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Diseases and Conditions

A Breakthrough Test for Lymphoma Patients: Predicting CAR T Cell Therapy Response with Machine Learning

A new article outlines a new tool that measures blood inflammation as a marker for poor CAR T therapy outcomes.

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The article reports on a significant breakthrough in cancer research, as City of Hope and Memorial Sloan Kettering (MSK) researchers have developed a tool using machine learning to predict the response of non-Hodgkin lymphoma patients to chimeric antigen receptor (CAR) T cell therapy. This test, called InflaMix, assesses inflammation in the blood, which is a potential cause of CAR T failure, and can identify patients at high risk for treatment failure.

The study involved 149 patients with NHL, and the machine learning model was able to find an inflammatory biomarker from a series of unique blood tests not usually employed in standard clinical practice. By analyzing this inflammatory signature, researchers found it was associated with a high risk of CAR T treatment failing, including increased risk of death or disease relapse.

The InflaMix model is an unsupervised machine learning approach, meaning it was trained without any knowledge of clinical outcomes. The team’s studies demonstrate that by using machine learning and blood tests, they could develop a highly reliable tool that can help predict who will respond well to CAR T cell therapy.

The researchers used three independent cohorts comprising 688 patients with NHL who had a wide range of clinical characteristics and disease subtypes and used different CAR T products to validate their initial findings. The study’s results were published in Nature Medicine.

City of Hope and MSK plan to investigate whether blood inflammation defined by InflaMix directly influences CAR T cell function and learn more about the source of this inflammation. This research has the potential to improve patient outcomes and inform new clinical trials that can boost the effectiveness of CAR T with additional treatment strategies.

The team’s studies were funded in part by the National Institutes of Health, the National Cancer Institute, and an MSK Support Grant. The work was primarily done at MSK where Dr. Van den Brink worked for more than two decades before coming to City of Hope in 2024.

City of Hope has treated over 1,700 patients since its CAR T program started in the late 1990s and continues to have one of the most comprehensive CAR T cell clinical research programs in the world, with about 70 ongoing clinical trials using immune cell products.

Birth Control

A Safer, Cheaper Vision Correction Method May Be on the Horizon

Scientists are developing a surgery-free alternative to LASIK that reshapes the cornea using electricity instead of lasers. In rabbit tests, the method corrected vision in minutes without incisions.

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This revolutionary approach to vision correction is called electromechanical reshaping (EMR). This method utilizes electrical impulses to reshape the cornea, potentially providing a safer and more affordable alternative to traditional LASIK surgery. Researchers at Occidental College have made significant progress in this area, with initial studies demonstrating promising results on rabbit eyeballs.

The researchers’ innovative technique involves using platinum “contact lenses” that provide a template for the corrected shape of the cornea. By applying an electric potential to these contact lenses, they create a precise pH change within the tissue, loosening its rigidity and making it malleable. This enables them to reshape the cornea without any incisions or ablative procedures.

In their experiments on rabbit eyeballs, the team successfully reshaped the corneas of 12 separate specimens, 10 of which were treated as if they had myopia (nearsightedness). The treatment effectively corrected the focusing power of the eye in all “myopic” eyeballs. Moreover, the cells within the eyeball survived this procedure because the researchers carefully controlled the pH gradient.

The researchers emphasize that while these initial results are promising, their work is still in its early stages. They plan to conduct further animal studies and investigate the potential of EMR for treating a range of vision problems, including astigmatism, near- and far-sightedness. However, the team’s scientific funding uncertainties have put them on hold.

Despite these challenges, the researchers remain optimistic about the potential of this new technique. They believe that if successful, EMR could provide a widely applicable, vastly cheaper, and potentially even reversible method for vision correction, surpassing current treatments like LASIK.

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Children's Health

Uncovering the Inaccuracy: Why Common Blood Pressure Readings May Miss 30% of Hypertension Cases

Cambridge scientists have cracked the mystery of why cuff-based blood pressure monitors often give inaccurate readings, missing up to 30% of high blood pressure cases. By building a physical model that replicates real artery behavior, they discovered that low pressure below the cuff delays artery reopening, leading to underestimated systolic readings. Their work suggests that simple tweaks, like raising the arm before testing, could dramatically improve accuracy without the need for expensive new devices.

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The measurement of blood pressure has been a cornerstone of medical practice for decades. However, despite its widespread use, research suggests that common cuff-based blood pressure readings may be inaccurate and potentially miss up to 30% of hypertension cases.

A team of researchers from the University of Cambridge has shed new light on this issue by building an experimental model that explains the physics behind these inaccuracies. Their findings, reported in the journal PNAS Nexus, have significant implications for patient health outcomes and highlight the need for more accurate measurement methods.

The auscultatory method, which relies on inflating a cuff around the upper arm to measure blood pressure, has long been considered the gold standard. However, this study reveals that it overestimates diastolic pressure while underestimating systolic pressure. The researchers attribute this discrepancy to a previously unidentified factor: the delayed reopening of arteries due to low downstream pressure.

To replicate this condition in their experimental rig, the Cambridge team used tubes that lay flat when deflated and fully closed when inflated with cuff pressure. This setup allowed them to study the effects of downstream blood pressure on artery closure and reopening, leading to a better understanding of the mechanics behind inaccurate readings.

The researchers propose several potential solutions to address this underestimation, including raising the arm before measurement to produce a predictable downstream pressure. This simple change does not require new devices but can make blood pressure measurements more accurate.

If new devices for monitoring blood pressure are developed, they may incorporate additional inputs that correlate with downstream pressure, such as age, BMI, or tissue characteristics, to adjust ‘ideal’ readings for each individual.

The study’s authors emphasize the need for clinical trials to test their findings in patients and collaborate with clinicians to implement changes to clinical practice. Funding from organizations like the Engineering and Physical Sciences Research Council (EPSRC) will be essential to support further research and development.

By uncovering the inaccuracies in common blood pressure readings, this study has significant implications for patient health outcomes and highlights the need for more accurate measurement methods. The proposed solutions have the potential to improve diagnosis and treatment of hypertension, ultimately saving lives and reducing healthcare costs.

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Allergy

“The Silent Invader: How a Parasitic Worm Evades Detection and What it Can Teach Us About Pain Relief”

Scientists have discovered a parasite that can sneak into your skin without you feeling a thing. The worm, Schistosoma mansoni, has evolved a way to switch off the body’s pain and itch signals, letting it invade undetected. By blocking certain nerve pathways, it avoids triggering the immune system’s alarms. This stealth tactic not only helps the worm survive, but could inspire new kinds of pain treatments and even preventative creams to protect people from infection.

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A new study published in The Journal of Immunology has made an intriguing discovery about how a parasitic worm evades detection and what it can teach us about pain relief. Researchers from Tulane School of Medicine found that the Schistosoma mansoni worm, which causes schistosomiasis, suppresses neurons in the skin to avoid triggering an immune response.

When this worm penetrates human skin, typically through contact with infested water, it produces molecules that block a protein called TRPV1+, which is responsible for sending pain signals to the brain. This clever mechanism allows the worm to infect the skin largely undetected.

The researchers believe that the S. mansoni worm evolved this strategy to enhance its own survival and found that blocking TRPV1+ also reduced disease severity in mice infected with the parasite. The study suggests that identifying the molecules responsible for suppressing TRPV1+ could lead to new painkillers that do not rely on opioids.

Moreover, the researchers discovered that TRPV1+ is essential for initiating host protection against S. mansoni infection. When this protein is activated, it triggers a rapid mobilization of immune cells, which induces inflammation and helps fight off the parasite. This finding highlights the critical role of neurons in pain-sensing and immune responses.

The study’s lead author, Dr. De’Broski R. Herbert, emphasizes that identifying these molecules could inform preventive treatments for schistosomiasis. He envisions a topical agent that activates TRPV1+ to prevent infection from contaminated water for individuals at risk of acquiring S. mansoni.

This groundbreaking research has the potential to revolutionize our understanding of pain relief and immune responses, offering new avenues for developing innovative therapies that could benefit millions worldwide.

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