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Newswise — WINSTON-SALEM, NC, JULY 19, 2021 -- Wake Forest researchers and clinicians are using patient-specific tumor ‘organoid’ models as a preclinical companion platform to better evaluate immunotherapy treatment for appendiceal cancer, one of the rarest cancers affecting only 1 in 100,000 people. Immunotherapies, also known as biologic therapies, activate the body’s own immune system to control, and eliminate cancer. Appendiceal cancer is historically resistant to systemic chemotherapy, and the effect of immunotherapy is essentially unknown because clinical trials are difficult to perform due to lack of adequate patient numbers, resulting in a lack of data and limited research models. Researchers at the Wake Forest Organoid Research Center (WFORCE), a joint venture between the Wake Forest Institute for Regenerative Medicine (WFIRM), and the Wake Forest Comprehensive Cancer Center, were the first to create appendiceal cancer organoids to use as a predictive model for potential treatment options (published 2018). The Comprehensive Cancer Center is a major high volume center with a global reputation in the treatment of appendiceal cancer. These cancer organoids are part of WFIRM’s “Body-on-a-Chip” system that allows scientists to engineer the organoids, or human tissue equivalents, that function in a very similar manner as actual human tissues and organs. In this new study, published in the journal Clinical Cancer Research, their results indicate that various types immunotherapies tested on the organoids can potentially support treatment decisions and can achieve personalized results, identifying beneficial treatments while sparing patients from harmful side effects of drugs for which they will obtain no benefit. “For this study we reconstructed patients’ tumors as organoids, supercharged with a built-in immune system directly obtained from the patient,” said senior author Konstantinos I. Votanopoulos, MD, PhD, professor of surgery at the Comprehensive Cancer Center and co-director of WFORCE.  “In this way we created a personalized interface to study how effective the immunotherapy drugs are in activating a patient’s own immune system to kill the cancer. This platform is breaking new ground for appendiceal cancer, and it can also be applied in research for other rare cancers where preclinical models are lacking.” This research study utilizes the WFIRM’s “Body-on-a-Chip” system that allows scientists to engineer the organoids, or humanoid tissue equivalents, that function in a very similar manner as actual human organs.  Cells from tumor biopsies from 26 patients were obtained to grow the organoids - tiny, 3D tissue-like structures, in the lab that that mimic the cancerous tumors. The immune enhanced tumor organoids were treated with one of three immunotherapy drugs and then assessed for responsiveness. “In the future, by verifying that that the tumor and its organoids behave in the same fashion, we could modify clinical trial design and optimize cost by targeting patients with organoids that have exhibited favorable results,” Votanopoulos said. Current strategies to understand tumor progression center on analyses of the tumor cells in isolation, but do not capture the interactions between a tumor and its surrounding space, known as the microenvironment or stroma. This leads to inaccuracies in predicting tumor progression and chemotherapy or immunotherapy response. Patient-derived tumor organoids are used as a testing and predicting platform to model diseases, evaluate efficacy and/or toxicity of new and existing drugs, and can be used to test environmental hazards. Co-author Shay Soker, PhD, professor of regenerative medicine who leads tumor organoid research at WFIRM and co-directs WFORCE, said new technologies and biological models that improve prognostication will have a significant effect on patient mortality. “Using the organoids as a preclinical platform can lead to development of novel therapeutics which target and control tumor cells specifically, sparing healthy tissue from the side effects of chemotherapy and immunotherapy treatments,” he said. “For rare cancers like appendiceal cancer, this technology can make a difference in overall quality of life for patients.” Additional co-authors include: Steven D Forsythe, MS, Richard A Erali, MD, Shyama Sasikumar, MS, Preston Laney, BS, Ethan Shelkey, BS, all of WFIRM; and Ralph D’Agostino Jr, PhD, Lance D Miller, PhD, Perry Shen, MD, and Edward A Levine, MD, all of the Comprehensive Cancer Center. The author’s report no conflicts of interest. Research support provided by: the Wake Forest Dean’s Hero Award, the Appendix Cancer Pseudomyxoma Peritonei Foundation, the National Organization of Rare Diseases, and the National Institute of Health. Results were first presented at the Society of Surgical Oncology Annual Meeting, March 2021.
Newswise — When visiting a health care provider, most people expect to have their body temperature, pulse, weight and blood pressure measured. Some Penn State Health patients can also anticipate questions about how much they exercise. The health system is one of six in the United States and the only one in Pennsylvania to incorporate physical activity as a vital sign.   Exercise has been shown to reduce or prevent chronic illness from diabetes, high blood pressure, cardiovascular disease, certain types of cancer, stroke, dementia, depression and anxiety. Recent research also shows that it may reduce a patient’s symptom severity and risk of dying from COVID-19. The Physical Activity Vital Sign (PAVS) involves providers asking patients questions about exercise during their pre-appointment assessment. Following screening questions about smoking or depression, patients will give information on how many minutes per day they exercise and whether that activity is light, moderate or vigorous. The answers are kept in each patient’s electronic medical record. PAVS is currently being piloted at two practices: Penn State Health Medical Group — Palmyra and Penn State Health Medical Group — Middletown. Once pilot testing is complete, Butts hopes to expand the use of PAVS to more practices across the health system. “Many Americans don’t get enough exercise and not enough health care providers ask about or encourage it with their patients,” said Dr. Jessica Butts, assistant professor of family and community medicine and of orthopedics and rehabilitation. “By incorporating physical activity as a vital sign, it opens the door for patients and providers to discuss and incorporate exercise into treatment and prevention plans more readily.” The U.S. Department of Health and Human Services recommends 150 minutes of moderate intensity exercise per week, 75 minutes of vigorous intensity per week or a combination of both. Health care providers then review the physical activity responses along with other vital signs and can begin a conversation with patients about how they might include exercise as part of their treatment and prevention plans for chronic disease. In addition to improving health outcomes, Butts said preliminary research indicates that PAVS could lead to hundreds of millions of dollars in health care savings. “Studies show that any improvement in physical activity is better than no activity at all,” Butts said. “If we can get patients to move more than they were before, our hope is that will lead to reduced levels of chronic disease, decreased health care costs and improved life expectancy.” Penn State Health patients also have access to more than 20 exercise-related clinical trials conducted by researchers at Penn State College of Medicine. These studies examine how exercise can be used to treat conditions from fatty liver disease, joint and muscle pain to breast, liver and prostate cancers. Butts said she hopes the physical activity vital sign data might be used to study patient health outcomes and add to the existing body of evidence showing that exercise is good for health. “The research is clear: exercise can favorably affect ailments in almost all organ systems, but it’s often undervalued and overlooked for pharmacologic or dietary interventions,” Butts said. “At Penn State Health and Penn State College of Medicine, we’re continuing to discover how physical activity might benefit the health of our patients.” 
A 27-question survey of Association of American Cancer Institutes (AACI) members, including many NCI-designated centers, identified several opportunities to improve coordination of care between main centers and their satellite locations. Newswise — PLYMOUTH MEETING, PA [July 6, 2021] — New research in the June 2021 issue of JNCCN—Journal of the National Comprehensive Cancer Network assesses the quality of cancer care delivered through extended sites coordinated by some of the country’s largest cancer centers. The study was developed to implement strategies for disseminating discoveries and expanding access to the highest quality cancer care as part of AACI’s Network Care Initiative, established by former AACI President Stanton L. Gerson, MD, Director of the Case Comprehensive Cancer Center. Results were calculated based on responses to a mixed-methods survey answered by 69 cancer centers between September 2017 and December 2018, at which time 56 reported at least one network practice site. Just over half indicated that network sites had full access to the main centers’ electronic medical records (EMRs), and even fewer main centers had complete access to records throughout their network sites. “Our findings demonstrate the need to improve network site alignment, particularly in patient navigators, care paths, and clinical trial access,” said Dr. Gerson, the study’s lead researcher and interim dean of the Case Western Reserve University School of Medicine. “Most federal cancer center reviews do not assess the total population of cancer patients served by major cancer centers and their affiliated sites. These data suggest that a very sizable portion of new cancer cases are cared for by these centers and their networks. Greater cancer center/network coordination could ultimately lead to improved access to clinical trials for the underrepresented communities many of these network sites serve.” According to the survey results, some key opportunities to improve coordination of care include: Implementing integrated EMRs across networks; Reviewing best clinical care practices, with more rigorous use of care paths and coordination of diagnosis and treatment planning across sites; Greater attention and support for cancer clinical trials across network sites; and Improved physician oversight of clinical and research expectations, hiring, review and other links with cancer center main campus sites. “Many studies show that consistency through care plans and guidelines improves patient outcomes, clinical response, and survival. More proactive approaches, including care paths, tumor boards across networks, and recognition of the value of placing disease experts at network sites, will improve the standardization of care across sites,” Dr. Gerson added. “Disparities in cancer care outcomes, most significantly patient survival, have been shown between NCI-designated cancer centers and community hospitals, where two-thirds of cancer patients are cared for in the U.S.” commented Lawrence N. Shulman, MD, Deputy Director for Clinical Services at the Abramson Cancer Center at the University of Pennsylvania, who was not involved in this research. “Rural cancer programs often have limited cancer physicians representing all relevant specialties and urban safety-net hospitals often have limited financial resources to support high-quality cancer programs. Partnerships between academic cancer centers and community and safety-net hospitals have the potential to improve outcomes for a broader spectrum of cancer patients in the U.S. One might consider support of these cancer programs an obligation of academic cancer centers. This study outlines some potential mechanisms of support.” The COVID-19 pandemic, which began well after this survey closed, and the growing call for increasing diversity in clinical trials, is also driving the need to better integrate network sites as a tool for delivering quality care to underserved populations. On June 7, NCCN presented a webinar on “Utilization of Network Satellite Locations” as part of a series on COVID-19 and Cancer Center Operations. Dr. Shulman was one of the panelists, along with other members of the NCCN Best Practices Committee. That video is available at: NCCN.org/covid-19. To read the entire study, visit JNCCN.org. Complimentary access to “Status of Cancer Care at Network Sites of the Nation’s Academic Cancer Centers” is available until September 10, 2021.
As Americans are managing life with the Coronavirus and now with the vaccine finally rolling out, and mask mandates lifting for the fully vaccinated, the travel industry is continuing to come back.  Hotels and travel destinations in many parts of the country are open in anticipation of travelers ready to throw off their cabin fever and venture out.  Your plans may be for a weekend get away to a cozy bed and breakfast, or perhaps a fishing trip to catch that “big one” that won’t get away this time. Maybe it’s a camping trip full of hiking adventures with stunning vistas, or possibly you would rather walk through America’s glorious past by taking in all the amenities offered in any of hundreds of museums.  How about a week’s stay at a ranch out west?  Whatever your travel desires are, your options are plentiful and, more importantly, clean, safe and following all CDC guidelines for Coronavirus.  Each week we will list state by state travel options we recommend to help make your vacation choices easy.   ALASKA: Kenai Magic Lodge – Anchorage. MD Discovery Alaskan Charters – Ketchikan.   ARIZONA: Stampede RV and Bed & Breakfast – Tombstone. Hall of Flame Fire Museum – Phoenix.   ARKANSAS: Beaver Lake Hideaway – Garfield. Urban Peddlers Retreat – VRBO-2039106 – Bentonville. Vista del Paradiso – VRBO-1744925 – Bella Vista.   CALIFORNIA: Mendo Parks – Mendocino. Catalina Island Museum – Avalon. Orangeland RV Park – Orange.   COLORADO: Inn at Lost Creek – Telluride. Valhalla Resort – Estes Park. Alpine Inn – Gunnison. Monarch Spur RV Park & Campground – Salida.   CONNECTICUT: Connecticut Trolley Museum – East Windsor.   FLORIDA: Pompano Beach Rentals – Pompano Beach. Barbara O’Donnell - 954.953.4992 Ramada Inn – Temple Terrace. Light Tackle Adventures – Odessa. El Caribe Resort and Conference Center – Daytona Beach.   GEORGIA: National Civil War Naval Museum – Columbus.   IDAHO: Pend Orielle Resort – Hope. The Roosevelt Inn – Coeur D’Alene.   ILLINOIS: Rooster Heaven Hunt Club – Forrest. Bear Branch – Eddyville. Keyesport Cabins – Keyesport.  618.749.5413 McLean County Museum of History – Bloomington.   INDIANA: Grissom Air Museum – Peru.   IOWA: Sanford Museum & Planetarium – Cherokee. Scenic View Ranch – Monona.   KANSAS: Combat Air Museum – Topeka. Covered Wagon RV Resort – Abilene.   KENTUCKY: Singing Hills RV Resort – Cave City. Riverside Inn Bed and Breakfast – Warsaw. Lynnhurst Family Resort – Murray. OH Kentucky Campground and RV Park – Berea.   LOUISIANA: City of Opelousas Tourism – Opelousas. Cajun Country Cottages – Breaux Bridge. Terrell House – New Orleans. La Quinta Inn – Slidell.   MAINE: Old Fort Western – Augusta. York Beach Camper Park – York Bench.   MICHIGAN: Days Inn & Suites by Wyndham – St. Ignace. Greenwood Acres RV – Jackson. Serendipity Bed & Breakfast – Saugatuck. US National Ski-Snowboard Hall of Fame – Ishpeming. Michigan Heroes Museum – Frankenmuth. Hotel Nichols – South Haven.   MINNESOTA: Starck’s Tamarck – Deer River. White Oak Inn & Suites – Deer River. Guest House International Inn & Suites – Rochester. Kecs Kove – Kabetagoma.   MISSISSIPPI: Magnolia Cottage Bed & Breakfast – Natchez.   MISSOURI:            KC Karting Association – Liberty. Best Western Branson Inn – Branson. Driftwater Resort – Branson.   MONTANA: Montana Military Museum – Fort Harrison.   NEVADA: Nevada Northern Railway Museum – Ely.   NEW MEXICO: NM Holocaust Museum – Albequerque.   NEW YORK: Adirondak Experience – Blue Mountain Lake. Victorian Bed & Breakfast – Staten Island. Fernbaugh Campground & Rec Center – Corning.   NORTH CAROLINA: The Groome Inn – Greensboro. Pinebrook Manor Bed and Breakfast – Hendersonville.   NORTH DAKOTA: Dakota Waters Resort – Beulah. McQuoid Outdoors & Lodging – Minnewaukan.   OHIO: Good Earth Cabins – Logan.   OREGON: The Fort Dalles Museum – The Dalles.   PENNSYLVANIA: Manayunk Chambers Guest House – Philadelphia. Inn at White Oak – Gettysburg.   TENNESSEE: The Olde Mill Inn Bed & Breakfast – Cumberland Gap. Mountain Breeze Motel – Pigeon Forge. Appleview River Resort – Sevierville.   TEXAS: Breeze Lake/Sunset Palms Campgrounds – Brownsville. American Undersea Warfare Museum – Galveston. National Museum of the Pacific War – Fredericksburg. Alamo RV Park – Alamo. Triple Creek RV Music Resort – Woodville.   VIRGINIA: Historic Smithfield – Blacksburg.   WASHINGTON D.C.: National Museum of the US Navy   WEST VIRGINIA: The Lost River Grill, Motel and Bed & Breakfast – Lost River.   WISCONSIN: Mid-Continent Railway and Museum – North Freedom.   BRITISH VIRGIN ISLANDS: M&M Apartment Suites & Bakery – Spanish Town.   When you are ready to travel, we are here to help!  Keep checking back every week for more featured locations.  Our travel hosts are eager to see you and work with you to provide safe and clean facilities.    
Newswise — BALTIMORE (June 14, 2021) – Researchers at the University of Maryland School of Medicine (UMSOM) analyzed data at the 13-hospital University of Maryland Medical System (UMMS) and found public health measures designed to reduce the spread of the COVID-19 virus may have fostered a substantial side benefit: Hospital admissions for chronic obstructive pulmonary disease (COPD) were reduced by 53 percent, according to a new study published in The American Journal of Medicine.  This is likely due to a drop in circulating seasonal respiratory viruses such as influenza. Hospitalizations for COPD, a group of lung diseases that make it hard to breathe and get worse over time, are commonly driven by flare-ups where symptoms are triggered by such factors as tobacco smoke, air pollution and respiratory infections. Seasonal respiratory viruses, including those that cause the common cold or influenza, trigger nearly half of those flare-ups. In the wake of a marked drop in COPD admissions during the pandemic, the researchers theorized that COVID-19 behavior changes – a mix of stay-at-home orders, social distancing, masking mandates and strict limitations on large gatherings – not only protected against COVID-19, but they may have also reduced exposure to other respiratory infections. Conversely, they worry that the return to normal behavior may lead to more COPD flare-ups. “Our study shows there’s a silver lining to the behavior changes beyond protecting against COVID-19,” said senior author Robert M. Reed, MD, UMSOM Professor of Medicine and pulmonologist at the University of Maryland Medical Center (UMMC). “If we completely eliminate masks and distancing during cold and flu season, we’ll allow all those viruses that have been effectively suppressed to come raging back. There could be a lot of illness.” Prior to the COVID-19 pandemic, COPD was the fourth-leading cause of death worldwide and a leading cause of hospital admissions in the United States. The pandemic has led to significant changes in health care delivery, including reduced admissions for COPD and other non-COVID illnesses, some of which may have stemmed from patients’ fear of contracting COVID in various hospital settings, as well as a shift toward telemedicine and outpatient COPD management during the pandemic. To understand what may have occurred to reduce COPD admissions, the researchers compared weekly hospital admissions for COPD in the pre-COVID-19 years of 2018 and 2019, with admissions after the COVID-19 public health measures were instituted. At UMMS, those measures were implemented before April 1, 2020, so the investigators chose the same five-month period in each year for their comparison, April 1 to Sept. 30. Co-lead author Jennifer Y. So, MD, UMSOM Assistant Professor of Medicine and COPD specialist at UMMC, said electronic medical records from multiple hospitals across a range of communities in the UMMS database facilitated a granular evaluation of changes over time. “We assessed a variety of possible causes that could affect COPD admissions including the presence of multiple diseases or medical conditions and the frequency of COPD exacerbations.” The database findings were correlated with data on respiratory viral trends from the U.S. Centers for Disease Control and Prevention for the period of Jan. 1, 2018, through Oct. 1, 2020. “We found a 53 percent drop in COPD admissions throughout UMMS during COVID-19. That is substantial, but equally significant, the drop in weekly COPD admissions was 36 percent lower than the declines seen in other serious medical conditions, including congestive heart failure, diabetes and heart attack,” said Dr. So. As more and more people are vaccinated against COVID-19 and many of the public health measures of the past year are relaxed, the researchers warn that a full return to normal may again expose COPD patients to the familiar seasonal triggers. “Our study did not assess which public health components worked to tame seasonal respiratory viruses, but a simple thing like wearing a mask while riding on public transit or working from home when you’re sick with a cold could go a long way to reduce virus exposure,” said Dr. Reed. Dr. So, who is from South Korea, said it is a cultural norm to wear masks during the winter in her native country. “The COVID-19 pandemic has helped a lot of people around the world become more aware of the role of masking and social distancing to reduce the spread of disease,” she said. “This is a compelling study that raises some important public health questions about protecting our most vulnerable patient populations after we are finished with the COVID-19 pandemic. I certainly think it warrants a fuller discussion,” said UMSOM Dean E. Albert Reece, MD, PhD, MBA, University Executive Vice President for Medical Affairs and the John Z. and Akiko K. Bowers Distinguished Professor. So JY, O’Hara NN, Kenaa B, Williams JG, deBorja CL, Slejko JF, Zafari Z, Sokolow M, Zimand P, Deming M, Marx J, Pollak A, Reed RM. Decline in COPD Admissions During the COVID-19 Pandemic Associated with Lower Burden of Community Respiratory Viral Infections. The American Journal of Medicine, June 11, 2021. doi: https://doi.org/10.1016/j.amjmed.2021.05.008
Newswise — A nasal therapy, built upon on the application of a new engineered IgM antibody therapy for COVID-19, was more effective than commonly used IgG antibodies at neutralizing the COVID-19 virus in animal models, according to research recently published by The University of Texas Health Science Center at Houston (UTHealth), The University of Texas Medical Branch at Galveston (UTMB Health), the University of Houston, and IGM Biosciences, Inc.  The study was published today in Nature. Researchers engineered IgM antibodies and found that in all cases, these antibodies were significantly more potent than standard IgG antibodies in neutralizing the COVID-19 virus. One of the engineered IgM antibodies, IGM-6268, demonstrated a significantly increased potency against the original SARS-CoV-2 and emerging variants such as the current U.K., South African, and Brazilian variants of concern (VOC) and variants of interest (VOI), as well as the antibody escape mutants for the current Emergency Use Authorization antibodies. Additionally, IGM-6268 was shown to be highly effective for prophylaxis and treatment in mouse models when administered intranasally.  “High viral load in the respiratory tract correlates with severe illness and mortality in patients with COVID-19,” said Zhiqiang An, PhD, director of UTHealth Texas Therapeutics Institute, professor and Robert A. Welch Distinguished University Chair in Chemistry at McGovern Medical School at UTHealth, and faculty member at MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences and one of the corresponding authors on the study. “Respiratory mucosal antibodies are key to clearing SARS-CoV-2 infection and reducing viral transmission and IgM antibodies are nature’s first line of defense against pathogens such as viruses.” The current government-approved antibodies, which are all IgG antibodies, are administered intravenously at high doses and don’t directly target the main sites of viral infection. “SARS-CoV-2 has evolved mutations that severely compromise the neutralizing activities of multiple IgG monoclonal antibodies, including those under clinical trials and authorized for emergency use. Therefore, developing new antibody therapies that can overcome these challenges is an urgent unmet need, and we are pleased with the data published today,” An said. “Synergizing the strengths of multiple institutions from academia and industry is the key to the rapid translation from ideas to therapeutic candidates. This is another example of such success. The cross-institutional and academic-industry collaborations should be expanded to other disease indications,” said Pei-Yong Shi, PhD, professor and co-senior author of the study from the Department of Biochemistry and Molecular Biology at UTMB Health. This antibody has been licensed to biotech partner IGM Biosciences for drug development. “The ability to use potently neutralizing IgM antibodies against SARS-CoV-2 with broad coverage of VOCs, VOIs, and viral escape mutants, is a very exciting application of the IGM platform,” said Fred Schwarzer, CEO of IGM Biosciences. “We are grateful to our collaborators at UTHealth, UTMB Health, and our scientists at IGM for the exceptional work described in Nature today.” Additional UTHealth authors: Zhiqiang Ku, PhD; Xiaohua Ye, PhD; Wei Xiong, MD, PhD; Junquan Liu, PhD; Ningyan Zhang, PhD; Hang Su, and Hui Deng.   Other authors include Xuping Xie, PhD; Antonio E. Muruato, PhD; Jing Zou, PhD; Yang Liu, PhD; and Vineet D. Menachery, PhD, with UTMB Health; Xinli Liu, PhD; and Sujit Biswas with the University of Houston; and Paul R. Hinton; Dean C. Ng, PhD; Yu-An Cao, PhD; Kevin B. Carlin, PhD; Elizabeth J. Haanes, PhD; Bruce A. Keyt, PhD; Stephen F. Carroll, PhD; Deepal Pandya, and Sachi Rahman with IGM Biosciences. The work was supported by grants from the Cancer Prevention and Research Institute of Texas, the National Institutes of Health, the Welch Foundation, the Sealy Smith Foundation, the Kleberg Foundation, the John S. Dunn Foundation, the Amon G. Carter Foundation, the Gillson Longenbaugh Foundation, and the Summerfield Robert Foundation.   Photo info:  Photo by UTHealth Zhiqiang An, PhD, was one of the lead authors of a study that revealed engineered IgM antibodies were more potent than standard ones against COVID-19.
Newswise — Washington, DC (June 1, 2021) — Many individuals with kidney failure have been unable to self-isolate during the COVID-19 pandemic because they require dialysis treatments in clinics several times a week. New research that will appear in an upcoming issue of CJASN highlights the risks faced by these patients and the factors involved. For the study, Ben Caplin, MBChB, PhD (University College London) and his colleagues, on behalf of the Pan-London COVID-19 Renal Audit Group, examined information on 5,755 patients who received dialysis in 51 clinics in London. Between March 2 and May 31, 2020, a total of 990 (17%) patients tested positive and 465 (8%) were admitted to hospitals with suspected COVID-19. COVID-19 risks were higher in patients who were older, had diabetes, lived in local communities with higher COVID-19 rates, and received dialysis at dialysis clinics that served a larger number of patients. Risks were lower in patients who received dialysis in clinics with a higher number of available side rooms and that had mask policies for asymptomatic patients. No independent association was seen with sex, ethnicity, or measures of deprivation. “Taken together, the findings confirm the high rates of symptomatic COVID-19 among patients receiving in-center dialysis and suggest sources of transmission both within dialysis units and patients’ home communities,” said Dr. Caplin. “The work also suggests that in addition to isolation of confirmed cases, addressing factors that might reduce transmission from patients without suspected or confirmed disease might provide an additional opportunity to further modify the impact of COVID-19 in this population.” Study co-authors include Damien Ashby, Kieran McCafferty, Richard Hull, Elham Asgari, Martin L. Ford, Nicholas Cole, Marilina Antonelou, Sarah A. Blakey, Vinay Srinivasa, Dandisonba C.B. Braide-Azikwe, Tayeba Roper, Grace Clark, Helen Cronin, Nathan J. Hayes, Bethia Manson, Alexander Sarnowski, Richard Corbett, Kate Bramham, Eirini Lioudak7, Nicola Kumar, Andrew Frankel, David Makanjuola, Claire C. Sharpe, Debasish Banerjee, and Alan D. Salama.  Disclosures: Dr. Caplin reports personal fees from Lifearc, grants from Astra Zeneca, grants from Colt Foundation, grants from Medical Research Council,  from Royal Free Charity,  outside the submitted work;  Dr. Ashby reports personal fees from Fibrogen,  outside the submitted work; Dr. Corbett has a patent WO2017148836A1: "A device for maintaining vascular connections" issued; Dr. Banerjee reports grants from AstraZeneca, grants from Kidney Research UK, personal fees from ViforPharma,  outside the submitted work. The article, titled “Risk of COVID-19 Disease, Dialysis Unit Attributes, and Infection Control Strategy among London In-Center Hemodialysis Patients,” will appear online at http://cjasn.asnjournals.org/ on June 1, 2021. The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies. Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has more than 21,000 members representing 131 countries. For more information, visit www.asn-online.org.
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.