Day: February 24, 2025

Categories : CancerTags : Leave a comment

Caner Signals may Promote Blood Clot Formation in the Lungs

On By ModernMedia
Thrombophilia. Credit: Scientific Animations CC4.0.

Blood clots form in response to signals from the lungs of cancer patients—not from other organ sites, as previously thought—according to a preclinical study. Clots are the second-leading cause of death among cancer patients with advanced disease or aggressive tumours.

While blood clots usually form to stop a wound from bleeding, cancer patients can form clots without injury, plugging up vessels and cutting off circulation to organs. The study, published in Cell, shows that tumours drive thrombosis by releasing chemokines, secreted proteins which then circulate to the lung. Once there, the chemokines prompt macrophages to release small vesicles that attach to platelets, forming life-threatening clots.

The findings may lead to diagnostic tests to determine blood clotting risk and safer therapies that target the root of the problem to prevent blood clots.

“This work redefines the concept of how thrombosis develops in cancer patients, compared to the traditional view that factors on blood vessel walls or tumour cells themselves are responsible,” said study lead Dr David Lyden, professor in paediatric cardiology, and cell and developmental biology at Weill Cornell Medicine. “It’s a revolutionary concept that thrombosis is initiated in the lung, which wasn’t appreciated before.”

Tumors in the Driver’s Seat

“We reviewed post-mortem studies and found that up to 60% of cancer patients died because of clots rather than cancer itself,” said first author Dr Serena Lucotti,  instructor of cell biology in paediatrics at Weill Cornell Medicine. “It is unfortunate because we have drugs that can prevent clots, but we can’t give them unconditionally to all patients because they can cause excessive bleeding in some. At the same time, we can’t predict who is at high risk for clots and would benefit from the drugs.”

In a series of experiments in mice and human tissues, the researchers showed that different tumours release varying amounts of the chemokine CXCL13. Breast cancers and melanomas release relatively small quantities of CXCL13. However, if these tumour cells spread to the lung, they can trigger clot formation by releasing CXCL13 and locally influencing interstitial macrophages. “In contrast, pancreatic cancer secretes high levels of CXCL13 into the bloodstream,” said Dr Lyden. “It’s so high that it circulates all the way to the macrophages in the lung, so these tumour cells don’t need to be close by.”

Blocking Clots—and Metastases

Other experiments revealed that after interacting with CXCL13, lung interstitial macrophages send out small vesicles loaded with an adhesion molecule, integrin β2, on their surface. The integrin β2 is in an open conformation that can attach to platelets and trigger clot formation.

Mice treated with an antibody that blocks vesicle-bound integrin β2 from binding to platelets had no side effects and didn’t have excessive bleeding. Strikingly, mice with early or advanced cancers that were treated with the antibody not only had fewer clots, but also had significantly fewer metastases than untreated controls. “This is important because there aren’t effective treatments for patients with metastases and will be further investigated,” Dr Lucotti said. She is developing a human antibody to block the integrin β2-platelet interaction in patients.

The researchers are also hopeful that integrin β2 can be a biomarker that indicates a patient’s risk for developing clots. As proof of concept, the team analyzed blood samples from some pancreatic cancer patients from Moores Cancer Center at the University of California San Diego Health. By analyzing blood samples collected before and after the patients experienced blood clots, the authors could easily and accurately distinguish between low-risk and high-risk patients based on integrin β2 levels on extracellular vesicles in the blood.

The study highlights that cancer is a disease that can affect many parts of the body. “Cancer is a systemic disease. We have to pay attention to not only future sites of metastasis, but other organs that may be affected independent of metastasis by systemic complications such as thrombosis, leading to morbidity and mortality,” Dr Lyden said.

Source: Weill Cornell Medicine

Categories : Expert Opinion Pain ManagementTags : Leave a comment

Continuation of Opioids for Chronic Pain: Experts Divided

On By ModernMedia
Photo by Usman Yousaf on Unsplash

Chronic pain is complex and difficult to treat. Prescribing opioid pain medications has become controversial but may help some patients.

With the goal of informing clinician practice, a new study explores the harms and benefits of continuing and of discontinuing the long-term prescription of opioid medicines to adults with chronic pain. The authors analysed the opinions of 28 experts on the harms versus benefits of maintaining, tapering or terminating opioid pain medication prescriptions for chronic pain, a common condition worldwide that is typically quite difficult to treat.

The study authors found a lack of consensus among the experts on how to treat chronic (lasting three or more months) non-cancer pain. Slightly more than a third of the experts (36%) believed that long-term opioid therapy is beneficial, while an equal percentage indicated that it should be discontinued.

More than half of the experts believed that patients can experience harm from overly rapid tapering and discontinuation, while some recommended attempting a slow taper (even with a prior unsuccessful taper), possibly with addition of medications to manage withdrawal) in order not to maintain opioid therapy.

Some of the experts advocated for switching patients to buprenorphine, which diminishes the effects of physical dependency to opioids, such as withdrawal symptoms and cravings, and is used to treat pain. Some considered adding non-opioid pain therapies (including re-trying these therapies even if they were unhelpful in the past) as well as engaging in shared decision-making with the patient, although there was little consensus on how to accomplish these options.

Some, but not all of the experts, noted the benefit of addressing co-occurring conditions related to patient safety, such as alcohol use, mental health symptoms and opioid side effects.

Few of the experts brought up assessing or addressing opioid use disorder or overdose risk.

“The potential harms of opioid pain medication are well known, nevertheless patients can become habituated to them and want their physicians to continue prescribing them. Taking patients off opiates may result in return or worsening of chronic pain, mental health issues, drug seeking and potentially overdose and death. Additionally, these drugs could be used by someone else, possibly winding up on the street,” said study co-author Kurt Kroenke, MD of the Regenstrief Institute and the Indiana University School of Medicine. “On the benefit side, these drugs may be helping relieve the patient’s often debilitating pain which can impact the ability to interact with family, to hold a job, participate in social activities and many other aspects of life.”

A substantial number of people who are prescribed opioid pain medications continue to experience chronic pain. Dr Kroenke notes that these individuals may be good candidates for tapering to a lower dose, prescription discontinuation and moving on to effective, safer treatments for pain.

The authors conclude their analysis of the experts’ opinions, “Guidelines on whether to continue or taper opioids prescribed long- term may be difficult to utilize given professional liability concerns, changing regulations and health system initiatives, differing provider-patient perspectives on long-term opioid benefits and harms, and some providers’ beliefs that opioid dependence interferes with patients’ objectivity. In the meantime, individual care decisions that involve weighing relative harms should draw on longstanding norms of ethical medical care that call for informed consent and patient-provider conversations grounded in mutual respect.”

The study is published in the peer-reviewed journal Pain Practice.

Source: EurekAlert

Categories : Dermatology Diet and NutritionTags : Leave a comment

Plant-rich, Low Saturated-fat Diet Linked to Reduced Psoriasis Severity

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Photo: CC0

A new study by researchers at King’s College London, published in the British Journal of Nutrition, has found significant associations between diet quality and the severity of psoriasis. The findings provide novel insights into how dietary patterns may be related to psoriasis severity in non-Mediterranean populations.

Psoriasis is a long-lasting inflammatory skin disease which causes flaky patches of skin that form scales. It affects millions worldwide and is believed to be caused by a problem with the immune system.

The research analysed data from 257 adults with psoriasis who had completed an online survey. Participants’ adherence to various diet quality scores, including the Mediterranean Diet Score, the Dietary Approaches to Stop Hypertension (DASH) score, and the Healthy Plant-based Diet Index, was assessed using a food frequency questionnaire. Psoriasis severity was self-assessed using a validated questionnaire.

Key findings from the study indicate that individuals with very low adherence to the DASH diet index and the Healthy Plant-based Diet Index were significantly more likely to report higher psoriasis severity.

Further analysis of the different elements of the DASH dietary pattern revealed that greater red and processed meat intake was associated with more severe psoriasis even when body mass index (BMI) was considered. Fruits, nuts and legume intakes were also associated with less severe psoriasis, but this relationship was not independent of BMI.

The study was published as part of the Asking People with Psoriasis about Lifestyle and Eating (APPLE) project and funded by the Psoriasis Association.

Our findings point to the potential benefits of dietary interventions in improving patient outcomes. Given the impact of psoriasis on physical and psychological well-being, incorporating dietary assessments into routine care could offer patients additional support in managing their condition.

Sylvia Zanesco, PhD student from the Department of Nutritional Sciences at King’s College London who led the research

The DASH dietary pattern was originally designed to lower blood pressure and emphasises fruits, vegetables, whole grains, low-fat dairy foods and lean meats while limiting salt, sugar, and saturated fats. A high Healthy Plant-based Diet Index characterises a dietary pattern rich in healthy plant foods including fruits and vegetables, whole grains, nuts and seeds, legumes and plant oils rich in unsaturated fats, as well as being low in animal foods and unhealthy plant foods such as sugary foods and drinks and refined starches.

The study accounted for several confounding factors, including age, sex, smoking status, alcohol, energy intake, and mental health, ensuring a comprehensive analysis of dietary patterns that are independently associated with psoriasis severity.

This research brings much-needed evidence that there may be a role for dietary advice, alongside standard clinical care, in managing symptoms of psoriasis. Our next steps will be to explore whether diets rich in healthy plant foods can reduce symptoms of psoriasis in a controlled clinical trial.

Professor Wendy Hall, Professor of Nutritional Sciences at King’s College London and senior author of the study

The findings of the study contribute to the growing body of evidence supporting dietary modification as a complementary strategy in psoriasis management to potentially alleviate disease severity and improve patients’ quality of life.

Source: King’s College London

Categories : Pain Management Substance UseTags : Leave a comment

Co-prescribed Stimulants and Opioids Linked to Higher Opioid Doses

On By ModernMedia
Photo from Pixabay CCO

The combination of prescribed central nervous system stimulants, such as drugs that relieve ADHD symptoms, with prescribed opioid medications is associated with a pattern of escalating opioid intake, a new study has found. 

The analysis of health insurance claims data from almost 3 million US patients investigated prescribed stimulants’ impact on prescription opioid use over 10 years, looking for origins of the so-called “twin epidemic” of combining the two classes of drugs, which can increase the risk for overdose deaths. 

“Combining the two drugs is associated with an increase in overdose deaths. This is something we know. But we didn’t know whether stimulant use has a causal role in high use of opioids, so we conducted a big data analysis of how these two patterns interacted over a long period of time,” said senior study author Ping Zhang, associate professor of computer science and engineering and biomedical informatics at The Ohio State University.

“What we found is that if someone is taking a stimulant and an opioid at the same time, they’re generally taking a high dose of the opioid,” he said. “And if the patient in this study population takes the stimulant before beginning opioid use, they are more likely to have higher doses of subsequent opioids.” 

The study was published in The Lancet Regional Health – Americas.     

The research team obtained data on 22 million patients with 96 million opioid prescriptions from a large US health insurance database. Researchers established a cohort for this study of 2.9 million patients with an average age of 44 who had at least two independent opioid prescriptions between 2012 and 2021. 

Because these prescriptions included a range of oral formulas – codeine, hydrocodone, methadone, oxycodone, morphine and others – researchers standardised every prescription to morphine milligram equivalents (MME) and calculated each patient’s monthly intake of opioids.

First author Seungyeon Lee, a PhD student in Zhang’s lab, used statistical modelling and classified patients into five baseline groups of opioid dosage trajectory over the 10-year study period: very low-dose, low-dose decreasing, low-dose increasing, moderate-dose increasing and high-dose sustained use. 

“Some patients had stable low-dose opioid use, while others had increasing or high dose patterns over time,” Lee said. 

Of the total cohort, 160 243 patients (5.5%) also were prescribed stimulants. The addition of a monthly calculated cumulative number of stimulant prescriptions to the model and statistical analysis showed a shift in the trajectory groups. Characteristics that could serve as risk factors for increasing opioid use also emerged in the data, Lee said. 

Moderate-dose increasing and high-dose groups had an overall higher average MME and a higher proportion of patients with diagnoses of depression, anxiety and attention-deficit/hyperactivity disorder compared to other groups. The low-dose increasing group also had a higher proportion of patients with ADHD compared to the low-dose decreasing group. 

The most common diagnoses linked to co-prescription of stimulants and opioids were depression and ADHD or ADHD and chronic pain. 

“This was an important finding, that many patients with ADHD and depression, also experiencing chronic pain, have an opioid prescription,” said Zhang. “This cohort represents a very realistic health care problem.” 

Even taking those factors into account, the model showed that stimulant use was key to driving up the odds that patients who took both stimulants and opioids would belong to a group of people who increased their doses of opioids. 

“Stimulant use before initiating opioids and stimulant co-prescription with opioids are both positively associated with escalating opioid doses compared to other factors,” Lee said. 

Analysis of geographic and gender data also offered some clues to opioid use patterns in the United States. Patients in the South and West regions had higher total opioid intakes over the 10-year study period compared to the Northeast and North Central regions, with the highest frequency of opioid prescriptions in the South and higher MMEs per prescription in the West. Males also had higher average daily opioid intakes than females. 

The results linking high opioid doses and stimulant use suggest stimulants may be a driving force behind the emergence of the twin epidemic and offer evidence that regulation of stimulant prescribing may be needed for patients already taking prescription opioids, the researchers said. In addition to the increased risk of overdose death, co-using prescription stimulants and opioids can increase the risk for cardiovascular events and mental health problems, previous research has shown. 

Source: Ohio State University

Categories : GastrointestinalTags : Leave a comment

Compound in Ginger might be a Treatment for Inflammatory Bowel Disease

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Irritable bowel syndrome. Credit: Scientific Animations CC4.0

An international team led by researchers at the University of Toronto has found a compound in ginger, called furanodienone (FDN), that selectively binds to and regulates a nuclear receptor involved in inflammatory bowel disease (IBD).

Through a screen to identify chemical components of ginger that bind to receptors associated with IBD, the team observed a strong interaction between FDN and the pregnane X receptor (PXR). FDN reduces inflammation in the colon by activating PXR’s ability to suppress the production of pro-inflammatory cytokines in the body. While researchers have been aware of FDN for decades, they had not determined its functions or targets in the body until now.

“We found that we could reduce inflammation in the colons of mice through oral injections of FDN,” said research associate Jiabao Liu. “Our discovery of FDN’s target nuclear receptor highlights the potential of complementary and integrative medicine for IBD treatment. We believe natural products may be able to regulate nuclear receptors with more precision than synthetic compounds, which could lead to alternative therapeutics that are cost-effective and widely accessible.”

The study was published recently in the journal Nature Communications.

IBD patients typically start to experience symptoms early in life; around 25% of patients are diagnosed before the age of 20. There is currently no cure for IBD, so patients must adhere to life-long treatments to manage their symptoms, including abdominal pain and diarrhoea, enduring significant psychological and economic consequences.

While patients with IBD have found some relief through changes to their diet and herbal supplements, it is not clear which chemical compounds in food and supplements are responsible for alleviating intestinal inflammation. With FDN now identified as a compound with potential to treat IBD, this specific component of ginger can be extracted to develop more effective therapies.

An additional benefit of FDN is that it can increase the production of tight junction proteins that repair damage to the gut lining caused by inflammation. The effects of FDN were demonstrated in the study to be restricted to the colon, preventing harmful side effects to other areas of the body.

Nuclear receptors serve as sensors within the body for a wide range of molecules, including those involved in metabolism and inflammation. PXR specifically plays a role in the metabolism of foreign substances, like dietary toxins and pharmaceuticals. Binding between FDN and PXR needs to be carefully regulated because over-activating the receptor can lead to an increase in the metabolism and potency of other drugs and signaling metabolites in the body.

FDN is a relatively small molecule that only fills a portion of the PXR binding pocket. The study shows that this allows for an additional compound to bind simultaneously, thereby increasing the overall strength of the bond and its anti-inflammatory effects in a controlled manner.

“The number of people diagnosed with IBD in both developed and developing countries is on the rise due to a shift towards diets that are more processed and are high in fat and sugar,” said Henry Krause, principal investigator on the study and professor of molecular genetics. “A natural product derived from ginger is a better option for treating IBD than current therapies because it does not suppress the immune system or affect liver function, which can lead to major side effects. FDN can form the basis of a treatment that is more effective while also being safer and cheaper.”

Source: University of Toronto