diseases (IRD) in the United States and Canada. Continuing their 2019 cost-of-illness of IRD studies in the Republic of Ireland and the United Kingdom (IRD Counts), Retina International sought to expand on the limited data illustrating the impact of IRDs from a socio-economic perspective. Given their larger population, data from the U.S. and Canada was a natural next step. In addition to the familial burden exposed in the study, the team noted that current assessment models of therapies do not appropriately reflect how little people living with IRD interact with health systems compared to the total cost burden of living with an IRD. “People living with an IRD interact with health systems at a very low level compared to the total cost burden of living with an IRD. The Cost of Illness study in the United States and Canada clearly demonstrates that current assessment models for reimbursement of therapies do not appropriately reflect this and therefore need urgent review,” says Avril Daly of Retina International. Notable results included: Productivity losses were the second highest burden in both the U.S. and Canada, amounting to US$4.056 billion, and CAN$205.1 million Persons with an IRD in the U.S. and Canada were 28.8% and 24.4% less likely to be in paid employment than the general population In the U.S. and Canada IRDs resulted in a 0.3% and 1.4% reduction in productivity while at work, respectively. The health systems cost in both regions was low at US$2.216 billion and CAN$37.8 million, respectively. Retina International and its partners developed the North American-based study, “to be utilized and referred to by populations across the globe to support access to services and care pathways, access to clinical trials and treatments. Most importantly, it highlights the need for continued research into IRDs to understand disease pathways and to find treatments and cures,” says Daly.
Newswise — As the COVID-19 pandemic has progressed, it has become clear that many survivors — even those who had mild cases — continue to manage a variety of health problems long after the initial infection should have resolved. In what is believed to be the largest comprehensive study of long COVID-19 to date, researchers at Washington University School of Medicine in St. Louis showed that COVID-19 survivors — including those not sick enough to be hospitalized — have an increased risk of death in the six months following diagnosis with the virus. The researchers also have catalogued the numerous diseases associated with COVID-19, providing a big-picture overview of the long-term complications of COVID-19 and revealing the massive burden this disease is likely to place on the world’s population in the coming years. The study, involving more than 87,000 COVID-19 patients and nearly 5 million control patients in a federal database, appears online April 22 in the journal Nature. “Our study demonstrates that up to six months after diagnosis, the risk of death following even a mild case of COVID-19 is not trivial and increases with disease severity,” said senior author Ziyad Al-Aly, MD, an assistant professor of medicine. “It is not an exaggeration to say that long COVID-19 — the long-term health consequences of COVID-19 — is America’s next big health crisis. Given that more than 30 million Americans have been infected with this virus, and given that the burden of long COVID-19 is substantial, the lingering effects of this disease will reverberate for many years and even decades. Physicians must be vigilant in evaluating people who have had COVID-19. These patients will need integrated, multidisciplinary care.” In the new study, the researchers were able to calculate the potential scale of the problems first glimpsed from anecdotal accounts and smaller studies that hinted at the wide-ranging side effects of surviving COVID-19, from breathing problems and irregular heart rhythms to mental health issues and hair loss. “This study differs from others that have looked at long COVID-19 because, rather than focusing on just the neurologic or cardiovascular complications, for example, we took a broad view and used the vast databases of the Veterans Health Administration (VHA) to comprehensively catalog all diseases that may be attributable to COVID-19,” said Al-Aly, also director of the Clinical Epidemiology Center and chief of the Research and Education Service at the Veterans Affairs St. Louis Health Care System. The investigators showed that, after surviving the initial infection (beyond the first 30 days of illness), COVID-19 survivors had an almost 60% increased risk of death over the following six months compared with the general population. At the six-month mark, excess deaths among all COVID-19 survivors were estimated at eight people per 1,000 patients. Among patients who were ill enough to be hospitalized with COVID-19 and who survived beyond the first 30 days of illness, there were 29 excess deaths per 1,000 patients over the following six months. “These later deaths due to long-term complications of the infection are not necessarily recorded as deaths due to COVID-19,” Al-Aly said. “As far as total pandemic death toll, these numbers suggest that the deaths we’re counting due to the immediate viral infection are only the tip of the iceberg.” The researchers analyzed data from the national health-care databases of the U.S. Department of Veterans Affairs. The dataset included 73,435 VHA patients with confirmed COVID-19 but who were not hospitalized and, for comparison, almost 5 million VHA patients who did not have a COVID-19 diagnosis and were not hospitalized during this time frame. The veterans in the study were primarily men (almost 88%), but the large sample size meant that the study still included 8,880 women with confirmed cases. To help understand the long-term effects of more severe COVID-19, the researchers harnessed VHA data to conduct a separate analysis of 13,654 patients hospitalized with COVID-19 compared with 13,997 patients hospitalized with seasonal flu. All patients survived at least 30 days after hospital admission, and the analysis included six months of follow-up data. The researchers confirmed that, despite being initially a respiratory virus, long COVID-19 can affect nearly every organ system in the body. Evaluating 379 diagnoses of diseases possibly related to COVID-19, 380 classes of medications prescribed and 62 laboratory tests administered, the researchers identified newly diagnosed major health issues that persisted in COVID-19 patients over at least six months and that affected nearly every organ and regulatory system in the body, including: Respiratory system: persistent cough, shortness of breath and low oxygen levels in the blood. Nervous system: stroke, headaches, memory problems and problems with senses of taste and smell. Mental health: anxiety, depression, sleep problems and substance abuse. Metabolism: new onset of diabetes, obesity and high cholesterol. Cardiovascular system: acute coronary disease, heart failure, heart palpitations and irregular heart rhythms. Gastrointestinal system: constipation, diarrhea and acid reflux. Kidney: acute kidney injury and chronic kidney disease that can, in severe cases, require dialysis. Coagulation regulation: blood clots in the legs and lungs. Skin: rash and hair loss. Musculoskeletal system: joint pain and muscle weakness. General health: malaise, fatigue and anemia. While no survivor suffered from all of these problems, many developed a cluster of several issues that have a significant impact on health and quality of life. Among hospitalized patients, those who had COVID-19 fared considerably worse than those who had influenza, according to the analysis. COVID-19 survivors had a 50% increased risk of death compared with flu survivors, with about 29 excess deaths per 1,000 patients at six months. Survivors of COVID-19 also had a substantially higher risk of long-term medical problems. “Compared with flu, COVID-19 showed remarkably higher burden of disease, both in the magnitude of risk and the breadth of organ system involvement,” Al-Aly said. “Long COVID-19 is more than a typical postviral syndrome. The size of the risk of disease and death and the extent of organ system involvement is far higher than what we see with other respiratory viruses, such as influenza.” In addition, the researchers found that the health risks from surviving COVID-19 increased with the severity of disease, with hospitalized patients who required intensive care being at highest risk of long COVID-19 complications and death. “Some of these problems may improve with time — for example, shortness of breath and cough may get better — and some problems may get worse,” Al-Aly added. “We will continue following these patients to help us understand the ongoing impacts of the virus beyond the first six months after infection. We’re only a little over a year into this pandemic, so there may be consequences of long COVID-19 that are not yet visible.” In future analyses of these same datasets, Al-Aly and his colleagues also plan to look at whether patients fared differently based on age, race and gender to gain a deeper understanding of the risk of death in people with long COVID-19. Photo Credit: Sara Moser A new study from Washington University School of Medicine in St. Louis shows that even mild cases of COVID-19 increase the risk of death in the six months following diagnosis and that this risk increases with disease severity. The comprehensive study also catalogues the wide-ranging and long-term health problems often triggered by the infection, even among those not hospitalized.
American Association for Cancer Research meeting is premier venue for presenting cancer research results Newswise — Atlantic Health System Cancer Care physicians are co-authors of five original studies presented at this year’s AACR Annual Meeting, held virtually April 10-15 and May 17-21. The AACR meeting is one of the world’s premier scientific gatherings of cancer specialists and researchers. “Atlantic Health System Cancer Care is extremely proud of its role, helping to lead these studies alongside some of the world’s best-known cancer researchers,” said Eric Whitman, MD, medical director, Atlantic Health System Cancer Care and director of the Atlantic Melanoma Center. “Our physicians conduct the most innovative research and provide world-class care seldom found outside of major academic medical centers. These innovative clinical trials offer more treatment options for patients, both in our area and in some cases, around the world.” Studies presented at the AACR meeting were co-authored by Dr. Whitman; Missak Haigentz, MD, chair of hematology/oncology at Morristown Medical Center, medical director of hematology/oncology for Atlantic Health System and principal investigator, Atlantic Health Cancer Consortium NCORP; and Angela Alistar, MD, medical director of GI medical oncology and the Breakthrough Treatment Center at Morristown Medical Center. See below for links to the study abstracts, which are now live, and brief descriptions of the studies: CT008 - Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced (unresectable or metastatic) melanoma: durable duration of response at 28 month follow up Dr. Whitman; presentation Dr. Whitman and colleagues presented 28-month follow-up data on the ongoing global phase 2, multicenter clinical trial of a new type of investigational cancer treatment known as lifileucel (LN-144) for advanced (Stage IV) melanoma. Lifileucel is a TIL (tumor infiltrating lymphocyte) therapy, in which the patient’s own immune system cells are removed from his/her tumor, treated with an immune booster and then infused back into the patient, along with a medication that stimulates the immune system. All participants in the study have metastatic melanoma that has progressed despite prior treatment with other therapies, including anti-PD-1 (checkpoint inhibitor) immunotherapy and BRAF/MEK inhibitor targeted therapy. At 28 months, lifileucel therapy has shown an overall response rate (ORR) of 36.4%. The study, which is ongoing, is sponsored by Iovance Biotherapeutics. Dr. Whitman and co-investigators presented earlier results at ASCO 2020. (NCT02360579CT201) Early report of a phase I/II study of human placental hematopoietic stem cell derived natural killer cells (CYNK-001) for the treatment of adults with COVID-19 (NCT04365101) Dr. Whitman; e-poster Dr. Whitman and colleagues published interim phase 1 results from the first study to evaluate the safety and efficacy of CYNK-001 (Celularity, Inc.) to treat patients with SARS-CoV-2 (the virus that causes COVID-19). The investigational drug was previously only tested against various types of cancer. CYNK-001 is the only cryopreserved, allogeneic, off-the-shelf, natural killer (NK) cell therapy being developed from placental hematopoietic stem cells as a potential treatment option for various blood cancers, solid tumors, and infectious disease. NK cells are a unique class of immune cells, innately capable of targeting cancer cells and interacting with adaptive immunity (specialized immunity to certain disease causing agents). CYNK-001 has been shown to be toxic to various types of cancer cells and secretes immune-modulating cell-signaling proteins (cytokines) when they reach their target. Patients with moderate to severe COVID-19 not requiring intensive care or mechanical ventilation were enrolled in this study. Infusions of CYNK-001 were generally well tolerated, and three of four patients showed improvement in oxygenation, lung inflammation and medical imaging findings. Phase 1 is still ongoing. Once it is complete, a randomized, phase 2 clinical trial will test the efficacy of this therapy for SARS-CoV-2 against the best available therapy. 1671 - Evaluation of total PD-1 expression using multi-color flow cytometry in metastatic non-small Cell lung cancer patients treated with multi-neoantigen vector (ADXS-503) alone and in combination of pembrolizumab to assess T-cell & T-cell memory subset Dr. Haigentz; e-poster Dr. Haigentz and colleagues tested novel laboratory assays developed by Precision for Medicine to be used as biomarkers in Advaxis clinical trials of ADXS-503 alone and in combination with pembrolizumab (Keytruda) for metastatic non-small cell lung cancer. ADXS-503 is a new type of investigational cancer drug that targets “hotspot” mutations that commonly occur in specific cancer types. Pembrolizumab is an immunotherapy that targets the PD-1 pathway, which protects cancer cells from immune attack. It is commonly used to treat this type of lung cancer. The researchers used the lab assays to examine frozen blood cells from individuals treated with the two-drug combination and those treated with ADXS-503 alone, in order to detect freestanding PD-1 proteins and PD-1 proteins bound to pembrolizumab. The assays were effective at detecting PD-1 on various immune T cells. Dr. Haigentz and colleagues state that the assays will help in the evaluation of total PD-1 expression in T cells when PD-1 blocking immunotherapies are used. These results may also support the combination of ADXS-503 with PD-1 focused therapies that could lead to more effective cancer immunotherapies. CT174 - Phase II study of avelumab and trastuzumab with FOLFOX chemotherapy in previously untreated HER2-amplified metastatic gastroesophageal adenocarcinoma Dr. Alistar; e-poster In a phase 2 study, Dr. Alistar and colleagues tested a combination of avelumab, trastuzumab and FOLFOX with patients with previously untreated metastatic gastric and gastric cancer that overexpresses the HER2 gene. Avelumab (Bavencio) is a monoclonal antibody immunotherapy known as an anti-PD-L1 therapy or immune checkpoint inhibitor, while trastuzumab (Herceptin) is also a monoclonal antibody that targets HER2 receptors. FOLFOX is a standard combination of chemotherapeutic drugs. The researchers added avelumab to the standard trastuzumab and FOLFOX regimen for these types of cancer. Study investigators showed that this combination therapy generated anti-tumor activity and compared favorably to previous studies of trastuzumab and chemotherapy. Dr. Alistar and colleagues are excited about the potential for adding checkpoint inhibitors to the chemotherapy/trastuzumab combination for these types of advanced gastrointestinal cancers. Some patients in the study were still being treated at the time the research abstract was submitted to the AACR. Additional lab-based studies are now underway. Atlantic Health System Cancer Care is the only cancer program in New Jersey involved in this study. (NCT03783936) CT177 - A multi-center phase 2a trial of the CXCR4 inhibitor motixafortide (BL-8040) (M) in combination with pembrolizumab (P) and chemotherapy (C), in patients with metastatic pancreatic adenocarcinoma (mPDAC) Dr. Alistar; e-poster To date, physicians have been unable to improve the health of people with metastatic pancreatic adenocarcinoma, the most common type of pancreatic cancer, with checkpoint inhibitor immunotherapy. Preclinical research has shown that the inhibition of the CXCR4 protein helps makes cancer cells more accessible to checkpoint inhibitors. In the second cohort of phase 2a COMBAT clinical trial, Dr. Alistar and colleagues tested BioLineRx Ltd.’s CXCR4 inhibitor BL-8040 in combination with checkpoint inhibitor pembrolizumab (Keytruda) and a type of chemotherapy against this Stage IV cancer. The study had encouraging results, with a confirmed objective response rate of 13.2%, 5.6 month median duration of benefit from the treatment, overall survival average of 6.5 months and progression free survival of four months. The investigators concluded that the therapeutic combination should be tested against this late-stage cancer in a randomized clinical trial. (NCT02826486) For information on current Atlantic Health System Cancer Care clinical trials, go to: www.atlantichealth.org/research. To learn more about the 2021 AACR Annual Meeting, go to: https://www.aacr.org/meeting/aacr-annual-meeting-2021/.
A new state-by-state analysis shows a statistical association between high adherence to mask wearing and reduced rates of COVID-19 in the U.S. Charlie Fischer and colleagues at the Boston University School of Public Health in Massachusetts present these findings in the open-access journal PLOS ONE on [DATE]. During the COVID-19 pandemic, different states have enacted different policies on mask wearing, with some states having no mask requirements and others requiring masks in all public spaces. Understanding the link between mask wearing and COVID-19 rates could help inform policies to mitigate stress on healthcare systems, economic instability, and death. To help clarify the effects of mask wearing, Fischer and colleagues examined publicly available data on mask-wearing policies, people’s self-reported habits on mask wearing in public, and COVID-19 rates for all 50 U.S. states and Washington, D.C. They accounted for a one-month delay between mask wearing and its subsequent potential impact on COVID-19 rates from May through October 2020. For this analysis, they considered rates of more than 200 cases per 100,000 residents to be high. The analysis showed that, out of 15 states that did not require people to wear masks in public, 14 had high COVID-19 rates. Meanwhile, eight states had self-reported adherence rates of 75 percent of greater, and none of these states had a high COVID-19 rate. States with the lowest adherence rates had the greatest likelihood of high COVID-19 rates in the subsequent month. The eight states with at least 75-percent adherence to mask wearing had a mean COVID-19 rate of 109.26 per 100,000 residents in the subsequent month, while the mean COVID-19 rate was 239.99 for states with less than 75 percent adherence. These findings provide new evidence in support of mask-wearing as a major factor that contributes to reduced COVID-19 rates. They suggest that policies and public health efforts to reduce the spread of COVID-19 should include a focus on improved mask adherence throughout the U.S.
Chicago, Ill. (March 25, 2021) – The Alden Network announced the promotion of Cyeria Brown, BSN, RN to Regional Nurse Consultant. As a new graduate in 2014, Brown was hired as a staff nurse at Alden Debes Rehabilitation and Health Care Center in Rockford, Illinois. Because of her integrity, passion for patient safety and her dedication to clinical excellence, she was promoted to Assistant Director of Nursing in 2017 and in less than a year was promoted to Director of Nursing. In her new role as Regional Nurse Consultant, Brown will focus on regulatory compliance, clinical outcomes and the provision of care, programs and services and will identify opportunities to improve patient care and safety throughout her assigned region of post-acute and rehabilitation facilities. Brown obtained her associate of applied science degree from Kishwaukee College and later obtained her bachelor’s degree in nursing from Chamberlain College of Nursing where she is currently pursuing her master’s degree. Additionally, she is licensed by the State of Illinois as a Registered Nurse and is a certified Infection Preventionist. For more than 50 years, The Alden Network has provided health care and residential solutions for seniors and has helped them function to the best of their ability and live life as independently as possible. To learn more about The Alden Network, please call 1-800-291-5900 or visit www.thealdennetwork.com.
Study author and board-certified dermatologist encourages the public to get vaccinated Newswise — ROSEMONT, Ill. (April 7, 2021) — As COVID-19 vaccination ramps up globally, new research published today in the Journal of the American Academy of Dermatology demonstrates the wide variety of skin rashes, including full-body rashes, observed after COVID-19 vaccination. The authors provide reassurance that these reactions are generally mild, resolve on their own, and should not deter the public from getting vaccinated. “We understand that some of these reactions may look scary, but when they appear more than four hours after receiving the COVID-19 vaccine, they are typically minor and in some cases, may indicate the body’s immune system is doing a good job of responding to the vaccine,” says senior study author and board-certified dermatologist Esther Freeman, MD, PhD, FAAD, director of Global Health Dermatology at Massachusetts General Hospital and principal investigator of the international COVID-19 Dermatology Registry. “Some rashes may appear a day or two after vaccination, and some have a delayed onset, as long as 7-14 days after vaccination. Most of these rashes resolve on their own with time or — depending on the rash — may require oral antihistamines, topical steroids, or other treatments as directed by a physician.” Dr. Freeman does note that any reactions that start immediately after vaccination, or within four hours of the shot, need to be taken very seriously, and patients experiencing these rare type of allergic symptoms should seek prompt medical attention, as recommended by the CDC. Dr. Freeman’s research examined the Moderna and Pfizer vaccines — two of the most widely administered vaccines authorized for emergency use by the FDA — in the U.S. from December 2020 to February 2021. The research of 414 skin reactions logged in the COVID-19 Dermatology Registry from healthcare workers, including board-certified dermatologists, identified a broad range of skin reactions. These include 218 cases of large, delayed reactions near the injection site — dubbed “COVID vaccine arm” — as well as other types of rashes that include rashes at the injection spot, hives, and full-body rashes similar to those typically seen after viral infections. Dr. Freeman also says that some patients have developed pernio/chilblains, or what has been called “COVID toes”, following COVID-19 vaccines. She notes that this is of particular interest because it shows that the vaccine is triggering a similar immune response as can be seen after the virus. While these reactions are uncomfortable, she says, they are not necessarily a bad thing. It shows that your body is mounting an immune response to the vaccine, she says, which, in some cases, shows up on your skin. “As dermatologists, we view the skin as a window into what is happening elsewhere in your body,” says Dr. Freeman. “Through this research, we have a deeper understanding of how the COVID-19 vaccine affects our patients and their skin, and I hope our findings, which show that people tolerated vaccination well even when they did develop skin side effects, offer greater reassurance for anyone who is hesitant to get vaccinated.” In addition to studying a large spectrum of skin reactions to the COVID-19 vaccines, the researchers assessed patients’ responses from the first dose to the second. They found that less than half of the people who experienced skin reactions after the first dose experienced a reaction after the second, and if they did, it was milder. “I hope this information encourages more people to get their second dose of the COVID-19 vaccine even if they experienced a skin reaction after their first dose,” says Dr. Freeman. “The COVID-19 vaccine will help protect you from getting the virus and can also prevent you from getting very sick if you do get infected.” If you have concerns about a rash or other skin reaction that develops after getting the COVID-19 vaccine, don’t hesitate to call your doctor or a board-certified dermatologist. To find a board-certified dermatologist in your area, visit aad.org/findaderm.
Which Senescent Cells Turn On Genes That Encode for Secreted Tumor-regulating Factors Newswise — PHILADELPHIA — (April 1, 2021) — Scientists at The Wistar Institute identified a new mechanism of transcriptional control of cellular senescence that drives the release of inflammatory molecules that influence tumor development through altering the surrounding microenvironment. The study, published in Nature Cell Biology, reports that methyltransferase-like 3 (METTL3) and 14 (METTL14) proteins moonlight as transcriptional regulators that allow for establishment of the senescence-associated secretory phenotype (SASP). Cellular senescence is a stable state of growth arrest in which cells stop dividing but remain viable and produce an array of inflammatory and growth-promoting molecules collectively defined as SASP. These molecules account for the complex crosstalk between senescent cells and neighbouring cells and the effect of cellular senescence in various physiological processes and diseases. Although senescence is regarded as a potent barrier for tumor development, the SASP plays a stage-dependent role during tumor development, mediating the clearance of premalignant lesions during intiation and promoting the growth of established tumors. “Senescent cells undergo widespread changes in gene expression needed to adapt their phenotype and functions,” said Rugang Zhang, Ph.D., deputy director of The Wistar Institute Cancer Center, Christopher M. Davis Professor and leader of the Immunology, Microenvironment & Metastasis Program. “We pointed out a new mechanism that allows cells to turn on a set of genes encoding for the SASP molecules and may potentially be targeted to inhibit this aspect of senescence while preserving its antitumor function.” Zhang, who is senior author on the study, and his team focused on METTL3 and METTL14, proteins known for chemically modifying messenger RNA to regulate its function. They found a new role of these proteins in senescence and regulation of gene expression that is independent of their RNA-modifying function. Depleting cells of METTL3 and METTL14, researchers observed reduced expression of SASP genes, such as inflammatory cytokines, but no effect on cell cycle arrest or other markers of senescence, indicating that decrease in SASP is not an indirect consequence of overall senescence inhibition. “Our results indicate that METTL3 and METTL14 promote expression of SASP genes, in accordance with other studies that revealed an oncogenic role for these two proteins,” said Pingyu Liu, Ph.D., first author of the study and a staff scientist in the Zhang Lab. The team further analyzed the association of METTL3 and METTL14 with DNA, comparing senescent and control cells. While the two proteins are found together on DNA in control cells, in senescent cells they have different distribution patterns, whereby METTL3 tends to sit upstream of SASP genes, near the transcription start site, while METTL14 binds away from gene bodies, on regulatory elements called enhancers. Researchers demonstrated that through this positioning pattern and interacting with each other, METTL3 and METTL14 bring closer together two DNA sequences that in non-senescent cells are distant, allowing the formation of promoter-enhancer chromatin loops. As a consequence, expression of the SASP genes is turned on. “Although we focused on senescence, we envision that the transcription-regulating function of METTL3 and METTL14 may be involved in many other biological processes beyond our current study,” concluded Zhang. Co-authors: Jianhuang Lin, Takeshi Fukumoto, Timothy Nacarelli, Xue Hao, and Andrew V. Kossenkov from The Wistar Institute; Fuming Li and M. Celeste Simon from University of Pennsylvania. Work supported by: National Institutes of Health (NIH) grants R01CA160331, R01CA163377, R01CA202919, R01CA239128, R01CA243142, P01AG031862 to R.Z., P50CA228991, and R50CA211199; U.S. Department of Defense grants OC180109 and OC190181. Additional support was provided by The Honorable Tina Brozman Foundation for Ovarian Cancer Research and The Tina Brozman Ovarian Cancer Research Consortium 2.0; and Ovarian Cancer Research Alliance (Collaborative Research Development Grant #596552 and Ann and Sol Schreiber Mentored Investigator Award #649658). Core support for The Wistar Institute was provided by the Cancer Center Support Grant P30CA010815. Publication information: m6A-independent genome-wide METTL3 and METTL14 redistribution drives senescence-associated secretory phenotype, Nature Cell Biology, 2021. Online publication. Photo: The Wistar Institute Wistar's Dr. Rugang Zhang (center) and lab members