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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.

Dementia

Ambroxol Shows Promise in Slowing Parkinson’s Dementia

Ambroxol, long used for coughs in Europe, stabilized symptoms and brain-damage markers in Parkinson’s dementia patients over 12 months, whereas placebo patients worsened. Those with high-risk genes even saw cognitive gains, hinting at real disease-modifying power.

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The devastating effects of dementia on individuals and their families have long been a major health challenge. Researchers at Lawson Research Institute are making groundbreaking strides by investigating whether Ambroxol, a commonly used cough medicine in Europe, can slow down dementia in people with Parkinson’s disease.

Published in the prestigious JAMA Neurology journal, this 12-month clinical trial involving 55 participants with Parkinson’s disease dementia (PDD) has provided promising results. The study, led by Cognitive Neurologist Dr. Stephen Pasternak, aimed to alter the course of Parkinson’s dementia and explore a new treatment avenue where few currently exist.

The clinical trial gave one group daily Ambroxol while the other received a placebo. Participants were monitored for memory loss, psychiatric symptoms, and GFAP, a blood marker linked to brain damage. The results indicate that Ambroxol may support brain function, especially in those genetically at risk of developing Parkinson’s disease dementia.

Ambroxol works by supporting the enzyme glucocerebrosidase (GCase), which is often low in individuals with Parkinson’s disease. This enzyme plays a crucial role in breaking down waste in brain cells, and when it doesn’t work properly, damage can occur. Dr. Pasternak learned about Ambroxol during his fellowship at The Hospital for Sick Children, where it was identified as a treatment for Gaucher disease – a rare genetic disorder caused by a deficiency of GCase.

The findings of this study are crucial because they suggest that Ambroxol may protect brain function in people with Parkinson’s-related diseases. This research is vital, especially since Parkinson’s dementia profoundly affects patients and families. If a drug like Ambroxol can help slow down its progression, it could offer real hope and improve lives.

Funded by the Weston Foundation, this study is an essential step toward developing new treatments for Parkinson’s disease and other cognitive disorders, including dementia with Lewy bodies. Dr. Pasternak and his team plan to start a follow-up clinical trial focused specifically on cognition later this year, further solidifying their commitment to finding effective solutions for individuals affected by these devastating diseases.

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Chronic Illness

The Surprising Link Between Hearing Loss, Loneliness, and Lifespan

People who treat hearing loss with hearing aids or cochlear implants regain rich conversations, escape isolation, and may even protect their brains and lifespans—proof that better hearing translates into fuller living.

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A groundbreaking new study has shed light on the surprising link between hearing loss, loneliness, and lifespan. Researchers from the USC Caruso Department of Otolaryngology – Head and Neck Surgery found that adults with hearing loss who used hearing aids or cochlear implants were more socially engaged and felt less isolated compared to those who didn’t use them.

The study, published in JAMA Otolaryngology – Head & Neck Surgery, is the first to link hearing aids and cochlear implants to improved social lives among adults with hearing loss. The researchers conducted a comprehensive review of 65 previously published studies, encompassing over five thousand participants, on how hearing aids and cochlear implants affect three key measures: social quality of life, perceived social handicap, and loneliness.

The findings suggest that hearing devices can help prevent the social disconnection and broader health consequences that can follow untreated hearing loss. When left unaddressed, hearing loss can make communication difficult, leading people to withdraw from conversations and social activities. This can lead to mental stimulation reduction, increased risk of loneliness, anxiety, depression, cognitive decline, and dementia.

The researchers found that adults using hearing devices feel more socially connected and less limited in social situations. They are better able to engage in group conversations and feel more at ease in noisy or challenging listening environments. Participants also reported feeling less socially handicapped by their hearing loss, with fewer barriers and frustrations during interactions and an improved ability to stay engaged without feeling excluded.

Those with cochlear implants reported the most improvement in their social quality of life, likely because cochlear implants offer greater hearing restoration than hearing aids, especially for individuals with more severe hearing loss. As a result, they may experience more noticeable improvements in social engagement once their hearing is restored.

While it was outside the scope of the study to measure how better social lives relate to improved cognitive outcomes, the researchers believe there may be a connection. Previous research has found managing hearing loss may be key to reducing the risk of cognitive decline and dementia. The study’s lead researcher, Janet Choi, MD, MPH, an otolaryngologist with Keck Medicine, believes that by restoring clearer communication, hearing devices may help preserve cognitive health by keeping the brain more actively involved and people more connected.

This research follows a January 2024 study by Choi showing that adults with hearing loss who use hearing aids have an almost 25% lower risk of mortality, suggesting that treating hearing loss can improve lifespan as well as social quality of life. These findings add to a growing body of research showing that hearing health is deeply connected to overall well-being.

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Alternative Medicine

Catching Parkinson’s Sooner: Tiny Twitches, Big Breakthroughs

These findings highlight the significance of rearing behavior and behavioral lateralization as potential behavioral markers for tracking the progression of Parkinson's disease.

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The study of Parkinson’s disease (PD) has long focused on understanding its symptoms and how they impact patients. However, a new discovery has shed light on a critical aspect of the disease: the subtle behaviors that can indicate its progression. Researchers from the Shenzhen Institutes of Advanced Technology have made a groundbreaking find that could revolutionize how we diagnose and treat PD.

Midbrain dopamine neurons play a vital role in regulating movement, emotion, and reward processing. Dysfunction in these neurons is directly linked to PD. However, previous research has primarily concentrated on their functions in mood regulation and reward mechanisms. The new study aims to close this knowledge gap by investigating the role of dopamine neurons in more subtle and spontaneous behaviors.

The researchers employed a machine learning-enhanced three-dimensional analysis system to examine detailed motor behaviors in two mouse models of dopamine neuron depletion: an MPTP-induced PD model and an AAV-mediated DA neuron loss model. This innovative approach enabled them to capture nuanced behavioral features that traditional methods might overlook.

One significant finding was the association between subtle behaviors such as rearing, walking, and hunching with the loss of substantia nigra pars compacta (SNc) dopamine neurons. These behaviors were not correlated with the ventral tegmental area (VTA) dopamine neurons. The results suggest that these behaviors can serve as key behavioral biomarkers for SNc DA neuron loss.

Moreover, researchers observed notable behavioral lateralization in PD mice and confirmed that climbing behavior was also strongly correlated with the loss of DA neurons in the SNc. These findings highlight the significance of rearing behavior and behavioral lateralization as potential markers for tracking PD progression.

The study’s lead researcher, Prof. Xuemei Liu, emphasized the importance of connecting behavioral changes to targeted neural damage in understanding PD progression and improving treatment strategies. This groundbreaking discovery opens doors to new research avenues and may ultimately aid in developing more effective treatments for Parkinson’s disease patients.

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