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Tag: Respiratory Diseases and Disorders

  • Rising flu, COVID, RSV rates: Johns Hopkins expert available for interviews

    Rising flu, COVID, RSV rates: Johns Hopkins expert available for interviews

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    Andrew Pekosz, PhD, professor and vice chair in the Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health, is available for media interviews to discuss the rising rates of respiratory illnesses, the declining rate of vaccinations, and the Centers for Disease Control and Prevention’s Health Advisory urging healthcare providers to encourage their patients to get vaccinated. 

    Journalists are also welcome to use the following comment from Andrew Pekosz:  

    “It’s troubling that we’re seeing increased hospitalizations from influenza and COVID-19 at the same time that vaccination rates are falling. It is critical that people stay up-to-date on their vaccinations, and that is particularly true for individuals in high-risk groups, to mitigate the chances of illness or even death.” 

    The CDC reported that in the past month, “hospitalizations among all age groups increased by 200% for influenza, 51% for COVID-19, and 60% for RSV. As of December 1, 2023, the weekly percentages of pediatric emergency department visits for pneumonia due to multiple etiologies were increasing since September in children, but remains consistent with prior fall and winter respiratory activity. To date, 12 pediatric influenza deaths have been reported during the 2023–2024 season. From September 1 through December 10, 2023, CDC received 30 reports of MIS-C, a rare complication that typically occurs 1 month after SARS-CoV-2 infection, with illness onset among cases occurring from August 6 to November 9, 2023, a relative increase compared with previous months. High RSV activity is also occurring across much of the United States.”

    The CDC also stated that “as of November 18, 2023, there were 7.4 million fewer influenza vaccine doses administered to adults in pharmacies and physician offices compared with the 2022–2023 influenza season” and that “as of December 2, 2023, the percent of the population reporting receipt of [the COVID-19] vaccine was 7.7% in children 6 months–17 years (including 2.8% in children 6 months–4 years), 17.2% in adults ≥18 years (including 36% in adults ≥65 years), and 9.6% in pregnant persons. … As of December 2, 2023, 15.9% of U.S. adults aged ≥60 years reported receiving an RSV vaccine.” 

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    Johns Hopkins Bloomberg School of Public Health

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  • Immune cells shape lungs prenatally, offering novel respiratory disease treatments.

    Immune cells shape lungs prenatally, offering novel respiratory disease treatments.

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    Newswise — Immune cells play an active and intimate role in directing the growth of human lung tissue during development, researchers find, revolutionising our understanding of early lung development and the role of immune cells outside of immunity.

    The research offers new insights for understanding and treating respiratory conditions, such as chronic obstructive pulmonary disease (COPD). Respiratory conditions account for almost 20 per cent of all deaths in children under five years worldwide1.

    The work reveals a surprising coordination between the immune and respiratory systems, much earlier in development than previously thought. This discovery raises questions about the potential role of immune cells in other developing organs across the body.

    Researchers from the Wellcome Sanger Institute, University College London (UCL) and their collaborators at EMBL’s European Bioinformatics Institute used advanced single-cell technologies to map the development of early human lung immune cells over time.

    This study has created a first-of-its-kind immune cell atlas of the developing lung2. It is part of the international Human Cell Atlas3 initiative, which is mapping every cell type in the human body, to transform our understanding of health, infection and disease.

    The findings, published today (15 December) in Science Immunology, will help shed light on the mechanisms behind childhood lung diseases.

    Immune cells make up a substantial portion of the airways and mature lungs, which have critical gas exchange and barrier functions, providing protection against infection of the respiratory tract. However, the roles of immune cells in the developing organ have remained unexplored compared to structural or lining cell types. Recent discoveries confirm the presence of immune cells in human lungs as early as five weeks into development4.

    To explore whether the immune system might influence how lungs grow, the team studied immune cells in early human lungs from 5 to 22 weeks of development. They used various techniques, including single-cell sequencing and experiments with lung cell cultures, to see if immune cells could affect lung cell development.

    They identified key regulators of lung development, including signalling molecule IL-1β and IL-13 that facilitate the coordination of lung stem cells differentiating into specialised mature cell types5.

    The researchers detected an infiltration of innate, followed by adaptive immune cells. Innate cells included innate lymphoid cells (ILCs), natural killer (NK) cells, myeloid cells and progenitor cells. With respect to adaptive immune cells, as well as T cells, both developing and mature B lineage cells were detected, indicating that the lung environment supports B cell development.

    The findings fundamentally change the understanding of the immune and epithelial interactions that are crucial for foetal lung maturation. They also suggest that early immune disturbances could manifest as paediatric lung disease.

    These new insights into mechanisms in early lung formation will also contribute to the development of new therapeutic approaches for regenerating damaged lung tissue and restoring lung function.

    Dr Peng He and Dr Jo Barnes, co-first authors of the study at the Wellcome Sanger Institute and EMBL’s European Bioinformatics Institute, and UCL Division of Medicine respectively, said: “By adopting a focused strategy in mapping the immune system, we reveal a symbiotic relationship between immune cells and developing lungs. These detailed insights open the door to potential regenerative therapies in not only the lung, but in other vital human organs.”

    Dr Marko Nikolić, senior author of the study at UCL Division of Medicine and honorary consultant in respiratory medicine, said: “We now know immune-epithelial crosstalk is a feature of early lung development. This vital baseline of healthy lung development will help us understand what happens when lung developmental processes get disrupted, for example in preterm births, which can lead to respiratory deficiencies.”

    Dr Kerstin Meyer, senior author of the study at the Wellcome Sanger Institute, said: “The active participation of immune cells expands the possibilities for understanding and addressing impaired lung formation. What is super exciting about this mechanism is that it may well apply in other organ systems too.”

    Dr Sarah Teichmann, senior author of the study at the Wellcome Sanger Institute and Co-founder of the Human Cell Atlas, said: “If we are to fully understand the root causes of disease, we require a complete view of cells at all stages in the human body. This important contribution towards a comprehensive Human Cell Atlas will be a valuable reference for studying lung diseases.”

    ENDS

    Notes to Editors:

    1. https://www.who.int/data/gho/indicator-metadata-registry/imr-details/3147
    2. The researchers analysed human embryonic and foetal lung tissue between 5 and 22 weeks post-conception. Human embryonic tissue was provided by the Joint MRC/Wellcome Trust Human Developmental Biology Resource (www.hdbr.org)
    3. The Human Cell Atlas (HCA) is an international collaborative consortium which is creating comprehensive reference maps of all human cells—the fundamental units of life—as a basis for understanding human health and for diagnosing, monitoring, and treating disease. The HCA is likely to impact every aspect of biology and medicine, propelling translational discoveries and applications and ultimately leading to a new era of precision medicine.
      The HCA was co-founded in 2016 by Dr Sarah Teichmann at the Wellcome Sanger Institute (UK) and Dr Aviv Regev, then at the Broad Institute of MIT and Harvard (USA). A truly global initiative, there are now more than 3,100 HCA members, from 98 countries around the world. https://www.humancellatlas.org
    4. https://www.cell.com/cell/fulltext/S0092-8674(22)01415-5?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867422014155%3Fshowall%3Dtrue
    5. Experimentation showed that IL-1β, a cytokine produced by immune cells, directly induced airway epithelial progenitor cells to differentiate into mature lung lining cells. They do this by decreasing SOX9 expression and proliferation, driving lung epithelial progenitor cells to stop self-renewal.

    Publication:
    J.L. Barnes et al. (2023) ‘Early human lung immune cell development and its role in epithelial cell fate.’ Science Immunology. DOI: 10.1126/sciimmunol.adf9988

    Funding:
    This research was supported by Wellcome. For full funding acknowledgements, please refer to the publication.

    Selected websites:

    About UCL (University College London)
    UCL was founded in 1826. We were the first English university established after Oxford and Cambridge, the first to open up university education to those previously excluded from it, and the first to provide systematic teaching of law, architecture and medicine. We are among the world’s top universities, as reflected by performance in a range of international rankings and tables. UCL currently has over 39,000 students from 150 countries and over 12,500 staff. Our annual income is more than £1 billion. www.ucl.ac.uk | Follow us on Twitter @uclnews | Watch our YouTube channel YouTube.com/UCLTV

    The Wellcome Sanger Institute
    The Wellcome Sanger Institute is a world leader in genomics research. We apply and explore genomic technologies at scale to advance understanding of biology and improve health. Making discoveries not easily made elsewhere, our research delivers insights across health, disease, evolution and pathogen biology. We are open and collaborative; our data, results, tools, technologies and training are freely shared across the globe to advance science.

    Funded by Wellcome, we have the freedom to think long-term and push the boundaries of genomics. We take on the challenges of applying our research to the real world, where we aim to bring benefit to people and society.

    Find out more at www.sanger.ac.uk or follow us on Twitter, Instagram, Facebook, LinkedIn and on our Blog.

    About Wellcome
    Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, infectious disease and climate and health. https://wellcome.org/

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    Wellcome Trust Sanger Institute

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  • Groundbreaking progress in treating severe asthma emerges.

    Groundbreaking progress in treating severe asthma emerges.

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    Newswise — A landmark study has shown that severe asthma can be controlled using biologic therapies, without the addition of regular high-dose inhaled steroids which can have significant side effects.

    The findings from the multinational SHAMAL study, published in The Lancet, demonstrated that 92% of patients using the biologic therapy benralizumab could safely reduce inhaled steroid dose and more than 60% could stop all use. 

    The study’s results could be transformative for severe asthma patients by minimising or eliminating the unpleasant, and often serious, side effects of inhaled steroids. These include osteoporosis which leads to increased risk of fractures, diabetes and cataracts.

    Asthma is one of the most common respiratory diseases worldwide – affecting almost 300 million people – and around 3 to 5% of these have severe asthma.  This leads to daily symptoms of breathlessness, chest tightness and cough, along with repeated asthma attacks which require frequent hospitalisation.

    The SHAMAL study was led by Professor David Jackson, head of the Severe Asthma Centre at Guy’s and St Thomas’ and Professor of Respiratory Medicine at King’s College London.

    Professor Jackson said: “Biological therapies such as benralizumab have revolutionised severe asthma care in many ways, and the results of this study show for the first time that steroid related harm can be avoided for the majority of patients using this therapy.” 

    Benralizumab is a biologic therapy that reduces the number of inflammatory cells called eosinophil. This is produced in abnormal numbers in the airway of patients with severe asthma and is critically involved in the development of asthma attacks. Benralizumab is injected every four to eight weeks and is available in specialist NHS asthma centres.

    The SHAMAL study took place across 22 sites in four countries – the UK, France, Italy and Germany.

    The 208 patients were randomly assigned to taper their high dose inhaled steroid by varying amounts over 32 weeks, followed by a 16 week maintenance period. Approximately 90% of patients experienced no worsening of asthma symptoms and remained free of any exacerbations throughout the 48 week study. 

    Similar studies to SHAMAL will be necessary before firm recommendations can be made regarding the safety and efficacy of reducing or eliminating high dose steroid use with other biologic therapies.

    The study was funded by AstaZeneca and carried out by researchers at renowned universities including Queens University Belfast, Université Paris-Saclay and Trinity College Dublin.

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    King’s College London

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  • UTHealth Houston researchers awarded $2.6M NIH grant to study molecular pathways and potential strategies for treatment of myocardial ischemia and reperfusion injury

    UTHealth Houston researchers awarded $2.6M NIH grant to study molecular pathways and potential strategies for treatment of myocardial ischemia and reperfusion injury

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    Newswise — A four-year, $2.6 million grant to study circadian rhythm and novel therapies to protect the heart during a heart attack or cardiac surgery has been awarded to UTHealth Houston by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.

    Principal investigator Holger Eltzschig, MD, PhD, professor, and co-investigator Wei Ruan, MD, PhD, assistant professor, from the Department of Anesthesiology, Critical Care and Pain Medicine at McGovern Medical School at UTHealth Houston, are studying translational, pharmacologic, and interventional strategies targeting circadian rhythm and hypoxia signaling that could help patients who are experiencing a heart attack or undergoing open-heart surgery.

    Previously published research in 2012 and 2021 by Eltzschig and Ruan showed that biological rhythms affect myocardial ischemia and reperfusion injury (IRI) severity. IRI can occur in the setting of a heart attack, open-heart surgery, or during circulatory arrest, where blood flow is temporarily cut off (ischemia). During this period, the affected heart tissues suffer from inadequate oxygen supply (hypoxia). Once the obstruction is removed and blood flow resumes (reperfusion), rather than bringing immediate relief, this sudden influx of blood can lead to additional stress and damage to the heart.  

    The previous research further indicated that larger infarctions or higher incidences of heart failure happen in patients with morning onset heart attacks rather than later in the day. This daytime variation of myocardial injury hints at a potential interaction between circadian rhythm and hypoxia signaling.

    “My laboratory has been very interested in studying IRI for over two decades,” said Eltzschig, the John P. and Kathrine G. McGovern Distinguished University Chair and the director of the Center for Perioperative Medicine at McGovern Medical School. “We undertook an unbiased look to understand the molecular mechanisms of why there are differences in heart attacks in the early morning versus the late afternoon.”

    In studies that led up to the current grant application, the team of scientists analyzed heart tissue samples from circadian rhythm-trained mice following heart attacks at different time points of the day. In addition, they analyzed samples derived from the left heart ventricle of patients undergoing cardiac surgery at different times of the day. They identified a highly differentially expressed gene, BMAL1, a core circadian transcription factor. The genetic deletion of BMAL1 in mouse hearts eliminates daytime variations in cardiac injury.

    Natural protective molecules called hypoxia-inducible factors (HIFs) are activated due to a lack of oxygen and promote the adaptation to limited oxygen availability. In addition, HIFs limit excessive tissue inflammation in order to prevent further tissue damage. Specifically, researchers uncovered that HIF2A works together with BMAL1 in heart tissues to provide circadian-dependent heart protection.

    With this grant, researchers will aim to understand how BMAL1 and HIF2A interact and their functional roles in modulating daytime variation of cardiac injury. High-resolution imaging techniques will be employed to study the molecular interactions between BMAL1 and HIF2A by Kuang-Lei Tsai, PhD, co-principal investigator and assistant professor, and postdoctoral researcher Tao Li, PhD, from the Department of Biochemistry and Molecular Biology at McGovern Medical School. They will further explore the possibility of targeting the BMAL1 and HIF2A pathways as therapeutic strategies to protect the heart from injuries during surgery.

    “We are using data to see if the pathways and transcriptional regulations are occurring in patients undergoing cardiac surgery in the morning or the afternoon,” Eltzschig said.

    The other co-principal investigator of the study is Jochen Daniel Muehlschlegel, MD, MMSc, MBA, professor and chair of the Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University. NIH Grant R01HL165748 funds this research.

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    University of Texas Health Science Center at Houston

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  • The mechanism of tuberculosis infection via cord-like bacterial aggregates.

    The mechanism of tuberculosis infection via cord-like bacterial aggregates.

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    Newswise — The ability of Mycobacterium tuberculosis (MTB), a serious respiratory infection, to form snake-like cords was first noted nearly 80 years ago. In a study published October 20 in the journal Cell, investigators report the biophysical mechanisms by which these cords form and demonstrate how several generations of dividing bacteria hang together to create these structures that enable resistance to antibiotics.

    “Our work clearly showed that cord formation is important for infection and why this highly ordered architecture might be important for pathogenesis,” says senior author Vivek Thacker (@DrVivekThacker), who led the work at the Global Health Institute at École Polytechnique Fédérale de Lausannen (EPFL) in Switzerland and is now based at the Department of Infectious Diseases at Heidelberg University in Germany.

    The study used a unique combination of technologies to address the role of MTB cord formation. One was a lung-on-chip model, which allowed the researchers to get a direct look at “first contact” between MTB and host cells at the air-liquid interface in the lungs. This revealed that cord formation is prominent in early infection. The researchers also used a mouse model that develops pathologies mimicking human tuberculosis, allowing them to obtain tissue that could be studied using confocal imaging and confirming that cording also occurs early in infection in vivo.

    The work yielded several new findings about how these cords interact with and compress the cell nucleus, how this compression affects the immune system and connections between host cells and epithelial cells, and how cord formation affects the alveoli in the lungs. The study also revealed how these cords retain their structural integrity and how they increase tolerance to antibiotic therapy.

    “There is an increasing understanding that these mechanical forces influence cellular behavior and responses, but this aspect has been overlooked since traditional cell culture models do not recapitulate the mechanical environment of a tissue,” says Melanie Hannebelle (@MelanieHanneb), formerly at EPFL’s Global Health Institute and now at Stanford University. “Understanding how forces at the cellular and tissue level or crowding at the molecular level affects cell and tissue function is therefore important to develop a complete picture of how biosystems work.”

    “By thinking of MTB in infection as aggregates and not single bacteria, we can imagine new interactions with host proteins for known effectors of MTB pathogenesis and a new paradigm in pathogenesis where forces from bacterial architectures affect host function,” says Thacker.

    Future research will focus on understanding whether cord formation enables new functionality to known effectors of MTB pathogenesis, many of which are located on the MTB cell wall. In addition, it will look at the consequence of tight-packing on the bacteria within the clump and how this may lead to a protective effect against antibiotics.

    “Antibiotic therapy is the mainstay of treatment for tuberculosis infections, but therapeutic regimens are long and complicated, with an increasing threat of drug resistance,” says Richa Mishra, the other first author who is currently at EPFL’s Global Health Institute. “There is a recognized need for host-directed therapies or therapies that inhibit specific virulence mechanisms that can shorten and improve antibiotic therapy.”

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    Cell Press

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  • Tobacco sales up after e-cigarette restrictions

    Tobacco sales up after e-cigarette restrictions

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    Newswise — New Haven, Conn. — The immense popularity of electronic cigarettes, or e-cigarettes, among young people has led many policymakers to restrict the sale of flavored varieties. But rather than nudging people away from “vapes,” as these e-cigarettes are called, such measures could backfire by driving users to instead buy conventional cigarettes, a much more dangerous product, according to researchers at the Yale School of Public Health (YSPH).

    In a large-scale, long-term analysis of policies and sales data, the researchers found that for every 0.7 milliliters of “e-liquid” (the consumable content inside e-cigarettes, also known as vape juice) that goes unsold due to flavor restrictions, 15 additional traditional cigarettes are sold. The substitution was especially evident among cigarette brands popular with young people aged 20 and under, suggesting that flavor restrictions may increase smoking among youth as well as adults.

    The results suggest that this type of policy, which is intended to curb nicotine-related harms, may instead magnify them.

    “While neither smoking nor vaping is entirely safe, current evidence indicates substantively greater health harm from smoking than vaping nicotine products,” said first author Abigail S. Friedman, an associate professor in the YSPH Department of Health Policy & Management. “These policies’ public health costs may outweigh their benefits.”

    The study appears online as a pre-print prior to peer review at Social Science Research Network.

    Tempting flavors
    While randomized clinical trials show that e-cigarettes can be effective tools for quitting smoking, their availability in a wide range of flavors such as strawberry banana, breakfast cereal, lemonade, bubblegum, and cheesecake can make them especially tempting to youth.

    A 2019 outbreak of vaping-associated lung injuries led to thousands of hospitalizations and at least 68 deaths. While the outbreak’s primary cause was eventually identified as an additive most common in cannabis vaping products, its initial attribution to e-cigarettes — as well as worries that nicotine e-cigarettes may be an on-ramp to youth tobacco use — led hundreds of localities in the U.S. to restrict the sale of flavored vapes.

    Previous studies of such policies have mostly examined local or temporary post-2019 state policies. The Yale study was the first to assess how flavor restrictions across most of the United States influence sales of both vapes and cigarettes.

    Laws and consequences
    The authors used rigorous statistical tools to estimate long-term effects of e-cigarette flavor restrictions on electronic and conventional cigarette sales in jurisdictions across 16 states. They also examined how these effects varied between brands disproportionately used by underage youth versus adults.

    The authors first created a comprehensive database of tobacco product flavor prohibition and restriction laws across the United States, including both state and local statutes. They reviewed each policy to identify which tobacco products were covered —including vapes, cigars, and conventional cigarettes — which flavors were restricted, when the policies would take effect, and any exemptions for certain types of businesses, such as adult-only tobacco stores.

    They compared this information against vape and cigarette sales data over four-week intervals from January 2018 through March 2023, a period during which flavor restrictions went from affecting 1.3% of the U.S. population to affecting 38%. The sales data came from ordinary brick-and-mortar establishments like gas stations, groceries, and convenience stores. Statistical analyses took into account a host of other factors that may affect tobacco product sales, such as concurrent restrictions on flavored cigar and menthol cigarette sales, tax rates, cannabis availability, and unemployment rates.

    The primary outcome of interest was volume sales of conventional cigarettes and e-cigarettes per capita, during each four-week period, both overall and by type of flavor. Cigarette volumes are measured in packs, while e-cigarettes are standardized to 0.7-milliliter units, given past industry claims that one 0.7-milliliter vape pod is equivalent to 20 conventional cigarettes, or one pack.

    These methods had limitations. Sales data did not include e-cigarette sales made online, in vape shops, or via illicit markets. However, the data did capture most sales of conventional cigarettes. While the study was not a randomized experiment, the analytical methods used were robust enough to identify causal relationships.

    Swapping cigarettes for vapes
    During the study period, hundreds of localities and seven states restricted or prohibited flavored e-cigarette sales. While these policies did reduce per-capita vape sales, they also substantially boosted cigarette sales.

    For each 0.7 milliliters of e-cigarette e-liquid not sold due to these policies, the authors calculated that 15 additional cigarettes were purchased. Similar results emerged when they excluded individual states with statewide policies from the analysis, showing that no one state was driving this effect. Bans on all vapes, including both flavored and unflavored, also resulted in more cigarette sales.

    Of the increase in cigarette sales, 71% were of non-menthol cigarettes, suggesting that restrictions on menthol cigarettes would not counteract this effect.

    Where e-cigarette flavor restrictions had been in effect for at least a year, sales of cigarette brands favored by adults went up by 10%, while sales of cigarette brands that disproportionately attract underage smokers saw a 20% bump.

    In light of these results, policymakers might want to consider other approaches to protect public health where tobacco is concerned, the authors wrote in the study.

    “Some leading scholars have advocated for regulating tobacco products proportionate to their risk,” they wrote. “This approach would avoid giving more lethal combustible products [such as cigarettes] a competitive advantage over less lethal alternatives…[and] could mean more flavors being available in [vapes] than cigarettes.”

    The authors report that they have no conflicts of interest. The research was funded by National Institutes of Health awards from the National Cancer Institute and Food and Drug Administration, as well as the National Institute on Drug Abuse.

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    Yale University

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  • Artificial intelligence helps to simplify lung cancer risk prediction

    Artificial intelligence helps to simplify lung cancer risk prediction

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    Newswise — Machine learning models to identify the simplest way to screen for lung cancer have been developed by researchers from UCL and the University of Cambridge, bringing personalised screening one step closer.

    The model was found to be as good or better at predicting an individual’s risk of getting lung cancer within five years compared to the best risk models available, and was able to do so using just a quarter of the information needed.

    Lung cancer is the most common cause of cancer death worldwide, with poor survival in the absence of early detection. It is estimated that there were 1.8 million lung cancer deaths globally in 20201.

    Screening for lung cancer amongst those at high-risk could reduce lung cancer-specific mortality by 20-24% amongst those screened, but the ideal way to determine if someone is high-risk remains uncertain and existing approaches are resource intensive.

    The UK is currently planning a national screening programme for lung cancer, which will include people aged 55-74 who have ever smoked, using a risk model based on 17 questions. This information is complex and time-consuming to gather and will require a 50-100 person-strong call centre to collect the data from one million people.

    In this study, researchers from UCL and the University of Cambridge used data from the UK Biobank and US National Lung Screening Trial to develop models to simplify the prediction of a person getting lung cancer within the next five years.

    The team used the datasets to experiment with over 60 different machine learning pipelines to see which were the most effective at predicting lung cancer risk using just three variables – age, how many years the individual smoked for, and the average number of cigarettes per day.

    From these, they selected four model pipelines and combined them into an ‘ensemble’ that was able to predict lung cancer risk with the same or improved accuracy, compared to the best available models currently is use2. Importantly, they were able to achieve this accuracy using only a third of the variables, greatly simplifying the process of gathering the data required.

    Dr Tom Callender (UCL Medicine), first author of the study, said: “Screening for cancer and other diseases saves lives and we are increasingly able to personalise this process. But such personalised screening and disease prevention programmes present important logistical challenges at scale. Our study shows that artificial intelligence can be used to accurately predict lung cancer risk using just three pieces of information that would be easy to gather during routine GP appointments, online or via apps. This approach has the potential to greatly simplify population level screening for lung cancer and help to make it a reality.”

    The models used in the study were externally validated in the US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and benchmarked against models that are either in use or have performed strongly in previous analyses. The authors believe the same approach could be viable for simplifying screening process for other diseases, such as type-2 diabetes and cardiovascular disease.

    Professor Mihaela van der Schaar, an author of the study from the University of Cambridge, said: “This research is a prime example of how machine learning tools such as AutoPrognosis, combined with innovative clinical researchers, can make a real impact in healthcare at a population level. While AutoPrognosis has already been applied for risk prediction and prognosis in numerous diseases, this is the first time it has been used to determine the minimal information needed to screen patients. I think this is the future of preventive medicine and I’m optimistic that the same approach could be applied to screening for other diseases.”

    The authors hope the findings will be used to make any national lung cancer screening programme quicker, easier and cheaper to implement, while still achieving the primary aim of reducing lung cancer mortality.

    Professor Sam Janes (UCL Medicine), senior author of the study, said: “It’s great news that the UK is working towards a national screening programme for lung cancer, which remains the leading cause of cancer-related deaths in this country as it does across the world. But as we’ve seen in the US, whose screening programme uptake is just eight per cent, there are hurdles to overcome. For any national screening programme to work, it will need to be feasible to run and succeed in getting people to participate. Our findings are good news on both counts.”

    This work was supported by Wellcome, the National Science Foundation, the Medical Research Council and Cancer Research UK.

    Notes to Editors:

    1 For more information on lung cancer, see the WHO website.

    2 The current NHS pilot combines two of the best-performing models available, the US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial 2012 (PLCOm2012) and Liverpool Lung Project version 2 (LLPv2).

    Publication:

    Thomas Callender et al. ‘Assessing eligibility for lung cancer screening using parsimonious ensemble machine learning models: A development and validation study’ will be published in PLOS Medicine and is strictly embargoed until 3 October 2023 19:00 BST / 14:00 ET.

    DOI: https://doi.org/10.1371/journal.pmed.1004287

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    University College London

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  • Computer model predicts who needs lung cancer screening

    Computer model predicts who needs lung cancer screening

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    Newswise — A machine learning model equipped with only data on people’s age, smoking duration and the number of cigarettes smoked per day can predict lung cancer risk and identify who needs lung cancer screening, according to a new study publishing October 3rd in the open access journal PLOS Medicine by Thomas Callender of University College London, UK, and colleagues.

    Lung cancer is the most common cause of cancer death worldwide, with poor survival in the absence of early detection. Screening for lung cancer among those at highest risk could reduce lung cancer deaths by nearly a quarter, but the ideal way to determine the high-risk population has been unclear. The current standard-of-care model of lung cancer risk requires 17 variables, few of which are routinely available in electronic health records.

    In the new study, researchers used data on 216,714 ever-smokers from the UK Biobank cohort and 26,616 ever-smokers participating in the US National Lung Screening Trial to develop new models of lung cancer risk.

    A machine learning model used three predictors — age, smoking duration and pack-years — to calculate people’s odds of both developing lung cancer and dying of lung cancer over the next five years. The researchers tested the new model on a third set of data, from the US Prostate, Lung, Colorectal and Ovarian Screening Trial. The model predicted lung cancer incidence with an 83.9% sensitivity and lung cancer deaths with an 85.5% sensitivity. All versions of the model had a higher sensitivity than the currently used risk prediction formulas at an equivalent specificity.

    Callender adds, “We know that screening for those who have a high chance of developing lung cancer can save lives. With machine learning, we’ve been able to substantially simplify how we work out who is at high risk, presenting an approach that could be an exciting step in the direction of widespread implementation of personalised screening to detect many diseases early.”

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    PLOS

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  • Cleveland Clinic Researchers Develop New Model for Prioritizing Lung Transplant Candidates

    Cleveland Clinic Researchers Develop New Model for Prioritizing Lung Transplant Candidates

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    Newswise — CLEVELAND: A team from Cleveland Clinic has developed a new model for prioritizing patients waiting for a lung transplant, aimed at improving outcomes and reducing deaths among those in need of donor lungs. The new method offers an improved strategy for organ allocation by taking into account how the time a patient has spent on the waiting list could impact the severity of their disease and the urgency of their need for a transplant.

    The results of a study looking at this new method were published today in The American Journal of Respiratory and Critical Care Medicine.

    Currently, lung transplant candidates are ranked by a scoring equation called the Composite Allocation Score (CAS). Candidates are assigned a number based on factors including how stable they are while waiting, chances of survival after receiving a new organ, and how easily they can be matched for available organs. Those with the highest scores are given priority and offered donor lungs first. However, the scores are based on tests given twice a year at transplant centers. That means that unless a patient’s health suddenly and drastically changes, their score will remain the same for at least six months.

    “The problem with this method is that the scoring equations fail to consider how a patient’s health status changes as they spend more time on the list,” said Maryam Valapour, M.D., M.P.P., director of Lung Transplant Outcomes at Cleveland Clinic. “The longer a patient lives with a severe lung disease, the more their risk of developing severe complications increases. This is something clinicians observe every day – that our patients’ risk of developing complications changes over time. Therefore, some patients’ scores may not reflect how urgently they need a transplant.”

    To determine how the amount of time on the waitlist affects clinical outcomes, the team of researchers analyzed data from 12,000 American adults listed for lung transplant between 2015 to 2020. The study showed that for many patients, their risk of death prior to transplant increased as they spent longer times waiting for donor lungs.

    When the team looked at patients who died on the waiting list, they found that many had not been given enough priority in the CAS. To more accurately score the candidates, the team developed a more dynamic method called the multistate composite model that accounted for the type of lung disease and time on the waiting list. When they recalculated the original scores with their new equation, it consistently marked those patients as high priority. However, for patients who originally received low-priority scores and remained stable over time, using the new method did not change their scores. 

    “The approaches we present in our paper are capable of identifying whose trajectory is more stable on the waiting list versus those whose trajectory is worsening between six-month clinical updates. The estimates in our model more closely align with observed trends in individual U.S. lung transplant patients,” says Jarrod Dalton, Ph.D., director of Lerner Research Institute’s Center for Populations and Health Research, who is first author of the paper. “This approach may allow us to more accurately prioritize time-sensitive lung transplant candidates and decrease waitlist mortality for patients with end-stage lung disease.”

    This study was done with the support of the National Institutes of Health.

    “This research advances us towards development of a more comprehensive prediction model for risk of mortality among lung transplant candidates that could help guide decisions about patients who are in greater need for lung transplant and increase their odds for survival,” said James P. Kiley, Ph.D., director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute (NHLBI).

    In 2022, there were over 3,000 candidates added to the lung transplant waitlist with over 2,600 lung transplants performed, according to UNOS. While the numbers of donors and transplants are improving, there is still a shortage of available organs in the United States.

    Research reported in this publication was supported by the National Institutes of Health under Award Number R01HL153175. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health.

     

    About Cleveland Clinic 

    Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. Cleveland Clinic is consistently recognized in the U.S. and throughout the world for its expertise and care. Among Cleveland Clinic’s 77,000 employees worldwide are more than 5,658 salaried physicians and researchers, and 19,000 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,699-bed health system that includes a 173-acre main campus near downtown Cleveland, 23 hospitals, more than 275 outpatient facilities, including locations in northeast Ohio; southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2022, there were 12.8 million outpatient encounters, 303,000 hospital admissions and observations, and 270,000 surgeries and procedures throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 185 countries. Visit us at clevelandclinic.org. Follow us at twitter.com/ClevelandClinic. News and resources available at newsroom.clevelandclinic.org. 

     

    Editor’s Note: Cleveland Clinic News Service is available to provide broadcast-quality interviews and B-roll upon request.

     

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  • Sylvester Research: Socioeconomic status linked with outcomes and survival in patients treated for non-small cell lung cancer

    Sylvester Research: Socioeconomic status linked with outcomes and survival in patients treated for non-small cell lung cancer

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    Newswise — MIAMI, FLORIDA (Sept. 22, 2023) – Researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine found an association between “social determinants of health” and outcomes and survival in patients undergoing surgery and treatment for non-small cell lung cancer.

    The findings are based on a statistical scoring system the researchers developed that consolidates and analyzes several measures of socioeconomic status and related factors.

    “We believe our social determinants of health scoring system is the first to provide a composite perspective on many of the nonmedical factors that affect outcomes in patients receiving treatment for non-small cell lung cancer,” said Dao Nguyen, M.D., Sylvester Thoracic Cancers Group co-leader. He said the study focused on patients with stage 2 or stage 3 NSCLC, with surgically confirmed metastasis to regional lymph nodes within the chest cavity.

    Ideally, Nguyen said, patients with these cancers should receive ‘multimodal’ care – chemotherapy, immunotherapy and, in some cases, radiotherapy – and this high level of expertise and care may best be provided by specialized, comprehensive centers like Sylvester, a National Cancer Institute-designated center.

    But studies have shown that better or worse outcomes result from more than just medical and surgical treatments. Socioeconomic disadvantages, for example, have been associated with lower-quality care and suboptimal outcomes. Social determinants of health, or SDH, include income, wealth, education, geographical location, access to specialized care and other nonmedical factors that influence health outcomes.

    “Our analysis shows that SDH scores can identify patients who are at increased risk even if they undergo adequate initial treatment. Our research also may help point the way toward improving strategies and care for patients with lung cancer who are socioeconomically disadvantaged,” said Nguyen, a thoracic surgeon who treats and studies lung and other cancers and is the senior author of an article published online ahead of print in The Journal of Thoracic and Cardiovascular Surgery.

    Nguyen and colleagues analyzed data from 11,274 patients with locally advanced NSCLC in the National Cancer Database (NCDB), a registry provided by the American College of Surgeons and the American Cancer Society. Patients with locally advanced disease make up about one-third of the NSCLC population. In the study sample, average patient age was about 68, and 57% of patients were female. Eighty-four percent of patients in the sample were non-Hispanic white, 8.8% were Black, 3.0% were Hispanic, and 3.3% were Asian.

    The researchers quantified results based on the medical research term “textbook oncological outcome,” which considers several metrics and translates to the most desirable or optimal outcome for patients undergoing surgery to remove a primary cancer. These factors include complete resection, adequate lymph node removal, timely initiation of other therapies when needed, and short hospital stay. Textbook outcomes also are reflected in statistics on mortality, re-intervention, readmission, and major complications.

    The Sylvester study aimed to determine the rate of achieving ideal outcomes in relation to social determinants of health scores, the association between these scores and optimal outcomes, and the association between SDH and overall survival.

    The researchers focused on income, place of residence, level of education, and location of hospitals in proximity to patient residence. Other variables of interest included patient demographics, types of treatment facilities, surgical volumes at treatment facilities (representing experience and expertise), and whether patients had other medical conditions or diseases in addition to NSCLC.

    “In this cohort, we found that socioeconomic status – indicated by SDH score – has an important association with both textbook outcomes and survival,” said Ahmed Alnajar, M.D., the paper’s first author. “Significant socioeconomic disadvantage was associated with a 21% decrease in textbook outcomes and a 32% decrease in overall survival when compared to a patient subgroup that was not disadvantaged. Vulnerable patient population groups living in areas with limited income, limited education, rural locations, and areas with limited access to specialized cancer care settings are at increased risk of poor outcomes and long-term mortality.”

    Among highlights from the article:

    • In this study, patients living in rural areas had a 30% decreased likelihood of overall survival and long-term outcomes.
    • Having access to only community hospitals adversely affected survival.
    • Having surgery performed in a high-volume hospital decreased mortality risk by 31% and increased textbook outcome likelihood by 93%, compared to having surgery completed in a low-volume hospital.
    • Black patients were 31% less likely to achieve optimal, textbook outcomes than were white patients.
    • The authors say policymakers should ensure equitable access to surgery and multimodality therapy to be sure all patients receive the best care. They also say surgeons and other care providers can strategically allocate resources and target interventions to counter the effects of SDH inequities.

    Authors: In addition to Nguyen and Alnajar, Karishma Kodia, M.D., and Nestor Villamizar, M.D., contributed from Sylvester and the University of Miami Miller School of Medicine. Syed Razi, M.D., contributed from Hackensack Meridian Health in Edison, New Jersey.

    Funding: This work received no external funding.

    Conflicts of interest: The authors declare no conflicts of interest or disclosures.

    Publication: The Journal of Thoracic and Cardiovascular Surgery, “The Impact of Social Determinants of Health on Textbook Oncological Outcomes and Overall Survival in Locally Advanced Non-Small Cell Lung Cancer.”

    DOI: 10.1016/j.xjon.2023.09.013

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  • Unveiling Asthma’s Molecular Secrets: How Blood Molecules Influence Airway Processes

    Unveiling Asthma’s Molecular Secrets: How Blood Molecules Influence Airway Processes

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    Newswise — New York, NY (September 20, 2023) – A new study by researchers at the Icahn School of Medicine at Mount Sinai has unraveled the intricate molecular interplay between systemic processes within the blood and localized processes within the airways of individuals with asthma.

    This pioneering research opens doors to potential novel treatments targeting specific molecules, with the aim of providing more effective relief for asthma patients. The research findings were published today in Genome Medicine.

    The study, which examined 341 participants comprising individuals with persistent asthma and non-asthmatic controls, used advanced transcriptomic sequencing techniques to analyze blood and nasal samples. Through this comprehensive approach, the researchers unveiled crucial molecules and processes that hold the key to understanding asthma better. Within the blood, the NK cell granule protein and perforin emerged as central players. In the nasal passages, the G3BP stress granule assembly factor 1 and InaD-like protein took on pivotal roles. Notably, the study underscored the profound influence of blood molecules on asthma by virtue of their effects on nasal molecules.

    Supinda Bunyavanich, MD, MPH, MPhil, the Mount Sinai Professor in Allergy and Systems Biology, Deputy Director of the Elliot and Roslyn Jaffe Food Allergy Institute, and a senior author of the study, highlighted the importance of this holistic approach: “Our findings represent a groundbreaking connection between systemic factors in the bloodstream and localized factors in the airways, working collaboratively to drive asthma. This discovery marks a significant stride towards understanding core mechanisms of asthma, transcending the conventional focus on only the airways.”

    However, Dr. Bunyavanich also sounded a note of caution, saying, “While these revelations provide invaluable insights into the molecular framework of asthma, it’s imperative to acknowledge that further research is needed before these breakthroughs can translate into immediate therapies.”

    Key Highlights:

    • The study offers an integrated perspective on the intricate relationship between systemic processes and airway-specific mechanisms in asthma.
    • Prominent blood molecules, including the NK cell granule protein and perforin, appear to exert their influence on asthma through their interactions with nasal molecules like the G3BP stress granule assembly factor 1.
    • The findings chart a path for future research endeavors, guiding the development of targeted asthma therapies that modulate these specific molecules.
    • Given that asthma affects millions globally, the implications of this research are far-reaching. This study paves the way for a deeper comprehension of the disease, instilling optimism for the emergence of more efficacious therapeutic strategies in the foreseeable future.

    For more details, read the full study in Genome Medicine.

    This study was funded supported by the National Institutes of Health grant R01 AI118833.

    Study details: Zhang L, Chun Y, Irizar H, et al. Integrated study of systemic and local airway transcriptomes in asthma reveals causal mediation of systemic effects by airway key drivers. Genome Medicine.

    Dr. Bunyavanich has no conflicts of interest to disclose.

     

    About the Mount Sinai Health System

    Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, more than 400 outpatient practices, more than 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

    Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,400 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. Hospitals within the System are consistently ranked by U.S. News & World Report‘s® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report‘s® “Best Hospitals” Honor Roll for 2023-2024.

    For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

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  • Intensity-modulated radiation therapy provides long-term benefits to patients with locally advanced lung cancer

    Intensity-modulated radiation therapy provides long-term benefits to patients with locally advanced lung cancer

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    Newswise — SINGAPORE ― Intensity-modulated radiation therapy (IMRT) should be the preferred choice when treating patients with locally advanced non-small cell lung cancer (NSCLC), as it reduces radiation exposure to the heart and lungs, according to researchers at The University of Texas MD Anderson Cancer Center.  

    Results from a long-term secondary analysis of the NRG Oncology-RTOG 0617 Phase III study, with a median follow-up of 5.2 years, revealed that patients receiving IMRT had a more than two-fold reduction in severe lung inflammation (pneumonitis) compared to those who received 3D-conformal radiotherapy (3D-CRT), 3.5% versus 8.2%.  

    The findings were presented today at the at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer by Stephen Chun, M.D., associate professor of Radiation Oncology.  

    “IMRT spared more normal tissue than 3D-CRT, which translated into a clinically meaningful benefit to patients,” Chun said. “Despite historical concerns of IMRT generating a low-dose radiation bath to a large area of normal lung tissue, we found no excess cancers, increased adverse events or survival detriment over the long term related to this approach.” 

    For decades, 3D-CRT has been the standard of care for locally advanced lung cancer when surgery is not an option. However, it is less precise than IMRT, which sculpts and molds radiation beams to tumor targets, reducing radiation exposure to certain organs.  

    The NRG Oncology-RTOG 0617 study enrolled 482 NSCLC patients from 2007 to 2011 and compared a high dose of radiation (74 Gy) to a standard dose (60 Gy). All patients underwent concurrent chemotherapy (carboplatin/paclitaxel, with or without cetuximab) and either 3D-CRT (53%) or IMRT (47%). 

    Although patients treated with both techniques had similar survival rates, closer inspection of the data demonstrated a correlation between survival and radiation exposure to the heart. IMRT treatment plans achieved significantly lower cardiac radiation doses.  

    Both the 3D-CRT and IMRT groups had similar rates of new cancer development over time. Scientists also saw no evidence that age impacted survival, meaning that age is no reason to exclude elderly patients from curative-intent chemoradiation for locally advanced NSCLC.  

    “The data from our study makes a compelling argument that we should use IMRT for locally advanced lung cancer. As a randomized clinical trial comparing 3D-CRT and IMRT is unlikely to be performed, this study represents the strongest prospective evidence we will ever have in support of IMRT,” Chun said. 

    This trial was funded by the National Cancer Institute (R50CA275822, U10CA21661, U10CA180868, and U10CA180822), Bristol Myers Squibb and Eli Lilly and Company. Chun reports financial relationships with Curio Science, Norton Healthcare, AstraZeneca, Binaytara Foundation, Henry Ford Health, Hong Kong Precision Oncology, ViewRay, the American Board of Radiology and the Japanese Society for Radiation Oncology. A full list of collaborating authors can be found with the abstract here.  

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    University of Texas MD Anderson Cancer Center

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  • Rutgers Researchers Identify Lipid Vascular ‘ZIP code’

    Rutgers Researchers Identify Lipid Vascular ‘ZIP code’

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    Newswise — New Brunswick, N.J., August 14, 2023 – Researchers at Rutgers Cancer Institute of New Jersey and Rutgers New Jersey Medical School (NJMS), together with other collaborating groups, have discovered the first lipid vascular ‘ZIP code’ in the lungs. Getting a drug to where it is needed in the human body is critical for successfully treating diseases including cancer and avoiding toxic side-effects, but it remains a major challenge. One creative option has been to identify the unique protein receptors that are present on the surface of blood vessels at specific sites in the body that act like vascular ZIP codes. These ZIP codes can be physically paired with a ligand such as a small protein or antibody that can be harnessed to guide and deliver a package such as a drug or a diagnostic imaging agent to their specific molecular addresses. Some of these ligand-receptor pairs are already undergoing testing in clinical trials with anti-cancer and anti-obesity drugs. 

    Prior to the researcher’s findings, all vascular ZIP codes have been proteins. Their discovery uncovers a previously unrecognized lipid network of ZIP codes in blood vessels and opens up a new world of possibilities for improved diagnostics and treatments, including patients with severe human respiratory diseases such as emphysema, COVID-19, COPD and lung cancer. 

    In 2008, the researchers discovered a ligand peptide that bound to the surface of lung vascular endothelial cells and could deliver a cell death notice directly to the lungs in mice. However, their usual biochemical and genetic methods failed to identify the corresponding lung vascular ZIP code that the ligand was binding to. “The problem was that we had been looking for a protein,” said Wadih Arap, MD, PhD, director of Rutgers Cancer Institute at University Hospital Newark, professor and chief of the Division of Hematology/Oncology, Department of Medicine, Rutgers NJMS and a co-lead author. “Our long series of frustrating failures led us to consider that the elusive target might be another type of molecule, perhaps a lipid; that was a eureka moment.”

    The lipid ZIP code that they discovered on lung blood vessels is called C16-ceramide (also known as palmitoyl ceramide). It belongs to a family of closely related lipid molecules that perform many important cellular functions. These include helping viruses like Ebola and SARS-CoV-2 get into cells, and also triggering cell death. Increased levels of ceramides have long been known to be associated with many lung diseases. Thus, C16-ceramide represents an unexplored avenue for many different diagnostic or therapeutic applications. As Renata Pasqualini, PhD, a resident member of Rutgers Cancer Institute and chief of the Division of Cancer Biology, Department of Radiation Oncology at NJMS another co-lead author remarked, “imaging plays such an essential role in evaluating the lungs—both, anatomically and functionally—that we felt it was an opportunity to make a clinical difference. Whether it is for pulmonary screening, establishing a diagnosis, or monitoring disease severity, our approach and findings will hopefully represent an advance in this area.” 

    To solidify their discovery of a new lipid vascular ZIP code and ligand pair, they tested their hypothesis in genetically engineered ceramide-deficient mice and showed that the ligand was no longer able to target the lungs. To begin to demonstrate what this might mean for patients, they tested two candidate medical applications. First, they showed that it could potentially be used for early diagnosis and monitoring of certain lung diseases by attaching the ligand to gold nanoparticles, which specifically lit up the lungs by using optical and molecular imaging techniques. Finally, given the ongoing COVID-19 pandemic, they showed that the ligand could also deliver a novel vaccine directly to the lungs and stimulate a local immune response, which could be more protective than currently existing vaccines that are injected into the arm.

    Daniela Staquicini, PhD, resident member of Rutgers Cancer Institute and assistant professor of the Division of Cancer Biology, Department of Radiation Oncology at Rutgers NJMS said, “this body of work actually encompasses an ensemble of three recently published manuscripts—including this one—on targeting different ZIP codes in the lung for multiple potential applications including non-invasive imaging and vaccine delivery, in which I had the privilege to serve as a co-first-author on behalf of several large teams of investigators.”

    Next, the team plans to focus on discovering more lipid vascular ZIP codes in the blood vessels that serve other organs and particularly tumors as a way to better target anti-cancer drugs and will work to further translate these discoveries into true clinical applications for patients.

    This work was recently published in the scientific journal, PNAS (10.1073/pnas.2220269120)

    A complete list of co-authors, funding, and disclosures is included in the paper here.

    About Rutgers Cancer Institute of New Jersey  As New Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center, Rutgers Cancer Institute, together with RWJBarnabas Health, offers the most advanced cancer treatment options including bone marrow transplantation, proton therapy, CAR T-cell therapy and complex surgical procedures.  Along with clinical trials and novel therapeutics such as precision medicine and immunotherapy – many of which are not widely available – patients have access to these cutting-edge therapies at Rutgers Cancer Institute of New Jersey in New Brunswick, Rutgers Cancer Institute of New Jersey at University Hospital in Newark, as well as through RWJBarnabas Health facilities. To make a tax-deductible gift to support the Cancer Institute of New Jersey, call 848-932-8013 or visit www.cinj.org/giving. 

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  • Actiphage TB awarded US Patent grant for diagnostic kit

    Actiphage TB awarded US Patent grant for diagnostic kit

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    Newswise — PBD Biotech developers of Actiphage TB, a ground-breaking phage-based diagnostic for laboratory tuberculosis testing, has today announced it has secured the grant of a US patent for its diagnostic kit. The company is exhibiting in the AACC Clinical Lab Expo on booth #4578.

    Grant of this US patent relating to Mycobacteria detection using bacteriophages, and specifically to the diagnostic kit, provides further important protection for the Actiphage technology.

    Jane Theaker CEO of PBD Biotech explains: “We already have a granted US Patent for the specific method steps, but this new allowance relates to the specific components that make up the Actiphage TB diagnostic kit, strengthening our rights.”

    “We are particularly pleased with this result, claims covering diagnostic kits are notoriously difficult to obtain before the USPTO as the components of the kit are generally considered individually and not in relation to how the kit is to be used.”

    PBD Biotech is a clinical-stage diagnostic company and pioneer in phage-based diagnostics. It is focused on the development of Actiphage TB as a blood test for the detection of tuberculosis in latent TB screening and drug management.

    PBD Biotech recently initiated one of the largest clinical trials for Actiphage TB to date, building on a prior study that demonstrated detection of Mycobacteria tuberculosis (Mtb) in the blood of naive pulmonary TB patients.

    PBD Biotech is one of eight start-ups selected to present at the DxPx Conference US 2023, part of the AACC Clinical Lab Expo in Anaheim, California on July 26 2023.

    PBD is actively seeking investment and life sciences partners to support Actiphage TB clinical development and commercialization.

    DxPx is the only conference dedicated to facilitating M&A, licensing, and financing opportunities for Diagnostics, Digital Health, Precision Medicine, and Life Sciences Tools companies. 

    PBD Biotech is exhibiting in the AACC Clinical Lab Expo on Booth #4578. 

    -ENDS-

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    2023 AACC Annual Scientific Meeting Press Program

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  • Assessment of Lung Cancer Risk Among Smokers for Whom Annual Screening Is Not Recommended

    Assessment of Lung Cancer Risk Among Smokers for Whom Annual Screening Is Not Recommended

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    Abstract

    Importance: The US Preventive Services Task Force does not recommend annual lung cancer screening with low-dose computed tomography (LDCT) for adults aged 50 to 80 years who are former smokers with 20 or more pack-years of smoking who quit 15 or more years ago or current smokers with less than 20 pack-years of smoking.

    Objective: To determine the risk of lung cancer in older smokers for whom LDCT screening is not recommended.

    Design, settings, and participants: This cohort study used the Cardiovascular Health Study (CHS) data sets obtained from the National Heart, Lung and Blood Institute, which also sponsored the study. The CHS enrolled 5888 community-dwelling individuals aged 65 years and older in the US from June 1989 to June 1993 and collected extensive baseline data on smoking history. The current analysis was restricted to 4279 individuals free of cancer who had baseline data on pack-year smoking history and duration of smoking cessation. The current analysis was conducted from January 7, 2022, to May 25, 2022.

    Exposures: Current and prior tobacco use.

    Main outcomes and measures: Incident lung cancer during a median (IQR) of 13.3 (7.9-18.8) years of follow-up (range, 0 to 22.6) through December 31, 2011. A Fine-Gray subdistribution hazard model was used to estimate incidence of lung cancer in the presence of competing risk of death. Cox cause-specific hazard regression models were used to estimate hazard ratios (HRs) and 95% CIs for incident lung cancer.

    Results: There were 4279 CHS participants (mean [SD] age, 72.8 [5.6] years; 2450 [57.3%] women; 663 [15.5%] African American, 3585 [83.8%] White, and 31 [0.7%] of other race or ethnicity) included in the current analysis. Among the 861 nonheavy smokers (<20 pack-years), the median (IQR) pack-year smoking history was 7.6 (3.3-13.5) pack-years for the 615 former smokers with 15 or more years of smoking cessation, 10.0 (5.3-14.9) pack-years for the 146 former smokers with less than 15 years of smoking cessation, and 11.4 (7.3-14.4) pack-years for the 100 current smokers. Among the 1445 heavy smokers (20 or more pack-years), the median (IQR) pack-year smoking history was 34.8 (26.3-48.0) pack-years for the 516 former smokers with 15 or more years of smoking cessation, 48.0 (35.0-70.0) pack-years for the 497 former smokers with less than 15 years of smoking cessation, and 48.8 (31.6-57.0) pack-years for the 432 current smokers. Incident lung cancer occurred in 10 of 1973 never smokers (0.5%), 5 of 100 current smokers with less than 20 pack-years of smoking (5.0%), and 26 of 516 former smokers with 20 or more pack-years of smoking with 15 or more years of smoking cessation (5.0%). Compared with never smokers, cause-specific HRs for incident lung cancer in the 2 groups for whom LDCT is not recommended were 10.54 (95% CI, 3.60-30.83) for the current nonheavy smokers and 11.19 (95% CI, 5.40-23.21) for the former smokers with 15 or more years of smoking cessation; age, sex, and race-adjusted HRs were 10.06 (95% CI, 3.41-29.70) for the current nonheavy smokers and 10.22 (4.86-21.50) for the former smokers with 15 or more years of smoking cessation compared with never smokers.

    Conclusions and relevance: The findings of this cohort study suggest that there is a high risk of lung cancer among smokers for whom LDCT screening is not recommended, suggesting that prediction models are needed to identify high-risk subsets of these smokers for screening.

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    JAMA – Journal of the American Medical Association

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  • Tip Sheet: Understanding cancer-related pain, newborn screening for deadly immune disorder — and new Fred Hutch leadership

    Tip Sheet: Understanding cancer-related pain, newborn screening for deadly immune disorder — and new Fred Hutch leadership

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    Newswise — SEATTLE — July 6, 2023 — Below are summaries of recent Fred Hutchinson Cancer Center research findings and other news.

    If you’re looking for resources who can comment on skin cancer awareness and skin protection during the summer months, see our list of experts and reach out to [email protected] to set up interviews.

    Cancer research and care

    Pinpointing pain: Is it cancer or cancer treatment? Distinguishing side effects of cancer treatment from potential metastatic recurrence can be difficult. In a Q&A, Dr. Hanna Hunter, medical director of cancer rehabilitation at Fred Hutch, s best practices on how doctors and patients can work together to manage pain symptoms.     

    American Society of Clinical Oncology Annual Meeting 2023 highlights: Fine-tuning cancer care Fred Hutch researchers at ASCO’s annual meeting d their latest findings in cellular immunotherapy, early detection cancer screening tests, interplays between the microbiome and genetics in colorectal cancer and more.    

    Cancer Health Equity Podcast: Nurses in cancer care The latest episode of Fred Hutch’s Office of Community Outreach and Engagement’s monthly podcast explores the role of nurses in cancer care and how they’re part of working toward health and well-being for everyone. Two Fred Hutch nurses on the blood and bone marrow transplant team — Arlyce Coumar and Jennifer Lynch — their stories of working with patients and families, as well as educating other nurses. They also discussed how nurses are getting more engaged in advocating for policies in health care. Fred Hutch community health educators Aden Afework, who works with African-American populations, and Snowy Johnson, who works with Indigenous populations, moderated the discussion.

    Severe combined immunodeficiency A new analysis published in The Lancet shows that newborn screening is the biggest factor in preventing deaths from the rare inherited disorder called severe combined immunodeficiency, also known as “bubble boy disease.” Babies born with SCID appear healthy at birth but are vulnerable to infections and usually die within the first two years of life unless they’re treated with immune-restoring treatment, such as stem cell transplant. Dr. Monica Thakar, pediatric bone marrow transplant physician, led the analysis which was published June 20. Read more in a National Institute of Allergy and Infectious Disease news release.

    Diversity, equity and inclusion

    Me Loving You: Themes of healing and moving forward Fred Hutch celebrated the start of Pride month with its fourth art installation as part of the Public Art & Community Dialogue Program featuring artist Ariadne Campanella. Initiated by Fred Hutch’s DEI Core, the program commissions artwork from artists representing diverse communities with the aim of engaging Fred Hutch employees and the broader community in conversations of solidarity with underrepresented groups. Campanella, a queer, non-binary trans woman and mixed media artist, was selected to create a piece focusing on LGBTQIA+ communities as they reflect on healing and moving from surviving to thriving.    

    New Fred Hutch leaders

    Dr. Sara Hurvitz joins Fred Hutch, University of Washington Breast oncologist Dr. Sara Hurvitz has been named the new senior vice president of the Clinical Research Division at Fred Hutch and head of the Division of Hematology and Oncology at the University of Washington Department of Medicine. She will begin her role Aug. 1. Currently at UCLA, Hurvitz is an international expert in breast oncology and a leader in clinical and laboratory-based oncology research, with extensive experience in leading clinical trials spanning all phases.   

    Fred Hutch announces new member, leadership on board of directors Fred Hutch announced one new member of its board of directors and its newly elected chair and vice chair. Pete Shimer, chief operating officer at Deloitte, will join the board. Leigh Morgan, chief strategy and operating officer at the Nia Tero Foundation, has been appointed the new chair of the board of directors, and Sean Boyle, chief operating officer at Omniva, has been appointed vice chair.    

    Awards and grants

    Dr. Mroj Alassaf named a 2023 Helen Hay Whitney Fellow Dr. Mroj Alassaf, postdoctoral fellow in Dr. Akhila Rajan’s lab, received a 3 year $215,000 Helen Hay Whitney foundation fellowship. Her work focuses on how mitochondrial components from fat can reach the brain and what influence they have on its health. A neurobiologist by training, Alassaf joined Rajan’s team after showing in her graduate work how a new mitochondrial protein contributes to neuronal health.    

    Dr. Sita Kugel receives V Foundation Translational Research Award Pancreatic cancer researcher Dr. Sita Kugel has received an inaugural Translational Research Award from the V Foundation for Cancer Research. The $800,000, four-year grant will allow Kugel to pursue an innovative Phase 1b clinical trial to translate from the lab to the clinic breakthroughs her group has made in developing a tailored treatment for a subtype of pancreatic cancer.    

    Dr. Cecilia Moens elected inaugural member of the Society for Developmental Biology Academy Developmental biologist Dr. Cecilia Moens joins nine other scientists elected to the newly created Society for Developmental Biology Academy. Moens work focuses on using zebrafish as a model to study the genes that control the brain’s early development. Her current research looks at how immature neurons make their connections to muscles and other neurons in the process of building functional circuits.    

    Lung cancer expert Dr. McGarry Houghton receives Satya and Rao Remala Family Endowed Chair Dr. McGarry Houghton, a pulmonary physician-scientist, studies the immune system’s role in cancer and lung cancer early detection. He was named the first recipient of the Satya and Rao Remala Family Endowed Chair, which provides support for a researcher working on both lung cancer and the promotion of equitable access to health and education. Houghton is pursuing a plasma-based diagnostic tool that would be used in conjunction with CT screening for lung cancer early detection.   

    Virus researchers Cohn and Blanco-Melo win coveted grants Drs. Lillian Cohn and Daniel Blanco-Melo are both early career scientists studying viruses and recently received support for their work through scholar programs. Cohn was named a biomedical scholar by the Pew Charitable Trust and Blanco-Melo was named a Searle scholar. Cohn’s research focuses on finding ways to cure HIV/AIDS by eradicating reservoirs of latently infected blood cells that persist despite continuous therapy with antiviral drugs. Blanco-Melo focuses on exploring how viruses evolve and how the human immune response to them changes over time.    

    Science spotlight Science Spotlight is a monthly installment of articles written by postdoctoral fellows at Fred Hutch that summarize new research papers from Fred Hutch scientists. If you’re interested in learning more or covering these topics, contact: [email protected]

    # # #

    Fred Hutchinson Cancer Center unites individualized care and advanced research to provide the latest cancer treatment options and accelerate discoveries that prevent, treat and cure cancer and infectious diseases worldwide.

    Based in Seattle, Fred Hutch is an independent, nonprofit organization and the only National Cancer Institute-designated cancer center in Washington. We have earned a global reputation for our track record of discoveries in cancer, infectious disease and basic research, including important advances in bone marrow transplantation, immunotherapy, HIV/AIDS prevention, and COVID-19 vaccines. Fred Hutch operates eight clinical care sites that provide medical oncology, infusion, radiation, proton therapy and related services and has network affiliations with hospitals in four states. Fred Hutch also serves as UW Medicine’s cancer program.

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    Fred Hutchinson Cancer Center

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  • EMSL postdoc investigates how algae affects climate, human health

    EMSL postdoc investigates how algae affects climate, human health

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    Many people may think of algae as green slime beneath their feet as they swim in a lake or the ocean. But what happens when small bits of algae, broken up by wind and waves, are swept into the air? 

    Harmful algae can cause serious health issues in people working and living along coastlines. Such health problems include respiratory distress, allergies, and skin irritation. Blue-green algae, known as cyanobacteria, even release neurotoxins such as β-Methylamino-L-alanine (BMAA) into the air. BMAA and similar toxins released are associated with Alzheimer’s and other neurodegenerative diseases—those that have the potential to degrade or even consume parts of the brain. 

    Mickey Rogers, a 2022 Linus Pauling Distinguished Postdoctoral Fellow at the Environmental Molecular Sciences Laboratory (EMSL) studies how algae are released into the atmosphere, how their composition changes once airborne, and how they affect the climate and human health. 

    Read the full transcript of the EMSL Podcast “Bonding Over Science” on the EMSL website.

    See more podcast episodes on PodBean, YouTube, or your favorite podcast streaming service.

    For more information on Rogers’ research, check out the full feature article. 

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    Environmental Molecular Sciences Laboratory – EMSL

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  • Half of global prison tuberculosis cases remain undetected

    Half of global prison tuberculosis cases remain undetected

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    Newswise — In 2019, incarcerated people across the globe developed tuberculosis (TB) at nearly 10 times the rate of people in the general population, according to a new study led by Boston University School of Public Health (BUSPH).

    Published in The Lancet Public Health, the study found that 125,105 of the 11 million people incarcerated worldwide developed tuberculosis in 2019, a rate of 1,148 cases per 100,000 persons per year.

    Despite this high case rate, nearly half of TB cases among incarcerated people were not detected.

    The findings reveal the first global and regional estimates of new TB cases among incarcerated people, a population at high risk of developing this life-threatening disease. Collectively, the high case rate and low detection underscore the need for greater awareness and resources to reduce the burden of TB in prisons and other high-risk settings.

    “Our study showed that only 53 percent of people that develop tuberculosis in prisons are diagnosed, which suggests that incarcerated people are neglected and have minimal healthcare services to diagnose tuberculosis,” says study lead and corresponding author Dr. Leonardo Martinez, assistant professor of epidemiology at BUSPH.

    To better understand TB rates among this population, Dr. Martinez and colleagues acquired data from published research and from countries’ federal officials to analyze TB prevalence and incidence in 193 countries at the country, regional, and global level between 2000-2019. The team also calculated TB case detection rates per year in each country for 193 countries.

    The African region had the highest rate of new TB cases in 2019, at 2,242 cases per 100,000 persons per year, but the Americas region—largely driven by Central and South America—had the greatest number of total cases, which increased nearly 90 percent since 2000. The countries with the highest number of new cases in prisons in 2019 were Brazil, Russia, China, the Philippines, and Thailand.

    Importantly, the team found that new TB case rates remained consistently between 1,100 and 1,200 cases per 100,000 persons per year from 2012-2019.

    “This stagnation suggests that current tuberculosis control policy in prisons is insufficient to decrease the tuberculosis burden and that supplementary interventions and policy implementation are needed,” says Dr. C. Robert Horsburgh, professor of global health at BUSPH.

    Mass incarceration is one major driver of TB transmission—both inside and outside of prisons.  Overcrowding, where some prison cells contain up to 30 people, causes TB to “spread like wildfire,” Dr. Martinez says, and this transmission can spill over easily into the community.

    “Contrary to popular belief, persons that are incarcerated are a mobile population, and in many countries, the duration of incarceration is very short,” he says. “People go into prison, then come out, then may go back in again. So, very often, people that develop tuberculosis in prison end up transmitting the disease to many people outside of prison once they are released. Since almost half of people with tuberculosis in prisons are not diagnosed, many still remain infectious when they enter back into the general community.”

    The team hopes that these findings will encourage global and regional health organizations to develop routine monitoring of TB among incarcerated people, as they do for other high-risk populations such as people with HIV and household contacts. The researchers say that their comprehensive compilation of TB case notifications—which they retrieved directly from federal officials, national and regional organizations, and non-governmental organizations—is a clear indication that information about TB in prisons is both accessible and retrievable by global organizations such as the World Health Organization.

    The team is currently working with several health organizations to attempt to update global guidelines on how to manage and reduce TB in prisons, as the most recent guidelines were written in the year 2000.

    “One of the reasons this population is so neglected is because of the lack of data,” Dr. Martinez says. “Our hope is that these results can help stakeholders understand the urgency of the issue and the amount of people in prisons that develop tuberculosis and remain undiagnosed for long periods of time and can spur them to take action.”

    **

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    Boston University School of Public Health

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  • Blood test aids in predicting lung cancer mortality risk

    Blood test aids in predicting lung cancer mortality risk

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    Newswise — HOUSTON ― A blood-based test developed by researchers at The University of Texas MD Anderson Cancer Center can predict an individual’s risk of dying from lung cancer when combined with a personalized risk model.

    According to new data published today in the Journal of Clinical Oncology, a blood-based four-protein panel (4MP), when combined with a lung cancer risk model (PLCOm2012), can better identify those at high risk of dying from lung cancer than the current U.S. Preventive Services Task Force (USPSTF) criteria.

    These findings build upon previous MD Anderson research demonstrating the combination test more accurately determined who is likely to benefit from lung cancer screening than the USPSTF criteria.

    “This simple blood test has the potential to save lives by determining the need for lung cancer screening on a personalized basis,” said co-corresponding author Samir Hanash, M.D., Ph.D., professor of Clinical Cancer Prevention. “Given the challenges associated with CT as a frontline screening method for lung cancer and the fact that most individuals diagnosed with the disease do not meet current guidelines, there is an urgent demand for an alternative approach.”

    For this study, MD Anderson researchers analyzed pre-diagnostic blood samples from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, including 552 individuals who later developed lung cancer and 2,193 who did not. Of the 552 individuals diagnosed during the six-year study period, 70% (387) died from lung cancer.

    Using hazard ratios, the researchers assessed the relationship between the risk scores generated by the combination model (4MP + PLCOm2012) and the incidence of lung cancer death. The combination showed improved sensitivity, specificity and positive predictive value compared to the 2013 and 2021 USPSTF criteria for predicting lung cancer-specific mortality among individuals who smoked at least 10 pack-years (PYs).

    The USPSTF recommends that adults at elevated risk for lung cancer receive a low-dose CT scan each year, which was shown to reduce lung cancer deaths in the 2011 National Lung Screening Trial (NLST). The 2021 USPSTF criteria applies to adults aged 50 to 80 who have at least a 20 PY smoking history and currently smoke or have quit within the past 15 years.

    “For individuals who currently are not eligible for lung cancer screening, a positive test may help to identify those possibly at risk for lung cancer death,” said co-corresponding author Edwin Ostrin, M.D., Ph.D., assistant professor of General Internal Medicine. “We envision this as a tool that could be deployed worldwide, as the future of early detection of this disease.”

    Lung cancer causes an estimated 25% of cancer deaths. Early detection improves prospects of survival, but most countries do not screen for it. Fewer than half of all U.S. cases are among people who are eligible under USPSTF guidelines.

    While the blood test could be implemented as a lab-developed test in the near future, Food and Drug Administration (FDA) approval likely would require evaluation through a prospective clinical trial.

    Hanash is an inventor on a patent application related to the blood test. A complete list of co-authors and their disclosures is included in the paper.

    This study was supported by the National Institutes of Health and National Cancer Institute (U01CA194733, U01CA213285, U01CA200468, U24CA086368), the Cancer Prevention & Research Institute of Texas, Lyda Hill Philanthropies, and the Lung Cancer Moon Shot®, part of MD Anderson’s Moon Shots Program®.

    Read the full release on the MD Anderson Newsroom. 

     

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    University of Texas MD Anderson Cancer Center

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  • ATS 2024 Call for Input Deadline Approaching

    ATS 2024 Call for Input Deadline Approaching

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    Newswise — The Call for Input deadline for the ATS 2024 International Conference is approaching! You have until 5 p.m. ET next Wednesday, June 28 to submit your proposals for programming in all areas of respiratory, critical care, and sleep medicine with a clinical, basic science, and/or translational focus.

    Submit your input online in the form of a session proposal in any of the following types:
    Postgraduate Course (Didactic Half-Day)
    Postgraduate Course (Didactic Full-Day)
    Postgraduate Course (Skills-Based Full-Day)
    Scientific Symposium
    Meet the Expert Seminar

    Submit Your Proposal for ATS 2024

    Deadline: 5 p.m. ET, Wednesday, June 28, 2023 

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    American Thoracic Society (ATS)

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